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Sample records for clinical trials as topic

  1. Lavender-thymol as a new topical aromatherapy preparation for episiotomy: A randomised clinical trial.

    PubMed

    Marzouk, T; Barakat, R; Ragab, A; Badria, F; Badawy, A

    2015-01-01

    The objective of this study was to evaluate the effectiveness of topical lavender-thymol in promoting episiotomy healing. This placebo-controlled, single-blinded, randomised clinical trial involved 60 primiparous women. REEDA score was used to evaluate the outcome of the trial. On the 7th post-partum day, women in Placebo-treated group had worse Redness, Edema, Ecchymosis, Discharge and Approximation (REEDA) score of 3.93 ± 3.65 compared with those in Lavender-thymol-treated group (2.03 ± 1.7) with significant difference (P = 0.013). Visual analogue Scale (VAS) score for pain at episiotomy in Lavender-thymol-treated group was 3.5 ± 1.9, whereas in Placebo-treated group it was 2.1 ± 2.2 (p = 0.011) for dyschezia, 3.8 ± 1.7 and 2.8 ± 1.6 in Placebo- and Lavender-thymol-treated women, respectively (p = 0.023). At 7th post-partum week, dyspareunia was more severe in Placebo-treated group compared with that in Lavender-thymol-treated group (5.3 ± 2.7 vs 2.7 ± 1.5 and p < 0.001). Topical aromatherapy using lavender-thymol was highly effective, suitable and safe for episiotomy wound care with little or no expected side effects compared with that using placebo. PMID:25384116

  2. [Clinical trials registers. Introduction to the topic and backgrounds].

    PubMed

    Antes, G; Dreier, G; Hasselblatt, H; Blümle, A; Schumacher, M

    2009-04-01

    It is a moral responsibility of those performing clinical studies towards patients, funding organizations, the scientific community and towards the general public to publish the results of clinical trials. Under-reporting of clinical trials with null or even negative results as well as over-reporting of trials with positive results can lead to a biased assessment of (new) treatments, which leads to overestimation of potential benefits and underestimation of potential risks. Comprehensive, publicly accessible clinical trial registries are now widely accepted as an essential tool to fill the information gap. Here, the background for implementing a clinical trials register in Germany is described, whereby publication bias, in particular, is addressed. PMID:19343283

  3. The first clinical experience on efficacy of topical flutamide on melasma compared with topical hydroquinone: a randomized clinical trial

    PubMed Central

    Adalatkhah, Hassan; Sadeghi-Bazargani, Homayoun

    2015-01-01

    Background Treatment of melasma is unsatisfactory most of the times. Hormonal role is shown to exist in pathogenesis of the melasma, and sex-hormone related drugs may have an effect on melasma. Aim To investigate efficacy of 1% flutamide cream versus 4% hydroquinone cream on melasma. Methods In a parallel randomized clinical trial, 74 women with melasma were allocated to receive a sunscreen along with 4% hydroquinone cream or 1% flutamide cream. Melasma Area and Severity Index (MASI), mexameter melanin assay, and patient satisfaction were investigated. Results Mean age of the participants was 33.8 years. Mean length of time suffering from Melasma was 96.3 months. The subjects reported in average 1.1 hours per day of exposure to sunlight. Mean standardized total patient satisfaction score was 28.8 (standard deviation [SD] 17.2) in flutamide group patients versus 18 (SD 15.5) in control group (P<0.01). Regardless of treatment group, the skin darkness assessed upon MASI scales was reduced over the treatment course (P<0.001). Using mixed effects, longitudinal modeling showed better treatment efficacy based on MASI scale for flutamide group compared to the hydroquinone group (P<0.05). However, longitudinal analysis of mexameter scores did not reveal any significant difference in melanin measurements between flutamide and hydroquinone. Conclusion Topical flutamide appeared as effective as topical hydroquinone in treating melasma using mexameter assessment but with a better MASI improvement trend and higher patient satisfaction in flutamide treatment versus topical hydroquinone. As the present study is possibly the first clinical experience on efficacy of topical flutamide on melasma, it would be quite unreasonable to recommend clinical use of it before future studies replicate the results on its efficacy and safety. PMID:26345129

  4. Randomized clinical trial of topical tranexamic acid after reduction mammoplasty

    PubMed Central

    Ausen, K; Fossmark, R; Spigset, O; Pleym, H

    2015-01-01

    Background The antifibrinolytic drug tranexamic acid is currently being rediscovered for both trauma and major surgery. Intravenous administration reduces the need for blood transfusion and blood loss by about one-third, but routine administration in surgery is not yet advocated owing to concerns regarding thromboembolic events. The aim of this study was to investigate whether topical application of tranexamic acid to a wound surface reduces postoperative bleeding. Methods This was a randomized double-blind placebo-controlled trial on 30 consecutive women undergoing bilateral reduction mammoplasty. On one side the wound surfaces were moistened with 25 mg/ml tranexamic acid before closure, and placebo (saline) was used on the other side. Drain fluid production was measured for 24 h after surgery, and pain was measured after 3 and 24 h. Postoperative complications including infection, seroma, rebleeding and suture reactions were recorded. Results Topical application of tranexamic acid to the wound surface after reduction mammoplasty reduced drain fluid production by 39 per cent (median 12·5 (range 0–44) versus 20·5 (0–100) ml; P = 0·038). Adverse effects were not observed. There were no significant differences in postoperative pain scores or complications. Conclusion Topical application of dilute tranexamic acid reduced bleeding in this model. The study adds to the evidence that this simple procedure may reduce wound bleeding after surgery. Registration number: NCT01964781 (http://www.clinicaltrials.gov). PMID:26349843

  5. Quality Randomized Clinical Trials of Topical Diabetic Foot Ulcer Healing Agents

    PubMed Central

    Bolton, Laura L.

    2016-01-01

    Significance: Diabetic foot ulcers (DFU) significantly add to global economic, social, and clinical burdens. Healing a DFU fast and well limits complications that can lead to lower extremity amputation, morbidity, and mortality. Recent Advances: Many promising topical DFU healing agents have been studied in randomized clinical trials (RCT), but only one, becaplermin, has been cleared for this use by the United States Food and Drug Administration (FDA). Critical Issues: This critical review of DFU topical healing RCTs summarizes issues identified in their design and conduct, highlighting ways to improve study quality so researchers can increase the likelihood of RCT success in propelling effective topical DFU healing agents toward clinical use. Key issues include (1) inadequate sample size, (2) risk of bias, (3) irrelevant or unreported inclusion criteria, (4) substandard outcome measures, (5) unmatched group characteristics that predict nonhealing at baseline, (6) unequal or uncontrolled concurrent interventions or standard of care, (7) heterogeneous subject or DFU samples (8) unblinded allocation, treatment, or outcome measures, or (9) inadequate follow-up for clinical relevance. These can add bias or unexplained variability to RCT outcomes, limiting clinical or statistical significance and accuracy of results. Future Directions: This critical review summarizes ways to overcome these deficiencies to optimize DFU clinical trial design and conduct. It provides a blueprint for future excellence in RCTs testing safety and efficacy of topical DFU healing agents and smoothing the path to their clinical use. PMID:26989579

  6. Successful treatment of mild to moderate acne vulgaris with Dr Michaels® (also branded as Zitinex®) topical products family: a clinical trial.

    PubMed

    Wollina, U; Tirant, M; Bayer, P; Coburn, M; Anderson, P; Donnelly, B; Kennedy, T; Gaibor, J; Arora, M; Clews, L; Walmsley, S; Hercogovấ, J; Fioranelli, M; Gianfaldoni, S; Chokoeva, A A; Tchernev, G; Novotny, F; Roccia, M G; Maximov, G K; França, K; Lotti, T

    2016-01-01

    Acne vulgaris is an epidemic inflammatory skin disease of multi-factorial origin, frequently seen in adolescents and often persisting or occurring through to adulthood. Acne vulgaris is a nearly universal skin disease afflicting 79-95% of the adolescent population in westernized societies and is a significant cause of psychological morbidity in affected patients. Despite the various treatment options available for acne, there is still a need for a safe and effective option. The aim of the study was to investigate the efficacy and tolerability of Dr Michaels® (Zitinex®) product family in the treatment of papulo-pustular acne. 25 patients (17 female/8 male), aged 15-22, with a mild to moderate papulo-pustular acne, localized on the face and on the trunk, were included in this study. None of the patients had used any other kind of treatment in the 3 months prior to commencing this study. All of the patients were treated with Dr Michaels® (Zitinex®) facial exfoliating cleanser, activator formula, a cream, PSC 200 and PSC 900 oral supplements. Application time of Dr Michaels® (Zitinex®) products was 12 weeks. The treatment was been evaluated clinically at 0, 4, 8 and 12 weeks. All of the patients showed an improvement in all parameters of their acne (comedones, papules, pustules, hyperpigmentation and scars). The acne lesions and erythema had mostly resolved. The hyperpigmentation and pitted scarring had significantly reduced also, with the skin appearing smoother. The treatment was well tolerated and no side effects have been described. Our study demonstrates that the Dr Michaels® (Zitinex®) facial exfoliating cleanser, activator formula, cream and oral supplements PSC 200 and PSC 900 are an effective therapeutic option for the treatment of moderately severe acne vulgaris. Moreover, it highlights the safety profile of the Dr Michaels® (Zitinex®) product family in a case of acne compared to traditional first-line treatments. PMID:27498658

  7. Double-blind clinical trial of topical steroids in anterior uveitis.

    PubMed Central

    Dunne, J A; Travers, J P

    1979-01-01

    We present the results of a double-blind trial comparing the efficacy of betamethasone phosphate 0.1%, clobetasone butyrate 0.1%, and placebo in the treatment of acute unilateral nongranulomatous uveitis. The 2 steroids were equally comparable in improvement of the patients' symptoms, though betamethasone phosphate was significantly more effective than clobetasone butyrate in improving the ocular signs of uveitis. However, clobetasone butyrate had significantly less effect on raising intraocular pressure in known steroid responders and ocular hypertensives than did dexamethasone. The use of a bolometer as an objective measure in uveitis was significant only in the more severe cases of uveitis. In comparing the placebo group of patients with those on topical steroids, the former group, though improving, appeared to lag behind by approximately one week. Four cases on placebo, however, had to be withdrawn because of worsening of the condition. Mild cases of anterior uveitis would probably resolve without using topical steroids. PMID:389282

  8. Topical tranexamic acid as a novel treatment for bleeding peptic ulcer: A randomised controlled trial

    PubMed Central

    Rafeey, Mandana; Shoaran, Maryam; Ghergherechi, Robabeh

    2016-01-01

    Background: Peptic ulcers are among the most common causes of upper gastrointestinal (GI) bleeding in children. The standard care for GI bleeding is endoscopy for diagnostic and therapeutic purposes. We aimed to assess the effect of topical tranexamic acid (TXA) via endoscopic procedures in children with GI bleeding caused by bleeding ulcers. Procedure: In this randomised controlled trial, 120 children were evaluated by diagnostic procedures for GI bleeding, of which 63 (30 girls, 33 boys) aged 1-month to 15 years were recruited. The patients were randomly divided into case and control groups. In the case group, TXA was administered directly under endoscopic therapy. In the control group, epinephrine (1/10,000) was submucosally injected to the four quadrants of ulcer margins as the routine endoscopic therapy. In both groups, the patients received supportive medical therapy with intravenous fluids and proton pump inhibitor drugs. Results: The mean ± standard deviation age of the children was 5 ± 2.03 years. Rebleeding occurred in 15 (11.4%) and 21 (9.8%) patients in the case and control groups, respectively (P = 0.50). The frequency of blood transfusion episodes (P = 0.06) and duration of hospital stay (P = 0.07) were not statistically different between the groups. Conclusion: Using topical TXA via endoscopic procedures may be effective in cases of GI bleedings caused by active bleeding ulcers. In order to establish this therapeutic effect, a large number of clinical studies are needed. PMID:27251517

  9. Can Clinical Trials Requiring Frequent Participant Contact Be Conducted Over the Internet? Results From an Online Randomized Controlled Trial Evaluating a Topical Ointment for Herpes Labialis

    PubMed Central

    Kabbara, Karim; Clark, Rachael; McAlindon, Tim

    2004-01-01

    Background The Internet has tremendous appeal for conducting randomized clinical trials and may be especially applicable to trials requiring frequent participant contact. Trials of cold sore remedies, for example, often require daily clinic visits during outbreaks, imposing substantial burden on participants. An Internet-based randomized clinical trial design may reduce this burden, permitting frequent symptom reports with considerably less effort. Objective To evaluate the feasibility of a Web-based randomized clinical trial requiring frequent participant interaction, using a 6-month, double-blind, randomized, placebo-controlled pilot trial of a topical ointment containing dioctyl sodium sulfosuccinate (DSS) (Zilex; Meditech Pharmaceuticals, Inc, Scottsdale, Arizona, USA) intended for treatment of recurrent herpes labialis. A secondary objective was to obtain preliminary data on effectiveness outcomes, to assist in planning a fully-powered trial of DSS. Methods Adults with physician-confirmed herpes labialis were recruited to apply to the trial. Eligible applicants were randomized to DSS or placebo, mailed to them upon enrolment with instructions to apply topically every 2 hours for the duration of every cold sore outbreak. Participants were instructed to complete online questionnaires at 2-week intervals and, at the initiation of a cold sore, daily "outbreak questionnaires" until outbreak termination. Feasibility outcome measures included trial participant characteristics, frequency of cold sores, participant retention and adherence (to study medication), and data completeness. Treatment effectiveness outcome measures included outbreak duration, days to crust formation, and pain. Results Of the 292 individuals applying, 182 screened eligible; 32 participants with confirmed herpes labialis enrolled in the trial. 16 were randomized into the verum group and 16 into the placebo group. 29 (91%) participants completed the trial. During the trial, 34 outbreaks were

  10. Clinical Trials

    MedlinePlus

    Clinical trials are research studies that test how well new medical approaches work in people. Each study answers ... prevent, screen for, diagnose, or treat a disease. Clinical trials may also compare a new treatment to a ...

  11. Clinical Trials

    MedlinePlus

    Clinical trials are research studies that test how well new medical approaches work in people. Each study ... prevent, screen for, diagnose, or treat a disease. Clinical trials may also compare a new treatment to ...

  12. Clinical Trials

    MedlinePlus

    ... of visits, and any adjustments to treatment. (back) Requirements for Participation Admission into a clinical trial is based on a rigid set of requirements. You must be diagnosed with the illness that ...

  13. Evaluating clinical trial design: systematic review of randomized vehicle-controlled trials for determining efficacy of benzoyl peroxide topical therapy for acne.

    PubMed

    Lamel, Sonia A; Sivamani, Raja K; Rahvar, Maral; Maibach, Howard I

    2015-11-01

    Determined efficacies of benzoyl peroxide may be affected by study design, implementation, and vehicle effects. We sought to elucidate areas that may allow improvement in determining accurate treatment efficacies by determining rates of active treatment and vehicle responders in randomized controlled trials assessing the efficacy of topical benzoyl peroxide to treat acne. We conducted a systematic review of randomized vehicle-controlled trials evaluating the efficacy of topical benzoyl peroxide for the treatment of acne. We compared response rates of vehicle treatment arms versus those in benzoyl peroxide arms. Twelve trials met inclusion criteria with 2818 patients receiving benzoyl peroxide monotherapy treatment and 2004 receiving vehicle treatment. The average percent reduction in total number of acne lesions was 44.3 (SD = 9.2) and 27.8 (SD = 21.0) for the active and vehicle treatment groups, respectively. The average reduction in non-inflammatory lesions was 41.5 % (SD = 9.4) in the active treatment group and 27.0 % (SD = 20.9) in the vehicle group. The average percent decrease in inflammatory lesions was 52.1 (SD = 10.4) in the benzoyl peroxide group and 34.7 (SD = 22.7) in the vehicle group. The average percentage of participants achieving success per designated study outcomes was 28.6 (SD = 17.3) and 15.2 (SD = 9.5) in the active treatment and vehicle groups, respectively. Patient responses in randomized controlled trials evaluating topical acne therapies may be affected by clinical trial design, implementation, the biologic effects of vehicles, and natural disease progression. "No treatment" groups may facilitate determination of accurate treatment efficacies. PMID:26048131

  14. Efficacy and tolerance of the topical application of potassium hydroxide (10% and 15%) in the treatment of molluscum contagiosum: Randomized clinical trial: Research protocol

    PubMed Central

    2011-01-01

    Background Molluscum contagiosum is a non-severe pediatric viral infection. Because it is highly contagious and current treatments have negative aesthetic and psychological effects, we want to test an alternative treatment in the primary care setting, consisting of two different concentrations of potassium hydroxide solution. Methods/design The study design is a double-blind, randomized clinical trial, using three types of topical treatment. The treatment consist of daily applications of potassium hydroxide (KOH) in aqueous solution at 10% and 15% concentration, and a placebo administered in the control group. Four follow-up visits (at 15, 30, 45 and 60 days) are planned to evaluate treatment effectiveness and patient tolerance. The main outcome measure of the trial will be the healing rate, defined as lesion disappearance in the affected zones after the topic application of the experimental treatment. Secondary measures will be the principal characteristics and evolution of the affected zone (surface area, number of lesions, size and density of lesions), treatment tolerance (hyperpigmentation, itching, burning, pain), recurrence rate and the natural evolution of lesions in the control group. Discussion KOH can potentially be an effective and safe treatment for MC in primary care, and can also reduce referrals to dermatologists and hospital pediatric departments. In addition, KOH may be a valid and less expensive alternative to current invasive treatments (surgical excision). Trial Registration ClinicalTrials.gov: NCT01348386 PMID:22011376

  15. Efficacy of Topical Alpha Ointment (Containing Natural Henna) Compared to Topical Hydrocortisone (1%) in the Healing of Radiation-Induced Dermatitis in Patients with Breast Cancer: A Randomized Controlled Clinical Trial

    PubMed Central

    Ansari, Mansour; Dehsara, Farzin; Mosalaei, Ahmad; Omidvari, Shapour; Ahmadloo, Niloofar; Mohammadianpanah, Mohammad

    2013-01-01

    Background: This two-arm, randomized clinical study aimed to compare efficacy between topical Alpha ointment and topical hydrocortisone cream (1%) in the healing of radiation-induced dermatitis in breast cancer patients. Methods: The inclusion criteria comprised newly pathologically proven, locally advanced breast cancer (treated with modified radical mastectomy followed by sequential adjuvant treatments, including chest wall radiotherapy [45-50.4 Gy]) and grade 2 and/or 3 chest wall dermatitis. The exclusion criteria were comprised of any underlying disease or medications interfering with the wound healing process, previous history of chest wall radiotherapy, and concurrent use of chemotherapy. Sixty eligible patients were randomly assigned to use either topical Alpha ointment (study arm, n=30) or topical hydrocortisone cream (1%) (control arm, n=30) immediately after receiving a total dose of 45-50 Gy chest wall radiotherapy. Results: The mean radiation dose was 49.1 Gy in the control arm and 48.8 Gy in the study arm. The mean dermatitis area was 13.54 cm2 in the control arm and 17.02 cm2 in the study arm. Topical Alpha ointment was more effective on the healing of radiation-induced dermatitis than was topical hydrocortisone cream (1%) (P=0.001). This effect was significant in the second week (P=0.007). In addition, Alpha ointment decreased the patients’ complaints such as pain (P<0.001), pruritus (P=0.009), and discharge (P=0.010) effectively and meaningfully. Conclusion: Topical Alpha ointment was more effective on the healing of radiation-induced dermatitis than was topical hydrocortisone cream (1%) in our patients with breast cancer. Trial Registration Numbers: IRCT201206099979N1, ACTRN12612000837820 PMID:24293782

  16. Animal research as a basis for clinical trials.

    PubMed

    Faggion, Clovis M

    2015-04-01

    Animal experiments are critical for the development of new human therapeutics because they provide mechanistic information, as well as important information on efficacy and safety. Some evidence suggests that authors of animal research in dentistry do not observe important methodological issues when planning animal experiments, for example sample-size calculation. Low-quality animal research directly interferes with development of the research process in which multiple levels of research are interconnected. For example, high-quality animal experiments generate sound information for the further planning and development of randomized controlled trials in humans. These randomized controlled trials are the main source for the development of systematic reviews and meta-analyses, which will generate the best evidence for the development of clinical guidelines. Therefore, adequate planning of animal research is a sine qua non condition for increasing efficacy and efficiency in research. Ethical concerns arise when animal research is not performed with high standards. This Focus article presents the latest information on the standards of animal research in dentistry, more precisely in the field of implant dentistry. Issues on precision and risk of bias are discussed, and strategies to reduce risk of bias in animal research are reported. PMID:25684017

  17. Patient Navigation As a Model to Increase Participation of African Americans in Cancer Clinical Trials

    PubMed Central

    Fouad, Mona N.; Acemgil, Aras; Bae, Sejong; Forero, Andres; Lisovicz, Nedra; Martin, Michelle Y.; Oates, Gabriela R.; Partridge, Edward E.; Vickers, Selwyn M.

    2016-01-01

    Purpose Less than 10% of patients enrolled in clinical trials are minorities. The patient navigation model has been used to improve access to medical care but has not been evaluated as a tool to increase the participation of minorities in clinical trials. The Increasing Minority Participation in Clinical Trials project used patient navigators (PNs) to enhance the recruitment of African Americans for and their retention in therapeutic cancer clinical trials in a National Cancer Institute–designated comprehensive cancer center. Methods Lay individuals were hired and trained to serve as PNs for clinical trials. African American patients potentially eligible for clinical trials were identified through chart review or referrals by clinic nurses, physicians, and social workers. PNs provided two levels of services: education about clinical trials and tailored support for patients who enrolled in clinical trials. Results Between 2007 and 2014, 424 African American patients with cancer were referred to the Increasing Minority Participation in Clinical Trials project. Of those eligible for a clinical trial (N = 378), 304 (80.4%) enrolled in a trial and 272 (72%) consented to receive patient navigation support. Of those receiving patient navigation support, 74.5% completed the trial, compared with 37.5% of those not receiving patient navigation support. The difference in retention rates between the two groups was statistically significant (P < .001). Participation of African Americans in therapeutic cancer clinical trials increased from 9% to 16%. Conclusion Patient navigation for clinical trials successfully retained African Americans in therapeutic trials compared with non–patient navigation trial participation. The model holds promise as a strategy to reduce disparities in cancer clinical trial participation. Future studies should evaluate it with racial/ethnic minorities across cancer centers. PMID:27189356

  18. Topical Treatment With an Agent Disruptive to P. acnes Biofilm Provides Positive Therapeutic Response: Results of a Randomized Clinical Trial.

    PubMed

    Bernhardt, Michael J; Myntti, Matthew F

    2016-06-01

    The traditional disease model of acne has been one of follicular plugging due to 'sticky epithelial cells' associated with increased sebum production with deep follicular anaerobic conditions favoring P. acnes- generated inflammation. P. acnes biofilms have been found more frequently in patients with acne than controls. Biofilms are genetically coded to create adhesion to the pilosebaceous unit followed by production of a mucopolysaccharide coating capable of binding to lipid surfaces. Traditional therapies for acne have involved mixtures of oral and topical antibiotics admixed with topical keratolytics and retinoids, which are aimed at traditional bacterial reduction as well as downregulating the inflammatory cascade. These approaches are limited by side effect and compliance/tolerability issues. As the P. acnes biofilm may, in fact, be the instigator of this process, we studied the use of a topical agent designed to reduce the P. acnes biofilm to see if reducing the biofilm would be therapeutically efficacious. We present data of a proprietary topical non-prescription agent with a novel pharmaco mechanism designed to attack the biofilm produced by P. acnes. Our data shows a decrease of inflammatory lesions by 44% and non-inflammatory lesions by 32% after 12 weeks and also provided for a meaningful improvement in the quality of life of the patients in the study. These improvements were achieved with a product that was not associated with burning, chafing, irritation, or erythema, which can be seen with topical treatments. It is apparent from this study that by addressing the biofilm which protects the P. acnes bacteria through the use of the Acne Gel, the incidence of acne symptoms can be greatly reduced, while having no negative impacts on the patients' skin (ClinicalTrials.gov registry number NCT02404285).

    J Drugs Dermatol. 2016;15(6):677-683. PMID:27272073

  19. Neuroimaging as a Selection Tool and Endpoint in Clinical and Pre-clinical Trials.

    PubMed

    Muir, Keith W; Macrae, I Mhairi

    2016-10-01

    Standard imaging in acute stroke enables the exclusion of non-stroke structural CNS lesions and cerebral haemorrhage from clinical and pre-clinical ischaemic stroke trials. In this review, the potential benefit of imaging (e.g., angiography and penumbral imaging) as a translational tool for trial recruitment and the use of imaging endpoints are discussed for both clinical and pre-clinical stroke research. The addition of advanced imaging to identify a "responder" population leads to reduced sample size for any given effect size in phase 2 trials and is a potentially cost-efficient means of testing interventions. In pre-clinical studies, technical failures (failed or incomplete vessel occlusion, cerebral haemorrhage) can be excluded early and continuous multimodal imaging of the animal from stroke onset is feasible. Pre- and post-intervention repeat scans provide real time assessment of the intervention over the first 4-6 h. Negative aspects of advanced imaging in animal studies include increased time under general anaesthesia, and, as in clinical studies, a delay in starting the intervention. In clinical phase 3 trial designs, the negative aspects of advanced imaging in patient selection include higher exclusion rates, slower recruitment, overestimated effect size and longer acquisition times. Imaging may identify biological effects with smaller sample size and at earlier time points, compared to standard clinical assessments, and can be adjusted for baseline parameters. Mechanistic insights can be obtained. Pre-clinically, multimodal imaging can non-invasively generate data on a range of parameters, allowing the animal to be recovered for subsequent behavioural testing and/or the brain taken for further molecular or histological analysis. PMID:27543177

  20. ClinicalTrials.gov as a Data Source for Semi-Automated Point-Of-Care Trial Eligibility Screening

    PubMed Central

    Pfiffner, Pascal B.; Oh, JiWon; Miller, Timothy A.; Mandl, Kenneth D.

    2014-01-01

    Background Implementing semi-automated processes to efficiently match patients to clinical trials at the point of care requires both detailed patient data and authoritative information about open studies. Objective To evaluate the utility of the ClinicalTrials.gov registry as a data source for semi-automated trial eligibility screening. Methods Eligibility criteria and metadata for 437 trials open for recruitment in four different clinical domains were identified in ClinicalTrials.gov. Trials were evaluated for up to date recruitment status and eligibility criteria were evaluated for obstacles to automated interpretation. Finally, phone or email outreach to coordinators at a subset of the trials was made to assess the accuracy of contact details and recruitment status. Results 24% (104 of 437) of trials declaring on open recruitment status list a study completion date in the past, indicating out of date records. Substantial barriers to automated eligibility interpretation in free form text are present in 81% to up to 94% of all trials. We were unable to contact coordinators at 31% (45 of 146) of the trials in the subset, either by phone or by email. Only 53% (74 of 146) would confirm that they were still recruiting patients. Conclusion Because ClinicalTrials.gov has entries on most US and many international trials, the registry could be repurposed as a comprehensive trial matching data source. Semi-automated point of care recruitment would be facilitated by matching the registry's eligibility criteria against clinical data from electronic health records. But the current entries fall short. Ultimately, improved techniques in natural language processing will facilitate semi-automated complex matching. As immediate next steps, we recommend augmenting ClinicalTrials.gov data entry forms to capture key eligibility criteria in a simple, structured format. PMID:25334031

  1. Design of clinical trials.

    PubMed

    Rollo, David; Machado, Sanjay; Ceschin, Mauro

    2010-09-01

    Clinical trial design for nuclear medicine diagnostic imaging radiopharmaceuticals must include a design for preclinical safety studies. These studies should establish that the investigational product (IP) does not have a toxic effect. As a further requirement, radiopharmaceutical clinical trials include a human study (phase 1) that provides biodistribution, pharmacokinetics, and radiation dosimetry information. These studies demonstrate to the Food and Drug Administration that the IP either meets or exceeds the toxicology and radiation exposure safety limits. Satisfying this requirement can result in the Food and Drug Administration approving the performance of late-phase (phase 2/3) clinical trials that are designed to validate the clinical efficacy of the diagnostic imaging agent in patients who have a confirmed diagnosis for the intended application. Emphasis is placed on the most typical trial design for diagnostic imaging agents that use a comparator to demonstrate that the new IP is similar in efficacy to an established standard comparator. Such trials are called equivalence, or noninferiority, trials that attempt to show that the new IP is not less effective than the comparator by more than a statistically defined amount. Importantly, the trial design must not inappropriately favor one diagnostic imaging agent over the other. Bias is avoided by the use of a core laboratory with expert physicians who are not involved in the trial for interpreting and objectively scoring the image sets obtained at the clinical trial sites. Clinical trial design must also follow Good Clinical Practice (GCP) guidelines. GCP stipulates the clinical trial process, including protocol and Case Report Form design, analyses planning, as well as analyzing and preparing interim and final clinical trial/study reports. PMID:20674592

  2. Using Vascular Quality Initiative as a Platform for Organizing Multicenter, Prospective, Randomized Clinical Trials: OVERPAR Trial

    PubMed Central

    Eslami, Mohammad H.; Doros, Gheorghe; Goodney, Philip P.; Elderup-Jorgenson, Jens; Cronenwett, Jack L.; Malikova, Marina; Farber, Alik

    2014-01-01

    Background We describe the organization of a prospective, randomized, multicenter trial comparing the effectiveness of open popliteal artery aneurysm repair (OPAR) and endovascular popliteal artery aneurysm repair (EPAR) of asymptomatic popliteal artery aneurysms (PAAs) as an example for how to use the Vascular Quality Initiative (VQI) framework. Given that many centers participate in the VQI, this model can be used to perform multicenters’ prospective trials on very modest budget. Methods VQI prospectively collects data on many vascular procedures. These data include many important perioperative, intraoperative, and postoperative details regarding both patients and their procedures. We describe a study where minimal changes to the collected data by participating centers can provide level-1 evidence regarding a significant clinical question. Data will be collected using modified VQI forms within the existing VQI data reporting structure. We plan to enroll 148 patients with asymptomatic PAAs into the open and endovascular surgery cohorts. Patients from participating VQI centers will be randomized 1:1 to either OPAR or EPAR and will be followed for an average of 2.5 years. Our primary hypothesis is that major adverse limb event–free survival is lower in the EPAR cohort and that EPAR is associated with more secondary interventions, improved quality of life, and decreased length of stay. The budget for this trial is fixed at $10,000/year for the course of the study, and the trial is judged to be feasible because of the functionality of the VQI platform. Conclusions Using the existing VQI infrastructure, Open versus Endovascular Repair of Popliteal Artery Aneurysm will provide level 1 data for PAA treatment on a modest budget. The proposed trial has an adequately powered comparative design that will use objective performance goals to describe limb-related morbidity and procedural reintervention rates. PMID:25311746

  3. Portfolio of Clinical Research in Adult Cardiovascular Disease as Reflected in ClinicalTrials.gov

    PubMed Central

    Alexander, Karen P.; Kong, David F.; Starr, Aijing Z.; Kramer, Judith; Chiswell, Karen; Tasneem, Asba; Califf, Robert M.

    2013-01-01

    Background Cardiovascular medicine is widely regarded as a vanguard for evidence‐based drug and technology development. Our goal was to describe the cardiovascular clinical research portfolio from ClinicalTrials.gov. Methods and Results We identified 40 970 clinical research studies registered between 2007 and 2010 in which patients received diagnostic, therapeutic, or other interventions per protocol. By annotating 18 491 descriptors from the National Library of Medicine's Medical Subject Heading thesaurus and 1220 free‐text terms to select those relevant to cardiovascular disease, we identified studies that related to the diagnosis, treatment, or prevention of diseases of the heart and peripheral arteries in adults (n=2325 [66%] included from review of 3503 potential studies). The study intervention involved a drug in 44.6%, a device or procedure in 39.3%, behavioral intervention in 8.1%, and biological or genetic interventions in 3.0% of the trials. More than half of the trials were postmarket approval (phase 4, 25.6%) or not part of drug development (no phase, 34.5%). Nearly half of all studies (46.3%) anticipated enrolling 100 patients or fewer. The majority of studies assessed biomarkers or surrogate outcomes, with just 31.8% reporting a clinical event as a primary outcome. Conclusions Cardiovascular studies registered on ClinicalTrials.gov span a range of study designs. Data have limited verification or standardization and require manual processes to describe and categorize studies. The preponderance of small and late‐phase studies raises questions regarding the strength of evidence likely to be generated by the current portfolio and the potential efficiency to be gained by more research consolidation. PMID:24072529

  4. Human Pulp Response to Direct Pulp Capping and Miniature Pulpotomy with MTA after Application of Topical Dexamethasone: A Randomized Clinical Trial

    PubMed Central

    Mousavi, Seyed Amir; Ghoddusi, Jamileh; Mohtasham, Nooshin; Shahnaseri, Shirin; Paymanpour, Payam; Kinoshita, Jun-Ichiro

    2016-01-01

    Introduction: The aim of this randomized clinical trial was to compare the histologic pulp tissue response to one-step direct pulp capping (DPC) and miniature pulpotomy (MP) with mineral trioxide aggregate (MTA) after application of dexamethasone in healthy human premolars. Methods and Materials: Forty intact premolars from 10 orthodontic patients, were randomly chosen for DPC (n=20) or MP (n=20). In 10 teeth from each group, after exposure of the buccal pulp horn, topical dexamethasone was applied over the pulp. In all teeth the exposed/miniaturely resected pulp tissue was covered with MTA and cavities were restored with glass ionomer. Teeth vitality was evaluated during the next 7, 21, 42, and 60 days. Signs and/or symptoms of irreversible pulpitis or pulp necrosis were considered as failure. According to the orthodontic schedule, after 60 days the teeth were extracted and submitted for histological examination. The Kruskal-Wallis and Fisher’s exact tests were used for statistical analysis of the data (P=0.05). Results: Although dexamethasone specimens showed less inflammation, calcified bridge, pulpal blood vasculature, collagen fibers and granulation tissue formation were not significantly different between the groups (P>0.05). Conclusion: Topical dexamethasone did not hindered pulp healing but reduced the amount of underlying pulpal tissue inflammation after DPC and MP in healthy human premolars. PMID:27141213

  5. Clinical trials of homoeopathy.

    PubMed Central

    Kleijnen, J; Knipschild, P; ter Riet, G

    1991-01-01

    OBJECTIVE--To establish whether there is evidence of the efficacy of homoeopathy from controlled trials in humans. DESIGN--Criteria based meta-analysis. Assessment of the methodological quality of 107 controlled trials in 96 published reports found after an extensive search. Trials were scored using a list of predefined criteria of good methodology, and the outcome of the trials was interpreted in relation to their quality. SETTING--Controlled trials published world wide. MAIN OUTCOME MEASURES--Results of the trials with the best methodological quality. Trials of classical homoeopathy and several modern varieties were considered separately. RESULTS--In 14 trials some form of classical homoeopathy was tested and in 58 trials the same single homoeopathic treatment was given to patients with comparable conventional diagnosis. Combinations of several homoeopathic treatments were tested in 26 trials; isopathy was tested in nine trials. Most trials seemed to be of very low quality, but there were many exceptions. The results showed a positive trend regardless of the quality of the trial or the variety of homeopathy used. Overall, of the 105 trials with interpretable results, 81 trials indicated positive results whereas in 24 trials no positive effects of homoeopathy were found. The results of the review may be complicated by publication bias, especially in such a controversial subject as homoeopathy. CONCLUSIONS--At the moment the evidence of clinical trials is positive but not sufficient to draw definitive conclusions because most trials are of low methodological quality and because of the unknown role of publication bias. This indicates that there is a legitimate case for further evaluation of homoeopathy, but only by means of well performed trials. PMID:1825800

  6. Skin-whitening and skin-condition-improving effects of topical oxidized glutathione: a double-blind and placebo-controlled clinical trial in healthy women

    PubMed Central

    Watanabe, Fumiko; Hashizume, Erika; Chan, Gertrude P; Kamimura, Ayako

    2014-01-01

    Purpose Glutathione is a tripeptide consisting of cysteine, glycine, and glutamate and functions as a major antioxidant. It is synthesized endogenously in humans. Glutathione protects thiol protein groups from oxidation and is involved in cellular detoxification for maintenance of the cell environment. Reduced glutathione (GSH) has a skin-whitening effect in humans through its tyrosinase inhibitory activity, but in the case of oxidized glutathione (GSSG) this effect is unclear. We examined the skin-whitening and skin-condition effects of topical GSSG in healthy women. Subjects and methods The subjects were 30 healthy adult women aged 30 to 50 years. The study design was a randomized, double-blind, matched-pair, placebo-controlled clinical trial. Subjects applied GSSG 2% (weight/weight [w/w]) lotion to one side of the face and a placebo lotion to the other side twice daily for 10 weeks. We objectively measured changes in melanin index values, moisture content of the stratum corneum, smoothness, wrinkle formation, and elasticity of the skin. The principal investigator and each subject also used subjective scores to investigate skin whitening, wrinkle reduction, and smoothness. Analysis of variance was used to evaluate differences between groups. Results The skin melanin index was significantly lower with GSSG treatment than with placebo from the early weeks after the start of the trial through to the end of the study period (at 10 weeks, P<0.001). In addition, in the latter half of the study period GSSG-treated sites had significant increases in moisture content of the stratum corneum, suppression of wrinkle formation, and improvement in skin smoothness. There were no marked adverse effects from GSSG application. Conclusion Topical GSSG is safe and effectively whitens the skin and improves skin condition in healthy women. PMID:25378941

  7. Clinical and serological efficacy of topical calcineurin inhibitors in oral lichen planus: a prospective randomized controlled trial.

    PubMed

    Vohra, Suruchi; Singal, Archana; Sharma, Suman Bala

    2016-01-01

    Oral lichen planus (OLP) is a T-cell-mediated disease characterized by immune-mediated basal cell degeneration releasing interleukins (ILs) such as IL-6 and IL-8 into the circulation. Their serum levels reportedly reflect disease activity. Although many therapeutic options are available, none are curative. We compared the efficacy of tacrolimus 0.1% ointment and pimecrolimus 1% cream in OLP and correlated with serum IL-6 and IL-8 levels before and after treatment. Forty patients with symptomatic OLP were randomized into two groups, to receive either topical tacrolimus 0.1% ointment or pimecrolimus 1% cream (twice daily for 8 weeks). Patients were assessed at 2, 4, 8, and 12 weeks. At each visit, objective improvement in the net clinical score (NCS), drug tolerability, and side effects were evaluated. Serum IL-6 and IL-8 levels were measured at baseline and at eight weeks. Baseline characteristics were comparable between the groups. The mean NCS declined from 10.9 ± 4.5 and 9.9 ± 4.6 at baseline to 5.4 ± 3.5 and 5.3 ± 4.2 at 12 weeks for tacrolimus and pimecrolimus group, respectively. At each visit, in both groups, the decline in mean NCS from baseline was statistically significant (P < 0.05) and so was the decline in mean serum IL-6 and IL-8 levels pre- and post-treatment. Pimecrolimus 1% cream seems to be as effective as tacrolimus 0.1% ointment. Serum IL-6 and IL-8 may act as markers of disease activity. However, future efforts are needed to objectify the use of serum interleukin levels in the disease severity index. PMID:26147635

  8. The Perfect Clinical Trial.

    PubMed

    Bril, V

    2016-01-01

    Multiple phase III clinical trials have failed to show disease-modifying benefits for diabetic sensorimotor polyneuropathy (DSP) and this may be due to the design of the clinical trials. The perfect clinical trial in DSP would enroll sufficiently large numbers of patients having early or minimal disease, as demonstrated by nerve conduction studies (NCS). These patients would be treated with an intervention given at an effective and well-tolerated dose for a sufficient duration of time to show change in the end points selected. For objective or surrogate measures such as NCS and for some small fiber measures, the duration needed to show positive change may be as brief as 6-12 months, but subsequently, trials lasting 5-8 years will be required to demonstrate clinical benefits. PMID:27133143

  9. Xylitol pediatric topical oral syrup to prevent dental caries: a double blind, randomized clinical trial of efficacy

    PubMed Central

    Milgrom, Peter; Ly, Kiet A.; Tut, Ohnmar K.; Mancl, Lloyd; Roberts, Marilyn C.; Briand, Kennar; Gancio, Mary Jane

    2009-01-01

    Objective To evaluate the effectiveness of a xylitol pediatric topical oral syrup to reduce the incidence of dental caries of very young children. Design Randomized, double-blinded, controlled trial. Setting Communities in the Republic of the Marshall Islands. Participants 108 children aged 9 to 15 months were screened and 100 were enrolled. Intervention Children were randomized and parents administered topical oral xylitol syrup two times (Xyl-2X, two xylitol 4.00 g/dose + one sorbitol dose) or three times (Xyl-3X, three xylitol 2.67 g/dose) per day (total 8 g) or control (one xylitol 2.67 g/dose + two sorbitol dose). Outcome Measures The outcome end-point of the study was the number of decayed primary teeth. Results Ninety-four of 100 children (mean±SD age, 15.0±2.7 months at randomization) with at least one follow-up exam were included in the intent-to-treat analysis. The mean±SD follow-up period was 10.5±2.2 months. Nearly 52% of children in the control condition had tooth decay compared to 40.6% among Xyl-3X and 24.2% among Xyl-2X conditions. The mean±SD number of decayed teeth was 1.9±2.4 for control, 1.0±1.4 for Xyl-3X, and 0.6±1.1 for Xyl-2X condition. Compared to controls, there was significantly fewer decayed teeth in the Xyl-2X (relative risk [RR], 0.30; 95% confidence interval [CI] 0.13, 0.66; P=.003) and Xyl-3X (RR, 0.50; 95% CI 0.26, 0.96; P=0.037) conditions. There was no statistical difference between the two xylitol treatment conditions (P=0.22). Conclusion Oral xylitol syrup administered topically two or three times each day at a total dose of 8 g was effective in preventing Early Childhood Caries. PMID:19581542

  10. ClinicalTrials.gov

    MedlinePlus

    ... Health ClinicalTrials.gov is a registry and results database of publicly and privately supported clinical studies of ... This Site ClinicalTrials.gov Background About the Results Database History, Policies, and Laws Media/Press Resources Linking ...

  11. Clinical Trials Infrastructure as a Quality Improvement Intervention in Low- and Middle-Income Countries.

    PubMed

    Denburg, Avram; Rodriguez-Galindo, Carlos; Joffe, Steven

    2016-06-01

    Mounting evidence suggests that participation in clinical trials confers neither advantage nor disadvantage on those enrolled. Narrow focus on the question of a "trial effect," however, distracts from a broader mechanism by which patients may benefit from ongoing clinical research. We hypothesize that the existence of clinical trials infrastructure-the organizational culture, systems, and expertise that develop as a product of sustained participation in cooperative clinical trials research-may function as a quality improvement lever, improving the quality of care and outcomes of all patients within an institution or region independent of their individual participation in trials. We further contend that this "infrastructure effect" can yield particular benefits for patients in low- and middle-income countries (LMICs). The hypothesis of an infrastructure effect as a quality improvement intervention, if correct, justifies enhanced research capacity in LMIC as a pillar of health system development. PMID:27216089

  12. Topical Rapamycin as a Treatment for Fibrofolliculomas in Birt-Hogg-Dubé Syndrome: A Double-Blind Placebo-Controlled Randomized Split-Face Trial

    PubMed Central

    Martens, Herm; Oduber, Charlene E. U.; Henquet, Charles J. M.; Starink, Theo M.; Prins, Martin H.; Menko, Fred H.; Nelemans, Patty J.; van Steensel, Maurice A. M.

    2014-01-01

    Background Birt-Hogg-Dubé syndrome (BHD) is a rare autosomal dominant disorder characterised by the occurrence of benign, mostly facial, skin tumours called fibrofolliculomas, multiple lung cysts, spontaneous pneumothorax and an increased renal cancer risk. Current treatments for fibrofolliculomas have high rates of recurrence and carry a risk of complications. It would be desirable to have a treatment that could prevent fibrofolliculomas from growing. Animal models of BHD have previously shown deregulation of mammalian target of rapamycin (mTOR). Topical use of the mTOR inhibitor rapamycin is an effective treatment for the skin tumours (angiofibromas) in tuberous sclerosis complex, which is also characterised by mTOR deregulation. In this study we aimed to determine if topical rapamycin is also an effective treatment for fibrofolliculomas in BHD. Methods We performed a double blinded, randomised, facial left-right controlled trial of topical rapamycin 0.1% versus placebo in 19 BHD patients. Trial duration was 6 months. The primary outcome was cosmetic improvement as measured by doctors and patients. Changes in fibrofolliculoma number and size were also measured, as was occurrence of side effects. Results No change in cosmetic status of fibrofolliculomas was reported in the majority of cases for the rapamycin treated (79% by doctors, 53% by patients) as well as the placebo treated facial sides (both 74%). No significant differences between rapamycin and placebo treated facial halves were observed (p = 1.000 for doctors opinion, p = 0.344 for patients opinion). No significant difference in fibrofolliculoma number or change in size of the fibrofolliculomas was seen after 6 months. Side effects occurred more often after rapamycin treatment (68% of patients) than after placebo (58% of patients; p = 0.625). A burning sensation, erythema, itching and dryness were most frequently reported. Conclusions This study provides no evidence that treatment of

  13. A randomised placebo-controlled trial of oral and topical antibiotics for children with clinically infected eczema in the community: the ChildRen with Eczema, Antibiotic Management (CREAM) study.

    PubMed Central

    Francis, Nick A; Ridd, Matthew J; Thomas-Jones, Emma; Shepherd, Victoria; Butler, Christopher C; Hood, Kerenza; Huang, Chao; Addison, Katy; Longo, Mirella; Marwick, Charis; Wootton, Mandy; Howe, Robin; Roberts, Amanda; Haq, Mohammed Inaam-Ul; Madhok, Vishnu; Sullivan, Frank

    2016-01-01

    consistent with the finding of no or limited difference and a trend towards worse outcomes in the intervention groups. Sensitivity analyses, including adjusting for compliance and imputation for missing data, were consistent with the main findings. CONCLUSIONS Our data suggest that oral and topical antibiotics have no effect, or a harmful effect, on subjective eczema severity in children with clinically infected eczema in the community. The CIs around our estimates exclude a meaningful beneficial effect (published minimal clinically important difference for POEM is 3.4). Although most patients in this trial had features suggestive of infection and S. aureus on their skin, participants primarily had mild-moderate eczema and those with signs of more severe infection were often excluded. Clinicians should consider avoiding oral and topical antibiotic use in children with suspected infected eczema in the community who do not have signs of 'severe infection'. Further research should seek to understand how best to encourage the use of topical steroids and limit use of antibiotics in those with eczema flares without signs of severe infection, as well as developing tools to better phenotype eczema flares, in order to better define a population that may benefit from antibiotic treatment. TRIAL REGISTRATION European Union Drug Regulating Authorities Clinical Trials (EudraCT) number 2011-003591-37 and Current Controlled Trials ISRCTN96705420. FUNDING The National Institute for Health Research Health Technology Assessment programme. PMID:26938214

  14. How Do Clinical Trials Work?

    MedlinePlus

    ... Trials Clinical Trial Websites How Do Clinical Trials Work? If you take part in a clinical trial, ... kol). This plan explains how the trial will work. The trial is led by a principal investigator ( ...

  15. Clinical trials face heightened scrutiny as science and commerce appear to merge.

    PubMed

    Lorman, Alvin J

    2001-01-01

    Clinical trials involving human subjects face increased scrutiny and regulation by the federal government that may lead to costly changes to the process. Prompted by a highly publicized death in a gene therapy trial, federal regulators are examining almost all aspects of clinical trial conduct, from how patients are recruited and how they give informed consent, to the relationship between the researchers and the company sponsoring the research. In addition to the heightened regulation, the government has announced that it will seek the power to impose civil money penalties on researchers who do not observe applicable patient protection regulations. In an effort to include more senior citizens in clinical trials, the government for the first time will cover certain costs of Medicare beneficiaries who participate in clinical trials. The risk of increased government involvement includes criminal prosecution of physicians for failing to follow the rules, as an innovative case in California demonstrates. PMID:12751494

  16. Research Areas: Clinical Trials

    Cancer.gov

    Information about NCI programs and initiatives that sponsor, conduct, develop, or support clinical trials, including NCI’s Clinical Trial Network (NCTN) and NCI Community Oncology Research Program (NCORP) initiatives.

  17. Research Areas - Clinical Trials

    Cancer.gov

    Information about NCI programs and initiatives that sponsor, conduct, develop, or support clinical trials, including NCI’s Clinical Trial Network (NCTN) and NCI Community Oncology Research Program (NCORP) initiatives.

  18. Topical antioxidants in radiodermatitis: a clinical review.

    PubMed

    Kodiyan, Joyson; Amber, Kyle T

    2015-09-01

    Radiation-induced skin toxicity is the most prevalent side effect of radiation therapy. Not only does it have a significant effect on patients' quality of life, but it also results in poor follow-up and early termination of radiotherapy treatment. Several skin care practices and topical applications have been studied in the field of radiodermatitis, including skin washing, topical steroids, and mechanical skin barriers. Aside from these methods, many patients turn to complementary and alternative medicine for the prevention and treatment of radiodermatitis. Many of these alternative therapies are topically applied antioxidants. While the rationale behind the use of antioxidants in treating radiodermatitis is strong, clinical studies have been far less consistent. Even in large scale randomised controlled trials, findings have been limited by the inconsistent use of topical vehicles and placebos. In this article, the authors review the role of topical antioxidants to better help the practitioner navigate through different available skin directed antioxidants. PMID:26412275

  19. Clinical Trials in Vision Research

    MedlinePlus

    ... Clinical Trials in Vision Research Clinical Trials in Vision Research Clinical studies depend on people who volunteer. ... about the treatment. How are clinical trials in vision different from other clinical trials? Eyes are one ...

  20. Randomized double-blind clinical trial comparing clobetasol and dexamethasone for the topical treatment of symptomatic oral chronic graft-versus-host disease.

    PubMed

    Noce, Cesar W; Gomes, Alessandra; Shcaira, Vanessa; Corrêa, Maria Elvira P; Moreira, Maria Cláudia R; Silva Júnior, Arley; Gonçalves, Lúcio Souza; Garnica, Marcia; Maiolino, Angelo; Torres, Sandra R

    2014-08-01

    Patients who undergo allogeneic stem cell transplantation frequently develop an immunologic disease caused by the reactivation of the graft to the host tissues. This disease is called graft-versus-host disease (GVHD) and it is usually a systemic disorder. In a large proportion of cases, oral disorders that are related to a chronic phase of GVHD (cGVHD) occur, and their treatment involves the use of topical immunosuppressive drugs. Several medications have been studied for this purpose, but only a small number of clinical trials have been published. The present study is a randomized, double-blind clinical trial that compares topical clobetasol and dexamethasone for the treatment of symptomatic oral cGVHD. Patients were randomly assigned to treatment with clobetasol propionate .05% or dexamethasone .1 mg/mL for 28 days. In both arms, nystatin 100,000 IU/mL was administered with the corticosteroid. Oral lesions were evaluated by the modified oral mucositis rating scale (mOMRS) and symptoms were registered using a visual analogue scale. Thirty-five patients were recruited, and 32 patients were randomized into the study groups: 18 patients (56.3%) to the dexamethasone group and 14 patients (43.8%) to the clobetasol group. The use of clobetasol resulted in a significant reduction in mOMRS total score (P = .04) and in the score for ulcers (P = .03). In both groups, there was significant symptomatic improvement but the response was significantly greater in the clobetasol group (P = .02). In conclusion, clobetasol was significantly more effective than dexamethasone for the amelioration of symptoms and clinical aspects of oral lesions in cGVHD. PMID:24727333

  1. Clinical Trials in Noninfectious Uveitis

    PubMed Central

    Kim, Jane S.; Knickelbein, Jared E.; Nussenblatt, Robert B.; Sen, H. Nida

    2015-01-01

    The treatment of noninfectious uveitis continues to remain a challenge for many ophthalmologists. Historically, clinical trials in uveitis have been sparse, and thus, most treatment decisions have largely been based on clinical experience and consensus guidelines. The current treatment paradigm favors initiation then tapering of corticosteroids with addition of steroid-sparing immunosuppressive agents for persistence or recurrence of disease. Unfortunately, in spite of a multitude of highly unfavorable systemic effects, corticosteroids are still regarded as the mainstay of treatment for many patients with chronic and refractory noninfectious uveitis. However, with the success of other conventional and biologic immunomodulatory agents in treating systemic inflammatory and autoimmune conditions, interest in targeted treatment strategies for uveitis has been renewed. Multiple clinical trials on steroid-sparing immunosuppressive agents, biologic agents, intraocular corticosteroid implants, and topical ophthalmic solutions have already been completed, and many more are ongoing. This review discusses the results and implications of these clinical trials investigating both alternative and novel treatment options for noninfectious uveitis. PMID:26035763

  2. [Role of the state as regulatory authority of clinical trials in Peru].

    PubMed

    Fuentes, Duilio; Minaya, Gabriela; Ayala-Quintanilla, Beatriz

    2012-01-01

    This article sheds the light on historical review of the clinical trials regulatory process to the publication of the Clinical Trials Regulation in Peru, by Supreme Decree 017-2006-SA. In this context, that Regulation was amended within one year, with many critics including from the Ombudsman. It also considers the achievements as a regulatory authority that has strengthened its steering and its main objective of protecting the rights, safety and welfare of human subjects in clinical trials. Those achievements are: the internal register of clinical trials, strengthening inspections on all stakeholders that take part in research, the Notification System of Serious Adverse Events (REAS-NET), the publication of the Guideline: "Ethical, Legal and methodology in clinical trials for use of the Ethical Review Board" which won an international award; the 1st prize in the category of fizcalization and accomplishment of the law by the Good Practice of Public Management: "Protecting the rights of human subjects in experimental studies", the publication of the new Manual of Procedures for Clinical Trials and the implementation Plan of the National Bioethics Network in Peru. PMID:23338638

  3. Comparison of clinical outcomes, patient, and surgeon satisfaction following topical versus peribulbar anesthesia for phacoemulsification and intraocular lens implantation: A randomized, controlled trial

    PubMed Central

    Dole, Kuldeep; Kulkarni, Sucheta; Shisode, Kavita D; Deshpande, Rahul; Kakade, Nilesh; Khandekar, Rajiv; Deshpande, Madan

    2014-01-01

    Background: Both cataract surgery and anesthesia techniques are rapidly evolving to become more patient friendly. However, comparison of topical anesthesia (TA) and peribulbar anesthesia (PA) for phacoemulsification and cataract surgery is limited. We evaluated the clinical outcomes and patient and surgeon satisfaction between anesthetic techniques. Materials and Methods: This randomized clinical trial was conducted between January and June 2012. Patients were randomly assigned to TA and PA groups for surgery. Visual acuity at 4 weeks postoperatively, status of the cornea and the wound and intraoperative complications were compared between groups at day 1, and 1 and 4 weeks after surgery. Patients and the surgeon completed a close-ended questionnaire on satisfaction with analgesia and comfort. The relative risk (RR) with 95% confidence intervals (CI) was calculated. Result: There were 500 patients in each group. There were no significant differences between groups preoperatively. Complications at 1-day postoperatively were significantly greater in the TA group (RR = 1.36, 95% CI: 1.17–1.58). Satisfaction with the mitigation of pain was statistically significantly greater in the PA group compared to the TA group (χ2 = 10.9, df = 3, P = 0.001). Surgeons were more satisfied with PA compared to TA (RR = 1.4, 95% CI: 1.34–1.63). There were more anesthesia-related complications in the PA group compared to the TA group. Conclusions: Patients who underwent surgery with topical anesthetic experienced lower complications by more pain compared to patients who underwent PA. Topical anesthetic supplemented with analgesic medications could help the patient and surgeon during cataract surgery. PMID:25370394

  4. Hepatitis C: Clinical Trials

    MedlinePlus

    ... and Public Home » Hepatitis C » Treatment Decisions Viral Hepatitis Menu Menu Viral Hepatitis Viral Hepatitis Home For ... can I find out about participating in a hepatitis C clinical trial? Many trials are being conducted ...

  5. Managing clinical trials.

    PubMed

    Farrell, Barbara; Kenyon, Sara; Shakur, Haleema

    2010-01-01

    Managing clinical trials, of whatever size and complexity, requires efficient trial management. Trials fail because tried and tested systems handed down through apprenticeships have not been documented, evaluated or published to guide new trialists starting out in this important field. For the past three decades, trialists have invented and reinvented the trial management wheel. We suggest that to improve the successful, timely delivery of important clinical trials for patient benefit, it is time to produce standard trial management guidelines and develop robust methods of evaluation. PMID:20626885

  6. A double-blind controlled clinical trial assessing the effect of topical gels on striae distensae (stretch marks): a non-invasive imaging, morphological and immunohistochemical study.

    PubMed

    Ud-Din, Sara; McAnelly, Sarah-Louise; Bowring, Alison; Whiteside, Sigrid; Morris, Julie; Chaudhry, Iskander; Bayat, Ardeshir

    2013-09-01

    Striae distensae (SD) are cutaneous lesions often presenting post-pregnancy with atrophy and flattening of the epidermis. SD is poorly understood and treatment remains ill-defined. Our aim was to assess the effect of topical application of silicone gel compared with placebo on SD using non-invasive devices and by immunohistochemical analysis of sequential tissue biopsies in a double-blind controlled trial. Twenty volunteers massaged silicone and placebo gels into separate sides of the abdomen, daily for 6 weeks. Objective non-invasive imaging plus subjective self-assessment of SD were performed on days 0, 21, 42, 90, in addition to tissue biopsies on days 0 and 42. Non-invasive imaging demonstrated an increase in melanin and a decrease in haemoglobin, collagen and pliability over the 6-week period on both sides. Additionally, collagen levels in SD were significantly higher (p value = 0.001) and melanin levels lower (p value = 0.048) with silicone gel compared with placebo. Histological analysis revealed epidermal flattening with a reduction of rete ridges in SD on both sides. Vascular count significantly decreased with placebo gel (p = 0.002). Corroborating the clinical results, melanin levels increased, whilst collagen type 1 and elastin decreased on both sides. Non-invasive techniques showed that the application of silicone gel increased collagen levels and reduced pigmentation compared with placebo. However, both clinical and histological data revealed that melanin increased whilst collagen, elastin and pliability decreased over the 6-week period with both gels. Furthermore, vascularity significantly decreased with placebo gel. These findings provide preliminary evidence of the utility of topical gels in the clinical management of SD. PMID:23579949

  7. [Critical reading of clinical trials].

    PubMed

    Aptel, F; Cucherat, M; Blumen-Ohana, E; Denis, P

    2011-12-01

    Clinical trials are playing an increasingly crucial role in modern evidence based medicine, allowing for rigorous scientific evaluation of treatment strategies and validation of patient care. The results of clinical trials often form the rational basis from which physicians draw information used to adapt their therapeutic practices. Critical reading and analysis of trials involves the assessment of whether the available data provide enough credible evidence that the treatment will result in a clinically significant and relevant improvement. Evaluating the quality of a clinical trial is a process that draws upon sometimes complex methodological and statistical concepts, with which the reader should nonetheless be familiar in order to come to impartial conclusions regarding the raw data presented in the clinical trials. The goal of the current article is to review the methodological and statistical concepts required for the design and interpretation of clinical trials, so as to allow for a critical analysis of publications or presentations of clinical trials. The first section describes the major methodological principles of clinical trial design required for a rigorous evaluation of the treatment benefit, as well as the various pitfalls or biases that could lead to erroneous conclusions. The second section briefly describes the main statistical tests used in clinical trials, as well as certain situations that may increase the risk of false positive findings (type 1 error), such as multiple, subgroup, intermediate and non-inferiority analysis. PMID:21992992

  8. Exploratory clinical trial to evaluate the efficacy of a topical traditional chinese herbal medicine in psoriasis vulgaris.

    PubMed

    Yan, Yuhe; Liu, Wali; Andres, Philippe; Pernin, Colette; Chantalat, Laurent; Briantais, Philippe; Lin, Albert; Feng, Lilian

    2015-01-01

    Objective. To evaluate the efficacy and safety of herbal ointment, Shi Du Ruan Gao, in patients with plaque-type psoriasis. Design. Single-center, randomized, investigator-blinded, parallel group, placebo-controlled study. Participants. One hundred outpatients with mild to moderate chronic plaque-type psoriasis were enrolled. Intervention. The patients applied either Shi Du Ruan Gao ointment or vehicle ointment topically to for 8 weeks. Main Outcome Measures. The outcomes were assessed using the following criteria: Total Severity Score (TSS, sum of erythema, scaling, and plaque elevation/induration, on a 0 to 4 scale), Investigator Global Assessment (IGA) evaluated on a 0 (Clear) to 4 (s to very severe) scale, and Global Subjects' Assessment of treatment response on a 7-point scale from -1 (worse) to 5 (Cleared). Results. Significant reductions in the Total Severity Score (P < 0.001) (mean score: 2.7 after Shi Du Ruan Gao treatment versus 5.1 in control subjects). Both Investigator Global Assessment (IGA) and Global Subjects' Assessment of treatment are better in the Shi Du Ruan Gao group than the control group (P < 0.001). Conclusion. Shi Du Ruan Gao ointment was a safe, and effective therapy for plaque-type psoriasis. PMID:25834623

  9. Exploratory Clinical Trial to Evaluate the Efficacy of a Topical Traditional Chinese Herbal Medicine in Psoriasis Vulgaris

    PubMed Central

    Yan, Yuhe; Liu, Wali; Andres, Philippe; Pernin, Colette; Chantalat, Laurent; Briantais, Philippe; Lin, Albert; Feng, Lilian

    2015-01-01

    Objective. To evaluate the efficacy and safety of herbal ointment, Shi Du Ruan Gao, in patients with plaque-type psoriasis. Design. Single-center, randomized, investigator-blinded, parallel group, placebo-controlled study. Participants. One hundred outpatients with mild to moderate chronic plaque-type psoriasis were enrolled. Intervention. The patients applied either Shi Du Ruan Gao ointment or vehicle ointment topically to for 8 weeks. Main Outcome Measures. The outcomes were assessed using the following criteria: Total Severity Score (TSS, sum of erythema, scaling, and plaque elevation/induration, on a 0 to 4 scale), Investigator Global Assessment (IGA) evaluated on a 0 (Clear) to 4 (s to very severe) scale, and Global Subjects' Assessment of treatment response on a 7-point scale from −1 (worse) to 5 (Cleared). Results. Significant reductions in the Total Severity Score (P < 0.001) (mean score: 2.7 after Shi Du Ruan Gao treatment versus 5.1 in control subjects). Both Investigator Global Assessment (IGA) and Global Subjects' Assessment of treatment are better in the Shi Du Ruan Gao group than the control group (P < 0.001). Conclusion. Shi Du Ruan Gao ointment was a safe, and effective therapy for plaque-type psoriasis. PMID:25834623

  10. Birth Control in Clinical Trials

    PubMed Central

    Stewart, J.; Beyer, B. K.; Chadwick, K.; De Schaepdrijver, L.; Desai, M.; Enright, B.; Foster, W.; Hui, J. Y.; Moffat, G. J.; Tornesi, B.; Van Malderen, K.; Wiesner, L.; Chen, C. L.

    2015-01-01

    The Health and Environmental Sciences Institute (HESI) Developmental and Reproductive Toxicology Technical Committee sponsored a pharmaceutical industry survey on current industry practices for contraception use during clinical trials. The objectives of the survey were to improve our understanding of the current industry practices for contraception requirements in clinical trials, the governance processes set up to promote consistency and/or compliance with contraception requirements, and the effectiveness of current contraception practices in preventing pregnancies during clinical trials. Opportunities for improvements in current practices were also considered. The survey results from 12 pharmaceutical companies identified significant variability among companies with regard to contraception practices and governance during clinical trials. This variability was due primarily to differences in definitions, areas of scientific uncertainty or misunderstanding, and differences in company approaches to enrollment in clinical trials. The survey also revealed that few companies collected data in a manner that would allow a retrospective understanding of the reasons for failure of birth control during clinical trials. In this article, suggestions are made for topics where regulatory guidance or scientific publications could facilitate best practice. These include provisions for a pragmatic definition of women of childbearing potential, guidance on how animal data can influence the requirements for male and female birth control, evidence-based guidance on birth control and pregnancy testing regimes suitable for low- and high-risk situations, plus practical methods to ascertain the risk of drug-drug interactions with hormonal contraceptives. PMID:27042398

  11. A comparative study of toluidine blue-mediated photodynamic therapy versus topical corticosteroids in the treatment of erosive-atrophic oral lichen planus: a randomized clinical controlled trial.

    PubMed

    Jajarm, Hasan Hoseinpour; Falaki, Farnaz; Sanatkhani, Majid; Ahmadzadeh, Meysam; Ahrari, Farzaneh; Shafaee, Hooman

    2015-07-01

    Recently, photodynamic therapy (PDT) has been suggested as a new treatment option that is free from side effects for erosive-atrophic oral lichen planus (OLP). The purpose of this study was to compare the effect of toluidine blue-mediated photodynamic therapy (TB-PDT) with local corticosteroids on treatment of erosive-atrophic OLP. In this randomized clinical trial, 25 patients with keratotic-atrophic-erosive oral lichen planus were allocated randomly into two groups. Group 1 (experimental): topical application of toluidine blue with micropipette was applied, and after 10 min, the patients were treated with a 630-nm GaAlAs laser (power density: 10 mW/cm(2)) during two visits. Group 2 (control) used mouthwash diluted with dexamethasone (tab 0/5 in 5 ml water) for 5 min, and then, it was spat out, and after 30 min, the mouth was rinsed with 30 drops of nystatin 100,000 units for 5 min and again spat out. Demographic data, type, and severity of the lesions and pain were recorded before and after treatment and then at the 1-month follow-up visit. Response rate was defined based on changes in intensity of the lesions and pain. In the experimental and control groups, sign scores of changes significantly reduced after treatment respectively (p = 0.021) and (p = 0.002), but between the two groups, no significant difference was observed (p = 0.72). In the experimental (p = 0.005) and control groups (p = 0.001), the intensity of lesions significantly reduced after treatment and there was a significant difference between the two groups (p = 0.001). The mean amount of improvement in pain was significantly greater in the control group compared with the experimental group (p < 0.001) (α = 0.05). Our study showed that TB-PDT with laser was effective in the management of OLP. PMID:25487185

  12. CLINICAL TRIALS.GOV

    EPA Science Inventory

    ClinicalTrials.gov provides patients, family members, health care professionals, and members of the public easy access to information on clinical trials for a wide range of diseases and conditions. The U.S. National Institutes of Health (NIH), through its National Library of Medi...

  13. The clinical trial research participant as an inside trader: a legal and policy analysis.

    PubMed

    Horwich, Allan

    2006-01-01

    This Article examines whether a participant in a clinical research trial for a drug obtains material nonpublic information about the drug and its manufacturer or licensor and, if so, whether the participant may lawfully trade securities based on that information. This issue has been noted but not examined in depth in several articles in recent years. After an introduction to the federal law of insider trading and a discussion of relevant aspects of a supervised research trial, the Article concludes that, absent an agreement to the contrary, the participant would be free to trade securities based on any material nonpublic information learned in the trial. The author evaluates the extent to which the information is material and nonpublic and then presents the policy issues surrounding whetherthe participantshould be precluded from trading when in possession of material nonpublic information gained as a result of participation in the trial. While not resolving the competing policy considerations, including the value of allowing participants to make disclosure of their experiences in the trial before publication of the results in a peer reviewed journal, the Article presents an approach for preventing the misuse of material nonpublic information gained in the clinical trial context, by obtaining an agreement from the participant, and an agreement from the limited circle of persons to whom the participant should be allowed to make disclosure in any event (such as his personal physician and family members), that would render any trading by them unlawful under the federal law of insider trading. PMID:16761384

  14. [Analysis on the requirements for clinical trial protocol writing of external treatment of TCM such as tuina].

    PubMed

    Gao, Shuang; Wang, Jingui; Wang, Hui

    2015-06-01

    According to Standard Protocol Items: Recommendations for Interventional Trials, Consolidated Standard of Reporting Trials 2010 Statement (CONSORT), CONSORT Extension for Non-Pharmacologic Treatment Interventions (CONSORT for NPT) and Good Clinical Practice, the detailed requirements for protocol writing, reporting, and practicing of clinical trial were classified and summarized in this article. By combining the practical situation of clinical trial of external treatment of TCM such as tuina, the requirernents for clinical trial protocol writing of external treatment of TCM were analyzed and acquired which could improve the quality of clinical trial protocol of external treatment of TCM, thus to provide references for standardized execution of TMC clinical trial and reports of research results. PMID:26480571

  15. Gateways to clinical trials.

    PubMed

    Bayes, M; Rabasseda, X; Prous, J R

    2006-06-01

    Gateways to Clinical Trials are a guide to the most recent clinical trials in current literature and congresses. The data in the following tables have been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: 131-I-chlorotoxin; Ad5CMV-p53, adalimumab, albumin interferon alfa, alemtuzumab, aliskiren fumarate, aminolevulinic acid methyl ester, anakinra, AR-C126532, atomoxetine hydrochloride; Bevacizumab, bosentan, botulinum toxin type B, brimonidine tartrate/timolol maleate; Calcipotriol/betamethasone dipropionate, cangrelor tetrasodium, cetuximab, ciclesonide, cinacalcet hydrochloride, collagen-PVP, Cypher; Darbepoetin alfa, darusentan, dasatinib, denosumab, desloratadine, dexosome vaccine (lung cancer), dexrazoxane, dextromethorphan/quinidine sulfate, duloxetine hydrochloride; ED-71, eel calcitonin, efalizumab, entecavir, etoricoxib; Falciparum merozoite protein-1/AS02A, fenretinide, fondaparinux sodium; gamma-Hydroxybutyrate sodium, gefitinib, ghrelin (human); hLM609; Icatibant acetate, imatinib mesylate, ipsapirone, irofulven; LBH-589, LE-AON, levocetirizine, LY-450139; Malaria vaccine, mapatumumab, motexafin gadolinium, muraglitazar, mycophenolic acid sodium salt; nab-paclitaxel, nelarabine; O6-Benzylguanine, olmesartan medoxomil, orbofiban acetate; Panitumumab, peginterferon alfa-2a, peginterferon alfa-2b, pemetrexed disodium, peptide YY3-36, pleconaril, prasterone, pregabalin; Ranolazine, rebimastat, recombinant malaria vaccine, rosuvastatin calcium; SQN-400; Taxus, tegaserod maleate, tenofovir disoproxil fumarate, teriparatide, troxacitabine; Valganciclovir hydrochloride, Val-Tyr sardine peptidase, VNP-40101M, vorinostat. PMID:16845450

  16. Post-use assay of vaginal rings (VRs) as a potential measure of clinical trial adherence.

    PubMed

    Spence, Patrick; Nel, Annalene; van Niekerk, Neliëtte; Derrick, Tiffany; Wilder, Susan; Devlin, Bríd

    2016-06-01

    Adherence measurement for microbicide use within the clinical trial setting remains a challenge for the HIV prevention field. This paper describes an assay method used for determining residual dapivirine levels in post-use vaginal rings from clinical trials conducted with the Dapivirine Vaginal Matrix Ring-004 developed by the International Partnership for Microbicides to prevent male to female HIV transmission. Post-use assay results from three Ring-004 clinical trials showed that of the 25mg drug load, approximately 4mg of dapivirine is released from the matrix ring over a 28-day use period. Data obtained by both in vitro and in vivo studies indicate that dapivirine is released according to a diffusion mechanism, as determined by conformance of both data sets to the Higuchi equation. This, coupled with the low variability associated with batch production over two manufacturing sites and 20 batches of material, provides evidence that post-use ring analysis can contribute to the assessment of adherence to ring use. Limitations of this method include the potential of intra-participant and inter-participant variability and uncertainty associated with measuring the low amount of dapivirine actually released relative to the drug load. Therefore, residual drug levels should not serve as the only direct measurement for microbicide adherence in vaginal ring clinical trials but should preferably be used as part of a multi-pronged approach towards understanding and assessing adherence to vaginal ring use. PMID:27016673

  17. Randomized clinical trials as reflexive-interpretative process in patients with rheumatoid arthritis: a qualitative study.

    PubMed

    de Jorge, Mercedes; Parra, Sonia; de la Torre-Aboki, Jenny; Herrero-Beaumont, Gabriel

    2015-08-01

    Patients in randomized clinical trials have to adapt themselves to a restricted language to capture the necessary information to determine the safety and efficacy of a new treatment. The aim of this study was to explore the experience of patients with rheumatoid arthritis after completing their participation in a biologic therapy randomized clinical trial for a period of 3 years. A qualitative approach was used. The information was collected using 15 semi-structured interviews of patients with rheumatoid arthritis. Data collection was guided by the emergent analysis until no more relevant variations in the categories were found. The data were analysed using the grounded theory method. The objective of the patients when entering the study was to improve their quality of life by initiating the treatment. However, the experience changed the significance of the illness as they acquired skills and practical knowledge related to the management of their disease. The category "Interactional Empowerment" emerged as core category, as it represented the participative experience in a clinical trial. The process integrates the follow categories: "weight of systematisation", "working together", and the significance of the experience: "the duties". Simultaneously these categories evolved. The clinical trial monitoring activities enabled patients to engage in a reflexive-interpretative mechanism that transformed the emotional and symbolic significance of their disease and improved the empowerment of the patient. A better communicative strategy with the health professionals, the relatives of the patients, and the community was also achieved. PMID:25636236

  18. Effect of Topical Application of the Cream Containing Magnesium 2% on Treatment of Diaper Dermatitis and Diaper Rash in Children A Clinical Trial Study

    PubMed Central

    Nourbakhsh, Seyyed Mohammad-Kazem; Rouhi-Boroujeni, Hojjatollah; Kheiri, Maryam; Mobasheri, Mahmoud; Shirani, Majid; Ahrani, Saeedeh; Karami, Javad

    2016-01-01

    Introduction Diaper dermatitis is referred to the inflammation in outer layers of the skin in the perineal area, lower abdomen, and inner thighs. The lesions are maculopapular and usually itchy, which could cause bacterial or candida infection, and predispose the infants to penis or vaginal and urinary infection and lead to discomfort, irritability, and restlessness. The drugs which have been so far administered for this disease (topical steroids) cause special complications for the sensitive skin in this area. Magnesium (Mg) is known for its anti-inflammatory and wound-healing properties. Aim The aim of the present study was to study the effect of the cream containing Mg 2% on treatment of diaper dermatitis and diaper rash in children. Materials and Methods In this clinical trial study, 64 children aged less than two years old with diaper dermatitis referring Paediatric Ward of Hajar Hospital were randomly assigned to two groups of 32. Group one was treated with the combined cream Mg 2% and Calendula and group two with Calendula cream alone. The duration of recovery was compared between the two groups. Results The duration of recovery was significantly lower in the intervention group than the control group (p-value<0.001), but there was no significant difference in the lesions size and diapers’ number between the two groups. Conclusion Based on the finding of this study, Mg is effective on treatment of diaper dermatitis and could be used for treating diaper dermatitis and other types of dermatitis. PMID:26894161

  19. Phase II trial of panitumumab with irinotecan as salvage therapy for patients with advanced or recurrent colorectal cancer (TOPIC study)

    PubMed Central

    NISHI, TOMOHIRO; HAMAMOTO, YASUO; NAGASE, MICHITAKA; DENDA, TADAMICHI; YAMAGUCHI, KENSEI; AMAGAI, KENJI; MIYATA, YOSHINORI; YAMANAKA, YASUHIRO; YANAI, KAI; ISHIKAWA, TSUTOMU; KUROKI, YOSHIFUMI; FUJII, HIROFUMI

    2016-01-01

    Little is known about the clinical impact of salvage panitumumab with irinotecan for metastatic colorectal cancer (mCRC) patients. The present study conducted a single-arm, multicenter phase II trial for mCRC with skin toxicity prevention program. The subjects were mCRC patients with wild-type KRAS, who showed resistance to fluoropyrimidine, oxaliplatin and irinotecan. Panitumumab was administered at a dose of 6 mg/kg every 2 weeks by intravenous infusion over 60 min, and irinotecan was administered at a dose of 100–180 mg/m2 every 2 weeks by intravenous infusion over 90 min, depending on the preceding treatment dose. To prevent skin toxicities, a moisturizer was applied and oral antibiotics (100 mg minocycline twice daily) were initiated for 6 weeks. The primary endpoint was the response rate (RR) determined by independent reviewers. Secondary endpoints were the disease control rate (DCR), progression-free survival (PFS) time, overall survival (OS) time and adverse events. A total of 35 patients were enrolled between October 2010 and March 2012. The median age was 61 years (range, 41–76 years), with 25 male and 10 female patients. The initial irinotecan dose was 150 mg/m2 in 19 patients and 180 mg/m2 in 1 patient. The remaining patients were treated with ≤120 mg/m2. A central review indicated a partial response in 8 patients (22.9%) and stable disease in 6 patients (17.1%), with an RR of 22.9% (95% confidence interval, 12.1–39.0) and a DCR of 40%. The RR of the patients with standard-dose irinotecan (150 or 180 mg/m2) was 30%, although that of low-dose irinotecan (100–120 mg/m2) was 13%. The median PFS time was 2.7 months, and the median OS time was 6.3 months. A grade 3 or above acne-like rash developed in 25.7% of patients. In conclusion, panitumumab and irinotecan as salvage therapy for mCRC KRAS wild-type patients with skin toxicity prevention exhibits limited efficacy. In particular, the effect of low-dose irinotecan with panitumumab appears to be

  20. AIDS Clinical Trials Group Network

    MedlinePlus

    ... Center Statistical and Data Management Center Glossaries Sites Clinical Trials About the Trial Process Trials Open to Enrollment Recent Study Results Access to Published Data Clinical Trials Resources Committees Executive Scientific Resource Community General Information ...

  1. Developing clinical trials for biosimilars.

    PubMed

    Bui, Lynne A; Taylor, Carrie

    2014-02-01

    Biosimilars offer the prospect of providing efficacious and safe treatment options for many diseases, including cancer, while potentially increasing accessibility with greater affordability relative to biologics. Because biologics are large, complex molecules that cannot be exactly duplicated, biosimilars cannot be considered "generic" versions of biologic drugs. This review will examine important considerations for biosimilar clinical trials. Since the aim of biosimilar manufacturing is to produce a molecule highly similar to the reference biologic, a comparability exercise is needed to demonstrate similarity with the reference biologic product based on physicochemical characterization. In vitro analytical studies and in vivo studies as well as pharmacokinetic/pharmacodynamic (PK/PD) assessments also are conducted. Lastly, because it may not be possible to fully characterize a biosimilar in relation to its reference biologic, robust pharmacovigilance strategies are utilized to ensure that any matters in regard to safety can be monitored. Other key topics will be discussed, including regulatory guidance for the evaluation of biosimilars, clinical trial design considerations, and whether data submitted for the approval of a biosimilar for one indication can be extrapolated to other indications for which the reference biologic is approved. European and Canadian experiences in biosimilar development will be reviewed. PMID:24560024

  2. Comparing community and specialty provider-based recruitment in a randomized clinical trial: clinical trial in fecal incontinence

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Recruitment of participants to clinical trials remains a significant challenge, especially for research addressing topics of a sensitive nature such as fecal incontinence (FI). The Fiber Study, a randomized controlled trial on symptom management for FI, successfully enrolled 189 community-living adu...

  3. Chocolate as a cough suppressant: rationale and justification for an upcoming clinical trial.

    PubMed

    Halfdanarson, Thorvardur R; Jatoi, Aminah

    2007-01-01

    Cough is a troubling symptom for many patients with cancer. Current cough suppressants can cause side effects and, at the same time, might not provide absolute cough palliation. Suprisingly, accumulating evience suggests that dark chocolate can carry antitussive effects. Although mechanisms remain unknown, it is thought that theobromine, a methylxanthine intrinsic to dark chocolate, might potentially suppress cough. To date, clinical trials with dark chocolate have not been undertaken. This article describes an upcoming trial to determine whether dark chocolate might serve as an antitussive in patients with cancer. PMID:18632476

  4. Clinical Trials - Participants

    MedlinePlus

    ... participating in was reviewed by an IRB. Further Reading For more information about research protections, see: Office ... data and decide whether the results have medical importance. Results from clinical trials are often published in ...

  5. Participating in Clinical Trials

    MedlinePlus Videos and Cool Tools

    ... experimental drug, therapy, medical device, lifestyle change, or test will help treat, find, or prevent a disease. A clinical trial may compare experimental products or tests to those already available or may compare existing ...

  6. Evidence and Clinical Trials.

    NASA Astrophysics Data System (ADS)

    Goodman, Steven N.

    1989-11-01

    This dissertation explores the use of a mathematical measure of statistical evidence, the log likelihood ratio, in clinical trials. The methods and thinking behind the use of an evidential measure are contrasted with traditional methods of analyzing data, which depend primarily on a p-value as an estimate of the statistical strength of an observed data pattern. It is contended that neither the behavioral dictates of Neyman-Pearson hypothesis testing methods, nor the coherency dictates of Bayesian methods are realistic models on which to base inference. The use of the likelihood alone is applied to four aspects of trial design or conduct: the calculation of sample size, the monitoring of data, testing for the equivalence of two treatments, and meta-analysis--the combining of results from different trials. Finally, a more general model of statistical inference, using belief functions, is used to see if it is possible to separate the assessment of evidence from our background knowledge. It is shown that traditional and Bayesian methods can be modeled as two ends of a continuum of structured background knowledge, methods which summarize evidence at the point of maximum likelihood assuming no structure, and Bayesian methods assuming complete knowledge. Both schools are seen to be missing a concept of ignorance- -uncommitted belief. This concept provides the key to understanding the problem of sampling to a foregone conclusion and the role of frequency properties in statistical inference. The conclusion is that statistical evidence cannot be defined independently of background knowledge, and that frequency properties of an estimator are an indirect measure of uncommitted belief. Several likelihood summaries need to be used in clinical trials, with the quantitative disparity between summaries being an indirect measure of our ignorance. This conclusion is linked with parallel ideas in the philosophy of science and cognitive psychology.

  7. Justification for conducting neurological clinical trials as part of patient care within private practice.

    PubMed

    Beran, R G; Stepanova, D; Beran, M E

    2016-05-01

    The aim of this review was to assess the benefits and drawbacks of conducting neurological clinical trials and research in private practice for the patients, clinician, Practice Manager, sponsors/Clinical Research Organisations (CROs) and Clinical Trial Coordinator (CTC) to determine if this is justified for all involved. A combination of literature reviews, original research articles and books were selected from 2005 to 2015. Provided that the practice has sufficient number of active trials to prevent financial loss, support staff, adequate facilities and equipment and time, the benefits outweigh the drawbacks. Clinical trials provide patients with more thorough monitoring, re-imbursement of trial-related expenses and the opportunity to try an innovative treatment at no charge when other options have failed. For the clinician, clinical trials provide more information to ensure better care for their patients and improved treatment methods, technical experience and global recognition. Trials collect detailed and up-to-date information on the benefits and risks of drugs, improving society's confidence in clinical research and pharmaceuticals, allow trial sponsors to explore new scientific questions and accelerate innovation. For the CTC, industry-sponsored clinical trials allow potential entry for a career in clinical research giving CTCs the opportunity to become Clinical Research Associates (CRAs), Study Start-Up Managers or Drug Safety Associates. PMID:27040457

  8. Gateways to clinical trials.

    PubMed

    Moral, M A; Tomillero, A

    2008-03-01

    Gateways to Clinical Trials are a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: 131-I-Chlorotoxin, 423557; Abatacept, Ad.Egr.TNF.11D, Adalimumab, AE-941, Ambrisentan, AMR-001, Anacetrapib, Anakinra, Aripiprazole, Atazanavir sulfate; BAY-639044, Bazedoxifene acetate, Belimumab, Bevacizumab, Bortezomib, Botulinum toxin type B, Brivaracetam, Bucindolol hydrochloride; Carfilzomib, Carisbamate, CCX-282, CD20Bi, Ceftobiprole, Certolizumab pegol, CF-101, Cinacalcet hydrochloride, Cypher; Darifenacin hydrobromide, Degarelix acetate, Denosumab, Desvenlafaxine succinate, Dexlansoprazole, Dexverapamil, Drotrecogin alfa (activated), Duloxetine hydrochloride, Dutasteride; Efalizumab, EPs-7630, Escitalopram oxalate, Etoricoxib; Fluticasone furoate, Fondaparinux sodium, Fospropofol disodium; Hexadecyloxypropyl-cidofovir, HIV gp120/NefTat/AS02A, HPV-6/11/16/18; INCB-18424, Incyclinide, Inhalable human insulin, Insulin detemir; KNS-760704, KW-0761; Lacosamide, Lenalidomide, Levetiracetam, Licofelone, Lidocaine/prilocaine; mAb 216, MEDI-528, Men ACWY, Meningococcal C-CRM197 vaccine, Methylnaltrexone bromide; Nemifitide ditriflutate, Nicotine conjugate vaccine, Nilotinib hydrochloride monohydrate; Octaparin; Parathyroid hormone (human recombinant), Pegaptanib octasodium, Pitrakinra, Prasterone, Pregabalin; Ranelic acid distrontium salt, Rasagiline mesilate, Retigabine, Rimonabant, RTS,S/AS02D; Sarcosine, Sitaxentan sodium, Solifenacin succinate, Sunitinib malate; Taranabant, Taxus, Teduglutide, Teriparatide, Ticagrelor, Travoprost, TRU-015; USlipristal acetate, Urocortin 2; Vardenafil hydrochloride hydrate; YM-155, Yttrium 90 (90Y) ibritumomab tiuxetan; Zanolimumab, Zoledronic acid monohydrate, Zotarolimus

  9. Shuffling Adaptive Clinical Trials.

    PubMed

    Gokhale, Sanjay G; Gokhale, Sankalp

    2016-01-01

    Clinical trials are interventional studies on human beings, designed to test the hypothesis for diagnostic techniques, treatments, and disease preventions. Any novel medical technology should be evaluated for its efficacy and safety by clinical trials. The costs associated with developing drugs have increased dramatically over the past decade, and fewer drugs are obtaining regulatory approval. Because of this, the pharmaceutical industry is continually exploring new ways of improving drug developments, and one area of focus is adaptive clinical trial designs. Adaptive designs, which allow for some types of prospectively planned mid-study changes, can improve the efficiency of a trial and maximize the chance of success without undermining validity and integrity of the trial. However it is felt that in adaptive trials; perhaps by using accrued data the actual patient population after the adaptations could deviate from the originally target patient population and so to overcome this drawback; special methods like Bayesian Statistics, predicted probability are used to deduce data-analysis. Here, in this study, mathematical model of a new adaptive design (shuffling adaptive trial) is suggested which uses real-time data, and because there is no gap between expected and observed data, statistical modifications are not needed. Results are obviously clinically relevant. PMID:23751329

  10. Gateways to clinical trials.

    PubMed

    Bayés, M; Rabasseda, X; Prous, J R

    2007-12-01

    Gateways to Clinical Trials are a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Trials Knowledge Area of Prous Science Intergrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: 249553, 2-Methoxyestradiol; Abatacept, Adalimumab, Adefovir dipivoxil, Agalsidase beta, Albinterferon alfa-2b, Aliskiren fumarate, Alovudine, Amdoxovir, Amlodipine besylate/atorvastatin calcium, Amrubicin hydrochloride, Anakinra, AQ-13, Aripiprazole, AS-1404, Asoprisnil, Atacicept, Atrasentan; Belimumab, Bevacizumab, Bortezomib, Bosentan, Botulinum toxin type B, Brivaracetam; Catumaxomab, Cediranib, Cetuximab, cG250, Ciclesonide, Cinacalcet hydrochloride, Curcumin, Cypher; Darbepoetin alfa, Denosumab, Dihydrexidine; Eicosapentaenoic acid/docosahexaenoic acid, Entecavir, Erlotinib hydrochloride, Escitalopram oxalate, Etoricoxib, Everolimus, Ezetimibe; Febuxostat, Fenspiride hydrochloride, Fondaparinux sodium; Gefitinib, Ghrelin (human), GSK-1562902A; HSV-tk/GCV; Iclaprim, Imatinib mesylate, Imexon, Indacaterol, Insulinotropin, ISIS-112989; L-Alanosine, Lapatinib ditosylate, Laropiprant; Methoxy polyethylene glycol-epoetin-beta, Mipomersen sodium, Motexafin gadolinium; Natalizumab, Nimotuzumab; OSC, Ozarelix; PACAP-38, Paclitaxel nanoparticles, Parathyroid Hormone-Related Protein-(1-36), Pasireotide, Pegfilgrastim, Peginterferon alfa-2a, Peginterferon alfa-2b, Pemetrexed disodium, Pertuzumab, Picoplatin, Pimecrolimus, Pitavastatin calcium, Plitidepsin; Ranelic acid distrontium salt, Ranolazine, Recombinant human relaxin H2, Regadenoson, RFB4(dsFv)-PE38, RO-3300074, Rosuvastatin calcium; SIR-Spheres, Solifenacin succinate, Sorafenib, Sunitinib malate; Tadalafil, Talabostat, Taribavirin hydrochloride, Taxus, Temsirolimus, Teriparatide, Tiotropium bromide, Tipifarnib, Tirapazamine, Tocilizumab; UCN-01, Ularitide

  11. Gateways to clinical trials.

    PubMed

    Tomillero, A; Moral, M A

    2010-11-01

    Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Trials Knowledge Area of Thomson Reuters Integrity(SM), the drug discovery and development portal, http://www.thomsonreutersintegrity.com. This issue focuses on the following selection of drugs: Abatacept, Adalimumab, AdCD40L, Adefovir, Aleglitazar, Aliskiren fumarate, AM-103, Aminolevulinic acid methyl ester, Amlodipine, Anakinra, Aprepitant, Aripiprazole, Atazanavir sulfate, Axitinib; Belimumab, Bevacizumab, Bimatoprost, Bortezomib, Bupropion/naltrexone; Calcipotriol/betamethasone dipropionate, Certolizumab pegol, Ciclesonide, CYT-997; Darbepoetin alfa, Darunavir, Dasatinib, Desvenlafaxine succinate, Dexmethylphenidate hydrochloride cogramostim; Eltrombopag olamine, Emtricitabine, Escitalopram oxalate, Eslicarbazepine acetate, Eszopiclone, Etravirine, Everolimus-eluting coronary stent, Exenatide, Ezetimibe; Fenretinide, Filibuvir, Fludarabine; Golimumab; Hepatitis B hyperimmunoglobulin, HEV-239, HP-802-247, HPV-16/18 AS04, HPV-6/11/16/18, Human albumin, Human gammaglobulin; Imatinib mesylate, Inotuzumab ozogamicin, Invaplex 50 vaccine; Lapatinib ditosylate, Lenalidomide, Liposomal doxorubicin, Lopinavir, Lumiliximab, LY-686017; Maraviroc, Mecasermin rinfabate; Narlaprevir; Ocrelizumab, Oral insulin, Oritavancin, Oxycodone hydrochloride/naloxone; Paclitaxel-eluting stent, Palonosetron hydrochloride, PAN-811, Paroxetine, Pazopanib hydrochloride, Peginterferon alfa-2a, Peginterferon alfa-2b, Pemetrexed disodium, Pertuzumab, Pitavastatin calcium, Posaconazole, Pregabalin, Prucalopride succinate; Raltegravir potassium, Ranibizumab, RHAMM R3 peptide, Rosuvastatin calcium; Salclobuzic acid sodium salt, SCY-635, Selenate sodium, Semapimod hydrochloride, Silodosin, Siltuximab, Silybin, Sirolimus-eluting stent, SIR-Spheres, Sunitinib malate; Tapentadol hydrochloride, Tenofovir disoproxil

  12. Gateways to clinical trials.

    PubMed

    Bayés, M; Rabasseda, X

    2008-01-01

    Gateways to Clinical Trials are a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Trials Knowledge Area of Prouse Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: 101M, 3F8; Abatacept, ABT-263, Adalimumab, AG-7352, Agatolimod sodium, Alfimeprase, Aliskiren fumarate, Alvimopan hydrate, Aminolevulinic acid hexyl ester, Ammonium tetrathiomolybdate, Anakinra, Aripiprazole, AS-1404, AT-9283, Atomoxetine hydrochloride, AVE-1642, AVE-9633, Axitinib, AZD-0530; Becocalcidiol, Belotecan hydrochloride, Bevacizumab, BG-9928, BIBF-1120, BMS-275183, Bortezomib, Bosentan; Catumaxomab, Cetuximab, CHR-2797, Ciclesonide, Clevidipine, Cypher, Cytarabine/daunorubicin; Darifenacin hydrobromide, Darunavir, Denosumab, Desvenlafaxine succinate, Disufenton sodium, Duloxetine hydrochloride, Dutasteride; Eculizumab, Efalizumab, Eicosapentaenoic acid/docosahexaenoic acid, Eplerenone, Epratuzumab, Erlotinib hydrochloride, Escitalopram oxalate, Ethynylcytidine, Etravirine, Everolimus, Ezetimibe; Fulvestrant; Garenoxacin mesilate, Gefitinib, Gestodene; HI-164, Hydralazine hydrochloride/isosorbide dinitrate; Icatibant acetate, ICX-RHY, Idraparinux sodium, Indacaterol, Ispronicline, Ivabradine hydrochloride, Ixabepilone; KB-2115, KW-2449; L-791515, Lapatinib ditosylate, LGD-4665, Licofelone, Liposomal doxorubicin, Lisdexamfetamine mesilate, Lumiracoxib; Methoxy polyethylene glycol-epoetin-beta, Miglustat, Mipomersen sodium, Mitumprotimut-T, MK-0822A, MK-0974; Nelarabine; Obatoclax mesylate, Olmesartan medoxomil, Olmesartan medoxomil/hydrochlorothiazide; Paliperidone, Palonosetron hydrochloride, Panitumumab, Pegfilgrastim, Peginterferon alfa-2a, Pemetrexed disodium, Perospirone hydrochloride, Pertuzumab, Pimecrolimus, Pitrakinra, Pixantrone maleate, Posaconazole, Pregabalin; Quercetin; RALGA, Raltegravir

  13. Social media in clinical trials.

    PubMed

    Thompson, Michael A

    2014-01-01

    Social media has potential in clinical trials for pointing out trial issues, addressing barriers, educating, and engaging multiple groups involved in cancer clinical research. Social media is being used in clinical trials to highlight issues such as poor accrual and barriers; educate potential participants and physicians about clinical trial options; and is a potential indirect or direct method to improve accrual. We are moving from a passive "push" of information to patients to a "pull" of patients requesting information. Patients and advocates are often driving an otherwise reluctant health care system into communication. Online patient communities are creating new information repositories. Potential clinical trial participants are using the Twittersphere and other sources to learn about potential clinical trial options. We are seeing more organized patient-centric and patient-engaged forums with the potential to crowd source to improve clinical trial accrual and design. This is an evolving process that will meet many individual, institutional, and regulatory obstacles as we move forward in a changed research landscape. PMID:24857086

  14. Suspected acute exacerbation of idiopathic pulmonary fibrosis as an outcome measure in clinical trials

    PubMed Central

    2013-01-01

    Background Acute exacerbation of idiopathic pulmonary fibrosis has become an important outcome measure in clinical trials. This study aimed to explore the concept of suspected acute exacerbation as an outcome measure. Methods Three investigators retrospectively reviewed subjects enrolled in the Sildenafil Trial of Exercise Performance in IPF who experienced a respiratory serious adverse event during the course of the study. Events were classified as definite acute exacerbation, suspected acute exacerbation, or other, according to established criteria. Results Thirty-five events were identified. Four were classified as definite acute exacerbation, fourteen as suspected acute exacerbation, and seventeen as other. Definite and suspected acute exacerbations were clinically indistinguishable. Both were most common in the winter and spring months and were associated with a high risk of disease progression and short-term mortality. Conclusions In this study one half of respiratory serious adverse events were attributed to definite or suspected acute exacerbations. Suspected acute exacerbations are clinically indistinguishable from definite acute exacerbations and represent clinically meaningful events. Clinical trialists should consider capturing both definite and suspected acute exacerbations as outcome measures. PMID:23848435

  15. Data fraud in clinical trials

    PubMed Central

    George, Stephen L; Buyse, Marc

    2015-01-01

    Highly publicized cases of fabrication or falsification of data in clinical trials have occurred in recent years and it is likely that there are additional undetected or unreported cases. We review the available evidence on the incidence of data fraud in clinical trials, describe several prominent cases, present information on motivation and contributing factors and discuss cost-effective ways of early detection of data fraud as part of routine central statistical monitoring of data quality. Adoption of these clinical trial monitoring procedures can identify potential data fraud not detected by conventional on-site monitoring and can improve overall data quality. PMID:25729561

  16. Quality Assurance for Clinical Trials

    PubMed Central

    Ibbott, Geoffrey S.; Haworth, Annette; Followill, David S.

    2013-01-01

    Cooperative groups, of which the Radiation Therapy Oncology Group is one example, conduct national clinical trials that often involve the use of radiation therapy. In preparation for such a trial, the cooperative group prepares a protocol to define the goals of the trial, the rationale for its design, and the details of the treatment procedure to be followed. The Radiological Physics Center (RPC) is one of several quality assurance (QA) offices that is charged with assuring that participating institutions deliver doses that are clinically consistent and comparable. The RPC does this by conducting a variety of independent audits and credentialing processes. The RPC has compiled data showing that credentialing can help institutions comply with the requirements of a cooperative group clinical protocol. Phantom irradiations have been demonstrated to exercise an institution’s procedures for planning and delivering advanced external beam techniques (1–3). Similarly, RPC data indicate that a rapid review of patient treatment records or planning procedures can improve compliance with clinical trials (4). The experiences of the RPC are presented as examples of the contributions that a national clinical trials QA center can make to cooperative group trials. These experiences illustrate the critical need for comprehensive QA to assure that clinical trials are successful and cost-effective. The RPC is supported by grants CA 10953 and CA 81647 from the National Cancer Institute, NIH, DHHS. PMID:24392352

  17. Gateways to clinical trials.

    PubMed

    Bayes, M; Rabasseda, X; Prous, J R

    2005-11-01

    Gateways to Clinical Trials are a guide to the most recent clinical trials in current literature and congresses. The data in the following tables have been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity(R), the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: (Z)-4-Hydroxytamoxifen, [18F]-FPS; Adalimumab, alefacept, alemtuzumab, alfimeprase, aprepitant, aripiprazole, atomoxetine hydrochloride; Belatacept, bortezomib; C340, caspofungin acetate, clazosentan sodium, Cypher; Darbepoetin alfa, DB-289, decitabine, dronedarone hydrochloride, duloxetine hydrochloride; Eletriptan, entecavir, ertapenem sodium, escitalopram oxalate, eszopiclone, etoricoxib; Gaboxadol, gadofosveset sodium, galiximab, gemifloxacin mesilate, glutamine; Human insulin; I-131 ch-TNT-1/B, indiplon, inhaled insulin, isatoribine; L-Arginine hydrochloride, liposomal doxorubicin, lopinavir/ritonavir, lumiracoxib; Magnesium sulfate; Natalizumab; Olmesartan medoxomil, omapatrilat, OncoVEX (GM-CSF); rDNA insulin, rupatadine fumarate; Sorafenib; Tadalafil, teduglutide, temsirolimus, tenofovir disoproxil fumarate, tiotropium bromide; Valdecoxib, vardenafil hydrochloride hydrate. PMID:16357953

  18. [Topical cyclosporine in ophthalmology: Pharmacology and clinical indications].

    PubMed

    Levy, O; Labbé, A; Borderie, V; Laroche, L; Bouheraoua, N

    2016-03-01

    Cyclosporine A (CsA) is a cyclic undecapeptide, which is an immunosuppressive drug in the calcineurin inhibitor class. CsA was initially used as a systemic immunosuppressant to minimize rejection of solid organ transplants. In ophthalmology, topically applied CsA was first used to inhibit corneal allograft rejection in the 1980s and later in various inflammatory ocular surface disorders (OSD). Currently, topical ophthalmic CsA is available as a licensed commercial emulsion or is prepared by hospital pharmacies with concentration ranging from 0.05 to 2%. Many of its pharmacological effects on the ocular surface are direct consequences of its ability to inhibit T ciclosporine activation and apoptosis. Topical CsA differs from topical steroids in its favourable local and systemic tolerability at the concentrations used. Most clinical studies have evaluated topical CsA in moderate to severe dry eye disease (DED) and demonstrated its efficacy for improvement of signs and symptoms, thus providing the sole indication for market approval and treatment protocols. For the other indications - corneal graft rejection, blepharitis, allergic or viral keratitis, and ocular surface disease due to graft versus host disease or post-operative DED - evidence-based medicine remains unclear due to the lack of major randomized controlled trials. Despite the lack of standardized protocols or market approval for these conditions, numerous studies suggest clinical efficacy. PMID:26997607

  19. Amyloid imaging as a surrogate marker in clinical trials in Alzheimer's disease.

    PubMed

    Scheinin, Noora M; Scheinin, Mika; Rinne, J O

    2011-06-01

    New treatments against Alzheimer's disease (AD) may be just around the corner. A common approach in developing these disease-modifying treatments is to target beta-amyloid (Aβ). Aβ is excessively present in the AD brain and it likely starts to accumulate long before clinical symptoms become apparent. As Aβ is hypothesized to be the causative agent in the pathophysiological cascade leading to progressive neurodegeneration in AD, efforts to e.g. prevent its formation, to promote its clearance from brain tissue, and to inhibit its toxicity, are warranted. This quest for an effective AD treatment needs valid biomarker outcome measures, for instance because clinical benefit takes long to present itself and is difficult to measure, and also because treatment would likely be most efficacious if administered already before symptoms occur. In vivo amyloid imaging has evolved in the past decade to be a feasible means to monitor brain Aβ deposits in the human brain. It effectively differentiates AD patients from healthy age-matched controls, and also shows promise in the early, even presymptomatic, detection of AD. Amyloid imaging will likely also broaden and deepen our understanding of AD and other neurodegenerative disorders. It could prove valuable e.g. in subject selection and stratification for clinical trials, in safety and proof-of-concept assessments, and in monitoring of treatment effects. This article aims to review the motives, prerequisites, potential, and challenges of using amyloid imaging as a surrogate marker in clinical therapeutic trials in AD. PMID:21532540

  20. Clinical Comparison: Fast-Acting and Traditional Topical Dental Anesthetic.

    PubMed

    DiMarco, Arthur C; Wetmore, Ann O'Kelley

    2016-01-01

    A randomized, nonblinded clinical trial compared the effectiveness of an application method of a fast-acting refrigerant topical agent to a 20% benzocaine gel topical. In a split-mouth design, right and left anterior middle superior alveolar injections (N = 30) were administered with a 27-gauge needle at least 24 hours apart with preinjection topicals. Using a cotton-tipped applicator, a refrigerant topical was applied for 5 seconds and 20% benzocaine gel for 2 minutes on opposite sides at 2 separate appointments. Subjects self-reported pain perception after each injection using a visual analog scale (VAS). The mean VAS ratings demonstrated no significant difference between the 5-second application of the refrigerant (M = 16.2, SD = 17.7) and the 2-minute application of 20% benzocaine topical gel anesthetic (M = 17.9, SD = 18.2). Fifty-seven percent of the subjects reported greater pain reduction with the refrigerant, 33% reported greater pain reduction with 20% benzocaine, and 10% reported no difference. Results suggest the described method of application of a refrigerant as an oral topical anesthetic has a faster onset and provides similar benefit in pain reduction compared with 20% benzocaine gel. The refrigerant was easy to accomplish and well received by subjects, indicating potential for routine use in dentistry. PMID:27269661

  1. Seeking harmony: estimands and sensitivity analyses for confirmatory clinical trials.

    PubMed

    Mehrotra, Devan V; Hemmings, Robert J; Russek-Cohen, Estelle

    2016-08-01

    In October 2014, the Steering Committee of the International Conference on Harmonization endorsed the formation of an expert working group to develop an addendum to the International Conference on Harmonization E9 guideline ("Statistical Principles for Clinical Trials"). The addendum will focus on two topics involving randomized confirmatory clinical trials: estimands and sensitivity analyses. Both topics are motivated, in part, by the need to improve the precision with which scientific questions of interest are formulated and addressed by clinical trialists and regulators, specifically in the context of post-randomization events such as use of rescue medication or missing data resulting from dropouts. Given the importance of these topics for the statistical and medical community, we articulate the reasons for the planned addendum. The resulting "ICH E9/R1" guideline will include a framework for improved trial planning, conduct, analysis, and interpretation; a draft is expected to be ready for public comment in the second half of 2016. PMID:26908545

  2. Patient-reported outcomes as primary end points in clinical trials of inflammatory bowel disease.

    PubMed

    Williet, Nicolas; Sandborn, William J; Peyrin-Biroulet, Laurent

    2014-08-01

    The Food and Drug Administration (FDA) is moving from the Crohn's Disease Activity Index to patient-reported outcomes (PROs) and objective measures of disease, such as findings from endoscopy. PROs will become an important aspect of assessing activity of inflammatory bowel disease (IBD) and for labeling specific drugs for this disease. PROs always have been considered in the management of patients with rheumatoid arthritis or multiple sclerosis, and have included measurements of quality of life, disability, or fatigue. Several disease-specific scales have been developed to assess these PROs and commonly are used in clinical trials. Outcomes reported by patients in clinical trials of IBD initially focused on quality of life, measured by the Short-Form 36 questionnaire or disease-specific scales such as the Inflammatory Bowel Disease Questionnaire or its shorter version. Recently considered factors include fatigue, depression and anxiety, and work productivity, as measured by the Functional Assessment Chronic Illness Therapy-Fatigue, the Hospital Anxiety Depression, and the Work Productivity Activity Impairment Questionnaire, respectively. However, few data are available on how treatment affects these factors in patients with IBD. Although disability generally is recognized in patients with IBD, it is not measured. The international IBD disability index currently is being validated. None of the PROs currently used in IBD were developed according to FDA guidance for PRO development. PROs will be a major primary end point of future trials. FDA guidance is needed to develop additional PROs for IBD that can be incorporated into trials, to better compare patients' experience with different therapies. PMID:24534550

  3. Topical Hyaluronic acid vs. Standard of Care for the Prevention of Radiation Dermatitis after Adjuvant Radiotherapy for Breast Cancer: Single-Blind Randomized Phase III Clinical Trial

    PubMed Central

    Pinnix, Chelsea; Perkins, George H.; Strom, Eric A.; Tereffe, Welela; Woodward, Wendy; Oh, Julia L.; Arriaga, Lisa; Munsell, Mark F.; Kelly, Patrick; Hoffman, Karen E.; Smith, Benjamin D.; Buchholz, Thomas A.; Yu, T. Kuan

    2014-01-01

    Purpose To determine the efficacy of an emulsion containing hyaluronic acid to reduce the development of ≥ grade 2 radiation dermatitis after adjuvant breast radiation (RT) compared with best supportive care. Materials and Methods Women with breast cancer who had undergone lumpectomy and were to receive whole-breast RT to 50 Gy with a 10- to 16-Gy surgical bed boost were enrolled in a prospective randomized trial to compare the effectiveness of a hyaluronic acid-based gel (RadiaPlex) and a petrolatum-based gel (Aquaphor) for preventing the development of dermatitis. Each patient was randomly assigned to use hyaluronic acid gel, on the medial half or the lateral half of the irradiated breast, and the control gel to the other half. Dermatitis was graded weekly according to the Common Terminology Criteria v3.0 by the treating physician, who was blinded as to which gel was used on which area of the breast. The primary endpoint was development of ≥grade 2 dermatitis. Results The study closed early based on a recommendation from the Data and Safety Monitoring Board after 74 of the planned 92 patients were enrolled. Breast skin treated with the hyaluronic acid gel developed significantly higher rate of ≥grade 2 dermatitis than did skin treated with petrolatum gel (61.5% [40/65] vs. 47.7% [31/65], P = 0.027). Only one patient developed grade 3 dermatitis using either gel. A higher proportion of patients had worse dermatitis in the breast segment treated with hyaluronic acid gel than petrolatum gel at the end of RT (42% vs. 14%, P = 0.003). Conclusion We found no benefit from use of a topical hyaluronic acid-based gel for reducing the development of grade ≥2 dermatitis after adjuvant RT for breast cancer. Additional studies are needed to determine the efficacy of hyaluronic acid-based gel in controlling radiation dermatitis symptoms after they develop. PMID:22172912

  4. Clinical Trials: CSDRG Overview

    ERIC Educational Resources Information Center

    Logemann, Jeri A.

    2004-01-01

    Recent importance placed upon efficacy research has spawned the development of the Communication Sciences and Disorders Clinical Trials Research Group (CSDRG). This group, funded by the National Institutes of Health (NIH), was organized by the American Speech Language and Hearing Association to address the need for more treatment efficacy research…

  5. [Clinical research on a new corticoid-containing topical drug].

    PubMed

    Sturde, H C

    1976-08-15

    In the present paper, the clinical trial of a new difluorinated corticosteroid suitable for topical use is reported. Because of its proven efficacy in very different dermatoses, it is useful as a new reliable product for external use having a broad spectrum of indications. Altogether, 50 patients were treated for a number of dermatoses (various forms of eczema, neurodermitis constitutionalis among other rare skin diseases). Complications, especially skin lesions due to corticosteroids, were not observed. The availability of the test preparation in three different forms has the advantage that it is not only suitable for the primary dermatosis, but it can also be adapted to the various degrees of acuteness. PMID:969808

  6. Comparison of topical 5% nicotinamid gel versus 2% clindamycin gel in the treatment of the mild-moderate acne vulgaris: A double-blinded randomized clinical trial

    PubMed Central

    Shahmoradi, Zabiolah; Iraji, Farib; Siadat, Amir Hossein; Ghorbaini, Azamosadat

    2013-01-01

    Background: Acne vulgaris is considered one of the most common disorders for which patients seek dermatologic care. In the current study, we evaluated efficacy of the 5% nicotinamide gel versus 2% clindamycin gel in the treatment of the mild-moderate acne vulgaris. Materials and Methods: This was a randomized, controlled clinical trial that was performed in 2009-2010. Sixty female patients with mild or moderate acne vulgaris were recurited to be treated either with 5% nicotinamide or 2% clindamycin gel for 8 weeks. Acne severity index (ASI) was used to evaluate response to treatment and SPSS software was used to analyze the data. Results: The mean of ASI at the baseline was 16.85 ± 8.5 and 18.2 ± 12.27 in nicotinamide gel and clindamycin gel, respectively (P > 0.05). The mean of ASI was significantly decreased compared with baseline ASI during the time in both groups (P < 0.0001). However, there was not a significant difference regarding reduction of ASI between the nicotinamide and clindamycin gel (P = 0.583). Conclusion: Five percent nicotinamide gel is as effective as 2% clindamycin gel for treatment of mild to moderate acne vulgaris. No side effect was observed during the treatment. PMID:23914212

  7. Overview: Progression-Free Survival as an Endpoint in Clinical Trials with Solid Tumors

    PubMed Central

    Korn, Ronald L.; Crowley, John J.

    2013-01-01

    Progression-free survival (PFS) is increasingly used as an important and even a primary endpoint in randomized cancer clinical trials in the evaluation of patients with solid tumors, because of both practical and clinical considerations. Although in its simplest form PFS is the time from randomization to a pre-defined endpoint, there are many factors that can influence the exact moment of when disease progression is recorded. In this overview, we review the circumstances that can devalue the use of PFS as a primary endpoint, and attempt to provide a pathway for a future desired state when PFS will become not just a secondary alternative to overall survival but rather an endpoint of choice. PMID:23669420

  8. [Randomized clinical trials and real clinical practice].

    PubMed

    Heerlein, Andrés

    2009-01-01

    One of the emerging problems in modern medicine is that part of its highly efficacious treatments do not show significant effectiveness in real world systems of care. Efficacy studies address the appropriate dosages, short term response and feasibility of treatments in carefully selected populations, but they do not necessarily provide information for decisions in clinical practice. This review aims to present strengths and limitations of different methodological types of trials and to offer an overview of how knowledge from clinical trials can be used for clinical practice. The important effect of funding source on the outcome of randomized controlled trials is discussed. Some key questions in the treatment assessment of depression, schizophrenia and different medical conditions are discussed, with a focus on the possibilities and restrictions of translating clinical trial results into real-world settings. Empirical evidence shows that although randomized controlled trials are the gold standard for proving efficacy of a therapeutic procedure they often suffer from funding source bias and from lack of generalizability. Effectiveness studies evaluate effects of treatments under conditions approximating usual care. Another key area that can be addressed by effectiveness studies is the impact on important health policy measures such as disability days, days of work or medical costs, etc. Conclusions show that the future assessment of treatment regimes for clinical utility requires less biased efficacy studies and more effectiveness studies addressing major issues from all relevant perspectives. PMID:19543562

  9. [Quality control in clinical trials].

    PubMed

    Fukushima, M

    1996-01-01

    Quality control (QC) in clinical trials means the procedures which insure protection of human subjects from research risk, reliability of the data, and thereby assures internal consistency. This has been developed since 1970s in the US, by establishing various regulations which are now called GCP. From the viewpoint of total QC, it should be emphasized that rigorous review of protocol by the Institutional Review Board and obtaining Informed Consent are prerequisites for insuring the quality of the given trial at high scientific level. When pursuing a clinical trial, first of all, facilities of the institutions and the ability of investigators must be of high quality. For this reason, at each institution previous data related to trials should be thoroughly reviewed and analyzed prior to developing a protocol. Educational courses in QC in clinical practice are invaluable. QC of diagnosis means, for example, central pathology review and standardization of diagnostic procedures and process. Secondly, at each institution, data managers collect the data and submit them to the central office at the indicated time. In order to evolve clinical trial, continuous education for data managers and expansion of their job are encouraged. Thirdly, at the statistical center independent from the research group office, subject-specific data managers, the biostatistical staff, must check submitted forms for completeness, consistency and accuracy. Finally, at the data analysis, quality evaluation of the research should also be carried out. Throughout the trial, monitoring and audit are particularly important to assure quality. The sponsor has the responsibility of monitoring the trial and make rigorous onsite visits, and the individual study group also have a monitoring program, while the FDA and the NCI audit by themselves. The purpose of audit is not only to assure data reliability but also to check out patient compliance to drug, education as to regulations and rules of clinical

  10. Inept media trials of clinical trials

    PubMed Central

    Ramamurthy, N. V.

    2012-01-01

    The Indian media in general, with the exception of a few domain expert journalists, have failed to comprehend the complexities involved in the clinical trial process. In the run up to the deadline-based coverage of a story, a majority of them fall short in conveying the right perspective to readers, but nevertheless they have been successful in sensationalizing an event in this arena. Possibly by unintended misrepresentation, or mostly out of ignorance of the nuances involved in the clinical trials process, the media has done more harm than good, and got away with it. On the other side, the industry has been reluctant to engage with the media in a meaningful dialog for too long now. It bears not only the consequences of damage to its professional reputation following such reportage, but also the repercussions of unnecessary clampdowns by the regulators. Science journalism in India has yet to rise as a profession. PMID:22701819

  11. Neutropenia as an Adverse Event following Vaccination: Results from Randomized Clinical Trials in Healthy Adults and Systematic Review

    PubMed Central

    Muturi-Kioi, Vincent; Lewis, David; Launay, Odile; Leroux-Roels, Geert; Anemona, Alessandra; Loulergue, Pierre; Bodinham, Caroline L.; Aerssens, Annelies; Groth, Nicola; Saul, Allan; Podda, Audino

    2016-01-01

    Background In the context of early vaccine trials aimed at evaluating the safety profile of novel vaccines, abnormal haematological values, such as neutropenia, are often reported. It is therefore important to evaluate how these trials should be planned not to miss potentially important safety signals, but also to understand the implications and the clinical relevance. Methodology We report and discuss the results from five clinical trials (two with a new Shigella vaccine in the early stage of clinical development and three with licensed vaccines) where the absolute neutrophil counts (ANC) were evaluated before and after vaccination. Additionally, we have performed a systematic review of the literature on cases of neutropenia reported during vaccine trials to discuss our results in a more general context. Principal Findings Both in our clinical trials and in the literature review, several cases of neutropenia have been reported, in the first two weeks after vaccination. However, neutropenia was generally transient and had a benign clinical outcome, after vaccination with either multiple novel candidates or well-known licensed vaccines. Additionally, the vaccine recipients with neutropenia frequently had lower baseline ANC than non-neutropenic vaccinees. In many instances neutropenia occurred in subjects of African descent, known to have lower ANC compared to western populations. Conclusions It is important to include ANC and other haematological tests in early vaccine trials to identify potential safety signals. Post-vaccination neutropenia is not uncommon, generally transient and clinically benign, but many vaccine trials do not have a sampling schedule that allows its detection. Given ethnic variability in the level of circulating neutrophils, normal ranges taking into account ethnicity should be used for determination of trial inclusion/exclusion criteria and classification of neutropenia related adverse events. Trial registration ClinicalTrials.gov NCT02017899

  12. Topical Hyaluronic Acid vs. Standard of Care for the Prevention of Radiation Dermatitis After Adjuvant Radiotherapy for Breast Cancer: Single-Blind Randomized Phase III Clinical Trial

    SciTech Connect

    Pinnix, Chelsea; Perkins, George H.; Strom, Eric A.; Tereffe, Welela; Woodward, Wendy; Oh, Julia L.; Arriaga, Lisa; Munsell, Mark F.; Kelly, Patrick; Hoffman, Karen E.; Smith, Benjamin D.; Buchholz, Thomas A.; Yu, T. Kuan

    2012-07-15

    Purpose: To determine the efficacy of an emulsion containing hyaluronic acid to reduce the development of {>=}Grade 2 radiation dermatitis after adjuvant breast radiation compared with best supportive care. Methods and Materials: Women with breast cancer who had undergone lumpectomy and were to receive whole-breast radiotherapy to 50 Gy with a 10- to 16-Gy surgical bed boost were enrolled in a prospective randomized trial to compare the effectiveness of a hyaluronic acid-based gel (RadiaPlex) and a petrolatum-based gel (Aquaphor) for preventing the development of dermatitis. Each patient was randomly assigned to use hyaluronic acid gel on the medial half or the lateral half of the irradiated breast and to use the control gel on the other half. Dermatitis was graded weekly according to the Common Terminology Criteria v3.0 by the treating physician, who was blinded as to which gel was used on which area of the breast. The primary endpoint was development of {>=}Grade 2 dermatitis. Results: The study closed early on the basis of a recommendation from the Data and Safety Monitoring Board after 74 of the planned 92 patients were enrolled. Breast skin treated with the hyaluronic acid gel developed a significantly higher rate of {>=}Grade 2 dermatitis than did skin treated with petrolatum gel: 61.5% (40/65) vs. 47.7% (31/65) (p = 0.027). Only 1ne patient developed Grade 3 dermatitis using either gel. A higher proportion of patients had worse dermatitis in the breast segment treated with hyaluronic acid gel than in that treated with petrolatum gel at the end of radiotherapy (42% vs. 14%, p = 0.003). Conclusion: We found no benefit from the use of a topical hyaluronic acid-based gel for reducing the development of {>=}Grade 2 dermatitis after adjuvant radiotherapy for breast cancer. Additional studies are needed to determine the efficacy of hyaluronic acid-based gel in controlling radiation dermatitis symptoms after they develop.

  13. Gateways to clinical trials.

    PubMed

    Bayés, M; Rabasseda, X; Prous, J R

    2005-09-01

    Gateways to Clinical Trials are a guide to the most recent clinical trials in the current literature and congresses. The data in the following tables have been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: AAV-NGFbeta, aprepitant, aripiprazole, atomoxetine hydrochloride; beta-Methyl-6-chloromelatonin, BMS-214662, bortezomib, bosentan; Calcipotriol/betamethasone dipropionate, CEA-TRICOM, cetuximab, ciclesonide, clofarabine, Cypher; Dalbavancin, darbepoetin alfa, darifenacin hydrobromide, desloratadine, Dexamet, drospirenone, drospirenone/ethinylestradiol, drotrecogin alfa (activated), duloxetine hydrochloride, dutasteride; Ecogramostim, efalizumab, ertapenem sodium, escitalopram oxalate, eszopiclone; Fenretinide; Gefitinib, gestodene, ghrelin (human); hMaxi-K, human papillomavirus vaccine; Imatinib mesylate, indiplon, iodine (i131) tositumomab, irofulven, ISS-1018; Lasofoxifene tartrate, levodopa/carbidopa/entacapone, liposomal doxorubicin; Nemifitide ditriflutate, nesiritide; Omalizumab; Pegfilgrastim, peginterferon alfa-2a, peginterferon alfa-2b, phVEGF-A165, pimecrolimus, pramlintide acetate; Rasburicase, rimonabant hydrochloride; Satraplatin, St. John's Wort extract, sunitinib malate; Tadalafil, tanaproget, Taxus, tiotropium bromide, treprostinil sodium; Valdecoxib, vardenafil hydrochloride hydrate; Ximelagatran; Zileuton. PMID:16258596

  14. Gateways to clinical trials.

    PubMed

    Bayés, M; Rabasseda, X; Prous, J R

    2005-03-01

    Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables have been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: 3-AP, 667-coumate, 9-aminocamptothecin; Ad5CMV-p53, AES-14, alefacept, anecortave acetate, APC-8024, APD-356, asoprisnil; Bevacizumab, bimakalim, bimatoprost, BLP-25, BR-1; Caspofungin acetate, cetuximab, cypher; Darbepoetin alfa, dexanabinol, dextromethorphan/quinidine sulfate, DNA.HIVA; Efaproxiral sodium, ertapenem sodium; Frovatriptan; HuMax-EGFr, HYB-2055, gamma-hydroxybutyrate sodium, Id-KLH vaccine, imatinib mesylate; Lapatinib, lonafarnib, Motexafin lutetium, MVA.HIVA, mycophenolic acid sodium salt; Nesiritide, NS-2330; Olmesartan medoxomil; Peginterferon alfa-2a, peginterferon alfa-2b, peginterferon alfa-2b/ribavirin, pemetrexed disodium, perifosine, pimecrolimus, pregabalin; QbG-10; Ralfinamide, rasburicase, rFGF-2, Ro-31-7453; Sitaxsentan sodium, sorafenib; Tadalafil, TC-1734, telmisartan/hydrochlorothiazide, tenofovir disoproxil fumarate, thymus nuclear protein, tipifarnib; Vandetanib, vibriolysin, vildagliptin, voriconazole. PMID:15834466

  15. Gateways to clinical trials.

    PubMed

    Bayés, M; Rabasseda, X; Prous, J R

    2005-12-01

    Gateways to Clinical Trials are a guide to the most recent clinical trials in current literature and congresses. The data in the following tables have been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity. prous.com. This issue focuses on the following selection of drugs: 131I-chTNT; Abatacept, adalimumab, alemtuzumab, APC-8015, aprepitant, atazanavir sulfate, atomoxetine hydrochloride, azimilide hydrochloride; Bevacizumab, bortezomib, bosentan, buserelin; Caspofungin acetate, CC-4047, ChAGCD3, ciclesonide, clopidogrel, curcumin, Cypher; Dabigatran etexilate, dapoxetine hydrochloride, darbepoetin alfa, darusentan, denosumab, DMXB-Anabaseine, drospirenone, drospirenone/estradiol, duloxetine hydrochloride, dutasteride; Edodekin alfa, efaproxiral sodium, elaidic acid-cytarabine, erlotinib hydrochloride, ertapenem sodium, escitalopram oxalate, eszopiclone, etonogestrel/testosterone decanoate, exenatide; Fulvestrant; Gefitinib, glycine, GVS-111; Homoharringtonine; ICC-1132, imatinib mesylate, iodine (I131) tositumomab, i.v. gamma-globulin; Levetiracetam, levocetirizine, lintuzumab, liposomal nystatin, lumiracoxib, lurtotecan; Manitimus, mapatumumab, melatonin, micafungin sodium, mycophenolic acid sodium salt; Oblimersen sodium, OGX-011, olmesartan medoxomil, omalizumab, omapatrilat, oral insulin; Parathyroid hormone (human recombinant), pasireotide, peginterferon alfa-2a, peginterferon alfa-2b, peginterferon alfa-2b/ribavirin, phVEGF-A165, pimecrolimus, pitavastatin calcium, plerixafor hydrochloride, posaconazole, pramlintide acetate, prasterone, pregabalin, PT-141; Quercetin; Ranolazine, rosuvastatin calcium, rubitecan, rupatadine fumarate; Sardomozide, sunitinib malate; Tadalafil, talactoferrin alfa, tegaserod maleate, telithromycin, testosterone transdermal patch, TH-9507, tigecycline, tiotropium bromide, tipifarnib, tocilizumab, treprostinil sodium; Valdecoxib, vandetanib

  16. Effectiveness of Topical Nigella sativa Seed Oil in the Treatment of Cyclic Mastalgia: A Randomized, Triple-Blind, Active, and Placebo-Controlled Clinical Trial.

    PubMed

    Huseini, Hasan Fallah; Kianbakht, Saeed; Mirshamsi, Mohammad Hossein; Zarch, Ali Babaei

    2016-03-01

    Cyclic mastalgia is common in women and has no optimal therapy. Analgesic effects of Nigella sativa have been reported. Thus, the effect of a standardized N. sativa seed oil (600 mg applied to the site of pain bis in die for 2 months) on the 10-centimeter visual analog scale scores of pain severity in 52 women with cyclic mastalgia was compared to that of topical diclofenac (20 mg bis in die) (n = 51) and placebo (n = 53). There was no significant difference between the 1- and 2-month pain scores in the active treatment groups (p > 0.05). The pain scores of the active treatment groups did not differ significantly at 1 and 2 months (p > 0.05). The endpoint pain scores of the active treatment groups decreased significantly compared with the baseline (both p < 0.001). The pain scores of the active treatment groups at 1 and 2 months were significantly smaller than those of the placebo group (both p < 0.001). The pain scores of the placebo group at 1 and 2 months were not significantly different from the baseline (p > 0.05). No adverse effect was observed. In conclusion, topical N. sativa seed oil is safe, more effective than placebo, and has clinical effectiveness comparable to topical diclofenac in the treatment of cyclic mastalgia. PMID:26584456

  17. PI3K inhibitors as new cancer therapeutics: implications for clinical trial design

    PubMed Central

    Massacesi, Cristian; Di Tomaso, Emmanuelle; Urban, Patrick; Germa, Caroline; Quadt, Cornelia; Trandafir, Lucia; Aimone, Paola; Fretault, Nathalie; Dharan, Bharani; Tavorath, Ranjana; Hirawat, Samit

    2016-01-01

    The PI3K–AKT–mTOR pathway is frequently activated in cancer. PI3K inhibitors, including the pan-PI3K inhibitor buparlisib (BKM120) and the PI3Kα-selective inhibitor alpelisib (BYL719), currently in clinical development by Novartis Oncology, may therefore be effective as anticancer agents. Early clinical studies with PI3K inhibitors have demonstrated preliminary antitumor activity and acceptable safety profiles. However, a number of unanswered questions regarding PI3K inhibition in cancer remain, including: what is the best approach for different tumor types, and which biomarkers will accurately identify the patient populations most likely to benefit from specific PI3K inhibitors? This review summarizes the strategies being employed by Novartis Oncology to help maximize the benefits of clinical studies with buparlisib and alpelisib, including stratification according to PI3K pathway activation status, selective enrollment/target enrichment (where patients with PI3K pathway-activated tumors are specifically recruited), nonselective enrollment with mandatory tissue collection, and enrollment of patients who have progressed on previous targeted agents, such as mTOR inhibitors or endocrine therapy. An overview of Novartis-sponsored and Novartis-supported trials that are utilizing these approaches in a range of cancer types, including breast cancer, head and neck squamous cell carcinoma, non-small cell lung carcinoma, lymphoma, and glioblastoma multiforme, is also described. PMID:26793003

  18. Gateways to clinical trials.

    PubMed

    Bayés, M; Rabasseda, X; Prous, J R

    2002-11-01

    Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Studies knowledge area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: Abacavir sulfate, abarelix, adalimumab, adefovir dipivoxil, AdGVVEGF121.10, anastrozole, anecortave acetate, aripiprazole, asulacrine isethionate, atazanavir, ATL-962, 16-Aza-epothilone B; Bevacizumab, bicalutamide, blonanserin, BMS-188667, bosentan; Celecoxib, celmoleukin, cetuximab, cilomilast, cinacalcet hydrochloride, CNTF(Ax15), colesevelam hydrochloride; Daclizumab, delavirdine mesilate, desogestrel, desoxyepothilone B, dexmethylphenidate hydrochloride, duloxetine hydrochloride; Ecogramostim, emtricitabine, epalrestat, escitalopram oxalate, examorelin, exendin-4, ezetimibe; Fidarestat, frovatriptan; HIV-1 Immunogen; Iloperidone, insulin detemir, insulin lispro, irinotecan hydrochloride; Keratinocyte growth factor; Lasofoxifene tartrate, levetiracetam, levormeloxifene, levosimendan, lumiracoxib, LY-307161 SR; Memantine hydrochloride, MEN-10755, metformin hydrochloride, metreleptin, motexafin gadolinium; Naratriptan hydrochloride, natalizumab, nesiritide, nicotine, NN-2211, NN-414; Olanzapine, omalizumab; Pegaptanib sodium, peginterferon alfa-2a, peginterferon alfa-2b, pegvisomant, pimecrolimus, pirfenidone, pramlintide acetate prasterone, pregabalin; Quetiapine fumarate; Rabeprazole sodium, raloxifene hydrochloride, raltitrexed, rDNA insulin, rFGF-2, risedronate sodium, rofecoxib, roflumilast, rosiglitazone maleate; SN-22995; Tacrolimus, tadalafil, tegaserod maleate, tiotropium bromide, tomoxetine hydrochloride, trastuzumab, trimegestone; Voglibose, Voriconazole; Ziprasidone hydrochloride. PMID:12616707

  19. Gateways to clinical trials.

    PubMed

    Bayes, M; Rabasseda, X; Prous, J R

    2002-05-01

    Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables can be retrieved from the Clinical Studies knowledge area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: Abacavir sulfate, abarelix, abciximab, acarbose, alefacept, alteplase, amisulpride, amoxicillin trihydrate, apomorphine hydrochloride, aprepitant, argatroban monohydrate, aspirin, atenolol; Betamethasone dipropionate, betamethasone valerate, bicalutamide, bleomycin sulfate; Calcium carbonate, candesartan cilexetil, celecoxib, cetirizine hydrochloride, cisplatin, clarithromycin, clavulanate potassium, clomethiazole edisilate, clopidogrel hydrogensulfate, cyclophosphamide, chorionic gonadotropin (human); Dalteparin sodium, desloratadine, dexamethasone, doxorubicin, DPC-083; Efalizumab, efavirenz, enoxaparin sodium, eprosartan mesilate, etanercept, etoposide, ezetimibe; Faropenem daloxate, fenofibrate, fluocinolone acetonide, flutamide, fluvastatin sodium, follitropin beta, fondaparinux sodium; Gabapentin, glibenclamide, goserelin, granisetron hydrochloride; Haloperidol, hydrochlorothiazide; Imiquimod, interferon beta-1a, irbesartan, iseganan hydrochloride; L-758298, lamivudine, lanoteplase, leflunomide, leuprorelin acetate, loratadine, losartan potassium; Melagatran, metformin hydrochloride, methotrexate, metronidazole, micafungin sodium, mitoxantrone hydrochloride; Nelfinavir mesilate, neutral insulin injection, nizatidine; Olopatadine hydrochloride, omeprazole, ondansetron hydrochloride; Pamidronate sodium, paracetamol, paroxetine hydrochloride, perindopril, pimecrolimus, pioglitazone hydrochloride, piroxicam, pleconaril, pralmorelin, pravastatin sodium, prednisolone, prednisone, propofol; Raloxifene hydrochloride, ranpirnase, remifentanil hydrochloride, risedronate sodium, risperidone, rofecoxib, ropinirole

  20. Gateways to clinical trials.

    PubMed

    Bayés, M; Rabasseda, X; Prous, J R

    2004-12-01

    Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Studies Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: Abetimus sodium, ademetionine, agalsidase alfa, agalsidase beta, alemtuzumab, alfimeprase, AMG-162, androgel, anidulafungin, antigastrin therapeutic vaccine, aripiprazole, atomoxetine hydrochloride; Bazedoxifene acetate, bevacizumab, bosentan; Caldaret hydrate, canfosfamide hydrochloride, choriogonadotropin alfa, ciclesonide, combretastatin A-4 phosphate, CY-2301; Darbepoetin alfa, darifenacin hydrobromide, decitabine, degarelix acetate, duloxetine hydrochloride; ED-71, enclomiphene citrate, eplerenone, epratuzumab, escitalopram oxalate, eszopiclone, ezetimibe; Fingolimod hydrochloride, FP-1096; HMR-3339A, HSV-TK/GCV gene therapy, human insulin, HuOKT3gamma1(Ala234-Ala235); Idursulfase, imatinib mesylate, indiplon, InnoVax C insulin glargine, insulin glulisine, irofulven; Labetuzumab, lacosamide, lanthanum carbonate, LyphoDerm, Lyprinol; Magnesium sulfate, metelimumab, methylphenidate hydrochloride; Natalizumab, NO-aspirin; OROS(R); PC-515, pegaptanib sodium, peginterferon alfa-2a, peginterferon alfa-2b, peginterferon alfa-2b/ribavirin, pemetrexed disodium, peptide YY3-36, posaconazole, pregabalin, PT-141, pyridoxamine; R-744, ramelteon, ranelic acid distrontium salt, rebimastat, repinotan hydrochloride, rhC1, rhGAD65, rosiglitazone maleate/metformin hydrochloride; Sardomozide, solifenacin succinate; Tadalafil, taxus, telavancin, telithromycin, tenofovir disoproxil fumarate, teriparatide, testosterone transdermal patch, tetomilast, tirapazamine, torcetrapib; Valspodar, vardenafil hydrochloride hydrate, vildagliptin; Yttrium Y90 epratuzumab; Ziprasidone hydrochloride. PMID:15672123

  1. Gateways to clinical trials.

    PubMed

    Bayes, M; Rabasseda, X; Prous, J R

    2002-01-01

    Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses, which has been retrieved from the Clinical Studies knowledge area of Prous Science Integrity, the world's first drug discovery and development portal, providing information on study design, treatments, conclusions and references. This issue focuses on the following selection of drugs: Abacavir sulfate; abciximab; abetimus sodium; adalimumab; aldesleukin; almotriptan; alteplase; amisulpride; amitriptyline hydrochloride; amoxicillin trihydrate; atenolol; atorvastatin calcium; atrasentan; Beclometasone dipropionate; bosentan; Captopril; ceftriaxone sodium; cerivastatin sodium; cetirizine hydrochloride; cisplatin; citalopram hydrobromide; Dalteparin sodium; darusentan; desirudin; digoxin; Efalizumab; enoxaparin sodium; ertapenem sodium; esomeprazole magnesium; estradiol; ezetimibe; Famotidine; farglitazar; fluorouracil; fluticasone propionate; fosamprenavir sodium; Glibenclamide; glucosamine sulfate; Heparin sodium; HSPPC-96; hydrochlorothiazide; Imatinib mesilate; implitapide; Lamivudine; lansoprazole; lisinopril; losartan potassium; l-Propionylcarnitine; Melagatran; metformin hydrochloride; methotrexate; methylsulfinylwarfarin; Nateglinide; norethisterone; Olmesartan medoxomil; omalizumab; omapatrilat; omeprazole; oseltamivir phosphate; oxatomide; Pantoprazole; piperacillin sodium; pravastatin sodium; Quetiapine hydrochloride; Rabeprazole sodium; raloxifene hydrochloride; ramosetron hydrochloride; ranolazine; rasburicase; reboxetine mesilate; recombinant somatropin; repaglinide; reteplase; rosiglitazone; rosiglitazone maleate; rosuvastatin calcium; Sertraline; simvastatin; sumatriptan succinate; Tazobactam sodium; tenecteplase; tibolone; tinidazole; tolterodine tartrate; troglitazone; Uniprost; Warfarin sodium; Ximelagatran. PMID:11980386

  2. Gateways to clinical trials.

    PubMed

    Bayés, M; Rabasseda, X; Prous, J R

    2002-12-01

    Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Studies knowledge area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: Abacavir sulfate, adalimumab, AERx morphine sulphate, alefacept, alemtuzumab, alendronic acid sodium salt, alicaforsen sodium, almotriptan, amprenavir, aripiprazole, atenolol, atorvastatin calcium; BSYX-A110; Cantuzumab mertansine, capravirine, CDP-571, CDP-870, celecoxib; Delavirdine mesilate, docetaxel, dofetilide, donepezil hydrochloride, duloxetine hydrochloride, dutasteride, dydrogesterone; Efavirenz, emtricitabine, enjuvia, enteryx, epristeride, erlotinib hydrochloride, escitalopram oxalate, etanercept, etonogestrel, etoricoxib; Fesoterodine, finasteride, flt3ligand; Galantamine hydrobromide, gemtuzumab ozogamicin, genistein, gepirone hydrochloride; Indinavir sulfate, infliximab; Lamivudine, lamivudine/zidovudine/abacavir sulfate, leteprinim potassium, levetiracetam, liposomal doxorubicin, lopinavir, lopinavir/ritonavir, losartan potassium; MCC-465, MRA; Nebivolol, nesiritide, nevirapine; Olanzapine, OROS(R)-Methylphenidate hydrochloride; Peginterferon alfa-2a, peginterferon alfa-2b, Pimecrolimus, polyethylene glycol 3350, pramlintide acetate, pregabalin, PRO-2000; Risedronate sodium, risperidone, ritonavir, rituximab, rivastigmine tartrate, rofecoxib, rosuvastatin calcium; Saquinavir mesilate, Stavudine; Tacrolimus, tadalafil, tamsulosin hydrochloride, telmisartan, tomoxetine hydrochloride, treprostinil sodium, trimegestone, trimetrexate; Valdecoxib, venlafaxine hydrochloride; Zoledronic acid monohydrate. PMID:12616965

  3. Gateways to clinical trials.

    PubMed

    Bayés, M; Rabasseda, X; Prous, J R

    2003-12-01

    Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Studies Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: Abetimus sodium, adalimumab, alefacept, alemtuzumab, almotriptan, AMGN-0007, anakinra, anti-CTLA-4 Mab, L-arginine hydrochloride, arzoxifene hydrochloride, astemizole, atazanavir sulfate, atlizumab; Belimumab, BG-9928, binodenoson, bosentan, botulinum toxin type B, bovine lactoferrin, BufferGel; Caspofungin acetate, ciclesonide,cilomilast, ciluprevir, clofarabine, CVT-3146; Darbepoetin alfa, desloratadine, diflomotecan, doripenem, dronedarone hydrochloride, drotrecogin alfa (activated), DT388-GM-CSF, duloxetine hydrochloride, E-5564, efalizumab, enfuvirtide, esomeprazole magnesium, estradiol acetate, ETC-642, exenatide, exisulind, ezetimib; Febuxostat; Gallium maltolate, ganirelix acetate, garenoxacin mesilate, gefitinib; H11, HuMax; IL-15, IDD-1, IGIV-C, imatinib mesylate, ISIS-14803, ITF-1697, ivabradine hydrochloride; KRN-5500; L-365260, levetiracetam, levosimendan, licofelone, linezolid, LJP-1082, lopinavir lumiracoxib; MCC-478, melatonin, morphine hydrochloride, morphine-6-glucuronide, moxidectin; N-Acetylcarnosine, natalizumab, NM-702, NNC-05-1869, NSC-703940; Ocinaplon OM-89, omalizumab, omeprazole/ sodium bicarbonate, OPC-28326, ospemifene; PEG-filgrastim peginterferon alfa-2a, pegsunercept, pirfenidone, pralmorelin, pregabalin; Recombinant glucagon-like peptide-1 (7-36) amide, repifermin, RSD-1235; S-8184, selodenoson, sodium dichloroacetate, suberanilohydroxamic acid; TAS-102, terfenadine, teriparatide, tipranavir troxacitabine; Ximelagatran; YM-337. PMID:14735233

  4. Gateways to clinical trials.

    PubMed

    Bayés, M; Rabasseda, X; Prous, J R

    2003-04-01

    Gateways to clinical trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Studies knowledge area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: 5A8; Agomelatine, alefacept, almotriptan, anakinra, APC-8015, atazanavir, atomoxetine hydrochloride, azimilide hydrochloride; Bicifadine; Cannabidiol, caspofungin acetate, CAT-213, CGP-51901, ciclesonide, cipamfylline; Darbepoetin alfa, desloratadine, dibotermin alfa, DX-9065a; Ecogramostim, efalizumab, eletriptan, eniluracil, EPI-KAL2, erlosamide, ertapenem sodium, etilevodopa, etoricoxib, ezetimibe; Fosamprenavir calcium, fosamprenavir sodium, fumagillin; Gadofosveset sodium, gefitinib, gemtuzumab ozogamicin; HSPPC-96, human papillomavirus vaccine; Icatibant Id-KLH, imatinib mesylate, INS-37217, iodine (I131) tositumomab; LAS-34475, levobupivacaine hydrochloride, levocetirizine, linezolid, 131I-lipiodol, lonafarnib, lopinavir, LY-450108; Magnetites, MBI-594AN, melagatran, melatonin, mepolizumab, mycophenolic acid sodium salt; NC-100100; 1-Octanol, omalizumab, omapatrilat, onercept; PEG-filgrastim, (PE)HRG21, peginterferon alfa-2a, peginterferon alfa-2b, pleconaril, pneumococcal 7-valent conjugate vaccine, prasterone; Ranelic acid distrontium salt, rasagiline mesilate, reslizumab, rFGF-2, rhOP-1, rosuvastatin calcium, roxifiban acetate; Sitaxsentan sodium, sodium lauryl sulfate; Tadalafil, telithromycin, tenofovir disoproxil fumarate, tipranavir, TMC-114, tucaresol; Valdecoxib, voriconazole; Ximelagatran; Zofenopril calcium, zosuquidar trihydrochloride. PMID:12743628

  5. Gateways to clinical trials.

    PubMed

    Bayés, M; Rabasseda, X; Prous, J R

    2003-10-01

    Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Studies Knowledge Area of Prous Science Integrity(R), the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: 3,4-DAP; Adefovir dipivoxil, ADL-10-0101, alefacept, alemtuzumab, alosetron hydrochloride, ALT-711, aprepitant, atazanavir sulfate, atlizumab, atvogen; Bortezomib; CETP vaccine, clevudine, crofelemer; DAC:GLP-1, darbepoetin alfa, decitabine, drotrecogin alfa (activated), DX-9065a; E-7010, edodekin alfa, emivirine, emtricitabine, entecavir, erlosamide, erlotinib hydrochloride, everolimus, exenatide; Fondaparinux sodium, frovatriptan, fulvestrant; Gemtuzumab ozogamicin, gestodene; Homoharringtonine, human insulin; Imatinib mesylate, indiplon, indium 111 (111In) ibritumomab tiuxetan, inhaled insulin, insulin detemir, insulin glargine, ivabradine hydrochloride; Lanthanum carbonate, lapatinib, LAS-34475, levetiracetam, liraglutide, lumiracoxib; Maxacalcitol, melagatran, micafungin sodium; Natalizumab, NSC-640488; Oblimersen sodium; Parecoxib sodium, PEG-filgrastim, peginterferon alfa-2(a), peginterferon alfa-2b, pexelizumab, pimecrolimus, pleconaril, pramlintide acetate, pregabalin, prucalopride; rAHF-PFM, Ranelic acid distrontium salt, ranolazine, rDNA insulin, recombinant human soluble thrombomodulin, rhGM-CSF, roxifiban acetate, RSD-1235, rubitecan, ruboxistaurin mesilate hydrate; SC-51, squalamine; Tegaserod maleate, telbivudine, tesaglitazar, testosterone gel, tezosentan disodium, tipranavir; Vatalanib succinate; Ximelagatran; Yttrium 90 (90Y) ibritumomab tiuxetan; Zoledronic acid monohydrate. PMID:14671684

  6. Gateways to clinical trials.

    PubMed

    Bayés, M; Rabasseda, X; Prous, J R

    2006-05-01

    Gateways to Clinical Trials are a guide to the most recent clinical trials in current literature and congresses. The data in the following tables have been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com/. This issue focuses on the following selection of drugs: Adalimumab, adenosine triphosphate, alemtuzumab, alendronate sodium/cholecalciferol, aliskiren fumarate, AMGN-0007, aminolevulinic acid methyl ester, anakinra, anidulafungin, aripiprazole, atomoxetine hydrochloride; Bevacizumab, bosentan; Calcipotriol/beta methasone dipropionate, caldaret hydrate, caspofungin acetate, cetuximab, cinacalcet hydrochloride, clopidogrel, cocaine-BSA conjugate, conivaptan hydrochloride, Cypher; Darbepoetin alfa, delmitide, desloratadine, desmoteplase, desoxyepothilone B, disufenton sodium, DU-176b, duloxetine hydrochloride, dutasteride; EBV-specific CTLs, ecogramostim, edodekin alfa, efalizumab, eletriptan, emtricitabine, entecavir, erlotinib hydrochloride, ertapenem sodium, escitalopram oxalate, etoricoxib, everolimus, ezetimibe; Fanapanel, fondaparinux sodium; Gefitinib, GTI-2040, GW-501516; Her2 E75-peptide vaccine, human insulin; Ibogaine, icatibant acetate, Id-KLH vaccine, imatinib mesylate, immune globulin subcutaneous [human], indacaterol, inolimomab, ipilimumab, i.v. gamma-globulin, ivabradine hydrochloride, ixabepilone; Lacosamide, lanthanum carbonate, lenalidomide, levocetirizine, levodopa methyl ester hydrochloride/carbidopa, levodopa/carbidopa/entacapone, lidocaine/prilocaine; Maraviroc, mecasermin, melevodopa hydrochloride, mepolizumab, mitumomab; Nesiritide; Omalizumab, oral insulin; Parathyroid hormone (human recombinant), patupilone, pegaptanib sodium, PEG-filgrastim, pemetrexed disodium, photochlor, pimecrolimus, posaconazole, prasterone, prasugrel, pregabalin, prilocaine, PRX-00023; QS-21; Ranibizumab, ranirestat, rhodamine 123, rotigaptide; Sarcosine, sirolimus

  7. Gateways to clinical trials.

    PubMed

    Bayés, M; Rabasseda, X; Prous, J R

    2006-01-01

    Gateways to Clinical Trials are a guide to the most recent clinical trials in current literature and congresses. The data in the following tables have been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: ABT-510, adalimumab, alefacept, ambrisentan, aminolevulinic acid methyl ester, armodafinil, aselizumab, asenapine maleate, azelnidipine; Bevacizumab, bexarotene, bimosiamose, biphasic insulin aspart, bortezomib, bosentan, BQ-123; C340, cannabidiol, caspofungin acetate, CC-4047, certolizumab pegol, cetuximab, ciclesonide, cilansetron, Cypher; Dabigatran etexilate, darbepoetin alfa, darifenacin hydrobromide, desloratadine, dexosome vaccine (melanoma), dimethyl fumarate, dronabinol/cannabidiol, drospirenone, drospirenone/estradiol, drotrecogin alfa (activated), duloxetine hydrochloride, dutasteride; Efalizumab, eglumetad hydrate, emoxipin hydrochloride, eplerenone, erlotinib hydrochloride, escitalopram oxalate, etonogestrel/ethinylestradiol; Garenoxacin mesilate, gamma-hydroxybutyrate sodium, gefitinib; H5N1 pandemic influenza vaccine, human growth hormone-(177-191), human insulin; Indacaterol, INKP-100, INKP-102, insulin glargine, i.v. gamma-globulin; KLH; Lapatinib, L-arginine hydrochloride, lasofoxifene tartrate, levocetirizine, licochalcone A, LMI vaccine, lomefloxacin, lubiprostone, lumiracoxib; Miglustat, mycograb; Natalizumab, NCX-4016, nortopixantrone hydrochloride; Olmesartan medoxomil, omalizumab, oral insulin, OrM3; Parathyroid hormone (human recombinant), parecoxib sodium, PCK-3145, PEG-filgrastim, peginterferon alfa-2a, pemetrexed disodium, pexelizumab, photochlor, pimecrolimus, pneumococcal 7-valent conjugate vaccine, polyphenon E; R-126638, R-411, resveratrol, roflumilast, RS-86, ruboxistaurin mesilate hydrate, rupatadine fumarate; Sipuleucel-T, somatropin, St. John's Wort extract; Tadalafil, Taxus

  8. Gateways to clinical trials.

    PubMed

    Bayes, M; Rabasseda, X; Prous, J R

    2006-01-01

    Gateways to Clinical Trials are a guide to the most recent clinical trials in current literature and congresses. The data in the following tables have been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs:(R)-Flurbiprofen, 90Yttrium-DOTA-huJ591; ABT-510, ACP-103, Ad5-FGF4, adalimumab, ademetionine, AG-7352, alemtuzumab, Amb a 1 ISS-DNA, anakinra, apaziquone, aprepitant, aripiprazole, atazanavir sulfate; BAL-8557, bevacizumab, BMS-188797, bortezomib, bosentan, brivudine; Calcipotriol/betamethasone dipropionate, cannabidiol, caspofungin acetate, catumaxomab, CERE-120, cetuximab, ciclesonide, cilomilast, cizolirtine citrate, Cypher, cystemustine; Dalbavancin, darifenacin hydrobromide, dasatinib, deferasirox, denosumab, desmoteplase, dihydrexidine, dimethyl fumarate, dutasteride, DW-166HC; Eculizumab, enfuvirtide, entecavir, epratuzumab, erlotinib hydrochloride, escitalopram oxalate, eszopiclone, etoricoxib, everolimus; Fallypride, febuxostat, fenretinide, fesoterodine, fingolimod hydrochloride; Gabapentin enacarbil, gefitinib; hMaxi-K, human papillomavirus vaccine, HYAL-CT1101; Imatinib mesylate, indiplon, inolimomab, ISAtx-247; J591; Lacosamide, landiolol, lasofoxifene tartrate, lestaurtinib, lidocaine/prilocaine, linezolid, lixivaptan, lonafarnib, lopinavir, lopinavir/ritonavir, lumiracoxib; Natalizumab, nesiritide; OC-108, omalizumab, onercept, OSC; Palifermin, palonosetron hydrochloride, parathyroid hormone (human recombinant), parecoxib sodium, PD-MAGE-3 vaccine, PEG-filgrastim, peginterferon alfa-2a, peginterferon alfa-2b, pegsunercept, pelitinib, pitavastatin calcium, plerixafor hydrochloride, posaconazole, prasterone sulfate, pregabalin; Ramelteon, ranelic acid distrontium salt, rasburicase, rosuvastatin calcium, rotigotine, RSD-1235, rufinamide, rupatadine fumarate; Sarizotan hydrochloride, SHL-749

  9. Gateways to clinical trials.

    PubMed

    Bayes, M; Rabasseda, X; Prous, J R

    2006-09-01

    Gateways to Clinical Trials are a guide to the most recent clinical trials in current literature and congresses. The data in the following tables have been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com This issue focuses on the following selection of drugs: A-007, A6, adalimumab, adenosine triphosphate, alefacept, alemtuzumab, AllerVax Ragweed, amphora, anakinra, angiotensin-(1-7), anidulafungin, apomine, aripiprazole, atomoxetine hydrochloride, avanafil; BAL-8557, becatecarin, bevacizumab, biphasic insulin aspart, BMS-188797, bortezomib, bosentan, botulinum toxin type B, brivudine; Calcipotriol/betamethasone dipropionate, caspofungin acetate, catumaxomab, certolizumab pegol, cetuximab, CG-0070, ciclesonide, cinacalcet hydrochloride, clindamycin phosphate/benzoyl peroxide, cryptophycin 52, Cypher; Dabigatran etexilate, darapladib, darbepoetin alfa, decitabine, deferasirox, desloratadine, dexanabinol, dextromethorphan/quinidine sulfate, DMF, drotrecogin alfa (activated), duloxetine hydrochloride; E-7010, edaravone, efalizumab, emtricitabine, entecavir, eplerenone, erlotinib hydrochloride, escitalopram oxalate, estradiol valerate/dienogest, eszopiclone, exenatide, ezetimibe; Fondaparinux sodium, fulvestrant; Gefitinib, gestodene, GYKI-16084; Hyaluronic acid, hydralazine hydrochloride/isosorbide dinitrate; Imatinib mesylate, indiplon, insulin glargine; Juzen-taiho-to; Lamivudine/zidovudine/abacavir sulfate, L-arginine hydrochloride, lasofoxifene tartrate, L-BLP-25, lenalidomide, levocetirizine, levodopa/carbidopa/entacapone, lexatumumab, lidocaine/prilocaine, lubiprostone, lumiracoxib; MAb-14.18, mitoquidone; Natalizumab, neridronic acid, neuradiab; Olpadronic acid sodium salt, omalizumab; p53-DC vaccine, parathyroid hormone (human recombinant), peginterferon alfa-2a, peginterferon alfa-2b, pemetrexed disodium, perifosine, pimecrolimus, prasterone, prasugrel, PRO-2000

  10. Gateways to clinical trials.

    PubMed

    Tomillero, A; Moral, M A

    2010-12-01

    Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Trials Knowledge Area of Thomson Reuters Integrity(SM), the drug discovery and development portal, http://www.thomsonreutersintegrity.com. This issue focuses on the following selection of drugs: 17-Hydroxyprogesterone caproate; Abacavir sulfate/lamivudine, Aclidinium bromide, Adalimumab, Adefovir, Alemtuzumab, Alkaline phosphatase, Amlodipine, Apilimod mesylate, Aripiprazole, Axitinib, Azacitidine; Belotecan hydrochloride, Berberine iodide, Bevacizumab, Bortezomib, Bosentan, Bryostatin 1; Calcipotriol/hydrocortisone, Carglumic acid, Certolizumab pegol, Cetuximab, Cinacalcet hydrochloride, Cixutumumab, Coumarin, Custirsen sodium; Darbepoetin alfa, Darifenacin hydrobromide, Darunavir, Dasatinib, Denibulin hydrochloride, Denosumab, Diacetylmorphine, Dulanermin, Duloxetine hydrochloride; Ecogramostim, Enfuvirtide, Entecavir, Enzastaurin hydrochloride, Eplerenone, Escitalopram oxalate, Esomeprazole sodium, Etravirine, Everolimus, Ezetimibe; Fenofibrate/pravastatin sodium, Ferric carboxymaltose, Flavangenol, Fondaparinux sodium; Glutamine, GSK-1024850A; Hepatitis B hyperimmunoglobulin, Hib-MenC, HIV-LIPO-5; Immunoglobulin intravenous (human), Indacaterol maleate, Indibulin, Indium 111 (¹¹¹In) ibritumomab tiuxetan, Influenza A (H1N1) 2009 Monovalent vaccine, Inhalable human insulin, Insulin glulisine; Lapatinib ditosylate, Leucovorin/UFT; Maraviroc, Mecasermin, MMR-V, Morphine hydrochloride, Morphine sulfate/naltrexone hydrochloride, Mycophenolic acid sodium salt; Naproxen/esomeprazole magnesium, Natalizumab; Oncolytic HSV; Paliperidone, PAN-811, Paroxetine, Pegfilgrastim, Peginterferon alfa-2a, Peginterferon alfa-2b/ribavirin, Pegvisomant, Pemetrexed disodium, Pimecrolimus, Posaconazole, Pregabalin; Raltegravir potassium, Ranelic acid distrontium salt, Rasburicase, Rilpivirine

  11. Gateways to clinical trials.

    PubMed

    Bayes, M; Rabasseda, X; Prous, J R

    2004-01-01

    Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Trials Know- ledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: ABI-007, Ad.Egr.TNF.11D, adefovir dipivoxil, AdPEDF.11, AES-14, albumex, alefacept, alemtuzumab, aliskiren fumarate, alvimopan hydrate, aAminolevulinic acid hydrochloride, aminolevulinic acid methyl ester, anakinra, anti-IL-12 MAb, aprepitant, atazanavir sulfate, atrasentan, avanafil; Banoxantrone, BG-12, bimatoprost, bortezomib, bosentan; Calcipotriol/betamethasone dipropionate, caspofungin acetate, CBT-1, ciclesonide, clofarabine, conivaptan hydrochloride, CpG-7909, C-Vax, Cypher; DA-8159, DAC:GLP-1, darbepoetin alfa, darifenacin, duloxetine hydrochloride; Eculizumab, efalizumab, efaproxiral sodium, EGF vaccine, eletriptan, epratuzumab, erlotinib hydrochloride, escitalopram oxalate, ETC-642, etoricoxib, everolimus, exenatide; Gefitinib, IV gamma-globulin; Human insulin, gamma-hydroxybutyrate sodium; IDN-6556, iguratimod, imatinib mesylate, indiplon, ixabepilone; Laquinimod, LB-80380, lidocaine/prilocaineliraglutide, lopinavir, lopinavir/ritonavir, lucinactant; MAb-14.18, melatonin, MLN-591-DM1; NC-531, neridronic acid, nesiritide, neutrophil-inhibitory factor, niacin/lovastatin; Oblimersen sodium, olcegepant, oral Insulin, ORV-105; Palonosetron hydrochloride, PAmAb, pegaptanib sodium, peginterferon alfa-2a, pegvisomant, perifosine, pexelizumab, phenoxodiol, phenserine tartrate, pimecrolimus, pramlintide acetate, pregabalin, PRO-542, prostate cancer vaccine, PT-141; Ramelteon, rasagiline mesilate, rDNA insulin, reslizumab, rh-Lactoferrin, ribamidine hydrochloride, rosuvastatin calcium; S-8184l, SC-1, sorafenib, St. John's Wort extract, SU-11248; Taxus, telbivudine, tenofovir disoproxil fumarate, teriparatide

  12. Gateways to clinical trials.

    PubMed

    Bayes, M; Rabasseda, X; Prous, J R

    2004-09-01

    Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: 101M, 166Ho-DOTMP, 3-AP; Abatacept, abetimus sodium, ACR-16, adefovir dipivoxil, alefacept, AMD-070, aminolevulinic acid hexyl ester, anatumomab mafenatox, anti-CTLA-4 MAb, antigastrin therapeutic vaccine, AP-12009, AP-23573, APC-8024, aripiprazole, ATL-962, atomoxetine hydrochloride; Bevacizumab, bimatoprost, bortezomib, bosentan, BR-1; Calcipotriol/betamethasone dipropionate, cinacalcet hydrochloride, clofazimine, colchicine, cold-adapted influenza vaccine trivalent, CRM197; Desloratadine, desoxyepothilone B, diethylhomospermine; Edodekin alfa, efalizumab, elcometrine, eletriptan, enfuvirtide, entecavir, EP-2101, eplerenone, erlotinib hydrochloride, etoricoxib, everolimus, exherin, ezetimibe; Febuxostat, fluorescein lisicol, fosamprenavir calcium, frovatriptan; Hemoglobin raffimer, HSPPC-96, human insulin; Imatinib mesylate, insulin detemir, insulin glargine, IRX-2, istradefylline, IV gamma-globulin, ixabepilone; Kahalalide F; L-759274, levodopa/carbidopa/entacapone, licofelone, lonafarnib, lopinavir, lurtotecan, LY-156735; MAb G250, mecasermin, melatonin, midostaurin, muraglitazar; Nesiritide, nitronaproxen; O6-Benzylguanine, olmesartan medoxomil, olmesartan medoxomil/hydrochlorothiazide, omapatrilat, oral insulin; Parecoxib sodium, PCK-3145, peginterferon alfa-2a, peginterferon alfa-2b, peginterferon alfa-2b/ ribavirin, pemetrexed disodium, peptide YY3-36, PG-CPT, phenoxodiol, pimecrolimus, posaconazole; Rasagiline mesilate, rDNA insulin, RG228, rimonabant hydrochloride, rosuvastatin calcium, rotigotine hydrochloride; S-3304, safinamide mesilate, salcaprozic acid sodium salt, SDZ-SID-791, SGN-30, soblidotin

  13. Gateways to clinical trials.

    PubMed

    Tomillero, A; Moral, M A

    2009-09-01

    Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: AAV1/SERCA2a, Abacavir sulfate/lamivudine, Adalimumab, Aliskiren fumarate, Ambrisentan, Aripiprazole, AT-7519, Atazanavir sulfate, Atomoxetine hydrochloride, Azacitidine, Azelnidipine; Besifloxacin hydrochloride, Bevacizumab, Bioabsorbable everolimus-eluting coronary stent, Bortezomib, Bosentan, Budesonide/formoterol fumarate; CAIV-T, Carisbamate, Casopitant mesylate, Certolizumab pegol, Cetuximab, Ciclesonide, Ciprofloxacin/dexamethasone, CTCE-9908; Dalcetrapib, Darunavir, Deferasirox, Desloratadine, Disitertide, Drotrecogin alfa (activated), DTA-H19, Duloxetine hydrochloride, Dutasteride; Ecogramostim, Efalizumab, Emtricitabine, Eribulin mesilate, Escitalopram oxalate, Eszopiclone, EUR-1008, Everolimus-eluting coronary stent, Exenatide; Fampridine, Fluticasone furoate, Formoterol fumarate/fluticasone propionate, Fosamprenavir calcium, Fulvestrant; Gabapentin enacarbil, GS-7904L; HPV-6/11/16/18, Human Secretin, Hydralazine hydrochloride/isosorbide dinitrate; Imatinib mesylate, Imexon, Inalimarev/Falimarev, Indacaterol, Indacaterol maleate, Inhalable human insulin, Insulin detemir, Insulin glargine, Ixabepilone; L-Alanosine, Lapatinib ditosylate, Lenalidomide, Levocetirizine dihydrochloride, Liraglutide, Lisdexamfetamine mesilate, Lopinavir, Loratadine/montelukast sodium, Lutropin alfa; MeNZB, Mepolizumab, Micafungin sodium, Morphine hydrochloride; Nabiximols, Nikkomycin Z; Olmesartan medoxomil, Omalizumab; Paclitaxel-eluting stent, Pegfilgrastim, Peginterferon alfa-2a, Peginterferon alfa-2b, Perifosine, PF-489791, Plitidepsin, Posaconazole, Pregabalin; QAX-576; Raltegravir potassium, Ramelteon, Rasagiline

  14. Gateways to clinical trials.

    PubMed

    Bayés, M; Rabasseda, X; Prous, J R

    2004-10-01

    Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: Abiraterone acetate, Ad5CMV-p53, adefovir dipivoxil, AE-941, ambrisentan, aripiprazole, atomoxetine hydrochloride, atrasentan; BCH-10618, bimatoprost, BMS-184476, BMS-275183, BMS-387032, botulinum toxin type B, BR-1, BR96-Doxorubicin; Capravirine, caspofungin acetate, cinacalcet hydrochloride; Darbepoetin alfa, desloratadine, dextrin sulfate, DJ-927, duloxetine hydrochloride; Elacridar, emtricitabine, eplerenone, ertapenem sodium, escitalopram oxalate, ESP-24217, etoricoxib, exenatide, ezetimibe; Ferumoxtran-10, fondaparinux sodium, fosamprenavir calcium; GS-7904L, GW-5634; HMN-214, human insulin; IC-14, imatinib mesylate, indiplon, insulin glargine, insulinotropin, iseganan hydrochloride; Lanthanum carbonate, L-Arginine hydrochloride, LEA29Y, lenalidomide, LE-SN38, lestaurtinib, L-MDAM, lometrexol, lopinavir, lopinavir/ritonavir; Magnesium sulfate, maraviroc, mepolizumab, metreleptin, milataxel, MNA-715, morphine hydrochloride; Nesiritide, neutrophil-inhibitory factor, NK-911; Olanzapine/fluoxetine hydrochloride, olmesartan medoxomil, omalizumab, ortataxel, oxycodone hydrochloride/ibuprofen; Panitumumab, patupilone, PC-515, PD-MAGE-3 Vaccine, peginterferon alfa-2a, peginterferon alfa-2b, peginterferon alfa-2b/ ribavirin, pemetrexed disodium, pimecrolimus, prasugrel, pregabalin, PRO-2000; Rosuvastatin calcium, RPR-113090; sabarubicin hydrochloride, safinamide mesilate, SB-715992, sitaxsentan sodium, soblidotin, synthadotin; Tadalafil, taltobulin, temsirolimus, tenofovir disoproxil fumarate, tenofovir disoproxil fumarate/emtricitabine, testosterone gel, tigecycline, tipranavir, tirapazamine, trabectedin

  15. Gateways to clinical trials.

    PubMed

    Bayes, M; Rabasseda, X; Prous, J R

    2005-10-01

    Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables have been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: (-)-Epigallocatechin gallate, (Z)-4-hydroxytamoxifen; Ad.muIFN-beta AD-237, adalimumab, adefovir dipivoxil, agalsidase alfa, alemtuzumab, almotriptan, ALVAC vCP1452, alvimopan hydrate, ambrisentan, anakinra, anti-IFN-gamma MAb; Bimatoprost, BMS-188797, BMS-214662, bortezomib, bosentan, bovine lactoferrin; Caffeine, canertinib dihydrochloride, canfosfamide hydrochloride, cannabidiol, caspofungin acetate, cetuximab, cH36, ChimeriVax-JE, ciclesonide, cilansetron, cinacalcet hydrochloride, clopidogrel, CpG-7909, Cypher; Daptomycin, darbepoetin alfa, darifenacin hydrobromide, decitabine, denufosol tetrasodium, Dexamet, diindolemethane, drotrecogin alfa (activated), duloxetine hydrochloride, DX-9065a; E-7010, edaravone, efalizumab, eicosapentaenoic acid/docosahexaenoic acid, elacridar, eletriptan, emtricitabine, epratuzumab, erlotinib hydrochloride, ertapenem sodium, eszopiclone, everolimus, ezetimibe; Fludarabine, fondaparinux sodium; gamma-Hydroxybutyrate sodium, gavestinel sodium, gefitinib, granisetron-Biochronomer; Human Albumin, human insulin; Imatinib mesylate, indiplon, interleukin-2 XL, isatoribine, ISS-1018, i.v. gamma-globulin, ivabradine hydrochloride, ixabepilone; Lanthanum carbonate, L-arginine hydrochloride, liposomal doxorubicin, LY-450139; Magnesium sulfate, melatonin, motexafin gadolinium, mycophenolic acid sodium salt; Natalizumab, nesiritide, niacin/lovastatin; OGX-011, olmesartan medoxomil, omalizumab, ospemifene; PACAP38, panitumumab, parathyroid hormone (human recombinant), parecoxib sodium, patupilone, pegfilgrastim, peginterferon alfa-2a, peginterferon alfa-2b, peginterferon alfa-2b

  16. Gateways to clinical trials.

    PubMed

    Bayés, M; Rabasseda, X; Prous, J R

    2005-04-01

    Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity. prous.com. This issue focuses on the following selection of drugs: ABX-IL-8, Acclaim, adalimumab, AGI-1067, alagebrium chloride, alemtuzumab, Alequel, Androgel, anti-IL-12 MAb, AOD-9604, aripiprazole, atomoxetine hydrochloride; Biphasic insulin aspart, bosentan, botulinum toxin type B, bovine lactoferrin, brivudine; Cantuzumab mertansine, CB-1954, CDB-4124, CEA-TRICOM, choriogonadotropin alfa, cilansetron, CpG-10101, CpG-7909, CTL-102, CTL-102/CB-1954; DAC:GRF, darbepoetin alfa, davanat-1, decitabine, del-1 Genemedicine, dexanabinol, dextofisopam, dnaJP1, dronedarone hydrochloride, dutasteride; Ecogramostim, eletriptan, emtricitabine, EPI-hNE-4, eplerenone, eplivanserin fumarate, erlotinib hydrochloride, ertapenem sodium, escitalopram oxalate, esomeprazole magnesium, etoricoxib, ezetimibe; Falecalcitriol, fingolimod hydrochloride; Gepirone hydrochloride; HBV-ISS, HSV-2 theracine, human insulin; Imatinib mesylate, Indiplon, insulin glargine, ISAtx-247; L612 HuMAb, levodopa/carbidopa/entacapone, lidocaine/prilocaine, LL-2113AD, lucinactant, LY-156735; Meclinertant, metelimumab, morphine hydrochloride, morphine-6-glucuronide; Natalizumab, nimotuzumab, NX-1207, NYVAC-HIV C; Omalizumab, onercept, osanetant; PABA, palosuran sulfate, parathyroid hormone (human recombinant), parecoxib sodium, PBI-1402, PCK-3145, peginterferon alfa-2a, peginterferon alfa-2b, peginterferon alfa-2b/ribavirin, pemetrexed disodium, pimecrolimus, PINC, pregabalin; Ramelteon, rasagiline mesilate, rasburicase, rimonabant hydrochloride, RO-0098557, rofecoxib, rosiglitazone maleate/metformin hydrochloride; Safinamide mesilate, SHL-749, sitaxsentan sodium, sparfosic acid, SprayGel, squalamine, St. John's Wort

  17. Overcoming Challenges to Initiating Cell Therapy Clinical Trials in Rapidly Developing Countries: India as a Model

    PubMed Central

    Rao, Mahendra; Keating, Armand; Srivastava, Alok

    2013-01-01

    Increasingly, a number of rapidly developing countries, including India, China, Brazil, and others, are becoming global hot spots for the development of regenerative medicine applications, including stem cell-based therapies. Identifying and overcoming regulatory and translational research challenges and promoting scientific and ethical clinical trials with cells will help curb the growth of stem cell tourism for unproven therapies. It will also enable academic investigators, local regulators, and national and international biotechnology and biopharmaceutical companies to accelerate stem cell-based clinical research that could lead to effective innovative treatments in these regions. Using India as a model system and obtaining input from regulators, clinicians, academics, and industry representatives across the stem cell field in India, we reviewed the role of key agencies and processes involved in this field. We have identified areas that need attention and here provide solutions from other established and functioning models in the world to streamline and unify the regulatory and ethics approval processes for cell-based therapies. We also make recommendations to check the growth and functioning of clinics offering unproven treatments. Addressing these issues will remove considerable hurdles to both local and international investigators, accelerate the pace of research and development, and create a quality environment for reliable products to emerge. By doing so, these countries would have taken one important step to move to the forefront of stem cell-based therapeutics. PMID:23836804

  18. Therapeutic hotline. Effectiveness of the association of cetirizine and topical steroids in lichen planus pilaris--an open-label clinical trial.

    PubMed

    d'Ovidio, Roberto; Rossi, Alfredo; Di Prima, Tiziana Maria

    2010-01-01

    Lichen planus is considered a T cell-mediated immunological disease. Even mast cells may contribute to the pathogenesis of the disease. Keratinocytes of the basal layer of the skin and/or the hair follicle may represent the "target/victim" of an immune aggression, determining the destruction of the hair follicle and thus scarring alopecia. Therefore, there is a compelling urgency for effective treatment of this potentially disfiguring dermatosis. Our data provide a further therapeutic opportunity: the use of an antihistaminic drug--cetirizine (CTZ)--in an "anti-inflammatory" regimen. We propose the use of CTZ at the dosage of 30 mg/daily. Twenty-one patients affected by lichen planus pilaris (LPP) of the scalp have been treated. Topical application of steroids has been coadministered in all cases during the therapy. Clinical effects, in the sense of stabilization with cessation of the inflammation (erythema, follicular hyperkeratosis, loss of anagen hair), were achieved in all patients but three. One patient developed cardiac arrhythmia after 3 months of successful treatment and dropped out. Our cases indicate that a combined therapy of topical steroid with CTZ can be a safe and effective choice even in severe cases of lichen planus pilaris, so often refractory to the therapy. PMID:20868410

  19. Likelihood and clinical trials.

    PubMed

    Hill, G; Forbes, W; Kozak, J; MacNeill, I

    2000-03-01

    The history of the application of statistical theory to the analysis of clinical trials is reviewed. The current orthodoxy is a somewhat illogical hybrid of the original theory of significance tests of Edgeworth, Karl Pearson, and Fisher, and the subsequent decision theory approach of Neyman, Egon Pearson, and Wald. This hegemony is under threat from Bayesian statisticians. A third approach is that of likelihood, stemming from the work of Fisher and Barnard. This approach is illustrated using hypothetical data from the Lancet articles by Bradford Hill, which introduced clinicians to statistical theory. PMID:10760630

  20. International Clinical Trial Day and clinical trials in Ethiopia and Africa.

    PubMed

    Fekadu, Abebaw; Teferra, Solomon; Hailu, Asrat; Gebre-Mariam, Tsige; Addissie, Adamu; Deressa, Wakgari; Yimer, Getnet; Reja, Ahmed

    2014-01-01

    Low income countries like Ethiopia are underrepresented in clinical research. As a major public commitment to clinical research, Ethiopia celebrated the International Clinical Trial Day (ICTD) for the first time on 20 May 2014 under the auspices of Addis Ababa University. The motto for the day was 'Clinical Trials for Excellence in Patient Care'. The celebration offered an opportunity to inform academic staff, researchers, students and the leadership about clinical trials being conducted and to discuss the future of clinical trials in the country. Although clear challenges to the conduct of trials abound, clinical trials registered from Ethiopia in trial registration databases is increasing. Cross-country collaborations, international funding support, motivation of academic staff to conduct clinical trials and the commitment and engagement of the leadership in research are all improving. The overall impact of clinical trials is also encouraging. For example, some of the trials conducted in Ethiopia have informed treatment guidelines. However, administrative capacity, research infrastructure as well as financial support remain weak. There is a need for enhanced university-industry linkage and translation of research findings into locally relevant evidence. Ethiopia, as well as the whole of Africa, has an unparalleled opportunity to lead the way in clinical trials, given its prospect of development and the need to have locally relevant evidence for its growing population. In this commentary we reflect on the celebration of ICTD, the status and opportunities for conducting clinical trials and the way forward for facilitating clinical trials in Ethiopia and Africa. PMID:25526797

  1. Gateways to clinical trials.

    PubMed

    Tomillero, A; Moral, M A

    2008-10-01

    Gateways to clinical trials is a guide to the most recent trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity(R), the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: (+)-Dapoxetine hydrochloride, (S)-Tenatoprazole sodium salt monohydrate 19-28z, Acotiamide hydrochloride hydrate, ADV-TK, AE-37, Aflibercept, Albinterferon alfa-2b, Aliskiren fumarate, Asenapine maleate, Axitinib; Bavituximab, Becatecarin, beta-1,3/1,6-Glucan, Bevacizumab, Bremelanotide; Calcipotriol/betamethasone dipropionate, Casopitant mesylate, Catumaxomab, CDX-110, Cediranib, CMD-193, Cositecan; Darinaparsin, Denosumab, DP-b99, Duloxetine hydrochloride; E75, Ecogramostim, Elacytarabine, EMD-273063, EndoTAG-1, Enzastaurin hydrochloride, Eplerenone, Eribulin mesilate, Esomeprazole magnesium, Etravirine, Everolimus, Ezetimibe; Faropenem daloxate, Febuxostat, Fenretinide; Ghrelin (human); I-131 ch-TNT-1/B, I-131-3F8, Iclaprim, Iguratimod, Iloperidone, Imatinib mesylate, Inalimarev/Falimarev, Indacaterol, Ipilimumab, Iratumumab, Ispinesib mesylate, Ixabepilone; Lapatinib ditosylate, Laquinimod sodium, Larotaxel dehydrate, Linezolid, LOR-2040; Mapatumumab, MKC-1, Motesanib diphosphate, Mycophenolic acid sodium salt; NK-012; Olanzapine pamoate, Oncolytic HSV, Ortataxel; Paclitaxel nanoparticles, Paclitaxel poliglumex, Paliperidone palmitate, Panitumumab, Patupilone, PCV-9, Pegfilgrastim, Peginterferon alfa-2a, Peginterferon alfa-2b, Pertuzumab, Picoplatin, Pimavanserin tartrate, Pimecrolimus, Plerixafor hydrochloride, PM-02734, Poly I:CLC, PR1, Prasugrel, Pregabalin, Progesterone caproate, Prucalopride, Pumosetrag hydrochloride; RAV-12, RB-006, RB-007, Recombinant human erythropoietin alfa, Rimonabant, Romidepsin; SAR-109659, Satraplatin, Sodium butyrate; Tadalafil, Talampanel, Tanespimycin, Tarenflurbil, Tariquidar

  2. Effectiveness of spirometry as a motivational tool for smoking cessation: a clinical trial, the ESPIMOAT study

    PubMed Central

    2013-01-01

    Background Smoking is the main preventable cause of morbidity and mortality in our region, it being the main causative agent of chronic obstructive pulmonary disease. There still is no consensus on the use of spirometry as a strategy for smoking cessation, given that there is insufficient scientific evidence from high quality studies to recommend the use of this technique. Methods/Design This is to be a randomized, multicentre, open-label clinical trial. A total of 444 smokers over 40 years of age will be recruited by 39 general practitioners from 22 health centers. Primary objective of this study is to assess the effectiveness of spirometry together with information regarding the test for smoking cessation after 1 year in smokers over 40 years of age with a more than 10 pack-year history and no previous diagnosis of chronic obstructive pulmonary disease. Groups of 45 patients who smoke will be randomly selected from the lists of the participating doctors. The names will be sent to the corresponding doctors who will contact candidate patients and assess whether they meet the selection criteria. Patients who meet these criteria will be randomly allocated to an intervention or control group. For patients in both groups, a nurse will conduct an interview and perform a spirometry test to measure forced vital capacity. Then, all patients will be referred for an appointment with their doctor for brief anti-smoking intervention, patients from the intervention group additionally being informed about the result of the spirometry test. After 1 year, smoking status will be assessed and, in those who report that they have quit smoking, abstinence will be confirmed by co-oximetry. Data will be analyzed on an intention-to-treat basis using the chi-squared test for outcomes and binary logistic regression if it is considered to be necessary to adjust for confounding variables. Discussion Performing a spirometry test and providing information on pulmonary function may increase

  3. Clinical trial: free fatty acid suppositories compared with enema as bowel preparation for flexible sigmoidoscopy

    PubMed Central

    Ormarsson, Orri Thor; Asgrimsdottir, Gudrun Marta; Loftsson, Thorsteinn; Stefansson, Einar; Kristinsson, Jon Orvar; Lund, Sigrun Helga; Bjornsson, Einar Stefan

    2015-01-01

    Objectives The purpose of this trial was to evaluate the efficacy and safety of recently developed suppositories containing free fatty acids as a bowel-cleansing agent prior to flexible sigmoidoscopy and compare them with Klyx (docusate sodium/sorbitol). Design A controlled, non-inferiority, single-blind, randomised study on outpatients undergoing flexible sigmoidoscopy. Setting Department of Gastroenterology, Landspitali-University Hospital and endoscopic clinic. Patients 53 outpatients undergoing flexible sigmoidoscopy. Intervention Participants were randomised to receive either free fatty acid suppositories (28) or a standard bowel preparation with Klyx enema (25). In the study group, two suppositories were administered the evening before as well as 2 h prior to the sigmoidoscopy. In the control group, Klyx enema (120 mL) was administered the evening before and repeated 2 h prior to the procedure. Main outcome measurements Quality of the bowel cleansing, height of scope insertion and safety. Results The mean height of scope insertion and bowel cleansing was 43 cm (SD=13.4) in the study group and 48 cm (SD=10.4) in the control group (NS). The investigating physicians were less satisfied with the bowel preparation in the study group compared with the control group with a difference of 20% (p<0.016). The amount of faeces noted in the rectum was similar in both groups with no significant difference (p<0.56). No serious side effects, toxic reaction or irritation were observed. Conclusions The suppositories are well tolerated with no significant side effects. The suppositories had distinct bowel emptying effect and as effective as Klyx in rectal cleansing. Although physician's satisfaction was slightly lower, the height of scope insertion was similar. Trial registration number EudraCT nr.: 2010-018761-35. PMID:26500756

  4. Microbicide clinical trial adherence: insights for introduction.

    PubMed

    Woodsong, Cynthia; MacQueen, Kathleen; Amico, K Rivet; Friedland, Barbara; Gafos, Mitzy; Mansoor, Leila; Tolley, Elizabether; McCormack, Sheena

    2013-01-01

    After two decades of microbicide clinical trials it remains uncertain if vaginally- delivered products will be clearly shown to reduce the risk of HIV infection in women and girls. Furthermore, a microbicide product with demonstrated clinical efficacy must be used correctly and consistently if it is to prevent infection. Information on adherence that can be gleaned from microbicide trials is relevant for future microbicide safety and efficacy trials, pre-licensure implementation trials, Phase IV post-marketing research, and microbicide introduction and delivery. Drawing primarily from data and experience that has emerged from the large-scale microbicide efficacy trials completed to-date, the paper identifies six broad areas of adherence lessons learned: (1) Adherence measurement in clinical trials, (2) Comprehension of use instructions/Instructions for use, (3) Unknown efficacy and its effect on adherence/Messages regarding effectiveness, (4) Partner influence on use, (5) Retention and continuation and (6) Generalizability of trial participants' adherence behavior. Each is discussed, with examples provided from microbicide trials. For each of these adherence topics, recommendations are provided for using trial findings to prepare for future microbicide safety and efficacy trials, Phase IV post-marketing research, and microbicide introduction and delivery programs. PMID:23561044

  5. Gateways to Clinical Trials.

    PubMed

    Bayes, M; Rabasseda, X; Prous, J R

    2002-04-01

    Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Studies knowledge area of Prous Science Integrity, the world's first drug discovery and development portal, and provides information on study design, treatments, conclusions and references. This issue focuses on the following selection of drugs: Abiciximab, acetylcholine chloride, acetylcysteine, alefacept, alemtuzumab, alicaforsen, alteplase, aminopterin, amoxicillin sodium, amphotericin B, anastrozole, argatroban monohydrate, arsenic trioxide, aspirin, atazanavir, atorvastatin, augmerosen, azathioprine; Benzylpenicillin, BMS-284756, botulinum toxin type A, botulinum toxin type B, BQ-123, budesonide, BXT-51072; Calcium folinate, carbamazepine, carboplatin, carmustine, ceftriaxone sodium, cefuroxime axetil, chorionic gonadotropin (human), cimetidine, ciprofloxacin hydrochloride, cisplatin, citalopram hydrobromide, cladribine, clarithromycin, clavulanic acid, clofarabine, clopidogrel hydrogensulfate, clotrimazole, CNI-1493, colesevelam hydrochloride, cyclophosphamide, cytarabine; Dalteparin sodium, daptomycin, darbepoetin alfa, debrisoquine sulfate, dexrazoxane, diaziquone, didanosine, docetaxel, donezepil, doxorubicin hydrochloride liposome injection, DX-9065a; Eberconazole, ecogramostim, eletriptan, enoxaparin sodium, epoetin, epoprostenol sodium, erlizumab, ertapenem sodium, ezetimibe; Fampridine, fenofibrate, filgrastim, fluconazole, fludarabine phosphate, fluorouracil, 5-fluorouracil/epinephrine, fondaparinux sodium, formoterol fumarate; Gabapentin, gemcitabine, gemfibrozil, glatiramer; Heparin sodium, homoharringtonine; Ibuprofen, iloprost, imatinib mesilate, imiquimod, interferon alpha-2b, interferon alpha-2c, interferon-beta; KW-6002; Lamotrigine, lanoteplase, metoprolol tartrate, mitoxantrone hydrochloride; Naproxen sodium, naratriptan, Natalizumab, nelfinavir mesilate

  6. Gateways to clinical trials.

    PubMed

    Bayés, M; Rabasseda, X; Prous, J R

    2004-04-01

    Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Studies Knowledge Area of Prous Science Integrity(R), the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: ABI-007, adalimumab, adefovir dipivoxil, alefacept, alemtuzumab, 3-AP, AP-12009, APC-8015, L-Arginine hydrochloride, aripiprazole, arundic acid, avasimibe; Bevacizumab, bivatuzumab, BMS-181176, BMS-184476, BMS-188797, bortezomib, bosentan, botulinum toxin type B, BQ-123, BRL-55730, bryostatin 1; CEP-1347, cetuximab, cinacalcet hydrochloride, CP-461, CpG-7909; D-003, dabuzalgron hydrochloride, darbepoetin alfa, desloratadine, desoxyepothilone B, dexmethylphenidate hydrochloride, DHA-paclitaxel, diflomotecan, DN-101, DP-b99, drotrecogin alfa (activated), duloxetine hydrochloride, duramycin; Eculizumab, Efalizumab, EKB-569, elcometrine, enfuvirtide, eplerenone, erlotinib hydrochloride, ertapenem sodium, eszopiclone, everolimus, exatecan mesilate, ezetimibe; Fenretinide, fosamprenavir calcium, frovatriptan; GD2L-KLH conjugate vaccine, gefitinib, glufosfamide, GTI-2040; Hexyl insulin M2, human insulin, hydroquinone, gamma-Hydroxybutyrate sodium; IL-4(38-37)-PE38KDEL, imatinib mesylate, indisulam, inhaled insulin, ixabepilone; KRN-5500; LY-544344; MDX-210, melatonin, mepolizumab, motexafin gadolinium; Natalizumab, NSC-330507, NSC-683864; 1-Octanol, omalizumab, ortataxel; Pagoclone, peginterferon alfa-2a, peginterferon alfa-2b, pemetrexed disodium, phenoxodiol, pimecrolimus, plevitrexed, polyphenon E, pramlintide acetate, prasterone, pregabalin, PX-12; QS-21; Ragaglitazar, ranelic acid distrontium salt, RDP-58, recombinant glucagon-like peptide-1 (7-36) amide, repinotan hydrochloride, rhEndostatin, rh-Lactoferrin, (R)-roscovitine; S-8184, semaxanib, sitafloxacin hydrate, sitaxsentan sodium, sorafenib, synthadotin

  7. Gateways to clinical trials.

    PubMed

    Bayés, M; Rabasseda, X; Prous, J R

    2003-01-01

    Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Studies knowledge area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: 81C6; Adefovir dipivoxil, Agalsidase alfa, AGM-1470, albumin interferon alfa, alefacept, alosetron hydrochloride, anakinra, anti-CTLA-4 Mab, aprepitant, aripiprazole, atazanavir; BAY-43-9006, BBR-3438, beta-L-Fd4C, bimatoprost, bortezomib, bosentanBR96-doxorubicin; Caspofungin acetate, ciclesonide, cilengitide, cilomilast, COL-1621, COL-3, CpG-7909, cyclosporine; DCVax-Brain, dexmethylphenidate hydrochloride, dexosome vaccine (melanoma), donepezil hydrochloride, drotrecogin alfa (activated), DTI-015, [99Tc]-DTPA-mannosyldextran, duloxetine hydrochloride; Emivirine, emtricitabine, entecavir, epothilone B, estradiol-MNP, etonogestrel/etonogestrel/ethinylestradiol, etoricoxib; Febuxostat, fondaparinux sodium, fosamprenavir calcium; Gefitinib, GVS-111; Heparinase I, HspE7, human alpha-glucosidase, human insulin; Imatinib mesylate, INGN-241, interferon alfa B/D hybrid, interferon alfa Biphasix, ISIS-14803; Lanicemine hydrochloride, 1311-lipiodol, liposome-encapsulated mitoxantrone, lixivaptan, lumiracoxib, lupus-AHP, LY-466700; Marimastat, MEN-10755, micafungin sodium; Nitronaproxen, NSC-683864 Omalizumab, oral insulin; Palonosetron hydrochloride, peginterferon alfa-2a, pimecrolimus, pralnacasan, pramlintide acetate, pregabalin, pyrazoloacridine; R-165335, ranolazine, risperidone, RPR-109881;, RSD-1235, Satraplatin, seocalcitol, sertindole, SMART anti-interferon gamma antibody, sulfasalazine; T-138067, TAK-013, tegaserod maleate, telithromycin, tenofovir disoproxil fumarate, teriparatide, tiotropium bromide, tipifarnib, TP-38; Valdecoxib, vatalanib succinate, voriconazole; ZD-9331. PMID:12690708

  8. Gateways to clinical trials.

    PubMed

    Bayes, M; Rabasseda, X; Prous, J R

    2004-06-01

    Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Studies Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: 101M; Adalimumab, adefovir dipivoxil, adenosine triphosphate, albumin interferon alfa, alefacept, alemtuzumab, aminolevulinic acid hexyl ester, autologous renal tumor vaccine, azimilide hydrochloride; Bortezomib, bosentan, BR-1; C340, cantuzumab mertansine, caspofungin acetate, CGP-36742, CHAMPION everolimus-eluting coronary stent, cypher; Dalbavancin, darbepoetin alfa, desloratadine, duloxetine hydrochloride, dutasteride; Efalizumab, emtricitabine, enfuvirtide, erlosamide, ertapenem sodium, everolimus, ezetimibe; Flesinoxan hydrochloride, fosamprenavir calcium, FR-901228, frovatriptan; Gadofosveset sodium, gadomer-17, galiximab, gamma-hydroxybutyrate sodium, gefitinib; HuOKT3gamma1(Ala234-Ala235); IDN-6556, imatinib mesylate, iodine (I131) tositumomab, iseganan hydrochloride, ixabepilone; Keratinocyte growth factor; LB-80380, levocetirizine, liposomal doxorubicin, LMB-9, lopinavir, lopinavir/ritonavir, lumiracoxib, lurtotecan; Mecasermin, midostaurin, morphine hydrochloride; Natalizumab, nelfinavir, nesiritide, niacin/lovastatin; Olcegepant, omalizumab, oregovomab; Parecoxib sodium, PEG-filgrastim, peginterferon alfa-2a, peginterferon alfa-2b, peginterferon alfa-2b/ ribavirin, perospirone hydrochloride, pexelizumab, pimecrolimus, prinomastat; Resiquimod, rhIGFBP-3, rhIGF-I/rhIGFBP-3, ritanserin, ro-31-7453, rosuvastatin calcium; SCIO-469, SDZ-SID-791, SU-11248, suberanilohydroxamic acid; Tadalafil, taxus, telithromycin, tenofovir disoproxil fumarate, TER-286, tezosentan disodium, TH-9507, tipifarnib, tipranavir, tolvaptan, tramadol hydrochloride/acetaminophen, travoprost, treprostinil sodium, tucaresol

  9. Gateways to clinical trials.

    PubMed

    Bayés, M; Rabasseda, X; Prous, J R

    2004-03-01

    Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Studies Knowledge Area of Prous Science Integrity(R), the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: Activated protein C concentrate, Ad-CD154, Adeno-Interferon gamma, alemtuzumab, APC-8024, 9-aminocamptothecin, aprepitant, l-arginine hydrochloride, aripiprazole, arsenic trioxide, asimadoline; O6-Benzylguanine, bevacizumab, Bi-20, binodenoson, biphasic insulin aspart, bivatuzumab, 186Re-bivatuzumab, BMS-181176, bosentan, botulinum toxin type B, BQ-123, bryostatin 1; Carboxy- amidotriazole, caspofungin acetate, CB-1954, CC-4047, CDP-860, cerivastatin sodium, clevidipine, CTL-102; 3,4-DAP, darbepoetin alfa, decitabine, desloratadine, DHA-paclitaxel, duloxetine hydrochloride; Efalizumab, EGF vaccine, eletriptan, eniluracil, ENMD-0997, eplerenone, eplivanserin, erlosamide, ertapenem sodium, escitalopram oxalate, esomeprazole magnesium, eszopiclone, everolimus, exatecan mesilate, exenatide, ezetimibe; Fondaparinux sodium, FR-901228, FTY-720; Gefitinib, gemtuzumab ozogamicin, gepirone hydrochloride; Hexyl insulin M2, human insulin; Imatinib mesylate, insulin detemir, insulin glargine, iodine (I131) tositumomab, ISV-205, ivabradine hydrochloride, ixabepilone; Levetiracetam, levocetirizine, linezolid, liposomal NDDP, lonafarnib, lopinavir, LY-156735; Mafosfamide cyclohexylamine salt, magnesium sulfate, maxacalcitol, meclinertant, melagatran, melatonin, MENT, mepolizumab, micafungin sodium, midostaurin, motexafin gadolinium; Nesiritide, NS-1209, NSC-601316, NSC-683864; Osanetant; Palonosetron hydrochloride, parecoxib sodium, pegaptanib sodium, peginterferon alfa-2a, peginterferon alfa-2b, pegylated OB protein, pemetrexed disodium, perillyl alcohol, picoplatin, pimecrolimus, pixantrone maleate, plevitrexed

  10. Gateways to clinical trials.

    PubMed

    Bayés, M; Rabasseda, X; Prous, J R

    2003-09-01

    Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Studies Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: Abetimus sodium, adefovir dipivoxil, AGI-1067, alefacept, alemtuzumab, ALVAC-p53, aminolevulinic acid hydrochloride, aminolevulinic acid methyl ester, Anti-CTLA-4 Mab, AOD-9604, apafant, aprinocarsen sodium, arsenic trioxide; Balaglitazone, BIM-23190, bimatoprost, bortezomib, bosentan, BR-1; Canertinib dihydrochloride, CDP-850, cevimeline hydrochloride, cinacalcet hydrochloride, clenoliximab, clevudine, CN-787; D-003, darusentan, deferasirox, desloratadine dexanabinol, duloxetine hydrochloride; E-5564, edaravone, efaproxiral sodium, elvucitabine emfilermin, EN-101, enfuvirtide, entecavir, epithalon, eplerenone, erlotinib hydrochloride, escitalopram oxalate, esomeprazole magnesium, eszopiclone, etilefrine pivalate hydrochloride etoricoxib, everolimus, exenatide; Fidarestat, fondaparinux sodium; Ganstigmine hydrochloride; Homoharringtonine, HuMax-IL-15, hyperimmune IVIG; Imatinib mesylate, IMC-1C11, Inhaled insulin, irofulven, iseganan hydrochloride, ISIS-14803, ISIS-5132, ivabradine hydrochloride; Keratinocyte growth factor; Lafutidine, lanthanum carbonate, LAS-34475, levocetirizine, liraglutide, LY-307161 SR; Magnesium sulfate, maribavir, melatonin, mycobacterium cell wall complex; NN-414, NO-aspirin, nociceptin, nolomirole hydrochloride; Olmesartan medoxomil oral insulin, ospemifene; PDX, perillyl alcohol, pimecrolimus, pitavastatin calcium, pramlintide acetate, prasterone, pregabalin, PRO-542, PV-701, pyrazoloacridine; R-744, ranelic acid distrontium salt, rasburicase, rDNA insulin, resiniferatoxin, reslizumab, ridogrel, riplizumab ropivacaine, rosuvastatin calcium, roxifiban acetate, ruboxistaurin mesilate

  11. Gateways to clinical trials.

    PubMed

    Bayés, M; Rabasseda, X; Prous, J R

    2004-01-01

    Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Studies Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: Abetimus sodium, Ad5-FGF4, adeno-Interferon gamma, AE-941, AERx, alemtuzumab, alicaforsen sodium, almotriptan, alpharadin, anakinra, anatumomab mafenatox, ANG-453, anti-CTLA-4 Mab, AP-12009, aprepitant, aripiprazole, arsenic trioxide, astemizole, atlizumab, atomoxetine hydrochloride; Bevacizumab, BG-9928, BMS-188667, botulinum toxin type B, BufferGel; Caffeine, CDP-870, cetuximab, cilomilast, ciluprevir, clofarabine, continuous erythropoiesis receptor activator, CP-461; Darbepoetin alfa, deferasirox, desloratadine, desoxyepothilone B, diflomotecan, dolasetron, drotrecogin alfa (activated), duloxetine hydrochloride; ED-71, efalizumab, efaproxiral sodium, EKB-569, eletriptan, EMD-72000, enfuvirtide, erlotinib hydrochloride, escitalopram oxalate, etoricoxib; Fampridine, ferumoxytol, fondaparinux sodium; Gadofosveset sodium, gastrazole, gefitinib, gemtuzumab ozogamicin, gepirone hydrochloride glutamine; hLM609, HSPPC-96, human insulin; IDD-1, imatinib mesylate, indisulam, inhaled insulin, ixabepilone; Keratinocyte growth factor; Lapatinib, laquinimod, LDP-02, LE-SN38, levetiracetam, levosimendan, licofelone, liposomal doxorubicin, liposomal NDDP, lopinavir, lumiracoxib, LY-156735; Morphine hydrochloride, morphine-6-glucuronide, motexafin gadolinium, MS-27-275, MVA-5T4, MVA-Muc1-IL-2; Nemifitide ditriflutate, neridronic acid nitronaproxen, NSC-683864, NSC-703940, NVP-LAF-237; Oblimersen sodium, ocinaplon, oncomyc-NG, OPC-28326, ortataxel, ospemifene; Palonosetron hydrochloride, PEG-filgrastim peginterferon alfa-2(a), peginterferon alfa-2b, pegsunercept, pemetrexed disodium, pregabalin, prilocaine, pyridoxamine; RDP

  12. Spiritual healing as a therapy for chronic pain: a randomized, clinical trial.

    PubMed

    Abbot, N C; Harkness, E F; Stevinson, C; Marshall, F P; Conn, D A; Ernst, E

    2001-03-01

    Spiritual healing is a popular complementary and alternative therapy; in the UK almost 13000 members are registered in nine separate healing organisations. The present randomized clinical trial was designed to investigate the efficacy of healing in the treatment of chronic pain. One hundred and twenty patients suffering from chronic pain, predominantly of neuropathic and nociceptive origin resistant to conventional treatments, were recruited from a Pain Management Clinic. The trial had two parts: face-to-face healing or simulated face-to-face healing for 30 min per week for 8 weeks (part I); and distant healing or no healing for 30 min per week for 8 weeks (part II). The McGill Pain Questionnaire was pre-defined as the primary outcome measure, and sample size was calculated to detect a difference of 8 units on the total pain rating index of this instrument after 8 weeks of healing. VASs for pain, SF36, HAD scale, MYMOP and patient subjective experiences at week 8 were employed as secondary outcome measures. Data from all patients who reached the pre-defined mid-point of 4 weeks (50 subjects in part I and 55 subjects in part II) were included in the analysis. Two baseline measurements of outcome measures were made, 3 weeks apart, and no significant differences were observed between them. After eight sessions there were significant decreases from baseline in McGill Pain Questionnaire total pain rating index score for both groups in part I and for the control group in part II. However, there were no statistically significant differences between healing and control groups in either part. In part I the primary outcome measure decreased from 32.8 (95% CI 28.5-37.0) to 23.3 (16.8-29.7) in the healing group and from 33.1 (27.2-38.9) to 26.1 (19.3-32.9) in the simulated healing group. In part II it changed from 29.6 (24.8-34.4) to 24.0 (18.7-29.4) in the distant healing group and from 31.0 (25.8-36.2) to 21.0 (15.7-26.2) in the no healing group. Subjects in healing groups

  13. Placebo Devices as Effective Control Methods in Acupuncture Clinical Trials: A Systematic Review

    PubMed Central

    Zhang, Claire Shuiqing; Tan, Hsiewe Ying; Zhang, George Shengxi; Zhang, Anthony Lin; Xue, Charlie Changli; Xie, Yi Min

    2015-01-01

    While the use of acupuncture has been recognised by the World Health Organisation, its efficacy for many of the common clinical conditions is still undergoing validation through randomised controlled trials (RCTs). A credible placebo control for such RCTs to enable meaningful evaluation of its efficacy is to be established. While several non-penetrating acupuncture placebo devices, namely the Streitberger, the Park and the Takakura Devices, have been developed and used in RCTs, their suitability as inert placebo controls needs to be rigorously determined. This article systematically reviews these devices as placebo interventions. Electronic searches were conducted on four English and two Chinese databases from their inceptions to July 2014; hand searches of relevant references were also conducted. RCTs, in English or Chinese language, comparing acupuncture with one of the aforementioned devices as the control intervention on human participants with any clinical condition and evaluating clinically related outcomes were included. Thirty-six studies were included for qualitative analysis while 14 were in the meta-analysis. The meta-analysis does not support the notion of either the Streitberger or the Park Device being inert control interventions while none of the studies involving the Takakura Device was included in the meta-analysis. Sixteen studies reported the occurrence of adverse events, with no significant difference between verum and placebo acupuncture. Author-reported blinding credibility showed that participant blinding was successful in most cases; however, when blinding index was calculated, only one study, which utilised the Park Device, seemed to have an ideal blinding scenario. Although the blinding index could not be calculated for the Takakura Device, it was the only device reported to enable practitioner blinding. There are limitations with each of the placebo devices and more rigorous studies are needed to further evaluate their effects and

  14. Placebo Devices as Effective Control Methods in Acupuncture Clinical Trials: A Systematic Review.

    PubMed

    Zhang, Claire Shuiqing; Tan, Hsiewe Ying; Zhang, George Shengxi; Zhang, Anthony Lin; Xue, Charlie Changli; Xie, Yi Min

    2015-01-01

    While the use of acupuncture has been recognised by the World Health Organisation, its efficacy for many of the common clinical conditions is still undergoing validation through randomised controlled trials (RCTs). A credible placebo control for such RCTs to enable meaningful evaluation of its efficacy is to be established. While several non-penetrating acupuncture placebo devices, namely the Streitberger, the Park and the Takakura Devices, have been developed and used in RCTs, their suitability as inert placebo controls needs to be rigorously determined. This article systematically reviews these devices as placebo interventions. Electronic searches were conducted on four English and two Chinese databases from their inceptions to July 2014; hand searches of relevant references were also conducted. RCTs, in English or Chinese language, comparing acupuncture with one of the aforementioned devices as the control intervention on human participants with any clinical condition and evaluating clinically related outcomes were included. Thirty-six studies were included for qualitative analysis while 14 were in the meta-analysis. The meta-analysis does not support the notion of either the Streitberger or the Park Device being inert control interventions while none of the studies involving the Takakura Device was included in the meta-analysis. Sixteen studies reported the occurrence of adverse events, with no significant difference between verum and placebo acupuncture. Author-reported blinding credibility showed that participant blinding was successful in most cases; however, when blinding index was calculated, only one study, which utilised the Park Device, seemed to have an ideal blinding scenario. Although the blinding index could not be calculated for the Takakura Device, it was the only device reported to enable practitioner blinding. There are limitations with each of the placebo devices and more rigorous studies are needed to further evaluate their effects and

  15. Investigation of the clinical efficacy of 0.2% topical stannous fluoride for the treatment of canine superficial pyoderma: a prospective, randomized, double-blinded, placebo-controlled trial.

    PubMed

    Seltzer, Judith D; Flynn-Lurie, Alison K; Marsella, Rosanna; Brennan, Meghan M

    2010-06-01

    Stannous fluoride (SF) is an antibacterial compound that has been successfully used to treat gingivitis in people and dogs, and cutaneous bacterial infections in horses. The purpose of this prospective, double-blinded, placebo-controlled clinical trial was to investigate the efficacy of 0.2% SF spray (BacDerm; Emerald 3 Enterprises Inc., Camdenton, MO, USA) for the treatment of canine superficial pyoderma. Twenty-six privately owned dogs with bacterial skin infections diagnosed on clinical signs, cytology and aerobic culture were enrolled. Dogs were randomly assigned to vehicle only or active ingredient treatment groups. The product was applied topically to affected areas once daily for 28 days, with assessments at days 0, 14, 28 and 42. Clinical and cytological evaluations were performed by the same investigators at each visit. Owners scored the improvement of hair coat, odour, pruritus and overall improvement at each recheck. Linear mixed models showed significant effects of treatment (P < 0.0001) and time (P = 0.0037) for investigator's scores, and a significant time effect for owners' haircoat (P = 0.0077) and odour (P = 0.0170) improvement scores. Dogs in both placebo and SF groups showed some improvement over time, and the investigator's scores on days 0 and 28 were not significantly different between groups for both (t-test P > 0.05). Spearman's rho correlation coefficients revealed a significant negative correlation between investigator's scores and all categories of owners' assessment scores in dogs of both groups. Although some dogs improved on SF, this study does not support the use of 0.2% SF as sole therapy for canine superficial pyoderma. PMID:20230586

  16. Gateways to clinical trials.

    PubMed

    Bayes, M; Rabasseda, X; Prous, J R

    2006-03-01

    Gateways to Clinical Trials are a guide to the most recent clinical trials in current literature and congresses. The data in the following tables have been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: 131I-labetuzumab; Abacavir sulfate, abatacept, adalimumab, ademetionine, adjuvanted influenza vaccine, alefacept, alemtuzumab, amlodipine, amphotericin B, anakinra, aripiprazole, aspirin, axitinib; Betamethasone dipropionate, bevacizumab, biphasic insulin aspart, bortezomib, bosentan, botulinum toxin type B, BQ-123; Calcium folinate, canertinib dihydrochloride, carboplatin, carmustine, cetirizine hydrochloride, cetuximab, cholecalciferol, ciclesonide, ciclosporin, cinacalcet hydrochloride, cisplatin, clarithromycin, clofazimine, cold-adapted influenza vaccine trivalent, CpG-7909; Darbepoetin alfa, darifenacin hydrobromide, DB-289, desloratadine, Dexamet, dicycloverine hydrochloride, dimethyl fumarate, docetaxel, dolastatin 10, drospirenone, drospirenone/estradiol, duloxetine hydrochloride; Ecogramostim, edotecarin, efaproxiral sodium, enalapril maleate, epoetin beta, epoprostenol sodium, epratuzumab, erlotinib hydrochloride, escitalopram oxalate, estradiol, etanercept; Fluconazole, fludarabine phosphate, fluorouracil; Gefitinib, gemcitabine, Ghrelin (human), glibenclamide, glimepiride, GTI-2040; Haloperidol, human insulin, hydrocortisone probutate; Imatinib mesylate, indisulam, influenza vaccine, inhaled insulin, insulin aspart, insulin glulisine, insulin lispro, irinotecan, ispronicline; Lamivudine, lamivudine/zidovudine/abacavir sulfate, lapatinib, letrozole, levocetirizine, lomustine, lonafarnib, lumiracoxib;Magnesium sulfate, MD-1100, melphalan, metformin hydrochloride, methotrexate, metoclopramide hydrochloride, mitiglinide calcium hydrate, monophosphoryl lipid A, montelukast sodium, motexafin gadolinium

  17. Gateways to clinical trials.

    PubMed

    Tomillero, A; Moral, M A

    2008-09-01

    Gateways to Clinical Trials are a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com.This issue focuses on the following selection of drugs: ABT-263, AC-2307, Aclidinium bromide, Adefovir dipivoxil, ADH-1, Agatolimod sodium, Alefacept, Aliskiren fumarate, Aminolevulinic acid methyl ester, Anakinra, Apaziquone, Aprepitant, Aripiprazole, ASM-8, Atiprimod hydrochloride, AVE-0277, AVE-1642, AVE-8062, Axitinib, Azacitidine, AZD-0530; Bazedoxifene acetate, Bevacizumab, Bexarotene, BI-2536, Biphasic insulin aspart, BMS-387032, BMS-663513, Bortezomib, BQ-123, Brivanib alaninate, BSI-201; Caspofungin acetate, CDX-110, Cetuximab, Ciclesonide, CR-011, Cypher; Daptomycin, Darbepoetin alfa, Dasatinib, Decitabine, Deferasirox, Denosumab, Dexlansoprazole, Dexmethylphenidate hydrochloride, DNA-Hsp65 vaccine, Dovitinib, Drotrecogin alfa (activated), DTaP-HBV-IPV/Hibvaccine, DTaP-IPV-HB-PRP-T, Duloxetine hydrochloride, Dutasteride; Ecogramostim, Elacytarabine, Emtricitabine, Endothelin, Entecavir, Eplivanserin fumarate, Escitalopram oxalate, Everolimus, Ezetimibe, Ezetimibe/simvastatin; Farletuzumab, Fesoterodine fumarate, Fibrin sealant (human), Fulvestrant; Gefitinib, Gemtuzumab ozogamicin, Glufosfamide, GSK-1562902A; Hib-TT; Imatinib mesylate, IMC-11F8, Imidazoacridinone, IMP-321, INCB-18424, Indiplon, Indisulam, INNO-406, Irinotecan hydrochloride/Floxuridine, ITF-2357, Ixabepilone; KRN-951; Lasofoxifene tartrate; Lenalidomide, LGD-4665, Lonafarnib, Lubiprostone, Lumiliximab; MDX-1100, Melan-A/MART-1/gp100/IFN-alfa, Methyl-CDDO, Metreleptin, MLN-2704, Mycophenolic acid sodium salt; Na-ASP-2, Naproxcinod, Nilotinib hydrochloride monohydrate, NPI-2358; Oblimersen sodium, Odanacatib; Paclitaxel nanoparticles, PAN-811, Panobinostat, PBI-1402, PC-515, Peginterferon alfa

  18. Gateways to clinical trials.

    PubMed

    Bayés, M; Rabasseda, X; Prous, J R

    2006-10-01

    Gateways to Clinical Trials are a guide to the most recent clinical trials in current literature and congresses. The data the following tables have been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issues focuses on the following selection of drugs: (-)-Epigallocatechin gallate, (-)-gossypol, 2-deoxyglucose, 3,4-DAP, 7-monohydroxyethylrutoside; Ad5CMV-p53, adalimumab, adefovir dipivoxil, ADH-1, alemtuzumab, aliskiren fumarate, alvocidib hydrochloride, aminolevulinic acid hydrochloride, aminolevulinic acid methyl ester, amrubicin hydrochloride, AN-152, anakinra, anecortave acetate, antiasthma herbal medicine intervention, AP-12009, AP-23573, apaziquone, aprinocarsen sodium, AR-C126532, AR-H065522, aripiprazole, armodafinil, arzoxifene hydrochloride, atazanavir sulfate, atilmotin, atomoxetine hydrochloride, atorvastatin, avanafil, azimilide hydrochloride; Bevacizumab, biphasic insulin aspart, BMS-214662, BN-83495, bortezomib, bosentan, botulinum toxin type B; Caspofungin acetate, cetuximab, chrysin, ciclesonide, clevudine, clofarabine, clopidogrel, CNF-1010, CNTO-328, CP-751871, CX-717, Cypher; Dapoxetine hydrochloride, darifenacin hydrobromide, dasatinib, deferasirox, dextofisopam, dextromethorphan/quinidine sulfate, diclofenac, dronedarone hydrochloride, drotrecogin alfa (activated), duloxetine hydrochloride, dutasteride; Edaravone, efaproxiral sodium, emtricitabine, entecavir, eplerenone, epratuzumab, erlotinib hydrochloride, escitalopram oxalate, etoricoxib, ezetimibe, ezetimibe/simvastatin; Finrozole, fipamezole hydrochloride, fondaparinux sodium, fulvestrant; Gabapentin enacarbil, gaboxadol, gefitinib, gestodene, ghrelin (human); Human insulin, human papillomavirus vaccine; Imatinib mesylate, immunoglobulin intravenous (human), indiplon, insulin detemir, insulin glargine, insulin glulisine, intranasal insulin, istradefylline, i.v. gamma

  19. Gateways to clinical trials.

    PubMed

    Bayes, M; Rabasseda, X; Prous, J R

    2005-01-01

    Gateways to Clinical Trials are a guide to the most recent clinical trials in current literature and congresses. The data in the following tables have been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: (-)-Epigallocatechin gallate; ACP-103, Ad.Egr.TNF.11 D, adalimumab, AF-IL 12, AIDSVAX gp120 B/B, alefacept, alemtuzumab, a-Galactosylceramide, ALVAC vCP 1452, alvimopan hydrate, alvocidib hydrochloride, aminolevulinic acid hydrochloride, aminolevulinic acid methyl ester, anakinra, anidulafungin, antarelix, aprepitant, aripiprazole, arsenic sulfide, asoprisnil, atazanavir sulfate, atomoxetine hydrochloride; Bevacizumab, bimatoprost, BMS-184476, bortezomib, bosentan, botulinum toxin type B, BrachySil, brivudine; Caffeine, calcipotriol/betamethasone dipropionate, cannabidiol, capsaicin for injection, caspofungin acetate, CC-4047, cetuximab, CGP-36742, clofazimine, CpG-7909, Cypher; Darbepoetin alfa, dextromethorphan/quinidine sulfate, dimethylfumarate, dronabinol/cannabidiol, drotrecogin alfa (activated), duloxetine hydrochloride, dutasteride; Ecogramostim, efalizumab, eletriptan, emtricitabine, enfuvirtide, eplerenone, esomeprazole magnesium, estradiol acetate, eszopiclone, etoricoxib, exenatide, ezetimibe, ezetimibe/simvastatin; Fampridine, fondaparinux sodium, fosamprenavir calcium; Gefitinib, GPI-0100; hA 20, HTU-PA, human insulin, HuOKT 3 gamma 1(Ala 234-Ala 235), hyaluronic acid; Icatibant, imatinib mesylate, Indiplon, INKP-100, INKP-102, iodine (I131) tositumomab, istradefylline, IV gamma-globulin, ivabradine hydrochloride, ixabepilone; Lacosamide, landiolol, lanthanum carbonate, lasofoxifene tartrate, LB-80380, lenalidomide, lidocaine/tetracaine, linezolid, liposomal doxorubicin, liposomal vincristine sulfate, lopinavir, lopinavir/ritonavir, lumiracoxib, lurtotecan; Maribavir, morphine glucuronide, MVA-5 T

  20. Potential of patient-reported outcomes as nonprimary endpoints in clinical trials

    PubMed Central

    2013-01-01

    Background The purpose of this research was to fully explore the impact of endpoint type (primary vs. nonprimary) on decisions related to patient-reported outcome (PRO) labeling claims supported by PRO measures and to determine if nonprimary PRO endpoints are being fully optimized. This review examines the use of PROs as both primary and nonprimary endpoints in support of demonstration of treatment benefit of new molecular entities (NMEs) and biologic license applications (BLAs) in the United States in the years 2000 to 2012. Methods All NMEs and BLAs approved by the Food and Drug Administration (FDA) between January 2000 and June 2012 were identified using the FDA Drug Approval Reports Web page. Generic products granted tentative approvals were excluded. For all identified products, medical review sections from publicly available drug approval packages were reviewed to identify PRO endpoint status. Product labels (indication, clinical trials sections) were reviewed to determine the number and type of PRO claim. Results A total of 308 NMEs/BLAs were identified. Of these, 70 NMEs/BLAs (23%) were granted PRO claims. The majority of product claims were for disease- or condition-specific signs and symptoms. Of the 70 products with PRO claims, a PRO was a primary endpoint for the vast majority (57 [81%]). A total of 19 of the 70 products were granted a PRO claim based on a nonprimary endpoint. While nonprimary endpoints were used most often to support claims of improved signs or symptoms, nonprimary endpoints were much more likely to support claims of higher order impacts. Conclusions Successful PRO labeling claims are typically based on primary endpoints assessing signs and symptoms. Based on this research, studies with PROs as primary endpoints are far more likely to facilitate positive regulatory review and acceptance of PROs in support of labeling claims. Although inclusion of PROs as nonprimary endpoints in clinical trials has its challenges, recent PRO labels

  1. Pain during venous cannulation: Double-blind, randomized clinical trial of analgesic effect between topical amethocaine and eutectic mixture of local anesthetic

    PubMed Central

    Yeoh, CN; Lee, CY

    2012-01-01

    Background: Venous cannulation is often a painful procedure for the patient. Eutectic mixture of local anesthetic (EMLA) is the commonest topical analgesic used but suffers from disadvantages such as slow onset and skin blanching, which may interfere with venous cannulation. Amethocaine is a newer topical analgesic which seems to be devoid of such problems. Materials and Methods: This prospective randomized double-blind study compared the analgesic efficacy of EMLA with amethocaine during venous cannulation in adults. Eighty ASA I-II patients, aged 18–65 years, were recruited. The test drug was applied on the designated site of venous cannulation and covered with an occlusive dressing for at least 60 min prior to the procedure. Data collected included visual analogue score (VAS) during first attempt at venous cannulation, the ease and success rate at cannulation, and cutaneous changes at the application site. Results: Mean and median VAS for the EMLA group were 27.9 ± 9.8 and 30 mm, respectively; while for the Amethocaine group were 19.1 ± 14.1 and 20 mm, respectively. Differences in VAS did not reach statistical significance. No statistically significant differences were observed in the ease and success rate at cannulation. Cutaneous changes in the form of local induration and erythema (three patients in the Amethocaine group) and blanching (eight patients in the EMLA group) were mild, localized, and required no further treatment. No patient developed severe allergic reactions. Conclusion: Topical EMLA and amethocaine were comparable in terms of analgesic efficacy and ease of venous cannulation in adult patients. PMID:22557744

  2. Patient-reported outcomes as end points in clinical trials in rheumatoid arthritis

    PubMed Central

    Gossec, Laure; Dougados, Maxime; Dixon, William

    2015-01-01

    There is a growing interest in patient-reported outcomes (PROs) in rheumatology, which goes with a global trend for more ‘patient-centred care’. This review considers the use of PROs in trials, including their strengths and limitations. In rheumatoid arthritis (RA) trials, the most frequently used PROs to assess treatments include pain, patient global assessment, assessment of functional status, but also health-related quality of life and less commonly fatigue. Other aspects of importance for patients, such as sleep, psychological well-being or ability to cope, are rarely assessed. PROs as outcome measures in RA trials have strengths as well as limitations. PROs have face validity, they are reproducible and sensitive to change and they bring additional information beyond joint counts or acute phase reactants. However, their predictive validity for later outcomes has been little explored, some PROs show redundancy (they bring similar information) and, due to the apparently moderate link between some PROs such as fatigue and the disease process, the use of some PROs to inform treatment choices has been questioned. We suggest the choice of PROs for trials depends on the study objective and on the viewpoint of the stakeholder. There needs to be agreed prioritisation across all stakeholders about what is most important to collect in a trial, which is why a prioritisation and selection process is necessary. Trials in RA will continue to include PROs and their interpretation will become easier as our knowledge progresses. PMID:26509052

  3. Clinical Research and Clinical Trials

    MedlinePlus

    ... you can get involved. Doing your own clinical research project? Then select the Guidance for Clinical Researchers link to learn more about the NICHD's clinical research processes and policies. Last Reviewed: 03/06/2012 ...

  4. Hybrid 10 Clinical Trial

    PubMed Central

    Gantz, Bruce J.; Hansen, Marlan R.; Turner, Christopher W.; Oleson, Jacob J.; Reiss, Lina A.; Parkinson, Aaron J.

    2010-01-01

    Acoustic plus electric (electric-acoustic) speech processing has been successful in highlighting the important role of articulation information in consonant recognition in those adults that have profound high-frequency hearing loss at frequencies greater than 1500 Hz and less than 60% discrimination scores. Eighty-seven subjects were enrolled in an adult Hybrid multicenter Food and Drug Administration clinical trial. Immediate hearing preservation was accomplished in 85/87 subjects. Over time (3 months to 5 years), some hearing preservation was maintained in 91% of the group. Combined electric-acoustic processing enabled most of this group of volunteers to gain improved speech understanding, compared to their preoperative hearing, with bilateral hearing aids. Most have preservation of low-frequency acoustic hearing within 15 dB of their preoperative pure tone levels. Those with greater losses (> 30 dB) also benefited from the combination of electric-acoustic speech processing. Postoperatively, in the electric-acoustic processing condition, loss of low-frequency hearing did not correlate with improvements in speech perception scores in quiet. Sixteen subjects were identified as poor performers in that they did not achieve a significant improvement through electric-acoustic processing. A multiple regression analysis determined that 91% of the variance in the poorly performing group can be explained by the preoperative speech recognition score and duration of deafness. Signal-to-noise ratios for speech understanding in noise improved more than 9 dB in some individuals in the electric-acoustic processing condition. The relation between speech understanding in noise thresholds and residual low-frequency acoustic hearing is significant (r = 0.62; p < 0.05). The data suggest that, in general, the advantages gained for speech recognition in noise by preserving residual hearing exist, unless the hearing loss approaches profound levels. Preservation of residual low

  5. Adaptive clinical trial designs in oncology

    PubMed Central

    Zang, Yong; Lee, J. Jack

    2015-01-01

    Adaptive designs have become popular in clinical trial and drug development. Unlike traditional trial designs, adaptive designs use accumulating data to modify the ongoing trial without undermining the integrity and validity of the trial. As a result, adaptive designs provide a flexible and effective way to conduct clinical trials. The designs have potential advantages of improving the study power, reducing sample size and total cost, treating more patients with more effective treatments, identifying efficacious drugs for specific subgroups of patients based on their biomarker profiles, and shortening the time for drug development. In this article, we review adaptive designs commonly used in clinical trials and investigate several aspects of the designs, including the dose-finding scheme, interim analysis, adaptive randomization, biomarker-guided randomization, and seamless designs. For illustration, we provide examples of real trials conducted with adaptive designs. We also discuss practical issues from the perspective of using adaptive designs in oncology trials. PMID:25811018

  6. Gateways to clinical trials.

    PubMed

    Bayés, M; Rabasseda, X; Prous, J R

    2005-06-01

    Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables have been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: Abiraterone acetate, acyline, adalimumab, adenosine triphosphate, AEE-788, AIDSVAX gp120 B/B, AK-602, alefacept, alemtuzumab, alendronic acid sodium salt, alicaforsen sodium, alprazolam, amdoxovir, AMG-162, aminolevulinic acid hydrochloride, aminolevulinic acid methyl ester, aminophylline hydrate, anakinra, anecortave acetate, anti-CTLA-4 MAb, APC-8015, aripiprazole, aspirin, atazanavir sulfate, atomoxetine hydrochloride, atorvastatin calcium, atrasentan, AVE-5883, AZD-2171; Betamethasone dipropionate, bevacizumab, bimatoprost, biphasic human insulin (prb), bortezomib, BR-A-657, BRL-55730, budesonide, busulfan; Calcipotriol, calcipotriol/betamethasone dipropionate, calcium folinate, capecitabine, capravirine, carmustine, caspofungin acetate, cefdinir, certolizumab pegol, CG-53135, chlorambucil, ciclesonide, ciclosporin, cisplatin, clofarabine, clopidogrel hydrogensulfate, clozapine, co-trimoxazole, CP-122721, creatine, CY-2301, cyclophosphamide, cypher, cytarabine, cytolin; D0401, darbepoetin alfa, darifenacin hydrobromide, DASB, desipramine hydrochloride, desloratadine, desvenlafaxine succinate, dexamethasone, didanosine, diquafosol tetrasodium, docetaxel, doxorubicin hydrochloride, drotrecogin alfa (activated), duloxetine hydrochloride, dutasteride; Ecallantide, efalizumab, efavirenz, eletriptan, emtricitabine, enfuvirtide, enoxaparin sodium, estramustine phosphate sodium, etanercept, ethinylestradiol, etonogestrel, etonogestrel/ethinylestradiol, etoposide, exenatide; Famciclovir, fampridine, febuxostat, filgrastim, fludarabine phosphate, fluocinolone acetonide, fluorouracil, fluticasone propionate

  7. Topical corticosteroids as adjunctive therapy for bacterial keratitis

    PubMed Central

    Herretes, Samantha; Wang, Xue; Reyes, Johann MG

    2014-01-01

    Background Bacterial keratitis is a serious ocular infectious disease that can lead to severe visual disability. Risk factors for bacterial corneal infection include contact lens wear, ocular surface disease, corneal trauma, and previous ocular or eyelid surgery. Topical antibiotics constitute the mainstay of treatment in cases of bacterial keratitis, whereas the use of topical corticosteroids as an adjunctive therapy to antibiotics remains controversial. Topical corticosteroids are usually used to control inflammation using the smallest amount of the drug. Their use requires optimal timing, concomitant antibiotics, and careful follow-up. Objectives The objective of the review was to assess the effectiveness and safety of corticosteroids as adjunctive therapy for bacterial keratitis. Secondary objectives included evaluation of health economic outcomes and quality of life outcomes. Search methods We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (2014, Issue 6), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to July 2014), EMBASE (January 1980 to July 2014), Latin American and Caribbean Health Sciences Literature Database (LILACS) (January 1982 to July 2014), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov) and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 14 July 2014. We also searched the Science Citation Index to identify additional studies that had cited the only trial included in the original version of this review, reference lists of included trials, earlier reviews, and the American Academy of Ophthalmology guidelines. We also contacted experts to identify any unpublished and

  8. Rationale and design of the randomised clinical trial comparing early medication change (EMC) strategy with treatment as usual (TAU) in patients with Major Depressive Disorder - the EMC trial

    PubMed Central

    2010-01-01

    Background In Major Depressive Disorder (MDD), the traditional belief of a delayed onset of antidepressants' effects has lead to the concept of current guidelines that treatment durations should be between 3-8 weeks before medication change in case of insufficient outcome. Post hoc analyses of clinical trials, however, have shown that improvement usually occurs within the first 10-14 days of treatment and that such early improvement (Hamilton Depression Rating Scale [HAMD] decrease ≥20%) has a substantial predictive value for final treatment outcome. Even more important, non-improvement (HAMD decrease <20%) after 14 days of treatment was found to be highly predictive for a poor final treatment outcome. Methods/Design The EMC trial is a phase IV, multi-centre, multi-step, randomized, observer-blinded, actively controlled parallel-group clinical trial to investigate for the first time prospectively, whether non-improvers after 14 days of antidepressant treatment with an early medication change (EMC) are more likely to attain remission (HAMD-17 ≤7) on treatment day 56 compared to patients treated according to current guideline recommendation (treatment as usual; TAU). In level 1 of the EMC trial, non-improvers after 14 days of antidepressant treatment will be randomised to an EMC strategy or TAU. The EMC strategy for this study schedules a first medication change on day 15; in case of non-improvement between days 15-28, a second medication change will be performed. TAU schedules the first medication change after 28 days in case of non-response (HAMD-17 decrease <50%). Both interventions will last 42 days. In levels 2 and 3, EMC strategies will be compared with TAU strategies in improvers on day 14, who experience a stagnation of improvement during the course of treatment. The trial is supported by the German Federal Ministry of Education and Research (BMBF) and will be conducted in cooperation with the BMBF funded Interdisciplinary Centre Clinical Trials (IZKS) at

  9. The ethics of clinical trials

    PubMed Central

    Nardini, Cecilia

    2014-01-01

    Over the past decades, randomised controlled trials (RCTs) have prevailed over clinical judgement, case reports, and observational studies and became the gold evidential standard in medicine. Furthermore, during the same time frame, RCTs became a crucial part of the regulatory process whereby a new therapeutic can gain access to the drug market. Today, clinical trials are large and tightly regulated enterprises that have to comply with ethical requirements while maintaining high epistemic standards, a balance that becomes increasingly difficult as the research questions become more sophisticated. In this review, the author will discuss some of the most important ethical issues surrounding RCTs, with an eye to the most recent debates and the context of oncological research in particular. PMID:24482672

  10. [Internet use in clinical trials].

    PubMed

    Refolo, P; Sacchini, D; Minacori, R; Spagnolo, A G

    2014-01-01

    Recruiting patients is a critical point of today's clinical research and, along the years, several solutions have been proposed, even if their efficacy seems to be doubtful. On the other hand, nowadays, Internet represents a great opportunity for improving clinical trial recruitments. Nevertheless, on-line recruitment services (e-recruitment) could ensure some advantages (such as facilitating interaction between supply and demand of clinical research, time and money savings/optimizations, data entry errors reduction), but also raise some issues (such as those related to sampling, information, consent, real identity of participants and risks for data breaches). The article debates on the difficulties to recruit patients for clinical research, in general, and e-recruitment particularly, discussing some ethical issues raised by internet enrolment. PMID:24589968

  11. Why are clinical trials necessary in India?

    PubMed Central

    Poongothai, Subramani; Unnikrishnan, Ranjit; Balasubramanian, Jeyakumar; Nair, Mohan Damodaran; Mohan, Viswanathan

    2014-01-01

    Clinical trials are emerging as an important activity in India as it is an essential component of the drug discovery and development program to which India is committed. The only robust way to evaluate a new medicine is by doing properly designed clinical trials. In addition to advancing science, clinical trials offer myriad benefits to the participants. The recent hue that created in India about clinical trials is probably an exaggeration of facts. However, these points to the need for ensuring proper compliance with the regulatory norms and proper training of concerned personnel in good clinical practice (GCP). This will ensure that India continues to reap the benefits of clinical trials and also become a world leader in this field. PMID:24741480

  12. The Dynamo Clinical Trial

    NASA Astrophysics Data System (ADS)

    Ayres, Thomas R.

    2016-04-01

    The Dynamo Clinical Trial evaluates long-term stellar magnetic health through periodic X-ray examinations (by the Chandra Observatory). So far, there are only three subjects enrolled in the DTC: Alpha Centauri A (a solar-like G dwarf), Alpha Cen B (an early K dwarf, more active than the Sun), and Alpha Canis Majoris A (Procyon, a mid-F subgiant similar in activity to the Sun). Of these, Procyon is a new candidate, so it is too early to judge how it will fare. Of the other two, Alpha Cen B has responded well, with a steady magnetic heartbeat of about 8 years duration. The sickest of the bunch, Alpha Cen A, was in magnetic cardiac arrest during 2005-2010, but has begun responding to treatment in recent years, and seems to be successfully cycling again, perhaps achieving a new peak of magnetic health in the 2016 time frame. If this is the case, it has been 20 years since A's last healthful peak, significantly longer than the middle-aged Sun's 11-year magnetic heartbeat, but perhaps in line with Alpha Cen A's more senescent state (in terms of "relative evolutionary age," apparently an important driver of activity). (By the way, don't miss the exciting movie of the Alpha Cen stars' 20-year X-ray dance.)

  13. Clinical effects of topical antifungal therapy in chronic rhinosinusitis: a randomized, double-blind, placebo-controlled trial of intranasal fluconazole

    PubMed Central

    Hashemian, Farshad; Hashemian, Farnaz; Molaali, Najmeh; Rouini, Mohammadreza; Roohi, Elnaz; Torabian, Saadat

    2016-01-01

    Several studies have been in favor of fungi as a possible pathogenesis of chronic rhinosinusitis (CRS); however, to date, there is no scientific consensus about the use of antifungal agents in disease management. The aim of the present study was to investigate the efficacy of intranasal fluconazole in improving disease symptoms and objective outcomes of patients with CRS. A randomized, double-blind, placebo-controlled study was conducted on 54 patients who were diagnosed with CRS and had not been responsive to routine medical treatments. They were randomly assigned to receive either fluconazole nasal drop 0.2 % or placebo in addition to the standard regimen for a duration of 8 weeks. Patients' outcomes were evaluated according to Sino-Nasal Outcome Test 20 (SNOT-20), endoscopic scores, and Computed Tomography (CT) scores. No statistically significant difference was found in SNOT-20 (p = 0.201), endoscopic (p = 0.283), and CT scores (p = 0.212) of the patients at baseline and after 8-week course of treatment between drug and placebo group. Similar to many studies, the use of topical antifungal treatment for patients with CRS was not shown to be significantly effective. However, further studies are needed to obtain high levels of consistent evidence in order to arrive at a decision whether antifungal therapy is effective in management of CRS or not. PMID:27065776

  14. Gender and Ethnicity as Moderators: Integrative Data Analysis of Multidimensional Family Therapy Randomized Clinical Trials

    PubMed Central

    Greenbaum, Paul E.; Wang, Wei; Hall, Kristin; Henderson, Craig E.; Kan, Lisa; Dakof, Gayle A.; Liddle, Howard A.

    2015-01-01

    This study examined gender and ethnicity as moderators of Multidimensional Family Therapy (MDFT) effectiveness for adolescent drug abuse and illustrated the utility of integrative data analysis (IDA, Bauer & Hussong, 2009) for assessing moderation. By pooling participant data from five independent MDFT randomized clinical trials (RCTs), IDA increased power to test moderation. Participants were 646 adolescents receiving treatment for drug use, aged 11 to 17 years (M = 15.31, SD = 1.30), with 19% female (n = 126), 14% (n = 92) European American, 35% (n = 225) Hispanic, and 51% (n = 329) African American. Participants were randomized to MDFT or active comparison treatments, which varied by study. Drug use involvement (i.e., frequency and consequences) was measured at study entry, 6-, and 12-months by a four-indicator latent variable. Growth curve change parameters from multiple calibration samples were regressed on treatment effects overall and by moderator subgroups. MDFT reduced drug use involvement (p < .05) for all participant groups. Pooled comparison groups reduced drug use involvement only for females and Hispanics (ps < .05). MDFT was more effective than comparisons for males, African Americans, and European Americans (ps <.05; Cohen's d = 1.17, 1.95, and 1.75, respectively). For females and Hispanics, there were no significant differences between MDFT and pooled comparison treatments, Cohen's d = 0.63 and 0.19, respectively. MDFT is an effective treatment for drug use among adolescents of both genders and varied ethnicity with males, African American, and White Non-Hispanic adolescents benefitting most from MDFT. PMID:26213796

  15. Efficacy of Contrasperm as a male contraceptive: clinical trials in Malaysian men.

    PubMed

    Hamid, A; Jaffar, A

    1983-01-01

    The efficacy of a recently marketed posttesticular male oral contraceptive, Contrasperm, was assessed in a clinical trial involving 32 Malaysian volunteers ages 21-39 years. Contrasperm is claimed to be a pure botanical extract free of toxic chemicals, steroids, and hormones. The drug is believed to cause cells surrounding the sperm in the seminiferous tubules to secrete carbon dioxide, producing a weakly acidic environment that greatly increases the sperms' metabolism and reduces the pH of semen from its normal level of 7.5 to 1.5. The manufacturer claims that this drop in pH decreases motility from 95% to 0%. Semen samples were collected by masturbation from subjects to provide baseline data. 3 days after the initial sperm analysis, subjects were given 1 capsule of Contrasperm containing 10 mcg of the active ingredient. Additional semen analyses were conducted 30 minutes, 6 hours, and 24 hours after ingestion. Sperm count and sperm motility were greatly reduced in most subjects 30 minutes after ingestion. However, 6 subjects had increased sperm counts and 4 subjects demonstrated increased sperm motility, indicating an enhancing effect. At 6 hours after ingestion, 20 subjects had lowered sperm motility and 12 subjects showed normal sperm motility, contradicting the manufacturer's claim that motility is reduced to 0%. Although Contrasperm is claimed to be effective for 6-8 hours after ingestion, its effect wore off in less than 6 hours in 37% of subjects. Both sperm count and sperm motility returned to normal levels 24 hours after ingestion, confirming the reversibility of this drug. Most subjects reported mild side effects such as muscle weakness, blurred vision, dizziness, perspiration, urgency, abnormal muscle tension, and dry throat which persisted longer than 24 hours. Further studies, with proper controls, are needed to assess the reliability and toxicity of this preparation. PMID:12279893

  16. How transparent are migraine clinical trials?

    PubMed Central

    Dufka, Faustine L.; Dworkin, Robert H.

    2014-01-01

    Transparency in research requires public access to unbiased information prior to trial initiation and openly available results upon study completion. The Repository of Registered Migraine Trials is a global snapshot of registered migraine clinical trials and scorecard of results availability via the peer-reviewed literature, registry databases, and gray literature. The 295 unique clinical trials identified employed 447 investigational agents, with 30% of 154 acute migraine trials and 11% of 141 migraine prophylaxis trials testing combinations of agents. The most frequently studied categories in acute migraine trials were triptans, nonsteroidal anti-inflammatory drugs, antiemetics, calcitonin gene-related peptide antagonists, and acetaminophen. Migraine prophylaxis trials frequently studied anticonvulsants, β-blockers, complementary/alternative therapies, antidepressants, and botulinum toxin. Overall, 237 trials were eligible for a results search. Of 163 trials completed at least 12 months earlier, 57% had peer-reviewed literature results, and registries/gray literature added another 13%. Using logistic regression analysis, studies with a sample size below the median of 141 subjects were significantly less likely to have results, but the dominant factor associated with availability of results was time since study completion. In unadjusted models, trials registered on ClinicalTrials.gov and trials with industry primary sponsorship were significantly more likely to have results. Recently completed trials rarely have publicly available results; 2 years after completion, the peer-reviewed literature contains results for fewer than 60% of completed migraine trials. To avoid bias, evidence-based therapy algorithms should consider factors affecting results availability. As negative trials are less likely to be published, special caution should be exercised before recommending a therapy with a high proportion of missing trial results. PMID:25194013

  17. Anaesthetic Efficacy of Topical Benzocaine Gel Combined with Hyaluronidase for Supplemental Intrapulpal Injection in Teeth with Irreversible Pulpitis- A Double Blinded Clinical Trial

    PubMed Central

    Sooraparaju, Sujatha Gopal; Abarajithan, M.; Sathish, Emmanuel Solomon; Suryakumari, Nujella Bhaskara Padma; Gade, Winner

    2015-01-01

    Objective Intrapulpal injection technique is one of the most commonly employed method to achieve profound pulpal anaesthesia during an endodontic procedure. To determine if the topical application of benzocaine gel along with hyaluronidase to the pulp chamber could reduce the pain felt with the intrapulpal injection technique. Materials and Methods Two hundred patients with chronic irreversible pulpitis undergoing endodontic treatment for mandibular first molars in which the primary anaesthetic technique failed were selected and randomly divided into 2 groups. In the control group intrapulpal injection was administered with backpressure. In the experimental group topical application of 20% benzocaine gel mixed with hyaluronidase was done over the exposed pulp following which intrapulpal injection was administered with backpressure. Pain assessment was done on a visual analogue scale. Results There was statistically significant difference (p<0.001) between the two groups. The mean value in the control group corresponded to the pain perception "strong”, whereas that of the experimental group corresponded to the pain perception "weak”. Conclusion Topical application of 20% benzocaine gel mixed with hyaluronidase to the exposed pulp reduces the pain encountered with the intrapulpal injection. PMID:26436058

  18. Clinical Trials and Older People

    MedlinePlus

    ... have a much wider applicability. Researchers need the participation of older people in their clinical trials so ... contact with questions about the study or your participation. Control group —the group of participants who get ...

  19. Pharmacogenomics in cardiovascular clinical trials.

    PubMed

    Shah, R; Darne, B; Atar, D; Abadie, E; Adams, K F; Zannad, F

    2004-12-01

    Genomics - having quickly emerged as the central discipline in basic science and biomedical research - is poised to take the center stage in clinical medicine as well over the next few decades. Although there is no specific regulatory guideline on the application of pharmacogenetics to drug development, some recommendations are already included in several published guidelines on drug development. The patients more likely to provide the most valuable information on the specific contribution of a given gene or its variant are those who fail to respond to a drug ('therapeutic failures') and those who develop toxicity to the drug. However, before drawing definite conclusions on subgroups following pharmacogenomic analyses, one must be aware of disease classification, data collection, and how much is known about the disease process. It seems reasonable to collect genomic DNA from all patients enrolled in clinical drug trials (along with appropriate consent to permit pharmacogenetic studies) for the purpose of post hoc analyses. One exception to post hoc genomic analysis is when patients with a specific genotype are excluded from randomization into a clinical trial. Physicians will need to understand the concept of genetic variability, its interactions with the environment (e.g. drug-drug or drug-disease interactions), and its implication for patient care. PMID:15548243

  20. Statistical Controversies in Reporting of Clinical Trials: Part 2 of a 4-Part Series on Statistics for Clinical Trials.

    PubMed

    Pocock, Stuart J; McMurray, John J V; Collier, Tim J

    2015-12-15

    This paper tackles several statistical controversies that are commonly faced when reporting a major clinical trial. Topics covered include: multiplicity of data, interpreting secondary endpoints and composite endpoints, the value of covariate adjustment, the traumas of subgroup analysis, assessing individual benefits and risks, alternatives to analysis by intention to treat, interpreting surprise findings (good and bad), and the overall quality of clinical trial reports. All is put in the context of topical cardiology trial examples and is geared to help trialists steer a wise course in their statistical reporting, thereby giving readers a balanced account of trial findings. PMID:26670066

  1. HLA-DR expression as a biomarker of inflammation for multicenter clinical trials of ocular surface disease.

    PubMed

    Epstein, Seth P; Gadaria-Rathod, Neha; Wei, Yi; Maguire, Maureen G; Asbell, Penny A

    2013-06-01

    There are currently no validated minimally invasive objective metrics for the classification and evaluation of ocular surface diseases and/or for evaluating treatment efficacy. We thus sought to establish a standardized methodology for determining the relative amount of the inflammatory biomarker HLA-DR on the ocular surface and to evaluate the precision, reliability and repeatability of its use for large multicenter clinical trials and translational research studies of ocular surface disease. Multiple studies were conducted to establish a Standard Operating Procedure (SOP) for utilizing HLA-DR expression as a minimally invasive, objective, ocular surface inflammatory biomarker. The established SOPs provide specific guidelines for HLA-DR collection and analysis, in order to incorporate it reliably into multicenter clinical trials and/or translational research. Duplicate cell samples from impression cytology (IC) samples of both normal and dry eye individuals were collected and split to assess repeatability (between the splits and between the duplicate samples). To determine storage capability, one duplicate was stained immediately and the other after 30 days cold storage. To demonstrate the feasibility of the use of the SOP for a multicenter clinical trial, clinicians out-of-state were trained to collect IC samples, and the samples shipped to our Biomarker Laboratory, logged, processed and analyzed. Demonstration of the ability to incorporate of IC into a randomized double masked clinical trial of dry eye disease (DED) was performed. In all cases, processing and analyses were performed by a masked independent observer. The validity/viability of the SOPs was established by demonstrating that: 1) sufficient numbers of cells can be collected via IC; 2) the precision/repeatability of the relative biomarker expression quantified in samples; 3) personnel at distant sites can be taught to collect, store and ship samples successfully; 4) samples can be stored for up to 30

  2. Malaria diagnostics in clinical trials.

    PubMed

    Murphy, Sean C; Shott, Joseph P; Parikh, Sunil; Etter, Paige; Prescott, William R; Stewart, V Ann

    2013-11-01

    Malaria diagnostics are widely used in epidemiologic studies to investigate natural history of disease and in drug and vaccine clinical trials to exclude participants or evaluate efficacy. The Malaria Laboratory Network (MLN), managed by the Office of HIV/AIDS Network Coordination, is an international working group with mutual interests in malaria disease and diagnosis and in human immunodeficiency virus/acquired immunodeficiency syndrome clinical trials. The MLN considered and studied the wide array of available malaria diagnostic tests for their suitability for screening trial participants and/or obtaining study endpoints for malaria clinical trials, including studies of HIV/malaria co-infection and other malaria natural history studies. The MLN provides recommendations on microscopy, rapid diagnostic tests, serologic tests, and molecular assays to guide selection of the most appropriate test(s) for specific research objectives. In addition, this report provides recommendations regarding quality management to ensure reproducibility across sites in clinical trials. Performance evaluation, quality control, and external quality assessment are critical processes that must be implemented in all clinical trials using malaria tests. PMID:24062484

  3. Malaria Diagnostics in Clinical Trials

    PubMed Central

    Murphy, Sean C.; Shott, Joseph P.; Parikh, Sunil; Etter, Paige; Prescott, William R.; Stewart, V. Ann

    2013-01-01

    Malaria diagnostics are widely used in epidemiologic studies to investigate natural history of disease and in drug and vaccine clinical trials to exclude participants or evaluate efficacy. The Malaria Laboratory Network (MLN), managed by the Office of HIV/AIDS Network Coordination, is an international working group with mutual interests in malaria disease and diagnosis and in human immunodeficiency virus/acquired immunodeficiency syndrome clinical trials. The MLN considered and studied the wide array of available malaria diagnostic tests for their suitability for screening trial participants and/or obtaining study endpoints for malaria clinical trials, including studies of HIV/malaria co-infection and other malaria natural history studies. The MLN provides recommendations on microscopy, rapid diagnostic tests, serologic tests, and molecular assays to guide selection of the most appropriate test(s) for specific research objectives. In addition, this report provides recommendations regarding quality management to ensure reproducibility across sites in clinical trials. Performance evaluation, quality control, and external quality assessment are critical processes that must be implemented in all clinical trials using malaria tests. PMID:24062484

  4. OARSI Clinical Trials Recommendations: Design and conduct of clinical trials of lifestyle diet and exercise interventions for osteoarthritis.

    PubMed

    Messier, S P; Callahan, L F; Golightly, Y M; Keefe, F J

    2015-05-01

    The objective was to develop a set of "best practices" for use as a primer for those interested in entering the clinical trials field for lifestyle diet and/or exercise interventions in osteoarthritis (OA), and as a set of recommendations for experienced clinical trials investigators. A subcommittee of the non-pharmacologic therapies committee of the OARSI Clinical Trials Working Group was selected by the Steering Committee to develop a set of recommended principles for non-pharmacologic diet/exercise OA randomized clinical trials. Topics were identified for inclusion by co-authors and reviewed by the subcommittee. Resources included authors' expert opinions, traditional search methods including MEDLINE (via PubMed), and previously published guidelines. Suggested steps and considerations for study methods (e.g., recruitment and enrollment of participants, study design, intervention and assessment methods) were recommended. The recommendations set forth in this paper provide a guide from which a research group can design a lifestyle diet/exercise randomized clinical trial in patients with OA. PMID:25952349

  5. Multiple comparisons in complex clinical trial designs.

    PubMed

    Hung, H M James; Wang, Sue-Jane

    2013-05-01

    Multiple comparisons have drawn a great deal of attention in evaluation of statistical evidence in clinical trials for regulatory applications. As the clinical trial methodology is increasingly more complex to properly take into consideration many practical factors, the multiple testing paradigm widely employed for regulatory applications may not suffice to interpret the results of an individual trial and of multiple trials. In a large outcome trial, an increasing need of studying more than one dose complicates a proper application of multiple comparison procedures. Additional challenges surface when a special endpoint, such as mortality, may need to be tested with multiple clinical trials combined, especially under group sequential designs. Another interesting question is how to study mortality or morbidity endpoints together with symptomatic endpoints in an efficient way, where the former type of endpoints are often studied in only one single trial but the latter type of endpoints are usually studied in at least two independent trials. This article is devoted to discussion of insufficiency of such a widely used paradigm applying only per-trial based multiple comparison procedures and to expand the utility of the procedures to such complex trial designs. A number of viable expanded strategies are stipulated. PMID:23620458

  6. Constructing a trial as a personal lifestyle change project: participants' experiences in a clinical study for nicotine vaccination.

    PubMed

    Wolters, Anna; de Wert, Guido; van Schayck, Onno; Horstman, Klasien

    2014-03-01

    The purpose of this study was to gain insight into the experiences and dynamics of the involvement of research participants in a randomized clinical trial for nicotine vaccination. Participants received an experimental nicotine vaccine or a placebo, in addition to quit smoking medication and counseling. The longitudinal design of this qualitative study allowed us to follow people from their first visit to the trial location until the unblinding of their treatment with either verum or placebo vaccine. The empirical data consisted of 49 semi-structured, in-depth interviews, field notes and memos, and trial documents collected in the Netherlands between 2010 and 2012. Participants' expectations and experiences of the innovative nicotine vaccine were characterized by ambivalence: Although they complied with the research design, throughout the study they tinkered with discourses, objects, and activities to make them serve their individual goals. They made the concepts of nicotine vaccination and placebo treatment meaningful for quitting, reshaped the meaning of research tests and obligatory visits to serve their own personal goals, and introduced a new element into the trial by creating space to discuss problems that might endanger the quit attempt. In short, the participants constructed the clinical study for nicotine vaccination as their own personal lifestyle change project. PMID:24581069

  7. Pooled analysis of clinical trial data evaluating the safety and effectiveness of diclofenac epolamine topical patch 1.3% for the treatment of acute ankle sprain

    PubMed Central

    Lionberger, David R; Joussellin, Eric; Yanchick, Jillmarie; Magelli, Merrell; Lanzarotti, Arturo

    2011-01-01

    This pooled analysis assessed the efficacy and safety of the diclofenac epolamine topical patch 1.3% (DETP) for the treatment of acute mild-to-moderate ankle sprain. Data from 2 randomized, double-blind, placebo-controlled studies enrolling 274 male and female patients aged 18 to 65 years with acute ankle sprain were pooled and evaluated. The primary end point was pain reduction on movement assessed using a 100 mm visual analog scale (VAS). Safety and tolerability were also assessed. Beginning approximately 3 hours after initial treatment, DETP-treated patients experienced statistically significant and sustained lower mean VAS scores in pain intensity on movement (mean ± SD, 54.1 ± 20.0 mm versus 60.3 ± 16.8 mm) compared with placebo-treated patients, representing a 20% versus 13% reduction in VA S pain scores from baseline (P = 0.012). This statistically significant difference in mean VAS score was maintained through day 7 (9.4 ± 14.4 mm versus 18.4 ± 18.2 mm, P < 0.0001). The DETP and placebo patches were well tolerated. These results further confirm the efficacy and safety of DETP for the treatment of acute pain from ankle sprains. PMID:24198574

  8. The Clinical Trials Transformation Initiative (CTTI).

    PubMed

    Grignolo, Alberto

    2011-01-01

    The Clinical Trials Transformation Initiative (CTTI) is a public-private partnership created in 2007 between the United States Food and Drug Administration (FDA) and Duke University for the purpose of identifying practices that will increase the quality and efficiency of clinical trials. The initiative was generated from the realization that the clinical trials system in the United States has been suffering as a result of increasingly longer study start-up times, slowing enrollment of patients into trials, increasing clinical trial costs, and declining investigator interest in participating in clinical trials. Although CTTI was created to address a crisis for US clinical research, it seeks to identify practice improvements that can be applied internationally, and is therefore engaging international collaborators with international efforts that have similar objectives. CTTI's approach is to involve all sectors in the selection, conduct, and interpretation of its projects; to keep the dialogue open across sectors; to provide evidence that can influence regulatory guidance, and to attempt to create a "level playing field" when recommending change. The hope is that a broad and diverse data-driven discussion of the important issues in clinical trials will lead to meaningful change for the benefit of all concerned, and importantly for patients. PMID:21430332

  9. Tuberculosis vaccines in clinical trials

    PubMed Central

    Rowland, Rosalind; McShane, Helen

    2011-01-01

    Effective prophylactic and/or therapeutic vaccination is a key strategy for controlling the global TB epidemic. The partial effectiveness of the existing TB vaccine, bacille Calmette–Guérin (BCG), suggests effective vaccination is possible and highlights the need for an improved vaccination strategy. Clinical trials are evaluating both modifications to the existing BCG immunization methods and also novel TB vaccines, designed to replace or boost BCG. Candidate vaccines in clinical development include live mycobacterial vaccines designed to replace BCG, subunit vaccines designed to boost BCG and therapeutic vaccines designed as an adjunct to chemotherapy. There is a great need for validated animal models, identification of immunological biomarkers of protection and field sites with the capacity for large-scale efficacy testing in order to develop and license a novel TB vaccine or regimen. PMID:21604985

  10. COMPETING COMMITMENTS in CLINICAL TRIALS

    PubMed Central

    Lidz, Charles W.; Appelbaum, Paul S.; Joffe, Steven; Albert, Karen; Rosenbaum, Jill; Simon, Lorna

    2013-01-01

    Most discussion about clinical care in clinical trials has concerned whether subjects’ care may be compromised by research procedures. The possibility that clinical researchers might give priority to helping their “patients” even if that required deviating from the imperatives of the research protocol largely has been ignored. We conducted an on-line survey with clinical researchers, including physicians, research nurses and other research staff, to assess the ways and frequency with which clinical trials may be at risk for being compromised by clinical researchers’ attempting to address the clinical needs of subjects. The survey covered recruitment, clinical management while in the trial, and termination decisions. It produced a 72.0% response rate. Over 20% of respondents agreed that researchers should deviate from the protocol to improve subjects’ care; 28% reported that medications restricted by the protocol were given; 21% reported that subjects who were not eligible had been recruited; and 9% said subjects had been retained in a trial despite meeting termination criteria. Some respondents reported that these deviations from the protocol happened many times. The ramifications of these findings are discussed. PMID:19873835

  11. Contraceptive development and clinical trials.

    PubMed

    Fraser, I S

    1986-02-01

    This article provides an overview of the contraceptive development process, with particular emphasis on the importance of clinical trials. Development of a new contraceptive drug begins with chemical synthesis of a large number of substances that may have antifertility effects. Before human trials are considered, drugs must undergo a complex process of animal toxicology testing. Such studies assess acute, subacute, and chronic toxicity. Once a drug has passed the initial screening process, human testing must follow a logical sequence of clinical trials: phase I, pharmacology testing; phase II, initial assessment of efficacy, safety, acceptability, and ease of use; phase III, acurate assessment of efficacy, side effects, and reasons for discontinuation under controlled conditions; and phase IV, evaluation of effectiveness under field conditions. When these have been satisfactorily completed, a detailed marketing application must be submitted to the drug regulatory agency in each country. The process of assessment of the application often takes as long as 2 years. Once marketing approval has been received, there is still a need for postmarketing surveillance of the performance of the new contraceptive method. In many cases, a careful program of training is required. Among the research and recording strategies for postmarketing surveillance are voluntary recording of possible adverse reactions, longterm prospective cohort studies, retrospective case-control studies, and registered release. As controls on the safety and performance of new contraceptive methods are being tightened, the time scale and costs of development are increasing. The time from the 1st synthesis of a drug to marketing approval often takes 13-14 years and costs US$25-50 million. Since the patent life of a new substance is limited to 17 years in most countries, pharmaceutical companies have little time to recoup development costs, which has caused fewer new methods to be developed. PMID:3708511

  12. Sharing clinical trial data on patient level: Opportunities and challenges

    PubMed Central

    Koenig, Franz; Slattery, Jim; Groves, Trish; Lang, Thomas; Benjamini, Yoav; Day, Simon; Bauer, Peter; Posch, Martin

    2015-01-01

    In recent months one of the most controversially discussed topics among regulatory agencies, the pharmaceutical industry, journal editors, and academia has been the sharing of patient-level clinical trial data. Several projects have been started such as the European Medicines Agency´s (EMA) “proactive publication of clinical trial data”, the BMJ open data campaign, or the AllTrials initiative. The executive director of the EMA, Dr. Guido Rasi, has recently announced that clinical trial data on patient level will be published from 2014 onwards (although it has since been delayed). The EMA draft policy on proactive access to clinical trial data was published at the end of June 2013 and open for public consultation until the end of September 2013. These initiatives will change the landscape of drug development and publication of medical research. They provide unprecedented opportunities for research and research synthesis, but pose new challenges for regulatory authorities, sponsors, scientific journals, and the public. Besides these general aspects, data sharing also entails intricate biostatistical questions such as problems of multiplicity. An important issue in this respect is the interpretation of multiple statistical analyses, both prospective and retrospective. Expertise in biostatistics is needed to assess the interpretation of such multiple analyses, for example, in the context of regulatory decision-making by optimizing procedural guidance and sophisticated analysis methods. PMID:24942505

  13. Globalization of Alzheimer's disease clinical trials

    PubMed Central

    2011-01-01

    Alzheimer's disease (AD) therapies are increasingly being tested in global clinical trials. A search of ClincalTrials.gov revealed that of 269 currently active trials, 28% are currently being conducted in the United States; the majority of trials and the majority of trial sites are ex-US. The US has the largest number of trial sites of any single country; cumulatively, nearly half of all sites are outside the US. The US conducts more trials in all phases of drug development but has a greater proportion of phase 3 trials. The increasing importance of global participants in clinical trials emphasizes the importance of considering the ethnic and international factors that may influence trial outcome. The International Conference on Harmonization guidelines divide ethnic factors that may affect drug development into intrinsic and extrinsic influences. These include language, cultural factors, educational levels, the general level of health and standard of care, as well as nutrition and diet. Ethnic influences on pharmacokinetics are known for some metabolic pathways. The biology of AD may also differ among the world's populations. The frequency of the apolipoprotein e4 allele, a major risk factor for AD, differs internationally. Genetic variations might also affect inflammatory, excitotoxic, and oxidative components of AD. Diagnostic standards and experience vary from country to country. Levels of practitioner training and experience, diagnostic approaches to AD, and attitudes regarding aging and AD may differ. Experience and sophistication with regard to clinical trial conduct also vary within and between countries. Experience with conducting the necessary examinations, as well as the linguistic and cultural validity of instrument translations, may affect trial outcomes. Operational and regulatory aspects of clinical trials vary and provide important barriers to seamless conduct of multiregional clinical trials. Collection and testing of biological samples, continuous

  14. Clinical Trials | Division of Cancer Prevention

    Cancer.gov

    Information about actively enrolling, ongoing, and completed clinical trials of cancer prevention, early detection, and supportive care, including phase I, II, and III agent and action trials and clinical trials management. |

  15. Smart Technology in Lung Disease Clinical Trials.

    PubMed

    Geller, Nancy L; Kim, Dong-Yun; Tian, Xin

    2016-01-01

    This article describes the use of smart technology by investigators and patients to facilitate lung disease clinical trials and make them less costly and more efficient. By "smart technology" we include various electronic media, such as computer databases, the Internet, and mobile devices. We first describe the use of electronic health records for identifying potential subjects and then discuss electronic informed consent. We give several examples of using the Internet and mobile technology in clinical trials. Interventions have been delivered via the World Wide Web or via mobile devices, and both have been used to collect outcome data. We discuss examples of new electronic devices that recently have been introduced to collect health data. While use of smart technology in clinical trials is an exciting development, comparison with similar interventions applied in a conventional manner is still in its infancy. We discuss advantages and disadvantages of using this omnipresent, powerful tool in clinical trials, as well as directions for future research. PMID:26135330

  16. HIV/AIDS Clinical Trials Fact Sheet

    MedlinePlus

    HIV Prevention HIV/AIDS Clinical Trials (Last updated 9/15/2015; last reviewed 9/15/2015) Key Points HIV/AIDS clinical trials are ... and effective in people. What is an HIV/AIDS clinical trial? HIV/AIDS clinical trials help researchers ...

  17. IPF clinical trial design and endpoints

    PubMed Central

    Nathan, Steven D.; Meyer, Keith C.

    2014-01-01

    Purpose of review There remains a dire need for therapies that impact the clinical course of patients with idiopathic pulmonary fibrosis (IPF). Indeed, there is a surge of interest in IPF therapeutics, with many candidate agents in various stages of development. Optimal design and implementation of the appropriate prospective clinical trials are essential to demonstrate clinical efficacy of promising drugs for the treatment of IPF. A key element in the success of such clinical trials is the choice of the best endpoint(s) to match the design of the study. Recent findings Although the results of many IPF clinical trials have been disappointing, these trials have provided valuable insights into the epidemiology and natural history of the disease and have sparked debate into the best clinical trial designs and endpoints. Summary This review will discuss the various clinical trial endpoints that have been used or proposed with a focus on their potential utility, as well as possible pitfalls that investigators should consider in the design of such studies. Video abstract http://links.lww.com/COPM/A13 PMID:25022315

  18. Effects of Topical Bimatoprost 0.01% and Timolol 0.5% on Circadian IOP, Blood Pressure and Perfusion Pressure in Patients with Glaucoma or Ocular Hypertension: A Randomized, Double Masked, Placebo-Controlled Clinical Trial

    PubMed Central

    Tanga, Lucia; Berardo, Francesca; Ferrazza, Manuela; Michelessi, Manuele; Roberti, Gloria

    2015-01-01

    Purpose To compare the 24-hour (24h) effects on intraocular pressure (IOP) and cardiovascular parameters of timolol 0.5% and bimatoprost 0.01% in open angle glaucoma and ocular hypertensive subjects. Methods In this prospective, randomized, double masked, crossover, clinical trial, after washout from previous medications enrolled subjects underwent 24h IOP, blood pressure (BP) and heart rate (HR) measurements and were randomized to either topical bimatoprost 0.01% at night plus placebo in the morning or to timolol 0.5% bid. After 8 weeks of treatment a second 24h assessment of IOP, BP and HR was performed and then subjects switched to the opposite treatment for additional 8 weeks when a third 24h assessment was performed. The primary endpoint was the comparison of the mean 24h IOP after each treatment. Secondary endpoints included the comparisons of IOP at each timepoint of the 24h curve and the comparison of BP, HR, ocular perfusion pressure and tolerability. Results Mean untreated 24h IOP was 20.3 mmHg (95%CI 19.0 to 21.6). Mean 24h IOP was significantly lower after 8 weeks of treatment with bimatoprost 0.01% than after 8 weeks of treatment with timolol 0.5% bid (15.7 vs 16.8 mmHg, p = 0.0003). Mean IOP during the day hours was significantly reduced from baseline by both drugs while mean IOP during the night hours was reduced by -2.3 mmHg (p = 0.0002) by bimatoprost 0.01% plus placebo and by -1.1 mmHg by timolol 0.5% bid (p = 0.06). Timolol 0.5% significantly reduced the mean 24h systolic BP from baseline, the diastolic BP during the day hours, the HR during the night hours, and the mean 24h systolic ocular perfusion pressure. Conclusion Both Bimatoprost 0.01% and Timolol 0.5% are effective in reducing the mean 24h IOP from an untreated baseline but Bimatoprost 0.01% is more effective than timolol 0.5% throughout the 24h. Timolol 0.5% effect on IOP is reduced during the night hours and is associated with reduced BP, HR and ocular perfusion pressure. Trial

  19. Cancer nanotherapeutics in clinical trials.

    PubMed

    Lytton-Jean, Abigail K R; Kauffman, Kevin J; Kaczmarek, James C; Langer, Robert

    2015-01-01

    To be legally sold in the United States, all drugs must go through the FDA approval process. This chapter introduces the FDA approval process and describes the clinical trials required for a drug to gain approval. We then look at the different cancer nanotherapeutics and in vivo diagnostics that are currently in clinical trials or have already received approval. These nanotechnologies are catagorized and described based on the delivery vehicle: liposomes, polymer micelles, albumin-bound chemotherapeutics, polymer-bound chemotherapeutics, and inorganic particles. PMID:25895874

  20. The effect of topical virgin coconut oil on SCORAD index, transepidermal water loss, and skin capacitance in mild to moderate pediatric atopic dermatitis: a randomized, double-blind, clinical trial.

    PubMed

    Evangelista, Mara Therese Padilla; Abad-Casintahan, Flordeliz; Lopez-Villafuerte, Lillian

    2014-01-01

    Atopic dermatitis (AD) is a chronic skin disease characterized by defects in the epidermal barrier function and cutaneous inflammation, in which transepidermal water loss (TEWL) is increased and the ability of the stratum corneum to hold water is impaired, causing decreased skin capacitance and hydration. This study investigated the effects of topical virgin coconut oil (VCO) and mineral oil, respectively, on SCORAD (SCORing of Atopic Dermatitis) index values, TEWL, and skin capacitance in pediatric patients with mild to moderate AD, using a randomized controlled trial design in which participants and investigators were blinded to the treatments allocated. Patients were evaluated at baseline, and at 2, 4, and 8 weeks. A total of 117 patients were included in the analysis. Mean SCORAD indices decreased from baseline by 68.23% in the VCO group and by 38.13% in the mineral oil group (P < 0.001). In the VCO group, 47% (28/59) of patients achieved moderate improvement and 46% (27/59) showed an excellent response. In the mineral oil group, 34% (20/58) of patients showed moderate improvement and 19% (11/58) achieved excellent improvement. The VCO group achieved a post-treatment mean TEWL of 7.09 from a baseline mean of 26.68, whereas the mineral oil group demonstrated baseline and post-treatment TEWL values of 24.12 and 13.55, respectively. In the VCO group, post-treatment skin capacitance rose to 42.3 from a baseline mean of 32.0, whereas that in the mineral oil group increased to 37.49 from a baseline mean of 31.31. Thus, among pediatric patients with mild to moderate AD, topical application of VCO for eight weeks was superior to that of mineral oil based on clinical (SCORAD) and instrumental (TEWL, skin capacitance) assessments. PMID:24320105

  1. A Comprehensive Review of Clinical Trials on EGFR Inhibitors Such as Cetuximab and Panitumumab as Monotherapy and in Combination for Treatment of Metastatic Colorectal Cancer.

    PubMed

    Yazdi, Mohammad Hossein; Faramarzi, Mohammad Ali; Nikfar, Shekoufeh; Abdollahi, Mohammad

    2015-01-01

    Metastatic colorectal cancer is the fourth most common cause of death due to cancer after those of lung, stomach, and liver. Anti epidermal growth factor receptor drugs as a targeting therapy seem to be good candidates for curing metastatic colorectal cancer. Two available anti epidermal growth factor receptor monoclonal antibodies are cetuximab and panitumumab which have been approved for metastatic colorectal cancer treatment. Through the available literature on NCBI and clinical trials, 31 clinical trials in which cetuximab or panitumumab as monotherapy or in combination with chemotherapy were used for the treatment of metastatic colorectal cancer patients in different line settings and 12 clinical trials in which bevacizumab was used for being compared with anti epidermal growth factor receptor monoclonal antibodies or chemotherapy were chosen for reviewing and comparing the results of overall survival, progression free survival and adverse effects. Cetuximab and panitumumab are well accepted for the treatment of mCRC patients at all stages in different line settings. Although cetuximab administration in metastatic colorectal cancer patients is mostly associated with better overall survival and panitumumab results in better progression free survival, to confirm the superiority of each of them in the treatment protocol of epidermal growth factor receptor monoclonal antibodies, more clinical trials with larger sample size are needed. Through current available data from clinical studies, it can be concluded that the best treatment outcome is achieved by a combination of anti epidermal growth factor receptor monoclonal antibodies with conventional chemotherapy. PMID:26605007

  2. A Comprehensive Review of Clinical Trials on EGFR Inhibitors Such as Cetuximab and Panitumumab as Monotherapy and in Combination for Treatment of Metastatic Colorectal Cancer

    PubMed Central

    Yazdi, Mohammad Hossein; Faramarzi, Mohammad Ali; Nikfar, Shekoufeh; Abdollahi, Mohammad

    2015-01-01

    Metastatic colorectal cancer is the fourth most common cause of death due to cancer after those of lung, stomach, and liver. Anti epidermal growth factor receptor drugs as a targeting therapy seem to be good candidates for curing metastatic colorectal cancer. Two available anti epidermal growth factor receptor monoclonal antibodies are cetuximab and panitumumab which have been approved for metastatic colorectal cancer treatment. Through the available literature on NCBI and clinical trials, 31 clinical trials in which cetuximab or panitumumab as monotherapy or in combination with chemotherapy were used for the treatment of metastatic colorectal cancer patients in different line settings and 12 clinical trials in which bevacizumab was used for being compared with anti epidermal growth factor receptor monoclonal antibodies or chemotherapy were chosen for reviewing and comparing the results of overall survival, progression free survival and adverse effects. Cetuximab and panitumumab are well accepted for the treatment of mCRC patients at all stages in different line settings. Although cetuximab administration in metastatic colorectal cancer patients is mostly associated with better overall survival and panitumumab results in better progression free survival, to confirm the superiority of each of them in the treatment protocol of epidermal growth factor receptor monoclonal antibodies, more clinical trials with larger sample size are needed. Through current available data from clinical studies, it can be concluded that the best treatment outcome is achieved by a combination of anti epidermal growth factor receptor monoclonal antibodies with conventional chemotherapy. PMID:26605007

  3. Optimizing biologically targeted clinical trials for neurofibromatosis

    PubMed Central

    Gutmann, David H; Blakeley, Jaishri O; Korf, Bruce R; Packer, Roger J

    2014-01-01

    Introduction The neurofibromatoses (neurofibromatosis type 1, NF1 and neurofibromatosis type 2, NF2) comprise the most common inherited conditions in which affected children and adults develop tumors of the central and peripheral nervous system. In this review, the authors discuss how the establishment of the Neurofibromatosis Clinical Trials Consortium (NFCTC) has positively impacted on the design and execution of treatment studies for individuals with NF1 and NF2. Areas covered Using an extensive PUBMED search in collaboration with select NFCTC members expert in distinct NF topics, the authors discuss the clinical features of NF1 and NF2, the molecular biology of the NF1 and NF2 genes, the development and application of clinically relevant Nf1 and Nf2 genetically engineered mouse models and the formation of the NFCTC to enable efficient clinical trial design and execution. Expert opinion The NFCTC has resulted in a more seamless integration of mouse preclinical and human clinical trials efforts. Leveraging emerging enabling resources, current research is focused on identifying subtypes of tumors in NF1 and NF2 to deliver the most active compounds to the patients most likely to respond to the targeted therapy. PMID:23425047

  4. [Clinical trial of a seven-peptide vaccine and tegafur-uracil/leucovorin as combination therapy for advanced colorectal cancer].

    PubMed

    Inoue, Keisuke; Sugiura, Fumiaki; Kogita, Akihiro; Yoshioka, Yasumasa; Sukegawa, Yasushi; Hida, Jinichi; Okuno, Kiyotaka

    2014-10-01

    We conducted a clinical trial of a seven-peptide vaccine in combination with tegafur-uracil/Leucovorin for advanced colorectal cancer. These antigenic peptides were derived from 5 proteins identified as cancer-testis antigens(ring finger protein 43 [RNF43], translocase of outer mitochondrial membrane 34[TOMM34], maternal embryonic leucine zipper kinase[MELK], forkhead box M1[FOXM1], and holliday junction recognition protein[HJURP])and 2 vascular endothelial growth factor receptors(VEGFR1 and VEGFR2). Thirty patients with advanced colorectal cancer were enrolled. We found that 25 patients had Grade 1 injection-site redness/induration and 1 patient had Grade 3 anaphylaxis. Tumor imaging revealed that 3 patients had a partial response (PR), 15 had stable disease(SD)and 12 had progressive disease(PD). This trial showed that treatment with the seven-peptide vaccine and UFT/LV was well tolerated and feasible for advanced colorectal cancer. PMID:25335716

  5. Complementary and Alternative Medicine Cancer Clinical Trials

    MedlinePlus

    ... patients. Currently, what cancer clinical trials are the NCI and medical community sponsoring involving CAM modalities? Cancer CAM clinical trials are listed in NCI’s PDQ ® (Physician Data Query) computer database of clinical ...

  6. Complementary and Alternative Medicine Cancer Clinical Trials

    MedlinePlus

    ... patients. Currently, what cancer clinical trials are the NCI and medical community sponsoring involving CAM modalities? Cancer CAM clinical trials are listed in NCI's PDQ ® (Physician Data Query) computer database of clinical ...

  7. Treatment of blepharitis: recent clinical trials.

    PubMed

    Pflugfelder, Stephen C; Karpecki, Paul M; Perez, Victor L

    2014-10-01

    Blepharitis is a chronic inflammatory disease of the eyelids that is frequently encountered in clinical practice. The etiology of the disorder is complex and not fully understood, but the general consensus is that bacteria and inflammation contribute to the pathology. Blepharitis can be classified into anterior blepharitis, involving the anterior lid margin and eyelashes, and posterior blepharitis, characterized by dysfunction of the meibomian glands. Long-term management of symptoms may include daily eyelid cleansing routines and the use of therapeutic agents that reduce infection and inflammation. A cure is not possible in most cases, and subjective symptoms may persist even when a clinical assessment of signs indicates that the condition has improved. There are no established guidelines regarding therapeutic regimens, but recent clinical trials have shown that antibiotics and topical corticosteroids can produce significant improvement in signs and symptoms of blepharitis. Fixed combinations of a topical antibiotic and a corticosteroid offer an effective and convenient treatment modality that addresses both infectious and inflammatory components of the disease. Further clinical trials are needed to determine optimal therapies for managing blepharitis. PMID:25284773

  8. [Results of a clinical trial with ambroxol as to postoperative therapy of bronchitis (author's transl)].

    PubMed

    Kranicke, R

    1978-01-01

    The clinical testing of trans-4-[(2-amino-3,5-dibromo-benzyl)amino]cyclohexanol-hydrochloride (ambroxol, NA 872) in surgical patients was carried out over a period of 7 days. Regular application of 60 mg/day showed a clear improvement in subjective symptoms, particularly in cases of bronchitic syndrome. In some patients improvement could be demonstrated objectively by means of sputum viscosimetry. The clinical effect is principally one of facilitation of expectoration and fluidification of mucus, which often prior to therapy is rather viscous. This leads to a favourable influence of the post-operative treatment period. As a rule the substance is well-tolerated. The recommended dose of the drug for the average treatment is 2 ampoules/day i.v. (30 mg) and a single to twice daily inhalation of 2 ml (15 mg) for 5--7 days post-operatively. PMID:581994

  9. Swiss regulations for controlling clinical trials.

    PubMed

    Zanini, G M

    1998-04-01

    Switzerland has recently issued regulations designed to control all trials with drugs in human subjects, namely the 'Regolamento dell'Ufficio Intercantonale per il controllo dei medicamenti in fase di studio clinico' (Intercantonal Regulations Controlling Drugs used in Clinical Trials), which have been operating since 1st January 1995. These new regulations are generally consistent with other international regulations and have introduced the concept of good clinical practice (GCP) into Switzerland. There are other regulations in Switzerland, such as Federal regulations on immunobiological products, special rules governing the administration of radiolabelled drugs to humans, drugs of abuse and medical devices. Any gap in the central regulations must be filled by cantonal regulations, where they exist. This is a comprehensive review of the regulations governing clinical trials in Switzerland, with special attention being devoted to trials with therapeutic compounds and to compatibility between Swiss and international procedures. PMID:9634649

  10. On the evolution of statistical methods as applied to clinical trials.

    PubMed

    Machin, D

    2004-05-01

    This paper describes how statistical methods have evolved in parallel with activities associated with randomized control trials. In particular we emphasize the pivotal role of two papers published in British Journal of Cancer, and the paper describing the Cox proportional hazards model. In addition, the importance of early papers on estimating the sample size required for trials is highlighted. Later developments including the increasing roles for competing risks, multilevel modelling and Bayesian methodologies are described. The interplay between computer software and statistical methodological developments is stressed. Finally some future directions are indicated. PMID:15078495

  11. Orthopedic cellular therapy: An overview with focus on clinical trials

    PubMed Central

    Noh, Moon Jong; Lee, Kwan Hee

    2015-01-01

    In this editorial, the authors tried to evaluate the present state of cellular therapy in orthopedic field. The topics the authors try to cover include not only the clinical trials but the various research areas as well. Both the target diseases for cellular therapy and the target cells were reviewed. New methods to activate the cells were interesting to review. Most advanced clinical trials were also included because several of them have advanced to phase III clinical trials. In the orthopedic field, there are many diseases with a definite treatment gap at this time. Because cellular therapies can regenerate damaged tissues, there is a possibility for cellular therapies to become disease modifying drugs. It is not clear whether cellular therapies will become the standard of care in any of the orthopedic disorders, however the amount of research being performed and the number of clinical trials that are on-going make the authors believe that cellular therapies will become important treatment modalities within several years. PMID:26601056

  12. Bayesian adaptive clinical trials: a dream for statisticians only?

    PubMed

    Chevret, Sylvie

    2012-05-20

    Adaptive or 'flexible' designs have emerged, mostly within frequentist frameworks, as an effective way to speed up the therapeutic evaluation process. Because of their flexibility, Bayesian methods have also been proposed for Phase I through Phase III adaptive trials; however, it has been reported that they are poorly used in practice. We aim to describe the international scientific production of Bayesian clinical trials by investigating the actual development and use of Bayesian 'adaptive' methods in the setting of clinical trials. A bibliometric study was conducted using the PubMed and Science Citation Index-Expanded databases. Most of the references found were biostatistical papers from various teams around the world. Most of the authors were from the US, and a large proportion was from the MD Anderson Cancer Center (University of Texas, Houston, TX). The spread and use of these articles depended heavily on their topic, with 3.1% of the biostatistical articles accumulating at least 25 citations within 5 years of their publication compared with 15% of the reviews and 32% of the clinical articles. We also examined the reasons for the limited use of Bayesian adaptive design methods in clinical trials and the areas of current and future research to address these challenges. Efforts to promote Bayesian approaches among statisticians and clinicians appear necessary. PMID:21905067

  13. [A review of international clinical trial registration].

    PubMed

    Yu, He; Liu, Jian-ping

    2007-05-01

    Clinical trials play a critical role in medical research. However, only a few clinical trials conducted at present have been registered at various clinical trial registries. Clinical trial registration can prevent bias in these registered trials effectively and avoid unnecessary waste of resources due to meaningless repeats. Moreover, it will benefit the development of evidence-based medicine, and promote human welfare. Great attention has been paid to the importance and necessity of clinical trial registration. This review briefly introduced the definition, justification, contents, history, current status of clinical trial registration, and introduced the information regarding important international clinical trial registries in detail. Clinical trial registration should be developed toward a transparent, compulsory and comprehensive stage. PMID:17498477

  14. Structural Integration as an Adjunct to Outpatient Rehabilitation for Chronic Nonspecific Low Back Pain: A Randomized Pilot Clinical Trial

    PubMed Central

    Jacobson, Eric E.; Meleger, Alec L.; Bonato, Paolo; Wayne, Peter M.; Langevin, Helene M.; Kaptchuk, Ted J.; Davis, Roger B.

    2015-01-01

    Structural Integration (SI) is an alternative method of manipulation and movement education. To obtain preliminary data on feasibility, effectiveness, and adverse events (AE), 46 outpatients from Boston area with chronic nonspecific low back pain (CNSLBP) were randomized to parallel treatment groups of SI plus outpatient rehabilitation (OR) versus OR alone. Feasibility data were acceptable except for low compliance with OR and lengthy recruitment time. Intent-to-treat data on effectiveness were analyzed by Wilcoxon rank sum, n = 23 per group. Median reductions in VAS Pain, the primary outcome, of −26 mm in SI + OR versus 0 in OR alone were not significantly different (P = 0.075). Median reductions in RMDQ, the secondary outcome, of −2 points in SI + OR versus 0 in OR alone were significantly different (P = 0.007). Neither the proportions of participants with nor the seriousness of AE were significantly different. SI as an adjunct to OR for CNSLBP is not likely to provide additional reductions in pain but is likely to augment short term improvements in disability with a low additional burden of AE. A more definitive trial is feasible, but OR compliance and recruitment might be challenging. This trial is registered with ClinicalTrials.gov (NCT01322399). PMID:25945112

  15. Biomarkers and Surrogate Endpoints In Clinical Trials

    PubMed Central

    Fleming, Thomas R.; Powers, John H

    2012-01-01

    One of the most important considerations in designing clinical trials is the choice of outcome measures. These outcome measures could be clinically meaningful endpoints that are direct measures of how patients feel, function and survive. Alternatively, indirect measures, such as biomarkers that include physical signs of disease, laboratory measures and radiological tests, often are considered as replacement endpoints or “surrogates” for clinically meaningful endpoints. We discuss the definitions of clinically meaningful endpoints and surrogate endpoints, and provide examples from recent clinical trials. We provide insight into why indirect measures such as biomarkers may fail to provide reliable evidence about the benefit-to-risk profile of interventions. We also discuss the nature of evidence that is important in assessing whether treatment effects on a biomarker reliably predict effects on a clinically meaningful endpoint, and provide insights into why this reliability is specific to the context of use of the biomarker. . PMID:22711298

  16. [International clinical trials: perspectives of clinical research coordinators].

    PubMed

    Aotani, Eriko

    2007-02-01

    There are several different task roles among the co-medicals who are involved in international clinical trials (ICTs). In this review article, several issues related with ICTs from the view point of clinical research coordinators (CRCs) will be discussed. The discussions include interview results from eight CRCs of four institutions who have been involved in ICTs, current status of education for co-medicals in the field of ICTs, and future perspectives of ICTs from the CRC's view point. The following topics are especially focused in the discussion. 1) It is necessary to establish the infra-structure for free discussion among the ICT team so that opinions of co-medicals as the operation managers of the participating institutions can be openly shared and importantly taken into account. 2) It is also important for co-medicals to conduct research studies to clarify the problems in the current ICT support systems. 3) Lastly, the significance of early involvement of CRCs into the ICT protocol development must be emphasized, because the quality of protocols will be better improved by the practical insight of CRCs, and consequently, the accomplishment of the ICT, such as the speed and the data quality, may be accelerated. PMID:17301551

  17. Clinical trials: new opportunities.

    PubMed

    Chapman, Sandra Bond; Cotman, Carl W; Fillit, Howard M; Gallagher, Michela; van Dyck, Christopher H

    2012-06-01

    Human cognitive aging has been too long neglected and underappreciated for its critical importance to quality of life in old age. The articles in this session present novel approaches to improving cognitive function in normal aging persons with drugs and interventions that are based on findings in epidemiology, studies in aged animals, and in vitro research. In addition, since aging is the primary risk factor for Alzheimer's disease, these studies also have implications as interventions for prevention and treatment. As a field of research, new knowledge regarding the causes and mechanisms of cognitive aging are ripe for translation into human studies, with the application of this knowledge leading the development of interventions and therapeutics for the prevention of cognitive decline in old age and Alzheimer's disease. PMID:22570132

  18. Gateways to clinical trials.

    PubMed

    Tomillero, A; Moral, M A

    2008-06-01

    (+)-Dapoxetine hydrochloride, (R)-Etodolac; Abatacept, ABT-510, Adalimumab, Agatolimod sodium, Alemtuzumab, Alvocidib hydrochloride, Aminolevulinic acid methyl ester, Aripiprazole, AS01B, AS02B, AS02V, Azacitidine; Becatecarin, Bevacizumab, Bevirimat, Bortezomib, Bremelanotide; CAIV-T, Canfosfamide hydrochloride, CHR-2797, Ciclesonide, Clevidipine; Darbepoetin alfa, Decitabine, Degarelix acetate, Dendritic cell-based vaccine, Denosumab, Desloratadine, DMXB-Anabaseine, Duloxetine hydrochloride, Dutasteride; Ecogramostim, Eicosapentaenoic acid/docosahexaenoic acid, Eletriptan, Enzastaurin hydrochloride, Erlotinib hydrochloride, Escitalopram oxalate, Etoricoxib, Everolimus, Ezetimibe, Ezetimibe/simvastatin; Ferumoxytol, Fesoterodine fumarate, Fulvestrant; Gefitinib, GM-CSF DNA, GSK-690693; H5N1 avian flu vaccine, Hepatitis B hyperimmunoglobulin, Human Fibroblast Growth Factor 1, Hypericin-PVP; Icatibant acetate, Iclaprim, Immunoglobulin intravenous (human), Ipilimumab, ISS-1018; L19-IL-2, Lapuleucel-T, Laropiprant, Liposomal doxorubicin, LP-261, Lumiracoxib, LY-518674; MDV-3100, MGCD-0103, Mirabegron, MyoCell; NASHA/Dx, Niacin/laropiprant; O6-Benzylguanine, Ocrelizumab, Olmesartan medoxomil, Omalizumab; P-276-00, Paclitaxel nanoparticles, Paclitaxel nanoparticles, Padoporfin, Paliperidone, PAN-811, Pegaptanib octasodium, Pegfilgrastim, Pemetrexed disodium, PF-00299804, Pimecrolimus, Prasugrel, Pregabalin; Reolysin, Rimonabant, Rivaroxaban, Rosuvastatin calcium; Satraplatin, SCH-697243,Selenite sodium, Silodosin, Sorafenib, Sunitinib malate; Talarozole, Taxus, Temsirolimus, Tocilizumab, Tolevamer potassium sodium, Tremelimumab, TTP-889; Uracil; V-260, Valsartan/amlodipine besylate, Vardenafil hydrochloride hydrate, Varenicline tartrate, Varespladib, Vitespen, Voclosporin, VX-001; Xience V; Zotarolimus-eluting stent. PMID:18806898

  19. Gateways to clinical trials.

    PubMed

    Bayes, Miriam; Rabasseda, X; Prous, J R

    2007-04-01

    1E10, 101M; AAV-ASPA, agomelatine, aliskiren fumarate, alvimopan hydrate, ambrisentan, apaziquone, axitinib; Becatecarin, belagenpumatucel-L, BMS-201038; Cannabidiol, Cannabis sativa L. extract, capromorelin, CBP-501, cediranib, cetuximab, CHR-2797; Dapoxetine hydrochloride, degarelix acetate, desvenlafaxine succinate, dimethyl fumarate, dronedarone hydrochloride; Ecogramostim, eprodisate sodium; Falciparum merozoite protein-1/AS02A, fospropofol disodium; Gefitinib, glucarpidase, GTI-2040; Hepatitis C vaccine, HMR-4902, human proinsulin C-peptide, hyaluronic acid; Ipilimumab, ixabepilone; Lapatinib, lenalidomide, lestaurtinib, liposome encapsulated doxorubicin; Manidipine hydrochloride/delapril hydrochloride, metreleptin, MG-98, MGCD-0103, morphine glucuronide; Nebicapone; O6-benzylguanine, ofatumumab, olmesartan medoxomil/hydrochlorothiazide; PAN-811, pemetrexed disodium, perifosine, pertuzumab, Peru-15, pexelizumab, pirfenidone, pralatrexate, prasugrel; Quercetin; Rivaroxaban; Semaxanib, St. John's Wort extract; Ticagrelor, tomopenem, triplatin tetranitrate; Ulipristal acetate; Vandetanib, vatalanib succinate, vildagliptin; XK-469; ZT-1. PMID:17520107

  20. Image deconvolution as an aid to feature identification: a clinical trial

    NASA Astrophysics Data System (ADS)

    O'Doherty, Triona; Shearer, Andrew; van der Putten, Wilhelm J.; Abbott, Phillip

    2000-06-01

    The focus of this paper is to evaluate the clinical performance of the image processing technique which we have developed for computed radiography x-rays. This algorithm, which was presented at the SPIE '99 medical imaging conference, uses iterative deconvolution with a measured point spread function to reduce the effect of scatter. Wavelet denoising is also carried out after each iteration to remove effects due to noise. A random selection of chest x-rays were processed using the algorithm. Both the raw and processed images were presented to the radiologists in a random order. They scored the images with regard to the visibility of anatomical detail and image quality as outlined in the european guidelines on quality criteria for diagnostic radiographic images. The most notable result of the technique is seen in the reduction of noise in the processed image.

  1. Use of nasal potential difference and sweat chloride as outcome measures in multicenter clinical trials in subjects with cystic fibrosis.

    PubMed

    Ahrens, Richard C; Standaert, Thomas A; Launspach, Janice; Han, Seung-Ho; Teresi, Mary E; Aitken, Moira L; Kelley, Thomas J; Hilliard, Kathleen A; Milgram, Laura J H; Konstan, Michael W; Weatherly, Mark R; McCarty, Nael A

    2002-02-01

    One of the goals of current research in cystic fibrosis (CF) is to develop treatments that correct or compensate for defects in function of the cystic fibrosis transmembrane regulator (CFTR) gene. The use of outcome measures that assess CFTR function such as nasal potential difference (NPD) measurements and sweat chloride determinations will be required to evaluate the efficacy of such treatments in multicenter clinical trials. The purpose of this work was to identify the sources and magnitude of variability in NPD and sweat chloride measurements when performed at multiple centers. For the variance component analysis presented here, we used NPD and sweat chloride measurements from 37 subjects with CF participating in a phase I, four-center clinical trial of CPX (8-cyclopentyl-1,3-dipropylxanthine), a drug intended to enhance trafficking of Delta F508 CFTR to the cell membrane. The specific techniques used to measure these outcomes were not standardized, and varied between the four sites. Variability of both NPD measurements (baseline potential difference during infusion with Ringer's solution; change in response to addition of 0.1 mM amiloride; and subsequent change in response to perfusion with low chloride solution containing 0.1 mM amiloride and 0.01 mM isoproterenol) and sweat chloride measurements differed significantly between study sites. For change in NPD, one study site had significantly greater variability (lower reproducibility) of measurement than the other three sites. For sweat chloride measurements, reproducibility was lower at two of the sites relative to the other two sites. Sample size calculations showed that lower reproducibility at one or more sites can substantially reduce the power of studies using NPD or sweat chloride determinations as outcome measures. Standardization of measurement protocols, careful operator training and certification, and ongoing monitoring of individual operator performance may help to improve reliability in

  2. Special article: 2014 Pediatric Clinical Trials Forum.

    PubMed

    Bogue, Clifford; DiMeglio, Linda A; Maldonado, Samuel; Portman, Ronald J; Smith, P Brian; Sullivan, Janice E; Thompson, Charles; Woo, Heide; Flinn, Susan

    2016-04-01

    In November 2014, the American Academy of Pediatrics convened key stakeholders to discuss the feasibility of accelerating children's medical advances by creating an independent global Pediatric Clinical Trials Network. The Forum identified challenges posed by the US and global clinical trial systems regarding testing and disseminating drugs and devices for pediatric patients. Stakeholders mapped a vision to improve the safety and efficacy of pediatric drugs, biological products, and medical devices by creating a global Pediatric Clinical Trials Network. Such a Network would act as a central infrastructure for pediatric subspecialties and enable dedicated staff to provide clinical research sites with scientific, medical, and operational support. A Network would facilitate development and availability of innovative, high-quality therapies to extend and enhance the lives of neonates, infants, children, adolescents, and young adults. Participants expressed strong interest in forming such a Network, since drugs and devices still come to market without adequate pediatric indications-particularly in neonatology and rare diseases. Participants developed a Consensus Statement expressing their shared vision for a Network: Attendees of the Pediatric Clinical Trials Stakeholder Forum resolved to establish a Global Pediatric Clinical Trials Network and are committed to engage in the work to create and sustain it. PMID:26650344

  3. Gateways to clinical trials.

    PubMed

    Tomillero, A; Moral, M A

    2009-01-01

    [90Y-DOTA-Tyr3]octreotate, Abatacept, ABT-888, ACE-011, Adefovir dipivoxil, Alosetron hydrochloride, Aminolevulinic acid methyl ester, Amlodipine, Apaziquone, Aripiprazole, AS-101, Atomoxetine hydrochloride, Atrasentan, Azacitidine; Bevacizumab, Biphasic insulin aspart, Bortezomib, Bosentan, Brivanib alaninate; CERE-120, Cetuximab, Ciclesonide, Cinacalcet hydrochloride, Combretastatin A-1 phosphate, Conatumumab, CT-322; Dabigatran etexilate, Darunavir, Deforolimus, Desloratadine, Doripenem, Doxorubicin eluting beads, Duloxetine hydrochloride, Dutasteride; Escitalopram oxalate, Eszopiclone, Etravirine, Exenatide, Ezetimibe, Ezetimibe/simvastatin; Fluticasone furoate, Fondaparinux sodium; Gabapentin enacarbil, Ghrelin (human), Golimumab; IC-51, IDM-2, JX-594; Lidocaine/prilocaine, Liraglutide, Lopinavir, Lopinavir/ritonavir, Lumiracoxib; Men ACWY, MxdnG1; Naproxcinod; OBP-301, Omalizumab; Paclitaxel nanoparticles, Pasireotide, Pazopanib hydrochloride, Pegaptanib octasodium, Peginterferon alfa-2a, Pegvisomant, Pemetrexed disodium, Pimecrolimus, Prasterone, Pregabalin; Raclopride, Ranelic acid distrontium salt, Ranibizumab, RB-006, Recombinant human relaxin H2, REG1, Regadenoson, Reximmune-C, Rilonacept; Saxagliptin, SCH-697243, Solifenacin succinate, Sorafenib; Tadalafil, Tapentadol hydrochloride, Tenofovir disoproxil fumarate, Tenofovir disoproxil fumarate/emtricitabine, Tipifarnib, Tolvaptan; Vardenafil hydrochloride hydrate, Vicriviroc, Volociximab, Vorinostat; WB-1001; Yttrium 90 (90Y) ibritumomab tiuxetan. PMID:19798455

  4. Gateways to clinical trials.

    PubMed

    Bayés, M; Rabasseda, X; Prous, J R

    2007-11-01

    1-Octanol, 9vPnC-MnCc; Abiraterone acetate, Adalimumab, Adefovir dipivoxil, Alemtuzumab, Aliskiren fumarate, Aminolevulinic acid hexyl ester, Amlodipine besylate/atorvastatin calcium, Amrubicin hydrochloride, Anakinra, Aripiprazole, ARRY-520, AS-1404, Asimadoline, Atazanavir sulfate, AVE-0277, Azelnidipine; Bevacizumab, Bimatoprost, Boceprevir, Bortezomib, Bosentan, Botulinum toxin type B; Certolizumab pegol, Cetuximab, Clevudine, Contusugene ladenovec, CP-751871, Crofelemer, Cypher, CYT006-AngQb; Darbepoetin alfa, Desmopressin, Dexlansoprazole, DG-041; E-5555, Ecogramostim, Entecavir, Erlotinib hydrochloride, Escitalopram oxalate, Eszopiclone, Everolimus, Ezetimibe, Ezetimibe/simvastatin; Falecalcitriol, Fampridine, Fesoterodine fumarate, Fingolimod hydrochloride; Gefitinib, Ghrelin (human), GS-7904L, GV-1001; HT-1001; Insulin detemir, ISIS-112989, Istradefylline; Laquinimod sodium, Latanoprost/timolol maleate, Lenalidomide, Levobetaxolol hydrochloride, Liposomal doxorubicin, Liposomal morphine sulfate, Lubiprostone, Lumiracoxib, LY-518674; MEM-1003, Mesna disulfide, Mipomersen sodium, MM-093, Mycophenolic acid sodium salt; Naptumomab estafenatox, Natalizumab; Olmesartan medoxomil, Olmesartan medoxomil/hydrochlorothiazide; Paclitaxel nanoparticles, Paclitaxel poliglumex, Pasireotide, Pazufloxacin mesilate, Pegfilgrastim, Peginterferon alfa-2a, Peginterferon alfa-2b, Peginterferon alfa-2b/ribavirin, Pegvisomant, Pemetrexed disodium, Pimagedine, Pimecrolimus, Pramlintide acetate, Prasterone, Pregabalin, Prulifloxacin; QAE-397; Rec-15/2615, RFB4(dsFv)-PE38, rhGAD65, Roflumilast, Romiplostim, Rosuvastatin calcium, Rotigotine, Rupatadine fumarate; Safinamide mesilate, SIR-Spheres, Sitagliptin phosphate, Sodium phenylacetate, Sodium phenylacetate/Sodium benzoate, Sorafenib, SSR-244738; Taribavirin hydrochloride, Taxus, Teduglutide, Tegaserod maleate, Telaprevir, Telbivudine, Tenofovir disoproxil fumarate, Tigecycline, Tiotropium bromide, Trabectedin, Travoprost

  5. 75 FR 47819 - Workshop on Optimizing Clinical Trial Design for the Development of Pediatric Cardiovascular Devices

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-08-09

    ... HUMAN SERVICES Food and Drug Administration Workshop on Optimizing Clinical Trial Design for the... ``Optimizing Clinical Trial Design for the Development of Pediatric Cardiovascular Devices.'' The topic to be... various efficient and pragmatic clinical trial designs that are conducive to overcoming the challenges...

  6. Gateways to clinical trials.

    PubMed

    Tomillero, A; Moral, M A

    2009-03-01

    ABT-869, Acadesine, Acetylsalicylic acid/omeprazole, Adefovir, Adefovir dipivoxil, AEG-35156, Agatolimod sodium, Albiglutide, Alemtuzumab, Alipogene tiparvovec, Alogliptin benzoate, AMG-386, Amrubicin hydrochloride, Apremilast, Aripiprazole, Asoprisnil, Atorvastatin/fenofibrate, AVN-944, Axitinib; Belinostat, Bevacizumab, BHT-3021, BI-2536, Biapenem, Bilastine, Biphasic insulin aspart, Blinatumomab, Bortezomib, Bosentan; Catumaxomab, CD-NP, Cediranib, Certolizumab pegol, Cetuximab, Choline fenofibrate, Ciclesonide, CK-1827452,Clevudine, Clofarabine, CSL-360, CYT-997; Dapagliflozin, Darinaparsin, Denosumab, Densiron 68, Desloratadine, Dulanermin; Edoxaban tosilate, Emtricitabine, Entecavir, Erlotinib hydrochloride, Everolimus, Exenatide, Ezetimibe, Ezetimibe/simvastatin; Fidaxomicintiacumiv, Fulvestrant; G-207, GCR-8015, Gefitinib, Ghrelin (human), Glufosfamide; HPV16L1E7CVLP; Ibutamoren mesilate, Imatinib mesylate, Insulin detemir, Insulin glargine, Iodine (I131) tositumomab, Istaroxime, ITMN-191, Ixabepilone; JZP-4, Lenalidomide; Levetiracetam, Linaclotide acetate, Liposomal cytarabine/daunorubicin, Liposomal doxorubicin, Liraglutide, LY-518674; Milatuzumab, MMR-V, Motesanib diphosphate, Mycophenolic acid sodium salt; Niacin/simvastatin; Obatoclax mesylate, Odanacatib; Paclitaxel nanoparticles, Paclitaxel-eluting stent, Pazufloxacin, PBT-2, Pegfilgrastim, Peginterferon alfa-2a, Peginterferon alfa-2b, Peginterferon alfa-2b/ribavirin, Pemetrexed disodium, Perampanel, PfCP2.9, Pitavastatin calcium, Poly I:CLC, Pomalidomide, Pralatrexate, Pramlintide acetate, Prucalopride; rhGAD65, Roflumilast; RTS,S/AS02D; SCH-530348, Semagacestat, Sirolimus-eluting coronary stent, Sirolimus-Eluting Stent, SIR-Spheres, Sivelestat sodium hydrate, Sorafenib, Sunitinib malate; Tadalafil, Tafluprost, Tanespimycin, Teduglutide, Telaprevir, Telbivudine, Tenofovir disoproxil fumarate, Tiotropium bromide, TMC-435350, Tositumomab/iodine (I131) tositumomab, Travoprost/timolol, Triciribine

  7. Gateways to clinical trials.

    PubMed

    Bayes, M; Rabasseda, X; Prous, J R

    2007-10-01

    (-)-Epigallocatechin gallate, [188Re]-P2045, 12B75, 89-12; Abacavir sulfate/lamivudine, Abatacept, Abiraterone acetate, ABT-869, Adalimumab, Ad-rh Endostatin, AI-700, Alemtuzumab, Alvimopan hydrate, Amrubicin hydrochloride, AP-12009, Apomab 7.3, Arformoterol tartrate, Aripiprazole, AS-1404, Azacitidine, AZD-0530; Bevacizumab, BHT-3009, Biapenem, Bortezomib, Bosentan, Bremelanotide; CA9-SCAN, Calcitonin gene-related peptide, Canertinib dihydrochloride, Cannabidiol, Carboxyamidotriazole, Caspofungin acetate, Celgosivir, Certolizumab pegol, Cinacalcet hydrochloride, Clevudine, CP-751871, Curcumin, Cx-401, Cypher; Darunavir, Decitabine, Deforolimus, Dexamet, Dipyridamole/prednisolone, Drospirenone, Drospirenone/estradiol, DTPw-HepB-Hib, Duloxetine hydrochloride; Efalizumab, Emtricitabine, Erlotinib hydrochloride, Escitalopram oxalate, Eszopiclone; Ferumoxtran-10, Ferumoxytol, Fondaparinux sodium, Fosaprepitant dimeglumine; gamma-Hydroxybutyrate sodium, Gefitinib, Genistein, Ghrelin (human), Gimatecan, GM-CSF PMED, Golimumab, gp100 PMED; Imatinib mesylate, Immunoglobulin intravenous (human), IV Gamma-globulin; LA-419, Laropiprant, L-BLP-25, Levodopa/carbidopa/entacapone, Lidocaine/prilocaine, Lopinavir/ritonavir, Lumiracoxib, LY-2076962; Mepolizumab, Methylnaltrexone bromide, Mitiglinide calcium hydrate, Mycophenolic acid sodium salt, Myristyl nicotinate; Natalizumab, Nesiritide, Niacin/lovastatin; Oblimersen sodium, Ofatumumab, Olmesartan medoxomil, Olmesartan medoxomil/hydrochlorothiazide, Ozarelix; Palonosetron hydrochloride, Parathyroid hormone (human recombinant), Pazopanib hydrochloride, Pegaptanib octasodium, Pegfilgrastim, Peginterferon alfa- 2a, Peginterferon alfa-2b, Pegvisomant, Pemetrexed disodium, Pexelizumab, Picoplatin, Pimecrolimus, Posaconazole, Pregabalin, PRO-1762, Progesterone caproate, Prulifloxacin; Ramelteon, Ranelic acid distrontium salt, Reparixin, Rosuvastatin calcium; Rotigotine; Satraplatin, Sertraline, Sipuleucel-T, SLIT-cisplatin, SNDX-275

  8. Comfrey root: from tradition to modern clinical trials.

    PubMed

    Staiger, Christiane

    2013-02-01

    Comfrey (Symphytum officinale L.) has been used over many centuries as a medicinal plant. In particular, the use of the root has a longstanding tradition. Today, several randomised controlled trials have demonstrated the efficacy and safety. Comfrey root extract has been used for the topical treatment of painful muscle and joint complaints. It is clinically proven to relieve pain, inflammation and swelling of muscles and joints in the case of degenerative arthritis, acute myalgia in the back, sprains, contusions and strains after sports injuries and accidents, also in children aged 3 years and older. This paper provides information on clinical trials, non-interventional studies and further literature published on comfrey root till date. PMID:23224633

  9. Quality of clinical trials: A moving target

    PubMed Central

    Bhatt, Arun

    2011-01-01

    Quality of clinical trials depends on data integrity and subject protection. Globalization, outsourcing and increasing complexicity of clinical trials have made the target of achieving global quality challenging. The quality, as judged by regulatory inspections of the investigator sites, sponsors/contract research organizations and Institutional Review Board, has been of concern to the US Food and Drug Administration, as there has been hardly any change in frequency and nature of common deficiencies. To meet the regulatory expectations, the sponsors need to improve quality by developing systems with specific standards for each clinical trial process. The quality systems include: personnel roles and responsibilities, training, policies and procedures, quality assurance and auditing, document management, record retention, and reporting and corrective and preventive action. With an objective to improve quality, the FDA has planned new inspection approaches such as risk-based inspections, surveillance inspections, real-time oversight, and audit of sponsor quality systems. The FDA has partnered with Duke University for Clinical Trials Transformation Initiative, which will conduct research projects on design principles, data quality and quantity including monitoring, study start-up, and adverse event reporting. These recent initiatives will go a long way in improving quality of clinical trials. PMID:22145122

  10. A Randomized Clinical Trial of Foster Care as an Intervention for Early Institutionalization: Long Term Improvements in White Matter Microstructure

    PubMed Central

    Bick, Johanna; Zhu, Tong; Stamoulis, Catherine; Fox, Nathan A.; Zeanah, Charles

    2015-01-01

    Importance Severe early life neglect is associated with compromises in brain development and associated behavioral functioning. Although early intervention has been shown to support more normative trajectories of brain development, specific improvements in white matter pathways that underlie emotional and cognitive development are unknown. Objective To examine associations between early life neglect, early intervention, and microstructural integrity of white matter pathways in middle childhood. Design, setting, and participants The Bucharest Early Intervention Project is a randomized clinical trial of high quality foster care as an intervention for institutionally reared children in Bucharest, Romania. During infancy, children were randomly selected to remain in an institution or to be placed into foster care. Developmental trajectories of these children were compared to a group of socio-demographically matched children reared in biological families at baseline and several points throughout development. At around eight years of age, 69 of the original 136 children underwent structural MRI scans. Intervention(s) for Clinical Trials Institutionally reared children were randomized into high quality foster homes in Bucharest, Romania. Main Outcome Measure(s) Four estimates of white matter integrity (Fractional Anisotropy, and Mean, Radial, and Axial Diffusivity) for 48 white matter tracts throughout the brain were obtained through Diffusion Tensor Imaging. Results Significant associations emerged between early life neglect and microstructural integrity of the body of the corpus callosum and tracts involved in limbic circuitry (fornix crus, cingulum), fronto-striatal circuitry (anterior and superior corona radiata, external capsule) and sensory processing (medial lemniscus, retrolenticular internal capsule). Follow up analyses revealed that early intervention promoted more normative white matter development among previously neglected children who entered foster care

  11. RECENT CLINICAL TRIALS IN LUPUS NEPHRITIS

    PubMed Central

    Ward, Michael M.

    2014-01-01

    SYNOPSIS Recent clinical trials have provided evidence for the efficacy of low-dose intravenous cyclophosphamide and mycophenolate mofetil as induction treatment for patients with proliferative lupus nephritis in comparative trials with standard-dose intravenous cyclophosphamide. Trials of maintenance treatments have had more variable results, but suggest that mycophenolate mofetil may be similar to quarterly standard-dose intravenous cyclophosphamide and somewhat more efficacious than azathioprine. Differential responses to mycophenolate mofetil based on ethnicity suggest that it may be more effective in black and Hispanic patients. Rituximab was not efficacious as an adjunct to induction treatment with mycophenolate mofetil. PMID:25034160

  12. Examining Longitudinal Stimulant Use and Treatment Attendance as Parallel Outcomes in Two Contingency Management Randomized Clinical Trials.

    PubMed

    McPherson, Sterling; Brooks, Olivia; Barbosa-Leiker, Celestina; Lederhos, Crystal; Lamp, Amanda; Murphy, Sean; Layton, Matthew; Roll, John

    2016-02-01

    The primary aim of this study was to examine stimulant use and longitudinal treatment attendance in one 'parallel outcomes' model in order to determine how these two outcomes are related to one another during treatment, and to quantify how the intervention impacts these two on- and off-target outcomes differently. Data came from two multi-site randomized clinical trials (RCTs) of contingency management (CM) that targeted stimulant use. We used parallel multilevel modeling to examine the impact of multiple pre-specified covariates, including selected Addiction Severity Index (ASI) scores, age and sex, in addition to CM on concurrent attendance and stimulant use in two separate analyses, i.e., one per trial. In one trial, CM was positively associated with attending treatment throughout the trial (β=0.060, p<0.05). In the second trial, CM predicted negative urinalysis ((-)UA) over the 12-week treatment period (β=0.069, p<0.05). In both trials, there was a significant, positive relationship between attendance and (-)UA submission, but in the first trial a (-)UA at both baseline and over time was related to attendance over time (r=0.117; r=0.013, respectively) and in the second trial, a (-)UA submission at baseline was associated with increased attendance over time (r=0.055). These findings indicate that stimulant use and treatment attendance over time are related but distinct outcomes that, when analyzed simultaneously, portray a more informative picture of their predictors and the separate trajectories of each. This 'indirect reinforcement' between two clinically meaningful on-target (directly reinforced behavior) and off-target (indirectly reinforced behavior) outcomes is in need of further examination in order to fully exploit the potential clinical benefits that could be realized in substance use disorder treatment trials. PMID:26456717

  13. Clinical Trials: Key to Medical Progress

    MedlinePlus

    Skip Navigation Bar Home Current Issue Past Issues Clinical Trials: Key to Medical Progress Past Issues / Summer 2008 ... this page please turn Javascript on. Photo iStock Clinical trials are research studies that test how well new ...

  14. Clinical trial designs incorporating predictive biomarkers.

    PubMed

    Renfro, Lindsay A; Mallick, Himel; An, Ming-Wen; Sargent, Daniel J; Mandrekar, Sumithra J

    2016-02-01

    Development of oncologic therapies has traditionally been performed in a sequence of clinical trials intended to assess safety (phase I), preliminary efficacy (phase II), and improvement over the standard of care (phase III) in homogeneous (in terms of tumor type and disease stage) patient populations. As cancer has become increasingly understood on the molecular level, newer "targeted" drugs that inhibit specific cancer cell growth and survival mechanisms have increased the need for new clinical trial designs, wherein pertinent questions on the relationship between patient biomarkers and response to treatment can be answered. Herein, we review the clinical trial design literature from initial to more recently proposed designs for targeted agents or those treatments hypothesized to have enhanced effectiveness within patient subgroups (e.g., those with a certain biomarker value or who harbor a certain genetic tumor mutation). We also describe a number of real clinical trials where biomarker-based designs have been utilized, including a discussion of their respective advantages and challenges. As cancers become further categorized and/or reclassified according to individual patient and tumor features, we anticipate a continued need for novel trial designs to keep pace with the changing frontier of clinical cancer research. PMID:26827695

  15. Gatekeepers for pragmatic clinical trials.

    PubMed

    Whicher, Danielle M; Miller, Jennifer E; Dunham, Kelly M; Joffe, Steven

    2015-10-01

    To successfully implement a pragmatic clinical trial, investigators need access to numerous resources, including financial support, institutional infrastructure (e.g. clinics, facilities, staff), eligible patients, and patient data. Gatekeepers are people or entities who have the ability to allow or deny access to the resources required to support the conduct of clinical research. Based on this definition, gatekeepers relevant to the US clinical research enterprise include research sponsors, regulatory agencies, payers, health system and other organizational leadership, research team leadership, human research protections programs, advocacy and community groups, and clinicians. This article provides a framework to help guide gatekeepers' decision-making related to the use of resources for pragmatic clinical trials. Relevant ethical considerations for gatekeepers include (1) concern for the interests of individuals, groups, and communities affected by the gatekeepers' decisions, including protection from harm and maximization of benefits; (2) advancement of organizational mission and values; and (3) stewardship of financial, human, and other organizational resources. Separate from these ethical considerations, gatekeepers' actions will be guided by relevant federal, state, and local regulations. This framework also suggests that to further enhance the legitimacy of their decision-making, gatekeepers should adopt transparent processes that engage relevant stakeholders when feasible and appropriate. We apply this framework to the set of gatekeepers responsible for making decisions about resources necessary for pragmatic clinical trials in the United States, describing the relevance of the criteria in different situations and pointing out where conflicts among the criteria and relevant regulations may affect decision-making. Recognition of the complex set of considerations that should inform decision-making will guide gatekeepers in making justifiable choices regarding

  16. Clinical Trials in Head Injury

    PubMed Central

    NARAYAN, RAJ K.; MICHEL, MARY ELLEN; Ansell, Beth; Baethmann, Alex; Biegon, Anat; Bracken, Michael B.; Bullock, M. Ross; Choi, Sung C.; Clifton, Guy L.; Contant, Charles F.; Coplin, William M.; Dietrich, W. Dalton; Ghajar, Jamshid; Grady, Sean M.; Grossman, Robert G.; Hall, Edward D.; Heetderks, William; Hovda, David A.; Jallo, Jack; Katz, Russell L.; Knoller, Nachshon; Kochanek, Patrick M.; Maas, Andrew I.; Majde, Jeannine; Marion, Donald W.; Marmarou, Anthony; Marshall, Lawrence F.; McIntosh, Tracy K.; Miller, Emmy; Mohberg, Noel; Muizelaar, J. Paul; Pitts, Lawrence H.; Quinn, Peter; Riesenfeld, Gad; Robertson, Claudia S.; Strauss, Kenneth I.; Teasdale, Graham; Temkin, Nancy; Tuma, Ronald; Wade, Charles; Walker, Michael D.; Weinrich, Michael; Whyte, John; Wilberger, Jack; Young, A. Byron; Yurkewicz, Lorraine

    2006-01-01

    Traumatic brain injury (TBI) remains a major public health problem globally. In the United States the incidence of closed head injuries admitted to hospitals is conservatively estimated to be 200 per 100,000 population, and the incidence of penetrating head injury is estimated to be 12 per 100,000, the highest of any developed country in the world. This yields an approximate number of 500,000 new cases each year, a sizeable proportion of which demonstrate signficant long-term disabilities. Unfortunately, there is a paucity of proven therapies for this disease. For a variety of reasons, clinical trials for this condition have been difficult to design and perform. Despite promising pre-clinical data, most of the trials that have been performed in recent years have failed to demonstrate any significant improvement in outcomes. The reasons for these failures have not always been apparent and any insights gained were not always shared. It was therefore feared that we were running the risk of repeating our mistakes. Recognizing the importance of TBI, the National Institute of Neurological Disorders and Stroke (NINDS) sponsored a workshop that brought together experts from clinical, research, and pharmaceutical backgrounds. This workshop proved to be very informative and yielded many insights into previous and future TBI trials. This paper is an attempt to summarize the key points made at the workshop. It is hoped that these lessons will enhance the planning and design of future efforts in this important field of research. PMID:12042091

  17. Environmental Enrichment as a Therapy for Autism: A Clinical Trial Replication and Extension

    PubMed Central

    Woo, Cynthia C.; Donnelly, Joseph H.; Steinberg-Epstein, Robin; Leon, Michael

    2015-01-01

    Based on work done in animal models showing that autism-like symptoms are ameliorated following exposure to an enriched sensorimotor environment, we attempted to develop a comparable therapy for children with autism. In an initial randomized controlled trial, children with autism who received sensorimotor enrichment at home for six months had significant improvements in both their cognitive ability and the severity of their autism symptoms (Woo & Leon, 2013). We now report the outcomes of a similar randomized controlled trial in which children with autism, aged 3-6 years old, were randomly assigned to groups that received either daily sensorimotor enrichment, administered by their parents, along with standard care, or they received standard care alone. After six months, enriched children showed statistically significant gains in their IQ scores, a decline in their atypical sensory responses, and an improvement in their receptive language performance, compared to controls. Furthermore, after six months of enrichment therapy, 21% of the children who initially had been given an autism classification, using the Autism Diagnostic Observation Schedule, improved to the point that, although they remained on the autism spectrum, they no longer met the criteria for classic autism. None of the standard care controls reached an equivalent level of improvement. Finally, the outcome measures for children who received only a subset of sensory stimuli were similar to those receiving the full complement of enrichment exercises. Sensorimotor enrichment therapy therefore appears to be a cost-effective means of treating a range of symptoms for children with autism. PMID:26052790

  18. Environmental enrichment as a therapy for autism: A clinical trial replication and extension.

    PubMed

    Woo, Cynthia C; Donnelly, Joseph H; Steinberg-Epstein, Robin; Leon, Michael

    2015-08-01

    Based on work done in animal models showing that autism-like symptoms are ameliorated following exposure to an enriched sensorimotor environment, we attempted to develop a comparable therapy for children with autism. In an initial randomized controlled trial, children with autism who received sensorimotor enrichment at home for 6 months had significant improvements in both their cognitive ability and the severity of their autism symptoms (Woo & Leon, 2013). We now report the outcomes of a similar randomized controlled trial in which children with autism, 3 to 6 years old, were randomly assigned to groups that received either daily sensorimotor enrichment, administered by their parents, along with standard care, or they received standard care alone. After 6 months, enriched children showed statistically significant gains in their IQ scores, a decline in their atypical sensory responses, and an improvement in their receptive language performance, compared to controls. Furthermore, after 6 months of enrichment therapy, 21% of the children who initially had been given an autism classification, using the Autism Diagnostic Observation Schedule, improved to the point that, although they remained on the autism spectrum, they no longer met the criteria for classic autism. None of the standard care controls reached an equivalent level of improvement. Finally, the outcome measures for children who received only a subset of sensory stimuli were similar to those receiving the full complement of enrichment exercises. Sensorimotor enrichment therapy therefore appears to be a cost-effective means of treating a range of symptoms for children with autism. PMID:26052790

  19. Clinical Trials Management | Division of Cancer Prevention

    Cancer.gov

    Information for researchers about developing, reporting, and managing NCI-funded cancer prevention clinical trials. Protocol Information Office The central clearinghouse for clinical trials management within the Division of Cancer Prevention.Read more about the Protocol Information Office. | Information for researchers about developing, reporting, and managing NCI-funded cancer prevention clinical trials.

  20. MindTrial: An Intelligent System for Clinical Trials

    PubMed Central

    Lee, Yugyung; Dinakarpandian, Deendayal; Katakam, Nikhilesh; Owens, Dennis

    2010-01-01

    The recruitment of human subjects for clinical trials research is a critically important step in the discovery of new cures for diseases. However, the current recruitment methodologies are inherently inefficient. Considerable resources are expended in efforts to recruit adequate numbers of patient volunteers who meet the inclusion/exclusion criteria for clinical trials. Recruitment is particularly challenging for trials involving vulnerable, psychiatrically disordered groups. We have developed a prototype system, called MindTrial, that is based on an online model to enhance the efficiency and quality of recruitment of patients with psychiatric disorders for clinical research. The intelligent component of the MindTrial system can facilitate highly specific matches between clinical trial criteria and volunteers for self-enrollment of sufficient numbers of patient volunteers. We believe this system is particularly valuable in optimizing recruitment for clinical trial studies for development of new drugs. PMID:21347017

  1. Skin care education and individual counselling versus treatment as usual in healthcare workers with hand eczema: randomised clinical trial

    PubMed Central

    Jemec, Gregor B E; Diepgen, Thomas L; Gluud, Christian; Lindschou Hansen, Jane; Winkel, Per; Thomsen, Simon Francis; Agner, Tove

    2012-01-01

    Objective To evaluate the effect of a secondary prevention programme with education on skin care and individual counselling versus treatment as usual in healthcare workers with hand eczema. Design Randomised, observer blinded parallel group superiority clinical trial. Setting Three hospitals in Denmark. Participants 255 healthcare workers with self reported hand eczema within the past year randomised centrally and stratified by profession, severity of eczema, and hospital. 123 were allocated to the intervention group and 132 to the control group. Interventions Education in skin care and individual counselling based on patch and prick testing and assessment of work and domestic related exposures. The control was treatment as usual. Main outcome measures The primary outcome was clinical severity of disease at five month follow-up measured by scores on the hand eczema severity index. The secondary outcomes were scores on the dermatology life quality index, self evaluated severity of hand eczema, skin protective behaviours, and knowledge of hand eczema from onset to follow-up. Results Follow-up data were available for 247 of 255 participants (97%). At follow-up, the mean score on the hand eczema severity index was significantly lower (improved) in the intervention group than control group: difference of means, unadjusted −3.56 (95% confidence interval −4.92 to −2.14); adjusted −3.47 (−4.80 to −2.14), both P<0.001 for difference. The mean score on the dermatology life quality index was also significantly lower (improved) in the intervention group at follow-up: difference of means: unadjusted −0.78, non-parametric test P=0.003; adjusted −0.92, −1.48 to −0.37). Self evaluated severity and skin protective behaviour by hand washings and wearing of protective gloves were also statistically significantly better in the intervention group, whereas this was not the case for knowledge of hand eczema. Conclusion A secondary prevention programme for hand eczema

  2. Parents as Agents of Change (PAC) in pediatric weight management: The protocol for the PAC randomized clinical trial

    PubMed Central

    2012-01-01

    Background There is an urgent need to develop and evaluate weight management interventions to address childhood obesity. Recent research suggests that interventions designed for parents exclusively, which have been named parents as agents of change (PAC) approaches, have yielded positive outcomes for managing pediatric obesity. To date, no research has combined a PAC intervention approach with cognitive behavioural therapy (CBT) to examine whether these combined elements enhance intervention effectiveness. This paper describes the protocol our team is using to examine two PAC-based interventions for pediatric weight management. We hypothesize that children with obesity whose parents complete a CBT-based PAC intervention will achieve greater reductions in adiposity and improvements in cardiometabolic risk factors, lifestyle behaviours, and psychosocial outcomes than children whose parents complete a psycho-education-based PAC intervention (PEP). Methods/Design This study is a pragmatic, two-armed, parallel, single-blinded, superiority, randomized clinical trial. The primary objective is to examine the differential effects of a CBT-based PAC vs PEP-based PAC intervention on children’s BMI z-score (primary outcome). Secondary objectives are to assess intervention-mediated changes in cardiometabolic, lifestyle, and psychosocial variables in children and parents. Both interventions are similar in frequency of contact, session duration, group facilitation, lifestyle behaviour goals, and educational content. However, the interventions differ insofar as the CBT-based intervention incorporates theory-based concepts to help parents link their thoughts, feelings, and behaviours; these cognitive activities are enabled by group leaders who possess formal training in CBT. Mothers and fathers of children (8–12 years of age; BMI ≥85th percentile) are eligible to participate if they are proficient in English (written and spoken) and agree for at least one parent to attend

  3. 'Cloud computing' and clinical trials: report from an ECRIN workshop.

    PubMed

    Ohmann, Christian; Canham, Steve; Danielyan, Edgar; Robertshaw, Steve; Legré, Yannick; Clivio, Luca; Demotes, Jacques

    2015-01-01

    Growing use of cloud computing in clinical trials prompted the European Clinical Research Infrastructures Network, a European non-profit organisation established to support multinational clinical research, to organise a one-day workshop on the topic to clarify potential benefits and risks. The issues that arose in that workshop are summarised and include the following: the nature of cloud computing and the cloud computing industry; the risks in using cloud computing services now; the lack of explicit guidance on this subject, both generally and with reference to clinical trials; and some possible ways of reducing risks. There was particular interest in developing and using a European 'community cloud' specifically for academic clinical trial data. It was recognised that the day-long workshop was only the start of an ongoing process. Future discussion needs to include clarification of trial-specific regulatory requirements for cloud computing and involve representatives from the relevant regulatory bodies. PMID:26220186

  4. Target population for clinical trials

    PubMed Central

    Studenski, S

    2016-01-01

    The target population for clinical trials aimed at sarcopenia depends on the goals of treatment and the expected natural history of sarcopenia. Based on a natural history where loss of muscle mass and/or quality leads to loss of strength, and eventually to reduced mobility and functional dependence, treatment goals can be defined for both preventive and therapeutic interventions. For example, a target population with low muscle mass and poor strength could be treated to prevent the onset of mobility disability, or a target population with low muscle mass and poor strength with mobility disability could be treated therapeutically to improve mobility. Eligibility for a trial should also be based on careful consideration of factors that affect 1) the ability to respond to treatment, 2) the safety of treatment, 3) expected prevalence and 4) feasibility. PMID:19657558

  5. Comparing Mindfulness-Based Group Therapy With Treatment as Usual for Opioid Dependents: A Pilot Randomized Clinical Trial Study Protocol

    PubMed Central

    Imani, Saeed; Atef Vahid, Mohammad Kazem; Gharraee, Banafsheh; Habibi, Mojtaba; Bowen, Sarah; Noroozi, Alireza

    2015-01-01

    Background: In response to high burden of opioid abuse in Iran, Ministry of Health has launched a large-scale opioid maintenance treatment program, delivered through a network of certified drug treatment centers. To promote opioid pharmacotherapies, there is an urgent need to develop and introduce evidence-based psychosocial interventions into the network. Patients and Methods: This is a randomized clinical trial (RCT) to investigate feasibility and effectiveness of adding mindfulness-based group therapy to opioid pharmacotherapies as compared to opioid pharmacotherapies alone. The primary outcomes were treatment retention and percentage of weekly morphine, methamphetamine, and benzodiazepine negative tests. Discussion: This is the first RCT that explores the effectiveness of mindfulness-based relapse prevention group therapy among opioid dependent clients in Iran. The feasibility of group therapy and comparison of outcomes in intervention and control groups should be discussed in the outcome article. PMID:26251659

  6. Comparative effectiveness of topical drugs in dermatologic priority diseases: geometry of randomized trial networks.

    PubMed

    Maruani, Annabel; Samimi, Mahtab; Lorette, Gérard; le Cleach, Laurence

    2015-01-01

    Among the 100 initial priority topics for comparative effectiveness research, three concern topical drugs in the following dermatologic diseases: psoriasis, chronic lower-extremity wounds (CLEWs), and acne vulgaris (AV). Our objective was to explore the geometry of the corresponding networks of randomized controlled trials (RCTs). We performed a review of RCTs on topical drugs in psoriasis, CLEWs, and AV. We searched MEDLINE, Embase, and CENTRAL for published trials from 2007 to 2012 and ClinicalTrials.gov for unpublished trials registered since 2011. RCTs comparing at least one topical treatment with any active or inactive comparator, regardless of RCT design and outcomes, were eligible. We produced network graphs (each node representing a treatment and links between nodes representing trials) and tested for co-occurrence (preference or avoidance of specific comparisons). We included 60 RCTs on psoriasis (14,255 patients) and 19 registered RCTs, 50 of CLEWs (5,916 patients) and 7 registered RCTs, and 90 of AV (22,984 patients) and 21 registered RCTs. Head-to-head comparisons were made in 78%, 32%, and 57% of published RCTs of these conditions, respectively. The co-occurrence test suggested that no specific head-to-head comparison was significantly preferred or avoided (P-value=0.53, 0.20, and 0.57, respectively). This study has limitations, the main being that the search period was restricted to 5 years. In conclusion, more comparative effectiveness trials are needed for CLEWs, for which head-to-head comparisons are fewer than those for psoriasis and AV. PMID:25046338

  7. Smartphones as Multimodal Communication Devices to Facilitate Clinical Knowledge Processes: Randomized Controlled Trial

    PubMed Central

    Mateescu, Magdalena; Zahn, Carmen; Genewein, Urs

    2013-01-01

    Background Despite the widespread use and advancements of mobile technology that facilitate rich communication modes, there is little evidence demonstrating the value of smartphones for effective interclinician communication and knowledge processes. Objective The objective of this study was to determine the effects of different synchronous smartphone-based modes of communication, such as (1) speech only, (2) speech and images, and (3) speech, images, and image annotation (guided noticing) on the recall and transfer of visually and verbally represented medical knowledge. Methods The experiment was conducted from November 2011 to May 2012 at the University Hospital Basel (Switzerland) with 42 medical students in a master’s program. All participants analyzed a standardized case (a patient with a subcapital fracture of the fifth metacarpal bone) based on a radiological image, photographs of the hand, and textual descriptions, and were asked to consult a remote surgical specialist via a smartphone. Participants were randomly assigned to 3 experimental conditions/groups. In group 1, the specialist provided verbal explanations (speech only). In group 2, the specialist provided verbal explanations and displayed the radiological image and the photographs to the participants (speech and images). In group 3, the specialist provided verbal explanations, displayed the radiological image and the photographs, and annotated the radiological image by drawing structures/angle elements (speech, images, and image annotation). To assess knowledge recall, participants were asked to write brief summaries of the case (verbally represented knowledge) after the consultation and to re-analyze the diagnostic images (visually represented knowledge). To assess knowledge transfer, participants analyzed a similar case without specialist support. Results Data analysis by ANOVA found that participants in groups 2 and 3 (images used) evaluated the support provided by the specialist as

  8. Topical diclofenac therapy for osteoarthritis: a meta-analysis of randomized controlled trials.

    PubMed

    Deng, Zhen-Han; Zeng, Chao; Yang, Ye; Li, Yu-Sheng; Wei, Jie; Yang, Tuo; Li, Hui; Lei, Guang-Hua

    2016-05-01

    The objective of this study was to evaluate the efficacy and safety of topical diclofenac therapy for osteoarthritis (OA). A meta-analysis of randomized controlled trials was conducted. A comprehensive literature search, covering the databases of Medline, the Cochrane Central Register of Controlled Trials, and EMBASE, was conducted in September 2014 to identify the randomized controlled trials which adopted the topical diclofenac therapy for OA. A total of nine papers were included in this meta-analysis. Topical diclofenac appears to be effective in both pain relief (standard mean differences (SMD) = 0.40; 95 % confidence interval (CI) 0.19 to 0.62; P = 0.0003) and function improvement (SMD = 0.23; 95 % CI 0.03 to 0.43; P = 0.03) when compared with the control group. The sensitivity analysis and subgroup analysis showed that the result of pain intensity was stable and reliable, while the result of physical function improvement was vague. With respect to safety, topical diclofenac demonstrated a higher incidence of adverse events such as dry skin, rash, dermatitis, neck pain, and withdrawal. Topical diclofenac is effective in pain relief as a treatment of OA. It may also have a potential effect in function improvement, which needs further studies to be explored. Although, some adverse effects were observed in the application of topical diclofenac, none of them was serious. PMID:26242469

  9. Clinical trials for stem cell transplantation: when are they needed?

    PubMed

    Van Pham, Phuc

    2016-01-01

    In recent years, both stem cell research and the clinical application of these promising cells have increased rapidly. About 1000 clinical trials using stem cells have to date been performed globally. More importantly, more than 10 stem cell-based products have been approved in some countries. With the rapid growth of stem cell applications, some countries have used clinical trials as a tool to diminish the rate of clinical stem cell applications. However, the point at which stem cell clinical trials are essential remains unclear. This commentary discusses when stem cell clinical trials are essential for stem cell transplantation therapies. PMID:27121227

  10. Transfusion of fresh frozen plasma in non-bleeding ICU patients -TOPIC TRIAL: study protocol for a randomized controlled trial

    PubMed Central

    2011-01-01

    Background Fresh frozen plasma (FFP) is an effective therapy to correct for a deficiency of multiple coagulation factors during bleeding. In past years, use of FFP has increased, in particular in patients on the Intensive Care Unit (ICU), and has expanded to include prophylactic use in patients with a coagulopathy prior to undergoing an invasive procedure. Retrospective studies suggest that prophylactic use of FFP does not prevent bleeding, but carries the risk of transfusion-related morbidity. However, up to 50% of FFP is administered to non-bleeding ICU patients. With the aim to investigate whether prophylactic FFP transfusions to critically ill patients can be safely omitted, a multi-center randomized clinical trial is conducted in ICU patients with a coagulopathy undergoing an invasive procedure. Methods A non-inferiority, prospective, multicenter randomized open-label, blinded end point evaluation (PROBE) trial. In the intervention group, a prophylactic transfusion of FFP prior to an invasive procedure is omitted compared to transfusion of a fixed dose of 12 ml/kg in the control group. Primary outcome measure is relevant bleeding. Secondary outcome measures are minor bleeding, correction of International Normalized Ratio, onset of acute lung injury, length of ventilation days and length of Intensive Care Unit stay. Discussion The Transfusion of Fresh Frozen Plasma in non-bleeding ICU patients (TOPIC) trial is the first multi-center randomized controlled trial powered to investigate whether it is safe to withhold FFP transfusion to coagulopathic critically ill patients undergoing an invasive procedure. Trial Registration Trial registration: Dutch Trial Register NTR2262 and ClinicalTrials.gov: NCT01143909 PMID:22196464

  11. Biomarkers in T cell therapy clinical trials

    PubMed Central

    2011-01-01

    T cell therapy represents an emerging and promising modality for the treatment of both infectious disease and cancer. Data from recent clinical trials have highlighted the potential for this therapeutic modality to effect potent anti-tumor activity. Biomarkers, operationally defined as biological parameters measured from patients that provide information about treatment impact, play a central role in the development of novel therapeutic agents. In the absence of information about primary clinical endpoints, biomarkers can provide critical insights that allow investigators to guide the clinical development of the candidate product. In the context of cell therapy trials, the definition of biomarkers can be extended to include a description of parameters of the cell product that are important for product bioactivity. This review will focus on biomarker studies as they relate to T cell therapy trials, and more specifically: i. An overview and description of categories and classes of biomarkers that are specifically relevant to T cell therapy trials, and ii. Insights into future directions and challenges for the appropriate development of biomarkers to evaluate both product bioactivity and treatment efficacy of T cell therapy trials. PMID:21851646

  12. Clinical trials and gender medicine.

    PubMed

    Cassese, Mariarita; Zuber, Veronica

    2011-01-01

    Women use more medicines than men because they fall ill more often and suffer more from chronic diseases, but also because women pay more attention to their health and have more consciousness and care about themselves. Although medicines can have different effects on women and men, women still represent a small percentage in the first phases of trials (22%) which are essential to verify drugs dosage, side effects, and safety. Even though women are more present in trials, studies results are not presented with a gender approach. This situation is due to educational, social, ethical and economical factors. The scientific research must increase feminine presence in clinical trials in order to be equal and correct, and all the key stakeholder should be involved in this process. We still have a long way to cover and it doesn't concern only women but also children and old people. The aim is to have a medicine not only illness-focused but patient-focused: a medicine able to take into consideration all the patient characteristics and so to produce a really personalized therapy. What above described is part of the reasons why in 2005 was founded the National Observatory for Women's Health (Osservatorio Nazionale sulla Salute della Donna, ONDa) which promotes a gender health awareness and culture in Italy, at all the levels of the civil and scientific society. PMID:21430348

  13. Enhancing Adherence in Clinical Exercise Trials.

    ERIC Educational Resources Information Center

    O'Neal, Heather A.; Blair, Steven N.

    2001-01-01

    Discusses exercise adherence from the perspective of adhering to an exercise treatment in a controlled trial, focusing on: adherence (to intervention and measurement); the development of randomized clinical trials; exemplary randomized clinical trials in exercise science (exercise training studies and physical activity interventions); and study…

  14. What Are Clinical Trials? | NIH MedlinePlus the Magazine

    MedlinePlus

    ... of this page please turn Javascript on. Feature: Clinical Trials What Are Clinical Trials? Past Issues / Fall 2010 Table of Contents ... conducted all the time. The Different Phases of Clinical Trials Clinical trials related to drugs are classified ...

  15. A multi-centred open trial of “Dr Michaels®” (also branded as Soratinex®) topical product family in psoriasis.

    PubMed

    Wollina, U; Hercogovấ, J; Fioranelli, M; Gianfaldoni, S; Chokoeva, A A; Tchernev, G; Tirant, M; Novotny, F; Roccia, M G; Maximov, G K; França, K; Lotti, T

    2016-01-01

    Psoriasis is a chronic, recurring skin disease affecting 2-4% of the population. Genetic predisposition and precipitating factors play a role in its etiology. The disease can occur in any age or gender group. The most frequently affected areas of the body include scalp, extensor surfaces of the extremities, skin folds and nails. While a number of therapies exist for the treatment of psoriasis with a total resolution of the skin, achieving remission in a high percentage of sufferers, a treatment that results in the maintenance of remission and is free of side effects is still a desirable goal. The aim of the study was to investigate the efficacy and tolerability of Dr Michaels® (Soratinex®) topical product family in psoriasis, in terms of decreasing parakeratosis, inflammation, infiltration and involved area. Seven-hundred-and-twenty-two subjects, mean age 42.3 years (range: 18-68 years) with mild to moderately severe psoriasis, with no other current anti-psoriatic therapy, consisting of 382 males and 340 females, above 18 years of age were included and the observations were subjected to statistical analysis. Triphasic application of Dr Michaels® (Soratinex®) products was employed for 8 weeks, using Cleansing Gel, Scalp and Body Ointment and Skin Conditioner. The treatment proved to be ineffective for 22 patients (3.1%) out of 722. 84 patients (11.6%) had moderate improvement with 26-50% of cleared skin lesions; 102 patients (14.1%) had good improvement with 51-75% of cleared skin lesions; 484 patients (67.0%) experienced outstanding improvement with 76-100% of the cleared skin lesions, with 52% of them achieving total resolution. Twelve patients worsened and discontinued treatment; 18 patients discontinued because of non-compliance; 33 patients developed folliculitis as a side effect. Based on the results of this study, the Dr Michaels® (Soratinex®) product family can be successfully applied in mild to moderately severe psoriasis when considering the

  16. Oxalic acid under adhesive restorations as a means to reduce dentin sensitivity: a four-month clinical trial.

    PubMed

    Barrientos, Claudia; Xaus, Gloria; Leighton, Catherine; Martin, Javier; Gordan, Valeria V; Moncada, Gustavo

    2011-01-01

    The aim of this double-blind randomized controlled clinical trial was to evaluate the reduction of dentin sensitivity using an oxalate-based compound, placed under adhesive restorations, during a four-month period. One hundred three preoperatively sensitive teeth, on 36 patients aged 25-66 years (mean, 40.3±7), were included in the study. Group A (experimental) was treated with oxalic acid (BisBlock) before resin-based composite (RBC) restorations (n=52), and group B (control) was treated with distilled water before RBC restorations (n=51). The first tooth in each patient was randomly assigned to group A, and the second tooth received group B. Clinical evaluation as made by a thermal/evaporation test with an air syringe and measurement by visual analog scale (VAS) at baseline and four months after treatment. The results showed sensitivity reduction during the evaluation period (expressed in VAS values): group A, 7.6 to 0.8; group B, 7.3 to 2.6. We concluded from this study that both treatments reduced dentin sensitivity during the evaluation period, with group A showing significantly less dentin sensitivity after four months (p<0.05). PMID:21777095

  17. Limitations of clinical trials in chronic diseases: is the efficacy of methotrexate (MTX) underestimated in polyarticular psoriatic arthritis on the basis of limitations of clinical trials more than on limitations of MTX, as was seen in rheumatoid arthritis?

    PubMed

    Pincus, Theodore; Bergman, Martin J; Yazici, Yusuf

    2015-01-01

    Clinical trials are the optimal method to establish efficacy of a drug versus placebo or another drug. Nonetheless, important limitations are seen, particularly in chronic diseases over long periods, although most are ignored. Pragmatic limitations of clinical trials include a relatively short observation period, suboptimal dosage schedules, suboptimal surrogate markers for long-term outcomes, statistically significant results which may not be clinically unimportant and vice versa. Even ideal clinical trials have intrinsic limitations, including the influence of design on results, data reported in groups which ignore individual variation, non-standard observer-dependent interpretation of a balance of efficacy and toxicity, and distortion of a "placebo effect." Limitations are seen in many clinical trials of methotrexate (MTX) in rheumatoid arthritis (RA) and psoriatic arthritis (PsA). The first MTX clinical trial in rheumatology documented excellent efficacy in PsA, but frequent adverse events in 1964, explained by intravenous doses up to 150 kg. MTX was abandoned until the 1980s for RA, while gold salts and penicillamine were termed "remission-inducing," on the basis limitations of clinical trials. In the most recent MTX in PsA (MIPA) trial, all outcomes favoured MTX, but only patient and physician global estimates met the p<0.05 criterion. A conclusion of "no evidence for MTX improving synovitis" appears explained by insufficient statistical power, wide individual variation, no subsets, low doses, and other limitations. MTX appears less efficacious in PsA than RA, but may be underestimated in PsA, similar to historical problems in RA, resulting more from limitations of clinical trials than from limitations of MTX. PMID:26472658

  18. A clinical trial of the Buteyko Breathing Technique in asthma as taught by a video.

    PubMed

    Opat, A J; Cohen, M M; Bailey, M J; Abramson, M J

    2000-01-01

    The Buteyko Breathing Technique (BBT) is promoted as a drug-free asthma therapy. It is based on the premise that raising blood PaCO2 through hypoventilation can treat asthma. Our study was designed to examine whether the Buteyko Breathing Technique, as taught by a video, is an efficacious asthma therapy. Thirty-six adult subjects with mild to moderate asthma were randomized to receive either a BBT or placebo video to watch at home twice per day for 4 weeks. Asthma-related quality of life, peak expiratory flow (PEF), symptoms, and asthma medication intake were assessed both before and after intervention. Our results demonstrated a significant improvement in quality of life among those assigned to the BBT compared with placebo (p = 0.043), as well as a significant reduction in inhaled bronchodilator intake (p = 0.008). We conclude that the BBT may be effective in improving the quality of life and reducing the intake of inhaled reliever medication in patients with asthma. These results warrant further investigation. PMID:11059522

  19. Women's involvement in clinical trials: historical perspective and future implications.

    PubMed

    Liu, Katherine A; Mager, Natalie A Dipietro

    2016-01-01

    The importance of considering the differences between the male and female sex in clinical decision-making is crucial. However, it has been acknowledged in recent decades that clinical trials have not always adequately enrolled women or analyzed sex-specific differences in the data. As these deficiencies have hindered the progress of understanding women's response to medications, agencies in the United States have worked towards the inclusion of women in clinical trials and appropriate analysis of sex-specific data from clinical trials. This review outlines the history and progress of women's inclusion in clinical trials for prescription drugs and presents considerations for researchers, clinicians, and academicians on this issue. PMID:27011778

  20. Written Exposure as an Intervention for PTSD: A Randomized Clinical Trial with Motor Vehicle Accident Survivors

    PubMed Central

    Sloan, Denise M.; Marx, Brian P.; Bovin, Michelle J.; Feinstein, Brian A.; Gallagher, Matthew W.

    2012-01-01

    The present study examined the efficacy of a brief, written exposure therapy (WET) for posttraumatic stress disorder (PTSD). Participants were 46 adults with a current primary diagnosis of motor vehicle accident-related PTSD. Participants were randomly assigned to either WET or a wait list (WL) condition. Independent assessments took place at baseline and 6-, 18-, and 30- weeks post baseline (WL condition not assessed at 30 weeks). Participants assigned to WET showed significant reductions in PTSD symptom severity at 6- and 18- week post-baseline, relative to WL participants, with large between-group effect sizes. In addition, significantly fewer WET participants met diagnostic criteria for PTSD at both the 6- and 18- week post-baseline assessments, relative to WL participants. Treatment gains were maintained for the WET participants at the 30-week post baseline assessment. Notably, only 9% of participants dropped out of WET and the WET participants reported a high degree of satisfaction with the treatment. These findings suggest that a brief, written exposure treatment may efficaciously treat PTSD. Future research should examine whether WET is efficacious with other PTSD samples, as well as compare the efficacy of WET with that of evidence-based treatments for PTSD. PMID:22863540

  1. Using e-technologies in clinical trials.

    PubMed

    Rosa, Carmen; Campbell, Aimee N C; Miele, Gloria M; Brunner, Meg; Winstanley, Erin L

    2015-11-01

    Clinical trials have been slow to incorporate e-technology (digital and electronic technology that utilizes mobile devices or the Internet) into the design and execution of studies. In the meantime, individuals and corporations are relying more on electronic platforms and most have incorporated such technology into their daily lives. This paper provides a general overview of the use of e-technologies in clinical trials research, specifically within the last decade, marked by rapid growth of mobile and Internet-based tools. Benefits of and challenges to the use of e-technologies in data collection, recruitment and retention, delivery of interventions, and dissemination are provided, as well as a description of the current status of regulatory oversight of e-technologies in clinical trials research. As an example of ways in which e-technologies can be used for intervention delivery, a summary of e-technologies for treatment of substance use disorders is presented. Using e-technologies to design and implement clinical trials has the potential to reach a wide audience, making trials more efficient while also reducing costs; however, researchers should be cautious when adopting these tools given the many challenges in using new technologies, as well as threats to participant privacy/confidentiality. Challenges of using e-technologies can be overcome with careful planning, useful partnerships, and forethought. The role of web- and smartphone-based applications is expanding, and the increasing use of those platforms by scientists and the public alike make them tools that cannot be ignored. PMID:26176884

  2. Genomic sequencing in clinical trials

    PubMed Central

    2011-01-01

    Human genome sequencing is the process by which the exact order of nucleic acid base pairs in the 24 human chromosomes is determined. Since the completion of the Human Genome Project in 2003, genomic sequencing is rapidly becoming a major part of our translational research efforts to understand and improve human health and disease. This article reviews the current and future directions of clinical research with respect to genomic sequencing, a technology that is just beginning to find its way into clinical trials both nationally and worldwide. We highlight the currently available types of genomic sequencing platforms, outline the advantages and disadvantages of each, and compare first- and next-generation techniques with respect to capabilities, quality, and cost. We describe the current geographical distributions and types of disease conditions in which these technologies are used, and how next-generation sequencing is strategically being incorporated into new and existing studies. Lastly, recent major breakthroughs and the ongoing challenges of using genomic sequencing in clinical research are discussed. PMID:22206293

  3. Clinical effect of azithromycin as an adjunct to non-surgical treatment of chronic periodontitis: a meta-analysis of randomized controlled clinical trials.

    PubMed

    Zhang, Z; Zheng, Y; Bian, X

    2016-06-01

    The results of recent published studies focusing on the effect of azithromycin as an adjunct to scaling and root planing (SRP) in the treatment of chronic periodontitis are inconsistent. We conducted a meta-analysis of randomized controlled clinical trials to examine the effect of azithromycin combined with SRP on periodontal clinical parameters as compared to SRP alone. An electronic search was carried out on Pubmed, Embase and the Cochrane Central Register of Controlled Trials from their earliest records through December 28, 2014 to identify studies that met pre-stated inclusion criteria. Reference lists of retrieved articles were also reviewed. Data were extracted independently by two authors. Either a fixed- or random-effects model was used to calculate the overall effect sizes of azithromycin on probing depth, attachment level (AL) and bleeding on probing (BOP). Heterogeneity was evaluated using the Q test and I(2) statistic. Publication bias was evaluated by Begg's test and Egger's test. A total of 14 trials were included in the meta-analysis. Compared with SRP alone, locally delivered azithromycin plus SRP statistically significantly reduced probing depth by 0.99 mm (95% CI 0.42-1.57) and increased AL by 1.12 mm (95% CI 0.31-1.92). In addition, systemically administered azithromycin plus SRP statistically significantly reduced probing depth by 0.21 mm (95% CI 0.12-0.29), BOP by 4.50% (95% CI 1.45-7.56) and increased AL by 0.23 mm (95% CI 0.07-0.39). Sensitivity analysis yielded similar results. No evidence of publication bias was observed. The additional benefit of systemic azithromycin was shown at the initially deep probing depth sites, but not at shallow or moderate sites. The overall effect sizes of systemic azithromycin showed a tendency to decrease with time, and meta-regression analysis suggested a negative relation between the length of follow-up and net change in probing depth (r = -0.05, p = 0.02). This meta-analysis provides further

  4. Key concepts of clinical trials: a narrative review.

    PubMed

    Umscheid, Craig A; Margolis, David J; Grossman, Craig E

    2011-09-01

    The recent focus of federal funding on comparative effectiveness research underscores the importance of clinical trials in the practice of evidence-based medicine and health care reform. The impact of clinical trials not only extends to the individual patient by establishing a broader selection of effective therapies, but also to society as a whole by enhancing the value of health care provided. However, clinical trials also have the potential to pose unknown risks to their participants, and biased knowledge extracted from flawed clinical trials may lead to the inadvertent harm of patients. Although conducting a well-designed clinical trial may appear straightforward, it is founded on rigorous methodology and oversight governed by key ethical principles. In this review, we provide an overview of the ethical foundations of trial design, trial oversight, and the process of obtaining approval of a therapeutic, from its pre-clinical phase to post-marketing surveillance. This narrative review is based on a course in clinical trials developed by one of the authors (DJM), and is supplemented by a PubMed search predating January 2011 using the keywords "randomized controlled trial," "patient/clinical research," "ethics," "phase IV," "data and safety monitoring board," and "surrogate endpoint." With an understanding of the key principles in designing and implementing clinical trials, health care providers can partner with the pharmaceutical industry and regulatory bodies to effectively compare medical therapies and thereby meet one of the essential goals of health care reform. PMID:21904102

  5. Regulatory aspects of clinical trials in children.

    PubMed

    Mentzer, Dirk

    2009-01-01

    Since introduction of the EU Paediatric Regulation in January 2007 the development and the life cycle of a drug in pre- and post-authorisation period has changed significantly. Pharmacovigilance science has traditionally been a discipline focussed on the post-marketing or post-authorisation period, with due attention directed towards pre-clinical safety data, clinical trials and adverse events. As the biological sciences have evolved, pharmacovigilance has slowly shifted toward earlier, proactive consideration of risks and potential benefits of drugs in the pre- and post-approval stages of drug development, leading to a maturing of drug safety risk management. The development of drugs for the paediatric population has changed the awareness that not only the safety issues need to be thoroughly investigated for a safe treatment of the children. In conjunction with the knowledge about efficacy, pharmacokinetic/pharmacodynamic and the age appropriate formulation for the concerned drug, the impact on the aim to apply safe medicines for children will steadily increase. Therefore, a proposal for a joint effort performing clinical research and appropriate drug development and clinical trials in children needs a strong support from a number of stakeholders like Clinical Trial Network, Paediatric Society, pharmaceutical industry and authorities. PMID:20799462

  6. Potency and Stability of Intradermal Capsaicin: Implications for Use as a Human Model of Pain in Multicenter Clinical Trials.

    PubMed

    Balabathula, Pavan; Bhattacharjee, Himanshu; Thoma, Laura A; Nolly, Robert J; Horton, Frank P; Stornes, Gwendolyn D; Wan, Jim Y; Brooks, Ian M; Bachmann, Gloria A; Foster, David C; Brown, Candace S

    2014-01-01

    Intradermally injected capsaicin has been used extensively both as a human pain model and to assess analgesic efficacy. Factors such as dose, formulation, route, and site are known to affect its sensitivity. We determined whether potency and stability of capsaicin solutions were further sources of variability when following strict manufacturing guidelines. Capsaicin solution (1.0 mg/mL) was prepared according to Current Good Manufacturing Practice (cGMP) guidelines and aseptically filled into sterile amber borosilicate vials and stored at 5°C, 25°C, and 30°C. All samples were analyzed at one, three, six, and twelve months. Chemical stability was determined using HPLC and physical stability was evaluated by visual inspection of color changes, clarity, particulate matter, and product/ container closure abnormalities during each sampling time. Capsaicin intradermal injection was found to be sterile and retained 95% of the initial concentration for at least one year, regardless of studied storage temperatures (P<0.0001). Visual inspection indicated no changes in color, clarity, particulate matter, and product/ container closure abnormalities in all samples. These data show that capsaicin solutions (1.0 mg/mL) maintain their potency and stability over one year when manufactured according to cGMP guidelines. These results suggest that in clinical trials manufacturing of capsaicin solutions is recommended over extemporaneous compounding. PMID:25105064

  7. Repurposing celecoxib as a topical antimicrobial agent

    PubMed Central

    Thangamani, Shankar; Younis, Waleed; Seleem, Mohamed N.

    2015-01-01

    There is an urgent need for new antibiotics and alternative strategies to combat multidrug-resistant bacterial pathogens, which are a growing clinical issue. Repurposing existing approved drugs with known pharmacology and toxicology is an alternative strategy to accelerate antimicrobial research and development. In this study, we show that celecoxib, a marketed inhibitor of cyclooxygenase-2, exhibits broad-spectrum antimicrobial activity against Gram-positive pathogens from a variety of genera, including Staphylococcus, Streptococcus, Listeria, Bacillus, and Mycobacterium, but not against Gram-negative pathogens. However, celecoxib is active against all of the Gram-negative bacteria tested, including strains of, Acinetobacter, and Pseudomonas, when their intrinsic resistance is artificially compromised by outer membrane permeabilizing agents such as colistin. The effect of celecoxib on incorporation of radioactive precursors into macromolecules in Staphylococcus aureus was examined. The primary antimicrobial mechanism of action of celecoxib was the dose-dependent inhibition of RNA, DNA, and protein synthesis. Further, we demonstrate the in vivo efficacy of celecoxib in a methicillin-resistant S. aureus (MRSA) infected Caenorhabditis elegans whole animal model. Topical application of celecoxib (1 and 2%) significantly reduced the mean bacterial count in a mouse model of MRSA skin infection. Further, celecoxib decreased the levels of all inflammatory cytokines tested, including tumor necrosis factor-α, interleukin-6, interleukin-1 beta, and monocyte chemo attractant protein-1 in wounds caused by MRSA infection. Celecoxib also exhibited synergy with many conventional antimicrobials when tested against four clinical isolates of S. aureus. Collectively, these results demonstrate that celecoxib alone, or in combination with traditional antimicrobials, has a potential to use as a topical drug for the treatment of bacterial skin infections. PMID:26284040

  8. GFR decline as an end point for clinical trials in CKD: a scientific workshop sponsored by the National Kidney Foundation and the US Food and Drug Administration.

    PubMed

    Levey, Andrew S; Inker, Lesley A; Matsushita, Kunihiro; Greene, Tom; Willis, Kerry; Lewis, Edmund; de Zeeuw, Dick; Cheung, Alfred K; Coresh, Josef

    2014-12-01

    The US Food and Drug Administration currently accepts halving of glomerular filtration rate (GFR), assessed as doubling of serum creatinine level, as a surrogate end point for the development of kidney failure in clinical trials of kidney disease progression. A doubling of serum creatinine level generally is a late event in chronic kidney disease (CKD); thus, there is great interest in considering alternative end points for clinical trials to shorten their duration, reduce sample size, and extend their conduct to patients with earlier stages of CKD. However, the relationship between lesser declines in GFR and the subsequent development of kidney failure has not been well characterized. The National Kidney Foundation and Food and Drug Administration sponsored a scientific workshop to critically examine available data to determine whether alternative GFR-based end points have sufficiently strong relationships with important clinical outcomes of CKD to be used in clinical trials. Based on a series of meta-analyses of cohorts and clinical trials and simulations of trial designs and analytic methods, the workshop concluded that a confirmed decline in estimated GFR of 30% over 2 to 3 years may be an acceptable surrogate end point in some circumstances, but the pattern of treatment effects on GFR must be examined, specifically acute effects on estimated GFR. An estimated GFR decline of 40% may be more broadly acceptable than a 30% decline across a wider range of baseline GFRs and patterns of treatment effects on GFR. However, there are other circumstances in which these end points could lead to a reduction in statistical power or erroneous conclusions regarding benefits or harms of interventions. We encourage careful consideration of these alternative end points in the design of future clinical trials. PMID:25441437

  9. Extracellular Hsp90 (eHsp90) as the Actual Target in Clinical Trials: Intentionally or Unintentionally

    PubMed Central

    Li, Wei; Tsen, Fred; Sahu, Divya; Bhatia, Ayesha; Chen, Mei; Multhoff, Gabriele; Woodley, David T.

    2014-01-01

    Despite extensive investigative studies and clinical trials over the past two decades, we still do not understand why cancer cells are more sensitive to the cellular toxicity of Hsp90 inhibitors than normal cells. We still do not understand why only some cancer cells are sensitive to the Hsp90 inhibitors. Based on studies of the past few years, we argue that the selected sensitivity of cancer cells to Hsp90 inhibitors, such as 17-N-allylamino-17-demethoxygeldanamycin, is due to inhibition of the extracellular Hsp90 (eHsp90) rather than intracellular Hsp90 by these inhibitors. Because not all tumor cells utilize eHsp90 for motility, invasion and metastasis, only the group of “eHsp90-dependent” cancer cells is sensitive to Hsp90 inhibitors. If these notions prove to be true, pharmaceutical agents that selectively target eHsp90 should be more effective on tumor cells and less toxic on normal cells than current inhibitors that nondiscriminatively target both extracellular and intracellular Hsp90. PMID:23445811

  10. Oral Zinc Sulfate as Adjuvant Treatment in Children With Nephrolithiasis: a Randomized, Double-Blind, Placebo-Controlled Clinical Trial

    PubMed Central

    Yousefichaijan, Parsa; Cyrus, Ali; Dorreh, Fatemeh; Rafeie, Mohammad; Sharafkhah, Mojtaba; Frohar, Faryar; Safi, Fatemeh

    2015-01-01

    Background: Nephrolithiasis in children is associated with a high rate of complications and recurrence. Objectives: Since some evidences reported that zinc has an important place amongst inhibitors of crystallization and crystal growth, we decided to assess the effectiveness of oral zinc sulfate as adjuvant treatment in children with nephrolithiasis. Patients and Methods: This was a randomized, double-blind, placebo-controlled clinical trial. 102 children in the age range 1 month to 11 years with first nephrolithiasis were recruited. Patients were randomly divided into two equal groups (intervention and control groups). Intervention group received conservative measures for stones and 1 mg/kg/day (maximum 20 mg/day) oral zinc sulfate syrup for 3 months. Control group received placebo in addition to conservative measures, also for 3 months. Patients were followed up by ultrasonography for 9 months, in 5 steps (at the end of 1st, 2nd, 3rd, 6th and 9th month after treatment) assessing size and number of stones in the kidneys. Results: Only at the end of the first month, the average number (intervention: 1.15 ± 3.78, control: 1.3 ± 2.84) (P = 0.001) and size (cm) (intervention: 0.51 ± 1.76, control: 0.62 ± 1.39) (P = 0.001) of stones was significantly lower in the intervention group, and in other points there was no significant therapeutic efficacy in oral zinc adjuvant treatment compared to conservative treatment alone. Also, during the 9-month follow-up, the number and size of stones in both groups decreased significantly (both: P < 0.0001) in a way that the decrease in the intervention group showed no difference with the control group. Conclusions: Adjuvant treatment with zinc is not more effective than consecutive treatment in children with nephrolithiasis. However, further studies are recommended due to the lack of clinical evidence in this field. PMID:26635934

  11. Rest versus exercise as treatment for patients with low back pain and Modic changes. a randomized controlled clinical trial

    PubMed Central

    2012-01-01

    Background Clinical experience suggests that many patients with Modic changes have relatively severe and persistent low back pain (LBP), which typically appears to be resistant to treatment. Exercise therapy is the recommended treatment for chronic LBP, however, due to their underlying pathology, Modic changes might be a diagnostic subgroup that does not benefit from exercise. The objective of this study was to compare the current state-of-the art treatment approach (exercise and staying active) with a new approach (load reduction and daily rest) for people with Modic changes using a randomized controlled trial design. Methods Participants were patients from an outpatient clinic with persistent LBP and Modic changes. They were allocated using minimization to either rest therapy for 10 weeks with a recommendation to rest for two hours daily and the option of using a flexible lumbar belt or exercise therapy once a week for 10 weeks. Follow-up was at 10 weeks after recruitment and 52 weeks after intervention and the clinical outcome measures were pain, disability, general health and global assessment, supplemented by weekly information on low back problems and sick leave measured by short text message (SMS) tracking. Results In total, 100 patients were included in the study. Data on 87 patients at 10 weeks and 96 patients at one-year follow-up were available and were used in the intention-to-treat analysis. No statistically significant differences were found between the two intervention groups on any outcome. Conclusions No differences were found between the two treatment approaches, 'rest and reduced load' and 'exercise and staying active', in patients with persistent LBP and Modic changes. Trial Registration ClinicalTrials.gov: NCT00454792 PMID:22376791

  12. Clinical trials in developing countries: Discussions at the '9th International Symposium on Long Term Clinical Trials', London, UK, 19-20 June 2000

    PubMed Central

    Johnatty, Rachel N

    2000-01-01

    This symposium provided a useful forum for the discussion of issues relating to the design and conduct of clinical trials. There is a need for greater awareness of the complexity of modern day trials, in which a host of statistical, logistical, regulatory and ethical issues are involved. Issues discussed ranged from the effect of sample size on the outcome, and subgroup analysis, to defining and maintaining discrete endpoints. Some useful debate centred on the use of meta-analysis and the current limitations of combining information from different data sets. This brought up the subjects of trial registries and raw data repositories for all clinical trials. Progress and relevance of the Cochrane collaboration were reviewed. The economics of clinical trials was another important topic. Regulatory issues such as the role of data and safety monitoring boards (DSMB) and the guidelines in place for effective data monitoring and progress analysis were discussed. Representatives of government organisations and industry gave both European and American perspectives. This report however focuses specifically on the section devoted to the subject of clinical trials in developing countries. PMID:11714410

  13. A data grid for imaging-based clinical trials

    NASA Astrophysics Data System (ADS)

    Zhou, Zheng; Chao, Sander S.; Lee, Jasper; Liu, Brent; Documet, Jorge; Huang, H. K.

    2007-03-01

    Clinical trials play a crucial role in testing new drugs or devices in modern medicine. Medical imaging has also become an important tool in clinical trials because images provide a unique and fast diagnosis with visual observation and quantitative assessment. A typical imaging-based clinical trial consists of: 1) A well-defined rigorous clinical trial protocol, 2) a radiology core that has a quality control mechanism, a biostatistics component, and a server for storing and distributing data and analysis results; and 3) many field sites that generate and send image studies to the radiology core. As the number of clinical trials increases, it becomes a challenge for a radiology core servicing multiple trials to have a server robust enough to administrate and quickly distribute information to participating radiologists/clinicians worldwide. The Data Grid can satisfy the aforementioned requirements of imaging based clinical trials. In this paper, we present a Data Grid architecture for imaging-based clinical trials. A Data Grid prototype has been implemented in the Image Processing and Informatics (IPI) Laboratory at the University of Southern California to test and evaluate performance in storing trial images and analysis results for a clinical trial. The implementation methodology and evaluation protocol of the Data Grid are presented.

  14. Surgeons: A Future Role in Clinical Trials?

    PubMed

    Rusch

    1997-01-01

    Clinical trials, particularly large cooperative group trials, establish the standards that we use to treat many of our cancer patients. The process by which multi-institutional clinical trials are developed, performed and peer-reviewed in the United States is equaled by few other countries around the world. Our clinical cooperative groups should be considered an important national resource. However, they stand at an embattled crossroads. Traditionally, only two to three percent of cancer patients have been entered onto clinical trials. In the past few years, national accrual has declined even further-from approximately 22,000 to 16,000 patients annually. The reasons for this decline are unclear. Although it could simply reflect a hiatus in the activity of some groups (such as the recent reorganization of the National Surgical Adjuvant Breast and Bowel Project [NSABP]), it more likely reflects changes in our health care environment. Few managed care insurance plans permit patient entry into clinical studies on the premise that trials increase patient care costs. Yet, individualized patient care not delivered according to strict peer-reviewed standards may cost more. While this remains undetermined, oncologists in both academic and private practice are being pressured to work harder for fewer rewards. They are being told that investigational treatments are not allowed even if trials evaluating these treatments may ultimately lead to better and more cost-effective patient care. This is a sad state of affairs at a time when, on one hand, treatment for many solid tumors remains desperately inadequate and, on the other hand, new insights into tumor biology promise to alter fundamentally our approach to cancer care. Where do surgeons fit into this picture? The cooperative groups were initiated in the mid-1950s, primarily to evaluate the potential role of chemotherapy in cancer treatment. During the past forty years, surgeons have usually played a supporting role in

  15. Ethics of clinical trials in Nigeria

    PubMed Central

    Okonta, Patrick I.

    2014-01-01

    The conduct of clinical trials for the development and licensing of drugs is a very important aspect of healthcare. Drug research, development and promotion have grown to a multi-billion dollar global business. Like all areas of human endeavour involving generation and control of huge financial resources, it could be subject to deviant behaviour, sharp business practices and unethical practices. The main objective of this review is to highlight potential ethical challenges in the conduct of clinical trials in Nigeria and outline ways in which these can be avoided. Current international and national regulatory and ethical guidelines are reviewed to illustrate the requirements for ethical conduct of clinical trials. Past experiences of unethical conduct of clinical trials especially in developing countries along with the increasing globalisation of research makes it imperative that all players should be aware of the ethical challenges in clinical trials and the benchmarks for ethical conduct of clinical research in Nigeria. PMID:25013247

  16. [Global views on clinical trials and data quality].

    PubMed

    Liu, Daniel; Han, Xiu-lan; Sun, Hua-long; Dai, Nan

    2015-11-01

    The quality and integrity of clinical trials and associated data are not only derived from accuracy of trial data analyses, but also closely embodied to the authenticity and integrity of those data and data documents as well as the compliant procedures obtaining those data and relevant files in the life cycle of clinical trials. The compliances of good clinical practices and standards suggest the reliability, complete and accuracy of data and data documents, which is constructing the convincible foundation of drug efficacy and safety validated via clinical trials. Therefore, the monitoring and auditing on clinical trials and associated data quality keep eyes on not only verifications of reliability and correctness on the data analytic outcomes, but also validation of science and compliance of the trial management procedure and documentations in the process of data collections. PMID:26911039

  17. The unintended consequences of clinical trials regulations.

    PubMed

    McMahon, Alex D; Conway, David I; Macdonald, Tom M; McInnes, Gordon T

    2009-11-01

    Alex McMahon and colleagues critique the International Conference on Harmonisation (ICH) guidance on good clinical practice (GCP), arguing that it is having a disastrous effect on noncommerical randomized clinical trials in Europe. PMID:19918557

  18. Clinical trials in India: Where do we stand globally?

    PubMed Central

    Selvarajan, Sandhiya; George, Melvin; Kumar, Suresh S; Dkhar, Steven Aibor

    2013-01-01

    Aims: To evaluate the trend of clinical trials in India over the last 4 years compared to the well-established countries using clinical trial registries since the advent of clinical trial registry of India (CTRI). Materials and Methods: The data of clinical trials registered in India, United States (US), and European Union (EU) were obtained from websites of CTRI, clinicaltrial.gov and EU clinical trial registry, respectively from July 20, 2007 to August 29, 2011 for a period of 4 years. Trials registered in Australia, Canada, China, and Japan were obtained from WHO's international clinical trial registry platform for the same period. We used search words for the common diseases such as diabetes, hypertension, etc., Results: The total number of clinical trials registered during the study period was 67,448 across seven study nations. Clinical trials from India constituted only 2.7% of the total number of trials carried out, compared to US constituting 47% of the total number of trials registered, followed by 18% from EU and 11% from Japan. However, India, China, and Japan have been found to show an increase of 3.7%, 5.1%, and 13.1% increase in the number of trials registered in 2011 compared to 2007. In contrast, US and EU showed a decline of 11.3% and 11.95% respectively in the total number of trials registered in 2011 compared to 2007. Conclusions: Although India shows gradual increase in trials registered since the advent of CTRI, still it continues to lag behind established countries in clinical research. PMID:24010056

  19. Enhancing clinical evidence by proactively building quality into clinical trials

    PubMed Central

    Meeker-O’Connell, Ann; Glessner, Coleen; Behm, Mark; Mulinde, Jean; Roach, Nancy; Sweeney, Fergus; Tenaerts, Pamela; Landray, Martin J

    2016-01-01

    Background: Stakeholders across the clinical trial enterprise have expressed concern that the current clinical trial enterprise is unsustainable. The cost and complexity of trials have continued to increase, threatening our ability to generate reliable evidence essential for making appropriate decisions concerning the benefits and harms associated with clinical interventions. Overcoming this inefficiency rests on improving protocol design, trial planning, and quality oversight. Methods: The Clinical Trials Transformation Initiative convened a project to evaluate methods to prospectively build quality into the scientific and operational design of clinical trials (“quality-by-design”), such that trials are feasible to conduct and important errors are prevented rather than remediated. A working group evaluated aspects of trial design and oversight and developed the Clinical Trials Transformation Initiative quality-by-design principles document, outlining a series of factors generally relevant to the reliability of trial conclusions and to patient safety. These principles were then applied and further refined during a series of hands-on workshops to evaluate their utility in facilitating proactive, cross-functional dialogue, and decision-making about trial design and planning. Following these workshops, independent qualitative interviews were conducted with 19 workshop attendees to explore the potential challenges for implementing a quality-by-design approach to clinical trials. The Clinical Trials Transformation Initiative project team subsequently developed recommendations and an online resource guide to support implementation of this approach. Conclusion: The Clinical Trials Transformation Initiative quality-by-design principles provide a framework for assuring that clinical trials adequately safeguard participants and provide reliable information on which to make decisions on the effects of treatments. The quality-by-design workshops highlighted the value of

  20. Rett Syndrome: Reaching for Clinical Trials.

    PubMed

    Pozzo-Miller, Lucas; Pati, Sandipan; Percy, Alan K

    2015-07-01

    Rett syndrome (RTT) is a syndromic autism spectrum disorder caused by loss-of-function mutations in MECP2. The methyl CpG binding protein 2 binds methylcytosine and 5-hydroxymethycytosine at CpG sites in promoter regions of target genes, controlling their transcription by recruiting co-repressors and co-activators. Several preclinical studies in mouse models have identified rational molecular targets for drug therapies aimed at correcting the underlying neural dysfunction. These targeted therapies are increasingly translating into human clinical trials. In this review, we present an overview of RTT and describe the current state of preclinical studies in methyl CpG binding protein 2-based mouse models, as well as current clinical trials in individuals with RTT. PMID:25861995

  1. Clinical efficacy of oral and topical acyclovir in herpes simplex virus stromal necrotizing keratitis

    PubMed Central

    Dutt, Surabhi; Acharya, Manisha; Gour, Abha; Sapra, Neelam; Chauhan, Lokesh; Mathur, Umang

    2016-01-01

    Purpose: To evaluate the efficacy of systemic and topical antiviral therapy in the treatment of active herpes simplex virus (HSV) necrotizing stromal keratitis (NSK). Design: Prospective interventional case series. Methodology: Patients with a diagnosis of HSV NSK based on history and clinical findings were enrolled in the study. A standard protocol was used for microbiologic investigations. Ten weeks regime of systemic acyclovir and 2 weeks of topical acyclovir was given. Complete ophthalmic examination was performed at every visit. Outcome measures were a reduction in the area of infiltration and improvement in visual acuity. Results: Fifteen patients were enrolled in the study. The mean age of presentation was 51.53 years. The duration of symptoms at presentation ranged from 2 to 8 weeks. HSV1 DNA polymerase chain reaction was positive in 70% cases of those tested. Area of infiltration at trial entry and at the end of 2 weeks of antiviral treatment reduced significantly (P = 0.007). All patients showed a complete resolution of keratitis at the end of study. Conclusion: Topical and systemic acyclovir for treatment of NSK facilitates healing of ulceration. Topical steroids after initial antiviral therapy are safe and decreases inflammation and improve visual recovery. Early initiation of therapy has better outcomes as compared to late presentations. PMID:27221681

  2. How ethical is your clinical trial?

    PubMed Central

    Miller, L; Folayan, M; Allman, D; Nkala, B; Kasirye, L M; Mingote, L R; Calazans, G; Mburu, R; Ntombela, F; Ditmore, M

    2010-01-01

    Is Institutional Review Board (IRB) approval and a rigorous informed consent process enough? It is our view that this is no longer the case. Conventional research ethics emphasise the importance of weighing the risks and benefits for prospective participants as one of the key determinants of deeming a clinical trial ethical. We support the notion that ethical obligations of research should include considerations not only at the individual level, but also at the community level (1,2). PMID:20561091

  3. Prudent precaution in clinical trials of nanomedicines.

    PubMed

    Marchant, Gary E; Lindor, Rachel A

    2012-01-01

    Clinical trials of nanotechnology medical products present complex risk management challenges that involve many uncertainties and important risk-risk trade-offs. This paper inquires whether the precautionary principle can help to inform risk management approaches to nanomedicine clinical trials. It concludes that prudent precaution may be appropriate for ensuring the safety of such trials, but that the precautionary principle itself, especially in its more extreme forms, does not provide useful guidance for specific safety measures. PMID:23289685

  4. The Cooperative Landscape of Multinational Clinical Trials

    PubMed Central

    Hsiehchen, David; Espinoza, Magdalena; Hsieh, Antony

    2015-01-01

    The scale and nature of cooperative efforts spanning geopolitical borders in clinical research have not been elucidated to date. In a cross-sectional study of 110,428 interventional trials registered in Clinicaltrials.gov, we characterized the evolution, trial demographics, and network properties of multinational clinical research. We reveal that the relative growth of international collaboratives has remained stagnant in the last two decades, although clinical trials have evolved to become much larger in scale. Multinational clinical trials are also characterized by higher patient enrollments, industry funding, and specific clinical disciplines including oncology and infectious disease. Network analyses demonstrate temporal shifts in collaboration patterns between countries and world regions, with developing nations now collaborating more within themselves, although Europe remains the dominant contributor to multinational clinical trials worldwide. Performances in network centrality measures also highlight the differential contribution of nations in the global research network. A city-level clinical trial network analysis further demonstrates how collaborative ties decline with physical distance. This study clarifies evolving themes and highlights potential growth mechanisms and barriers in multinational clinical trials, which may be useful in evaluating the role of national and local policies in organizing transborder efforts in clinical endeavors. PMID:26103155

  5. Novel ocular antihypertensive compounds in clinical trials

    PubMed Central

    Chen, June; Runyan, Stephen A; Robinson, Michael R

    2011-01-01

    Introduction: Glaucoma is a multifactorial disease characterized by progressive optic nerve injury and visual field defects. Elevated intraocular pressure (IOP) is the most widely recognized risk factor for the onset and progression of open-angle glaucoma, and IOP-lowering medications comprise the primary treatment strategy. IOP elevation in glaucoma is associated with diminished or obstructed aqueous humor outflow. Pharmacotherapy reduces IOP by suppressing aqueous inflow and/or increasing aqueous outflow. Purpose: This review focuses on novel non-FDA approved ocular antihypertensive compounds being investigated for IOP reduction in ocular hypertensive and glaucoma patients in active clinical trials within approximately the past 2 years. Methods: The mode of IOP reduction, pharmacology, efficacy, and safety of these new agents were assessed. Relevant drug efficacy and safety trials were identified from searches of various scientific literature databases and clinical trial registries. Compounds with no specified drug class, insufficient background information, reformulations, and fixed-combinations of marketed drugs were not considered. Results: The investigational agents identified comprise those that act on the same targets of established drug classes approved by the FDA (ie, prostaglandin analogs and β-adrenergic blockers) as well as agents belonging to novel drug classes with unique mechanisms of action. Novel targets and compounds evaluated in clinical trials include an actin polymerization inhibitor (ie, latrunculin), Rho-associated protein kinase inhibitors, adenosine receptor analogs, an angiotensin II type 1 receptor antagonist, cannabinoid receptor agonists, and a serotonin receptor antagonist. Conclusion: The clinical value of novel compounds for the treatment of glaucoma will depend ultimately on demonstrating favorable efficacy and benefit-to-risk ratios relative to currently approved prostaglandin analogs and β-blockers and/or having complementary

  6. Is wound infiltration with anesthetic effective as pre-emptive analgesia? A clinical trial in appendectomy patients

    PubMed Central

    Willard, Peter T.; Blair, N. Peter

    1997-01-01

    Objective To assess the efficacy of wound infiltration with local anesthetic in reducing postoperative pain after a muscle-splitting incision for appendectomy. Design A double-blind, placebo-controlled, randomized clinical trial. Setting The Royal Columbian Hospital, a university-affiliated community hospital. Participants Forty-three patients scheduled to undergo emergency appendectomy were randomized into treatment (21) and control (22) groups. Five patients were excluded from the treatment group. Interventions Local anesthetic infiltration of the wound before incision (treatment group) and saline infiltration (control group). Main outcome measures Postoperative analgesic requirements, pain assessment by visual analogue scale and length of hospital stay. Results No significant difference in analgesic use was seen between the 2 groups, as measured at 3 stages (Mc = control mean [standard deviation], Mt = treatment mean [standard deviation]): (a) in the recovery room, intravenous morphine use was Mt = 6.6 mg [8.6] v. Mc = 10.1 mg [7.2]; (b) in the first 2 postoperative days, intramuscular meperidine use was Mt = 309 mg [181] v. Mc = 278 mg [125] on day 1 and was Mt = 121 mg [132] v. Mc = 97 mg [128] on day 2; (c) in the final 5 days of follow-up, oral analgesic use was Mt = 11 [17] tablets v. Mc = 21 [16] tablets (acetaminophen with codeine). Pain assessments at rest, on a scale of 1 to 10, were found to be no different between groups, ratings being Mt = 4.7 [2.1] v. Mc = 4.5 [2.0] on day 1. Length of hospital stay averaged 3.0 days in both groups. Conclusion Infiltration with local anesthetic before incision does not pre-empt postoperative pain from a muscle-splitting incision used for appendectomy. PMID:9194783

  7. Colloids versus crystalloids as priming solutions for cardiopulmonary bypass: a meta-analysis of prospective, randomised clinical trials.

    PubMed

    Himpe, D

    2003-01-01

    Using Cochrane methodology a review was performed of prospective randomized clinical trials comparing colloidal pump priming solutions for cardiopulmonary bypass. Dextrans were not considered. Database searches from 1966 through December 2002 delivered 265 articles. Seventeen studies finally met the eligibility criteria involving 997 patients. Summary odds ratio estimates from the 5 studies reporting mortality were 1.46 (n = 326; 95%-Confidence-Interval: .55 to 3.85; p = .49) for crystalloids against colloids and .74 (n = 150; 95%-Confidence-Interval: .17 to 3.36; p = .49) for albumin versus synthetic colloids. Most commonly used outcome measures further included postoperative blood loss, platelet-count, fluid-balance and, colloid osmotic pressures from which Standardized Mean Differences (SMD) and their 95%-Confidence-Interval (95%CI) were extracted. Colloids produced significantly higher oncotic pressures and less positive fluid-balances. Although across 9 studies postoperative bleeding between colloids and crystalloids did not differ (n = 663; SMD: -.03, 95%CI: -.18 to .12; p = .69), platelet counts significantly favoured crystalloids (n = 465; SMD: -.42; 95%CI: -.68 to -.16; p = .00). However, compared to albumin platelet counts were significantly disfavoured only by starches (n = 321; SMD: -.55; 95%CI: -.77 to -.32; p = .00). To conclude, using mere crystalloids produced more pronounced positive fluid balances and their avoidance as a single pump-prime component can be suggested. Since albumin is not necessarily associated with better outcomes and is more expensive, it is hard to continue its use. However, there is still insufficient evidence available to allow definitive conclusions. PMID:14598617

  8. Lessons learned from radiation oncology clinical trials.

    PubMed

    Liu, Fei-Fei; Okunieff, Paul; Bernhard, Eric J; Stone, Helen B; Yoo, Stephen; Coleman, C Norman; Vikram, Bhadrasain; Brown, Martin; Buatti, John; Guha, Chandan

    2013-11-15

    A workshop entitled "Lessons Learned from Radiation Oncology Trials" was held on December 7-8, 2011, in Bethesda, MD, to present and discuss some of the recently conducted radiation oncology clinical trials with a focus on those that failed to refute the null hypothesis. The objectives of this workshop were to summarize and examine the questions that these trials provoked, to assess the quality and limitations of the preclinical data that supported the hypotheses underlying these trials, and to consider possible solutions to these challenges for the design of future clinical trials. Several themes emerged from the discussions: (i) opportunities to learn from null-hypothesis trials through tissue and imaging studies; (ii) value of preclinical data supporting the design of combinatorial therapies; (iii) significance of validated biomarkers; (iv) necessity of quality assurance in radiotherapy delivery; (v) conduct of sufficiently powered studies to address the central hypotheses; and (vi) importance of publishing results of the trials regardless of the outcome. The fact that well-designed hypothesis-driven clinical trials produce null or negative results is expected given the limitations of trial design and complexities of cancer biology. It is important to understand the reasons underlying such null results, however, to effectively merge the technologic innovations with the rapidly evolving biology for maximal patient benefit through the design of future clinical trials. PMID:24043463

  9. Methodology Series Module 4: Clinical Trials

    PubMed Central

    Setia, Maninder Singh

    2016-01-01

    In a clinical trial, study participants are (usually) divided into two groups. One group is then given the intervention and the other group is not given the intervention (or may be given some existing standard of care). We compare the outcomes in these groups and assess the role of intervention. Some of the trial designs are (1) parallel study design, (2) cross-over design, (3) factorial design, and (4) withdrawal group design. The trials can also be classified according to the stage of the trial (Phase I, II, III, and IV) or the nature of the trial (efficacy vs. effectiveness trials, superiority vs. equivalence trials). Randomization is one of the procedures by which we allocate different interventions to the groups. It ensures that all the included participants have a specified probability of being allocated to either of the groups in the intervention study. If participants and the investigator know about the allocation of the intervention, then it is called an “open trial.” However, many of the trials are not open – they are blinded. Blinding is useful to minimize bias in clinical trials. The researcher should familiarize themselves with the CONSORT statement and the appropriate Clinical Trials Registry of India. PMID:27512184

  10. Methodology Series Module 4: Clinical Trials.

    PubMed

    Setia, Maninder Singh

    2016-01-01

    In a clinical trial, study participants are (usually) divided into two groups. One group is then given the intervention and the other group is not given the intervention (or may be given some existing standard of care). We compare the outcomes in these groups and assess the role of intervention. Some of the trial designs are (1) parallel study design, (2) cross-over design, (3) factorial design, and (4) withdrawal group design. The trials can also be classified according to the stage of the trial (Phase I, II, III, and IV) or the nature of the trial (efficacy vs. effectiveness trials, superiority vs. equivalence trials). Randomization is one of the procedures by which we allocate different interventions to the groups. It ensures that all the included participants have a specified probability of being allocated to either of the groups in the intervention study. If participants and the investigator know about the allocation of the intervention, then it is called an "open trial." However, many of the trials are not open - they are blinded. Blinding is useful to minimize bias in clinical trials. The researcher should familiarize themselves with the CONSORT statement and the appropriate Clinical Trials Registry of India. PMID:27512184

  11. Timing and Completeness of Trial Results Posted at ClinicalTrials.gov and Published in Journals

    PubMed Central

    Riveros, Carolina; Dechartres, Agnes; Perrodeau, Elodie; Haneef, Romana; Boutron, Isabelle; Ravaud, Philippe

    2013-01-01

    Background The US Food and Drug Administration Amendments Act requires results from clinical trials of Food and Drug Administration–approved drugs to be posted at ClinicalTrials.gov within 1 y after trial completion. We compared the timing and completeness of results of drug trials posted at ClinicalTrials.gov and published in journals. Methods and Findings We searched ClinicalTrials.gov on March 27, 2012, for randomized controlled trials of drugs with posted results. For a random sample of these trials, we searched PubMed for corresponding publications. Data were extracted independently from ClinicalTrials.gov and from the published articles for trials with results both posted and published. We assessed the time to first public posting or publishing of results and compared the completeness of results posted at ClinicalTrials.gov versus published in journal articles. Completeness was defined as the reporting of all key elements, according to three experts, for the flow of participants, efficacy results, adverse events, and serious adverse events (e.g., for adverse events, reporting of the number of adverse events per arm, without restriction to statistically significant differences between arms for all randomized patients or for those who received at least one treatment dose). From the 600 trials with results posted at ClinicalTrials.gov, we randomly sampled 50% (n = 297) had no corresponding published article. For trials with both posted and published results (n = 202), the median time between primary completion date and first results publicly posted was 19 mo (first quartile = 14, third quartile = 30 mo), and the median time between primary completion date and journal publication was 21 mo (first quartile = 14, third quartile = 28 mo). Reporting was significantly more complete at ClinicalTrials.gov than in the published article for the flow of participants (64% versus 48% of trials, p<0.001), efficacy results (79% versus 69%, p = 0

  12. Personalized medicine: ethics for clinical trials.

    PubMed

    Sharrer, G Terry

    2012-01-01

    Modern ethical codes in medicine were developed following World War II to provide respect for persons, beneficence, and justice in clinical research. Clinical trial medicine involves greater scrutiny than most research activities. In every instance, clinical trials have institutional review boards to ensure the medical procedure under study complies with regulatory requirements, privacy, informed consent, good practices, safety monitoring, adverse events reporting, and is free of conflicting interests. Mandatory training in medical ethics for all clinical staff is becoming more common, and at some institutions, knowledgeable patient advocates play a watchdog role. In personalized medicine, each patient becomes a clinical trial of one, based on the uniqueness of the person's illness and the relatively tailored treatment. These features imply a shared responsibility between the patient and the researchers because uncertainty exists over the outcome for each individual patient. This chapter introduces ethical considerations using case studies, with historical context, and describes general ethical guidelines for initiating a clinical trial. PMID:22081337

  13. Paperless clinical trials: Myth or reality?

    PubMed

    Gupta, Sandeep K

    2015-01-01

    There is an urgent need to expedite the time-to-market for new drugs and to make the approval process simpler. But clinical trials are a complex process and the increased complexity leads to decreased efficiency. Hence, pharmaceutical organizations want to move toward a more technology-driven clinical trial process for recording, analyzing, reporting, archiving, etc., In recent times, the progress has certainly been made in developing paperless systems that improve data capture and management. The adaptation of paperless processes may require major changes to existing procedures. But this is in the best interests of these organizations to remain competitive because a paperless clinical trial would lead to a consistent and streamlined framework. Moreover, all major regulatory authorities also advocate adoption of paperless trial. But challenges still remain toward implementation of paperless clinical trial process. PMID:26288464

  14. End points in dermatologic clinical trials: A review for clinicians.

    PubMed

    Wei, Erin X; Kirsner, Robert S; Eaglstein, William H

    2016-07-01

    Clinical trials are critical for the development of new therapies in dermatology, and their results help determine US Food and Drug Administration (FDA) approval and guide care. Of special relevance is the clinical trial efficacy end point, the metric from which statistically significant outcome is derived. Clinicians' understanding of a clinical trial's end point is necessary for critical analysis of the trial results and for applying those results to daily practice. This review provides practical knowledge and critical evaluation of end points used in treatment approvals by the FDA. The end points for actinic keratosis, acne vulgaris, atopic dermatitis, onychomycosis, and cutaneous ulcer serve as examples. PMID:26936300

  15. Randomised controlled trial of topical kanuka honey for the treatment of rosacea

    PubMed Central

    Braithwaite, Irene; Hunt, Anna; Riley, Judith; Fingleton, James; Kocks, Janwillem; Corin, Andrew; Helm, Colin; Sheahan, Davitt; Tofield, Christopher; Montgomery, Barney; Holliday, Mark; Weatherall, Mark; Beasley, Richard

    2015-01-01

    Objective To investigate the efficacy of topical 90% medical-grade kanuka honey and 10% glycerine (Honevo) as a treatment for rosacea. Design Randomised controlled trial with blinded assessment of primary outcome variable. Setting Outpatient primary healthcare population from 5 New Zealand sites. Participants 138 adults aged ≥16, with a diagnosis of rosacea, and a baseline blinded Investigator Global Assessment of Rosacea Severity Score (IGA-RSS) of ≥2. 69 participants were randomised to each treatment arm. 1 participant was excluded from the Honevo group, and 7 and 15 participants withdrew from the Honevo and control groups, respectively. Interventions Participants were randomly allocated 1:1 to Honevo or control cream (Cetomacrogol), applied twice daily for 8 weeks. Main outcome measures The primary outcome measure was the proportion of participants who had a ≥2 improvement in the 7-point IGA-RSS at week 8 compared to baseline. Secondary outcomes included change in IGA-RSS and subject-rated visual analogue score of change in severity (VAS-CS) on a 100 mm scale (0 mm ‘much worse’, 100 mm ‘much improved’) at weeks 2 and 8. Results 24/68 (34.3%) in the Honevo group and 12/69 (17.4%) in the control group had a ≥2 improvement in IGA-RSS at week 8 compared to baseline (relative risk 2.03; 95% CI 1.11 to 3.72, p=0.020). The change in IGA-RSS for Honevo compared to control at week 2 minus baseline was −1 (Hodges-Lehman estimate, 95% CI −1 to 0, p=0.03), and at week 8 minus baseline was −1 (Hodges-Lehman estimate, 95% CI −1 to 0, p=0.005). The VAS-CS at week 2 was 9.1 (95% CI 3.5 to 14.7), p=0.002, and at week 8 was 12.3 (95% CI 5.7 to 18.9)¸ p<0.001 for Honevo compared to control. Conclusions Honevo is an effective treatment for rosacea. Trial registration number This trial was registered in the Australian and New Zealand Clinical Trials Registry ACTRN12614000004662. PMID:26109117

  16. Cytomegalovirus vaccine: phase II clinical trial results.

    PubMed

    Rieder, F; Steininger, C

    2014-05-01

    Cytomegalovirus (CMV) is one of the most significant viral pathogens during pregnancy and in immunocompromised patients. Antiviral prophylactic strategies are limited by toxicities, drug-drug interactions and development of antiviral resistance. A safe and protective vaccine against CMV is highly desirable in view of the potential positive impact on CMV-associated morbidity and mortality as well as healthcare costs. Unfortunately, this demand could not be met in the past four decades although development of a CMV vaccine has been ranked at the highest priority by the US Institute of Medicine. Multiple different vaccine candidates have been developed and evaluated in phase I clinical trials and few succeeded to phase II trials. Nevertheless, two different vaccines showed recently promising results in trials that studied healthy adults and immunocompromised solid-organ and bone-marrow transplant recipients, respectively. The gB/MF59 vaccine exhibited a vaccine efficacy of 50% in healthy, postpartum females. In transplant patients, gB/MF59 and the DNA vaccine TransVax both limited the periods of viraemia and consequently the need for antiviral treatment. The success of these trials is encouraging and will probably give new impetus to the development of an effective CMV vaccine. Sterilizing immunity may not be attainable in the near future and may not be necessary for a CMV vaccine to have a significant impact on health care as discussed in the present review. PMID:24283990

  17. Future vision for the quality assurance of oncology clinical trials.

    PubMed

    Fitzgerald, Thomas J; Bishop-Jodoin, Maryann; Bosch, Walter R; Curran, Walter J; Followill, David S; Galvin, James M; Hanusik, Richard; King, Steven R; Knopp, Michael V; Laurie, Fran; O'Meara, Elizabeth; Michalski, Jeff M; Saltz, Joel H; Schnall, Mitchell D; Schwartz, Lawrence; Ulin, Kenneth; Xiao, Ying; Urie, Marcia

    2013-01-01

    The National Cancer Institute clinical cooperative groups have been instrumental over the past 50 years in developing clinical trials and evidence-based process improvements for clinical oncology patient care. The cooperative groups are undergoing a transformation process as we further integrate molecular biology into personalized patient care and move to incorporate international partners in clinical trials. To support this vision, data acquisition and data management informatics tools must become both nimble and robust to support transformational research at an enterprise level. Information, including imaging, pathology, molecular biology, radiation oncology, surgery, systemic therapy, and patient outcome data needs to be integrated into the clinical trial charter using adaptive clinical trial mechanisms for design of the trial. This information needs to be made available to investigators using digital processes for real-time data analysis. Future clinical trials will need to be designed and completed in a timely manner facilitated by nimble informatics processes for data management. This paper discusses both past experience and future vision for clinical trials as we move to develop data management and quality assurance processes to meet the needs of the modern trial. PMID:23508883

  18. DICOM Structured Reporting and Cancer Clinical Trials Results

    PubMed Central

    Clunie, David A

    2007-01-01

    The use of biomarkers derived from radiological images as surrogate end-points in therapeutic cancer clinical trials is well established. DICOM is the ubiquitous standard for the interchange of images for both clinical use as well as research. It also has capabilities for the exchange of image-related information, including categorical and quantitative information derived from images. The use of DICOM Structured Reporting for the encoding and interchange of clinical trial results in a standard manner is reviewed. PMID:19390663

  19. [Difficulties with conducting clinical trials in France].

    PubMed

    Zannad, F; Plétan, Y

    2001-01-01

    France ranks third among European countries as regards the level of investment in clinical R&D and, overall, accounts for a contributive effort proportional to the size of its population and pharmaceutical market respectively. However, there is a trend for phase II and III studies to become proportionally fewer than in the past, while the number of phase IV studies is increasing. In a growing proportion of the mega-trials, which are instrumental for establishing evidence-based practice, French experts, investigators and, even more seriously, French patients, are insufficiently represented. Though studies in France are initiated relatively fast due to a clear regulatory framework and perform equally well as far as quantitative and qualitative factors are concerned, compared with most European countries involved in clinical research the costs incurred per completed patient are higher than those recorded in the other countries. Academic research shares most of these constraints and suffers from a lack of financial and human resources, while it faces additional delays in implementing studies because of longer administrative processes. Given the stakes in play, specific solutions should be implemented to maintain and further develop French competitiveness in clinical R&D. At the patient level, positive perception and awareness of the usefulness and safety of participating in clinical trials need to be emphasized. Education at the school level and using the lay media should be developed. Intervention of institutional and government officials is much needed. Direct patient recruitment should be developed through advertisement and the Internet, as well as within doctors' offices and through collaboration with patients' organizations. Patient information and consent forms should be made much simpler than those imposed within the framework of global studies because of FDA requirements. The French health system discourages the recruitment of patients by investigators who are

  20. Topical Turmeric Microemulgel in the Management of Plaque Psoriasis; A Clinical Evaluation

    PubMed Central

    Sarafian, Golnaz; Afshar, Minoo; Mansouri, Parvin; Asgarpanah, Jinous; Raoufinejad, Kosar; Rajabi, Mehdi

    2015-01-01

    Psoriasis is an autoimmune and recurrent chronic inflammatory skin disease. About 1-3% of the world wide populations are affected. The characteristic features are hyperprolifration of keratinocytes leading to redness, thickening and scaling of epidermis followed with itching and appearance of the lesions which in most cases bother the patients medically and psychologically. Psoriasis is symptomatically treated by the range of oral and topical medications, however, major side effects in some cases are associated with them. Based on several studies, Curcuma longa can inhibit several inflammatory enzymes mainly involved in the inflammatory process of Psoriasis. Therefore, we decided to target this well-known herbal agent with fantastic safety profile to be formulated as a novel topical microemulgel. The clinical and therapeutic benefit of this novel topical formulation was evaluated on 34 patients with mild to moderate plaque psoriasis in a randomized, prospective intra-individual, right–left comparative, placebo-controlled, double-blind clinical trial. The Dermatology Life Quality Index (DLQI) Questionnaire and Psoriasis area & severity index (PASI) score as well as photos before and after treatment was used to evaluate the outcomes. The results show that the clinical and quality of life parameters in treated lesions in comparison with untreated lesions have improved (P<0.05). The reported side effects were also recorded and were trivial. Based on our findings, the proposed microemulgel may well be considered as an alternative in some patients and most likely as an add-on therapeutic option for many patients suffering with plaque psoriasis. PMID:26330875

  1. Topical Turmeric Microemulgel in the Management of Plaque Psoriasis; A Clinical Evaluation.

    PubMed

    Sarafian, Golnaz; Afshar, Minoo; Mansouri, Parvin; Asgarpanah, Jinous; Raoufinejad, Kosar; Rajabi, Mehdi

    2015-01-01

    Psoriasis is an autoimmune and recurrent chronic inflammatory skin disease. About 1-3% of the world wide populations are affected. The characteristic features are hyperprolifration of keratinocytes leading to redness, thickening and scaling of epidermis followed with itching and appearance of the lesions which in most cases bother the patients medically and psychologically. Psoriasis is symptomatically treated by the range of oral and topical medications, however, major side effects in some cases are associated with them. Based on several studies, Curcuma longa can inhibit several inflammatory enzymes mainly involved in the inflammatory process of Psoriasis. Therefore, we decided to target this well-known herbal agent with fantastic safety profile to be formulated as a novel topical microemulgel. The clinical and therapeutic benefit of this novel topical formulation was evaluated on 34 patients with mild to moderate plaque psoriasis in a randomized, prospective intra-individual, right-left comparative, placebo-controlled, double-blind clinical trial. The Dermatology Life Quality Index (DLQI) Questionnaire and Psoriasis area & severity index (PASI) score as well as photos before and after treatment was used to evaluate the outcomes. The results show that the clinical and quality of life parameters in treated lesions in comparison with untreated lesions have improved (P<0.05). The reported side effects were also recorded and were trivial. Based on our findings, the proposed microemulgel may well be considered as an alternative in some patients and most likely as an add-on therapeutic option for many patients suffering with plaque psoriasis. PMID:26330875

  2. Tyranny of the randomised clinical trial.

    PubMed

    Rosenbek, John C

    2016-06-01

    Researchers and clinicians often disagree about what it means to provide the best possible care. This paper's purpose is to propose ways of resolving the disagreements. The first is to have both groups re-examine the three equal components of evidence-based practice, a re-examination that begins with rejection of the randomised clinical trial's tyranny. The second is for researchers to design rehabilitation research based on a biopsychosocial rather than a biomedical model. The third is for both groups to redefine translational research so that it means both translation from the laboratory to the clinic and from the clinic to the laboratory. The fourth is to advocate for a science of dissemination that is as robust as rehabilitation's present science of discovery. Most examples are drawn from the literature on acquired neurologic speech and language disorders. PMID:27124262

  3. Self-reported adherence with the use of a device in a clinical trial as validated by electronic monitors: the VIBES study

    PubMed Central

    2012-01-01

    Background Adherences to treatments that require a behavioral action often rely on self-reported recall, yet it is vital to determine whether real time self reporting of adherence using a simple logbook accurately captures adherence. The purpose of this study was to determine whether real time self-reported adherence is an accurate measurement of device usage during a clinical trial by comparing it to electronic recording. Methods Using data collected from older adult men and women (N=135, mean age 82.3 yrs; range 66 to 98 yrs) participating in a clinical trial evaluating a vibrating platform for the treatment of osteoporosis, daily adherence to platform treatment was monitored using both self-reported written logs and electronically recorded radio-frequency identification card usage, enabling a direct comparison of the two methods over one year. Agreement between methods was also evaluated after stratification by age, gender, time in study, and cognition status. Results The two methods were in high agreement (overall intraclass correlation coefficient = 0.96). The agreement between the two methods did not differ between age groups, sex, time in study and cognitive function. Conclusions Using a log book to report adherence to a daily intervention requiring a behavioral action in older adults is an accurate and simple approach to use in clinical trials, as evidenced by the high degree of concordance with an electronic monitor. Trial registration Clinicaltrials.gov NCT00396994 PMID:23150931

  4. Good Clinical Practice Guidance and Pragmatic Clinical Trials: Balancing the Best of Both Worlds.

    PubMed

    Mentz, Robert J; Hernandez, Adrian F; Berdan, Lisa G; Rorick, Tyrus; O'Brien, Emily C; Ibarra, Jenny C; Curtis, Lesley H; Peterson, Eric D

    2016-03-01

    Randomized, clinical trials are commonly regarded as the highest level of evidence to support clinical decisions. Good Clinical Practice guidelines have been constructed to provide an ethical and scientific quality standard for trials that involve human subjects in a manner aligned with the Declaration of Helsinki. Originally designed to provide a unified standard of trial data to support submission to regulatory authorities, the principles may also be applied to other studies of human subjects. Although the application of Good Clinical Practice principles generally led to improvements in the quality and consistency of trial operations, these principles have also contributed to increasing trial complexity and costs. Alternatively, the growing availability of electronic health record data has facilitated the possibility for streamlined pragmatic clinical trials. The central tenets of Good Clinical Practice and pragmatic clinical trials represent potential tensions in trial design (stringent quality and highly efficient operations). In the present article, we highlight potential areas of discordance between Good Clinical Practice guidelines and the principles of pragmatic clinical trials and suggest strategies to streamline study conduct in an ethical manner to optimally perform clinical trials in the electronic age. PMID:26927005

  5. The duty to disclose adverse clinical trial results.

    PubMed

    Liao, S Matthew; Sheehan, Mark; Clarke, Steve

    2009-08-01

    Participants in some clinical trials are at risk of being harmed and sometimes are seriously harmed as a result of not being provided with available, relevant risk information. We argue that this situation is unacceptable and that there is a moral duty to disclose all adverse clinical trial results to participants in clinical trials. This duty is grounded in the human right not to be placed at risk of harm without informed consent. We consider objections to disclosure grounded in considerations of commercial interest, and we argue that these concerns are insufficient to override the moral duty to disclose adverse clinical trial results. However, we also develop a proposal that enables commercial interests to be protected, while promoting the duty to disclose adverse clinical trial results. PMID:19998154

  6. Marketing and clinical trials: a case study

    PubMed Central

    Francis, David; Roberts, Ian; Elbourne, Diana R; Shakur, Haleema; Knight, Rosemary C; Garcia, Jo; Snowdon, Claire; Entwistle, Vikki A; McDonald, Alison M; Grant, Adrian M; Campbell, Marion K

    2007-01-01

    Background Publicly funded clinical trials require a substantial commitment of time and money. To ensure that sufficient numbers of patients are recruited it is essential that they address important questions in a rigorous manner and are managed well, adopting effective marketing strategies. Methods Using methods of analysis drawn from management studies, this paper presents a structured assessment framework or reference model, derived from a case analysis of the MRC's CRASH trial, of 12 factors that may affect the success of the marketing and sales activities associated with clinical trials. Results The case study demonstrates that trials need various categories of people to buy in – hence, to be successful, trialists must embrace marketing strategies to some extent. Conclusion The performance of future clinical trials could be enhanced if trialists routinely considered these factors. PMID:18028537

  7. Use of mifepristone to treat endometriosis: a review of clinical trials and trial-like studies conducted in China.

    PubMed

    Guo, Sun-Wei; Liu, Maohua; Shen, Fanghua; Liu, Xishi

    2011-01-01

    China was the first country in the world that approved mifepristone (RU-486) for abortion. A total of 6 years after the report published in the Western world indicated that mifepristone may also be effective in treating endometriosis, the first paper on the same topic was published in China in 1997. Since then, over 160 studies on this topic have been published in China. We retrieved 104 papers on clinical trials and trial-like studies conducted in China evaluating the use of mifepristone to treat endometriosis that were published in the last 11 years. We found that the quality of these studies is well below an acceptable level, making it difficult to judge whether mifepristone is truly efficacious. There are intriguing signs that these studies, as a whole, have serious anomalies. The areas that are glaringly deficient are informed consent, choice of outcome measures, the evaluation of outcome measures, data analysis and randomization. The uniformly low quality is disquieting, given the large quantity of studies, the enormous amount of resource and energy put into these studies and, above all, the weighty issue of treatment efficacy that concerns each and every patient with endometriosis. Equally disquieting are the low-quality repetition, the absence of a critical, systematic review on the subject, the lack of suggestions for multicenter clinical trials and the seemingly unnecessary duplication of clinical trials without due informed consent. In view of this, it may be time to institute changes in attitude and practice, and to change education and training programs in the methodology of clinical trials in obstetrics and gynecology research in China. PMID:21175391

  8. Trials on Trial: The Push for Clinical Data Disclosure

    PubMed Central

    CARROLL, JOHN

    2004-01-01

    Momentum is growing for disclosure of all clinical trial data, not just information that supports a trial sponsor’s product. The importance to patients and P&T committees is clear: Ideally, they would use this information to make informed decisions. The result of this activity, though, could be a cacophony of competing registries with the potential to muddy the very waters they’re designed to clear up. PMID:23390393

  9. Statistical challenges for central monitoring in clinical trials: a review.

    PubMed

    Oba, Koji

    2016-02-01

    Recently, the complexity and costs of clinical trials have increased dramatically, especially in the area of new drug development. Risk-based monitoring (RBM) has been attracting attention as an efficient and effective trial monitoring approach, which can be applied irrespectively of the trial sponsor, i.e., academic institution or pharmaceutical company. In the RBM paradigm, it is expected that a statistical approach to central monitoring can help improve the effectiveness of on-site monitoring by prioritizing and guiding site visits according to central statistical data checks, as evidenced by examples of actual trial datasets. In this review, several statistical methods for central monitoring are presented. It is important to share knowledge about the role and performance capabilities of statistical methodology among clinical trial team members (i.e., sponsors, investigators, data managers, monitors, and biostatisticians) in order to adopt central statistical monitoring for assessing data quality in the actual clinical trial. PMID:26499195

  10. Topical Tacrolimus versus Hydrocortisone on Atopic Dermatitis in Paediatric Patients: A Randomized Controlled Trial.

    PubMed

    Rahman, M F; Nandi, A K; Kabir, S; Kamal, M; Basher, M S; Banu, L A

    2015-07-01

    Atopic dermatitis (AD) is a chronic, inflammatory skin disease in early childhood. Atopic dermatitis is familial disease, often coexists with other atopic diseases with multiple risk factors associated with atopic eczema. The disease is more frequent in urban areas compared with rural areas. Changes in nutrition and a decrease in infant breast-feeding and respiratory allergies are contributory factors for the condition. A Randomized Controlled Trial (RCT) was carried to compare the efficacy and safety of Tacrolimus ointment with a topical corticosteroid reference therapy. A total 60 patients aged between 2 to 10 years, having atopic dermatitis for at least one year and comply Hanifin-Rajka criteria were selected using random number table and allocated into study and control groups through randomization. Study group was treated with topical Tacrolimus 0.03% twice daily for three weeks, while the control group was treated with 1% Hydrocortisone acetate for the same period. Both groups had a washed out phase for 2 weeks with a follow up period of 6 weeks. Eczema Area and Severity lndex (EASI) was assessed at baseline and three weeks after treatment. Efficacy was evaluated at each visit by six clinical signs of atopic dermatitis through measurement of the affected surface area and the EASI score in each of four body regions. Before intervention, in study group mean EASI score was 11.29 with a SD of 2.14, while in control group it was 11.05 with a SD of 2.46. Difference was statistically insignificant (p>0.05). At the end of the treatment, in study group mean EASI score was 4.86 with a SD of 1.01, while in control group it was 7.97 with a SD of 1.80. Statistically high significant difference was observed between EASI scores of two groups before and after the treatment (p<0.001). After getting treatment with Tacrolimus, median reduction of EASI score was 56.07 in study group, while getting treatment with Hydrocortisone, median reduction of EASI score was 27

  11. A guide to clinical trials for cancer

    MedlinePlus

    There are strict federal rules in place to protect your safety during a clinical trial. Safety guidelines (protocols) are agreed to before the study begins. These guidelines are reviewed by health ...

  12. How transparent are migraine clinical trials? Repository of Registered Migraine Trials (RReMiT).

    PubMed

    Dufka, Faustine L; Dworkin, Robert H; Rowbotham, Michael C

    2014-10-01

    Transparency in research requires public access to unbiased information prior to trial initiation and openly available results upon study completion. The Repository of Registered Migraine Trials is a global snapshot of registered migraine clinical trials and scorecard of results availability via the peer-reviewed literature, registry databases, and gray literature. The 295 unique clinical trials identified employed 447 investigational agents, with 30% of 154 acute migraine trials and 11% of 141 migraine prophylaxis trials testing combinations of agents. The most frequently studied categories in acute migraine trials were triptans, nonsteroidal anti-inflammatory drugs, antiemetics, calcitonin gene-related peptide antagonists, and acetaminophen. Migraine prophylaxis trials frequently studied anticonvulsants, β-blockers, complementary/alternative therapies, antidepressants, and botulinum toxin. Overall, 237 trials were eligible for a results search. Of 163 trials completed at least 12 months earlier, 57% had peer-reviewed literature results, and registries/gray literature added another 13%. Using logistic regression analysis, studies with a sample size below the median of 141 subjects were significantly less likely to have results, but the dominant factor associated with availability of results was time since study completion. In unadjusted models, trials registered on ClinicalTrials.gov and trials with industry primary sponsorship were significantly more likely to have results. Recently completed trials rarely have publicly available results; 2 years after completion, the peer-reviewed literature contains results for fewer than 60% of completed migraine trials. To avoid bias, evidence-based therapy algorithms should consider factors affecting results availability. As negative trials are less likely to be published, special caution should be exercised before recommending a therapy with a high proportion of missing trial results. PMID:25194013

  13. Gender Analysis of Moxifloxacin Clinical Trials

    PubMed Central

    Ruiz-Cantero, Ma Teresa; Pardo, Ma Angeles

    2014-01-01

    Abstract Purpose: To determine the inclusion of women and the sex-stratification of results in moxifloxacin Clinical Trials (CTs), and to establish whether these CTs considered issues that specifically affect women, such as pregnancy and use of hormonal therapies. Previous publications about women's inclusion in CTs have not specifically studied therapeutic drugs. Although this type of drug is taken by men and women at a similar rate, adverse effects occur more frequently in the latter. Methods: We reviewed 158 published moxifloxacin trials on humans, retrieved from MedLine and the Cochrane Library (1998–2010), to determine whether they complied with the gender recommendations published by U.S. Food and Drug Administration Guideline. Results: Of a total of 80,417 subjects included in the moxifloxacin CTs, only 33.7% were women in phase I, in contrast to phase II, where women accounted for 45%, phase III, where they represented 38.3% and phase IV, where 51.3% were women. About 40.9% (n=52) of trials were stratified by sex and 15.3% (n=13) and 9% (n=7) provided data by sex on efficacy and adverse effects, respectively. We found little information about the influence of issues that specifically affect women. Only 3 of the 59 journals that published the moxifloxacin CTs stated that authors should stratify their results by sex. Conclusions: Women are under-represented in the published moxifloxacin trials, and this trend is more marked in phase I, as they comprise a higher proportion in the other phases. Data by sex on efficacy and adverse effects are scarce in moxifloxacin trials. These facts, together with the lack of data on women-specific issues, suggest that the therapeutic drug moxifloxacin is only a partially evidence-based medicine. PMID:24180298

  14. New generation of breast cancer clinical trials implementing molecular profiling

    PubMed Central

    Zardavas, Dimitrios; Piccart-Gebhart, Martine

    2016-01-01

    The implementation of molecular profiling technologies in oncology deepens our knowledge for the molecular landscapes of cancer diagnoses, identifying aberrations that could be linked with specific therapeutic vulnerabilities. In particular, there is an increasing list of molecularly targeted anticancer agents undergoing clinical development that aim to block specific molecular aberrations. This leads to a paradigm shift, with an increasing list of specific aberrations dictating the treatment of patients with cancer. This paradigm shift impacts the field of clinical trials, since the classical approach of having clinico-pathological disease characteristics dictating the patients' enrolment in oncology trials shifts towards the implementation of molecular profiling as pre-screening step. In order to facilitate the successful clinical development of these new anticancer drugs within specific molecular niches of cancer diagnoses, there have been developed new, innovative trial designs that could be classified as follows: i) longitudinal cohort studies that implement (or not) "nested" downstream trials, 2) studies that assess the clinical utility of molecular profiling, 3) "master" protocol trials, iv) "basket" trials, v) trials following an adaptive design. In the present article, we review these innovative study designs, providing representative examples from each category and we discuss the challenges that still need to be addressed in this era of new generation oncology trials implementing molecular profiling. Emphasis is put on the field of breast cancer clinical trials. PMID:27458530

  15. Exploring the ethical and regulatory issues in pragmatic clinical trials.

    PubMed

    Califf, Robert M; Sugarman, Jeremy

    2015-10-01

    The need for high-quality evidence to support decision making about health and health care by patients, physicians, care providers, and policy-makers is well documented. However, serious shortcomings in evidence persist. Pragmatic clinical trials that use novel techniques including emerging information and communication technologies to explore important research questions rapidly and at a fraction of the cost incurred by more "traditional" research methods promise to help close this gap. Nevertheless, while pragmatic clinical trials can bridge clinical practice and research, they may also raise difficult ethical and regulatory challenges. In this article, the authors briefly survey the current state of evidence that is available to inform clinical care and other health-related decisions and discuss the potential for pragmatic clinical trials to improve this state of affairs. They then propose a new working definition for pragmatic research that centers upon fitness for informing decisions about health and health care. Finally, they introduce a project, jointly undertaken by the National Institutes of Health Health Care Systems Research Collaboratory and the National Patient-Centered Clinical Research Network (PCORnet), which addresses 11 key aspects of current systems for regulatory and ethical oversight of clinical research that pose challenges to conducting pragmatic clinical trials. In the series of articles commissioned on this topic published in this issue of Clinical Trials, each of these aspects is addressed in a dedicated article, with a special focus on the interplay between ethical and regulatory considerations and pragmatic clinical research aimed at informing "real-world" choices about health and health care. PMID:26374676

  16. From Laboratory Research to a Clinical Trial

    PubMed Central

    Keevil, C. William; Salgado, Cassandra D.; Schmidt, Michael G.

    2015-01-01

    Objective: This is a translational science article that discusses copper alloys as antimicrobial environmental surfaces. Bacteria die when they come in contact with copper alloys in laboratory tests. Components made of copper alloys were also found to be efficacious in a clinical trial. Background: There are indications that bacteria found on frequently touched environmental surfaces play a role in infection transmission. Methods: In laboratory testing, copper alloy samples were inoculated with bacteria. In clinical trials, the amount of live bacteria on the surfaces of hospital components made of copper alloys, as well as those made from standard materials, was measured. Finally, infection rates were tracked in the hospital rooms with the copper components and compared to those found in the rooms containing the standard components. Results: Greater than a 99.9% reduction in live bacteria was realized in laboratory tests. In the clinical trials, an 83% reduction in bacteria was seen on the copper alloy components, when compared to the surfaces made from standard materials in the control rooms. Finally, the infection rates were found to be reduced by 58% in patient rooms with components made of copper, when compared to patients' rooms with components made of standard materials. Conclusions: Bacteria die on copper alloy surfaces in both the laboratory and the hospital rooms. Infection rates were lowered in those hospital rooms containing copper components. Thus, based on the presented information, the placement of copper alloy components, in the built environment, may have the potential to reduce not only hospital-acquired infections but also patient treatment costs. PMID:26163568

  17. Learning from hackers: open-source clinical trials.

    PubMed

    Dunn, Adam G; Day, Richard O; Mandl, Kenneth D; Coiera, Enrico

    2012-05-01

    Open sharing of clinical trial data has been proposed as a way to address the gap between the production of clinical evidence and the decision-making of physicians. A similar gap was addressed in the software industry by their open-source software movement. Here, we examine how the social and technical principles of the movement can guide the growth of an open-source clinical trial community. PMID:22553248

  18. Paying clinicians to join clinical trials: a review of guidelines and interview study of trialists

    PubMed Central

    Raftery, James; Kerr, Christine; Hawker, Sheila; Powell, John

    2009-01-01

    Background The motivations of clinicians to participate in clinical trials have been little studied. This project explored the potential role of payment for participation in publicly funded clinical trials in the UK. The aims were to review relevant guidelines and to collate and analyse views of clinical trialists on the role of payments and other factors that motivated clinicians to join clinical trials. Methods Review of guidelines governing payments to clinicians for recruitment to trials. Semi-structured interviews with a range of NHS clinical trial leaders, analysed using qualititative methods. Results While UK guidelines had little to say specifically on payments linked to recruitment, all payments have become highly regulated and increasingly transparent. Interview participants believed that expenses arising from research should be covered. Payments in excess of expenses were seen as likely to increase participation but with the risk of reducing quality. Motivations such as interest in the topic, the scope for patients to benefit and intellectual curiosity were considered more important. Barriers to involvement included bureaucracy and lack of time. Discussion Limited scope exists for paying clinicians over-and-above the cost of their time to be involved in research. Most trialists favour full payment of all expenses related to research. Conclusion Payment of clinicians beyond expenses is perceived to be a less important motivating factor than researching important, salient questions, and facilitating research by reducing bureaucracy and delay. PMID:19272166

  19. Integrated safety in tocilizumab clinical trials

    PubMed Central

    2011-01-01

    Introduction The efficacy and safety of tocilizumab in patients with rheumatoid arthritis have been evaluated in a comprehensive phase 3 program. Patients from these randomized trials could receive tocilizumab treatment in open-label extension trials. Here, the long-term safety profile of tocilizumab, using pooled data from all of these trials, is reported. Methods Cumulative safety data (as of February 6, 2009) from five core phase 3 trials, two ongoing extension trials, and one clinical pharmacology study were analyzed. Two patient populations were evaluated: an all-control population (n = 4,199), which included all patients randomly assigned in the placebo-controlled portions of the five core studies, and an all-exposed population (n = 4,009), which included patients from any of the eight studies who received at least one dose of tocilizumab. Results Total exposure to tocilizumab was 8,580 patient years (PY), and total duration of observation was 9,414 PY. Overall adverse event (AE) and serious AE (SAE) rates were 278.2/100 PY and 14.4/100 PY, respectively. These events included serious infections (4.7/100 PY), opportunistic infections (0.23/100 PY), gastrointestinal perforations (0.28/100 PY), malignancy (1.1/100 PY), myocardial infarction (0.25/100 PY), and stroke (0.19/100 PY). The rates of SAEs and serious infections were stable over time; no increase with prolonged exposure was noted. Conclusions The longer-term safety profile of tocilizumab (mean treatment duration, 2.4 years) is consistent with that observed in the phase 3 studies (duration up to 1 year). PMID:21884601

  20. Why do – or don’t – patients with urinary tract infection participate in a clinical trial? A qualitative study in German family medicine

    PubMed Central

    Bleidorn, Jutta; Bucak, Sermin; Gágyor, Ildikó; Hummers-Pradier, Eva; Dierks, Marie-Luise

    2015-01-01

    Background: Insufficient patient recruitment can impair the conduct of clinical trials substantially, not least because a significant number of eligible patients decline trial participation. Though barriers and motivational factors have been worked out for patients with cancer or chronic diseases, little is known about primary care patients’ perceptions towards trial participation when visiting their family practitioner (FP) with acute uncomplicated conditions. This study aims to assess primary care patients’ motivation and barriers to participate in trials, and to identify factors that optimize patient recruitment in future trials. Methods: This study was embedded in a drug trial comparing two treatment strategies for women with uncomplicated urinary tract infection in primary care. Semi-structured telephone interviews both with trial participants and decliners were conducted. The interview guideline focused on patients’ personal motivational or hampering factors. Further topics were study theme, FPs’ role, randomization, trial procedures, and potential motivational factors or barriers presumed to be relevant for other patients. Transcripts were analyzed by summarizing content analysis. Results: 20 interviews with trial participants and 5 interviews with trial decliners were conducted. Results show various reasons for trial participation from three categories: personal aspects, trial related aspects and patient-physician-relationship. A relevant trial topic and perceived personal benefit promotes participation as well as the wish to support research in general. Additionally, a maximum of safety concerning symptom relief reassures patients significantly. Trust in the FP plays also an important role in the decision process. Trial decliners show strong individual treatment preferences, which, together with individual reasons, lead to trial refusals. Conclusions: To optimize recruitment conditions for further clinical trials on acute and common conditions in

  1. A double-blind, placebo-controlled trial of a topical treatment for chemotherapy-induced peripheral neuropathy: NCCTG trial N06CA

    PubMed Central

    Wos, Edward J.; Qin, Rui; Mattar, Bassam I.; Green, Nathan Benjamin; Lanier, Keith S.; Bearden, James Dewitt; Kugler, John W.; Hoff, Kay L.; Reddy, Pavan S.; Rowland, Kendrith M.; Riepl, Mike; Christensen, Bradley; Loprinzi, Charles L.

    2012-01-01

    Background Chemotherapy-induced peripheral neuropathy (CIPN) is a troublesome chronic symptom that has no proven pharmacologic treatment. The purpose of this double-blind randomized placebo-controlled trial was to evaluate a novel compounded topical gel for this problem. Methods Patients with CIPN were randomized to baclofen 10 mg, amitriptyline HCL 40 mg, and ketamine 20 mg in a pluronic lecithin organogel (BAK-PLO) versus placebo (PLO) to determine its effect on numbness, tingling, pain, and function. The primary endpoint was the baseline-adjusted sensory subscale of the EORTC QLQ-CIPN20, at 4 weeks. Results Data in 208 patients reveal a trend for improvement that is greater in the BAK-PLO arm over placebo in both the sensory (p=0.053) and motor subscales (p=0.021). The greatest improvements were related to the symptoms of tingling, cramping, and shooting/burning pain in the hands as well as difficulty in holding a pen. There were no undesirable toxicities associated with the BAK-PLO and no evidence of systemic toxicity. Conclusion Topical treatment with BAK-PLO appears to somewhat improve symptoms of CIPN. This topical gel was well tolerated, without evident systemic toxicity. Further research is needed with increased doses to better clarify the clinical role of this treatment in CIPN. PMID:20496177

  2. Interview "Problems" as Topics for Analysis

    ERIC Educational Resources Information Center

    Roulston, Kathryn

    2011-01-01

    In this article the author argues that interactional difficulties and questioning practices identified in the methodological literature on qualitative interviewing as "problems" provide topics of analysis. Methodological examinations of interview data drawing on conversation analysis also explicate how interview "problems" may be conceptualized in…

  3. Key Concepts of Clinical Trials: A Narrative Review

    PubMed Central

    Umscheid, Craig A.; Margolis, David J.; Grossman, Craig E.

    2012-01-01

    The recent focus of federal funding on comparative effectiveness research underscores the importance of clinical trials in the practice of evidence-based medicine and health care reform. The impact of clinical trials not only extends to the individual patient by establishing a broader selection of effective therapies, but also to society as a whole by enhancing the value of health care provided. However, clinical trials also have the potential to pose unknown risks to their participants, and biased knowledge extracted from flawed clinical trials may lead to the inadvertent harm of patients. Although conducting a well-designed clinical trial may appear straightforward, it is founded on rigorous methodology and oversight governed by key ethical principles. In this review, we provide an overview of the ethical foundations of trial design, trial oversight, and the process of obtaining approval of a therapeutic, from its pre-clinical phase to post-marketing surveillance. This narrative review is based on a course in clinical trials developed by one of the authors (DJM), and is supplemented by a PubMed search predating January 2011 using the keywords “randomized controlled trial,” “patient/clinical research,” “ethics,” “phase IV,” “data and safety monitoring board,” and “surrogate endpoint.” With an understanding of the key principles in designing and implementing clinical trials, health care providers can partner with the pharmaceutical industry and regulatory bodies to effectively compare medical therapies and thereby meet one of the essential goals of health care reform. PMID:21904102

  4. Orienting to Topic in Clinical Discourse Elicitation of Everyday Conversation

    ERIC Educational Resources Information Center

    Fond, Marissa Joanne

    2013-01-01

    Talking topically, as it is understood intuitively and evoked metadiscursively, requires constructing an intersubjective orientation to talk that must be continually renewed. Analysis of interactants' ability to orient to topic emergence provides evidence of what is achieved in interaction, as well as why conversational coordination can lapse…

  5. Gene therapy clinical trials worldwide 1989-2004-an overview.

    PubMed

    Edelstein, Michael L; Abedi, Mohammad R; Wixon, Jo; Edelstein, Richard M

    2004-06-01

    In 1989, Rosenberg et al. performed the first human gene therapy trial when they used a retrovirus to introduce the gene coding for resistance to neomycin into human tumor-infiltrating lymphocytes before infusing them into five patients with advanced melanoma. This study demonstrated the feasibility of using retroviral gene transduction in humans and set the stage for further studies. Since then, over 900 clinical trials have been completed, are ongoing or have been approved worldwide. These trials have been designed to establish feasibility and safety, to demonstrate the reality of expression of therapeutic protein(s) in vivo by the genes transferred and, in some cases, to show therapeutic benefit. There is no single source of information that presents an overview of all the clinical trials undertaken worldwide. In 1997 we set up a database to bring all the information on clinical trials together as comprehensively and as globally as possible. The data were compiled and are regularly updated from official agency sources, the published literature, presentations at conferences and from information kindly provided by investigators or trial sponsors themselves. As of January 31, 2004, we have identified 918 trials in 24 countries. The USA accounts for two-thirds of these trials. Cancer is by far the most common disease indication, followed by inherited monogenic diseases, and cardiovascular diseases. Viral vectors have been the most frequently used vehicles for transferring genes into human cells, with retroviruses and adenoviruses representing the vast majority. Plasmid (naked) DNA and other non-viral vectors have been used in one-quarter of the trials. Over 100 distinct genes have been transferred. This article aims to provide a descriptive overview of the clinical trials that, to the best of our knowledge, have been or are being performed worldwide. Details of the data presented, including an interactive, searchable database that currently holds information on 918

  6. Are clinical trials really the answer?

    PubMed

    Block, G

    1995-12-01

    It has been asserted that clinical trials hold the answer to questions about the role of nutrients in preventing chronic diseases. This is not the case. Clinical trials give us rigorous answers to restricted questions. Rarely can more than one or two substances be tested, usually at a single dose. Subjects usually have to be persons with precancerous conditions or an extremely high risk of the disease in question. Rarely can any diseases other than the most common ones be studied. Most important, clinical trials test the efficacy of an agent that is administered for a limited time, beginning fairly late in life. Few trials will tell us anything about whether dietary amounts of nutrients might contribute to prevention of long-term chronic diseases. They also tell us nothing about whether agents at high doses might reduce disease risk if taken throughout the lifetime. Furthermore, they tell us nothing about other antioxidants, other combinations, or other doses. Clinical trials were developed for therapeutic situations to determine which treatment was better for curing a specific disease. However, the questions about prevention that are of interest may involve persons with no unusual risk of disease, lifetimes of exposure, enormously complex interactions among nutrients, and the effects of these nutrients on hundreds of often uncommon disease conditions. Clinical trials simply cannot answer these questions. Only a solid examination of the laboratory and epidemiologic evidence can approximate the answers to most of the questions of interest. PMID:7495253

  7. Topical ascorbic acid on photoaged skin. Clinical, topographical and ultrastructural evaluation: double-blind study vs. placebo.

    PubMed

    Humbert, Philippe G; Haftek, Marek; Creidi, Pierre; Lapière, Charles; Nusgens, Betty; Richard, Alain; Schmitt, Daniel; Rougier, André; Zahouani, Hassan

    2003-06-01

    Vitamin C is known for its antioxidant potential and activity in the collagen biosynthetic pathway. Photoprotective properties of topically applied vitamin C have also been demonstrated, placing this molecule as a potential candidate for use in the prevention and treatment of skin ageing. A topically applied cream containing 5% vitamin C and its excipient were tested on healthy female volunteers presenting with photoaged skin on their low-neck and arms in view to evaluate efficacy and safety of such treatment. A double-blind, randomized trial was performed over a 6-month period, comparing the action of the vitamin C cream vs. excipient on photoaged skin. Clinical assessments included evaluation at the beginning and after 3 and 6 months of daily treatment. They were performed by the investigator and compared with the volunteer self assessment. Skin relief parameters were determined on silicone rubber replicas performed at the same time-points. Cutaneous biopsies were obtained at the end of the trial and investigated using immunohistochemistry and electron microscopy. Clinical examination by a dermatologist as well as self-assessment by the volunteers disclosed a significant improvement, in terms of the 'global score', on the vitamin C-treated side compared with the control. A highly significant increase in the density of skin microrelief and a decrease of the deep furrows were demonstrated. Ultrastructural evidence of the elastic tissue repair was also obtained and well corroborated the favorable results of the clinical and skin surface examinations. Topical application of 5% vitamin C cream was an effective and well-tolerated treatment. It led to a clinically apparent improvement of the photodamaged skin and induced modifications of skin relief and ultrastructure, suggesting a positive influence of topical vitamin C on parameters characteristic for sun-induced skin ageing. PMID:12823436

  8. 78 FR 39736 - Draft Guidance for Industry: Considerations for the Design of Early-Phase Clinical Trials of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-07-02

    ... clinical trial design, including product characteristics, manufacturing considerations and preclinical... document provides recommendations with respect to these products as to clinical trial design, including... of Early-Phase Clinical Trials of Cellular and Gene Therapy Products; Availability AGENCY: Food...

  9. Project Management of Randomized Clinical Trials: A Narrative Review

    PubMed Central

    Goodarzynejad, Hamidreza; Babamahmoodi, Abdolreza

    2015-01-01

    Context: A well-structured protocol for a clinical trial may be able to answer clinical questions, but it cannot be deemed enough to ensure success in the face of incompetent management of time as well as human and economic resources. To address this problem, in this article, we present our literature review on evidence as to how a good knowledge of proper management among researchers can enhance the likelihood of the success of clinical trial projects. Evidence Acquisition: Using multiple search strategies, we conducted a literature review on published studies in the English language from 2002 to 2012 by searching the Cochrane Database of Systematic Reviews, MEDLINE, Google Scholar, and EMBASE. Results: Our review suggests that a successful trial requires a work plan or work scope as well as a timeline. The trial manager should subsequently manage the study in accordance with the plan and the timeline. Many research units have called for a clinical project manager with scientific background and regulatory skills to effect coordination among various aspects of a clinical trial. Conclusions: Project management may benefit both the managerial and scientific aspects of medical projects and reduce fund waste. However, little has been written to date on project management in the context of clinical research. The suggestions represent the views of the individual authors. To provide a high level of evidence in this regard, we recommend that a randomized controlled trial be performed to compare trial projects progressed with and without the use of project management. PMID:26430517

  10. Photodynamic therapy as adjunct to non-surgical periodontal treatment in patients on periodontal maintenance: a randomized controlled clinical trial.

    PubMed

    Chondros, Panos; Nikolidakis, Dimitris; Christodoulides, Nicos; Rössler, Ralf; Gutknecht, Norbert; Sculean, Anton

    2009-09-01

    Recent preclinical and clinical data have suggested the potential benefit of photodynamic therapy (PDT) in the treatment of periodontitis. However, currently, there are very limited data from controlled clinical trials evaluating the effect of PDT in the treatment of periodontitis. The aim of the present study was to evaluate the clinical and microbiological effects of the adjunctive use of PDT in non-surgical periodontal treatment in patients receiving supportive periodontal therapy. Twenty-four patients receiving regularly supportive periodontal therapy were randomly treated with either subgingival scaling and root planing followed by a single episode of PDT (test) or subgingival scaling and root planing alone (control). The following parameters were evaluated at baseline and at 3 months and 6 months after therapy: full mouth plaque score (FMPS), full mouth bleeding score (FMBS), bleeding on probing (BOP) at experimental sites, probing pocket depth (PPD), gingival recession (REC), and clinical attachment level (CAL). Primary outcome variables were changes in PPD and CAL. Microbiological evaluation of Aggregatibacter actinomycetemcomitans (A.a.), Porphyromonas gingivalis (P.g.), Prevotella intermedia (P.i.), Tannerella forsythensis (T.f.), Treponema denticola (T.d.), Peptostreptococcus micros (P.m.), Fusobacterium nucleatum (F.n.), Campylobacter rectus (C.r.), Eubacterium nodatum (E.n.), Eikenella corrodens (E.c.), and Capnocytophaga species (C.s.) was also performed at baseline and at 3 months and 6 months after therapy, using a commercially available polymerase chain reaction test. No differences in any of the investigated parameters were observed at baseline between the two groups. At 3 months and 6 months after treatment, there were no statistically significant differences between the groups in terms of PPD, CAL and FMPS. At 3 months and 6 months, a statistically significantly higher improvement of BOP was found in the test group. At 3 months after therapy

  11. Future Clinical Trials in DIPG: Bringing Epigenetics to the Clinic

    PubMed Central

    Morales La Madrid, Andres; Hashizume, Rintaro; Kieran, Mark W.

    2015-01-01

    In spite of major recent advances in diffuse intrinsic pontine glioma (DIPG) molecular characterization, this body of knowledge has not yet translated into better treatments. To date, more than 250 clinical trials evaluating radiotherapy along with conventional cytotoxic chemotherapy as well as newer biologic agents have failed to improve the dismal outcome when compared to palliative radiation alone. The biology of DIPG remained unknown until recently when the neurosurgical expertise along with the recognition by the scientific and clinical community of the importance of tissue sampling at diagnosis; ideally, in the context of a clinical trial and by trained neurosurgical teams to maximize patient safety. These pre-treatment tumor samples, and others coming from tissue obtained post-mortem, have yielded new insights into DIPG molecular pathogenesis. We now know that DIPG comprises a heterogeneous disease with variable molecular phenotypes, different from adult high-grade glioma, other non-pontine pediatric high-grade gliomas, and even between pontine gliomas. The discovery of histone H3.3 or H3.1 mutations has been an important step forward in understanding tumor formation, maintenance, and progression. Pharmacologic reversal of DIPG histone demethylation therefore offers an important potential intervention strategy for the treatment of DIPG. To date, clinical trials of newly diagnosed or progressive DIPG with epigenetic (histone) modifiers have been unsuccessful. Whether this failure represents limited activity of the agents used, their CNS penetration, redundant pathways within the tumor, or the possibility that histone mutations are necessary only to initiate DIPGs but not maintain their growth, suggest that a great deal still needs to be elucidated in both the underlying biology of these pathways and the drugs designed to target them. In this review, we will discuss the role of both epigenetic and genetic mutations within DIPG and the development of treatment

  12. Maximizing Effectiveness Trials in PTSD and SUD Through Secondary Analysis: Benefits and Limitations Using the National Institute on Drug Abuse Clinical Trials Network "Women and Trauma" Study as a Case Example.

    PubMed

    Hien, Denise A; Campbell, Aimee N C; Ruglass, Lesia M; Saavedra, Lissette; Mathews, Abigail G; Kiriakos, Grace; Morgan-Lopez, Antonio

    2015-09-01

    Recent federal legislation and a renewed focus on integrative care models underscore the need for economical, effective, and science-based behavioral health care treatment. As such, maximizing the impact and reach of treatment research is of great concern. Behavioral health issues, including the frequent co-occurrence of substance use disorders (SUD) and posttraumatic stress disorder (PTSD), are often complex, with a myriad of factors contributing to the success of interventions. Although treatment guides for comorbid SUD/PTSD exist, most patients continue to suffer symptoms following the prescribed treatment course. Further, the study of efficacious treatments has been hampered by methodological challenges (e.g., overreliance on "superiority" designs (i.e., designs structured to test whether or not one treatment statistically surpasses another in terms of effect sizes) and short term interventions). Secondary analyses of randomized controlled clinical trials offer potential benefits to enhance understanding of findings and increase the personalization of treatment. This paper offers a description of the limits of randomized controlled trials as related to SUD/PTSD populations, highlights the benefits and potential pitfalls of secondary analytic techniques, and uses a case example of one of the largest effectiveness trials of behavioral treatment for co-occurring SUD/PTSD conducted within the National Drug Abuse Treatment Clinical Trials Network (NIDA CTN) and producing 19 publications. The paper concludes with implications of this secondary analytic approach to improve addiction researchers' ability to identify best practices for community-based treatment of these disorders. Innovative methods are needed to maximize the benefits of clinical studies and better support SUD/PTSD treatment options for both specialty and non-specialty healthcare settings. Moving forward, planning for and description of secondary analyses in randomized trials should be given equal

  13. Statistical properties of randomization in clinical trials.

    PubMed

    Lachin, J M

    1988-12-01

    This is the first of five articles on the properties of different randomization procedures used in clinical trials. This paper presents definitions and discussions of the statistical properties of randomization procedures as they relate to both the design of a clinical trial and the statistical analysis of trial results. The subsequent papers consider, respectively, the properties of simple (complete), permuted-block (i.e., blocked), and urn (adaptive biased-coin) randomization. The properties described herein are the probabilities of treatment imbalances and the potential effects on the power of statistical tests; the permutational basis for statistical tests; and the potential for experimental biases in the assessment of treatment effects due either to the predictability of the random allocations (selection bias) or the susceptibility of the randomization procedure to covariate imbalances (accidental bias). For most randomization procedures, the probabilities of overall treatment imbalances are readily computed, even when a stratified randomization is used. This is important because treatment imbalance may affect statistical power. It is shown, however, that treatment imbalance must be substantial before power is more than trivially affected. The differences between a population versus a permutation model as a basis for a statistical test are reviewed. It is argued that a population model can only be invoked in clinical trials as an untestable assumption, rather than being formally based on sampling at random from a population. On the other hand, a permutational analysis based on the randomization actually employed requires no assumptions regarding the origin of the samples of patients studied. The large sample permutational distribution of the family of linear rank tests is described as a basis for easily conducting a variety of permutation tests. Subgroup (stratified) analyses, analyses when some data are missing, and regression model analyses are also

  14. Is Religiosity Related to Attitudes Towards Clinical Trials Participation?

    PubMed Central

    Daverio-Zanetti, Svetlana; Schultz, Kathryn; del Campo, Miguel A. Martin; Malcarne, Vanessa; Riley, Natasha; Sadler, Georgia Robins

    2014-01-01

    Research indicates that a low percentage of cancer patients enroll in cancer clinical trials. This is especially true among minority groups such as Hispanic Americans. Considering the importance of religion in the Hispanic American community, it is important to understand its relationship to perceptions of clinical trials. Five hundred and three Latina women completed the Barriers to Clinical Trials Participation Scale and the Duke University Religion Index. For the total sample, higher organizational and intrinsic religiosity were significantly associated with perceived lack of community support for clinical trials participation. In subgroup analysis, the relationship between organizational religiosity and lack of support was stronger among Latinas who were Spanish language-preference, and Latinas who were Catholic. Intrinsic religiosity was associated with mistrust among Spanish language-preference Latinas, and both organizational and intrinsic religiosity were associated with lack of familiarity with clinical trials among Christian (non-Catholic) Latinas. These results indicate religious institutions that serve Latinas may be an effective venue for disseminating clinical trial education programs to improve attitudes toward clinical trials participation. PMID:24953236

  15. Is religiosity related to attitudes toward clinical trials participation?

    PubMed

    Daverio-Zanetti, Svetlana; Schultz, Kathryn; del Campo, Miguel A Martin; Malcarne, Vanessa; Riley, Natasha; Sadler, Georgia Robins

    2015-06-01

    Research indicates that a low percentage of cancer patients enroll in cancer clinical trials. This is especially true among minority groups such as Hispanic Americans. Considering the importance of religion in the Hispanic American community, it is important to understand its relationship to perceptions of clinical trials. Five hundred and three Latina women completed the Barriers to Clinical Trials Participation Scale and the Duke University Religion Index. For the total sample, higher organizational and intrinsic religiosity was significantly associated with a perceived lack of community support for clinical trials participation. In subgroup analysis, the relationship between organizational religiosity and lack of support was stronger among Latinas who were Spanish language preferred and Latinas who were Catholic. Intrinsic religiosity was associated with mistrust among Spanish language-preferred Latinas, and both organizational and intrinsic religiosities were associated with a lack of familiarity with clinical trials among Christian (non-Catholic) Latinas. These results indicate that religious institutions that serve Latinas may be an effective venue for disseminating clinical trial education programs to improve attitudes toward clinical trials participation. PMID:24953236

  16. Choosing Alzheimer's disease prevention clinical trial populations.

    PubMed

    Grill, Joshua D; Monsell, Sarah E

    2014-03-01

    To assist investigators in making design choices, we modeled Alzheimer's disease prevention clinical trials. We used longitudinal Clinical Dementia Rating Scale Sum of Boxes data, retention rates, and the proportions of trial-eligible cognitively normal participants age 65 and older in the National Alzheimer's Coordinating Center Uniform Data Set to model trial sample sizes, the numbers needed to enroll to account for drop out, and the numbers needed to screen to successfully complete enrollment. We examined how enrichment strategies affected each component of the model. Relative to trials enrolling 65-year-old individuals, trials enriching for older (minimum 70 or 75) age required reduced sample sizes, numbers needed to enroll, and numbers needed to screen. Enriching for subjective memory complaints reduced sample sizes and numbers needed to enroll more than age enrichment, but increased the number needed to screen. We conclude that Alzheimer's disease prevention trials can enroll elderly participants with minimal effect on trial retention and that enriching for older individuals with memory complaints might afford efficient trial designs. PMID:24119546

  17. Social Media Ups Clinical Trial Enrollment.

    PubMed

    2016-08-01

    In just seven months, the Metastatic Breast Cancer Project has collected clinical and genetic data from more than 2,000 patients who learned about this effort from social media and volunteered to participate. The project could become a model for other cancer types where recruiting sufficient patients for clinical trials through traditional channels is often a challenge. PMID:27329925

  18. Research misconduct among clinical trial staff.

    PubMed

    Redman, Barbara K; Templin, Thomas N; Merz, Jon F

    2006-07-01

    Between 1993 and 2002, 39 clinical trial staff were investigated for scientific misconduct by the Office of Research Integrity (ORI). Analysis of ORI case records reveals practices regarding workload, training and supervision that enable misconduct. Considering the potential effects on human subjects protection, quality and reliability of data, and the trustworthiness of the clinical research enterprise, regulations or guidance on use of clinical trial staff ought to be available. Current ORI regulations do not hold investigators or institutions responsible for supervision and training of clinical trial staff. Given the important issues at stake, the definition of research misconduct should encompass the intentional or negligent mismanagement of scientific projects. Individual institutions and professional associations not only can but should adopt stricter standards of conduct than those reflected in federal regulations. PMID:16909150

  19. DO CANCER CLINICAL TRIAL POPULATIONS TRULY REPRESENT CANCER PATIENTS? A COMPARISON OF OPEN CLINICAL TRIALS TO THE CANCER GENOME ATLAS

    PubMed Central

    Geifman, Nophar; Butte, Atul J.

    2016-01-01

    Open clinical trial data offer many opportunities for the scientific community to independently verify published results, evaluate new hypotheses and conduct meta-analyses. These data provide a springboard for scientific advances in precision medicine but the question arises as to how representative clinical trials data are of cancer patients overall. Here we present the integrative analysis of data from several cancer clinical trials and compare these to patient-level data from The Cancer Genome Atlas (TCGA). Comparison of cancer type-specific survival rates reveals that these are overall lower in trial subjects. This effect, at least to some extent, can be explained by the more advanced stages of cancer of trial subjects. This analysis also reveals that for stage IV cancer, colorectal cancer patients have a better chance of survival than breast cancer patients. On the other hand, for all other stages, breast cancer patients have better survival than colorectal cancer patients. Comparison of survival in different stages of disease between the two datasets reveals that subjects with stage IV cancer from the trials dataset have a lower chance of survival than matching stage IV subjects from TCGA. One likely explanation for this observation is that stage IV trial subjects have lower survival rates since their cancer is less likely to respond to treatment. To conclude, we present here a newly available clinical trials dataset which allowed for the integration of patient-level data from many cancer clinical trials. Our comprehensive analysis reveals that cancer-related clinical trials are not representative of general cancer patient populations, mostly due to their focus on the more advanced stages of the disease. These and other limitations of clinical trials data should, perhaps, be taken into consideration in medical research and in the field of precision medicine. PMID:26776196

  20. Triple peptide vaccination as consolidation treatment in women affected by ovarian and breast cancer: Clinical and immunological data of a phase I/II clinical trial

    PubMed Central

    ANTONILLI, MORENA; RAHIMI, HASSAN; VISCONTI, VALERIA; NAPOLETANO, CHIARA; RUSCITO, ILARY; ZIZZARI, ILARIA GRAZIA; CAPONNETTO, SALVATORE; BARCHIESI, GIACOMO; IADAROLA, ROBERTA; PIERELLI, LUCA; RUGHETTI, AURELIA; BELLATI, FILIPPO; PANICI, PIERLUIGI BENEDETTI; NUTI, MARIANNA

    2016-01-01

    Vaccination with priming and expansion of tumour reacting T cells is an important therapeutic option to be used in combination with novel checkpoint inhibitors to increase the specificity of the T cell infiltrate and the efficacy of the treatment. In this phase I/II study, 14 high-risk disease-free ovarian (OC) and breast cancer (BC) patients after completion of standard therapies were vaccinated with MUC1, ErbB2 and carcinoembryonic antigen (CEA) HLA-A2+-restricted peptides and Montanide. Patients were subjected to 6 doses of vaccine every two weeks and a recall dose after 3 months. ECOG grade 2 toxicity was observed at the injection site. Eight out of 14 patients showed specific CD8+ T cells to at least one antigen. None of 4 patients vaccinated for compassionate use showed a CD8 activation. An OC patient who suffered from a lymph nodal recurrence, showed specific anti-ErbB2 CD8+ T cells in the bulky aortic lymph nodes suggesting homing of the activated T cells. Results confirm that peptide vaccination strategy is feasible, safe and well tolerated. In particular OC patients appear to show a higher response rate compared to BC patients. Vaccination generates a long-lasting immune response, which is strongly enhanced by recall administrations. The clinical outcome of patients enrolled in the trial appears favourable, having registered no deceased patients with a minimum follow-up of 8 years. These promising data, in line with the results of similar studies, the high compliance of patients observed and the favourable toxicity profile, support future trials of peptide vaccination in clinically disease-free patients who have completed standard treatments. PMID:26892612

  1. Triple peptide vaccination as consolidation treatment in women affected by ovarian and breast cancer: Clinical and immunological data of a phase I/II clinical trial.

    PubMed

    Antonilli, Morena; Rahimi, Hassan; Visconti, Valeria; Napoletano, Chiara; Ruscito, Ilary; Zizzari, Ilaria Grazia; Caponnetto, Salvatore; Barchiesi, Giacomo; Iadarola, Roberta; Pierelli, Luca; Rughetti, Aurelia; Bellati, Filippo; Panici, Pierluigi Benedetti; Nuti, Marianna

    2016-04-01

    Vaccination with priming and expansion of tumour reacting T cells is an important therapeutic option to be used in combination with novel checkpoint inhibitors to increase the specificity of the T cell infiltrate and the efficacy of the treatment. In this phase I/II study, 14 high-risk disease-free ovarian (OC) and breast cancer (BC) patients after completion of standard therapies were vaccinated with MUC1, ErbB2 and carcinoembryonic antigen (CEA) HLA-A2+-restricted peptides and Montanide. Patients were subjected to 6 doses of vaccine every two weeks and a recall dose after 3 months. ECOG grade 2 toxicity was observed at the injection site. Eight out of 14 patients showed specific CD8+ T cells to at least one antigen. None of 4 patients vaccinated for compassionate use showed a CD8 activation. An OC patient who suffered from a lymph nodal recurrence, showed specific anti-ErbB2 CD8+ T cells in the bulky aortic lymph nodes suggesting homing of the activated T cells. Results confirm that peptide vaccination strategy is feasible, safe and well tolerated. In particular OC patients appear to show a higher response rate compared to BC patients. Vaccination generates a long-lasting immune response, which is strongly enhanced by recall administrations. The clinical outcome of patients enrolled in the trial appears favourable, having registered no deceased patients with a minimum follow-up of 8 years. These promising data, in line with the results of similar studies, the high compliance of patients observed and the favourable toxicity profile, support future trials of peptide vaccination in clinically disease-free patients who have completed standard treatments. PMID:26892612

  2. Effectiveness of platelet-rich plasma as an adjunctive material to bone graft: a systematic review and meta-analysis of randomized controlled clinical trials.

    PubMed

    Pocaterra, A; Caruso, S; Bernardi, S; Scagnoli, L; Continenza, M A; Gatto, R

    2016-08-01

    The use of platelet-rich plasma (PRP) has become a strategic therapy in tissue regeneration medicine. PRP represents a good source of growth factors. Due to this property, it has been considered a reliable adjunctive material in bone augmentation procedures, such as the sinus lift technique. The aim of this review was to assess the scientific evidence on the effectiveness of PRP as an adjunctive material in the sinus floor elevation technique. The following databases were searched for relevant published studies: Medline, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, CINAHL, Science Direct, ISI Web of Knowledge, and SCOPUS. Only randomized controlled clinical trials comparing a group receiving PRP as an adjunctive material to a control group without PRP, involving adult human subjects (age >18 years) with no systemic disease, were included. Of the studies identified, only one reported a significant difference in bone augmentation in favour of the adjunctive use of PRP, while four studies did not find any significant difference. None of the studies included reported a significant difference in the implant survival rate. Further randomized clinical trials are needed to clarify the effectiveness of adjunctive PRP. PMID:26987695

  3. Elderly patients’ participation in clinical trials

    PubMed Central

    Shenoy, Premnath; Harugeri, Anand

    2015-01-01

    The elderly population is a large and the fastest-growing portion of the population worldwide. The elderly make up the lion's share of patients for certain health conditions including cancer, cardiovascular disease, arthritis, and Parkinson's disease, among others in most parts of the world. Furthermore, elderly make up the majority of patients for many medications treating chronic conditions. Typically, clinical trials conducted in adult population include patients between the ages of 18 and 64 years. However, drugs should be studied in all age groups and trial participants should be representative of the patient population receiving the therapy in daily medical practice. Elderly patients are poorly represented in clinical trials. Hence, there is inadequate evidence and knowledge about responses of geriatric patients to medications. Regulatory authorities in developed countries urge to avoid arbitrary upper age limits and advise researchers and industry not to exclude elderly people from clinical trials without a valid reason. Since last few years Indian regulatory authority has been stipulating upper age limit for studies conducted in India. The Central Drugs Standard Control Organization (CDSCO) will be doing a great contribution to the researchers if it changes its view on stipulating upper age restrictions in clinical studies. This article describes the need for including elderly patients in the clinical trials in order to garner data from geriatric patients who form major medication users in most of the chronic diseases. PMID:26623388

  4. The use of green coffee extract as a weight loss supplement: a systematic review and meta-analysis of randomised clinical trials.

    PubMed

    Onakpoya, Igho; Terry, Rohini; Ernst, Edzard

    2011-01-01

    The purpose of this paper is to assess the efficacy of green coffee extract (GCE) as a weight loss supplement, using data from human clinical trials. Electronic and nonelectronic searches were conducted to identify relevant articles, with no restrictions in time or language. Two independent reviewers extracted the data and assessed the methodological quality of included studies. Five eligible trials were identified, and three of these were included. All studies were associated with a high risk of bias. The meta-analytic result reveals a significant difference in body weight in GCE compared with placebo (mean difference: -2.47 kg; 95%CI: -4.23, -0.72). The magnitude of the effect is moderate, and there is significant heterogeneity amongst the studies. It is concluded that the results from these trials are promising, but the studies are all of poor methodological quality. More rigorous trials are needed to assess the usefulness of GCE as a weight loss tool. PMID:20871849

  5. The Use of Green Coffee Extract as a Weight Loss Supplement: A Systematic Review and Meta-Analysis of Randomised Clinical Trials

    PubMed Central

    Onakpoya, Igho; Terry, Rohini; Ernst, Edzard

    2011-01-01

    The purpose of this paper is to assess the efficacy of green coffee extract (GCE) as a weight loss supplement, using data from human clinical trials. Electronic and nonelectronic searches were conducted to identify relevant articles, with no restrictions in time or language. Two independent reviewers extracted the data and assessed the methodological quality of included studies. Five eligible trials were identified, and three of these were included. All studies were associated with a high risk of bias. The meta-analytic result reveals a significant difference in body weight in GCE compared with placebo (mean difference: −2.47 kg; 95%CI: −4.23, −0.72). The magnitude of the effect is moderate, and there is significant heterogeneity amongst the studies. It is concluded that the results from these trials are promising, but the studies are all of poor methodological quality. More rigorous trials are needed to assess the usefulness of GCE as a weight loss tool. PMID:20871849

  6. Newer Antibacterials in Therapy and Clinical Trials

    PubMed Central

    Paknikar, Simi S; Narayana, Sarala

    2012-01-01

    In order to deal with the rising problem of antibiotic resistance, newer antibacterials are being discovered and added to existing pool. Since the year 2000, however, only four new classes of antibacterials have been discovered. These include the oxazolidinones, glycolipopeptides, glycolipodepepsipeptide and pleuromutilins. Newer drugs were added to existing classes of antibiotics, such as streptogramins, quinolones, beta-lactam antibiotics, and macrolide-, tetracycline- and trimethoprim-related drugs. Most of the antibacterials are directed against resistant S. aureus infections, with very few against resistant gram-negative infections. The following article reviews the antibacterials approved by the FDA after the year 2000 as well as some of those in clinical trials. Data was obtained through a literature search via Pubmed and google as well as a detailed search of our library database. PMID:23181224

  7. The Mock Trial: A Dynamic Exercise for Thinking Critically about Management Theories, Topics, and Practices

    ERIC Educational Resources Information Center

    Farmer, Kevin; Meisel, Steven I.; Seltzer, Joe; Kane, Kathleen

    2013-01-01

    The Mock Trial is an experiential exercise adapted from a law school process that encourages students to think critically about theories, topics, and the practice of management in an innovative classroom experience. Playing the role of attorneys and witnesses, learners ask questions and challenge assumptions by playing roles in a trial with…

  8. Sample sizes in dosage investigational clinical trials: a systematic evaluation.

    PubMed

    Huang, Ji-Han; Su, Qian-Min; Yang, Juan; Lv, Ying-Hua; He, Ying-Chun; Chen, Jun-Chao; Xu, Ling; Wang, Kun; Zheng, Qing-Shan

    2015-01-01

    The main purpose of investigational phase II clinical trials is to explore indications and effective doses. However, as yet, there is no clear rule and no related published literature about the precise suitable sample sizes to be used in phase II clinical trials. To explore this, we searched for clinical trials in the ClinicalTrials.gov registry using the keywords "dose-finding" or "dose-response" and "Phase II". The time span of the search was September 20, 1999, to December 31, 2013. A total of 2103 clinical trials were finally included in our review. Regarding sample sizes, 1,156 clinical trials had <40 participants in each group, accounting for 55.0% of the studies reviewed, and only 17.2% of the studies reviewed had >100 patient cases in a single group. Sample sizes used in parallel study designs tended to be larger than those of crossover designs (median sample size 151 and 37, respectively). In conclusion, in the earlier phases of drug research and development, there are a variety of designs for dosage investigational studies. The sample size of each trial should be comprehensively considered and selected according to the study design and purpose. PMID:25609916

  9. Advances in designs for Alzheimer’s disease clinical trials

    PubMed Central

    Cummings, Jeffrey; Gould, Heath; Zhong, Kate

    2012-01-01

    There is an urgent need to identify new treatments for the rapidly growing population of people with Alzheimer’s disease (AD). Innovations in clinical trial designs many help to reduce development time, provide more definitive answers regarding drug efficacy, and facilitate prioritizing compounds to be advanced to Phase III clinical trials. Standard designs compare drug and placebo changes from baseline on a rating scale. Baysian adaptive clinical trials allow the use of data collected in the trial to modify doses, sample size, trial duration, and entry criteria in an ongoing way as the data are collected. Disease-modification is supported by findings on staggered start and delayed withdrawal designs. Futility designs can use historical controls and may shorten trial duration. Combination therapy designs may allow investigation of additive or synergistic treatment effects. Novel trial selection criteria allow investigation of treatment effects in asymptomatic or minimally symptomatic, prodromal AD populations. The Clinical Dementia Rating-Sum of Boxes (CDR-SOB) can be considered as a single trial outcome in early disease populations. Alternate forms of the Alzheimer’s Disease Assessment Scale-Cognitive Portion (ADAS-cog), computerized measures, and pharmacoeconomic scales provide new and relevant information on drug effects. Comparative dose strategies are used in trials of symptomatic agents, and novel methods including withdrawal designs, symptom emergence analyses, and sequential designs are being utilized to assess the efficacy of putative psychotropic agents. The choice of trial design is driven by the question to be answered by the clinical trial; an increasing number of design approaches are available and may be useful in accelerating and refining AD drug development. PMID:23383393

  10. African American women's perceptions of cancer clinical trials.

    PubMed

    Haynes-Maslow, Lindsey; Godley, Paul; Dimartino, Lisa; White, Brandolyn; Odom, Janice; Richmond, Alan; Carpenter, William

    2014-10-01

    Cancer clinical trials are important for resolving cancer health disparities for several reasons; however, clinical trial participation among African Americans is significantly lower than Caucasians. This study engaged focus groups of 82 female African American cancer survivors or cancer caregivers, including those in better resourced, more urban areas and less resourced, more rural areas. Informed by an integrated conceptual model, the focus groups examined perceptions of cancer clinical trials and identified leverage points that future interventions may use to improve enrollment rates. Study findings highlight variation in community knowledge regarding cancer clinical trials, and the importance of community education regarding clinical trials and overcoming historical stigma associated with clinical research specifically and the health care system more generally. Study participants commented on the centrality of churches in their communities, and thus the promise of the church as loci of such education. Findings also suggested the value of informed community leaders as community information sources, including community members who have a previous diagnosis of cancer and clinical trial experience. The sample size and location of the focus groups may limit the generalizability of the results. Since the women in the focus groups were either cancer survivors or caregivers, they may have different experiences than nonparticipants who lack the close connection with cancer. Trust in the health system and in one's physician was seen as important factors associated with patient willingness to enroll in clinical trials, and participants suggested that physicians who were compassionate and who engaged and educated their patients would build important trust requisite for patient participation in clinical trials. PMID:24905181

  11. African American women's perceptions of cancer clinical trials

    PubMed Central

    Haynes-Maslow, Lindsey; Godley, Paul; Dimartino, Lisa; White, Brandolyn; Odom, Janice; Richmond, Alan; Carpenter, William

    2014-01-01

    Cancer clinical trials are important for resolving cancer health disparities for several reasons; however, clinical trial participation among African Americans is significantly lower than Caucasians. This study engaged focus groups of 82 female African American cancer survivors or cancer caregivers, including those in better resourced, more urban areas and less resourced, more rural areas. Informed by an integrated conceptual model, the focus groups examined perceptions of cancer clinical trials and identified leverage points that future interventions may use to improve enrollment rates. Study findings highlight variation in community knowledge regarding cancer clinical trials, and the importance of community education regarding clinical trials and overcoming historical stigma associated with clinical research specifically and the health care system more generally. Study participants commented on the centrality of churches in their communities, and thus the promise of the church as loci of such education. Findings also suggested the value of informed community leaders as community information sources, including community members who have a previous diagnosis of cancer and clinical trial experience. The sample size and location of the focus groups may limit the generalizability of the results. Since the women in the focus groups were either cancer survivors or caregivers, they may have different experiences than nonparticipants who lack the close connection with cancer. Trust in the health system and in one's physician was seen as important factors associated with patient willingness to enroll in clinical trials, and participants suggested that physicians who were compassionate and who engaged and educated their patients would build important trust requisite for patient participation in clinical trials. PMID:24905181

  12. 75 FR 45646 - Design of Clinical Trials of Aerosolized Antimicrobials for the Treatment of Cystic Fibrosis...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-08-03

    ... clinical trial endpoints to establish efficacy is a major challenge in the design of informative clinical.... The workshop will include discussion of clinical trial endpoints to establish efficacy, such as timing... HUMAN SERVICES Food and Drug Administration Design of Clinical Trials of Aerosolized Antimicrobials...

  13. Clinical Trials in Retinal Dystrophies

    PubMed Central

    Grob, Seanna R.; Finn, Avni; Papakostas, Thanos D.; Eliott, Dean

    2016-01-01

    Research development is burgeoning for genetic and cellular therapy for retinal dystrophies. These dystrophies are the focus of many research efforts due to the unique biology and accessibility of the eye, the transformative advances in ocular imaging technology that allows for in vivo monitoring, and the potential benefit people would gain from success in the field – the gift of renewed sight. Progress in the field has revealed the immense complexity of retinal dystrophies and the challenges faced by researchers in the development of this technology. This study reviews the current trials and advancements in genetic and cellular therapy in the treatment of retinal dystrophies and also discusses the current and potential future challenges. PMID:26957839

  14. Advances in cardiology: clinical trial update.

    PubMed

    Howe, Andrew J; Shand, James A; Menown, Ian B A

    2011-05-01

    Multiple key cardiology trials have been presented or published over recent months, several with the potential to change clinical practice. In this article, we summarize and place in clinical context new trial findings regarding anticoagulation in the cardiac catheterization laboratory (enoxaparin, fondaparinux and unfractionated heparin), the implications of genetic polymorphisms and functional testing for antiplatelet therapy (clopidogrel and ticagrelor), new oral anticoagulants for use in atrial fibrillation (apixiban and rivaroxaban), optimal pacing strategies and pharmacological agents in heart failure (ivabradine, eplerenone, cardiac resynchronization therapy, telemonitoring and intracoronary bone marrow stem cell infusion). Clinical trials in percutaneous structural intervention (transcatheter aortic valve implantation, MONARC™ mitral annular implant, STARFlex(®) patent foramen ovale device) and advanced percutaneous coronary intervention (everolimus-eluting stents, biodegradable polymer/polymer-free technologies and contemporary use of intravascular ultrasound) are also discussed. PMID:21627472

  15. Disease-mongering through clinical trials.

    PubMed

    González-Moreno, María; Saborido, Cristian; Teira, David

    2015-06-01

    Our goal in this paper is to articulate a precise concept of at least a certain kind of disease-mongering, showing how pharmaceutical marketing can commercially exploit certain diseases when their best definition is given through the success of a treatment in a clinical trial. We distinguish two types of disease-mongering according to the way they exploit the definition of the trial population for marketing purposes. We argue that behind these two forms of disease-mongering there are two well-known problems in the statistical methodology of clinical trials (the reference class problem and the distinction between statistical and clinical significance). Overcoming them is far from simple. PMID:25863220

  16. Randomized control trial of topical clonidine for treatment of painful diabetic neuropathy

    PubMed Central

    Campbell, Claudia M.; Kipnes, Mark S.; Stouch, Bruce C.; Brady, Kerrie L.; Kelly, Margaret; Schmidt, William K.; Petersen, Karin L.; Rowbotham, Michael C.; Campbell, James N.

    2012-01-01

    A length-dependent neuropathy with pain in the feet is a common complication of diabetes (painful diabetic neuropathy, PDN). It was hypothesized that pain may arise from sensitized-hyperactive cutaneous nociceptors, and that this abnormal signaling may be reduced by topical administration of the α2-adrenergic agonist, clonidine, to the painful area. This was a randomized, double-blind, placebo-controlled, parallel-group, multi-center trial. Nociceptor function was measured by determining the painfulness of 0.1% topical capsaicin applied to the pre-tibial area of each subject for 30 minutes during screening. Subjects were then randomized to receive 0.1% topical clonidine gel (n=89) or placebo gel (n=90) applied t.i.d. to their feet for 12 weeks. The difference in foot pain at week 12 in relation to baseline, rated on a 0-10 numerical pain rating scale (NPRS), was compared between groups. Baseline NPRS was imputed for missing data for subjects who terminated the study early. The subjects treated with clonidine showed a trend toward decreased foot pain compared to the placebo-treated group (the primary endpoint; p=0.07). In subjects who felt any level of pain to capsaicin, clonidine was superior to placebo (p<0.05). In subjects with a capsaicin pain rating ≥2 (0-10, NPRS), the mean decrease in foot pain was 2.6 for active compared to 1.4 for placebo (p=0.01). Topical clonidine gel significantly reduces the level of foot pain in PDN subjects with functional (and possibly sensitized) nociceptors in the affected skin as revealed by testing with topical capsaicin. Screening for cutaneous nociceptor function may help distinguish candidates for topical therapy for neuropathic pain. PMID:22683276

  17. A method for discovering and inferring appropriate eligibility criteria in clinical trial protocols without labeled data

    PubMed Central

    2013-01-01

    Background We consider the user task of designing clinical trial protocols and propose a method that discovers and outputs the most appropriate eligibility criteria from a potentially huge set of candidates. Each document d in our collection D is a clinical trial protocol which itself contains a set of eligibility criteria. Given a small set of sample documentsD′,|D′|≪|D|, a user has initially identified as relevant e.g., via a user query interface, our scoring method automatically suggests eligibility criteria from D, D ⊃ D', by ranking them according to how appropriate they are to the clinical trial protocol currently being designed. The appropriateness is measured by the degree to which they are consistent with the user-supplied sample documents D'. Method We propose a novel three-step method called LDALR which views documents as a mixture of latent topics. First, we infer the latent topics in the sample documents using Latent Dirichlet Allocation (LDA). Next, we use logistic regression models to compute the probability that a given candidate criterion belongs to a particular topic. Lastly, we score each criterion by computing its expected value, the probability-weighted sum of the topic proportions inferred from the set of sample documents. Intuitively, the greater the probability that a candidate criterion belongs to the topics that are dominant in the samples, the higher its expected value or score. Results Our experiments have shown that LDALR is 8 and 9 times better (resp., for inclusion and exclusion criteria) than randomly choosing from a set of candidates obtained from relevant documents. In user simulation experiments using LDALR, we were able to automatically construct eligibility criteria that are on the average 75% and 70% (resp., for inclusion and exclusion criteria) similar to the correct eligibility criteria. Conclusions We have proposed LDALR, a practical method for discovering and inferring appropriate eligibility criteria in clinical

  18. Clinical Effects of Topical Tacrolimus on Fox-Fordyce Disease.

    PubMed

    Kaya Erdoğan, Hilal; Bulur, Işıl; Kaya, Zeliha

    2015-01-01

    Fox-Fordyce Disease (FFD) is a rare, chronic, pruritic, inflammatory disorder of apocrine glands. It is characterized by dome-shaped, firm, discrete, skin-colored, and monomorphic perifollicular papules. The most common sites of involvement are axillae and anogenital and periareolar regions which are rich in apocrine sweat glands. Treatment is difficult. Topical, intralesional steroids, topical tretinoin, adapalene, clindamycin, benzoyl peroxide, oral contraceptives, isotretinoin, phototherapy, electrocauterisation, excision-liposuction and curettage, and fractional carbon dioxide laser are among the treatment options. In the literature, there are articles reporting beneficial effects of pimecrolimus in FFD. Nevertheless, there have not been any reports about the use of tacrolimus in FFD. We report two patients diagnosed with FFD by clinical and histopathologic examination and discussed therapeutic effects of topical tacrolimus on FFD in the light of literature. PMID:26171257

  19. Clinical Effects of Topical Tacrolimus on Fox-Fordyce Disease

    PubMed Central

    Kaya Erdoğan, Hilal; Bulur, Işıl; Kaya, Zeliha

    2015-01-01

    Fox-Fordyce Disease (FFD) is a rare, chronic, pruritic, inflammatory disorder of apocrine glands. It is characterized by dome-shaped, firm, discrete, skin-colored, and monomorphic perifollicular papules. The most common sites of involvement are axillae and anogenital and periareolar regions which are rich in apocrine sweat glands. Treatment is difficult. Topical, intralesional steroids, topical tretinoin, adapalene, clindamycin, benzoyl peroxide, oral contraceptives, isotretinoin, phototherapy, electrocauterisation, excision-liposuction and curettage, and fractional carbon dioxide laser are among the treatment options. In the literature, there are articles reporting beneficial effects of pimecrolimus in FFD. Nevertheless, there have not been any reports about the use of tacrolimus in FFD. We report two patients diagnosed with FFD by clinical and histopathologic examination and discussed therapeutic effects of topical tacrolimus on FFD in the light of literature. PMID:26171257

  20. The Place of Adoption in the NIDA Clinical Trials Network

    PubMed Central

    Jessup, Martha A.; Guydish, Joseph; Manser, Sarah Turcotte; Tajima, Barbara

    2009-01-01

    The National Institute on Drug Abuse (NIDA) Clinical Trials Network (CTN) was established in 1999 to determine effectiveness of drug abuse treatment interventions among diverse client populations and settings. To address dissemination of research findings, the CTN also has as its mission the transfer of research findings to treatment providers. In a qualitative study of adoption of evidence based practice in the context of two CTN clinical trials, we interviewed 29 participants from seven organizational levels of the multisite study organization about post-trial adoption, their role in the clinical trial, and interactions between the research initiative and clinic staff and setting. Analysis of interview data revealed a range of opinion among participants on the place of adoption within the CTN. Innovation within the CTN to support adoption and further observational research on dynamics of adoption within the CTN can increase dissemination of evidence-based drug abuse treatment interventions in the future. PMID:20126428

  1. Processes for quality improvements in radiation oncology clinical trials.

    PubMed

    FitzGerald, T J; Urie, Marcia; Ulin, Kenneth; Laurie, Fran; Yorty, Jeffrey; Hanusik, Richard; Kessel, Sandy; Jodoin, Maryann Bishop; Osagie, Gani; Cicchetti, M Giulia; Pieters, Richard; McCarten, Kathleen; Rosen, Nancy

    2008-01-01

    Quality assurance in radiotherapy (RT) has been an integral aspect of cooperative group clinical trials since 1970. In early clinical trials, data acquisition was nonuniform and inconsistent and computational models for radiation dose calculation varied significantly. Process improvements developed for data acquisition, credentialing, and data management have provided the necessary infrastructure for uniform data. With continued improvement in the technology and delivery of RT, evaluation processes for target definition, RT planning, and execution undergo constant review. As we move to multimodality image-based definitions of target volumes for protocols, future clinical trials will require near real-time image analysis and feedback to field investigators. The ability of quality assurance centers to meet these real-time challenges with robust electronic interaction platforms for imaging acquisition, review, archiving, and quantitative review of volumetric RT plans will be the primary challenge for future successful clinical trials. PMID:18406943

  2. Ethical Issues in Clinical Trials Involving Nanomedicine

    PubMed Central

    Resnik, David B.; Tinkle, Sally S.

    2009-01-01

    Nanomedicine shows tremendous promise for improving medical diagnosis, treatment, and prevention, but it also raises a variety of ethical concerns. Because of the paucity of data on the physicochemical properties of nanoscale materials in biological systems, clinical trials of nanomedicine products present some unique challenges related to risk minimization, management and communication involving human subjects. Although these clinical trials do not raise any truly novel ethical issues, the rapid development of nanotechnology and its potentially profound social and environmental impacts, add a sense of urgency to the problems that arise. PMID:17166777

  3. Maximal Usage Trial: An Overview of the Design of Systemic Bioavailability Trial for Topical Dermatological Products

    PubMed Central

    Bashaw, Edward Dennis; Tran, Doanh C.; Shukla, Chinmay G.; Liu, Xiaomei

    2015-01-01

    Dermatologic diseases can present in varying forms and severity, ranging from the individual lesion and up to almost total skin involvement. Pharmacokinetic assessment of topical drug products has previously been plagued by bioanalytical assay limitations and the lack of a standardized study design. Since the mid-1990's the US Food and Drug Administration has developed and implemented a pharmacokinetic maximal usage trial (MUsT) design to help address these issues. The MUsT design takes into account the following elements: the enrollment of patients rather than normal volunteers, the frequency of dosing, duration of dosing, use of highest proposed strength, total involved surface area to be treated at one time, amount applied per square centimeter, application method and site preparation, product formulation, and use of a sensitive bioanalytical method that has been properly validated. This paper provides a perspective of pre-MUsT study designs and a discussion of the individual elements that make up a MUsT. PMID:26634191

  4. Implications of Look AHEAD for Clinical Trials and Clinical Practice

    PubMed Central

    Wing, Rena R.

    2014-01-01

    Look AHEAD was a randomized clinical trial designed to examine the long-term health effects of weight loss in overweight and obese individuals with type 2 diabetes. The primary result was that the incidence of cardiovascular events over a median follow up of 9.6 years was not reduced in the intensive lifestyle group relative to the control group. This finding is discussed, with emphasis on its implications for design of clinical trials and clinical treatment of obese people with type 2 diabetes. PMID:24853636

  5. Topical tranexamic acid as a promising treatment for melasma

    PubMed Central

    Ebrahimi, Bahareh; Naeini, Farahnaz Fatemi

    2014-01-01

    Background: In recent times, tranexamic acid (TA) is claimed to have whitening effects especially for ultraviolet-induced hyperpigmentation including melasma. The aim of our study was to evaluate the efficacy and safety of topical solution of TA and compare it with combined solution of hydroquinone and dexamethasone as the gold standard treatment of melasma in Iranian women. Materials and Methods: This was a double-blind split-face trial of 12 weeks which was conducted in Isfahan, Iran. Fifty Iranian melasma patients applied topical solution of 3% TA on one side of the face, and topical solution of 3% hydroquinone + 0.01% dexamethasone on the other side two times a day. The Melasma Area and Severity Index (MASI) and the side effects were evaluated at baseline and every 4 weeks before and after photographs to be compared by a dermatologist were taken. The patient satisfaction was documented at week 12. Results: A repeated measurement analysis was used to evaluate the changes in the MASI score before and after treatments. A significant decreasing trend was observed in the MASI score of both groups with no significant difference between them during the study (P < 0.05). No differences were seen in patients’ and investigator's satisfaction of melasma improvement between two groups (P < 0.05). However, the side effects of hydroquinone + dexamethasone were significantly prominent compared with TA (P = 0.01). Conclusion: This study's results introduce the topical TA as an effective and safe medication for the treatment of melasma. PMID:25422661

  6. Gene Therapy in Cardiac Surgery: Clinical Trials, Challenges, and Perspectives

    PubMed Central

    Katz, Michael G.; Fargnoli, Anthony S.; Kendle, Andrew P.; Hajjar, Roger J.; Bridges, Charles R.

    2016-01-01

    The concept of gene therapy was introduced in the 1970s after the development of recombinant DNA technology. Despite the initial great expectations, this field experienced early setbacks. Recent years have seen a revival of clinical programs of gene therapy in different fields of medicine. There are many promising targets for genetic therapy as an adjunct to cardiac surgery. The first positive long-term results were published for adenoviral administration of vascular endothelial growth factor with coronary artery bypass grafting. In this review we analyze the past, present, and future of gene therapy in cardiac surgery. The articles discussed were collected through PubMed and from author experience. The clinical trials referenced were found through the Wiley clinical trial database (http://www.wiley.com/legacy/wileychi/genmed/clinical/) as well as the National Institutes of Health clinical trial database (Clinicaltrials.gov). PMID:26801060

  7. Gene Therapy in Cardiac Surgery: Clinical Trials, Challenges, and Perspectives.

    PubMed

    Katz, Michael G; Fargnoli, Anthony S; Kendle, Andrew P; Hajjar, Roger J; Bridges, Charles R

    2016-06-01

    The concept of gene therapy was introduced in the 1970s after the development of recombinant DNA technology. Despite the initial great expectations, this field experienced early setbacks. Recent years have seen a revival of clinical programs of gene therapy in different fields of medicine. There are many promising targets for genetic therapy as an adjunct to cardiac surgery. The first positive long-term results were published for adenoviral administration of vascular endothelial growth factor with coronary artery bypass grafting. In this review we analyze the past, present, and future of gene therapy in cardiac surgery. The articles discussed were collected through PubMed and from author experience. The clinical trials referenced were found through the Wiley clinical trial database (http://www.wiley.com/legacy/wileychi/genmed/clinical/) as well as the National Institutes of Health clinical trial database (Clinicaltrials.gov). PMID:26801060

  8. The wild Egyptian artichoke as a promising functional food for the treatment of hepatitis C virus as revealed via UPLC-MS and clinical trials.

    PubMed

    Elsebai, Mahmoud Fahmi; Abass, Khaled; Hakkola, Jukka; Atawia, Ahmed Rezk; Farag, Mohamed A

    2016-07-13

    Infection by hepatitis C virus (HCV) and its subsequent complications are a major cause of mortality worldwide. The water extract of the wild Egyptian artichoke (WEA) (Cynara cardunculus L. var. sylvestris (Lam.) Fiori) leaves is a freely available herbal product that is used for treatment of HCV-infection complications such as jaundice and ascites. The purpose of this study was to evaluate whether WEA exhibits activity against HCV, identify bioactive chemicals in its extract and to tentatively examine the potential inhibitory interactions of WEA with human drug-metabolizing enzymes. The current pilot clinical trial revealed that the water extract of a WEA plant decreased the HCV viral load below the detection level in 12 out of 15 patients. Furthermore, the liver enzymes ALT and AST, as well as the level of bilirubin were normalized. The total WEA extract inhibited CYP2B6 (OH-BUP) and CYP2C19 (5-OH-OME) with high affinity, IC50 ∼ 20 μg ml(-1), while moderate inhibitory interactions were observed for CYP1A2, CYP2D6, CYP2E1 and CYP3A4. Results presented herein suggest that the WEA exhibits strong antiviral activity against HCV and may be useful for its treatment. Compared to the artichoke product "Hepar SL Forte(®)", WEA was found to be more enriched in sesquiterpenes versus the abundance of phenolic compounds, especially flavonoids in Hepar SL Forte(®) as revealed via UPLC-MS analysis coupled to chemometrics. PMID:27296047

  9. Analyzing acute procedural pain in clinical trials.

    PubMed

    Lang, Elvira V; Tan, Gabriel; Amihai, Ido; Jensen, Mark P

    2014-07-01

    Because acute procedural pain tends to increase with procedure time, assessments of pain management strategies must take that time relationship into account. Statistical time-course analyses are, however, complex and require large patient numbers to detect differences. The current study evaluated the abilities of various single and simple composite measures such as averaged pain or individual patient pain slopes to detect treatment effects. Secondary analyses were performed with the data from 3 prospective randomized clinical trials that assessed the effect of a self-hypnotic relaxation intervention on procedural pain, measured every 10-15 minutes during vascular/renal interventions, breast biopsies, and tumor embolizations. Single point-in-time and maximal pain comparisons were poor in detecting treatment effects. Linear data sets of individual patient slopes yielded the same qualitative results as the more complex repeated measures analyses, allowing the use of standard statistical approaches (eg, Kruskal-Wallis), and promising analyses of smaller subgroups, which otherwise would be underpowered. With nonlinear data, a simple averaged score was highly sensitive in detecting differences. Use of these 2 workable and relatively simple approaches may be a first step towards facilitating the development of data sets that could enable meta-analyses of data from acute pain trials. PMID:24731852

  10. Access to medications and conducting clinical trials in LMICs.

    PubMed

    Okpechi, Ikechi G; Swanepoel, Charles R; Venter, Francois

    2015-03-01

    Access to essential medications is limited in many low-to-middle income countries (LMICs) and those that are available may be prohibitively expensive to the general population. Clinical trials have been suggested as an approach to improve drug access in LMICs but the number of trials conducted in these countries is small because of regulatory issues and a lack of infrastructure. In this article, Nature Reviews Nephrology asks three experts their opinions on how to improve drug access and increase the numbers of clinical trials conducted in LMICs. PMID:25668002

  11. Clinical Trials: past, current and future for atypical parkinsonian syndromes

    PubMed Central

    Tsai, Richard M.; Boxer, Adam L.

    2016-01-01

    There are currently no effective, Food and Drug Administration (FDA) approved treatments for atypical parkinsonian disorders such as progressive supranuclear palsy (PSP), corticobasal degeneration (CBD), dementia with lewy bodies (DLB) or multiple system atrophy (MSA). Previous treatment trials for these disorders were focused on symptomatic support and did not affect disease progression. Recent breakthroughs in neuropathology and pathophysiology have allowed a new eunderstanding of these disorders and investigation into potentially disease modifying therapies. Randomized, placebo-controlled clinical trials of these disorders will be reviewed here. Suggestions for future therapeutic targets, clinical trial design, with a focus on PSP will also be provided. PMID:24963682

  12. CARLA TASK FORCE ON SARCOPENIA: PROPOSITIONS FOR CLINICAL TRIALS*

    PubMed Central

    VAN KAN, G. ABELLAN; ANDRÉ, E.; BISCHOFF-FERRARI, H.A.; BOIRIE, Y.; ONDER, G.; PAHOR, M.; RITZ, P.; ROLLAND, Y.; SAMPAIO, C.; STUDENSKI, S.; VISSER, M.; VELLAS, B.

    2015-01-01

    In the presence of an aging population, public health priorities need to evolve. As the populations gets older, the already existing pathologies have become commonplace with specific geriatric clinical syndromes like frailty, mobility disability, or cognitive impairment, among others. Sarcopenia is a good example for which geriatricians, neurologists, physiologists, nutritionists and epidemiologists need to find a consensual definition and diagnostic tool as well as guidelines for the management of clinical trials and possible treatments. The Carla Sarcopenia Task Force, which met in the south of France (Toulouse) for an expert consensus meeting called “Les Entretiens du Carla”, have addressed a series of existing issues to place Sarcopenia into a nosological context: a definition which should be a composite of a change in muscle mass and a change in strength/function depending on either a progressive and chronic wasting process or an acute onset of loss of muscle mass; a recommendation for DXA and the Short Physical Performance Battery as a clinical pragmatic approach of Sarcopenia; a differentiated approach for clinical studies according to prevention or treatment objectives and depending on the sub-groups and target populations; and finally, a summary of therapeutic strategies currently recommended. The aim of “Les Entretiens du Carla”, based on an expert meeting panel, was to address a series of unsolved issues in the field of Sarcopenia by combining the expert opinion with a revision of the existing literature on the topic. Through this report, the reader will appreciate the determination to find conclusions on the various issues and further studies to be developed to determine the best multidisciplinary approach needed. PMID:19657553

  13. Clinical trials at AHCs: the perspective of an academic clinical trials office.

    PubMed

    Paller, Mark S; Hostetler, Lisa; Dykhuis, Debra A

    2002-12-01

    Industry-sponsored clinical trials represent a substantial portion of the clinical investigator's portfolio of patient-oriented research. In academia's efforts to reclaim lost ground with respect to the performance of industry-sponsored clinical trials, many academic health centers have established clinical trials offices. An underlying assumption has been that with improved service on the part of universities will come new opportunities for clinical research. The experiences and vantage points of academic research offices have sometimes been ignored and an analysis of what new business might ensue has not been reported. The authors discuss the rationale for creating a centralized clinical trials office and the means of financing such an effort. They then describe the initial experiences (1997-2000) of a central clinical trials office (the Research Services Organization, or RSO) at the University of Minnesota Academic Health Center, analyze the value of such an office to the academic health center, and, based on their experiences with the RSO and elsewhere, consider how industry and academia might further enhance their collaborations. Of 354 clinical research proposals evaluated by the RSO, only 62% were found to be acceptable or highly likely to be acceptable to investigators and the institution. Reasons for not participating in specific clinical trials are discussed. Academic health centers contemplating developing clinical trials offices must be aware of the significant overhead cost associated with evaluating the appropriateness and feasibility of clinical trial proposals that may never be performed. Valuable lessons learned from working with sponsors and from working with investigators are also reviewed. PMID:12480622

  14. Niacin as potential treatment for dyslipidemia and hyperphosphatemia associated with chronic renal failure: the need for clinical trials.

    PubMed

    Ahmed, Mohamed H

    2010-06-01

    Niacin has profound and unique effects on lipid metabolism. In addition to increasing high-density lipoprotein cholesterol, it is also known to decrease total cholesterol, low-density lipoprotein cholesterol, and triglyceride. Interestingly, the plasma concentration of lipoprotein(a) [Lp(a)], which has been suggested to play a role as an independent risk factor for coronary heart disease, is also decreased by niacin. Therefore, it is not surprising that in the literature it was given unique description as broad-spectrum lipid drug. Its impact is referred to as desirable normalization of a range of cardiovascular risk factors. However, its clinical use is limited due to harmless but unpleasant unique side effect of cutaneous flushing. Interestingly, recent experimental and clinical studies suggest the potential benefit of niacin as a treatment of dyslipidemia and high plasma phosphate associated with chronic kidney disease (CKD). Both dyslipidemia and high serum phosphate levels are shown to be associated with higher cardiovascular mortality. Furthermore, niacin administration improves renal tissue lipid metabolism, renal function and structure, hypertension, proteinuria, and histological tubulointerstitial injury. Further studies are required before the use of niacin for the treatment of both dyslipidemia and hyperphosphatemia with CKD advocated. PMID:20486851

  15. Clinical trials and the new good clinical practice guideline in Japan. An economic perspective.

    PubMed

    Ono, S; Kodama, Y

    2000-08-01

    Japanese clinical trials have been drastically changing in response to the implementation of the International Conference on Harmonisation-Good Clinical Practice (ICH-GCP) guideline in 1997. The most important aim of the new guideline is to standardise the quality of clinical trials in the US, European Union and Japan, but it inevitably imposes substantial costs on investigators, sponsors and even patients in Japan. The study environment in Japan differs from that in the US in several ways: (i) historical lack of a formal requirement for informed consent; (ii) patients' attitudes to clinical trials in terms of expectation of positive outcomes; (iii) the implications of universal health insurance for trial participation; (iv) the historical absence of on-site monitoring by the sponsor, with the attendant effects on study quality; and (v) the lack of adequate financial and personnel support for the conduct of trials. Implementation of the new GCP guideline will improve the ethical and scientific quality of trials conducted in Japan. It may also lead to an improved relationship between medical professionals and patients if the requirement for explicit informed consent in clinical trials leads to the provision of a similar level of patient information in routine care and changes the traditional paternalistic attitude of physicians to patients. The initial response of the Japanese 'market' for clinical trials to the implementation of the ICH-GCP guideline has been clinical trial price increases and a decrease in the number of study contracts. These changes can be explained by applying a simple demand-supply scheme. Whether clinical trials undertaken in Japan become more or less attractive to the industry in the long term will depend on other factors such as international regulations on the acceptability of foreign clinical trials and the reform of domestic healthcare policies. PMID:11067647

  16. Perceptions of Reimbursement for Clinical Trial Participation

    PubMed Central

    Breitkopf, Carmen Radecki; Loza, Melissa; Vincent, Kathleen; Moench, Thomas; Stanberry, Lawrence R.; Rosenthal, Susan L.

    2012-01-01

    A greater understanding of participant views regarding reimbursement will help investigators plan studies that have better potential for reaching target enrollment, maximize efficient recruitment, maintain scientific integrity, and enhance retention over time. As part of a clinical trial in the area of sexual health, healthy women’s perceptions of reimbursement for research participation were investigated. Semi-structured, audio-recorded, qualitative interviews were conducted immediately upon women’s completion of the clinical trial to enable a participant-driven understanding of perceptions about monetary reimbursement. Audio-recordings were transcribed and analyzed using framework analysis. Women (N = 30) had a mean age of 29.5 ± 5.7 years (range 22–45 years). Sixty-three percent of participants (n = 19) were non-Hispanic (white n = 13, black n = 4, and Asian n = 2), while the remaining were Hispanic (n = 11). Seventy-three percent (n = 22) reported previous participation in research. In general, women viewed reimbursement as a benefit to research participation, the amount of which should reflect time, the inconvenience to the research subject, and the potential for unknown risks in the short- and long-term. They believed reimbursement should take into account the degree of risk of the study, with investigations of experimental products offering greater reimbursement. Women believed that monetary reimbursement is unlikely to coerce an individual to volunteer for a study involving procedures or requirements that they found unacceptable. The results of this study can be used to provide guidance to those planning and evaluating reimbursement for research participation. PMID:21931235

  17. Building data quality into clinical trials.

    PubMed

    Crerand, William J; Lamb, Jana; Rulon, Vera; Karal, Bilun; Mardekian, Jack

    2002-01-01

    Meaningful data begin with the collection process. Pharmaceutical companies are using several different strategies in clinical trials to ensure the highest quality of data. This article will examine these approaches, with an emphasis on case report form development through database release. PMID:12432815

  18. Catheter ablation of ventricular tachycardia: Lessons learned from past clinical trials and implications for future clinical trials.

    PubMed

    Pokorney, Sean D; Friedman, Daniel J; Calkins, Hugh; Callans, David J; Daoud, Emile G; Della-Bella, Paolo; Jackson, Kevin P; Shivkumar, Kalyanam; Saba, Samir; Sapp, John; Stevenson, William G; Al-Khatib, Sana M

    2016-08-01

    Catheter ablation of ventricular tachycardia (VT) has evolved in recent years, especially in patients with ischemic heart disease. Data from prospective studies show that VT catheter ablation reduces the risk of recurrent VT; however, there is a paucity of data on the effect of VT catheter ablation on mortality and patient-centered outcomes such as quality of life. Performing randomized clinical trials of VT catheter ablation can be fraught with challenges, and, as a result, several prior trials of VT catheter ablation had to be stopped prematurely. The main challenges are inability to blind the patient to therapy to obtain a traditional control group, high crossover rates between the 2 arms of the study, patient refusal to participate in trials in which they have an equal chance of receiving a "pill" vs an invasive procedure, heterogeneity of mapping and ablation techniques as well as catheters and equipment, rapid evolution of technology that may make findings of any long trial less relevant to clinical practice, lack of consensus on what constitutes acute procedural and long-term success, and presentation of patients to electrophysiologists late in the course of their disease. In this article, a panel of experts on VT catheter ablation and/or clinical trials of VT catheter ablation review challenges faced in conducting prior trials of VT catheter ablation and offer potential solutions for those challenges. It is hoped that the proposed solutions will enhance the feasibility of randomized clinical trials of VT catheter ablation. PMID:27050910

  19. 77 FR 22578 - Submission for OMB Review; Comment Request; Information Program on Clinical Trials: Maintaining a...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-04-16

    ... clinical trial registry under section 113 of the Food and Drug Administration Modernization Act of 1997... ``responsible parties,'' which are defined as sponsors of the clinical trial (as defined in 21 CFR 50.3) or... information will be integrated into a single record for each clinical trial, which is entered through the...

  20. Legal and ethical obligations to conduct a clinical drug trial in Australia as an investigator initiated and sponsored study for an overseas pharmaceutical company.

    PubMed

    Beran, Roy G

    2004-01-01

    Most multi-centre trials are both financed and sponsored by the pharmaceutical company involved. What follows will map the path adopted for an investigator initiated and sponsored study for a new indication of an established medication. The chief investigators of a company-sponsored, investigator-initiated, multi-centre, placebo-controlled study of an established medication, Pharmaceutical Benefit Scheme (PBS) listed for treatment of one condition but trialled in the management of another condition (trial of off-label use), were approached to submit a protocol to repeat the type of study with a different compound. The new study would test a different agent, also PBS listed, for the same condition as in the initial study and with the same off-licence application. The company would finance the study, provide the medication and matched placebo but only review the investigator-initiated protocol which would be sponsored by the principal investigator. This required the investigator to implement the trial, as would normally be done by the pharmaceutical company, yet also act as its principal investigator. The principal investigator, with colleagues and a Clinical Research Organisation (CRO), developed a protocol, adapted for the new agent, and submitted it for approval. Upon acceptance a contract was negotiated with the pharmaceutical company which had to overcome jurisdictional conflicts between common law and civil law legal systems. A CRO was contracted to undertake administrative functions which dictated special contractual agreements to overcome possible conflicts of interest for a sponsor/investigator to protect patient interests. There was need to find indemnification insurance with jurisdictional problems, co-investigators, ethics committee approvals and finance management as just some of the difficulties encountered. The paper will outline how these obstacles were overcome and how ethical and legal issues were respected through compromise. The ethical and legal

  1. Randomization in clinical trials: conclusions and recommendations.

    PubMed

    Lachin, J M; Matts, J P; Wei, L J

    1988-12-01

    The statistical properties of simple (complete) randomization, permuted-block (or simply blocked) randomization, and the urn adaptive biased-coin randomization are summarized. These procedures are contrasted to covariate adaptive procedures such as minimization and to response adaptive procedures such as the play-the-winner rule. General recommendations are offered regarding the use of complete, permuted-block, or urn randomization. In a large double-masked trial, any of these procedures may be acceptable. For a given trial, the relative merits of each procedure should be carefully weighed in relation to the characteristics of the trial. Important considerations are the size of the trial, overall as well as within the smallest subgroup to be employed in a subgroup-specific analysis, whether or not the trial is to be masked, and the resources needed to perform the proper randomization-based permutational analysis. PMID:3203526

  2. A General Framework for the Evaluation of Clinical Trial Quality

    PubMed Central

    Berger, Vance W.; Alperson, Sunny Y.

    2009-01-01

    Flawed evaluation of clinical trial quality allows flawed trials to thrive (get funded, obtain IRB approval, get published, serve as the basis of regulatory approval, and set policy). A reasonable evaluation of clinical trial quality must recognize that any one of a large number of potential biases could by itself completely invalidate the trial results. In addition, clever new ways to distort trial results toward a favored outcome may be devised at any time. Finally, the vested financial and other interests of those conducting the experiments and publishing the reports must cast suspicion on any inadequately reported aspect of clinical trial quality. Putting these ideas together, we see that an adequate evaluation of clinical quality would need to enumerate all known biases, update this list periodically, score the trial with regard to each potential bias on a scale of 0% to 100%, offer partial credit for only that which can be substantiated, and then multiply (not add) the component scores to obtain an overall score between 0% and 100%. We will demonstrate that current evaluations fall well short of these ideals. PMID:19463104

  3. Unfulfilled translation opportunities in industry sponsored clinical trials.

    PubMed

    Smed, Marie; Getz, Kenneth A

    2013-05-01

    Knowledge generated by site representatives through their participation in clinical trials is valuable for testing new products in use and obtaining final market approval. The leverage of this important knowledge is however challenged as the former direct relationships between in-house staff in the industry and site representatives are changing. The process of clinical trials has increased in complexity over the years, resulting in additional management layers. Besides an increase in internal management layers, sponsors often also outsource various tasks related to clinical trials to a CRO (Contract Research Organization) and thereby adding another link in the relationships between site and sponsor. These changes are intended to optimize the time-consuming and costly trial phases; however, there is a need to study whether valuable knowledge and experience is compromised in the process. Limited research exists on the full range of clinical practice insights obtained by investigators during and after clinical trials and how well these insights are transferred to study sponsors. This study explores the important knowledge-transfer processes between sites and sponsors and to what extent sites' knowledge gained in clinical trials is utilized by the industry. Responses from 451 global investigative site representatives are included in the study. The analysis of the extensive dataset reveals that the current processes of collaboration between sites and the industry restrict the leverage of valuable knowledge gained by physicians in the process of clinical trials. These restrictions to knowledge-transfer between site and sponsor are further challenged if CRO partners are integrated in the trial process. PMID:23454567

  4. Wrongful termination: lessons from the Geron clinical trial.

    PubMed

    Scott, Christopher Thomas; Magnus, David

    2014-12-01

    Geron Corporation is a publically traded company that launched a phase I clinical trial of a human embryonic stem cell-based therapy for spinal cord injury. The company enrolled the first patient in October 2010 and stopped the trial 1 year later. The fifth patient had been enrolled but not transplanted when the company announced the trial's end. After discussions with clinical staff and family, an agreement was reached to add her to the cohort and proceed with the transplant. Two and half years later, the research is still waiting to restart. With this background in mind, we discuss the major ethical and social questions raised by the Geron case. We offer recommendations for institutional review boards and clinical sites as they deliberate approvals of early-phase trials in frontier medicine. PMID:25298371

  5. Consent to clinical trials in anaesthesia.

    PubMed

    Montgomery, J E; Sneyd, J R

    1998-03-01

    In order to evaluate satisfaction with, and recollection of, the consent process, we sent a postal questionnaire to 204 patients who had taken part in one of six clinical trials. Three trials were multicentre commercial studies and three were 'in house'. The readability of the different patient information sheets was compared. Seventy-seven per cent of patients responded, of whom 82% remembered having an information sheet. Most (99%) thought this was easy to read and understand. Five patients claimed that they had felt pressurised to take part in the trials. Nearly all patients (97%) realised that participation was voluntary and that other treatment would not be affected; 83% knew they could have changed their minds. There were no differences in the response patterns between the patients taking part in the different trials although the patient information sheets produced by pharmaceutical companies were longer and more complex than the 'in hospital' variety. We conclude that increasing the amount and complexity of information does not alter patient satisfaction. Taken overall, patients were content with the way they were approached when asked for consent for clinical trials. PMID:9613266

  6. [Clinical trial of the new percutaneously active antirheumatic etofenamate. Summarising report (author's transl)].

    PubMed

    Heindl, I; Lorenz, D; Sieberns, S; Blumberger, W

    1977-01-01

    2-(2-Hydroxyethoxy)ethyl-N-(a,a,a-trifluoro-m-tolyl)anthranilate (etofenamate, Rheumon Gel), a percutaneously active antirheumatic containing etofenamate as active principle has been subjected to clinical studies in both hospitalized and out-patients in various types of rheumatic disease. These trials included double-blind studies against placebo gel, controlled comparative studies against two topical commercial products (ointmentI: combination of 2-hydroxyethyl salicylate and p-menthan-3-ol; ointment II: 3,5-dioxo-1,2-diphenyl-4-n-butylpyrazolidine) and open trials for efficacy and tolerance. Of the 760 patients taking part in the trials, 556 were treated with Rheumon Gel. PMID:144509

  7. Multi-armed Bandit Models for the Optimal Design of Clinical Trials: Benefits and Challenges

    PubMed Central

    Villar, Sofía S.; Bowden, Jack; Wason, James

    2016-01-01

    Multi-armed bandit problems (MABPs) are a special type of optimal control problem well suited to model resource allocation under uncertainty in a wide variety of contexts. Since the first publication of the optimal solution of the classic MABP by a dynamic index rule, the bandit literature quickly diversified and emerged as an active research topic. Across this literature, the use of bandit models to optimally design clinical trials became a typical motivating application, yet little of the resulting theory has ever been used in the actual design and analysis of clinical trials. To this end, we review two MABP decision-theoretic approaches to the optimal allocation of treatments in a clinical trial: the infinite-horizon Bayesian Bernoulli MABP and the finite-horizon variant. These models possess distinct theoretical properties and lead to separate allocation rules in a clinical trial design context. We evaluate their performance compared to other allocation rules, including fixed randomization. Our results indicate that bandit approaches offer significant advantages, in terms of assigning more patients to better treatments, and severe limitations, in terms of their resulting statistical power. We propose a novel bandit-based patient allocation rule that overcomes the issue of low power, thus removing a potential barrier for their use in practice. PMID:27158186

  8. Anticariogenic effect of xylitol versus fluoride - a quantitative systematic review of clinical trials.

    PubMed

    Mickenautsch, Steffen; Yengopal, Veerasamy

    2012-02-01

    The objective of this study was to appraise the clinical evidence and its bias risk regarding the anticariogenic effect of xylitol in comparison with that of fluoride. Databases were searched for clinical trials up to 18 March 2011. Article inclusion criteria were as follows: caries-related primary outcomes were tested; xylitol was compared with topical fluoride in some form; two-arm (or more) clinical trial including test/control group(s); prospective study design. Article exclusion criteria were as follows: no computable data were reported; test and control groups were not followed up in the same way; chewing gum was the main form of clinical application in either group. Individual continuous datasets were extracted from accepted articles. Selection and performance/detection bias were assessed. Sensitivity analysis was used to investigate attrition bias risk. Egger's regression and funnel plot was used to investigate publication bias risk. Twelve articles were included. Of these, six were accepted and six excluded, and 21 continuous datasets were extracted. Owing to the high clinical heterogeneity, no meta-analysis was performed. The addition of xylitol to existing fluoride regimes may be beneficial in the prevention of caries. However, all identified trials were limited by potential risk of selection, performance/detection and attrition bias. The funnel plot and Egger's regression results (-2.80; 95% confidence interval -4.01, -1.58; P = 0.0001) indicated possible publication bias risk. External fluoride access may have confounded the measured anticariogenic effect of xylitol. The evidence found contains a high risk of bias and may be limited by confounder effects. Future high-quality randomised controlled trials are needed in order to provide conclusive evidence on this topic. PMID:22251032

  9. Trends in global clinical trial registration: an analysis of numbers of registered clinical trials in different parts of the world from 2004 to 2013

    PubMed Central

    Viergever, Roderik F; Li, Keyang

    2015-01-01

    Objectives To analyse developments (and their causes) in the number and proportion of clinical trials that were registered in different parts of the world after the International Committee of Medical Journal Editors (ICMJE) announced in 2004 that it would require registration of clinical trials as a condition for publication. Setting The International Clinical Trials Registry Platform (ICTRP). Design The ICTRP database was searched for all clinical trials that were registered up to 31 December 2013. Results The ICTRP database contained data on 186 523 interventional clinical trials. The annual number of registered clinical trials increased from 3294 in 2004 to 23 384 in 2013. Relative to the number of clinical trial research publications, the global number of registered clinical trials increased fivefold between 2004 and 2013, rising particularly strongly between 2004 and 2005. In certain regions, especially Asia, the annual number of registered trials increased more gradually and continued to increase up to 2013. In India and Japan, two countries with marked but more gradual increases, these increases only happened after several local measures were implemented that encouraged and enforced registration. In most regions, there was a trend toward trials being registered at local registries. Conclusions Clinical trial registration has greatly improved transparency in clinical trial research. However, these improvements have not taken place equally in all parts of the world. Achieving compliance with registration requires a coalescence of global and local measures, and remains a key challenge in many countries. Poor quality of registered trial data and the inaccessibility of trial protocols, results and participant-level data further undermine the potential benefits of clinical trial registration. National and regional registries and the ICTRP have played a leading role in achieving the successes of trial registration to date and should be supported in addressing

  10. Adding a treatment arm to an ongoing clinical trial: a review of methodology and practice.

    PubMed

    Cohen, Dena R; Todd, Susan; Gregory, Walter M; Brown, Julia M

    2015-01-01

    Incorporating an emerging therapy as a new randomisation arm in a clinical trial that is open to recruitment would be desirable to researchers, regulators and patients to ensure that the trial remains current, new treatments are evaluated as quickly as possible, and the time and cost for determining optimal therapies is minimised. It may take many years to run a clinical trial from concept to reporting within a rapidly changing drug development environment; hence, in order for trials to be most useful to inform policy and practice, it is advantageous for them to be able to adapt to emerging therapeutic developments. This paper reports a comprehensive literature review on methodologies for, and practical examples of, amending an ongoing clinical trial by adding a new treatment arm. Relevant methodological literature describing statistical considerations required when making this specific type of amendment is identified, and the key statistical concepts when planning the addition of a new treatment arm are extracted, assessed and summarised. For completeness, this includes an assessment of statistical recommendations within general adaptive design guidance documents. Examples of confirmatory ongoing trials designed within the frequentist framework that have added an arm in practice are reported; and the details of the amendment are reviewed. An assessment is made as to how well the relevant statistical considerations were addressed in practice, and the related implications. The literature review confirmed that there is currently no clear methodological guidance on this topic, but that guidance would be advantageous to help this efficient design amendment to be used more frequently and appropriately in practice. Eight confirmatory trials were identified to have added a treatment arm, suggesting that trials can benefit from this amendment and that it can be practically feasible; however, the trials were not always able to address the key statistical considerations

  11. Developments in clinical trials: a Pharma Matters report.

    PubMed

    Arjona, A; Nuskey, B; Rabasseda, X; Arias, E

    2014-08-01

    As the pharmaceutical industry strives to meet the ever-increasing complexity of drug development, new technology in clinical trials has become a beacon of hope. With big data comes the promise of accelerated patient recruitment, real-time monitoring of clinical trials, bioinformatics empowerment of quicker phase progression, and the overwhelming benefits of precision medicine for select trials. Risk-based monitoring stands to benefit as well. With a strengthening focus on centralized data by the FDA and industry's transformative initiative, TransCelerate, a new era in trial risk mitigation has begun. The traditional method of intensive on-site monitoring is becoming a thing of the past as statistical, real-time analysis of site and trial-wide data provides the means to monitor with greater efficiency and effectiveness from afar. However, when it comes to big data, there are challenges that lie ahead. Patient privacy, commercial investment protection, technology woes and data variability are all limitations to be met with considerable thought. At the Annual Meeting of the American Academy of Dermatology this year, clinical trials on psoriasis, atopic dermatitis and other skin diseases were discussed in detail. This review of clinical research reports on novel therapies for psoriasis and atopic dermatitis reveals the impact of these diseases and the drug candidates that have been successful in phase II and III studies. Data-focused highlights of novel dermatological trials, as well as real-life big data approaches and an insight on the new methodology of risk-based monitoring, are all discussed in this edition of Developments in Clinical Trials. PMID:25187907

  12. Design of clinical trials for therapeutic cancer vaccines development.

    PubMed

    Mackiewicz, Jacek; Mackiewicz, Andrzej

    2009-12-25

    Advances in molecular and cellular biology as well as biotechnology led to definition of a group of drugs referred to as medicinal products of advanced technologies. It includes gene therapy products, somatic cell therapeutics and tissue engineering. Therapeutic cancer vaccines including whole cell tumor cells vaccines or gene modified whole cells belong to somatic therapeutics and/or gene therapy products category. The drug development is a multistep complex process. It comprises of two phases: preclinical and clinical. Guidelines on preclinical testing of cell based immunotherapy medicinal products have been defined by regulatory agencies and are available. However, clinical testing of therapeutic cancer vaccines is still under debate. It presents a serious problem since recently clinical efficacy of the number of cancer vaccines has been demonstrated that focused a lot of public attention. In general clinical testing in the current form is very expensive, time consuming and poorly designed what may lead to overlooking of products clinically beneficial for patients. Accordingly regulatory authorities and researches including Cancer Vaccine Clinical Trial Working Group proposed three regulatory solutions to facilitate clinical development of cancer vaccines: cost-recovery program, conditional marketing authorization, and a new development paradigm. Paradigm includes a model in which cancer vaccines are investigated in two types of clinical trials: proof-of-principle and efficacy. The proof-of-principle trial objectives are: safety; dose selection and schedule of vaccination; and demonstration of proof-of-principle. Efficacy trials are randomized clinical trials with objectives of demonstrating clinical benefit either directly or through a surrogate. The clinical end points are still under debate. PMID:19835869

  13. Imaging and Data Acquisition in Clinical Trials for Radiation Therapy.

    PubMed

    FitzGerald, Thomas J; Bishop-Jodoin, Maryann; Followill, David S; Galvin, James; Knopp, Michael V; Michalski, Jeff M; Rosen, Mark A; Bradley, Jeffrey D; Shankar, Lalitha K; Laurie, Fran; Cicchetti, M Giulia; Moni, Janaki; Coleman, C Norman; Deye, James A; Capala, Jacek; Vikram, Bhadrasain

    2016-02-01

    Cancer treatment evolves through oncology clinical trials. Cancer trials are multimodal and complex. Assuring high-quality data are available to answer not only study objectives but also questions not anticipated at study initiation is the role of quality assurance. The National Cancer Institute reorganized its cancer clinical trials program in 2014. The National Clinical Trials Network (NCTN) was formed and within it was established a Diagnostic Imaging and Radiation Therapy Quality Assurance Organization. This organization is Imaging and Radiation Oncology Core, the Imaging and Radiation Oncology Core Group, consisting of 6 quality assurance centers that provide imaging and radiation therapy quality assurance for the NCTN. Sophisticated imaging is used for cancer diagnosis, treatment, and management as well as for image-driven technologies to plan and execute radiation treatment. Integration of imaging and radiation oncology data acquisition, review, management, and archive strategies are essential for trial compliance and future research. Lessons learned from previous trials are and provide evidence to support diagnostic imaging and radiation therapy data acquisition in NCTN trials. PMID:26853346

  14. Creating clinical trial designs that incorporate clinical outcome assessments.

    PubMed

    Gilbert, Mark R; Rubinstein, Lawrence; Lesser, Glenn

    2016-03-01

    Clinical outcome assessments (COAs) are increasingly being used in determining the efficacy of new treatment regimens. This was typified in the recent use of a symptom-based instrument combined with an organ-based measure of response for the approval of ruxolitinib in myelofibrosis. There are challenges in incorporating these COAs into clinical trials, including designating the level of priority, incorporating these measures into a combined or composite endpoint, and dealing with issues related to compliance and interpretation of results accounting for missing data. This article describes the results of a recent panel discussion that attempted to address these issues and provide guidance to the incorporation of COAs into clinical trials, including novel statistical designs, so that the testing of new treatments in patients with cancers of the central nervous system can incorporate these important clinical endpoints. PMID:26989129

  15. Privacy and confidentiality in pragmatic clinical trials.

    PubMed

    McGraw, Deven; Greene, Sarah M; Miner, Caroline S; Staman, Karen L; Welch, Mary Jane; Rubel, Alan

    2015-10-01

    With pragmatic clinical trials, an opportunity exists to answer important questions about the relative risks, burdens, and benefits of therapeutic interventions. However, concerns about protecting the privacy of this information are significant and must be balanced with the imperative to learn from the data gathered in routine clinical practice. Traditional privacy protections for research uses of identifiable information rely disproportionately on informed consent or authorizations, based on a presumption that this is necessary to fulfill ethical principles of respect for persons. But frequently, the ideal of informed consent is not realized in its implementation. Moreover, the principle of respect for persons—which encompasses their interests in health information privacy—can be honored through other mechanisms. Data anonymization also plays a role in protecting privacy but is not suitable for all research, particularly pragmatic clinical trials. In this article, we explore both the ethical foundation and regulatory framework intended to protect privacy in pragmatic clinical trials. We then review examples of novel approaches to respecting persons in research that may have the added benefit of honoring patient privacy considerations. PMID:26374682

  16. Multi-modality neuro-monitoring: conventional clinical trial design.

    PubMed

    Georgiadis, Alexandros L; Palesch, Yuko Y; Zygun, David; Hemphill, J Claude; Robertson, Claudia S; Leroux, Peter D; Suarez, Jose I

    2015-06-01

    Multi-modal monitoring has become an integral part of neurointensive care. However, our approach is at this time neither standardized nor backed by data from randomized controlled trials. The goal of the second Neurocritical Care Research Conference was to discuss research priorities in multi-modal monitoring, what research tools are available, as well as the latest advances in clinical trial design. This section of the meeting was focused on how such a trial should be designed so as to maximize yield and avoid mistakes of the past. PMID:25832350

  17. Using phrases and document metadata to improve topic modeling of clinical reports.

    PubMed

    Speier, William; Ong, Michael K; Arnold, Corey W

    2016-06-01

    Probabilistic topic models provide an unsupervised method for analyzing unstructured text, which have the potential to be integrated into clinical automatic summarization systems. Clinical documents are accompanied by metadata in a patient's medical history and frequently contains multiword concepts that can be valuable for accurately interpreting the included text. While existing methods have attempted to address these problems individually, we present a unified model for free-text clinical documents that integrates contextual patient- and document-level data, and discovers multi-word concepts. In the proposed model, phrases are represented by chained n-grams and a Dirichlet hyper-parameter is weighted by both document-level and patient-level context. This method and three other Latent Dirichlet allocation models were fit to a large collection of clinical reports. Examples of resulting topics demonstrate the results of the new model and the quality of the representations are evaluated using empirical log likelihood. The proposed model was able to create informative prior probabilities based on patient and document information, and captured phrases that represented various clinical concepts. The representation using the proposed model had a significantly higher empirical log likelihood than the compared methods. Integrating document metadata and capturing phrases in clinical text greatly improves the topic representation of clinical documents. The resulting clinically informative topics may effectively serve as the basis for an automatic summarization system for clinical reports. PMID:27109931

  18. A Model of Placebo Response in Antidepressant Clinical Trials

    PubMed Central

    Rutherford, Bret R; Roose, Steven P.

    2012-01-01

    Placebo response in clinical trials of antidepressant medications is substantial and increasing. High placebo response rates hamper efforts to detect signals of efficacy for new antidepressant medications, contributing to more failed trials and delaying the delivery of new treatments to market. Media reports seize upon increasing placebo response and modest advantages for active drugs as reasons to question the value of antidepressant medication, which may further stigmatize treatments for depression and dissuade patients from accessing mental health care. Conversely, enhancing the factors responsible for placebo response may represent a strategy for improving available treatments for Major Depressive Disorder. A conceptual framework describing the causes of placebo response is needed in order to develop strategies for minimizing placebo response in clinical trials, maximizing placebo response in clinical practice, and talking with depressed patients about the risks and benefits of antidepressant medications. This review examines contributors to placebo response in antidepressant clinical trials and proposes an explanatory model. Research aimed at reducing placebo response should focus on limiting patient expectancy and the intensity of therapeutic contact in antidepressant clinical trials, while the optimal strategy in clinical practice may be to combine active medication with a presentation and level of therapeutic contact that enhances treatment response. PMID:23318413

  19. HbA1c as a Predictor of Diabetes and as an Outcome in the Diabetes Prevention Program: A Randomized Clinical Trial

    PubMed Central

    2015-01-01

    OBJECTIVE Glycated hemoglobin (HbA1c), a standard measure of chronic glycemia for managing diabetes, has been proposed to diagnose diabetes and identify people at risk. The Diabetes Prevention Program (DPP) was a 3.2-year randomized clinical trial of preventing type 2 diabetes with a 10-year follow-up study, the DPP Outcomes Study (DPPOS). We evaluated baseline HbA1c as a predictor of diabetes and determined the effects of treatments on diabetes defined by an HbA1c ≥6.5% (48 mmol/mol). RESEARCH DESIGN AND METHODS We randomized 3,234 nondiabetic adults at high risk of diabetes to placebo, metformin, or intensive lifestyle intervention and followed them for the development of diabetes as diagnosed by fasting plasma glucose (FPG) and 2-h postload glucose (2hPG) concentrations (1997 American Diabetes Association [ADA] criteria). HbA1c was measured but not used for study eligibility or outcomes. We now evaluate treatment effects in the 2,765 participants who did not have diabetes at baseline according to FPG, 2hPG, or HbA1c (2010 ADA criteria). RESULTS Baseline HbA1c predicted incident diabetes in all treatment groups. Diabetes incidence defined by HbA1c ≥6.5% was reduced by 44% by metformin and 49% by lifestyle during the DPP and by 38% by metformin and 29% by lifestyle throughout follow-up. Unlike the primary DPP and DPPOS findings based on glucose criteria, metformin and lifestyle were similarly effective in preventing diabetes defined by HbA1c. CONCLUSIONS HbA1c predicted incident diabetes. In contrast to the superiority of the lifestyle intervention on glucose-defined diabetes, metformin and lifestyle interventions had similar effects in preventing HbA1c-defined diabetes. The long-term implications for other health outcomes remain to be determined. PMID:25336746

  20. Clinical Trial Design Issues in Systemic Sclerosis: an Update.

    PubMed

    Gordon, Jessica K; Domsic, Robyn T

    2016-06-01

    Systemic sclerosis (scleroderma, SSc) is a multisystem disease characterized by vasculopathy, autoimmunity, and fibrosis. SSc has the highest disease-related mortality rate among the rheumatologic illnesses. In the USA, there remains no FDA-approved therapy. As our understanding of SSc pathogenesis improves, targeted therapies interrupting key pathways and mediators will be studied in clinical trials. However, clinical trials in SSc are fraught with challenges. Validated clinical outcome measures do not exist for all disease manifestations. It can be difficult to discern disease activity from damage. SSc is highly heterogeneous, with multiple different phenotypes, and predicting who will have progressive disease is not currently well understood. Biomarkers are in early stages of development and do not represent surrogate outcomes at this time. Given that SSc is uncommon, studies of similar disease aspects or populations can lead to competition for patients. This review will focus on current issues in SSc clinical trial design. PMID:27146381

  1. Reporting, access, and transparency: better infrastructure of clinical trials.

    PubMed

    Antonelli, Massimo; Mercurio, Giovanna

    2009-01-01

    Open access to information in medical science and adequate reporting of clinical trials may allow investigators and editors to recognize bias in study designs and avoid unnecessary duplication of efforts. Unfortunately, most of clinical trials are very expensive and are often supported by industries that may have financial reasons to hide or partially disclose results. However, investigators and editors have a greater interest in publishing results that can immediately change clinical practice rather than negative results, thus contributing to facilitate publication biases. Several years ago, legislation in several countries mandated the registration of clinical trials as an effective means of promoting information access and full transparency in medical research. However, comprehensive registers have not been adequately supported by law, particularly in Europe, where legislation has ironically contributed to fragmented research, and dampened its competitiveness and productivity. In this context, appropriate strategies help to protect the independence of academic research and ensure full transparency in medical science. PMID:19104221

  2. Are We Ready to Abandon Placebo in Randomised Clinical Trials for Inflammatory Bowel Disease? Pros and Cons.

    PubMed

    Danese, Silvio; Schabel, Elmer; Masure, Johan; Plevy, Scott; Schreiber, Stefan

    2016-09-01

    The role of placebo in clinical trials for drug development in inflammatory bowel disease [IBD] was the topic of a panel discussion held during the 10th Congress of the European Crohn's and Colitis Organisation [ECCO], in Barcelona, Spain, in 2015. Panellists discussed a number of issues around placebo-controlled trials in IBD, noting issues such as difficulties with recruitment, leading to less then representative patient populations in clinical studies. It was noted that, whereas the easiest answer may be to drop placebo, it is much more complicated than that. The relevance of placebo is affected by a number of factors, including the phase of the trial, as well as the nature of the drug. In most cases where placebo has been left out in drug development, it has been for trials involving a new formulation, a new dosing schedule, or a biosimilar, for example. The panel agreed that placebo-controlled trials are of particular importance early in the development programme, perhaps not so much in phase III, although placebo is important for monitoring safety. The current trial paradigm, in which patients remain on a plethora of, likely ineffective and toxic, background medication, was also questioned. The applicability of placebo in the paediatric population was also discussed. The overall consensus from this panel discussion was that placebo is still necessary in clinical trials in inflammatory bowel disease, but there remain questions as to how and when placebo should be used. PMID:27604979

  3. Clinical Trials For Cytoprotection In Stroke

    PubMed Central

    Labiche, Lise A.; Grotta, James C.

    2004-01-01

    Summary: To date, many cytoprotective drugs have reached the stage of pivotal phase 3 efficacy trials in acute stroke patients. (Table 1) Unfortunately, throughout the neuroprotective literature, the phrase “failure to demonstrate efficacy” prevails as a common thread among the many neutral or negative trials, despite the largely encouraging results encountered in preclinical studies. The reasons for this discrepancy are multiple, and have been discussed by Dr. Zivin in his review. Many of the recent trials have addressed deficiencies of the previous ones with more rigorous trial design, including more specific patient selection criteria (ensure homogeneity of stroke location and severity), stratified randomization algorithms (time-to-treat), narrowed therapeutic time-window and pharmacokinetic monitoring. Current trials have also incorporated biologic surrogate markers of toxicity and outcome such as drug levels and neuroimaging. Lastly, multi-modal therapies and coupled cytoprotection/reperfusion strategies are being investigated to optimize tissue salvage. This review will focus on individual therapeutic strategies and we will emphasize what we have learned from these trials both in terms of trial design and the biologic effect (or lack thereof) of these agents. PMID:15717007

  4. Patient and physician attitudes regarding clinical trials in neurofibromatosis 1.

    PubMed

    McQueen, Mary; MacCollin, Mia; Gusella, James; Plotkin, Scott R

    2008-12-01

    Neurofibromatosis 1 (NF1) is a multisystem genetic disorder that primarily affects the skin (freckling and café-au-lait macules), nervous system (neurofibromas, optic gliomas, and learning disabilities), and skeletal system (pseudoarthroses). The interest in pharmacological intervention for patients with NF1 has grown in recent years. However, little is known about the attitudes and priorities of patients, families, and physicians regarding participation in clinical trials. We surveyed 74 adult patients or parents of patients with NF1 and 69 care providers participating in a neurofibromatosis clinic to assess their willingness to participate in clinical trials and their opinions about which conditions they thought were most important to treat. Both patients and care providers are willing to participate in clinical trials for NF1 and both groups rate malignant peripheral nerve sheath tumors as the most urgent for new treatments. There are concordant views among patients and physicians concerning clinical trials for NF1, and patients do not dismiss participation in placebo-controlled trials. Neuroscience nurses are poised to facilitate the research process from conception through implementation as they take the viewpoints of our study populations into consideration. PMID:19170300

  5. Children's behavioral pain reactions during local anesthetic injection using cotton-roll vibration method compared with routine topical anesthesia: A randomized controlled trial

    PubMed Central

    Bagherian, Ali; Sheikhfathollahi, Mahmood

    2016-01-01

    Background: Topical anesthesia has been widely advocated as an important component of atraumatic administration of intraoral local anesthesia. The aim of this study was to use direct observation of children's behavioral pain reactions during local anesthetic injection using cotton-roll vibration method compared with routine topical anesthesia. Materials and Methods: Forty-eight children participated in this randomized controlled clinical trial. They received two separate inferior alveolar nerve block or primary maxillary molar infiltration injections on contralateral sides of the jaws by both cotton-roll vibration (a combination of topical anesthesia gel, cotton roll, and vibration for physical distraction) and control (routine topical anesthesia) methods. Behavioral pain reactions of children were measured according to the author-developed face, head, foot, hand, trunk, and cry (FHFHTC) scale, resulting in total scores between 0 and 18. Results: The total scores on the FHFHTC scale ranged between 0-5 and 0-10 in the cotton-roll vibration and control methods, respectively. The mean ± standard deviation values of total scores on FHFHTC scale were lower in the cotton-roll vibration method (1.21 ± 1.38) than in control method (2.44 ± 2.18), and this was statistically significant (P < 0.001). Conclusion: It may be concluded that the cotton-roll vibration method can be more helpful than the routine topical anesthesia in reducing behavioral pain reactions in children during local anesthesia administration. PMID:27274349

  6. Existing data sources for clinical epidemiology: Aarhus University Clinical Trial Candidate Database, Denmark.

    PubMed

    Nørrelund, Helene; Mazin, Wiktor; Pedersen, Lars

    2014-01-01

    Denmark is facing a reduction in clinical trial activity as the pharmaceutical industry has moved trials to low-cost emerging economies. Competitiveness in industry-sponsored clinical research depends on speed, quality, and cost. Because Denmark is widely recognized as a region that generates high quality data, an enhanced ability to attract future trials could be achieved if speed can be improved by taking advantage of the comprehensive national and regional registries. A "single point-of-entry" system has been established to support collaboration between hospitals and industry. When assisting industry in early-stage feasibility assessments, potential trial participants are identified by use of registries to shorten the clinical trial startup times. The Aarhus University Clinical Trial Candidate Database consists of encrypted data from the Danish National Registry of Patients allowing an immediate estimation of the number of patients with a specific discharge diagnosis in each hospital department or outpatient specialist clinic in the Central Denmark Region. The free access to health care, thorough monitoring of patients who are in contact with the health service, completeness of registration at the hospital level, and ability to link all databases are competitive advantages in an increasingly complex clinical trial environment. PMID:24748818

  7. Existing data sources for clinical epidemiology: Aarhus University Clinical Trial Candidate Database, Denmark

    PubMed Central

    Nørrelund, Helene; Mazin, Wiktor; Pedersen, Lars

    2014-01-01

    Denmark is facing a reduction in clinical trial activity as the pharmaceutical industry has moved trials to low-cost emerging economies. Competitiveness in industry-sponsored clinical research depends on speed, quality, and cost. Because Denmark is widely recognized as a region that generates high quality data, an enhanced ability to attract future trials could be achieved if speed can be improved by taking advantage of the comprehensive national and regional registries. A “single point-of-entry” system has been established to support collaboration between hospitals and industry. When assisting industry in early-stage feasibility assessments, potential trial participants are identified by use of registries to shorten the clinical trial startup times. The Aarhus University Clinical Trial Candidate Database consists of encrypted data from the Danish National Registry of Patients allowing an immediate estimation of the number of patients with a specific discharge diagnosis in each hospital department or outpatient specialist clinic in the Central Denmark Region. The free access to health care, thorough monitoring of patients who are in contact with the health service, completeness of registration at the hospital level, and ability to link all databases are competitive advantages in an increasingly complex clinical trial environment. PMID:24748818

  8. Gateways to clinical trials. December 2008.

    PubMed

    Tomillero, A; Moral, M A

    2008-12-01

    Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables have been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: AAV1/SERCA2a; Abatacept, ABT-263, Adalimumab, Aflibercept, Afobazole, Aliskiren fumarate, Anakinra, Atazanavir/ritonavir, Aviscumine, Axitinib, Azacitidine; Bevacizumab, Biphasic insulin aspart, Bortezomib, Briobacept; Carmoterol hydrochloride, CCX-282, Ceftobiprole medocaril, Certolizumab pegol, Cetuximab; Darifenacin hydrobromide, Dasatinib, Denosumab, Doripenem, Duloxetine hydrochloride; E-7080, Epratuzumab, Erlotinib hydrochloride, Everolimus, Exenatide, Ezetimibe/simvastatin; Gefitinib, Golimumab; gamma-Hydroxybutyrate sodium; Imatinib mesylate, Insulin detemir, Insulin glulisine, IVX-0142; Laquinimod sodium, Linezolid, Lopinavir/ritonavir; Ocrelizumab, Omalizumab; Parecoxib sodium, Pemetrexed disodium, Pregabalin; Rosuvastatin calcium, Rotigotine; Sorafenib, Sugammadex sodium; Tapentadol hydrochloride, Tenofovir disoproxil fumarate/emtricitabine, Tocilizumab; Ularitide, Ustekinumab; Valsartan/amlodipine besylate, Varenicline tartrate, Vatalanib succinate, Vildagliptin, Vorinostat. PMID:19271026

  9. Women’s health and clinical trials

    PubMed Central

    Schiebinger, Londa

    2003-01-01

    Women have traditionally been underrepresented in clinical trials. In order to translate recent advances in our understanding of the molecular and physiological bases of sex differences into new therapeutics and health practices, sound sex-specific clinical data are imperative. Since the founding of the Office of Research on Women’s Health within the Office of the Director at the NIH in 1990, inequities in federally funded biomedical research, diagnosis, and treatment of diseases affecting women in the US have been reviewed. Discussed herein is the evolution of gender-related research innovations, primarily within the last decade, and strategies and challenges involved in the success of this recent development. PMID:14523031

  10. New clinical trials for nonmotor manifestations of Parkinson's disease.

    PubMed

    Schrag, Anette; Sauerbier, Anna; Chaudhuri, Kallol Ray

    2015-09-15

    Nonmotor manifestations in Parkinson's disease (PD) encompass a range of clinical features, including neuropsychiatric problems, autonomic dysfunction, sleep disorders, fatigue, and pain. Despite their importance for patients' quality of life, the evidence base for their treatment is relatively sparse. Nevertheless, the last few years have seen a number of new trials starting that specifically address nonmotor features as an outcome measure in clinical trials. Large randomized, controlled trials in the last 3 years reported improvement of psychosis with the new selective serotonin 5-HT2A inverse agonist pimavanserin and of postural hypotension with the oral norepinephrine precursor droxidopa. Smaller new randomized, controlled trials support the effectiveness of Deep Brain Stimulation and opiates for pain, of rivastigmine for apathy and piribedil for apathy post-DBS, group cognitive behavioral therapy for depression and/or anxiety, continuous positive airway pressure for sleep apnea in PD and doxepin for insomnia, and of solifenacin succinate and transcutaneous tibial nerve stimulation for urinary symptoms. A number of new smaller or open trials as well as post-hoc analyses of randomized, controlled trials have suggested usefulness of other treatments, and new randomized, controlled trials are currently ongoing. PMID:26371623

  11. Clinical trials in palliative care: an ethical evaluation.

    PubMed

    Janssens, R; Gordijn, B

    2000-08-01

    On first sight, clinical trials do not seem to fit well within the concept of palliative care. In palliative care, the needs and wishes of the patient set the norm while participation in experimental trials is potentially harmful for the patient. The dilemma seems hard to solve as optimal care for the dying and improvement of treatment for future patients are both imperative. Yet, the one seems to exclude the other. However, on closer examination it becomes less evident that clinical trials in palliative care confront us with an unsolvable dilemma. Some patients' lives may gain meaning through participation in trials out of solidarity with future patients. In order to clarify this, the notions of authenticity and hope can be illuminative. PMID:10900367

  12. The FDA and designing clinical trials for chronic cutaneous ulcers.

    PubMed

    Maderal, Andrea D; Vivas, Alejandra C; Eaglstein, William H; Kirsner, Robert S

    2012-12-01

    Treatment of chronic wounds can present a challenge, with many patients remaining refractory to available advanced therapies. As such, there is a strong need for the development of new products. Unfortunately, despite this demand, few new wound-related drugs have been approved over the past decade. This is in part due to unsuccessful clinical trials and subsequent lack of Food and Drug Administration (FDA) approval. In this article, we discuss the FDA approval process, how it relates to chronic wound trials, common issues that arise, and how best to manage them. Additionally, problems encountered specific to diabetic foot ulcers (DFU) and venous leg ulcers (VLU) are addressed. Careful construction of a clinical trial is necessary in order to achieve the best possible efficacy outcomes and thereby, gain FDA approval. How to design an optimal trial is outlined. PMID:23063664

  13. Formulation and clinical evaluation of topical dosage forms of Indian Penny Wort, walnut and turmeric in eczema.

    PubMed

    Khiljee, Sonia; Rehman, Nisarur; Khiljee, Tanzila; Loebenberg, Raimar; Ahmad, Rao Saeed

    2015-11-01

    Eczema is characterized by itching, lichenification, scaling, oedema and erythema. Current management strategies include corticosteroids, which are limited due to side effects. Many herbal remedies are used traditionally but unfortunately have not been validated in controlled clinical trials. Three popular traditional treatments of eczema include Indian pennywort, Walnut and Turmeric. In this study three topical formulations (micro emulsion, gel and ointment) were prepared from extracts of Indian pennywort, Walnut and Turmeric. These formulations were monitored for stability for a period of three months. Controlled clinical trials were conducted on 360 eczema patients. Clinical parameters observed were degree of erythema, oedema, scaling, itching and lichenification. Effects of each formulation on these clinical parameters were compared with placebo formulations. Micro emulsion formulations in all cases proved to be more effective in reducing semi quantitative scores of erythema and oedema. Itching was relieved more by gel formulation. The ointment showed more efficacy towards scaling and lichenification. Comparison of the effects of placebo and the specific formulations was performed by chi-square statistics and found to be highly significant. In summary it is concluded that all the formulations could be used as promising source for treatment of eczema. PMID:26639477

  14. Risk of discontinuation of Advanced Therapy Medicinal Products clinical trials

    PubMed Central

    Hanna, Eve; Rémuzat, Cecile; Auquier, Pascal; Toumi, Mondher

    2016-01-01

    Objective Advanced therapy medicinal products (ATMPs) constitute a class of innovative products that encompasses gene therapy, somatic cell therapy, and tissue-engineered products (TEP). There is an increased investment of commercial and non-commercial sponsors in this field and a growing number of ATMPs randomized clinical trials (RCT) and patients enrolled in such trials. RCT generate data to prove the efficacy of a new therapy, but the discontinuation of RCTs wastes scarce resources. Our objective is to identify the number and characteristics of discontinued ATMPs trials in order to evaluate the rate of discontinuation. Methods We searched for ATMPs trials conducted between 1999 to June 2015 using three databases, which are Clinicaltrials.gov, the International Clinical Trials Registry Platform (ICTRP), and the EU Drug Regulating Authorities Clinical Trials (EudraCT). We selected the ATMPs trials after elimination of the duplicates. We identified the disease areas and the sponsors as commercial or non-commercial organizations. We classified ATMPs by type and trial status, that is, ongoing, completed, terminated, discontinued, and prematurely ended. Then, we calculated the rate of discontinuation. Results Between 1999 and June 2015, 143 withdrawn, terminated, or prematurely ended ATMPs clinical trials were identified. Between 1999 and June 2013, 474 ongoing and completed clinical trials were identified. Therefore, the rate of discontinuation of ATMPs trials is 23.18%, similar to that for non-ATMPs drugs in development. The probability of discontinuation is, respectively, 27.35, 16.28, and 16.34% for cell therapies, gene therapies, and TEP. The highest discontinuation rate is for oncology (43%), followed by cardiology (19.2%). It is almost the same for commercial and non-commercial sponsors; therefore, the discontinuation reason may not be financially driven. Conclusion No failure risk rate per development phase is available for ATMPs. The discontinuation rate may

  15. The protection of patients' rights in clinical trials.

    PubMed

    Czarkowski, Marek

    2006-01-01

    The Helsinki Declaration is a very important document regarding the protection of patients' rights in clinical trials and one of the fundamental sources of operational principles for every ethics committee. Although they have been updated, the international guidelines for ethics committees continually fail to address certain issues pertaining to the protection of patients' rights in clinical trials. These issues include, most significantly, the method of electing ethics committees (a free, secret ballot should be preferred to direct appointment), the avoidance of conflict of interest during the election of ethics committee members, and the necessary insurance coverage for the participants of clinical trials. Polish law should, on the other hand, be developed in such way as to not limit the effectiveness of ethics committees in protecting patients' rights in clinical trials. The ideal solution would be to draft a uniform law concerning not only clinical trials, but all medical experiments. The opinions of experts who have been reviewing medical research projects for several years may prove to be especially valuable in this setting. PMID:16501654

  16. Phase I/II Clinical Trial of Encapsulated, Cytochrome P450 Expressing Cells as Local Activators of Cyclophosphamide to Treat Spontaneous Canine Tumours

    PubMed Central

    Michałowska, Monika; Winiarczyk, Stanislaw; Adaszek, Łukasz; Łopuszyński, Wojciech; Grądzki, Zbigniew; Salmons, Brian; Günzburg, Walter H.

    2014-01-01

    Based upon promising preclinical studies, a clinical trial was performed in which encapsulated cells overexpressing cytochrome P450 enzyme isoform 2B1 were implanted around malignant mammary tumours arising spontaneously in dogs. The dogs were then given cyclophosphamide, one of the standard chemotherapeutic agents used for the treatment of mammary tumours. The dogs were assessed for a number of clinical parameters as well as for reduction in tumour size. The treatment was well tolerated with no evidence of adverse reactions or side effects being associated with the administration of the encapsulated cells. Reductions in tumour size of more than 50% were observed for 6 out of the 11 tumours analysed while 5 tumours showing minor responses, i.e. stable disease. In contrast, the tumours that received cyclophosphamide alone showed only stable disease. Taken together, this data suggests that encapsulated cytochrome P450 expressing cells combined with chemotherapy may be useful in the local treatment of a number of dog mammary tumours and support the performance of further clinical studies to evaluate this new treatment. PMID:25028963

  17. Progesterone neuroprotection: The background of clinical trial failure.

    PubMed

    Schumacher, Michael; Denier, Christian; Oudinet, Jean-Paul; Adams, David; Guennoun, Rachida

    2016-06-01

    Since the first pioneering studies in the 1990s, a large number of experimental animal studies have demonstrated the neuroprotective efficacy of progesterone for brain disorders, including traumatic brain injury (TBI). In addition, this steroid has major assets: it easily crosses the blood-brain-barrier, rapidly diffuses throughout the brain and exerts multiple beneficial effects by acting on many molecular and cellular targets. Moreover, progesterone therapies are well tolerated. Notably, increased brain levels of progesterone are part of endogenous neuroprotective responses to injury. The hormone thus emerged as a particularly promising protective candidate for TBI and stroke patients. The positive outcomes of small Phase 2 trials aimed at testing the safety and potential protective efficacy of progesterone in TBI patients then provided support and guidance for two large, multicenter, randomized and placebo-controlled Phase 3 trials, with more than 2000 TBI patients enrolled. The negative outcomes of both trials, named ProTECT III and SyNAPSE, came as a big disappointment. If these trials were successful, progesterone would have become the first efficient neuroprotective drug for brain-injured patients. Thus, progesterone has joined the numerous neuroprotective candidates that have failed in clinical trials. The aim of this review is a reappraisal of the preclinical animal studies, which provided the proof of concept for the clinical trials, and we critically examine the design of the clinical studies. We made efforts to present a balanced view of the strengths and limitations of the translational studies and of some serious issues with the clinical trials. We place particular emphasis on the translational value of animal studies and the relevance of TBI biomarkers. The probability of failure of ProTECT III and SyNAPSE was very high, and we present them within the broader context of other unsuccessful trials. PMID:26598278

  18. Aspects of vulnerable patients and informed consent in clinical trials

    PubMed Central

    Kuthning, Maria; Hundt, Ferdinand

    2013-01-01

    Scope: To discuss the rationale behind informed consent in clinical trials focusing on vulnerable patients from a European and German viewpoint. Methods: Scientific literature search via PubMed, Medline, Google. Results: Voluntary informed consent is the cornerstone of policies regulating clinical trials. To enroll a patient into a clinical trial without having obtained written and signed consent is to be considered as a serious issue in the conduct of a clinical trial. Development of ethical guidance for physicians started before Christ Era with the Hippocratic Oath. Main function of consent, as articulated in all guidelines developed for clinical research, is to facilitate an individual’s freedom of choice, respect autonomy, and thus to ensure welfare of the participants in clinical trials. Minors are unable to provide legally binding informed consent, this issue is addressed through a combination of parental permission and minor’s assent. Illiteracy is a critical problem that affects all corners of our earth; it has no boundaries and exists among every race and ethnicity, age group, and economic class. New strategies to improve communication with patients including the use of videotapes or animated cartoon illustrations could be taught. Finally the time with the potential participant seems to be the best way to improve understanding. Conclusion: Discovery of life saving and life enhancing new treatments requires partnership that is based on good communication and trust between patients and researchers, sponsors, ethics committees, authorities, lawyers and politicians so that vulnerable patients can benefit from the results of well controlled clinical trials. PMID:23346043

  19. Improving Alzheimer's disease phase II clinical trials.

    PubMed

    Greenberg, Barry D; Carrillo, Maria C; Ryan, J Michael; Gold, Michael; Gallagher, Kim; Grundman, Michael; Berman, Robert M; Ashwood, Timothy; Siemers, Eric R

    2013-01-01

    Over the past 30 years, many drugs have been studied as possible treatments for Alzheimer's disease, but only four have demonstrated sufficient efficacy to be approved as treatments, of which three are in the same class. This lack of success has raised questions both in the pharmaceutical industry and academia about the future of Alzheimer's disease therapy. The high cost and low success rate of drug development across many disease areas can be attributed, in large part, to late-stage clinical failures (Schachter and Ramoni, Nat Rev Drug Discov 2007;6:107-8). Thus, identifying in phase II, or preferably phase I, drugs that are likely to fail would have a dramatic impact on the costs associated with developing new drugs. With this in mind, the Alzheimer's Association convened a Research Roundtable on June 23 and 24, 2011, in Washington, DC, bringing together scientists from academia, industry, and government regulatory agencies to discuss strategies for improving the probability of phase II trial results predicting success when considering the go/no-go decision-making process leading to the initiation of phase III. PMID:23164548

  20. Critical care clinical trials: getting off the roller coaster.

    PubMed

    Goodwin, Andrew J

    2012-09-01

    Optimizing care in the ICU is an important goal. The heightened severity of illness in patients who are critically ill combined with the tremendous costs of critical care make the ICU an ideal target for improvement in outcomes and efficiency. Incorporation of evidence-based medicine into everyday practice is one method to optimize care; however, intensivists have struggled to define optimal practices because clinical trials in the ICU have yielded conflicting results. This article reviews examples where such conflicts have occurred and explores possible causes of these discrepant data as well as strategies to better use critical care clinical trials in the future. PMID:22948575

  1. Clinical trials in Huntington's disease: Interventions in early clinical development and newer methodological approaches.

    PubMed

    Sampaio, Cristina; Borowsky, Beth; Reilmann, Ralf

    2014-09-15

    Since the identification of the Huntington's disease (HD) gene, knowledge has accumulated about mechanisms directly or indirectly affected by the mutated Huntingtin protein. Transgenic and knock-in animal models of HD facilitate the preclinical evaluation of these targets. Several treatment approaches with varying, but growing, preclinical evidence have been translated into clinical trials. We review major landmarks in clinical development and report on the main clinical trials that are ongoing or have been recently completed. We also review clinical trial settings and designs that influence drug-development decisions, particularly given that HD is an orphan disease. In addition, we provide a critical analysis of the evolution of the methodology of HD clinical trials to identify trends toward new processes and endpoints. Biomarker studies, such as TRACK-HD and PREDICT-HD, have generated evidence for the potential usefulness of novel outcome measures for HD clinical trials, such as volumetric imaging, quantitative motor (Q-Motor) measures, and novel cognitive endpoints. All of these endpoints are currently applied in ongoing clinical trials, which will provide insight into their reliability, sensitivity, and validity, and their use may expedite proof-of-concept studies. We also outline the specific opportunities that could provide a framework for a successful avenue toward identifying and efficiently testing and translating novel mechanisms of action in the HD field. PMID:25216371

  2. Remote ischemic conditioning: a clinical trial's update.

    PubMed

    Candilio, Luciano; Hausenloy, Derek J; Yellon, Derek M

    2011-01-01

    Coronary artery disease (CAD) is the leading cause of death and disability worldwide, and early and successful restoration of myocardial reperfusion following an ischemic event is the most effective strategy to reduce final infarct size and improve clinical outcome. This process can, however, induce further myocardial damage, namely acute myocardial ischemia-reperfusion injury (IRI) and worsen clinical outcome. Therefore, novel therapeutic strategies are required to protect the myocardium against IRI in patients with CAD. In this regard, the endogenous cardioprotective phenomenon of "ischemic conditioning," in which the heart is put into a protected state by subjecting it to one or more brief nonlethal episodes of ischemia and reperfusion, has the potential to attenuate myocardial injury during acute IRI. Intriguingly, the heart can be protected in this manner by applying the "ischemic conditioning" stimulus to an organ or tissue remote from the heart (termed remote ischemic conditioning or RIC). Furthermore, the discovery that RIC can be noninvasively applied using a blood pressure cuff on the upper arm to induce brief episodes of nonlethal ischemia and reperfusion in the forearm has greatly facilitated the translation of RIC into the clinical arena. Several recently published proof-of-concept clinical studies have reported encouraging results with RIC, and large multicenter randomized clinical trials are now underway to investigate whether this simple noninvasive and virtually cost-free intervention has the potential to improve clinical outcomes in patients with CAD. In this review article, we provide an update of recently published and ongoing clinical trials in the field of RIC. PMID:21821533

  3. Clinical Trial and Research Study Recruiters' Verbal Communication Behaviors.

    PubMed

    Morgan, Susan E; Mouton, Ashton; Occa, Aurora; Potter, Jonell

    2016-07-01

    The lack of accrual to research studies and clinical trials is a persistent problem with serious consequences: Advances in medical science depend on the participation of large numbers of people, including members of minority and underserved populations. The current study examines a critical determinant of accrual: the approach of patients by professional recruiters who request participation in research studies and clinical trials. Findings indicate that recruiters use a number of verbal strategies in the communication process, including translating study information (such as simplifying, using examples, and substituting specific difficult or problematic words), using linguistic reframing or metaphors, balancing discussions of research participation risks with benefits, and encouraging potential participants to ask questions. The identification of these verbal strategies can form the basis of new communication protocols that will help medical and nonmedical professionals communicate more clearly and effectively with patients and other potential participants about research studies and clinical trials, which should lead to increased accrual in the future. PMID:27259754

  4. Patient-reported outcomes in lupus clinical trials with biologics.

    PubMed

    Annapureddy, N; Devilliers, H; Jolly, M

    2016-09-01

    Therapeutic advances in systemic lupus erythematosus (SLE) are greatly needed. Despite advances in our knowledge of pathogenesis of the disease and targets, treatment remains a significant challenge. Finding effective and relatively safe medications remains one of the top priorities. SLE significantly impairs quality of life (QoL), and patient-reported outcomes (PROs) measure a unique aspect of the disease not captured by disease activity. Inclusion of PRO measurements is encouraged in SLE clinical trials, as they allow capturing benefits of a proposed intervention in language patients can relate to and in areas deemed pertinent and important to and by patients. Availability of patient-reported and patient-centric clinical trials data may facilitate patients in informed and shared decision making, and allow for comparative cost-effectiveness evaluation for future resource allocation and reimbursements. Herein we review clinical trials with biologic therapies wherein PRO tools were included in the study design. PMID:27497256

  5. Clinical Trials Methods for Evaluation of Potential Reduced Exposure Products

    PubMed Central

    Hatsukami, Dorothy K.; Hanson, Karen; Briggs, Anna; Parascandola, Mark; Genkinger, Jeanine M.; O'Connor, Richard; Shields, Peter

    2009-01-01

    Potential reduced exposure tobacco products (PREPs) may have promise in reducing tobacco-related morbidity or mortality or may promote greater harm to individuals or the population. Critical to determining the risks or benefits from these products are valid human clinical trial PREP assessment methods. Assessment involves determining the effects of these products on biomarkers of exposure and of effect, which serve as proxies for harm, and assessing the potential for consumer uptake and abuse of the product. This article raises the critical methodological issues associated with PREP assessment, reviews the methods that have been used to assess PREPs, and describes the strengths and limitations of these methods. Additionally, recommendations for clinical trials PREP assessment methods and future research directions in this area based on this review and on the deliberations from a National Cancer Institute sponsored Clinical Trials PREP Methods Workshop are provided. PMID:19959672

  6. Wrongful Termination: Lessons From the Geron Clinical Trial

    PubMed Central

    Magnus, David

    2014-01-01

    SUMMARY Geron Corporation is a publically traded company that launched a phase I clinical trial of a human embryonic stem cell-based therapy for spinal cord injury. The company enrolled the first patient in October 2010 and stopped the trial 1 year later. The fifth patient had been enrolled but not transplanted when the company announced the trial’s end. After discussions with clinical staff and family, an agreement was reached to add her to the cohort and proceed with the transplant. Two and half years later, the research is still waiting to restart. With this background in mind, we discuss the major ethical and social questions raised by the Geron case. We offer recommendations for institutional review boards and clinical sites as they deliberate approvals of early-phase trials in frontier medicine. PMID:25298371

  7. Integrating pain metrics into oncology clinical trials.

    PubMed

    Cleeland, Charles S; O'Mara, Ann; Zagari, Martin; Baas, Carole

    2011-11-01

    Cancer-related pain is highly prevalent and often severe, and as a result is often one of the defining experiences for patients with malignancy. Patients and patients' families almost always live with the ever-present reality that cancer treatment and progression may be accompanied by pain. For patients nearing the end of life, most fear that their final days will be spent living with the terrible effects of the disease, the most important of which is pain. Despite this, there is far less systematic research on the mechanisms of cancer-related pain or on the development of new agents to reduce or eliminate pain in cancer patients compared with research to combat the disease itself. Further, even when the focus of research is treatment of the tumor, the effects of anticancer treatments on pain are often underreported in publications and other forums. To illustrate the relative drought in the cancer pain control area, there have been no new drugs approved for cancer-related pain in recent years. A number of methodologic and logistical challenges that hinder the ability to assess pain response in clinical trials are discussed in this article. Possible ways to address these challenges are also discussed. PMID:22046026

  8. Smoking cessation via the internet: a randomized clinical trial of an internet intervention as adjuvant treatment in a smoking cessation intervention.

    PubMed

    Japuntich, Sandra J; Zehner, Mark E; Smith, Stevens S; Jorenby, Douglas E; Valdez, José A; Fiore, Michael C; Baker, Timothy B; Gustafson, David H

    2006-12-01

    Internet interventions for smoking cessation are ubiquitous. Yet, to date, there are few randomized clinical trials that gauge their efficacy. This study is a randomized clinical trial (N= 284, n= 140 in the treatment group, n= 144 in the control group) of an Internet smoking cessation intervention. Smokers were randomly assigned to receive either bupropion plus counseling alone, or bupropion and counseling in addition to 12 weeks of access to the Comprehensive Health Enhancement Support System for Smoking Cessation and Relapse Prevention (CHESS SCRP; a Web site which provided information on smoking cessation as well as support). We found that access to CHESS SCRP was not significantly related to abstinence at the end of the treatment period (OR= 1.13, 95% CI 0.66-2.62) or at 6 months postquit (OR= 1.48, 95% CI 0.66-2.62). However, the number of times participants used CHESS SCRP per week was related to abstinence at both end of treatment (OR= 1.79, 95% CI 1.25-2.56) and at the 6-month follow-up (OR= 1.59, 95% CI 1.06-2.38). Participants with access to CHESS SCRP logged in an average of 33.64 times (SD=30.76) over the 90-day period of access. Rates of CHESS SCRP use did not differ by ethnicity, level of education or gender (all p>.05). In sum, results suggest that participants used CHESS SCRP frequently, CHESS SCRP use was related to success, but the effects in general did not yield intergroup effects. PMID:17491172

  9. ADULTS: A RANDOMIZED CONTROLLED CLINICAL TRIAL

    PubMed Central

    Shah, Krupa N.; Majeed, Zahraa; Yoruk, Yilmaz B.; Yang, Hongmei; Hilton, Tiffany N.; McMahon, James M.; Hall, William J.; Walck, Donna; Luque, Amneris E.; Ryan, Richard M.

    2016-01-01

    Objective HIV-infected older adults (HOA) are at risk of functional decline. Interventions promoting physical activity that can attenuate functional decline and are easily translated into the HOA community are of high priority. We conducted a randomized, controlled clinical trial to evaluate whether a physical activity counseling intervention based on self-determination theory (SDT) improves physical function, autonomous motivation, depression and the quality of life (QOL) in HOA. Methods A total of 67 community-dwelling HOA with mild-to-moderate functional limitations were randomized to one of two groups: a physical activity counseling group or the usual care control group. We used SDT to guide the development of the experimental intervention. Outcome measures that were collected at baseline and final study visits included a battery of physical function tests, levels of physical activity, autonomous motivation, depression, and QOL. Results The study participants were similar in their demographic and clinical characteristics in both the treatment and control groups. Overall physical performance, gait speed, measures of endurance and strength, and levels of physical activity improved in the treatment group compared to the control group (p<0.05). Measures of autonomous regulation such as identified regulation, and measures of depression and QOL improved significantly in the treatment group compared to the control group (p<0.05). Across the groups, improvement in intrinsic regulation and QOL correlated with an improvement in physical function (p<0.05). Conclusion Our findings suggest that a physical activity counseling program grounded in SDT can improve physical function, autonomous motivation, depression, and QOL in HOA with functional limitations. PMID:26867045

  10. Ethical and regulatory issues for clinical trials in xenotransplantation.

    PubMed

    González, Jorge Guerra

    2012-01-01

    Clinical trials in xenotransplantation (XTx) that have just started to fulfil a long delayed promise should certainly be performed under the same guarantees for the subjects involved as any other experimentation in human medicine. The most important is the absolute respect for their fundamental rights and freedoms, especially for their autonomy, which is expressed through their informed consent as essential requirement for the carrying out of any clinical trial. This chapter focuses on the legal and ethical adaption of the clinical trial's general rules to the particular conditions of xenografting. They are mainly related to the possibility that transmissible xenogeneic agents come into being and become a risk for third parties, even for the whole society. This aspect makes XTx different from any other therapy in (bio)medicine. According to most literature and norm proposals, such xenogeneic infection risk would justify important changes in clinical trial regulation: last but not least, it could mean fundamental right limitations for the xenografted subjects. However, an analysis of the present ethical and legal background at national and international levels shows that such special treatment would be awkwardly acceptable. Information and recommendations on XTx and on its chances and risks when consenting to the trial would be more advisable than right constraining approaches. PMID:22566003

  11. Twenty questions about multiple sclerosis clinical trials methodologies.

    PubMed

    Pryse-Phillips, W

    2001-04-01

    The heterogeneity of methods used in multiple sclerosis (MS) clinical trials prevents fair comparison of trials and reduces confidence in the validity of the therapeutic claims made. The validity of recent clinical trials is lessened by the following factors: MS shows variability in type and in rates of disease progression; primary progressive MS may not be the same disease as typical MS, and inclusion of subjects with this condition may have skewed results of trials to date. Using a new model, "relapsing-remitting" and "secondary progressive" MS are considered to represent earlier and later stages of the same disease. The variety of endpoints used in clinical trials impairs comparisons. The differences between EDSS stages vary at different levels and it is concluded that this is no longer the most appropriate tool, although it could be improved by modifying the scoring or scales to assess certain focused items. The clinical significance of a reduction in relapse rate is questioned, as are the inclusion criteria employed in recent trials. Drug doses based upon body mass differ from those based on surface area, making it hard to compare the effects of trial agents. The definitions of "sustained worsening" are not uniform and the concept is complicated by regression to the mean. Trials should continue for long enough to be sure that any beneficial effects noted are permanent. Although extensions provide better long-term data, they are usually statistically underpowered and clinically and demographically imbalanced. Ethically, if benefit is determined to be present, a trial should be stopped so that all subjects may be offered the beneficial agent, but determination of benefit may be imperfect. The "intention to treat" paradigm is a shibboleth, providing data on effectiveness rather than efficacy. The simple listing and addition of unwanted effects (UEs) is unproductive. Trivial UEs detract little from quality of life and are unimportant. The remainder should be

  12. The Joys of Clinical Trials: A Case Study of a Multicenter Pharmaceutical Trial.

    ERIC Educational Resources Information Center

    Soronson, Bryan M.; Shaw, Diana V.

    1994-01-01

    A discussion of clinical trials in the pharmaceutical industry describes typical processes and administrative issues, then presents a case in which a foreign pharmaceutical company negotiated with a university for sponsorship of a multicenter clinical trial of a new drug therapy. Problems and important considerations in clinical trials are…

  13. UK Dermatology Clinical Trials Network’s STOP GAP trial (a multicentre trial of prednisolone versus ciclosporin for pyoderma gangrenosum): protocol for a randomised controlled trial

    PubMed Central

    2012-01-01

    Background Pyoderma gangrenosum (PG) is a rare inflammatory skin disorder characterised by painful and rapidly progressing skin ulceration. PG can be extremely difficult to treat and patients often require systemic immunosuppression. Recurrent lesions of PG are common, but the relative rarity of this condition means that there is a lack of published evidence regarding its treatment. A systematic review published in 2005 found no randomised controlled trials (RCTs) relating to the treatment of PG. Since this time, one small RCT has been published comparing infliximab to placebo, but none of the commonly used systemic treatments for PG have been formally assessed. The UK Dermatology Clinical Trials Network’s STOP GAP Trial has been designed to address this lack of trial evidence. Methods The objective is to assess whether oral ciclosporin is more effective than oral prednisolone for the treatment of PG. The trial design is a two-arm, observer-blind, parallel-group, randomised controlled trial comparing ciclosporin (4 mg/kg/day) to prednisolone (0.75 mg/kg/day). A total of 140 participants are to be recruited over a period of 4 years, from up to 50 hospitals in the UK and Eire. Primary outcome of velocity of healing at 6 weeks is assessed blinded to treatment allocation (using digital images of the ulcers). Secondary outcomes include: (i) time to healing; (ii) global assessment of improvement; (iii) PG inflammation assessment scale score; (iv) self-reported pain; (v) health-related quality of life; (vi) time to recurrence; (vii) treatment failures; (viii) adverse reactions to study medications; and (ix) cost effectiveness/utility. Patients with a clinical diagnosis of PG (excluding granulomatous PG); measurable ulceration (that is, not pustular PG); and patients aged over 18 years old who are able to give informed consent are included in the trial. Randomisation is by computer generated code using permuted blocks of randomly varying size, stratified by

  14. Topics

    ERIC Educational Resources Information Center

    Mathematics Teaching, 1972

    1972-01-01

    Topics discussed in this column include patterns of inverse multipliers in modular arithmetic; diagrams for product sets, set intersection, and set union; function notation; patterns in the number of partitions of positive integers; and tessellations. (DT)

  15. OARSI Clinical Trials Recommendations: Hand imaging in clinical trials in osteoarthritis.

    PubMed

    Hunter, D J; Arden, N; Cicuttini, F; Crema, M D; Dardzinski, B; Duryea, J; Guermazi, A; Haugen, I K; Kloppenburg, M; Maheu, E; Miller, C G; Martel-Pelletier, J; Ochoa-Albíztegui, R E; Pelletier, J-P; Peterfy, C; Roemer, F; Gold, G E

    2015-05-01

    Tremendous advances have occurred in our understanding of the pathogenesis of hand osteoarthritis (OA) and these are beginning to be applied to trials targeted at modification of the disease course. The purpose of this expert opinion, consensus driven exercise is to provide detail on how one might use and apply hand imaging assessments in disease modifying clinical trials. It includes information on acquisition methods/techniques (including guidance on positioning for radiography, sequence/protocol recommendations/hardware for MRI); commonly encountered problems (including positioning, hardware and coil failures, sequences artifacts); quality assurance/control procedures; measurement methods; measurement performance (reliability, responsiveness, validity); recommendations for trials; and research recommendations. PMID:25952345

  16. Prostate Cancer Prevention: Concepts and Clinical Trials.

    PubMed

    Hamilton, Zachary; Parsons, J Kellogg

    2016-04-01

    Prevention is an important treatment strategy for diminishing prostate cancer morbidity and mortality and is applicable to both early- and late-stage disease. There are three basic classifications of cancer prevention: primary (prevention of incident disease), secondary (identification and treatment of preclinical disease), and tertiary (prevention of progression or recurrence). Based on level I evidence, 5-alpha reductase inhibitors (5-ARIs) should be considered in selected men to prevent incident prostate cancer. Level I evidence also supports the consideration of dutasteride, a 5-ARI, for tertiary prevention in active surveillance and biochemical recurrence patients. Vitamins and supplements, including selenium or vitamin E, have not been proven in clinical trials to prevent prostate cancer and in the case of Vitamin E has been found to increase the risk of incident prostate cancer. Ongoing and future trials may further elucidate the role of diet and immunotherapy for prevention of prostate cancer. PMID:26957512

  17. Tumor Shrinkage With Lanreotide Autogel 120 mg as Primary Therapy in Acromegaly: Results of a Prospective Multicenter Clinical Trial

    PubMed Central

    Bevan, John S.; Petersenn, Stephan; Flanagan, Daniel; Tabarin, Antoine; Prévost, Gaëtan; Maisonobe, Pascal; Clermont, Antoine

    2014-01-01

    Context: Methodological shortcomings often compromise investigations into the effects of primary somatostatin-analog treatment on tumor size in acromegaly. There are also limited data for the long-acting lanreotide formulation. Objective: The aim of the study was to better characterize the effects of primary lanreotide Autogel treatment on tumor size in patients with GH-secreting macroadenomas. Design: PRIMARYS was a 48-week, multicenter, open-label, single-arm study. Setting: The study was conducted at specialist endocrine centers. Patients: Treatment-naïve acromegalic patients with GH-secreting macroadenomas participated in the study. Intervention: Lanreotide Autogel 120 mg was administered sc every 28 days (without dose titration). Outcome Measures: The primary endpoint was the proportion of patients with clinically significant (≥20%) tumor volume reduction (TVR) at week 48/last post-baseline value available using central assessments from three readers. The null hypothesis (H0) for the primary endpoint was that the proportion with TVR was ≤55%. Secondary endpoints included: TVR at other time points, GH and IGF-1, acromegalic symptoms, quality of life (QoL), and safety. Results: Sixty-four of 90 (71.1%) patients completed the study. Clinically significant TVR at 48 weeks/last post-baseline value available was achieved by 62.9% (95% confidence interval, 52.0, 72.9) of 89 patients in the primary analysis (intention-to-treat population; H0 not rejected) and 71.9–75.3% in sensitivity (n = 89) and secondary analyses (n = 63) (H0 rejected). At 12 weeks, 54.1% had clinically significant TVR. Early and sustained improvements also occurred in GH and IGF-1, acromegalic symptoms, and QoL. No patients withdrew due to gastrointestinal intolerance. Conclusions: Primary treatment with lanreotide Autogel, administered at 120 mg (highest available dose) without dose titration, in patients with GH-secreting macroadenomas provides early and sustained reductions in tumor

  18. The pharmaceutical industry's responsibility for protecting human subjects of clinical trials in developing nations.

    PubMed

    Kelleher, Finnuala

    2004-01-01

    Pharmaceutical companies increasingly perform clinical trials in developing nations. Governments of host nations see the trials as a way to provide otherwise unaffordable medical care, while trial sponsors are drawn to those countries by lower costs, the prevalence of diseases rare in developed nations, and large numbers of impoverished patients. Local governments, however, fail to police trials, and the FDA does not monitor trials in foreign countries, resulting in the routine violation of international standards for the protection of human subjects. This Note proposes independent accreditation of those institutions involved in clinical trials--the institutional review boards which oversee trial protocol; the organizations, such as pharmaceutical companies, which sponsor the trials; and the research organizations that conduct the trials. Accreditation, similar to that used in the footwear and apparel industries, would increase the transparency of pharmaceutical trials and would enable the United States government and consumers to hold trial sponsors accountable for their actions. PMID:16755695

  19. The status of platinum anticancer drugs in the clinic and in clinical trials.

    PubMed

    Wheate, Nial J; Walker, Shonagh; Craig, Gemma E; Oun, Rabbab

    2010-09-21

    Since its approval in 1979 cisplatin has become an important component in chemotherapy regimes for the treatment of ovarian, testicular, lung and bladder cancers, as well as lymphomas, myelomas and melanoma. Unfortunately its continued use is greatly limited by severe dose limiting side effects and intrinsic or acquired drug resistance. Over the last 30 years, 23 other platinum-based drugs have entered clinical trials with only two (carboplatin and oxaliplatin) of these gaining international marketing approval, and another three (nedaplatin, lobaplatin and heptaplatin) gaining approval in individual nations. During this time there have been more failures than successes with the development of 14 drugs being halted during clinical trials. Currently there are four drugs in the various phases of clinical trial (satraplatin, picoplatin, Lipoplatin and ProLindac). No new small molecule platinum drug has entered clinical trials since 1999 which is representative of a shift in focus away from drug design and towards drug delivery in the last decade. In this perspective article we update the status of platinum anticancer drugs currently approved for use, those undergoing clinical trials and those discontinued during clinical trials, and discuss the results in the context of where we believe the field will develop over the next decade. PMID:20593091

  20. A comprehensive framework for quality assurance in clinical trials

    NASA Astrophysics Data System (ADS)

    El Gazzar, Omar; Onken, Michael; Eichelberg, Marco; Hein, Andreas; Kotter, Elmar

    2012-02-01

    Biomarkers captured by medical images are increasingly used as indicators for the efficacy or safety of a certain drug or treatment for clinical trials. For example, medical images such as CT or MR are often used for extracting quantitative measurements for the assessment of tumor treatment response while evaluating a chemotherapy drug for therapeutic cancer trials. Quality assurance is defined as "All those planned and systematic actions that are established to ensure that the trial is performed and the data are generated, documented (recorded), and reported in compliance with good clinical practice (GCP) and the applicable regulatory requirement(s)" [1]. Our objective is to build a generalized and an automated framework for quality assurance within the clinical trials workflow. In order to reach this goal, a set of standardized software tools have been developed for quality assurance. Furthermore, we outline some guidelines as recommendations for the users handling the image data within the research workflow. The software tools developed include tools for image selection, image pseudonymization and image quality conformance check. The export tools are developed based on the specifications of the Integrating the Healthcare Enterprise (IHE) Teaching and Clinical Trial Export (TCE) profile. A DICOM-based quality conformance approach has been developed by validating the DICOM header attributes required for a certain imaging application (e.g. CAD, MPR, 3D) and comparing imaging acquisition parameters against the protocol specification. A formal description language is used to represent such quality requirements. For evaluation, imaging data collected from a clinical trial site were validated against Multi-Planar Reconstruction (MPR). We found that out of 60 studies, about 30% of image series volumes failed the MPR check for some common reasons.

  1. Gateways to clinical trials. March 2003.

    PubMed

    Bayés, M; Rabasseda, X; Prous, J R

    2003-03-01

    Gateways to clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Studies knowledge area of Prous Science Integrity, the drug discovery and devlopment protal, http://integrity.prous.com. This issue focuses on the following selection of drugs: AAV-CF, adalimumab, ademetionine, afeletecan hydrochloride, agomelatine, alemtuzumab, almotriptan, amdoxovir, aplidine, aranose, arsenic sulfide, atazanavir, atlizumab; Bimatoprost, BMS-181176, BMS-188667, bortezomib, bryostatin 1; Combretastatin A-4 phosphate; Darbepoetin alfa, darusentan, deferasirox, desloratadine, DTaP-HBV-IPV/Hib-vaccine, DTI-0009; Eculizumab, edodekin alfa, emtricitabine, enfuvirtide, epoetin, esomeprazole magnesium etoricoxib; Fampridine, fenretinide, FR-146687; Galiximab, gamma-Hydroxybutyrate sodium, ganirelix acetate, gefitinib, Gemtuzumab ozogamicin, gimatecan; HEA125xOKT3, hIL-13-PE38QQR, HSV-2 theracine, Hu14.18-IL-2, human gammaglobulin; Idraparinux sodium, imatinib mesylate, IMiD3, insulin detemir, interleukin-4, irofulven, ISAtx-247; JT-1001; Levetiracetam, levosimendan, liposomal doxorubicin, liposomal vincristine sulfate, lixivaptan, lopinavir, lumiracoxib; Maxacalcitol, melatonin, midostaurin, MLN-518; Neridronic acid, nesiritide, nitronaproxen; Oblimersen sodium, oregovomab; PEG-filgrastim polyglutamate paclitaxel, prasterone, pregabalin; Rosuvastatin calcium, rotigotine hydrochloride; SGN-30; T-1249, tenofovir disoproxil fumarate, teriparatide, tiotropium bromide, tipranavir, TMC-114, trabectedin, transdermal selegiline; UK-427857; Valdecoxib, valganciclovir hydrochloride, vardenafil, vatalanib succinate, vincristine sulfate TCS; Zofenopril calcium. PMID:12731460

  2. 77 FR 6808 - Proposed Collection; Comment Request: Information Program on Clinical Trials; Maintaining a...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-02-09

    ... (73 FR 58972, Oct. 8, 2008), and feedback from respondents who have submitted results to Clinical... as a clinical trial registry under section 113 of the Food and Drug Administration Modernization Act... referred to as ``responsible parties,'' which are defined as sponsors of the clinical trial (as defined...

  3. [Clinical trial data management and quality metrics system].

    PubMed

    Chen, Zhao-hua; Huang, Qin; Deng, Ya-zhong; Zhang, Yue; Xu, Yu; Yu, Hao; Liu, Zong-fan

    2015-11-01

    Data quality management system is essential to ensure accurate, complete, consistent, and reliable data collection in clinical research. This paper is devoted to various choices of data quality metrics. They are categorized by study status, e.g. study start up, conduct, and close-out. In each category, metrics for different purposes are listed according to ALCOA+ principles such us completeness, accuracy, timeliness, traceability, etc. Some general quality metrics frequently used are also introduced. This paper contains detail information as much as possible to each metric by providing definition, purpose, evaluation, referenced benchmark, and recommended targets in favor of real practice. It is important that sponsors and data management service providers establish a robust integrated clinical trial data quality management system to ensure sustainable high quality of clinical trial deliverables. It will also support enterprise level of data evaluation and bench marking the quality of data across projects, sponsors, data management service providers by using objective metrics from the real clinical trials. We hope this will be a significant input to accelerate the improvement of clinical trial data quality in the industry. PMID:26911027

  4. Randomised controlled trial of topical kanuka honey for the treatment of acne

    PubMed Central

    Semprini, Alex; Corin, Andrew; Sheahan, Davitt; Tofield, Christopher; Helm, Colin; Montgomery, Barney; Fingleton, James; Weatherall, Mark; Beasley, Richard

    2016-01-01

    Objective To investigate the efficacy of Honevo, a topical 90% medical-grade kanuka honey, and 10% glycerine (honey product) as a treatment for facial acne. Design Randomised controlled trial with single blind assessment of primary outcome variable. Setting Outpatient primary care from 3 New Zealand localities. Participants Of 136 participants aged between 16 and 40 years with a diagnosis of acne and baseline Investigator's Global Assessment (IGA) for acne score of ≥2.68, participants were randomised to each treatment arm. Interventions All participants applied Protex, a triclocarban-based antibacterial soap twice daily for 12 weeks. Participants randomised to the honey product treatment arm applied this directly after washing off the antibacterial soap, twice daily for 12 weeks. Outcome measures The primary outcome was ≥2 point decrease in IGA score from baseline at 12 weeks. Secondary outcomes included mean lesion counts and changes in subject-rated acne improvement and severity at weeks 4 and 12, and withdrawals for worsening acne. Results 4/53 (7.6%) participants in the honey product group and 1/53 (1.9%) of participants in the control group had a ≥ 2 improvement in IGA score at week 12, compared with baseline, OR (95% CI) for improvement 4.2 (0.5 to 39.3), p=0.17. There were 15 and 14 participants who withdrew from the honey product group and control group, respectively. Conclusions This randomised controlled trial did not find evidence that addition of medical-grade kanuka honey in combination with 10% glycerine to standard antibacterial soap treatment is more effective than the use of antibacterial soap alone in the treatment of acne. Trial registration number ACTRN12614000003673; Results. PMID:26832428

  5. International Society for Cellular Therapy perspective on immune functional assays for mesenchymal stromal cells as potency release criterion for advanced phase clinical trials.

    PubMed

    Galipeau, Jacques; Krampera, Mauro; Barrett, John; Dazzi, Francesco; Deans, Robert J; DeBruijn, Joost; Dominici, Massimo; Fibbe, Willem E; Gee, Adrian P; Gimble, Jeffery M; Hematti, Peiman; Koh, Mickey B C; LeBlanc, Katarina; Martin, Ivan; McNiece, Ian K; Mendicino, Michael; Oh, Steve; Ortiz, Luis; Phinney, Donald G; Planat, Valerie; Shi, Yufang; Stroncek, David F; Viswanathan, Sowmya; Weiss, Daniel J; Sensebe, Luc

    2016-02-01

    Mesenchymal stromal cells (MSCs) as a pharmaceutical for ailments characterized by pathogenic autoimmune, alloimmune and inflammatory processes now cover the spectrum of early- to late-phase clinical trials in both industry and academic sponsored studies. There is a broad consensus that despite different tissue sourcing and varied culture expansion protocols, human MSC-like cell products likely share fundamental mechanisms of action mediating their anti-inflammatory and tissue repair functionalities. Identification of functional markers of potency and reduction to practice of standardized, easily deployable methods of measurements of such would benefit the field. This would satisfy both mechanistic research as well as development of release potency assays to meet Regulatory Authority requirements for conduct of advanced clinical studies and their eventual registration. In response to this unmet need, the International Society for Cellular Therapy (ISCT) addressed the issue at an international workshop in May 2015 as part of the 21st ISCT annual meeting in Las Vegas. The scope of the workshop was focused on discussing potency assays germane to immunomodulation by MSC-like products in clinical indications targeting immune disorders. We here provide consensus perspective arising from this forum. We propose that focused analysis of selected MSC markers robustly deployed by in vitro licensing and metricized with a matrix of assays should be responsive to requirements from Regulatory Authorities. Workshop participants identified three preferred analytic methods that could inform a matrix assay approach: quantitative RNA analysis of selected gene products; flow cytometry analysis of functionally relevant surface markers and protein-based assay of secretome. We also advocate that potency assays acceptable to the Regulatory Authorities be rendered publicly accessible in an "open-access" manner, such as through publication or database collection. PMID:26724220

  6. International Society for Cellular Therapy perspective on immune functional assays for mesenchymal stromal cells as potency release criterion for advanced phase clinical trials

    PubMed Central

    Galipeau, Jacques; Krampera, Mauro; Barrett, John; Dazzi, Francesco; Deans, Robert J.; Debruijn, Joost; Dominici, Massimo; Fibbe, Willem E.; Gee, Adrian P.; Gimble, Jeffery M.; Hematti, Peiman; Koh, Mickey B.C.; Leblanc, Katarina; Martin, Ivan; Mcniece, Ian K.; Mendicino, Michael; Oh, Steve; Ortiz, Luis; Phinney, Donald G.; Planat, Valerie; Shi, Yufang; Stroncek, David F.; Viswanathan, Sowmya; Weiss, Daniel J.; Sensebe, Luc

    2016-01-01

    Mesenchymal stromal cells (MSCs) as a pharmaceutical for ailments characterized by pathogenic autoimmune, alloimmune and inflammatory processes now cover the spectrum of early- to late-phase clinical trials in both industry and academic sponsored studies. There is a broad consensus that despite different tissue sourcing and varied culture expansion protocols, human MSC-like cell products likely share fundamental mechanisms of action mediating their anti-inflammatory and tissue repair functionalities. Identification of functional markers of potency and reduction to practice of standardized, easily deployable methods of measurements of such would benefit the field. This would satisfy both mechanistic research as well as development of release potency assays to meet Regulatory Authority requirements for conduct of advanced clinical studies and their eventual registration. In response to this unmet need, the International Society for Cellular Therapy (ISCT) addressed the issue at an international workshop in May 2015 as part of the 21st ISCT annual meeting in Las Vegas. The scope of the workshop was focused on discussing potency assays germane to immunomodulation by MSC-like products in clinical indications targeting immune disorders. We here provide consensus perspective arising from this forum. We propose that focused analysis of selected MSC markers robustly deployed by in vitro licensing and metricized with a matrix of assays should be responsive to requirements from Regulatory Authorities. Workshop participants identified three preferred analytic methods that could inform a matrix assay approach: quantitative RNA analysis of selected gene products; flow cytometry analysis of functionally relevant surface markers and protein-based assay of secretome. We also advocate that potency assays acceptable to the Regulatory Authorities be rendered publicly accessible in an “open-access” manner, such as through publication or database collection. PMID:26724220

  7. Placebo Effect in Clinical Trial Design for Irritable Bowel Syndrome

    PubMed Central

    Shah, Eric; Pimentel, Mark

    2014-01-01

    Ongoing efforts to improve clinical trial design in irritable bowel syndrome have been hindered by high placebo response rates and ineffective outcome measures. We assessed established strategies to minimize placebo effect as well as the various approaches to placebo effect which can affect trial design. These include genetic markers such as catechol-O-methyltransferase, opioidergic and dopaminergic neurobiologic theory, pre-cebo effect centered on expectancy theory, and side effect unblinding grounded on conditioning theory. We reviewed endpoints used in the study of IBS over the past decade including adequate relief and subjective global relief, emphasizing their weaknesses in fully evaluating the IBS condition, specifically their motility effects based on functional net value and relative benefit-harm based on dropouts due to adverse events. The focus of this review is to highlight ongoing efforts to improve clinical trial design which can lead to better outcomes in a real-world setting. PMID:24840369

  8. Creative arts program as an intervention for PTSD: a randomized clinical trial with motor vehicle accident survivors.

    PubMed

    Wang, Xiuling; Lan, Chao; Chen, Juwu; Wang, Wenying; Zhang, Hua; Li, Li

    2015-01-01

    The aim of this study is to determine whether the creative arts program (HA) is effective in preventing the onset of Posttraumatic stress disorder (PTSD). PTSD develops in 10-20% of motor vehicle accident survivors (MVAs). MVAs in the initial months after the accident were randomly assigned to receive 8-week HA intervention (n = 26) or wait the list (WL, n = 26). The arts program consisted of writing and drawing. PTSD severity was assessed at 2, 6, and 12 months post injury with a clinical interview (Clinician-Administered PTSD Scale, CAPS) and self-report instrument (Impact of Event Scale-Revised, IES-R). Secondary outcomes were post-traumatic growth (PTG), depression and anxiety symptoms. Repeated measures analysis of variance indicated that both HA and WL group exhibited a significant effect of time (P < 0.01) on CAPS, but no significant group differences over time. There were no group differences on depression or anxiety over time. Pessimists did not benefit more from attending the HA than they did from attending the WL. Our results fail to support the hypothesis that the creative arts program is effect in avoiding MVA-related PTSD symptoms. But it only seems to be a short-term, rather than a long-term effect. PMID:26550298

  9. Creative arts program as an intervention for PTSD: a randomized clinical trial with motor vehicle accident survivors

    PubMed Central

    Wang, Xiuling; Lan, Chao; Chen, Juwu; Wang, Wenying; Zhang, Hua; Li, Li

    2015-01-01

    The aim of this study is to determine whether the creative arts program (HA) is effective in preventing the onset of Posttraumatic stress disorder (PTSD). PTSD develops in 10-20% of motor vehicle accident survivors (MVAs). MVAs in the initial months after the accident were randomly assigned to receive 8-week HA intervention (n = 26) or wait the list (WL, n = 26). The arts program consisted of writing and drawing. PTSD severity was assessed at 2, 6, and 12 months post injury with a clinical interview (Clinician-Administered PTSD Scale, CAPS) and self-report instrument (Impact of Event Scale-Revised, IES-R). Secondary outcomes were post-traumatic growth (PTG), depression and anxiety symptoms. Repeated measures analysis of variance indicated that both HA and WL group exhibited a significant effect of time (P < 0.01) on CAPS, but no significant group differences over time. There were no group differences on depression or anxiety over time. Pessimists did not benefit more from attending the HA than they did from attending the WL. Our results fail to support the hypothesis that the creative arts program is effect in avoiding MVA-related PTSD symptoms. But it only seems to be a short-term, rather than a long-term effect. PMID:26550298

  10. Potential Risks and Mitigation Strategies Before the Conduct of a Clinical Trial: An Industry Perspective.

    PubMed

    Bhagat, Seema; Kapatkar, Vaibhavi K; Mourya, Meenakshi; Roy, Sucheta; Jha, Shailendra; Reddy, Rajasekhar; Kadhe, Ganesh; Mane, Amey; Sawant, Sandesh

    2016-01-01

    Conduct of clinical trials has undergone substantial changes over the last two decades. Newer markets, evolving guidelines and documentation and high cost involved in conducting the trials have led pharmaceutical companies to prepare a risk mitigation plan. Extensive monitoring of potential risks is an essential element of clinical trials which helps to ensure quality and integrity of a clinical investigation. Every clinical trial has pre (before the trial), conduct and post phase. This article which has been developed as a result of extensive research at ground level by a reputed pharmaceutical company to identify the potential stages of risks that could affect the overall quality and safety of a trial and its outcome during the pre-phase of trial (the stage of the trial where the study design is being planned before initiation of the clinical trial). It includes risks associated with basic study concept, protocol design, Confidential Disclosure Agreement (CDA) and Clinical Trial Authorization (CTA) application signing, vendors of central drug laboratory, site and investigator selection, Clinical Research Coordinator (CRC) meet, Informed Consent Form (ICF), Case Report Form (CRF)/ Status Report Form (SRF) preparation, Ethics Committee (EC) submission, etc. have been highlighted. The risk based mitigation strategy (to develop an effective risk monitoring plan before staring a clinical trial) has also been suggested by authors. A well-tailored and integrated plan, recognition of potential risks and their mitigation strategy can result in the pre exclusion or end to end solution of all the risks associated with pre- phase of clinical trials. PMID:26435140

  11. Epothilones: from discovery to clinical trials

    PubMed Central

    Forli, Stefano

    2015-01-01

    Epothilones are natural compounds isolated from a myxobacterium at the beginning of the 1990s, and showed a remarkable anti-neoplastic activity. They act through the same mechanism of action of paclitaxel, by stabilizing microtubules and inducing apoptosis. Although, their chemical structure, simpler than taxanes, makes them more suitable for derivatization. Their interesting pharmacokinetic and bioavailabilty profiles, and the activity against paclitaxel-resistant cell lines make them interesting therapeutic agents. Here a brief historical perspective of epothilones is presented, since their isolation, the identification of their mechanism of action and activity, to the recent clinical trials. PMID:25434353

  12. A survey of clinical trials with fenbufen.

    PubMed

    Mawdsley, P

    1980-01-01

    To date, the efficacy and safety of gamma-oxo(1,1'-biphenyl)-4-butanoic acid (fenbufen) have been evaluated in over 200 clinical trials involving several thousand patients. The program of clinical investigation consisted of open dose ranging studies in patients; short-term, double-blind controlled studies of both cross-over and parallel group design to evaluate efficacy and safety compared to placebo and active reference drugs; long-term, double-blind controlled studies of parallel group design versus an active reference agent; open studies to evaluate the long-term efficacy and safety of fenbufen; and special studies to investigate possible effects on eyes, ears and heart. The overall experience with fenbufen in 60 US and 37 foreign clinical trials is summarized in this report with respect to the following: therapeutic efficacy and safety in rheumatoid arthritis, osteoarthritis, ankylosing spondylitis, analgesia and gout. The age range covered in these studies was 13 to 87 years, and included 206 patients over the age of 70. 3457 patients received fenbufen in all phases of these clinical trials, including short-term and long-term studies. The patient total includes: 1462 patients (664 US, 798 foreign) with rheumatoid arthritis, 1225 (420 US, 805 foreign) with osteoarthritis, 55 (19 US, 36 foreign) with ankylosing spondylitis, 39 (foreign) with gout, and 676 patients (103 US, 573 (foreign) who participated in analgesia studies. The worldwide clinical studies have demonstrated very good clinical efficacy of fenbufen in comparison to other non-steroidal antirheumatic (nsa) drugs. The tolerance was much better in many cases compared with tolerance levels of other nsa-drugs. The good results were confirmed by new papers presented during IX International Congress of Rheumatology, Wiesbaden/FR Germany, September 1979. Fenbufen is currently marketed in Brazil, Columbia, Costa Rica, Dominican Republic, Ecuador, El Salvador, Great Britain, Greece, Guatemala, Honduras

  13. Strategies for clinical trials in type 1 diabetes.

    PubMed

    Ehlers, Mario R

    2016-07-01

    During the past one to two decades, substantial progress has been made in our understanding of the immunopathology of type 1 diabetes (T1D) and the potential for immune interventions that can alter the natural history of the disease. This progress has resulted from the use of standardized study designs, endpoints, and, to a certain extent, mechanistic analyses in intervention trials in the setting of new-onset T1D. To date, most of these trials have involved single-agent interventions but, increasingly, future trials will test therapeutic combinations that are based on a compelling scientific rationale and testable mechanistic hypotheses. These increasingly complex trials will benefit from novel trial designs (such as factorial or adaptive designs), enhanced clinical endpoints that more directly assess islet pathology (such as β-cell death assays and islet or pancreatic imaging), improved responder analyses, and sophisticated mechanistic assays that provide deep phenotyping of lymphocyte subsets, gene expression profiling, in vitro T cell functional assessments, and antigen-specific responses. With this developing armamentarium of enhanced trial designs, endpoints, and clinical and mechanistic response analyses, we can expect substantial progress in better understanding the breakdown in immunologic tolerance in T1D and how to restore it to achieve significant and long-lasting preservation of islet function. PMID:27068279

  14. Matching Patient Records to Clinical Trials Using Ontologies

    NASA Astrophysics Data System (ADS)

    Patel, Chintan; Cimino, James; Dolby, Julian; Fokoue, Achille; Kalyanpur, Aditya; Kershenbaum, Aaron; Ma, Li; Schonberg, Edith; Srinivas, Kavitha

    This paper describes a large case study that explores the applicability of ontology reasoning to problems in the medical domain. We investigate whether it is possible to use such reasoning to automate common clinical tasks that are currently labor intensive and error prone, and focus our case study on improving cohort selection for clinical trials. An obstacle to automating such clinical tasks is the need to bridge the semantic gulf between raw patient data, such as laboratory tests or specific medications, and the way a clinician interprets this data. Our key insight is that matching patients to clinical trials can be formulated as a problem of semantic retrieval. We describe the technical challenges to building a realistic case study, which include problems related to scalability, the integration of large ontologies, and dealing with noisy, inconsistent data. Our solution is based on the SNOMED CT® ontology, and scales to one year of patient records (approx. 240,000 patients).

  15. Review of topical beta blockers as treatment for infantile hemangiomas.

    PubMed

    Painter, Sally L; Hildebrand, Göran Darius

    2016-01-01

    The treatment of infantile hemangiomas changed from the use of oral corticosteroids to oral propranolol on the serendipitous discovery of propanolol's clinical effectiveness in 2008. Since then, clinicians have begun to use topical beta blockers--in particular, timolol maleate 0.5% gel forming solution--with good effect. Topical beta blockers are now used for lesions with both deep and superficial components and those that are amblyogenic. When initiated in the proliferative phase of the lesion, the effectiveness of the treatment can be seen within days. There is no consensus on dosing, treatment bioavailability, or clinical assessment of lesions, but these are topics for future research. PMID:26408055

  16. Comparison of ADM and Connective Tissue Graft as the Membrane in Class II Furcation Defect Regeneration: A Randomized Clinical Trial

    PubMed Central

    Esfahanian, Vahid; Farhad, Shirin; Sadighi Shamami, Mehrnaz

    2014-01-01

    Background and aims. Furcally-involved teeth present unique challenges to the success of periodontal therapy and influence treatment outcomes. This study aimed to assess to compare use of ADM and connective tissue membrane in class II furcation defect regeneration. Materials and methods. 10 patient with 2 bilaterally class II furcation defects in first and/or second maxilla or man-dibular molar without interproximal furcation involvement, were selected. Four weeks after initial phase of treatment, before and thorough the surgery pocket depth (PD), clinical attachment level to stent (CAL-S), free gingival margin to stent(FGM-S) , crestal bone to stent (Crest-S), horizontal defect depth to stent (HDD-S) and vertical defect depth to stent (VDD-S) and crestal bone to defect depth measured from stent margin. Thereafter, one side randomly treated using connective tissue and DFDBA (study group) and opposite side received ADM and DFDBA (control group). After 6 months, soft and hard tissue parameters measured again in re-entry. Results. Both groups presented improvements after therapies (P & 0.05). No inter-group differences were seen in PD re-duction (P = 0.275), CAL gain (P = 0.156), free gingival margin (P = 0.146), crest of the bone (P = 0.248), reduction in horizontal defects depth (P = 0.139) and reduction in vertical defects depth (P = 0.149). Conclusion. Both treatments modalities have potential of regeneration without any adverse effect on healing process. Connective tissue grafts did not have significant higher bone fill compared to that of ADM. PMID:25093054

  17. A randomized, placebo-controlled trial of 1% topical minoxidil solution in the treatment of androgenetic alopecia in Japanese women.

    PubMed

    Tsuboi, Ryoji; Tanaka, Takao; Nishikawa, Tooru; Ueki, Rie; Yamada, Hidekazu; Katsuoka, Kensei; Ogawa, Hideoki; Takeda, Katsuyuki

    2007-01-01

    Minoxidil is effective in inducing hair growth in patients with androgenetic alopecia by stimulating hair follicles to undergo transition from early to late anagen phase. However, there have been no controlled studies of topical minoxidil in Asian women. The objective of this trial was to investigate the efficacy of 1% topical minoxidil for androgenetic alopecia in Japanese female patients using a double-blind controlled method. This trial included 280 Japanese female patients aged 20 years or older with androgenetic alopecia who were administered either 1% topical minoxidil (n = 140) or placebo (n = 140) for 24 weeks. The primary efficacy variable was mean change from baseline in non-vellus hair count/cm(2). The mean change was 8.15 in the 1% topical minoxidil group and 2.03 in the placebo group, with a significant difference between groups (p < 0.001) [difference: 6.12 (two-sided 95% confidence interval (CI): 3.29-8.96)]. Secondary variables included investigators' assessments and patients' self-assessments. As assessed by investigators, 29.2% (40/137) of the patients had moderate or better improvement in the 1% topical minoxidil group compared to 11.8% (16/136) in the placebo group (p < 0.001 versus placebo). The effect on hair growth was assessed as improved or better by 36.5% (50/137) of the patients themselves in the 1% topical minoxidil group compared to 23.5% (32/136) in the placebo group (p = 0.019 versus placebo). The patients tolerated treatment with 1% topical minoxidil well without significant adverse effects. PMID:17324826

  18. Updates on the Clinical Trials in Diabetic Macular Edema

    PubMed Central

    Demirel, Sibel; Argo, Colby; Agarwal, Aniruddha; Parriott, Jacob; Sepah, Yasir Jamal; Do, Diana V.; Nguyen, Quan Dong

    2016-01-01

    In this era of evidence-based medicine, significant progress has been made in the field of pharmacotherapeutics for the management of diabetic macular edema (DME). A. number of landmark clinical trials have provided strong evidence of the safety and efficacy of agents such as anti-vascular endothelial growth factors for the treatment of DME. Decades of clinical research, ranging from the early treatment of diabetic retinopathy study to the present-day randomized clinical trials (RCTs) testing novel agents, have shifted the goal of therapy from preventing vision loss to ensuring a maximum visual gain. Systematic study designs have provided robust data with an attempt to optimize the treatment regimens including the choice of the agent and timing of therapy. However, due to a number of challenges in the management of DME with approved agents, further studies are needed. For the purpose of this review, an extensive database search in English language was performed to identify prospective, RCTs testing pharmacological agents for DME. In order to acquaint the reader with the most relevant data from these clinical trials, this review focuses on pharmacological agents that are currently approved or have widespread applications in the management of DME. An update on clinical trials presently underway for DME has also been provided. PMID:26957834

  19. Topical, Biological and Clinical Challenges in the Management of Patients with Acne Vulgaris.

    PubMed

    Al-Hammadi, Anwar; Al-Ismaily, Abla; Al-Ali, Sameer; Ramadurai, Rajesh; Jain, Rishi; McKinley-Grant, Lynn; Mughal, Tariq I

    2016-05-01

    Acne vulgaris is one of the most common chronic inflammatory skin disorders among adolescents and young adults. It is associated with substantial morbidity and, rarely, with mortality. The exact worldwide incidence and prevalence are currently unknown. Current challenges involve improving understanding of the underlying pathophysiology of acne vulgaris and developing a practical treatment consensus. Expert panel discussions were held in 2013 and 2014 among a group of scientists and clinicians from the Omani and United Arab Emirate Dermatology Societies to ascertain the current optimal management of acne vulgaris, identify clinically relevant end-points and construct suitable methodology for future clinical trial designs. This article reviews the discussions of these sessions and recent literature on this topic. PMID:27226905

  20. Topical, Biological and Clinical Challenges in the Management of Patients with Acne Vulgaris

    PubMed Central

    Al-Hammadi, Anwar; Al-Ismaily, Abla; Al-Ali, Sameer; Ramadurai, Rajesh; Jain, Rishi; McKinley-Grant, Lynn; Mughal, Tariq I.

    2016-01-01

    Acne vulgaris is one of the most common chronic inflammatory skin disorders among adolescents and young adults. It is associated with substantial morbidity and, rarely, with mortality. The exact worldwide incidence and prevalence are currently unknown. Current challenges involve improving understanding of the underlying pathophysiology of acne vulgaris and developing a practical treatment consensus. Expert panel discussions were held in 2013 and 2014 among a group of scientists and clinicians from the Omani and United Arab Emirate Dermatology Societies to ascertain the current optimal management of acne vulgaris, identify clinically relevant end-points and construct suitable methodology for future clinical trial designs. This article reviews the discussions of these sessions and recent literature on this topic. PMID:27226905

  1. Recent NIMH Clinical Trials and Implications for Practice

    ERIC Educational Resources Information Center

    Vitiello, Benedetto; Kratochvil, Christopher J.

    2008-01-01

    Optimal treatment of adolescent depression requires the use of antidepressants such as fluoxetine, and the addition of cognitive-behavioral therapy (CBT) offers better potential. Second-step pharmacological treatment of the disorder offers a success rate of around 50%. Clinical trial for the use of sertraline and CBT in treating…

  2. Malaria vaccine clinical trials: what’s on the horizon

    PubMed Central

    Moreno, Alberto; Joyner, Chester

    2015-01-01

    Significant progress towards a malaria vaccine, specifically for Plasmodium falciparum, has been made in the past few years with the completion of numerous clinical trials. Each trial has utilized a unique combination of antigens, delivery platforms, and adjuvants, and the data that has been obtained provides critical information that has poises the research community for the development of next generation malaria vaccines. Despite the progress towards a P. falciparum vaccine, P. vivax vaccine research requires more momentum and additional investigations to identify novel vaccine candidates. In this review, recently completed and ongoing malaria vaccine clinical trials as well as vaccine candidates that are in the development pipeline are reviewed. Perspectives for future research using post-genomic mining, nonhuman primate models, and systems biology are also discussed. PMID:26172291

  3. Clinical benefit of adenosine as an adjunct to reperfusion in ST-elevation myocardial infarction patients: An updated meta-analysis of randomized controlled trials

    PubMed Central

    Bulluck, Heerajnarain; Sirker, Alex; Loke, Yoon K.; Garcia-Dorado, David; Hausenloy, Derek J.

    2016-01-01

    Background Adenosine administered as an adjunct to reperfusion can reduce coronary no-reflow and limit myocardial infarct (MI) size in ST-segment elevation myocardial infarction (STEMI) patients. Whether adjunctive adenosine therapy can improve clinical outcomes in reperfused STEMI patients is not clear and is investigated in this meta-analysis of 13 randomized controlled trials (RCTs). Methods We performed an up-to-date search for all RCTs investigating adenosine as an adjunct to reperfusion in STEMI patients. We calculated pooled relative risks using a fixed-effect meta-analysis assessing the impact of adjunctive adenosine therapy on major clinical endpoint including all-cause mortality, non-fatal myocardial infarction, and heart failure. Surrogate markers of reperfusion were also analyzed. Results 13 RCTs (4273 STEMI patients) were identified and divided into 2 subgroups: intracoronary adenosine versus control (8 RCTs) and intravenous adenosine versus control (5 RCTs). In patients administered intracoronary adenosine, the incidence of heart failure was significantly lower (risk ratio [RR] 0.44 [95% CI 0.25–0.78], P = 0.005) and the incidence of coronary no-reflow was reduced (RR for TIMI flow<3 postreperfusion 0.68 [95% CI 0.47–0.99], P = 0.04). There was no difference in heart failure incidence in the intravenous adenosine group but most RCTs in this subgroup were from the thrombolysis era. There was no difference in non-fatal MI or all-cause mortality in both subgroups. Conclusion We find evidence of improved clinical outcome in terms of less heart failure in STEMI patients administered intracoronary adenosine as an adjunct to reperfusion. This finding will need to be confirmed in a large adequately powered prospective RCT. PMID:26402450

  4. Letrozole as the first-line treatment of infertile women with poly cystic ovarian syndrome (PCOS) compared with clomiphene citrate: A clinical trial

    PubMed Central

    Ghahiri, Ataollah; Mogharehabed, Neda; Mamourian, Mahboobeh

    2016-01-01

    Background: The purpose of this study was to determine the efficacy and safety of letrozole on ovulation induction and pregnancy in comparison with clomiphene citrate in PCOS patients. Materials and Methods: The study was based on prospective randomized clinical trial comparing the efficacy of letrozole as the first-line management of the PCOS patients in comparison to clomiphene citrate during 2009 to 2011 and was performed in one private infertility clinic. The study included 100 patients divided into 2 equal groups. Results: Pregnancy occurred in 29 of 50 patients in letrozole group (58%) and 24 of 51 patients in clomiphene group (47%). The difference was not statistically significant (P value = 0.23). Thirty patients in clomiphene group and 36 patients in letrozole group showed regular menses after or during the treatment course. No significant difference between the 2 groups was observed (P value = 0.21). Conclusion: Our findings suggest letrozole and clomiphene citrate are equally effective for induction of ovulation and achieving pregnancy in patients with PCOS. PMID:26962508

  5. The Internet and Clinical Trials: Background, Online Resources, Examples and Issues

    PubMed Central

    Seib, Rachael; Prescott, Todd

    2005-01-01

    Both the Internet and clinical trials were significant developments in the latter half of the twentieth century: the Internet revolutionized global communications and the randomized controlled trial provided a means to conduct an unbiased comparison of two or more treatments. Large multicenter trials are often burdened with an extensive development time and considerable expense, as well as significant challenges in obtaining, backing up and analyzing large amounts of data. Alongside the increasing complexities of the modern clinical trial has grown the power of the Internet to improve communications, centralize and secure data as well as to distribute information. As more and more clinical trials are required to coordinate multiple trial processes in real time, centers are turning to the Internet for the tools to manage the components of a clinical trial, either in whole or in part, to produce lower costs and faster results. This paper reviews the historical development of the Internet and the randomized controlled trial, describes the Internet resources available that can be used in a clinical trial, reviews some examples of online trials and describes the advantages and disadvantages of using the Internet to conduct a clinical trial. We also extract the characteristics of the 5 largest clinical trials conducted using the Internet to date, which together enrolled over 26000 patients. PMID:15829477

  6. Clinical Trials for Predictive Medicine—New Challenges and Paradigms*

    PubMed Central

    Simon, Richard

    2014-01-01

    Background Developments in biotechnology and genomics have increased the focus of biostatisticians on prediction problems. This has led to many exciting developments for predictive modeling where the number of variables is larger than the number of cases. Heterogeneity of human diseases and new technology for characterizing them presents new opportunities and challenges for the design and analysis of clinical trials. Purpose In oncology, treatment of broad populations with regimens that do not benefit most patients is less economically sustainable with expensive molecularly targeted therapeutics. The established molecular heterogeneity of human diseases requires the development of new paradigms for the design and analysis of randomized clinical trials as a reliable basis for predictive medicine[1, 2]. Results We have reviewed prospective designs for the development of new therapeutics with candidate predictive biomarkers. We have also outlined a prediction based approach to the analysis of randomized clinical trials that both preserves the type I error and provides a reliable internally validated basis for predicting which patients are most likely or unlikely to benefit from the new regimen. Conclusions Developing new treatments with predictive biomarkers for identifying the patients who are most likely or least likely to benefit makes drug development more complex. But for many new oncology drugs it is the only science based approach and should increase the chance of success. It may also lead to more consistency in results among trials and has obvious benefits for reducing the number of patients who ultimately receive expensive drugs which expose them risks of adverse events but no benefit. This approach also has great potential value for controlling societal expenditures on health care. Development of treatments with predictive biomarkers requires major changes in the standard paradigms for the design and analysis of clinical trials. Some of the key assumptions

  7. Operation of a radiopharmacy for a clinical trial.

    PubMed

    Norenberg, Jeffrey P; Petry, Neil A; Schwarz, Sally

    2010-09-01

    Clinical investigations of radiopharmaceuticals are undertaken to advance promising compounds toward approval by the Food and Drug Administration (FDA) as "legend drugs." This FDA approval requires that the safety and efficacy of the investigational drug (ID) be demonstrated through clinical trials. The investigational radiopharmaceutical drug service (IRDS) is a pharmacy service that plays a critical role in the acquisition, preparation, accountability, and distribution of radiopharmaceuticals used in clinical research. Due to their radioactive and other unique properties, and their potential role as biomarkers or tools in clinical trials of other therapeutic drugs, radiopharmaceutical drugs must be managed by a qualified IRDS rather than by a typical pharmacy-based investigational drug service (IDS). The IRDS is responsible for establishing study-specific procedures for appropriate radiopharmaceutical drug accountability, billing, procurement, storage, preparation, dispensing and destruction of investigational drugs within the hospital. All drugs, and particularly parenteral drug products, must be safe for administration to human subjects enrolled in clinical trials regardless of their FDA regulatory status as approved or investigational new drug products. The United States Pharmacopeia (USP) <797> sterile compounding requirements provides enforceable minimum practice and quality standards for compounded sterile preparations of drug products based on current scientific information and best sterile compounding practices. Consequently, they apply equally to facilities dedicated to IDS and IRDS operations. The FDA also regulates drug manufacturing through current Good Manufacturing Practices (cGMP). This rule (21CFR Part 212) establishes cGMP regulations specific to positron emission tomography radiopharmaceuticals, separate from the regular drug cGMP rule (Parts 210 and 211). Compliance with regulatory, statutory, and sponsor requirements is a major consideration

  8. Effects of centrophenoxine on body composition and some biochemical parameters of demented elderly people as revealed in a double-blind clinical trial.

    PubMed

    Fülöp, T; Wórum, I; Csongor, J; Leövey, A; Szabó, T; Pék, G; Zs -Nagy, I

    1990-01-01

    A double-blind clinical trial was performed on 50 persons (25 men, 25 women, average age 77 years) suffering from dementias of medium level (DSM III, Category 1, ICD No. 299). All subjects were residents in an old age home. The patients were treated first for 2 weeks by placebo tablets. During this period, body composition parameters were determined and these data served as controls. This was then followed by an 8-week-long treatment with the nootropic drug, centrophenoxine (CPH), 2 g/day distributed in 2x2 tablets of Helfergin(500) (Promonta, Hamburg, F.R.G.), or placebo tablets of identical size. After 8 weeks the laboratory tests were repeated again. The randomization code for verum or placebo treatment was revealed only after completing the trial. Four dropouts occurred during the treatment period. The total body water, extracellular water volume and exchangable Na(+) were determined by means of radioisotope methods. Plasma volume (PV) was measured by indocyanine-green dilution test. Body weights were also recorded. From the above data further parameters could be calculated. Serum lipid data as well as several hormone levels were also checked in the blood samples. The main results were better performance in psychometric tests (Pék et al., 1989) and a significant increase of the average intracellular water content (2.2-2.5% by weight) in the verum-treated group. The rehydration of the intracellular mass due to CPH treatment is consistent with the OH(*.) free radical scavenger properties of CPH and the predictions of the membrane hypothesis of aging. PMID:15374499

  9. 76 FR 51375 - Dialogues in Diversifying Clinical Trials: Successful Strategies for Engaging Women and...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-08-18

    ... HUMAN SERVICES Food and Drug Administration Dialogues in Diversifying Clinical Trials: Successful Strategies for Engaging Women and Minorities in Clinical Trials AGENCY: Food and Drug Administration, HHS... Diversifying Clinical Trials: Successful Strategies for Engaging Women and Minorities in Clinical Trials....

  10. Clinical Trial Results Vary Widely, But Always Advance Research | NIH MedlinePlus the Magazine

    MedlinePlus

    ... of this page please turn Javascript on. Feature: Clinical Trials Clinical Trial Results Vary Widely, But Always Advance Research Past ... very emotional." Should You Be Interested in a Clinical Trial People volunteer to take part in clinical trials ...

  11. Current status of quality in Japanese clinical trials.

    PubMed

    Saito, Kazuyuki; Kodama, Yasuo; Ono, Shunsuke; Mutoh, Mizue; Kawashima, Susumu; Fujimura, Akio

    2005-08-01

    The changes in the quality of Japanese clinical trials were evaluated by comparing the results of Good Clinical Practice (GCP) audits conducted from April 1997 to March 2000 (fiscal year (FY) 1997-1999) with those from April 2001 to March 2002 (FY2001). During both of the periods inspections were undertaken by the Organization for Pharmaceutical Safety and Research (OPSR). The audit findings in the former period were based on the audits that covered 331 hospitals and 775 trials conducted under the old GCP guideline. The audits in the latter period targeted 147 hospitals and 238 trials conducted under the old or new GCP guideline. The total number of deficiencies detected by GCP audits in the former three-year period (FY 1997-1999) was 1529, and the corresponding number in the latter single year (FY 2001) was 912. Two remarkable changes in OPSR's findings were observed between FY 1997-1999 and FY 2001 as follows; the proportion of protocol deviations increased from 14.7% (225/1529) to 53.1% (484/912), while the proportion of errors in case report forms (CRFs) decreased from 43.6% (666/1529) to 15.4% (140/912). The new GCP guideline sets very high standards for a hospital's qualification: to have sufficient equipment and hospital resources, to have capacity for promptly responding to urgent trial-related problems, to have an IRB, and to have appropriate staff including clinical research coordinators (CRCs) assigned to the clinical trial. Our results suggest that the impact of the regulatory changes of applicable standard is large for a hospital's qualification for conducting clinical trials in Japan. PMID:16054582

  12. A comparative randomized double-blind clinical trial of isoaminile citrate and chlophedianol hydrochloride as antitussive agents.

    PubMed

    Diwan, J; Dhand, R; Jindal, S K; Malik, S K; Sharma, P L

    1982-08-01

    The efficacy and safety of a new centrally acting antitussive agent, isoaminile citrate, was compared with that of chlophedianol hydrochloride in a double-blind, randomized interpatient study. A total of 66 patients participated, two and four patients were lost to follow-up with isoaminile and chlophedianol, respectively. In the experimentally induced cough in 12 normal human subjects, isoaminile (40 mg) was as effective as chlophedianol (20 mg), but its duration of action was somewhat longer. One subject developed allergic skin rash with chlophedianol and was withdrawn from the study. In 60 patients with cough associated with chest diseases, isoaminile (40 mg, 3 x daily) was as effective as chlophedianol (20 mg, 3 x daily) in suppressing cough as judged from the 3-h and 24-h cough counts. The increase in PEFR at day 7 of treatment was somewhat more marked with chlophedianol as compared with isoaminile. None of the drugs interfered with the expectoration process. The side effects observed were few, mild in nature, and did not require a decrease in dose or withdrawal of treatment in any of the patients. Isoaminile citrate was concluded to be an effective and relatively safe antitussive agent. Isoaminile citrate, alpha(isopropyl)-alpha-(beta-dimethylaminoproyl) phenylacetonitrile citrate, is a centrally acting antitussive agent. In animal experiments this drug was as efficacious as codeine but was devoid of any respiratory depressant effect [Krause 1958, Kuroda et al. 1971]. This controlled double-randomized interpatient study was designed to test the comparative efficacy and safety of isoaminile and chlophedianol, another centrally acting antitussive, in humans. PMID:6749701

  13. Clinical Trial of 2-Phenethyl Isothiocyanate as an Inhibitor of Metabolic Activation of a Tobacco-Specific Lung Carcinogen in Cigarette Smokers.

    PubMed

    Yuan, Jian-Min; Stepanov, Irina; Murphy, Sharon E; Wang, Renwei; Allen, Sharon; Jensen, Joni; Strayer, Lori; Adams-Haduch, Jennifer; Upadhyaya, Pramod; Le, Chap; Kurzer, Mindy S; Nelson, Heather H; Yu, Mimi C; Hatsukami, Dorothy; Hecht, Stephen S

    2016-05-01

    2-Phenethyl isothiocyanate (PEITC), a natural product found as a conjugate in watercress and other cruciferous vegetables, is an inhibitor of the metabolic activation and lung carcinogenicity of the tobacco carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) in F344 rats and A/J mice. We carried out a clinical trial to determine whether PEITC also inhibits the metabolic activation of NNK in smokers. Cigarette smokers were recruited and asked to smoke cigarettes containing deuterium-labeled [pyridine-D4]NNK for an acclimation period of at least 1 week. Then subjects were randomly assigned to one of two arms: PEITC followed by placebo, or placebo followed by PEITC. During the 1-week treatment period, each subject took PEITC (10 mg in 1 mL of olive oil, 4 times per day). There was a 1-week washout period between the PEITC and placebo periods. The NNK metabolic activation ratio [pyridine-D4]hydroxy acid/total [pyridine-D4]NNAL was measured in urine samples to test the hypothesis that PEITC treatment modified NNK metabolism. Eighty-two smokers completed the study and were included in the analysis. Overall, the NNK metabolic activation ratio was reduced by 7.7% with PEITC treatment (P = 0.023). The results of this trial, while modest in effect size, provide a basis for further investigation of PEITC as an inhibitor of lung carcinogenesis by NNK in smokers. Cancer Prev Res; 9(5); 396-405. ©2016 AACR. PMID:26951845

  14. Citation Sentiment Analysis in Clinical Trial Papers

    PubMed Central

    Xu, Jun; Zhang, Yaoyun; Wu, Yonghui; Wang, Jingqi; Dong, Xiao; Xu, Hua

    2015-01-01

    In scientific writing, positive credits and negative criticisms can often be seen in the text mentioning the cited papers, providing useful information about whether a study can be reproduced or not. In this study, we focus on citation sentiment analysis, which aims to determine the sentiment polarity that the citation context carries towards the cited paper. A citation sentiment corpus was annotated first on clinical trial papers. The effectiveness of n-gram and sentiment lexicon features, and problem-specified structure features for citation sentiment analysis were then examined using the annotated corpus. The combined features from the word n-grams, the sentiment lexicons and the structure information achieved the highest Micro F-score of 0.860 and Macro-F score of 0.719, indicating that it is feasible to use machine learning methods for citation sentiment analysis in biomedical publications. A comprehensive comparison between citation sentiment analysis of clinical trial papers and other general domains were conducted, which additionally highlights the unique challenges within this domain. PMID:26958274

  15. Clinical trials involving cats: What factors affect owner 1 participation?