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Sample records for 6-month clinical trial

  1. Stability, survival, and tolerability of a 4.5-mm-wide bone-anchored hearing implant: 6-month data from a randomized controlled clinical trial.

    PubMed

    Nelissen, Rik C; den Besten, Christine A; Mylanus, Emmanuel A M; Hol, Myrthe K S

    2016-01-01

    The objective of this study was to compare the stability, survival, and tolerability of 2 percutaneous osseointegrated titanium implants for bone conduction hearing: a 4.5-mm diameter implant (test) and a 3.75-mm diameter implant (control). Fifty-seven adult patients were included in this randomized controlled clinical trial. Sixty implants were allocated in a 2:1 (test-control) ratio. Follow-up visits were scheduled at 7, 14, 21, and 28 days; 6 and 12 weeks; and 6 months. At every visit, implant stability quotient (ISQ) values were recorded by means of resonance frequency analysis (RFA) and skin reactions were evaluated according to the Holgers classification. Implants were loaded with the bone conduction device at 3 weeks. Hearing-related quality of life was evaluated using the Abbreviated Profile of Hearing Aid Benefit (APHAB), the Glasgow Benefit Inventory (GBI), and the Glasgow Health Status Inventory (GHSI). ISQ values were statistically significantly higher for the test implant compared to the control implant. No implants were lost and soft tissue reactions were comparable for both implants. Positive results were reported in the hearing-related quality of life questionnaires. These 6-month results indicate that both implants and their corresponding hearing devices are safe options for hearing rehabilitation in patients with the appropriate indications. Loading at 3 weeks did not affect the stability of either implant.

  2. In Alzheimer's Disease, 6-Month Treatment with GLP-1 Analog Prevents Decline of Brain Glucose Metabolism: Randomized, Placebo-Controlled, Double-Blind Clinical Trial.

    PubMed

    Gejl, Michael; Gjedde, Albert; Egefjord, Lærke; Møller, Arne; Hansen, Søren B; Vang, Kim; Rodell, Anders; Brændgaard, Hans; Gottrup, Hanne; Schacht, Anna; Møller, Niels; Brock, Birgitte; Rungby, Jørgen

    2016-01-01

    In animal models, the incretin hormone GLP-1 affects Alzheimer's disease (AD). We hypothesized that treatment with GLP-1 or an analog of GLP-1 would prevent accumulation of Aβ and raise, or prevent decline of, glucose metabolism (CMRglc) in AD. In this 26-week trial, we randomized 38 patients with AD to treatment with the GLP-1 analog liraglutide (n = 18), or placebo (n = 20). We measured Aβ load in brain with tracer [(11)C]PIB (PIB), CMRglc with [(18)F]FDG (FDG), and cognition with the WMS-IV scale (ClinicalTrials.gov NCT01469351). The PIB binding increased significantly in temporal lobe in placebo and treatment patients (both P = 0.04), and in occipital lobe in treatment patients (P = 0.04). Regional and global increases of PIB retention did not differ between the groups (P ≥ 0.38). In placebo treated patients CMRglc declined in all regions, significantly so by the following means in precuneus (P = 0.009, 3.2 μmol/hg/min, 95% CI: 5.45; 0.92), and in parietal (P = 0.04, 2.1 μmol/hg/min, 95% CI: 4.21; 0.081), temporal (P = 0.046, 1.54 μmol/hg/min, 95% CI: 3.05; 0.030), and occipital (P = 0.009, 2.10 μmol/hg/min, 95% CI: 3.61; 0.59) lobes, and in cerebellum (P = 0.04, 1.54 μmol/hg/min, 95% CI: 3.01; 0.064). In contrast, the GLP-1 analog treatment caused a numerical but insignificant increase of CMRglc after 6 months. Cognitive scores did not change. We conclude that the GLP-1 analog treatment prevented the decline of CMRglc that signifies cognitive impairment, synaptic dysfunction, and disease evolution. We draw no firm conclusions from the Aβ load or cognition measures, for which the study was underpowered. PMID:27252647

  3. In Alzheimer’s Disease, 6-Month Treatment with GLP-1 Analog Prevents Decline of Brain Glucose Metabolism: Randomized, Placebo-Controlled, Double-Blind Clinical Trial

    PubMed Central

    Gejl, Michael; Gjedde, Albert; Egefjord, Lærke; Møller, Arne; Hansen, Søren B.; Vang, Kim; Rodell, Anders; Brændgaard, Hans; Gottrup, Hanne; Schacht, Anna; Møller, Niels; Brock, Birgitte; Rungby, Jørgen

    2016-01-01

    In animal models, the incretin hormone GLP-1 affects Alzheimer’s disease (AD). We hypothesized that treatment with GLP-1 or an analog of GLP-1 would prevent accumulation of Aβ and raise, or prevent decline of, glucose metabolism (CMRglc) in AD. In this 26-week trial, we randomized 38 patients with AD to treatment with the GLP-1 analog liraglutide (n = 18), or placebo (n = 20). We measured Aβ load in brain with tracer [11C]PIB (PIB), CMRglc with [18F]FDG (FDG), and cognition with the WMS-IV scale (ClinicalTrials.gov NCT01469351). The PIB binding increased significantly in temporal lobe in placebo and treatment patients (both P = 0.04), and in occipital lobe in treatment patients (P = 0.04). Regional and global increases of PIB retention did not differ between the groups (P ≥ 0.38). In placebo treated patients CMRglc declined in all regions, significantly so by the following means in precuneus (P = 0.009, 3.2 μmol/hg/min, 95% CI: 5.45; 0.92), and in parietal (P = 0.04, 2.1 μmol/hg/min, 95% CI: 4.21; 0.081), temporal (P = 0.046, 1.54 μmol/hg/min, 95% CI: 3.05; 0.030), and occipital (P = 0.009, 2.10 μmol/hg/min, 95% CI: 3.61; 0.59) lobes, and in cerebellum (P = 0.04, 1.54 μmol/hg/min, 95% CI: 3.01; 0.064). In contrast, the GLP-1 analog treatment caused a numerical but insignificant increase of CMRglc after 6 months. Cognitive scores did not change. We conclude that the GLP-1 analog treatment prevented the decline of CMRglc that signifies cognitive impairment, synaptic dysfunction, and disease evolution. We draw no firm conclusions from the Aβ load or cognition measures, for which the study was underpowered. PMID:27252647

  4. Effects of the SpeechEasy on Objective and Perceived Aspects of Stuttering: A 6-Month, Phase I Clinical Trial in Naturalistic Environments

    ERIC Educational Resources Information Center

    Pollard, Ryan; Ellis, John B.; Finan, Don; Ramig, Peter R.

    2009-01-01

    Purpose: Effects of the SpeechEasy when used under extraclinical conditions over several months were investigated. Primary purposes were to help establish Phase I level information about the therapeutic utility of the SpeechEasy and to compare those results with previous findings obtained in laboratory and clinical settings. Method: Eleven adults…

  5. Metformin effects on clinical features, endocrine and metabolic profiles, and insulin sensitivity in polycystic ovary syndrome: a randomized, double-blind, placebo-controlled 6-month trial, followed by open, long-term clinical evaluation.

    PubMed

    Moghetti, P; Castello, R; Negri, C; Tosi, F; Perrone, F; Caputo, M; Zanolin, E; Muggeo, M

    2000-01-01

    In the last few years some studies assessed the effects of attenuation of hyperinsulinemia and insulin resistance, obtained by insulin sensitizing agents, in women with polycystic ovary syndrome (PCOS), suggesting potential scope for these drugs in treating the whole spectrum of reproductive, endocrine, and metabolic abnormalities found in such subjects. However, the results of these studies, mostly uncontrolled and short-term, are still inconclusive, and there is no long-term follow-up. In the present study, 23 PCOS subjects [mean (+/- SE) body mass index 30.0+/-1.1 kg/m2] were randomly assigned to double-blind treatment with metformin (500 mg tid) or placebo for 6 months, while maintaining their usual eating habits. Before and after treatment, menstrual history, endocrine and metabolic profiles, serum 17-hydroxyprogesterone response to GnRH-agonist testing, and insulin sensitivity measured by the glucose clamp technique were assessed. Eighteen of these women, as well as 14 additional PCOS patients, were subsequently given metformin in an open trial for 11.0+/-1.3 months (range 4-26), to assess long-term effects of treatment and baseline predictors of metformin efficacy on reproductive abnormalities. After metformin treatment, mean frequency of menstruation improved (P = 0.002), due to striking amelioration of menstrual abnormalities in about 50% of subjects. Women given metformin showed reduced plasma insulin (at fasting: P = 0.057; during the clamp studies: P<0.01) and increased insulin sensitivity (P<0.05). Concurrently, ovarian hyperandrogenism was attenuated, as indicated by significant reductions in serum free testosterone (P<0.05) and in the 17-hydroxyprogesterone response to GnRH-agonist testing (P<0.05). No changes were found in the placebo group. Only comparable minor changes in body mass index were found both in the metformin group and in the placebo group. In the open, long-term trial 17 women (54.8%) showed striking improvements of their menstrual

  6. Data analysis of 87 tic patients for 6 months' treatment in a Korean medicine clinic.

    PubMed

    Chun, Young-Ho; Kim, Won-Ill; Kim, Bo-Kyung

    2013-10-01

    This study was carried out to investigate the relationship between the therapeutic effects of treatment for tic disorder and Korean medicine clinical tests, including body mass index (BMI) and heart variability rate (HRV). This study was not a clinical trial, but a data analysis of 87 tic patients who were treated for 6 months during the time period from Nov. 2010 to Jan. 2012. The clinical evaluation of the symptoms was recorded using the Korean version of the Yale Global Tic Severity Scale (YGTSS). The BMI and the HRV were measured according to a schedule, and various kinds of statistical methods were used. Among the 87 patients, the number of males was 3.34 times the number of females, and 58 patients (66.7%) had been suffering for more than 12 months. The onset age of the males was significantly lower than that of the females, and males had the symptoms longer than females had. Also, males with a family history of tics were 2.5 times as many as females, and their onset ages were substantially lower. At the first medical examinations, the average score on the YGTSS was 34.08, and it decreased linearly as the treatment progressed. After 4 and 6 months of treatment, it had decreased significantly. The YGTSS score and the period of suffering correlated positively. At the first visit, each HRV datum was in the normal range. After the 6 months' treatment, Ln (TP), Ln (LF), and Ln (HF) had dropped substantially in the normal range while Ln (VLF) and the LF/HF ratio had not changed in a meaningful way. During the treatment period, the BMI stayed relatively constant without any meaningful changes.

  7. 6-Month Outcomes from a Randomized Controlled Trial to Prevent Perinatal Depression in Low-Income Home Visiting Clients

    PubMed Central

    Tandon, S. Darius; Leis, Julie A.; Mendelson, Tamar; Perry, Deborah F.; Kemp, Karen

    2013-01-01

    Objectives Perinatal depression (PD) has negative consequences for mothers and children and is more prevalent among women of low socioeconomic status. Home visitation programs serve low-income pregnant women at risk for PD. This study tested the efficacy of a group-based cognitive behavioral intervention (Mothers and Babies Course; MB) in reducing depressive symptoms and preventing the onset of perinatal depression among low-income women enrolled in home visitation. Methods A randomized controlled trial was conducted. Seventy-eight women who were pregnant or had a child less than 6 months of age and who were assessed as at risk for PD were randomized to the MB intervention or usual home visiting services. Depressive symptoms were assessed at baseline and 1-week, 3- and 6-months post-intervention; depressive episodes were assessed with a clinical interview at the 6-month follow-up. Results Depressive symptoms declined at a significantly greater rate for intervention participants than usual care participants between baseline and 1-week, 3 months, and 6 months post-intervention. At the six-month follow-up, 15% of women who received the MB intervention had experienced a major depressive episode as compared with 32% of women receiving usual care. Conclusions Integrating mental health interventions into home visitation appears to be a promising approach for preventing PD. Cognitive behavioral techniques can be effective in preventing depression in perinatal populations and treating it. PMID:23793487

  8. Effect of testosterone supplementation on sexual functioning in aging men: a 6-month randomized controlled trial.

    PubMed

    Emmelot-Vonk, M H; Verhaar, H J J; Nakhai-Pour, H R; Grobbee, D E; van der Schouw, Y T

    2009-01-01

    Serum testosterone levels decline significantly with aging and this has been associated with reduced sexual function. We have conducted a double-blind, randomized, placebo-controlled trial to investigate the effect of testosterone supplementation on sexual function in 237 elderly men with a testosterone level <13.7 nmol l(-1). Participants were randomly assigned to receive oral testosterone undecanoate or a placebo for 6 months. A total of 207 men completed the study. After treatment, there were no differences in scores on sexual function between the groups. Subanalysis showed that although a baseline testosterone level in the lowest tertile was associated with significantly lower scores for sexual fantasies, desire of sexual contact and frequency of sexual contact, supplementation of testosterone did not result in improvement on any of these items in this group. In conclusion, the findings do not support the view that testosterone undecanoate supplementation for 6 months to elderly men with low-normal testosterone concentrations favorably affects sexual function. PMID:19225466

  9. Replicating ¡Cuídate!: 6-Month Impact Findings of a Randomized Controlled Trial

    PubMed Central

    Layzer, Carolyn; Layzer, Jean; Price, Cristofer; Juras, Randall; Blocklin, Michelle; Mendez, Jacqueline

    2016-01-01

    Objectives. To test whether ¡Cuídate!, a program culturally adapted for Hispanic youths, affects sexual risk behavior. Methods. We evaluated 3 replications of ¡Cuídate! in California, Arizona, and Massachusetts in a randomized controlled trial (registry no. NCT02540304) in which 2169 primarily Hispanic participants were randomly assigned to an intervention (n = 1326) or a control (n = 870) group. Youths were surveyed at baseline (September 2012–April 2014) and 6 months postbaseline (March 2013–October 2014). We estimated pooled and subgroup impacts using a regression framework with baseline covariates to increase statistical precision (1216 youths analyzed in the treatment group, 806 analyzed in the control group). Results. We found no impacts on the study’s primary outcomes of recent sexual activity or recent unprotected sexual activity. However, ¡Cuídate! improved knowledge (10%–20% increase; P < .001), attitudes (effect size = .24; P < .001), and skills (effect size = .14; P = .002). Exploratory subgroup analyses suggest potentially problematic effects for some groups. Conclusions. Findings suggest that ¡Cuídate! was effective in improving youths’ knowledge and attitudes. However, after 6 months, these changes did not translate to improvements in reported sexual risk behaviors. PMID:27689498

  10. Crown lengthening in the maxillary anterior region: a 6-month prospective clinical study.

    PubMed

    Deas, David E; Mackey, Scott A; Sagun, Ruben S; Hancock, Raymond H; Gruwell, Scott F; Campbell, Casey M

    2014-01-01

    The purpose of this study was to assess osseous parameters and stability of maxillary anterior teeth following crown lengthening surgery. Thirty-six patients requiring facial crown lengthening of 277 maxillary anterior and first premolar teeth were included. Presurgical and intraoperative clinical measurements were recorded at baseline and 1, 3, and 6 months postsurgery at midfacial, mesiofacial, and distofacial line angles. The data presented here suggest that when crown lengthening anterior maxillary teeth, the distance between the desired gingival margin and alveolar crest is usually insufficient to allow for biologic width. In addition, there is significant tissue rebound that may stabilize by 6 months. Tissue rebound appears related to flap position relative to the alveolar crest at suturing. These findings suggest that clinicians should establish proper anterior crown length with osseous resection.

  11. Mississippi Communities for Healthy Living: Results of a 6-month nutrition education comparative effectiveness trial

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The United States Lower Mississippi Delta (LMD) region suffers from high prevalence of chronic health conditions with nutritional etiologies, including obesity, high cholesterol, hypertension, and diabetes. Responding to the need for effective nutrition interventions in the LMD, a 2-arm, 6-month, n...

  12. Child-Parent Psychotherapy: 6-Month Follow-up of a Randomized Controlled Trial

    ERIC Educational Resources Information Center

    Lieberman, Alicia F.; Ippen, Chandra Ghosh; Van Horn, Patricia

    2006-01-01

    Objective: To examine the durability of improvement in child and maternal symptoms 6 months after termination of child-parent psychotherapy (CPP). Method: Seventy-five multiethnic preschool-age child-mother dyads from diverse socioeconomic backgrounds were randomly assigned to (1) CPP or (2) case management plus community referral for individual…

  13. A 6-month randomized controlled trial to test the efficacy of a lifestyle intervention for weight gain management in schizophrenia

    PubMed Central

    2013-01-01

    Background Patients with schizophrenia have lower longevity than the general population as a consequence of a combination of risk factors connected to the disease, lifestyle and the use of medications, which are related to weight gain. Methods A multicentric, randomized, controlled-trial was conducted to test the efficacy of a 12-week group Lifestyle Wellness Program (LWP). The program consists of a one-hour weekly session to discuss topics like dietary choices, lifestyle, physical activity and self-esteem with patients and their relatives. Patients were randomized into two groups: standard care (SC) and standard care plus intervention (LWP). Primary outcome was defined as the weight and body mass index (BMI). Results 160 patients participated in the study (81 in the intervention group and 79 in the SC group). On an intent to treat analysis, after three months the patients in the intervention group presented a decrease of 0.48 kg (CI 95% -0.65 to 1.13) while the standard care group showed an increase of 0.48 kg (CI 95% 0.13 to 0.83; p=0.055). At six-month follow-up, there was a significant weight decrease of −1.15 kg, (CI 95% -2.11 to 0.19) in the intervention group compared to a weight increase in the standard care group (+0.5 kg, CI 95% -0.42–1.42, p=0.017). Conclusion In conclusion, this was a multicentric randomized clinical trial with a lifestyle intervention for individuals with schizophrenia, where the intervention group maintained weight and presented a tendency to decrease weight after 6 months. It is reasonable to suppose that lifestyle interventions may be important long-term strategies to avoid the tendency of these individuals to increase weight. Clinicaltrials.gov identifier NCT01368406 PMID:23418863

  14. Clinical efficacy of a dentifrice and oral rinse containing sanguinaria extract and zinc chloride during 6 months of use.

    PubMed

    Harper, D S; Mueller, L J; Fine, J B; Gordon, J; Laster, L L

    1990-06-01

    The efficacy of combined use of toothpaste and oral rinse containing sanguinaria extract and zinc chloride was compared to placebo products in a 6-month clinical trial. Sixty subjects with moderate levels of plaque and gingivitis were randomly assigned to active and placebo groups. Noninvasive measures of plaque and gingivitis were assessed at baseline and at 2, 6, 8, 14, 20, and 28 weeks. Bleeding on probing was measured at baseline and 6, 14, and 28 weeks. Active group scores were significantly lower (P less than .0001) than placebo scores at each post-baseline time point for all indices, with the exception of plaque at 2 weeks. The 28 week active group scores were 21% lower than the placebo group for plaque, 25% lower for gingivitis, and 43% lower for bleeding on probing. No dental staining or taste alteration was reported in the active group. Three of 30 active group subjects exhibited minor soft tissue irritations that resolved spontaneously without discontinuation of product use. Results indicate that the test products showed good levels of safety and efficacy when administered in a combined use regimen for 6 months.

  15. Physical Exercise with Multicomponent Cognitive Intervention for Older Adults with Alzheimer's Disease: A 6-Month Randomized Controlled Trial

    PubMed Central

    Kim, Min-Ji; Han, Chang-Wan; Min, Kyoung-Youn; Cho, Chae-Yoon; Lee, Chae-Won; Ogawa, Yoshiko; Mori, Etsuro; Kohzuki, Masahiro

    2016-01-01

    Aims This study aimed to investigate the effect of 6-month physical exercise with a multicomponent cognitive program (MCP) on the cognitive function of older adults with moderate to severe Alzheimer's disease (AD). Methods We included 33 participants with AD in a 6-month randomized controlled trial. The intervention group participated in physical exercise and received a MCP. The control group received only the MCP. Before and after the intervention, cognitive outcomes were assessed using the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-cog), Mini-Mental State Examination, and the Clock Drawing Test. Physical performance was evaluated by exercise time, the number of pedal rotation, total load, grip strength, and the Berg Balance Scale (BBS). Results In all cognitive measures, there were no significant improvements between the two groups after 6 months in the baseline value-adjusted primary analysis. However, the ADAS-cog score was significantly lower between the two groups in secondary analysis adjusted for baseline value, age, sex, and education years. All physical outcomes were significantly higher in the intervention group except for total load compared with baseline measurements. Conclusion This study indicates that it is possible to improve cognitive function in older adults with moderate to severe AD through 6-month physical exercise with a multicomponent cognitive intervention. PMID:27403134

  16. Follow-Up of the Cues and Care Trial: Mother and Infant Outcomes at 6 Months

    ERIC Educational Resources Information Center

    Feeley, Nancy; Zelkowitz, Phyllis; Shrier, Ian; Stremler, Robyn; Westreich, Ruta; Dunkley, David; Steele, Russell; Rosberger, Zeev; Lefebvre, Francine; Papageorgiou, Apostolos

    2012-01-01

    The long-term effects of the Cues intervention to reduce anxiety and enhance the interactive behavior of mothers of very low birth weight (VLBW) infants were investigated. A randomized trial comparing the Cues intervention to an attention control condition was conducted. A total of 122 mothers of newborns weighing less than 1,500 g were…

  17. Tibial bone responses to 6-month calcium and vitamin D supplementation in young male jockeys: A randomised controlled trial.

    PubMed

    Silk, Leslie N; Greene, David A; Baker, Michael K; Jander, Caron B

    2015-12-01

    Young male jockeys compromise bone health by engaging in caloric restriction and high volumes of physical activity during periods of musculoskeletal growth and development. The aim of this randomised, double-blinded, placebo-controlled trial was to establish whether calcium and vitamin D supplementation would improve bone properties of young male jockeys. We conducted a 6-month trial with two groups of weight-, height- and age-matched apprentice male jockeys (age=20.2 ± 3.2 yrs). Participants were supplemented with 800 mg of calcium and 400 IU of vitamin D (S, n=8) or a placebo (cellulose) (P, n=9) daily for 6-months. Baseline calcium intake was (669.7 ± 274.3 (S) vs 790.4 ± 423.9 (P) and vitamin D 64.6 ± 19.5 (S) vs 81.2 ± 24.4 (P) with no statistical differences. Peripheral quantitative computed tomography (pQCT) measured ultra-distal (4%) and proximal (66%) tibial bone properties at baseline and 6 months. Blood-borne markers of bone turnover, P1NP and CTX and vitamin D concentration were assessed. After co-varying for height, weight and baseline bone measurements, the supplemented group displayed greater post-intervention bone properties at the 66% proximal site with cortical content (mgmm) 6.6% greater (p<0.001), cortical area (mm(2)) 5.9% larger (p<0.001), cortical density (mgcm(2)) 1.3% greater (p=0.001), and total area (mm(2)) 4% larger (p=0.003). No other between group differences in bone variables were observed. Blood analysis indicated higher vitamin D levels (18.1%, p=0.014) and lower CTx (ng/L) (-24.8%, p=0.011) in the supplemented group with no differences observed in P1NP. This is the first randomised controlled trial to examine the efficacy of calcium and vitamin D supplementation in improving bone properties in a highly vulnerable, young athletic, weight-restricted population. Results using pQCT indicate beneficial effects of supplementation on bone properties in as little as six months. Although the study size is small, this intervention

  18. 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 ...

  19. Vitamin A supplementation every 6 months with retinol in 1 million pre-school children in north India: DEVTA, a cluster-randomised trial

    PubMed Central

    Awasthi, Shally; Peto, Richard; Read, Simon; Clark, Sarah; Pande, Vinod; Bundy, Donald; the DEVTA (Deworming and Enhanced Vitamin A) team

    2013-01-01

    Summary Background In north India, vitamin A deficiency (retinol <0·70 μmol/L) is common in pre-school children and 2–3% die at ages 1·0–6·0 years. We aimed to assess whether periodic vitamin A supplementation could reduce this mortality. Methods Participants in this cluster-randomised trial were pre-school children in the defined catchment areas of 8338 state-staffed village child-care centres (under-5 population 1 million) in 72 administrative blocks. Groups of four neighbouring blocks (clusters) were cluster-randomly allocated in Oxford, UK, between 6-monthly vitamin A (retinol capsule of 200 000 IU retinyl acetate in oil, to be cut and dripped into the child's mouth every 6 months), albendazole (400 mg tablet every 6 months), both, or neither (open control). Analyses of retinol effects are by block (36 vs 36 clusters). The study spanned 5 calendar years, with 11 6-monthly mass-treatment days for all children then aged 6–72 months. Annually, one centre per block was randomly selected and visited by a study team 1–5 months after any trial vitamin A to sample blood (for retinol assay, technically reliable only after mid-study), examine eyes, and interview caregivers. Separately, all 8338 centres were visited every 6 months to monitor pre-school deaths (100 000 visits, 25 000 deaths at ages 1·0–6·0 years [the primary outcome]). This trial is registered at ClinicalTrials.gov, NCT00222547. Findings Estimated compliance with 6-monthly retinol supplements was 86%. Among 2581 versus 2584 children surveyed during the second half of the study, mean plasma retinol was one-sixth higher (0·72 [SE 0·01] vs 0·62 [0·01] μmol/L, increase 0·10 [SE 0·01] μmol/L) and the prevalence of severe deficiency was halved (retinol <0·35 μmol/L 6% vs 13%, decrease 7% [SE 1%]), as was that of Bitot's spots (1·4% vs 3·5%, decrease 2·1% [SE 0·7%]). Comparing the 36 retinol-allocated versus 36 control blocks in analyses of the primary outcome, deaths per child

  20. A Pilot Prospective Randomized Control Trial Comparing Exercises Using Videogame Therapy to Standard Physical Therapy: 6 Months Follow-Up.

    PubMed

    Parry, Ingrid; Painting, Lynda; Bagley, Anita; Kawada, Jason; Molitor, Fred; Sen, Soman; Greenhalgh, David G; Palmieri, Tina L

    2015-01-01

    Commercially available, interactive videogames that use body movements for interaction are used clinically in burn rehabilitation and have been shown to facilitate functional range of motion (ROM) but their efficacy with burn patients has not yet been proven. The purpose of this pilot randomized control study was to prospectively compare planar and functional ROM, compliance, pain, enjoyment, and exertion in pediatric burn patients receiving two types of rehabilitation therapy. Seventeen school-aged children with 31 affected limbs who demonstrated limited shoulder ROM from burn injury were randomized to receive exercises using either standard therapy ROM activities (ST) or interactive videogame therapy (VGT). Patients received 3 weeks of the designated therapy intervention twice daily. They were then given a corresponding home program of the same type of therapy to perform regularly for 6 months. Standard goniometry and three-dimensional motion analysis during functional tasks were used to assess ROM. Measures were taken at baseline, 3 weeks, 3 months, and 6 months. Pain was measured before and after each treatment session during the 3-week intervention. There was no difference in compliance, enjoyment, or exertion between the groups. Patients in both the ST and VGT groups showed significant improvement in shoulder flexion (P < .001), shoulder abduction (P <.001), shoulder external rotation (P = .01), and elbow flexion (P = .004) ROM from baseline to 6 months as measured with goniometry. Subjects also showed significant gains in elbow flexion (P = .04) during hand to head and shoulder flexion (P = .04) during high reach. There was no difference in ROM gains between the groups. Within group comparison showed that the VGT group had significantly more recovery of ROM during the first 3 weeks than any other timeframe in the study, whereas ST had most gains at 3 months. There was a significant difference between the groups in the subjects' pain response. ST subjects

  1. Efficacy of memantine in the treatment of fibromyalgia: A double-blind, randomised, controlled trial with 6-month follow-up.

    PubMed

    Olivan-Blázquez, Bárbara; Herrera-Mercadal, Paola; Puebla-Guedea, Marta; Pérez-Yus, Mari-Cruz; Andrés, Eva; Fayed, Nicolas; López-Del-Hoyo, Yolanda; Magallon, Rosa; Roca, Miquel; Garcia-Campayo, Javier

    2014-12-01

    Fibromyalgia (FM) is a prevalent and disabling chronic disease. Recent studies have found elevated levels of glutamate in several brain regions, leading to hypotheses about the usefulness of glutamate-blocking drugs such as memantine in the treatment of FM. The aim of this study was to evaluate the efficacy of memantine in the treatment of pain and other clinical variables (global function, clinical impression, depression, anxiety, quality of life) in FM patients. A double-blind, parallel randomised controlled trial was developed. A total of 63 patients diagnosed with FM were recruited from primary health care centres in Zaragoza, Spain. Memantine was administered at doses of 20mg/d after 1 month of titration. Assessments were carried out at baseline, posttreatment, and 3- and 6-month follow-up. Compared with a placebo group, memantine significantly decreased ratings on a pain visual analogue scale (Cohen's d=1.43 at 6 months) and pain measured with a sphygmomanometer (d=1.05). All other secondary outcomes except anxiety also improved, with moderate-to-large effect sizes at 6 months. Compared with placebo, the absolute risk reduction obtained with memantine was 16.13% (95% confidence interval=2.0% to 32.6%), and the number needed to treat was 6.2 (95% confidence interval=3 to 47). Tolerance was good, with dizziness (8 patients) and headache (4 patients) being the most frequent side effects of memantine. Although additional studies with larger sample sizes and longer follow-up times are needed, this study provides preliminary evidence of the utility of memantine for the treatment of FM.

  2. Population deworming every 6 months with albendazole in 1 million pre-school children in north India: DEVTA, a cluster-randomised trial

    PubMed Central

    Awasthi, Shally; Peto, Richard; Read, Simon; Richards, Susan M; Pande, Vinod; Bundy, Donald; the DEVTA (Deworming and Enhanced Vitamin A) team

    2013-01-01

    Summary Background In north India many pre-school children are underweight, many have intestinal worms, and 2–3% die at ages 1·0–6·0 years. We used the state-wide Integrated Child Development Service (ICDS) infrastructure to help to assess any effects of regular deworming on mortality. Methods Participants in this cluster-randomised study were children in catchment areas of 8338 ICDS-staffed village child-care centres (under-5 population 1 million) in 72 administrative blocks. Groups of four neighbouring blocks were cluster-randomly allocated in Oxford between 6-monthly vitamin A (retinol capsule of 200 000 IU retinyl acetate in oil, to be cut and dripped into the child's mouth every 6 months), albendazole (400 mg tablet every 6 months), both, or neither (open control). Analyses of albendazole effects are by block (36 vs 36 clusters). The study spanned 5 calendar years, with 11 6-monthly mass-treatment days for all children then aged 6–72 months. Annually, one centre per block was randomly selected and visited by a study team 1–5 months after any trial deworming to sample faeces (for presence of worm eggs, reliably assessed only after mid-study), weigh children, and interview caregivers. Separately, all 8338 centres were visited every 6 months to monitor pre-school deaths (100 000 visits, 25 000 deaths at age 1·0–6·0 years [the primary outcome]). This trial is registered at ClinicalTrials.gov, NCT00222547. Findings Estimated compliance with 6-monthly albendazole was 86%. Among 2589 versus 2576 children surveyed during the second half of the study, nematode egg prevalence was 16% versus 36%, and most infection was light. After at least 2 years of treatment, weight at ages 3·0–6·0 years (standardised to age 4·0 years, 50% male) was 12·72 kg albendazole versus 12·68 kg control (difference 0·04 kg, 95% CI −0·14 to 0·21, p=0·66). Comparing the 36 albendazole-allocated versus 36 control blocks in analyses of the primary outcome, deaths

  3. A 6-month home usage trial of a 1% chlorhexidine toothpaste (1). Effects on plaque, gingivitis, calculus and toothstaining.

    PubMed

    Yates, R; Jenkins, S; Newcombe, R; Wade, W; Moran, J; Addy, M

    1993-02-01

    Research and development has been aimed towards the development of toothpastes for oral hygiene and gingival health benefits. The most effective antiplaque agent to date, chlorhexidine, is difficult to formulate into active toothpaste products. Despite some encouraging findings for experimental chlorhexidine toothpastes, there are to date no commercially available products. Based on positive findings from an experimental gingivitis study, this investigation evaluated 2 chlorhexidine toothpastes, one with fluoride, as adjuncts to oral hygiene. The study was a double-blind controlled, parallel, balanced group design, extending over 6 months. A total of 297 volunteers commenced the study after screening for a minimum acceptance level of gingivitis. At baseline, 6, 12 and 24 weeks, stain, gingival, bleeding and plaque indices were recorded, together with a calculus index at 6, 12 and 24 weeks. After a baseline prophylaxis, volunteers used the allocated product 2 x per day, with no other oral hygiene instructions given. Plaque, gingival and bleeding scores improved in all 3 groups, but to an overall significantly greater extent in the active groups. However, staining and calculus indices were significantly increased in the active compared to the control group. If the local side-effects of chlorhexidine are considered to be acceptable, these chlorhexidine toothpastes could be recommended for the same clinical applications as other chlorhexidine products. The apparent compatibility of fluoride with chlorhexidine in the one product may be pertinent to caries prevention.

  4. 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 ...

  5. Clinical trials

    PubMed Central

    Garnham, J. C.

    1974-01-01

    The choice of standard drugs to be used in clinical trials must be based on consideration of human absorption data, in vitro characteristics, possible interactions, comparative efficacy and safety, previous data regarding the standard in relation to the syndrome to be studied, and correlation of blood levels, effectiveness and safety. PMID:4465771

  6. Participating in Clinical Trials

    MedlinePlus

    ... this page please turn Javascript on. Participating in Clinical Trials About Clinical Trials A Research Study With Human Subjects A clinical ... to treat or cure a disease. Phases of Clinical Trials Clinical trials of drugs are usually described based ...

  7. Comparison of AIK-C measles vaccine in infants at 6 months with Schwarz vaccine at 9 months: a randomized controlled trial in Ghana.

    PubMed Central

    Nkrumah, F. K.; Osei-Kwasi, M.; Dunyo, S. K.; Koram, K. A.; Afari, E. A.

    1998-01-01

    In a randomized controlled trial in a measles endemic area, standard-dose (4.0 log10pfu) AIK-C measles vaccine administered at 6 months of age was compared to standard-dose Schwarz vaccine (3.7log10pfu) given at 9 months. Seroconversion rates at 3 and 6 months after immunization in the two groups were comparable and similar. The geometric mean titres achieved were, however, significantly higher in the Schwarz group (P < 0.05). No immediate serious side-effects were observed with either vaccine. We conclude that standard-dose AIK-C measles vaccine can be recommended for measles immunization in children below 9 months of age, especially in highly endemic and high-risk areas in developing countries. PMID:9803586

  8. Effectiveness of group acceptance and commitment therapy for fibromyalgia: a 6-month randomized controlled trial (EFFIGACT study).

    PubMed

    Luciano, Juan V; Guallar, José A; Aguado, Jaume; López-Del-Hoyo, Yolanda; Olivan, Bárbara; Magallón, Rosa; Alda, Marta; Serrano-Blanco, Antoni; Gili, Margalida; Garcia-Campayo, Javier

    2014-04-01

    In the last decade, there has been burgeoning interest in the effectiveness of third-generation psychological therapies for managing fibromyalgia (FM) symptoms. The present study examined the effectiveness of acceptance and commitment therapy (ACT) on functional status as well as the role of pain acceptance as a mediator of treatment outcomes in FM patients. A total of 156 patients with FM were enrolled at primary health care centers in Zaragoza, Spain. The patients were randomly assigned to a group-based form of ACT (GACT), recommended pharmacological treatment (RPT; pregabalin + duloxetine), or wait list (WL). The primary end point was functional status (measured with the Fibromyalgia Impact Questionnaire, FIQ). Secondary end points included pain catastrophizing, pain acceptance, pain, anxiety, depression, and health-related quality of life. The differences between groups were calculated by linear mixed-effects (intention-to-treat approach) and mediational models through path analyses. Overall, GACT was statistically superior to both RPT and WL immediately after treatment, and improvements were maintained at 6months with medium effect sizes in most cases. Immediately after treatment, the number needed to treat for 20% improvement compared to RPT was 2 (95% confidence interval 1.2-2.0), for 50% improvement 46, and for achieving a status of no worse than mild impaired function (FIQ total score <39) also 46. Unexpectedly, 4 of the 5 tested path analyses did not show a mediation effect. Changes in pain acceptance only mediated the relationship between study condition and health-related quality of life. These findings are discussed in relation to previous psychological research on FM treatment.

  9. A 6-month follow-up study of the randomized controlled Ma-Pi macrobiotic dietary intervention (MADIAB trial) in type 2 diabetes

    PubMed Central

    Soare, A; Del Toro, R; Khazrai, Y M; Di Mauro, A; Fallucca, S; Angeletti, S; Skrami, E; Gesuita, R; Tuccinardi, D; Manfrini, S; Fallucca, F; Pianesi, M; Pozzilli, P

    2016-01-01

    Background: In the MADIAB trial (a 21-day randomized, controlled trial in patients with type 2 diabetes (T2D)), intervention with the Ma-Pi 2 macrobiotic diet resulted in significantly greater improvements in metabolic control compared with a standard recommended diet for patients with T2D. We report on a 6-month follow-up study, which investigated, whether these benefits extended beyond the 21-day intensive dietary intervention, in real-world conditions. Subjects: At the end of the MADIAB trial (baseline of this follow-up study), all participants continued their assigned diet (Ma-Pi or control) for 6 months. The Ma-Pi 2 group followed the Ma-Pi 4 diet during this follow-up study. Forty of the original 51 subjects (78.4%) participated in the follow-up (body mass index, 27–45 kg m−2; age, 40–75 years). Primary outcome was percentage change from baseline in HbA1c; secondary outcomes were anthropometric data and lipid panel. Results: A significantly greater median percentage reduction was observed for HbA1c in the Ma-Pi group (−11.27% (95% confidence interval (CI): −10.17; −12.36)) compared with the control group (−5.88% (95% CI: −3.79; −7.98)) (P < 0.001). Total and low-density lipoprotein (LDL) cholesterol increased in both groups with no differences between groups (P=0.331 and P=0.082, respectively). After correcting for age and gender, the Ma-Pi diet was associated with a higher percentage reduction in HbA1c (95% CI: 2.56; 7.61) and body weight (95% CI: 0.40; 3.99), and a higher percentage increase in LDL cholesterol (95% CI: −1.52; −33.16). However, all participants' total and LDL cholesterol levels remained within recommended ranges (<200 mg dl−1 and <100 mg dl−1, respectively). The Ma-Pi diet group achieved the target median HbA1c value (<5.7% (39 mmol mol−1)) at 6 months. Conclusions: Both the Ma-Pi and control diets maintained their benefits beyond the 21-day intensive monitored intervention over a 6-month follow

  10. An immersive “simulation week” enhances clinical performance of incoming surgical interns improved performance persists at 6 months follow-up

    PubMed Central

    Singh, Pritam; Aggarwal, Rajesh; Pucher, Philip H.; Hashimoto, Daniel A.; Beyer-Berjot, Laura; Bharathan, Rasiah; Middleton, Katherine E.; Jones, Joanne; Darzi, Ara

    2015-01-01

    Background The transition from student to intern can be challenging. The “August” or “July effect” describes increased errors and reduced patient safety during this transition. The study objectives were to develop, pilot, and evaluate clinical performance after an immersive simulation course for incoming interns. Methods Graduating students were recruited for a 1-week immersive simulation course. Controls received no simulation training. Primary outcome (at baseline, and 1 and 6 months) was clinical performance on Objective Structured Clinical Examinations (OSCE) of clinical procedures and surgical technical skills. Secondary outcomes were self-reported confidence and clinical procedure logbook data. Results Nineteen students were recruited. Sixteen completed the 6-month follow-up, 10 in the intervention group and 6 in the control group. No differences were demonstrated between interventions and controls at baseline (OSCE [median, 66 vs 78; P = .181], technical skills [48 vs 52.5; P = .381], and confidence [101 vs 96; P = .368]). Interventions outperformed controls at 1 month (OSCE [111 vs 82; P = .001], technical skills [78.5 vs 63; P = .030], and confidence [142 vs 119; P < .001]), and 6 months (OSCE [107 vs 93; P = .007], technical skills [92.5 vs 69; P = .044], and confidence [148 vs 129; P = .022]). No differences were observed in numbers of clinical procedures performed at 1 (P = .958), 4 (P = .093), or 6 months (P = .713). Conclusion The immersive simulation course objectively improved subjects’ clinical skills, technical skills, and confidence. Despite similar clinical experience as controls, the intervention group’s improved performance persisted at 6 months follow-up. This feasible and effective intervention to ease transition from student to intern could reduce errors and enhance patient safety. PMID:25633735

  11. Weight-Loss Outcomes: A Systematic Review and Meta-Analysis of Intermittent Energy Restriction Trials Lasting a Minimum of 6 Months.

    PubMed

    Headland, Michelle; Clifton, Peter M; Carter, Sharayah; Keogh, Jennifer B

    2016-01-01

    The aim of this systematic review and meta-analysis is to summarise the effects of intermittent energy restriction on weight and biological markers in long term intervention studies of >6 months duration. An electronic search was performed using the MEDLINE, EMBASE and the Cochrane Library databases for intervention trials lasting 6 months or longer investigating the effects of intermittent energy restriction. A total of nine studies were identified as meeting the pre-specified criteria. All studies included an intermittent energy restriction arm, with six being directly compared to continuous energy restriction. A total of 981 subjects were enrolled and randomised, with weight loss observed in all intermittent energy restriction arms regardless of study duration or follow up length. Eight interventions in six trials were used for the meta-analyses, with results indicating neither intermittent or continuous energy restriction being superior with respect to weight loss, 0.084 ± 0.114 (overall mean difference between groups ± standard error; p = 0.458). The effects of intermittent energy restriction in the long term remain unclear. The number of long term studies conducted is very limited, and participant numbers typically small (less than 50 completers), indicating the need for larger, long term trials of 12 months or more, to be conducted in order to understand the impact of intermittent energy restriction on weight loss and long term weight management. Blood lipid concentrations, glucose, and insulin were not altered by intermittent energy expenditure in values greater than those seen with continuous energy restriction. PMID:27338458

  12. Weight-Loss Outcomes: A Systematic Review and Meta-Analysis of Intermittent Energy Restriction Trials Lasting a Minimum of 6 Months

    PubMed Central

    Headland, Michelle; Clifton, Peter M.; Carter, Sharayah; Keogh, Jennifer B.

    2016-01-01

    The aim of this systematic review and meta-analysis is to summarise the effects of intermittent energy restriction on weight and biological markers in long term intervention studies of >6 months duration. An electronic search was performed using the MEDLINE, EMBASE and the Cochrane Library databases for intervention trials lasting 6 months or longer investigating the effects of intermittent energy restriction. A total of nine studies were identified as meeting the pre-specified criteria. All studies included an intermittent energy restriction arm, with six being directly compared to continuous energy restriction. A total of 981 subjects were enrolled and randomised, with weight loss observed in all intermittent energy restriction arms regardless of study duration or follow up length. Eight interventions in six trials were used for the meta-analyses, with results indicating neither intermittent or continuous energy restriction being superior with respect to weight loss, 0.084 ± 0.114 (overall mean difference between groups ± standard error; p = 0.458). The effects of intermittent energy restriction in the long term remain unclear. The number of long term studies conducted is very limited, and participant numbers typically small (less than 50 completers), indicating the need for larger, long term trials of 12 months or more, to be conducted in order to understand the impact of intermittent energy restriction on weight loss and long term weight management. Blood lipid concentrations, glucose, and insulin were not altered by intermittent energy expenditure in values greater than those seen with continuous energy restriction. PMID:27338458

  13. Effectiveness of 6 Months of Tailored Text Message Reminders for Obese Male Participants in a Worksite Weight Loss Program: Randomized Controlled Trial

    PubMed Central

    Oh, Sohee; Steinhubl, Steven; Kim, Sohye; Bae, Woo Kyung; Han, Jong Soo; Kim, Jeong-Hyun; Lee, Keehyuck; Kim, Mi Jin

    2015-01-01

    Background Worksite nutrition and physical activity interventions are important to help overweight and obese employees lose weight, but costs and insufficient sustained motivation prevent the majority of these programs from succeeding. Tailored text messaging in aiding weight management has been effective in several studies, but no studies have evaluated the effect of a tailored text message service on weight loss in a worksite health promotion program. Objective We studied the efficacy of a tailored text-messaging intervention for obese male participants in a worksite weight loss program of 6 months duration. Methods The study was an unblinded, randomized controlled trial. Men with a body mass index greater than 25 kg/m2 were recruited from the Korea District Heating Corporation, the Korea Expressway Corporation, and the Korea Gas Corporation. The participants were identified by nurse managers. Participants were randomly allocated to 1 of the following 2 groups for 24 weeks: (1) intervention group, which received tailored text message reminders every other day plus 4 offline education sessions and brief counseling with monthly weight check by nurses for weight control over 6 months and (2) control group, which received the 4 offline education sessions and brief counseling with monthly weight check by nurses about weight control over 6 months. The primary outcome was the difference in weight loss at 6 months. A mixed-model repeated-measures analysis was performed to evaluate the effect of the intervention group’s weight loss compared with the control group. Results A total of 205 obese men were randomized into either the intervention (n=104) or the control group (n=101). At the end of 6 months, the intervention group (n=63) had lost 1.71 kg (95% CI –2.53 to –0.88) and the control group (n=59) had lost 1.56 kg (95% CI –2.45 to –0.66); the difference between the 2 groups was not significant (mean difference –0.15, 95% CI –1.36 to 1.07). At the end of

  14. 14-day prulifloxacin treatment of acute uncomplicated cystitis in women with recurrent urinary tract infections: a prospective, open-label, pilot trial with 6-month follow-up.

    PubMed

    Cai, T; Mazzoli, S; Nesi, G; Boddi, V; Mondaini, N; Bartoletti, R

    2009-11-01

    Recurrent urinary tract infections (UTI) are very common in otherwise healthy young women, and can have a very negative social and economic impact. In order to evaluate the tolerability and efficacy of a 14-day course of prulifloxacin orally administered once daily, 51 young female patients, attending the same STD center between may and June 2007 for symptoms of cystitis, with a history of recurrent UTI and urine culture positive for uropathogens, were enrolled in this prospective study. Microbiological and clinical efficacy was tested over three follow-up visits at 1, 3 and 6 months. Quality of life (QoL) was measured and the impact of prulifloxacin in modifying the Lactobacillus vaginal flora was also evaluated. At baseline, the pathogens most commonly isolated were Enterococcus faecalis (43.2%) and Escherichia coli (27.5%). 41 of the 51 women, (80.3%) had Lactobacillus spp. in vaginal samples at baseline. microbiological results at follow-up examinations were as follows: after 1 month, 47 patients were recurrence-free and 4 had recurrence; after 3 months, 41 were recurrence-free, while 6 reported recurrence; finally, after 6 months, 36 were recurrence-free and 5 had recurrence. A statistically significant difference was reported between the QoL questionnaire mean scores at baseline (0.63), 1 (0.77), 3 (0.77) and 6 months (0.78) after treatment (all p<0.001). the vaginal swab cultures demonstrated that Lactobacillus spp. flora was maintained in 38 out of the 41 (92.6%) patients who had positive vaginal swab sample at baseline. in conclusion, a 14-day administration of prulifloxacin 600 mg is a safe, well tolerated and effective treatment for the management of UTI in young women. PMID:19933045

  15. Comparative clinical evaluation of laterally positioned pedicle graft and subepithelial connective tissue graft in the treatment of Miller's Class I and II gingival recession: A 6 months study

    PubMed Central

    Dulani, Kirti Satish; Bhavsar, Neeta Vijay; Trivedi, Sakshee Rahul; Trivedi, Rahul Anil

    2015-01-01

    Aim: The purpose of the study was to compare clinical outcomes of laterally positioned pedicle graft (LPPG) and subepithelial connective tissue graft (SCTG) for treatment of Miller's Class I and II gingival recession defects, at the end of 6 months. Materials and Methods: Sixty Miller's Class I or II gingival recession defects (≥3 mm) (n = 30 each) on the labial aspect of anterior teeth were treated by either of the above techniques. Clinical parameters including recession depth (RD), width of keratinized gingiva (WKG), percentage of root coverage (%RC), and complete RC were recorded at baseline and 6 months postoperatively. Data were recorded and statistical analysis was done for both intergroup and intragroup. Statistical Analysis Used: Paired t-test intragroup and Student's t-test intergroup. Results: In LPPG, RD decreased from 4.9 ± 0.99 mm to 1.1 ± 0.3 mm and WKG increased from 0.7 ± 0.87 to 4.5 ± 0.86 mm at 6 months, while in SCTG, RD decreased from 4.67 ± 1.12 mm to 0.46 ± 0.68 mm and WKG increased from 1.1 ± 0.99 to 5.33 ± 0.72 mm at 6 months postoperatively. The values of the soft tissue coverage remained stable for 6 months. Conclusions: Highly significant and effective soft tissue coverage was obtained by both techniques. LPPG resulted in effective soft tissue coverage for isolated deep narrow defects while SCTG in isolated and multiple, deep narrow and wide defects. PMID:26941517

  16. Developmental milestones record - 6 months

    MedlinePlus

    Normal childhood growth milestones - 6 months; Childhood growth milestones - 6 months; Growth milestones for children - 6 months ... the weight on hands (often occurs by 4 months) Able to pick up a dropped object Able ...

  17. Effect of a 6-month vegan low-carbohydrate (‘Eco-Atkins’) diet on cardiovascular risk factors and body weight in hyperlipidaemic adults: a randomised controlled trial

    PubMed Central

    Jenkins, David J A; Wong, Julia M W; Kendall, Cyril W C; Esfahani, Amin; Ng, Vivian W Y; Leong, Tracy C K; Faulkner, Dorothea A; Vidgen, Ed; Paul, Gregory; Mukherjea, Ratna; Krul, Elaine S; Singer, William

    2014-01-01

    Objective Low-carbohydrate diets may be useful for weight loss. Diets high in vegetable proteins and oils may reduce the risk of coronary heart disease. The main objective was to determine the longer term effect of a diet that was both low-carbohydrate and plant-based on weight loss and low-density lipoprotein cholesterol (LDL-C). Design, setting, participants A parallel design study of 39 overweight hyperlipidaemic men and postmenopausal women conducted at a Canadian university-affiliated hospital nutrition research centre from April 2005 to November 2006. Intervention Participants were advised to consume either a low-carbohydrate vegan diet or a high-carbohydrate lacto-ovo vegetarian diet for 6 months after completing 1-month metabolic (all foods provided) versions of these diets. The prescribed macronutrient intakes for the low-carbohydrate and high-carbohydrate diets were: 26% and 58% of energy from carbohydrate, 31% and 16% from protein and 43% and 25% from fat, respectively. Primary outcome Change in body weight. Results 23 participants (50% test, 68% control) completed the 6-month ad libitum study. The approximate 4 kg weight loss on the metabolic study was increased to −6.9 kg on low-carbohydrate and −5.8 kg on high-carbohydrate 6-month ad libitum treatments (treatment difference (95% CI) −1.1 kg (−2.1 to 0.0), p=0.047). The relative LDL-C and triglyceride reductions were also greater on the low-carbohydrate treatment (treatment difference (95% CI) −0.49 mmol/L (−0.70 to −0.28), p<0.001 and −0.34 mmol/L (−0.57 to −0.11), p=0.005, respectively), as were the total cholesterol:HDL-C and apolipoprotein B:A1 ratios (−0.57 (−0.83, −0.32), p<0.001 and −0.05 (−0.09, −0.02), p=0.003, respectively). Conclusions A self-selected low-carbohydrate vegan diet, containing increased protein and fat from gluten and soy products, nuts and vegetable oils, had lipid lowering advantages over a high-carbohydrate, low-fat weight loss

  18. Maternal Nutrition and Glycaemic Index during Pregnancy Impacts on Offspring Adiposity at 6 Months of Age—Analysis from the ROLO Randomised Controlled Trial

    PubMed Central

    Horan, Mary K.; McGowan, Ciara A.; Gibney, Eileen R.; Byrne, Jacinta; Donnelly, Jean M.; McAuliffe, Fionnuala M.

    2016-01-01

    Childhood obesity is associated with increased risk of adult obesity and metabolic disease. Diet and lifestyle in pregnancy influence fetal programming; however the influence of specific dietary components, including low glycaemic index (GI), remains complex. We examined the effect of a maternal low GI dietary intervention on offspring adiposity at 6 months and explored the association between diet and lifestyle factors in pregnancy and infant body composition at 6 months. 280 6-month old infant and mother pairs from the control (n = 142) and intervention group (n = 138), who received low GI dietary advice in pregnancy, in the ROLO study were analysed. Questionnaires (food diaries and lifestyle) were completed during pregnancy, followed by maternal lifestyle and infant feeding questionnaires at 6 months postpartum. Maternal anthropometry was measured throughout pregnancy and at 6 months post-delivery, along with infant anthropometry. No difference was found in 6 months infant adiposity between control and intervention groups. Maternal trimester three GI, trimester two saturated fats and trimester one and three sodium intake were positively associated with offspring adiposity, while trimester two and three vitamin C intake was negatively associated. In conclusion associations were observed between maternal dietary intake and GI during pregnancy and offspring adiposity at 6 months of age. PMID:26742066

  19. Maternal Nutrition and Glycaemic Index during Pregnancy Impacts on Offspring Adiposity at 6 Months of Age--Analysis from the ROLO Randomised Controlled Trial.

    PubMed

    Horan, Mary K; McGowan, Ciara A; Gibney, Eileen R; Byrne, Jacinta; Donnelly, Jean M; McAuliffe, Fionnuala M

    2016-01-04

    Childhood obesity is associated with increased risk of adult obesity and metabolic disease. Diet and lifestyle in pregnancy influence fetal programming; however the influence of specific dietary components, including low glycaemic index (GI), remains complex. We examined the effect of a maternal low GI dietary intervention on offspring adiposity at 6 months and explored the association between diet and lifestyle factors in pregnancy and infant body composition at 6 months. 280 6-month old infant and mother pairs from the control (n = 142) and intervention group (n = 138), who received low GI dietary advice in pregnancy, in the ROLO study were analysed. Questionnaires (food diaries and lifestyle) were completed during pregnancy, followed by maternal lifestyle and infant feeding questionnaires at 6 months postpartum. Maternal anthropometry was measured throughout pregnancy and at 6 months post-delivery, along with infant anthropometry. No difference was found in 6 months infant adiposity between control and intervention groups. Maternal trimester three GI, trimester two saturated fats and trimester one and three sodium intake were positively associated with offspring adiposity, while trimester two and three vitamin C intake was negatively associated. In conclusion associations were observed between maternal dietary intake and GI during pregnancy and offspring adiposity at 6 months of age.

  20. Clinical assessment following tibial tuberosity advancement in 28 stifles at 6 months and 1 year after surgery.

    PubMed

    MacDonald, Tamara L; Allen, David A; Monteith, Gabrielle J

    2013-03-01

    This prospective study evaluated the effect of tibial tuberosity advancement (TTA) on lameness, thigh circumference, range of motion (ROM), and radiographic osteoarthritis (OA) scores at 6 wk, 6 mo, and 1 y after surgery in 24 client-owned dogs with cranial cruciate ligament (CrCL) deficiency. Complications associated with TTA were also assessed. A significant improvement in lameness score and thigh circumference was observed in CrCL deficient limbs that received TTA, but no significant overall change in range of motion occurred in the affected limbs over the course of the study. Post-operative complications were identified in 33.3% of the dogs. This study demonstrates that TTA results in significant clinical improvement in patients up to 1 y after surgery. However, 21% of the dogs had post-operative recurrent lameness.

  1. 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 ( ...

  2. 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.

  3. PTH(1-84) replacement therapy in hypoparathyroidism: a randomized controlled trial on pharmacokinetic and dynamic effects after 6 months of treatment.

    PubMed

    Sikjaer, Tanja; Amstrup, Anne Kristine; Rolighed, Lars; Kjaer, Soren Geill; Mosekilde, Leif; Rejnmark, Lars

    2013-10-01

    Untreated, hypoparathyroidism (hypoPT) is a state of hypocalcemia with inappropriately low plasma parathyroid hormone (PTH) levels and hyperphosphatemia. PTH administration normalizes plasma calcium and phosphate levels and reduces the doses of calcium and active vitamin D analogues needed. To develop an evidence-based clinical algorithm to monitor hypoPT patients treated with recombinant human PTH (rhPTH[1-84]) injected subcutaneously in the thigh, we performed a 24-hour monitoring study of pharmacokinetic and pharmacodynamic effects in a group of 38 patients who had completed a 6-month randomized study on effects of treatment with a fixed rhPTH(1-84) dose of 100 µg/d or similar placebo as an add-on to conventional treatment. PTH levels rose immediately, reaching a median peak level of 26.5 (interquartile range [IQR], 20.1-42.5) pmol/L 15 minutes following injection. Thereafter, levels gradually decreased until reaching predosing levels after 16 hours, with a plasma half-life of 2.2 (1.7-2.5) hours. rhPTH(1-84) changed the diurnal rhythms of ionized calcium levels and 1,25-dihydroxyvitamin D (1,25[OH]2 D) levels, with rising levels following injection. Ionized calcium peaked after 7.0 (5.0-10.0) hours. Asymptomatic hypercalcemia was present in 71% of the rhPTH(1-84)-treated patients. Compared with placebo, 24-hour urinary calcium, phosphate, and magnesium did not change, although the diurnal variation in renal excretion rates changed significantly in response to treatment. In conclusion, as a safety precaution, we recommend occasionally measuring calcium levels at approximately 7 hours after administration in order to reveal episodes of hypercalcemia. A 100-µg daily dose of rhPTH(1-84) appears to be too high in some patients, suggesting a need for a device allowing for individual dose adjustments.

  4. Reduced platelet deposition on seeded versus unseeded segments of expanded polytetrafluoroethylene grafts: Clinical observations after a 6-month follow-up

    SciTech Connect

    Ortenwall, P.; Wadenvik, H.; Risberg, B. )

    1989-10-01

    The concept of autologous endothelial cell seeding has proved successful in animal models with respect to decrease of graft thrombogenicity and increase in patency. In the present study, application of this method in humans was explored. In 23 patients, random halves of expanded polytetrafluoroethylene grafts, used for lower limb arterial reconstructions, were seeded with endothelial cells at a seeding density of 3500 cells/cm{sup 2}. These cells were derived from the saphenous vein by enzymatic harvesting. The other half was sham seeded with culture medium. Graft thrombogenicity was estimated by measuring platelet deposition on graft surface 1 and 6 months after surgery, with indium 111-labeled platelets and external gamma-camera imaging. Seeded graft segments accumulated significantly (p less than 0.03) fewer platelets at all imaging times. It is concluded that seeding of expanded polytetrafluoroethylene vascular grafts in humans reduces graft surface thrombogenicity. The clinical implications of this remain to be demonstrated.

  5. 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 ...

  6. Family Perception and 6-Month Symptomatic and Functioning Outcomes in Young Adolescents at Clinical High Risk for Psychosis in a General Population in China

    PubMed Central

    Wang, Lu; Shi, JingYu; Chen, FaZhan; Yao, YuHong; Zhan, ChenYu; Yin, XiaoWen; Fang, XiaoYan; Wang, HaoJie; Yuan, JiaBei; Zhao, XuDong

    2015-01-01

    Background and Aims Given the difficulty of treating schizophrenia and other forms of psychosis, researchers have shifted focus to early detection and intervention of individuals at clinical high risk (CHR) for psychosis. Previous studies have shown that elements in family functioning could predict symptom outcome in CHR individuals. However, associations between self reported family functioning and symptom or functioning outcome of CHR individuals was rarely reported. Our study aimed to investigate the characteristics and the role of family functioning in the development of CHR individuals among young adolescents. Methods A sample of 32 CHR individuals was recruited from 2800 university students. The characteristics of family perception were evaluated by both Family Assessment Device (FAD) and Family cohesion and adaptability evaluation Scale II (FACES II). 6 month follow up data was available with 25 of the recruited CHR individuals. Baseline socio-demographic characteristics and family functioning were compared between CHR and control group. We also measured the associations between different dimensions of perceived family functioning and both severity of prodromal symptoms and global functioning at baseline and 6-month follow up. Results CHR individuals showed more maladaptive family functioning compared to control in nearly all of the dimensions of FAD and FACES II except for Affective Involvement. Better Problem Solving and Affective Responsiveness predicted less severe positive and negative symptoms respectively. Family cohesion and adaptability were not only correlated with the baseline severity of general symptoms, but also positively associated with the general and disorganized symptom outcome. Conclusions This study contributed preliminary evidence towards the associations between family perception and symptom outcome of CHR individuals. It also provided evidence for the importance of family interventions on CHR individuals. PMID:26394221

  7. 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.

  8. 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

  9. Does multicomponent physical exercise with simultaneous cognitive training boost cognitive performance in older adults? A 6-month randomized controlled trial with a 1-year follow-up

    PubMed Central

    Eggenberger, Patrick; Schumacher, Vera; Angst, Marius; Theill, Nathan; de Bruin, Eling D

    2015-01-01

    Background Cognitive impairment is a health problem that concerns almost every second elderly person. Physical and cognitive training have differential positive effects on cognition, but have been rarely applied in combination. This study evaluates synergistic effects of multicomponent physical exercise complemented with novel simultaneous cognitive training on cognition in older adults. We hypothesized that simultaneous cognitive–physical components would add training specific cognitive benefits compared to exclusively physical training. Methods Seniors, older than 70 years, without cognitive impairment, were randomly assigned to either: 1) virtual reality video game dancing (DANCE), 2) treadmill walking with simultaneous verbal memory training (MEMORY), or 3) treadmill walking (PHYS). Each program was complemented with strength and balance exercises. Two 1-hour training sessions per week over 6 months were applied. Cognitive performance was assessed at baseline, after 3 and 6 months, and at 1-year follow-up. Multiple regression analyses with planned comparisons were calculated. Results Eighty-nine participants were randomized to the three groups initially, 71 completed the training, while 47 were available at 1-year follow-up. Advantages of the simultaneous cognitive–physical programs were found in two dimensions of executive function. “Shifting attention” showed a time×intervention interaction in favor of DANCE/MEMORY versus PHYS (F[2, 68] =1.95, trend P=0.075, r=0.17); and “working memory” showed a time×intervention interaction in favor of DANCE versus MEMORY (F[1, 136] =2.71, trend P=0.051, R2=0.006). Performance improvements in executive functions, long-term visual memory (episodic memory), and processing speed were maintained at follow-up in all groups. Conclusion Particular executive functions benefit from simultaneous cognitive–physical training compared to exclusively physical multicomponent training. Cognitive–physical training programs

  10. The clinical trial.

    PubMed

    Chalmers, T C

    1981-01-01

    This paper argues that scientific clinical trials are the most ethical way to benefit patients whenever there is uncertainty about proper diagnosis and therapy. An increasing number of trials reported in clinical journals have employed randomization since the 1st extensive use of randomized controlled trials after the 2nd World War. A review of 4 examples of the response of physicians to trial results that differ from their own opinions indicates considerable reluctance to accept the results, no matter how well the trials were designed. Such reluctance may gradually disappear as physicians become better educated in clinical trial methodology. A good trial requires that unconscious bias be controlled, that data be recorded in detail and expertly analyzed, and that the sample size be considered when interpreting the results. Procedures designed to handle the ethical issues related to clinical trials include peer review, informed consent, initiation of randomization with the 1st use of a new therapy, reference to the previous outcomes in protocols and informed consent procedures and deferring decisions about when to stop studies to 3rd parties (such as data monitoring committees or policy advisory boards) and avoiding the use of placebos when an effective therapy is known. It is recommended that money for clinical trials be provided from the general medical care budget rather than the 2% that is devoted to all biomedical research.

  11. 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 ...

  12. Clinical trials in children

    PubMed Central

    Joseph, Pathma D; Craig, Jonathan C; Caldwell, Patrina HY

    2015-01-01

    Safety and efficacy data on many medicines used in children are surprisingly scarce. As a result children are sometimes given ineffective medicines or medicines with unknown harmful side effects. Better and more relevant clinical trials in children are needed to increase our knowledge of the effects of medicines and to prevent the delayed or non-use of beneficial therapies. Clinical trials provide reliable evidence of treatment effects by rigorous controlled testing of interventions on human subjects. Paediatric trials are more challenging to conduct than trials in adults because of the paucity of funding, uniqueness of children and particular ethical concerns. Although current regulations and initiatives are improving the scope, quantity and quality of trials in children, there are still deficiencies that need to be addressed to accelerate radically equitable access to evidence-based therapies in children. PMID:24325152

  13. Gaze Behavior and Affect at 6-Months: Predicting Clinical Outcomes and Language Development in Typically Developing Infants and Infants At-Risk for Autism

    PubMed Central

    Young, Gregory S.; Merin, Noah; Rogers, Sally J.; Ozonoff, Sally

    2009-01-01

    This paper presents follow-up longitudinal data to research that previously suggested the possibility of abnormal gaze behavior marked by decreased eye contact in a subgroup of 6-month-old infants at risk for autism (Merin et al., 2007). Using eye-tracking data and behavioral data recorded during a live mother-infant interaction involving the still-face procedure, the predictive utility of gaze behavior and affective behaviors at 6 months was examined using diagnostic outcome data obtained longitudinally over the following 18 months. Results revealed that none of the infants previously identified as showing lower rates of eye-contact had any signs of autism at outcome. In contrast, three infants who were diagnosed with autism demonstrated consistent gaze to the eye region and typical affective responses at 6 months. Individual differences in face scanning and affective responsivity during the live interaction were not related to any continuous measures of symptom frequency or symptom severity. In contrast, results of growth curve models for language development revealed significant relationships between face scanning and expressive language. Greater amounts of fixation to the mother’s mouth during live interaction predicted higher levels of expressive language at outcome and greater rates of growth. These findings suggest that although gaze behavior at 6 months may not provide early markers for autism as initially conceived, gaze to the mouth in particular may be useful in predicting individual differences in language development. PMID:19702771

  14. The Mediterranean Diet and Cognitive Function among Healthy Older Adults in a 6-Month Randomised Controlled Trial: The MedLey Study

    PubMed Central

    Knight, Alissa; Bryan, Janet; Wilson, Carlene; Hodgson, Jonathan M.; Davis, Courtney R.; Murphy, Karen J.

    2016-01-01

    Evidence from a limited number of randomised controlled intervention trials (RCTs) have shown that a Mediterranean dietary pattern may reduce the risk of cognitive decline and enhance cognitive function among healthy older adults. However, there are currently no data in non-Mediterranean older adult populations. The present study aimed to address this gap by examining the effect of a Mediterranean dietary pattern (MedDiet) for six months on aspects of cognitive function in a randomised controlled intervention trial (the MedLey study) that extended for a duration of 18 months. In the final analysed cohort, a total of 137 men and women (mean age of 72.1 ± 5.0 years) randomly assigned to either a MedDiet or control diet (HabDiet) (i.e., habitual dietary intake), were assessed on a comprehensive neuropsychological test battery, including 11 individual tests. In multivariable-adjusted models, the MedDiet group did not perform significantly better than the HabDiet control group for executive functioning (adjusted mean differences: +2.53, 95% CI −2.59 to 7.65, p = 0.33); speed of processing (adjusted mean differences: +3.24, 95% CI −1.21 to 7.70, p = 0.15); memory (adjusted mean differences: +2.00, 95% CI −3.88 to 7.88, p = 0.50); visual-spatial ability (adjusted mean differences: +0.21, 95% CI −0.38 to 0.81, 0.48); and overall age-related cognitive performance (adjusted mean differences: +7.99, 95% CI −4.00 to 19.9, p = 0.19). In conclusion, this study did not find evidence of a beneficial effect of a MedDiet intervention on cognitive function among healthy older adults. PMID:27657119

  15. Clinical and microbiological effects of a sanguinaria-containing mouthrinse and dentifrice with and without fluoride during 6 months of use.

    PubMed

    Kopczyk, R A; Abrams, H; Brown, A T; Matheny, J L; Kaplan, A L

    1991-10-01

    The purpose of this study was to test the efficacy and safety of sanguinaria-containing regimens with and without fluoride using the American Dental Association guidelines for evaluating chemotherapeutic agents. The study was a 6-month, double-blind, 4-cell, placebo-controlled, parallel investigation involving 120 subjects. Following screening procedures, subjects were randomly assigned to 4 groups. Group 1 received a dentifrice containing 0.075% sanguinaria extract (SaE) and 2.0% zinc chloride (ZnCl2) in a dicalcium phosphate base, plus an oral rinse containing 0.03% SaE and 0.2% ZnCl2. Group 2 received identical products without SaE or ZnCl2. Group 3 received a dentifrice containing 0.8% sodium monofluorophosphate, 0.075% SaE, and 0.05% ZnCl2 in a silica base, plus an oral rinse containing 0.03% SaE and 0.2% ZnCl2. Group 4 products were identical to those of Group 3 but without SaE and ZnCl2. Supragingival plaque and gingival inflammation were scored at 0, 1, 2, 1.5, 3, 4.5, and 6 months; bleeding upon probing was measured at 1, 1.5, 3, and 6 months. Microbiological samples were taken from plaque, tongue, and cheek areas. The active products produced statistically significantly lower scores than the placebo agents for all indices (P less than .0001). Six-month plaque scores were 13.1% lower for Group 1 and 17.4% lower for Group 3 compared to placebo products. When the Plaque Severity Index was applied, the percentage reductions were 33% for Group 1 and 41% for Group 3 compared to placebos. Gingival inflammation scores were 16.7% lower for Group 1 and 18.1% lower for Group 3 at 6 months compared to placebo scores.(ABSTRACT TRUNCATED AT 250 WORDS)

  16. 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…

  17. Innovative Clinical Trial Designs

    PubMed Central

    Lavori, Philip W.

    2015-01-01

    Whereas the 20th-century health care system sometimes seemed to be inhospitable to and unmoved by experimental research, its inefficiency and unaffordability have led to reforms that foreshadow a new health care system. We point out certain opportunities and transformational needs for innovations in study design offered by the 21st-century health care system, and describe some innovative clinical trial designs and novel design methods to address these needs and challenges. PMID:26140056

  18. Gateways to clinical trials.

    PubMed

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

    2005-05-01

    Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables 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, Adalimumab, adefovir dipivoxil, AeroDose albuterol inhaler, agalsidase alfa, alemtuzumab, aminolevulinic acid methyl ester, anidulafungin, anthrax vaccine, anti-CTLA-4 MAb, azimilide hydrochloride; Bevacizumab, BG-12, bimatoprost, bortezomib, bosentan, botulinum toxin type B; Caspofungin acetate, ceftobiprole, certolizumab pegol, CG-53135, cilansetron; Darbepoetin alfa, degarelix acetate, dimethylfumarate, duloxetine hydrochloride, dutasteride; Eicosapentaenoic acid/docosahexaenoic acid, eletriptan, entecavir, esomeprazole magnesium, exatecan mesilate, exenatide, ezetimibe; Falecalcitriol, fampridine, fondaparinux sodium, fontolizumab; Gefitinib, gepirone hydrochloride; Human insulin; IDEA-070, imatinib mesylate, iodine (I131) tositumomab; Lanthanum carbonate, lubiprostone; Mafosfamide cyclohexylamine salt, melatonin; NC-531, nemifitide ditriflutate, neridronic acid, nolatrexed dihydrochloride; Oral insulin; Palifermin, parecoxib sodium, PEG-filgrastim, peginterferon alfa-2a, peginterferon alfa-2b, plerixafor hydrochloride, posaconazole, pramlintide acetate, pregabalin, PT-141; Quercetin; Ranibizumab, renzapride hydrochloride, RSD-1235; Sabarubicin hydrochloride, semapimod hydrochloride, Semax, SHL-749; Tegaserod maleate, tenatoprazole, tetrodotoxin, tolevamer sodium, trabectedin, travoprost, travoprost/timolol; Valdecoxib, visilizumab, Xcellerated T cells, XP-828L; Zoledronic acid monohydrate.

  19. Gateways to clinical trials.

    PubMed

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

    2006-04-01

    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, alemtuzumab, AMG-531, anakinra, armodafinil, asenapine maleate, atazanavir sulfate, atorvastatin; Bortezomib, bosentan; CEB-1555, cetuximab, ciclesonide, clodronate, CT-011; Darifenacin hydrobromide, desloratadine; E-7010, ecallantide, eculizumab, efalizumab, eltrombopag, erlotinib hydrochloride, eslicarbazepine acetate, eszopiclone, ezetimibe; Febuxostat, fosamprenavir calcium, fulvestrant; Gefitinib, genistein; Haemophilus influenzae B vaccine, human papillomavirus vaccine; Imatinib mesylate, insulin glargine; Lenalidomide, liposomal cisplatin; MAb G250, mapatumumab, midostaurin, MP4, mycophenolic acid sodium salt; Natalizumab, neridronic acid, NSC-330507; Oblimersen sodium, ofatumumab, omalizumab, oral insulin, oregovomab; Paliperidone, parathyroid hormone (human recombinant), peginterferon alfa-2a, peginterferon alfa-2b, peginterferon alfa-2b/ribavirin, pegylated arginine deiminase 20000, pemetrexed disodium, pimecrolimus, pitavastatin, pneumococcal 7-valent conjugate vaccine, prasterone, pregabalin, pumosetrag hydrochloride; Recombinant malaria vaccine, retigabine, rivaroxaban, Ro-26-9228, romidepsin, rosuvastatin calcium, rotavirus vaccine; SGN-30, sitaxsentan sodium, solifenacin succinate, sorafenib, sunitinib malate; Tadalafil, tegaserod maleate, temsirolimus, TER-199, tifacogin, tiludronic acid, tiotropium bromide; Vildagliptin, VNP-40101M, vorinostat; YM-150, yttrium 90 (90Y) ibritumomab tiuxetan; Zanolimumab, zoledronic acid monohydrate. PMID:16810345

  20. 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

  1. 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

  2. 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

  3. Gateways to clinical trials.

    PubMed

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

    2005-05-01

    Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables 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, Adalimumab, adefovir dipivoxil, AeroDose albuterol inhaler, agalsidase alfa, alemtuzumab, aminolevulinic acid methyl ester, anidulafungin, anthrax vaccine, anti-CTLA-4 MAb, azimilide hydrochloride; Bevacizumab, BG-12, bimatoprost, bortezomib, bosentan, botulinum toxin type B; Caspofungin acetate, ceftobiprole, certolizumab pegol, CG-53135, cilansetron; Darbepoetin alfa, degarelix acetate, dimethylfumarate, duloxetine hydrochloride, dutasteride; Eicosapentaenoic acid/docosahexaenoic acid, eletriptan, entecavir, esomeprazole magnesium, exatecan mesilate, exenatide, ezetimibe; Falecalcitriol, fampridine, fondaparinux sodium, fontolizumab; Gefitinib, gepirone hydrochloride; Human insulin; IDEA-070, imatinib mesylate, iodine (I131) tositumomab; Lanthanum carbonate, lubiprostone; Mafosfamide cyclohexylamine salt, melatonin; NC-531, nemifitide ditriflutate, neridronic acid, nolatrexed dihydrochloride; Oral insulin; Palifermin, parecoxib sodium, PEG-filgrastim, peginterferon alfa-2a, peginterferon alfa-2b, plerixafor hydrochloride, posaconazole, pramlintide acetate, pregabalin, PT-141; Quercetin; Ranibizumab, renzapride hydrochloride, RSD-1235; Sabarubicin hydrochloride, semapimod hydrochloride, Semax, SHL-749; Tegaserod maleate, tenatoprazole, tetrodotoxin, tolevamer sodium, trabectedin, travoprost, travoprost/timolol; Valdecoxib, visilizumab, Xcellerated T cells, XP-828L; Zoledronic acid monohydrate. PMID:16082427

  4. Radiation With or Without 6 Months of Androgen Suppression Therapy in Intermediate- and High-Risk Clinically Localized Prostate Cancer: A Postrandomization Analysis by Risk Group

    SciTech Connect

    Nguyen, Paul L.; Chen, Ming-Hui; Beard, Clair J.; Suh, W. Warren

    2010-07-15

    Purpose: Six months of androgen suppression therapy (AST) plus radiation (RT) prolongs survival vs. RT alone in men with unfavorable risk localized prostate cancer (PCa), but it is unknown if this benefit applies to all risk subgroups and, in particular, the intermediate-risk group. Methods and Materials: Among 206 men with stages T1b to T2b PCa and either a prostate-specific antigen level of >10 or a Gleason score of {>=}7 or MRI evidence of T3 disease randomized to receive 70 Gy of RT with or without 6 months of AST, Cox multivariable analysis was used to assess the impact of AST on overall survival in intermediate- and high-risk localized PCa, adjusting for age, Adult Comorbidity Evaluation 27 comorbidity score, interaction between comorbidity and treatment, and known prognostic factors. Survival estimates were compared using a two-sided log-rank test. Results: After an 8.2-year median follow-up, 74 men died. Compared to treatment with AST plus RT, treatment with RT alone was associated with an increased risk of death in intermediate-risk (adjusted hazard ratio, 3.0 [95% confidence interval, 1.3-7.2]; p = 0.01) and high-risk PCa (adjusted hazard ratio, 3.3 [95% confidence interval, 0.94-11.3]; p = 0.06). The survival benefit of adding AST was restricted to men with no or mild comorbidity in both the intermediate-risk (90.9% vs. 85.8% survival, respectively, at 7 years for AST plus RT vs. RT alone; p = 0.009) and high-risk (88.9% vs. 51.2% survival, respectively, at 7 years for AST plus RT vs. RT alone; p = 0.007) subgroups. Conclusions: In men with localized PCa who have no or mild comorbidity, adding 6 months of AST to RT was associated with improved survival for those with both intermediate-risk and high-risk disease, but in men with moderate to severe comorbidity, no benefit was observed in either risk group.

  5. 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.

  6. 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.

  7. 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

  8. 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

  9. 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

  10. 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: ABT-510, ABX-EGF, acetyldinaline, ACIDFORM, acyline, afeletecan hydrochloride, anecortave acetate, apolizumab, l-arginine hydrochloride, asimadoline, atazanavir sufate, atlizumab; BMS-181176, BMS-188667; CAB-175, carnosine, CDP-870, CEP-701, CEP-7055, CGC-1072, ChimeriVax-JE, ciclesonide, cilomilast, clofarabine, combretastatin A-4 phosphate, cryptophycin 52; Duloxetine hydrochloride; E-5564, eculizumab, elcometrine, emtricitabine, ENO, epratuzumab, eszopiclone, everolimus; Fampridine, flurbiprofen nitroxybutyl ester; Garenoxacin mesilate, gestodene, GI-181771, gimatecan, gomiliximab; Halofuginone hydrobromide, hGH, hLM609; ICA-17043, IL-1 receptor type II, IMC-1C11, iodine (I131) tositumomab, irofulven, ISAtx-247; J591; L-778123, lanthanum carbonate Lasofoxifene tartrate, LDP-02, LE-AON, leteprinim potassium, lintuzumab, liraglutide, lubiprostone, lumiracoxib, lurtotecan, LY-450108, LY-451395; MAb G250, magnesium sulfate, MDX-210, melatonin, 2-methoxy-estradiol, monophosphoryl lipid A; NM-3, nolpitantium besilate; Ocinaplon, olpadronic acid sodium salt, oral heparin; Palonosetron hydrochloride, pemetrexed disodium, PI-88, picoplatin, plevitrexed, polyphenon E, pramlintide acetate, pregabalin, prinomastat, pyrazoloacridine; Resiniferatoxin, rhEndostatin, roxifiban acetate; S-18886, siplizumab, sitaxsentan sodium, solifenacin succinate, SU-11248, SU-6668; Talampanel, TAPgen, testosterone transdermal gel, trabectedin; VEGF-2 gene therapy, visilizumab; ZD-6416, ZD-6474. PMID:12949633

  11. Gateways to Clinical Trials.

    PubMed

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

    2002-09-01

    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: Adalimumab, aeroDose insulin inhaler, agomelatine, alendronic acid sodium salt, aliskiren fumarate, alteplase, amlodipine, aspirin, atazanavir; Bacillus Calmette-Guérin, basiliximab, BQ-788, bupropion hydrochloride; Cabergoline, caffeine citrate, carbamazepine, carvedilol, celecoxib, cyclosporine, clopidogrel hydrogensulfate, colestyramine; Dexamethasone, diclofenac sodium, digoxin, dipyridamole, docetaxel, dutasteride; Eletriptan, enfuvirtidie, eplerenone, ergotamine tartrate, esomeprazole magnesium, estramustine phosphate sodium; Finasteride, fluticasone propionate, fosinopril sodium; Ganciclovir, GBE-761-ONC, glatiramer acetate, gliclazide, granulocyte-CSF; Heparin sodium, human isophane insulin (pyr), Hydrochlorothiazide; Ibuprofen, inhaled insulin, interferon alfa, interferon beta-1a; Laminvudine, lansoprazole, lisinopril, lonafarnib, losartan potassium, lumiracoxib; MAb G250, meloxicam methotrexate, methylprednisolone aceponate, mitomycin, mycophenolate mofetil; Naproxen sodium, natalizumab, nelfinavir mesilate, nemifitide ditriflutate, nimesulide; Omalizumab, omapatrilat, omeprazole, oxybutynin chloride; Pantoprazole sodium, paracetamol, paroxetine, pentoxifylline, pergolide mesylate, permixon, phVEGF-A165, pramipexole hydrochloride, prasterone, prednisone, probucol, propiverine hydrochloride; Rabeprazole sodium, resiniferatoxin, risedronate sodium, risperidone, rofecoxib rosiglitazone maleate, ruboxistaurin mesilate hydrate; Selegiline transdermal system, sertraline, sildenafil citrate, streptokinase; Tadalafil, tamsulosin hydrochloride, technosphere/Insulin, tegaserod maleate, tenofovir disoproxil

  12. Gateways to clinical trials.

    PubMed

    Bayés, 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. 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: Aciclovir, alemtuzumab, alendronic acid sodium salt, alicaforsen sodium, alteplase, amifostine hydrate, antithymocyte globulin (equine), aspirin, atorvastatin calcium, azathioprine; Bacillus Calmette-Guérin, basiliximab, bicalutamide, bimatoprost, BMS-214662, brimonidine tartrate, buprenorphine hydrochloride; Cabergoline, carbamazepine, carboplatin, ciclosporine, cisplatin, cyclophosphamide; Daclizumab, desmopressin acetate, dihydroergotamine mesylate, dorzolamide hydrochloride, doxorubicin, dutasteride; Everolimus; Fluocinolone acetonide, frovatriptan, FTY-720, fulvestrant; Gabapentin, galantamine hydrobromide, ganciclovir, gemcitabine, glatiramer acetate; Hydrocodone bitartrate; Interferon beta, interferon beta-1a, interferon beta-1b, ipratropium bromide; Ketotifen; Lamivudine, latanoprost, levodopa, lidocaine hydrochloride, lonafarnib; Metformin hydrochloride, methylprednisolone, metoclopramide hydrochloride, mirtazapine, mitoxantrone hydrochloride, modafinil, muromonab-CD3, mycophenolate mofetil; NS-2330; Olopatadine hydrochloride, omalizumab, oxcarbazepine, oxycodone hydrochloride; Paclitaxel, paracetamol, piribedil, pramipexole hydrochloride, pravastatin sodium, prednisone; Quetiapine fumarate; Raloxifene hydrochloride, rituximab, rizatriptan sulfate, Ro-63-8695, ropinirole hydrochloride, rosiglitazone maleate; Simvastatin, siplizumab, sirolimus; Tacrolimus, tegaserod maleate, timolol maleate, tiotropium bromide, tipifarnib, tizanidine hydrochloride, tolterodine tartrate, topiramate, travoprost; Unoprostone isopropyl ester; Valganciclovir hydrochloride, visilizumab; Zidovudine. PMID:12224444

  13. 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

  14. 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

  15. 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

  16. 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

  17. 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

  18. 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

  19. 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

  20. Gateways to clinical trials.

    PubMed

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

    2005-01-01

    Gateways to Clinical Trials is a guide to the most recent clinical trials reported 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:[188Re]-HDD; A-179578, adalimumab, AK-602, albumin interferon alfa, alfimeprase, amelubant, anakinra, anti-CD2 MAb, APD-356, aripiprazole, atvogen; Bimatoprost, bimosiamose, BLP-25, brivaracetam; Caspofungin acetate, cilansetron, CMV vaccine (bivalent), conivaptan hydrochloride, Cypher; Darbepoetin alfa, darifenacin hydrobromide, D-D4FC, decitabine, dnaJP1, doranidazole, dronedarone hydrochloride; Efalizumab, efaproxiral sodium, emtricitabine, Endeavor, entecavir, erlotinib hydrochloride, escitalopram oxalate, etoricoxib, etravirine, ezetimibe; Fampridine, fenretinide, ferumoxtran-10, forodesine hydrochloride; Gantacurium chloride, gemi-floxacin mesilate, Glyminox, GW-501516; HBV-ISS, hepavir B, human insulin, HuMax-CD20, hyaluronic acid, HyCAMP; Icatibant, IDEA-070, IGN-311, imatinib mesylate, insulin detemir, insulin glargine, insulin glulisine; Lapatinib, lasofoxifene tartrate, LB-80380, liarozole fumarate, liposome encapsulated doxorubicin, lumiracoxib, LY-570310; MC-1, melatonin, merimepodib, metanicotine, midostaurin; Natalizumab, nicotine conjugate vaccine, NYVAC-HIV C; Patupilone, peginterferon alfa-2a, peginterferon alfa-2b, peginterferon alfa-2b/ribavirin, pelitinib, Peru-15, pexelizumab, PHP, pimecrolimus, prednisolone sodium metasulfobenzoate; Recombinant alfa1-antitrypsin (AAT), retigabine, rHA influenza vaccine, rifalazil, rofecoxib, rosiglitazone maleate/Metformin hydrochloride, rostaporfin, rosuvastatin calcium, rubitecan; Selenite sodium, semilente insulin, SMP-797, sorafenib; Talampanel, tenofovir disoproxil fumarate, TER-199, tiotropium bromide, torcetrapib, treprostinil sodium, TTA

  1. 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

  2. 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

  3. 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

  4. 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

  5. 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

  6. 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

  7. 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

  8. 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

  9. 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

  10. 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

  11. Clinical trials in India.

    PubMed

    Maiti, Rituparna; M, Raghavendra

    2007-07-01

    The concept of outsourcing for the development and global studies on new drugs has become widely accepted in the pharmaceutical industry due to its cost and uncertainty. India is going to be the most preferred location for contract pharma research and development due to its huge treatment naïve population, human resources, technical skills, adoption/amendment/implementation of rules/laws by regulatory authorities, and changing economic environment. But still 'miles to go' to fulfill the pre-requisites to ensure India's success. In spite of all the pitfalls, the country is ambitious and optimist to attract multinational pharmaceutical companies to conduct their clinical trials in India.

  12. 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

  13. 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

  14. 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

  15. 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

  16. 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

  17. 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

  18. 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

  19. 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

  20. 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

  1. 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

  2. [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.

  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. 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

  5. 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.)

  6. Prevalence and Incidence of Respiratory Syncytial Virus and Other Respiratory Viral Infections in Children Aged 6 Months to 10 Years With Influenza-like Illness Enrolled in a Randomized Trial

    PubMed Central

    Nolan, Terry; Borja-Tabora, Charissa; Lopez, Pio; Weckx, Lily; Ulloa-Gutierrez, Rolando; Lazcano-Ponce, Eduardo; Kerdpanich, Angkool; Weber, Miguel Angel Rodriguez; Mascareñas de Los Santos, Abiel; Tinoco, Juan-Carlos; Safadi, Marco Aurelio P.; Seng, Lim Fong; Hernandez-de Mezerville, Marcela; Faingezicht, Idis; Cruz-Valdez, Aurelio; Feng, Yang; Li, Ping; Durviaux, Serge; Haars, Gerco; Roy-Ghanta, Sumita; Vaughn, David W.; Taylor, Sylvia

    2015-01-01

    Background. The high burden of respiratory syncytial virus (RSV)-associated morbidity and mortality makes vaccine development a priority. Methods. As part of an efficacy trial of pandemic influenza vaccines (NCT01051661), RSV epidemiology in healthy children aged 6 months to <10 years at first vaccination with influenza-like illness (ILI) was evaluated in Australia, Brazil, Colombia, Costa Rica, Mexico, the Philippines, Singapore, and Thailand between February 2010 and August 2011. Active surveillance for ILI was conducted for approximately 1 year, with nasal and throat swabs analyzed by polymerase chain reaction. The prevalence and incidence of RSV among ILI episodes were calculated. Results. A total of 6266 children were included, of whom 2421 experienced 3717 ILI episodes with a respiratory sample available. RSV was detected for 359 ILI episodes, a prevalence of 9.7% (95% confidence interval: 8.7–10.7). The highest prevalence was in children aged 12–23 or 24–35 months in all countries except the Philippines, where it was in children aged 6–11 months. The incidence of RSV-associated ILI was 7.0 (6.3–7.7) per 100 person-years (PY). Eighty-eight ILI episodes resulted in hospitalization, of which 8 were associated with RSV (prevalence 9.1% [4.0–17.1]; incidence 0.2 [0.1–0.3] per 100 PY). The incidence of RSV-associated ILI resulting in medical attendance was 6.0 (5.4–6.7) per 100 PY. RSV B subtypes were observed more frequently than A subtypes. Conclusions. Active surveillance demonstrated the considerable burden of RSV-associated illness that would not be identified through hospital-based surveillance, with a substantial part of the burden occurring in older infants and children. PMID:25673560

  7. Bayesian Clinical Trials in Action

    PubMed Central

    Lee, J. Jack; Chu, Caleb T.

    2012-01-01

    Although the frequentist paradigm has been the predominant approach to clinical trial design since the 1940s, it has several notable limitations. The alternative Bayesian paradigm has been greatly enhanced by advancements in computational algorithms and computer hardware. Compared to its frequentist counterpart, the Bayesian framework has several unique advantages, and its incorporation into clinical trial design is occurring more frequently. Using an extensive literature review to assess how Bayesian methods are used in clinical trials, we find them most commonly used for dose finding, efficacy monitoring, toxicity monitoring, diagnosis/decision making, and for studying pharmacokinetics/pharmacodynamics. The additional infrastructure required for implementing Bayesian methods in clinical trials may include specialized software programs to run the study design, simulation, and analysis, and Web-based applications, which are particularly useful for timely data entry and analysis. Trial success requires not only the development of proper tools but also timely and accurate execution of data entry, quality control, adaptive randomization, and Bayesian computation. The relative merit of the Bayesian and frequentist approaches continues to be the subject of debate in statistics. However, more evidence can be found showing the convergence of the two camps, at least at the practical level. Ultimately, better clinical trial methods lead to more efficient designs, lower sample sizes, more accurate conclusions, and better outcomes for patients enrolled in the trials. Bayesian methods offer attractive alternatives for better trials. More such trials should be designed and conducted to refine the approach and demonstrate its real benefit in action. PMID:22711340

  8. 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.

  9. 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

  10. 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

  11. 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

  12. 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

  13. 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.

  14. 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

  15. 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. |

  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. 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 ...

  18. Clinical trials in head injury.

    PubMed

    Reinert, M M; Bullock, R

    1999-06-01

    Secondary brain damage, following severe head injury is considered to be a major cause for bad outcome. Impressive reductions of the extent of brain damage in experimental studies have raised high expectations for cerebral neuroprotective treatment, in the clinic. Therefore multiple compounds were and are being evaluated in trials. In this review we discuss the pathomechanisms of traumatic brain damage, based upon their clinical importance. The role of hypothermia, mannitol, barbiturates, steroids, free radical scavengers, arachidonic acid inhibitors, calcium channel blockers, N-methyl-D-aspartate (NMDA) antagonists, and potassium channel blockers, will be discussed. The importance of a uniform strategic approach for evaluation of potentially interesting new compounds in clinical trials, to ameliorate outcome in patients with severe head injury, is proposed. To achieve this goal, two nonprofit organizations were founded: the European Brain Injury Consortium (EBIC) and the American Brain Injury Consortium (ABIC). Their aim lies in conducting better clinical trials, which incorporate lessons learned from previous trials, such that the succession of negative, or incomplete studies, as performed in previous years, will cease.

  19. [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

  20. 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

  1. 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

  2. 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 ...

  3. Gatekeepers for Pragmatic Clinical Trials

    PubMed Central

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

    2015-01-01

    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 United States 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 manuscript provides a framework to help guide gatekeepers’ decision-making related to the use of resources for pragmatic clinical trials. These 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 the use of limited

  4. 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

  5. Multicomponent physical exercise with simultaneous cognitive training to enhance dual-task walking of older adults: a secondary analysis of a 6-month randomized controlled trial with 1-year follow-up

    PubMed Central

    Eggenberger, Patrick; Theill, Nathan; Holenstein, Stefan; Schumacher, Vera; de Bruin, Eling D

    2015-01-01

    Background About one-third of people older than 65 years fall at least once a year. Physical exercise has been previously demonstrated to improve gait, enhance physical fitness, and prevent falls. Nonetheless, the addition of cognitive training components may potentially increase these effects, since cognitive impairment is related to gait irregularities and fall risk. We hypothesized that simultaneous cognitive–physical training would lead to greater improvements in dual-task (DT) gait compared to exclusive physical training. Methods Elderly persons older than 70 years and without cognitive impairment were randomly assigned to the following groups: 1) virtual reality video game dancing (DANCE), 2) treadmill walking with simultaneous verbal memory training (MEMORY), or 3) treadmill walking (PHYS). Each program was complemented with strength and balance exercises. Two 1-hour training sessions per week over 6 months were applied. Gait variables, functional fitness (Short Physical Performance Battery, 6-minute walk), and fall frequencies were assessed at baseline, after 3 months and 6 months, and at 1-year follow-up. Multiple regression analyses with planned comparisons were carried out. Results Eighty-nine participants were randomized to three groups initially; 71 completed the training and 47 were available at 1-year follow-up. DANCE/MEMORY showed a significant advantage compared to PHYS in DT costs of step time variability at fast walking (P=0.044). Training-specific gait adaptations were found on comparing DANCE and MEMORY: DANCE reduced step time at fast walking (P=0.007) and MEMORY reduced gait variability in DT and DT costs at preferred walking speed (both trend P=0.062). Global linear time effects showed improved gait (P<0.05), functional fitness (P<0.05), and reduced fall frequency (−77%, P<0.001). Only single-task fast walking, gait variability at preferred walking speed, and Short Physical Performance Battery were reduced at follow-up (all P<0.05 or

  6. Comparative effectiveness of a fixed-dose combination of losartan + HCTZ versus bisoprolol + HCTZ in patients with moderate-to-severe hypertension: results of the 6-month ELIZA trial

    PubMed Central

    Radchenko, GD; Sirenko, YM; Kushnir, SM; Torbas, OO; Dobrokhod, AS

    2013-01-01

    Background The aim of this study was to compare the antihypertensive efficacy of losartan 100 mg + hydrochlorothiazide (HCTZ) 25 mg versus bisoprolol 10 mg + HCTZ 25 mg and their influence on arterial stiffness and central blood pressure (BP). Methods Of 60 patients with a mean BP of 173.3 ± 1.7/98.4 ± 1.2 mmHg, 59 were random-ized to losartan + HCTZ (n = 32) or bisoprolol + HCTZ (n = 27). Amlodipine was added if target BP was not achieved at 1 month, and doxazosin was added if target BP was not achieved after 3 months. Body mass index, office and 24-hour ambulatory BP, pulse wave velocity (carotid-femoral [PWVE] and radial [PWVM]), noninvasive central systolic BP, augmentation index (AIx), laboratory investigations, and electrocardiography were done at baseline and after 6 months of treatment. Results Losartan + HCTZ was as effective as bisoprolol + HCTZ, with target office BP achieved in 96.9% and 92.6% of patients and target 24-hour BP in 75% and 66.7% of patients, respectively, after 6 months. Effective treatment of BP led to significant lowering of central systolic BP, but this was decreased to a significantly (P < 0.05) greater extent by losartan + HCTZ (−23.0 ± 2.3 mmHg) than by bisoprolol + HCTZ (−15.4 ± 2.9 mmHg) despite equal lowering of brachial BP. Factors correlated with central systolic BP and its lowering differed between the treatment groups. Losartan + HCTZ did not alter arterial stiffness patterns significantly, but bisoprolol + HCTZ significantly increased AIx. We noted differences in ΔPWVE, ΔPWVM, and ΔAIx between the groups in favor of losartan + HCTZ. Decreased heart rate was associated with higher central systolic BP and AIx in the bisoprolol + HCTZ group, but was not associated with increased AIx in the losartan + HCTZ group. Conclusion Although both treatments decreased both office and 24-hour BP, losartan + HCTZ significantly decreased central systolic BP and had a more positive influence on pulse wave velocity, with a less

  7. 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.

  8. A Double-Blind, Placebo Controlled, Randomized Trial to Assess the Impact of a Monthly Administration of 50,000 IU of Vitamin D3 for 6 Months on Serum Levels of 25-Hydroxyvitamin D in Healthy Young Adults

    PubMed Central

    Brunel, E.; Schnitzler, M.; Foidart-Dessalle, M.; Souberbielle, J. C.; Cavalier, E.

    2013-01-01

    In this double blind, unicentre, randomized, placebo controlled study, we evaluated the changes in 25-hydroxyvitamin D (25(OH)D) serum levels in 150 young Belgian adults (18–30 years), monthly supplemented with 50,000 IU of vitamin D (VTD) or placebo for 6 months, from November 2010 to May 2011. At T0, 30% of the population presented 25(OH)D serum levels below 20 ng/mL. In the VTD-treated group, mean serum levels increased from 21.2 ± 8.2 to 30.6 ± 8.8 ng/mL (P < 0.001) at T3mo and to 36.0 ± 9.2 ng/mL (P < 0.001) at T6mo. Despite documented VTD intake, no changes in serum levels were, however, observed in 10% of the treated group. In the placebo group, mean 25(OH)D serum levels decreased from 22.8 ± 8.5 to 14.0 ± 6.9 ng/mL at T3mo (P < 0.001) but returned to values not significantly different from those observed at T0 (23.5 ± 8.6 ng/mL) at T6mo. No difference between serum calcium levels was observed between the groups throughout the study. In conclusion, monthly supplementation with 50,000 UI of VTD in winter can warrant serum 25(OH)D levels above 20 ng/mL in 96.2% of those healthy young adults without inducing unacceptably high 25(OH)D concentration. This supplementation is safe and may be proposed without 25(OH)D testing. PMID:24324493

  9. 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…

  10. 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

  11. 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

  12. AIDS clinical trials at John Hopkins.

    PubMed

    2000-01-01

    AIDS clinical trials at Johns Hopkins are described. Contact information, criteria for volunteers, and a brief description are provided. Trial topics include treatments for HIV-1 disease, neurology, and ocular immunology.

  13. Clinical trials update 2015: Year in review.

    PubMed

    Peroutka, Stephen J

    2016-01-01

    This section of Headache annually reviews the status of recently completed and ongoing major clinical trials involving common headache disorders. The review will focus on multicenter trials of new therapies, as well as novel formulations of previously approved therapeutics. The Table summarizes the major therapeutic headache trials that were ongoing at the end of 2015, according to data obtained from both the "ClinicalTrials.Gov" website and from corporate press releases and presentations.

  14. 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

  15. Trial analytics--a tool for clinical trial management.

    PubMed

    Bose, Anindya; Das, Suman

    2012-01-01

    Prolonged timelines and large expenses associated with clinical trials have prompted a new focus on improving the operational efficiency of clinical trials by use of Clinical Trial Management Systems (CTMS) in order to improve managerial control in trial conduct. However, current CTMS systems are not able to meet the expectations due to various shortcomings like inability of timely reporting and trend visualization within/beyond an organization. To overcome these shortcomings of CTMS, clinical researchers can apply a business intelligence (BI) framework to create Clinical Research Intelligence (CLRI) for optimization of data collection and analytics. This paper proposes the usage of an innovative and collaborative visualization tool (CTA) as CTMS "add-on" to help overwhelm these deficiencies of traditional CTMS, with suitable examples.

  16. 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

    2014-12-19

    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.

  17. 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

  18. The Quality of Registration of Clinical Trials

    PubMed Central

    Viergever, Roderik F.; Ghersi, Davina

    2011-01-01

    Background Lack of transparency in clinical trial conduct, publication bias and selective reporting bias are still important problems in medical research. Through clinical trials registration, it should be possible to take steps towards resolving some of these problems. However, previous evaluations of registered records of clinical trials have shown that registered information is often incomplete and non-meaningful. If these studies are accurate, this negates the possible benefits of registration of clinical trials. Methods and Findings A 5% sample of records of clinical trials that were registered between 17 June 2008 and 17 June 2009 was taken from the International Clinical Trials Registry Platform (ICTRP) database and assessed for the presence of contact information, the presence of intervention specifics in drug trials and the quality of primary and secondary outcome reporting. 731 records were included. More than half of the records were registered after recruitment of the first participant. The name of a contact person was available in 94.4% of records from non-industry funded trials and 53.7% of records from industry funded trials. Either an email address or a phone number was present in 76.5% of non-industry funded trial records and in 56.5% of industry funded trial records. Although a drug name or company serial number was almost always provided, other drug intervention specifics were often omitted from registration. Of 3643 reported outcomes, 34.9% were specific measures with a meaningful time frame. Conclusions Clinical trials registration has the potential to contribute substantially to improving clinical trial transparency and reducing publication bias and selective reporting. These potential benefits are currently undermined by deficiencies in the provision of information in key areas of registered records. PMID:21383991

  19. Data monitoring committees for pragmatic clinical trials.

    PubMed

    Ellenberg, Susan S; Culbertson, Richard; Gillen, Daniel L; Goodman, Steven; Schrandt, Suzanne; Zirkle, Maryan

    2015-10-01

    In any clinical trial, it is essential to monitor the accumulating data to be sure that the trial continues to be safe for participants and that the trial is being conducted properly. Data monitoring committees, independent expert panels who undertake regular reviews of the data as the trial progresses, serve an important role in safeguarding the interests of research participants and ensuring trial integrity in many trials. Many pragmatic clinical trials, which aim to inform healthcare decisions by comparing alternate interventions in heterogeneous healthcare delivery settings, will warrant review by an independent data monitoring committee due to their potential impact on clinical practice. However, the very features that make a trial "pragmatic" may pose challenges in terms of which aspects of a trial to monitor and when it is appropriate for a data monitoring committee to intervene. Using the Pragmatic-Explanatory Continuum Indicator Summary tool that draws distinctions between pragmatic and explanatory clinical trials, we review characteristics of pragmatic clinical trials that may have implications for data monitoring committees and interim monitoring plans. These include broad eligibility criteria, a focus on subjective patient-centered outcomes, and in some cases a lack of standardized follow-up procedures across study sites. Additionally, protocol adherence is often purposefully not addressed in pragmatic trials in order to accurately represent the clinical practice setting and maintain practicability of implementation; there are differing viewpoints as to whether adherence should be assessed and acted upon by data monitoring committees in these trials. Some other issues not specifically related to the Pragmatic-Explanatory Continuum Indicator Summary criteria may also merit special consideration in pragmatic trials. Thresholds for early termination of a pragmatic clinical trial might be controversial. The distinguishing features of pragmatic clinical

  20. Ethics of clinical trials in Nigeria.

    PubMed

    Okonta, Patrick I

    2014-05-01

    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

  1. Ethics of clinical trials in Nigeria.

    PubMed

    Okonta, Patrick I

    2014-05-01

    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.

  2. Add-on prolonged-release melatonin for cognitive function and sleep in mild to moderate Alzheimer’s disease: a 6-month, randomized, placebo-controlled, multicenter trial

    PubMed Central

    Wade, Alan G; Farmer, Mildred; Harari, Gil; Fund, Naama; Laudon, Moshe; Nir, Tali; Frydman-Marom, Anat; Zisapel, Nava

    2014-01-01

    Purpose A link between poor sleep quality and Alzheimer’s disease (AD) has recently been suggested. Since endogenous melatonin levels are already reduced at preclinical AD stages, it is important to ask whether replenishing the missing hormone would be beneficial in AD and whether any such effects would be related to the presence of sleep disorder in patients. Patients and methods The effects of add-on prolonged-release melatonin (PRM) (2 mg) to standard therapy on cognitive functioning and sleep were investigated in 80 patients (men [50.7%], women [49.3%], average age 75.3 years [range, 52–85 years]) diagnosed with mild to moderate AD, with and without insomnia comorbidity, and receiving standard therapy (acetylcholinesterase inhibitors with or without memantine). In this randomized, double-blind, parallel-group study, patients were treated for 2 weeks with placebo and then randomized (1:1) to receive 2 mg of PRM or placebo nightly for 24 weeks, followed by 2 weeks placebo. The AD Assessment Scale–Cognition (ADAS-Cog), Instrumental Activities of Daily Living (IADL), Mini–Mental State Examination (MMSE), sleep, as assessed by the Pittsburgh Sleep Quality Index (PSQI) and a daily sleep diary, and safety parameters were measured. Results Patients treated with PRM (24 weeks) had significantly better cognitive performance than those treated with placebo, as measured by the IADL (P=0.004) and MMSE (P=0.044). Mean ADAS-Cog did not differ between the groups. Sleep efficiency, as measured by the PSQI, component 4, was also better with PRM (P=0.017). In the comorbid insomnia (PSQI ≥6) subgroup, PRM treatment resulted in significant and clinically meaningful effects versus the placebo, in mean IADL (P=0.032), MMSE score (+1.5 versus −3 points) (P=0.0177), and sleep efficiency (P=0.04). Median ADAS-Cog values (−3.5 versus +3 points) (P=0.045) were significantly better with PRM. Differences were more significant at longer treatment duration. PRM was well

  3. Innovative clinical trial design for pediatric therapeutics.

    PubMed

    Laughon, Matthew M; Benjamin, Daniel K; Capparelli, Edmund V; Kearns, Gregory L; Berezny, Katherine; Paul, Ian M; Wade, Kelly; Barrett, Jeff; Smith, Phillip Brian; Cohen-Wolkowiez, Michael

    2011-09-01

    Until approximately 15 years ago, sponsors rarely included children in the development of therapeutics. US and European legislation has resulted in an increase in the number of pediatric trials and specific label changes and dosing recommendations, although infants remain an understudied group. The lack of clinical trials in children is partly due to specific challenges in conducting trials in this patient population. Therapeutics in special populations, including premature infants, obese children and children receiving extracorporeal life support, are even less studied. National research networks in Europe and the USA are beginning to address some of the gaps in pediatric therapeutics using novel clinical trial designs. Recent innovations in pediatric clinical trial design, including sparse and scavenged sampling, population pharmacokinetic analyses and 'opportunistic' studies, have addressed some of the historical challenges associated with clinical trials in children.

  4. Human clinical trials of plasmid DNA vaccines.

    PubMed

    Liu, Margaret A; Ulmer, Jeffrey B

    2005-01-01

    This article gives an overview of DNA vaccines with specific emphasis on the development of DNA vaccines for clinical trials and an overview of those trials. It describes the preclinical research that demonstrated the efficacy of DNA vaccines as well as an explication of the immunologic mechanisms of action. These include the induction of cognate immune responses, such as the generation of cytolytic T lymphocytes (CTL) as well as the effect of the plasmid DNA upon the innate immune system. Specific issues related to the development of DNA as a product candidate are then discussed, including the manufacture of plasmid, the qualification of the plasmid DNA product, and the safety testing necessary for initiating clinical trials. Various human clinical trials for infectious diseases and cancer have been initiated or completed, and an overview of these trials is given. Finally, because the early clinical trials have shown less than optimal immunogenicity, methods to increase the potency of the vaccines are described. PMID:16291211

  5. 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

  6. Prognostic utility of routine chimerism testing at 2 to 6 months after allogeneic hematopoietic cell transplantation.

    PubMed

    Mossallam, Ghada I; Kamel, Azza M; Storer, Barry; Martin, Paul J

    2009-03-01

    The utility of routine chimerism analysis as a prognostic indicator of subsequent outcomes after allogeneic hematopoietic cell transplantation (HCT) with myeloablative conditioning regimens remains controversial. To address this controversy, routine chimerism test results at 2 to 6 months after HCT with myeloablative conditioning regimens were evaluated for association with subsequent risk of chronic graft-versus-host disease (GVHD), nonrelapse mortality (NRM), relapse, and overall mortality. Only 70 of 1304 patients (5%) had < 95% donor-derived cells in the marrow. Low donor chimerism in the marrow occurred more often in patients with low-risk diseases compared with those with higher-risk diseases and was significantly associated with a reduced risk of chronic GVHD. Among 673 patients evaluated, 164 (24%) had < 85% donor-derived T cells in the blood. Low donor T cell chimerism was more frequent in patients with low-risk diseases compared with those with higher-risk diseases, in those who received conditioning with busulfan compared with those who received conditioning with total body irradiation, and in those with lower-grade acute GVHD. Low donor T cell chimerism in the blood was significantly associated with a reduced risk of chronic GVHD but not with a reduced risk of relapse, NRM, or overall mortality. Routine testing of chimerism in the marrow and blood at 2 to 6 months after HCT with myeloablative conditioning regimens may be helpful in documenting engraftment in clinical trials, but provides only limited prognostic information in clinical practice.

  7. 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

  8. Paperless clinical trials: Myth or reality?

    PubMed Central

    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

  9. Improving Function in Age-Related Macular Degeneration: A Randomized Clinical Trial

    PubMed Central

    Rovner, Barry W.; Casten, Robin J.; Hegel, Mark T.; Massof, Robert W.; Leiby, Benjamin E.; Ho, Allen C.; Tasman, William S.

    2013-01-01

    Purpose To compare the efficacy of Problem-Solving Therapy (PST) with Supportive Therapy (ST) to improve Targeted Vision Function in Age-Related Macular Degeneration (AMD). Design Single-masked, attention controlled randomized clinical trial with outcome assessments at 3 months (main trial endpoint) and 6 months (maintenance effects). Participants Patients with AMD (N = 241) attending retina practices. Interventions PST uses a structured problem-solving approach to reduce vision-related task difficulty. ST is a standardized attention control treatment. Main Outcome Measures Targeted Vision Function (TVF); National Eye Institute Vision Function Questionnaire - 25 plus Supplement (NEI VFQ); Activities Inventory (AI); and Vision-Related Quality of Life. Results There were no significant between-group differences in TVF scores at 3 months (p = 0.47) or 6 months (p = 0.62). For PST subjects, mean [standard deviation (SD)] TVF scores improved from 2.71 (0.52) at baseline to 2.18 (0.88) at 3 months (p = 0.001) and were 2.18 (0.95) at 6 months (change from 3 to 6 months, p = .74). For ST subjects, TVF scores improved from 2.73 (0.52) at baseline to 2.14 (0.96) at 3 months (p = 0.001) and were 2.15 (0.96) at 6 months (change from 3 to 6 months, p = .85). Similar proportions of PST and ST subjects had less difficulty performing a TVF goal at 3 months (77.4% vs. 78.6%, respectively; p = 0.83) and 6 months (76.2% vs. 79.1%, respectively; p = 0.61). There were no significant changes in the NEI VFQ or AI. Vision-related quality-of-life improved for PST relative to ST subjects at 3 months [F (4,192) = 2.46; p = 0.05] and 6 months [F (4,178) = 2.55; p = 0.05)]. PST subjects also developed more adaptive coping strategies than ST subjects. Conclusions We found that PST was not superior to ST at improving vision function in patients with AMD but PST improved their vision-related quality of life. Despite the benefits of anti-vascular endothelial growth factor (anti-VEGF) treatments

  10. 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.

  11. Malignant hyperthermia in a 6-month-old infant.

    PubMed

    Mathur, P R; Rundla, M; Jain, N; Mathur, V

    2016-01-01

    Malignant hyperthermia (MH) is a rare hypermetabolic disorder of skeletal muscles that manifests as a life-threatening crisis in susceptible individuals, after exposure to triggering agents, most commonly halothane and succinylcholine. MH presents with multiple nonspecific signs and laboratory findings such as tachycardia, hyperthermia, hypercarbia, acidosis, and muscle rigidity. Caffeine halothane contracture test is not available at most centers in India. Larach et al. have described a clinical grading scale for determining the MH raw score based on clinical findings and biochemical tests. The high degree of suspicion, early recognition and aggressive treatment should commence immediately. It is imperative to avoid triggering agents, such as volatile anesthetics and succinylcholine, and promote the use of total intravenous anesthesia in MH susceptible patients. We report a case of 6-month-old child undergoing laparotomy under general anesthesia, who presented with signs and symptoms of MH, had MH rank 5 and raw score 36. PMID:27375398

  12. Malignant hyperthermia in a 6-month-old infant

    PubMed Central

    Mathur, PR; Rundla, M; Jain, N; Mathur, V

    2016-01-01

    Malignant hyperthermia (MH) is a rare hypermetabolic disorder of skeletal muscles that manifests as a life-threatening crisis in susceptible individuals, after exposure to triggering agents, most commonly halothane and succinylcholine. MH presents with multiple nonspecific signs and laboratory findings such as tachycardia, hyperthermia, hypercarbia, acidosis, and muscle rigidity. Caffeine halothane contracture test is not available at most centers in India. Larach et al. have described a clinical grading scale for determining the MH raw score based on clinical findings and biochemical tests. The high degree of suspicion, early recognition and aggressive treatment should commence immediately. It is imperative to avoid triggering agents, such as volatile anesthetics and succinylcholine, and promote the use of total intravenous anesthesia in MH susceptible patients. We report a case of 6-month-old child undergoing laparotomy under general anesthesia, who presented with signs and symptoms of MH, had MH rank 5 and raw score 36. PMID:27375398

  13. 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

  14. 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

  15. Justifying clinical trials for porcine islet xenotransplantation.

    PubMed

    Ellis, Cara E; Korbutt, Gregory S

    2015-01-01

    The development of the Edmonton Protocol encouraged a great deal of optimism that a cell-based cure for type I diabetes could be achieved. However, donor organ shortages prevent islet transplantation from being a widespread solution as the supply cannot possibly equal the demand. Porcine islet xenotransplantation has the potential to address these shortages, and recent preclinical and clinical trials show promising scientific support. Consequently, it is important to consider whether the current science meets the ethical requirements for moving toward clinical trials. Despite the potential risks and the scientific unknowns that remain to be investigated, there is optimism regarding the xenotransplantation of some types of tissue, and enough evidence has been gathered to ethically justify clinical trials for the most safe and advanced area of research, porcine islet transplantation. Researchers must make a concerted effort to maintain a positive image for xenotransplantation, as a few well-publicized failed trials could irrevocably damage public perception of xenotransplantation. Because all of society carries the burden of risk, it is important that the public be involved in the decision to proceed. As new information from preclinical and clinical trials develops, policy decisions should be frequently updated. If at any point evidence shows that islet xenotransplantation is unsafe, then clinical trials will no longer be justified and they should be halted. However, as of now, the expected benefit of an unlimited supply of islets, combined with adequate informed consent, justifies clinical trials for islet xenotransplantation.

  16. OARSI Clinical Trials Recommendations: Design and conduct of clinical trials of rehabilitation interventions for osteoarthritis.

    PubMed

    Fitzgerald, G K; Hinman, R S; Zeni, J; Risberg, M A; Snyder-Mackler, L; Bennell, K L

    2015-05-01

    A Task Force of the Osteoarthritis Research Society International (OARSI) has previously published a set of guidelines for the conduct of clinical trials in osteoarthritis (OA) of the hip and knee. Limited material available on clinical trials of rehabilitation in people with OA has prompted OARSI to establish a separate Task Force to elaborate guidelines encompassing special issues relating to rehabilitation of OA. The Task Force identified three main categories of rehabilitation clinical trials. The categories included non-operative rehabilitation trials, post-operative rehabilitation trials, and trials examining the effectiveness of devices (e.g., assistive devices, bracing, physical agents, electrical stimulation, etc.) that are used in rehabilitation of people with OA. In addition, the Task Force identified two main categories of outcomes in rehabilitation clinical trials, which include outcomes related to symptoms and function, and outcomes related to disease modification. The guidelines for rehabilitation clinical trials provided in this report encompass these main categories. The report provides guidelines for conducting and reporting on randomized clinical trials. The topics include considerations for entering patients into trials, issues related to conducting trials, considerations for selecting outcome measures, and recommendations for statistical analyses and reporting of results. The focus of the report is on rehabilitation trials for hip, knee and hand OA, however, we believe the content is broad enough that it could be applied to rehabilitation trials for other regions as well.

  17. Clinical Trials | NIH MedlinePlus the Magazine

    MedlinePlus

    ... of this page please turn JavaScript on. Feature: Clinical Trials Clinical Trials, A Healthier Future for All Fall 2016 Table ... in was reviewed by an IRB. Find a Clinical Trial Near You Health research takes place at hospitals, ...

  18. 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

  19. 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

  20. 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.

  1. Emerging innovations in clinical trial design.

    PubMed

    Berry, D A

    2016-01-01

    Designs of clinical trials have changed little since the advent of randomization in the 1940s. Modern innovations in designs are being driven by the increasing recognition in clinical research that diseases are heterogeneous and patients who apparently have the same disease require different therapies. This article describes some innovations in clinical trial design across therapeutic areas but with a focus on oncology. No one knows what the future holds for clinical trial design but the status quo of large trials that pretend the patient population is homogeneous is not sustainable, either economically or scientifically/medically. No one knows what the eventual business model and regulatory model will be, but they will be very different from today's. PMID:26561040

  2. Dasatinib first-line: Multicentric Italian experience outside clinical trials.

    PubMed

    Breccia, Massimo; Stagno, Fabio; Luciano, Luigiana; Abruzzese, Elisabetta; Annunziata, Mario; D'Adda, Mariella; Maggi, Alessandro; Sgherza, Nicola; Russo-Rossi, Antonella; Pregno, Patrizia; Castagnetti, Fausto; Iurlo, Alessandra; Latagliata, Roberto; Cedrone, Michele; Di Renzo, Nicola; Sorà, Federica; Rege-Cambrin, Giovanna; La Nasa, Giorgio; Scortechini, Anna Rita; Greco, Giovanna; Franceschini, Luca; Sica, Simona; Bocchia, Monica; Crugnola, Monica; Orlandi, Esther; Guarini, Attilio; Specchia, Giorgina; Rosti, Gianantonio; Saglio, Giuseppe; Alimena, Giuliana

    2016-01-01

    Dasatinib was approved for the treatment of chronic phase (CP) chronic myeloid leukemia (CML) patients in first line therapy based on the demonstration of efficacy and safety reported in patients enrolled in clinical trials. We describe a multicentric Italian "real-life" experience of dasatinib used as frontline treatment outside clinical trials. One hundred and nine patients (median age 54 years) were treated from January 2012 to December 2013. Increased incidence of high risk patients were detected according to stratification (26% according to Sokal score, 19% according to Euro score and 16% according to EUTOS) when compared to company sponsored studies. Median time from diagnosis to start of dasatinib was 18 days. Ten patients received unscheduled starting dose (6 patients 50mg and 4 patients 80 mg QD), whereas 99 patients started with 100mg QD. At 3 months, 92% of patients achieved a BCR-ABL ratio less than 10%. At 6 months, the rate of CCyR was 91% and the rate of MR3 was 40%, with 8% of the patients reaching MR4.5. Ninety-three patients were evaluable at 12 months: the rate of MR3 was 62%, with MR4.5 being achieved by 19% of the patients. At a median follow-up of 12 months, 27 patients (24.7%) were receiving the drug at reduced dose. Two patients (1.8%) experienced a lymphoid blast crisis and the overall incidence of resistance was 8%. As regards safety, the major side effects recorded were thrombocytopenia, neutropenia and pleural effusions, which occurred in 22%, 10% and 8% of patients, respectively. Present results, achieved in a large cohort of patients treated outside clinical trials, further confirm the efficacy and safety of dasatinib as firstline treatment in CML.

  3. Dasatinib first-line: Multicentric Italian experience outside clinical trials.

    PubMed

    Breccia, Massimo; Stagno, Fabio; Luciano, Luigiana; Abruzzese, Elisabetta; Annunziata, Mario; D'Adda, Mariella; Maggi, Alessandro; Sgherza, Nicola; Russo-Rossi, Antonella; Pregno, Patrizia; Castagnetti, Fausto; Iurlo, Alessandra; Latagliata, Roberto; Cedrone, Michele; Di Renzo, Nicola; Sorà, Federica; Rege-Cambrin, Giovanna; La Nasa, Giorgio; Scortechini, Anna Rita; Greco, Giovanna; Franceschini, Luca; Sica, Simona; Bocchia, Monica; Crugnola, Monica; Orlandi, Esther; Guarini, Attilio; Specchia, Giorgina; Rosti, Gianantonio; Saglio, Giuseppe; Alimena, Giuliana

    2016-01-01

    Dasatinib was approved for the treatment of chronic phase (CP) chronic myeloid leukemia (CML) patients in first line therapy based on the demonstration of efficacy and safety reported in patients enrolled in clinical trials. We describe a multicentric Italian "real-life" experience of dasatinib used as frontline treatment outside clinical trials. One hundred and nine patients (median age 54 years) were treated from January 2012 to December 2013. Increased incidence of high risk patients were detected according to stratification (26% according to Sokal score, 19% according to Euro score and 16% according to EUTOS) when compared to company sponsored studies. Median time from diagnosis to start of dasatinib was 18 days. Ten patients received unscheduled starting dose (6 patients 50mg and 4 patients 80 mg QD), whereas 99 patients started with 100mg QD. At 3 months, 92% of patients achieved a BCR-ABL ratio less than 10%. At 6 months, the rate of CCyR was 91% and the rate of MR3 was 40%, with 8% of the patients reaching MR4.5. Ninety-three patients were evaluable at 12 months: the rate of MR3 was 62%, with MR4.5 being achieved by 19% of the patients. At a median follow-up of 12 months, 27 patients (24.7%) were receiving the drug at reduced dose. Two patients (1.8%) experienced a lymphoid blast crisis and the overall incidence of resistance was 8%. As regards safety, the major side effects recorded were thrombocytopenia, neutropenia and pleural effusions, which occurred in 22%, 10% and 8% of patients, respectively. Present results, achieved in a large cohort of patients treated outside clinical trials, further confirm the efficacy and safety of dasatinib as firstline treatment in CML. PMID:26643920

  4. 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

  5. Current HIV clinical trial design issues.

    PubMed

    Lange, J M

    1995-01-01

    Aids-free time and survival time of people with HIV infection has gradually increased since the first clinical trial of zidovudine(AZT) in 1987. This change in pattern of disease course has, however, made it difficult for current clinical trials to rely on "hard" clinical end points, such as progression to AIDS or death, to demonstrate antiretroviral efficacy. These trials must continue for a number of years and enroll large numbers of patients; as a result, maintaining patients on protocolled therapy is difficult to achieve. Furthermore, patients can be prevented from reaching clinical end points by prophylaxis of opportunistic infections. Combined with the move toward treating individuals earlier in the course of infection, current clinical trials using "hard" clinical end points are unlikely to demonstrate drug efficacy. The concept of using "soft" clinical end points and laboratory end points such as decline in CD4 cell count to a threshold value, was first introduced in study EACG 020 of patients with early stage infection, and made it possible for this study to demonstrate the efficacy of AZT in this patient population. Further accurate markers of disease progression are required for current clinical trials. There is growing consensus that the primary end point of any antiviral drug study should be the effect of the drug on the virus itself. It is now possible to quantify viral burden and to assess the amount of virus present in different tissues. To validate viral load as a marker of disease progression, it is necessary to achieve a profound and long-term reduction in viral load. It is very likely that this will be achieved only in studies of multiple combination therapy at early stages of infection. Moreover, clinical trials are required to validate the use of viral load. In the meantime, regulatory authorities should be encouraged to license drugs on the basis of viral load data with the provision of intense post-licensing follow-up.

  6. Quantitative Imaging in Cancer Clinical Trials.

    PubMed

    Yankeelov, Thomas E; Mankoff, David A; Schwartz, Lawrence H; Lieberman, Frank S; Buatti, John M; Mountz, James M; Erickson, Bradley J; Fennessy, Fiona M M; Huang, Wei; Kalpathy-Cramer, Jayashree; Wahl, Richard L; Linden, Hannah M; Kinahan, Paul E; Zhao, Binsheng; Hylton, Nola M; Gillies, Robert J; Clarke, Laurence; Nordstrom, Robert; Rubin, Daniel L

    2016-01-15

    As anticancer therapies designed to target specific molecular pathways have been developed, it has become critical to develop methods to assess the response induced by such agents. Although traditional, anatomic CT, and MRI examinations are useful in many settings, increasing evidence suggests that these methods cannot answer the fundamental biologic and physiologic questions essential for assessment and, eventually, prediction of treatment response in the clinical trial setting, especially in the critical period soon after treatment is initiated. To optimally apply advances in quantitative imaging methods to trials of targeted cancer therapy, new infrastructure improvements are needed that incorporate these emerging techniques into the settings where they are most likely to have impact. In this review, we first elucidate the needs for therapeutic response assessment in the era of molecularly targeted therapy and describe how quantitative imaging can most effectively provide scientifically and clinically relevant data. We then describe the tools and methods required to apply quantitative imaging and provide concrete examples of work making these advances practically available for routine application in clinical trials. We conclude by proposing strategies to surmount barriers to wider incorporation of these quantitative imaging methods into clinical trials and, eventually, clinical practice. Our goal is to encourage and guide the oncology community to deploy standardized quantitative imaging techniques in clinical trials to further personalize care for cancer patients and to provide a more efficient path for the development of improved targeted therapies.

  7. 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.

  8. A clinical and radiological evaluation of the relative efficacy of demineralized freeze-dried bone allograft versus anorganic bovine bone xenograft in the treatment of human infrabony periodontal defects: A 6 months follow-up study

    PubMed Central

    Blaggana, Vikram; Gill, Amarjit Singh; Blaggana, Anshu

    2014-01-01

    Background: The ultimate goal of periodontal therapy entails regeneration of the periodontal tissues lost as a consequence of periodontitis. Predictable correction of vertical osseous defects has however posed as a constant therapeutic challenge. The aim of our present study is to evaluate the relative efficacy of demineralized freeze-dried bone allograft (DFDBA) vs anorganic bovine bone xenograft (ABBX) in the treatment of human infrabony periodontal defects. Materials and Methods: 15 patients with 30 bilaterally symmetrical defect sites in either of the arches, in the age group of 25-50 years were selected as part of split-mouth study design. Defect-A (right side) was grafted with DFDBA while Defect-B (left side) was grafted with ABBX. Various clinical and radiographic parameters viz. probing depth(PD), clinical attachment level(CAL) and linear bone fill were recorded preoperatively, 12- & 24-weeks postoperatively. Results: Both defect-A & defect-B sites exhibited a highly significant reduction in probing depth, and gain in clinical attachment level and linear bone fill at 12-weeks & at the end of 24-weeks. Comparative evaluation between the study groups revealed a statistically non-significant reduction in probing depth (P<0.1) and mean gain in linear bone fill (P<0.1). However, there was a statistically significant gain in clinical attachment level (P<0.05) in Defect-A (CD=0.356) as compared to Defect-B (CD=0.346). Conclusions: Within the limits of this study, both the materials viz. ABBX and DFDBA are beneficial for the treatment of periodontal infrabony defects. Both the materials were found to be equally effective in all respects except the gain in attachment level, which was found to be more with DFDBA. Long-term studies are suggested to evaluate further the relative efficacy of the two grafts. PMID:25425822

  9. India's growing participation in global clinical trials.

    PubMed

    Gupta, Yogendra K; Padhy, Biswa M

    2011-06-01

    Lower operational costs, recent regulatory reforms and several logistic advantages make India an attractive destination for conducting clinical trials. Efforts for maintaining stringent ethical standards and the launch of Pharmacovigilance Program of India are expected to maximize the potential of the country for clinical research.

  10. India's growing participation in global clinical trials.

    PubMed

    Gupta, Yogendra K; Padhy, Biswa M

    2011-06-01

    Lower operational costs, recent regulatory reforms and several logistic advantages make India an attractive destination for conducting clinical trials. Efforts for maintaining stringent ethical standards and the launch of Pharmacovigilance Program of India are expected to maximize the potential of the country for clinical research. PMID:21489644

  11. 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

  12. [Role of government in clinical trials].

    PubMed

    Mazzetti, Pilar; Silva-Paredes, Gustavo; Cornejo-Olivas, Mario

    2012-01-01

    The regulation of clinical trials by the Government is a process of continuous change and adaptation, current challenge is to ensure the safety of participants and get balance of administrative procedures. Development and regulation of clinical trials in different countries vary according to the situation, context national or international execution, determining the insufficiency of national regulation requiring review of international regulation. The aim of this publication is to present a comprehensive overview of the role of Government in the regulation of clinical trials in different realities. It includes a review of the regulation in The European Union, The United States and some Latin American countries and finally the regulation in Peru. Contemporary trends in the regulation of clinical trials, are characterized by increasing standards of quality, ensuring the safety of the participants, promote transparency, lower bureaucratic processes and strengthening ethics IRB committees in the framework of open democratic processes, involving all stakeholders in dynamic processes based on current knowledge and changing tendencies. The challenge is to promote the development of clinical trials from the government institutions (universities, research centers, institutes, hospitals, etc.) priorizing local needs including orphan drugs, prevalent and neglected diseases, and therapeutic use of active components of local native plants.

  13. Patient-centeredness in the design of clinical trials

    PubMed Central

    Mullins, C. Daniel; Vandigo, Joseph E.; Zheng, Jason; Wicks, Paul

    2014-01-01

    Evidence from clinical trials should contribute to informed decision making and a learning health care system. People frequently, however, find participating in clinical trials meaningless or disempowering. Moreover, people often do not incorporate trial results directly into their decision making. The lack of patient centeredness in clinical trials may be partially addressed through trial design. For example, Bayesian adaptive trials designed to adjust in a pre-specified manner to changes in clinical practice could motivate people and their health care providers to view clinical trials as more applicable to real-world clinical decisions. The way in which clinical trials are designed can transform the evidence generation process to be more patient centered, providing people with an incentive to participate or continue participating in clinical trials. In order to achieve the transformation to patient-centeredness in clinical trial decisions, however, there is a need for transparent and reliable methods and education of trial investigators and site personnel. PMID:24969009

  14. On the scientific inference from clinical trials.

    PubMed

    Holmberg, L; Baum, M; Adami, H O

    1999-05-01

    We have not been able to describe clearly how we generalize findings from a study to our own 'everyday patients'. This difficulty is not surprising, since generalization deals with how empirical observations are related to the growth of scientific knowledge, which is a major philosophical problem. An argument, sometimes used to discard evidence from a trial, is that the patient sample was too selected and therefore not 'representative' enough for the results to be meaningful for generalization. In this paper, we discuss issues of representativeness and generalizability. Other authors have shown that generalization cannot only depend on statistical inference. Then, how do randomized clinical trials contribute to the growth of knowledge? We discuss three aspects of the randomized clinical trial (Mant 1999), First, the trial is an empirical experiment set up to study the intervention on the question as specifically and as much in isolation from other -- biasing and confounding -- factors as possible (Rothman & Greenland 1998). Second, the trial is set up to challenge our prevailing hypotheses (or prejudices) and the trial is above all a help in error elimination (Popper 1992). Third, we need to learn to see new, unexpected and thought-provoking patterns in the data from a trial. Point one -- and partly point two -- refers to the paradigm of the controlled experiment in scientific method. How much a study contributes to our knowledge, with respect to points two and three, relates to its originality. In none of these respects is the representativeness of the patients, or the clinical situations, crucial for judging the study and its possible inferences. However, we also discuss that the biological domain of disease that was studied in a particular trial has to be taken into account. Thus, the inference drawn from a clinical study is not only a question of statistical generalization, but must include a jump from the world of experiences into the world of reason

  15. Clinical Trials in Retinal Dystrophies.

    PubMed

    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

  16. Tooth whitening clinical trials: a global perspective.

    PubMed

    Gerlach, Robert W

    2007-09-01

    Tooth whitening has been the subject of extensive clinical trials research since the introduction of the first hydrogen-peroxide whitening strips in 2000. Availability of digital image analysis, an unambiguous and reproducible method for assessing color change, has contributed to global clinical research and product development on whitening strips. The research has included a series of global randomized controlled trials in distinct sites and cultures, involving 6-6.5% hydrogen peroxide whitening strips used for 7-21 days. These studies, conducted at research hospitals, dental schools, and private dental practice, demonstrated significant color improvement with whitening strips relative to baseline and/or various controls without serious adverse events. This integrated clinical trials research provides important evidence of long-term safety and effectiveness of tooth whitening with 6-6.5% hydrogen peroxide whitening strips.

  17. 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.

  18. [Clinical trials with advanced therapy medicinal products].

    PubMed

    Schüssler-Lenz, M; Schneider, C K

    2010-01-01

    For advanced therapies, the same basic principles for assessment apply as for any other biotechnological medicinal product. Nevertheless, the extent of data for quality, safety, and efficacy can be highly specific. Until recently, advanced therapies were not uniformly regulated across Europe, e.g., tissue engineered products were regulated either as medicinal products or medical devices. Thus, for some products no data from clinical studies are available, e.g., for autologous chondrocyte products. The draft guideline on Good Clinical Practice for clinical trials with advanced therapies describes specific additional requirements, e.g., ensuring traceability. Most clinical studies with advanced therapies in Germany are still in early phase I or II trials with highly divergent types of products and clinical indications. The Committee for Advanced Therapies (CAT) at the European Medicines Agency (EMEA) has been established to meet the scientific and regulatory challenges with advanced therapies.

  19. Clinical Research Methodology 3: Randomized Controlled Trials.

    PubMed

    Sessler, Daniel I; Imrey, Peter B

    2015-10-01

    Randomized assignment of treatment excludes reverse causation and selection bias and, in sufficiently large studies, effectively prevents confounding. Well-implemented blinding prevents measurement bias. Studies that include these protections are called randomized, blinded clinical trials and, when conducted with sufficient numbers of patients, provide the most valid results. Although conceptually straightforward, design of clinical trials requires thoughtful trade-offs among competing approaches-all of which influence the number of patients required, enrollment time, internal and external validity, ability to evaluate interactions among treatments, and cost.

  20. Clinical designs of recent robot rehabilitation trials.

    PubMed

    Lo, Albert C

    2012-11-01

    Rehabilitation robots are increasingly being tested and promoted for clinical neurorehabilitation. Compared with conventional and manual methods, robots allow for a variety of advantages, particularly in the areas of interventional control and the ability to provide a high volume of facilitated movement. Since 1997, there have been more than 60 clinical trials reporting the use of two dozen different robots for neurorehabilitation. Although there are a number of smaller pilot studies, there are only few larger clinical trials. There may be a number of reasons why pilot robot studies do not materialize into larger studies. Beyond devices that failed to perform as intended, what are the clinical design issues that have limited these studies? Some basic considerations include randomization, inclusion of a control group, power calculation based on a clinically meaningful outcome, and finally, reproducible descriptions of the intervention being tested. Although many of these issues are general challenges presented for all rehabilitation studies, there are clinical design features that would likely greatly improve interpretation of results and better position robot devices toward the next clinical trial step. On the other hand, the absence of these elements, even in the setting of a pilot study, may significantly hamper the interpretation of results and not yield sufficient information on treatment effects, adverse event rates, dropout rate, and so on, to allow further testing to proceed to follow-up Food and Drug Administration phase II and III studies. Development of rehabilitation robots for clinical use needs to occur hand in hand with well-conducted clinical trials to provide evidence of efficacy while also taking into account costs.

  1. 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

  2. Clinical Trials in Peripheral Vascular Disease: Pipeline and Trial Designs: An Evaluation of the ClinicalTrials.gov Database

    PubMed Central

    Subherwal, Sumeet; Patel, Manesh R.; Chiswell, Karen; Tidemann-Miller, Beth A.; Jones, W. Schuyler; Conte, Michael S.; White, Christopher J.; Bhatt, Deepak L.; Laird, John R.; Hiatt, William R.; Tasneem, Asba; Califf, Robert M.

    2014-01-01

    Background Tremendous advances have occurred in therapies for peripheral vascular disease (PVD); however, until recently it has not been possible to examine the entire clinical trial portfolio of studies for treatment of PVD (both arterial and venous disease). Methods and Results We examined interventional trials registered in ClinicalTrials.gov from October 2007 through September 2010 (n=40,970) and identified 676 (1.7%) PVD trials (n=493 arterial only, n=170 venous only, n=13 both arterial and venous). Most arterial studies investigated lower extremity peripheral artery disease and acute stroke (35% and 24%, respectively), while most venous studies examined deep vein thrombosis/pulmonary embolus prevention (42%) or venous ulceration (25%). A placebo-controlled trial design was used in 27% of the PVD trials, and 4% of the PVD trials excluded patients aged >65 years. Enrollment in at least 1 US site decreased from 51% in 2007 to 41% of trials in 2010. Compared with non-cardiology disciplines, PVD trials were more likely to be double-blinded, investigate use of devices and procedures, and have industry sponsorship and assumed funding source, and less likely to investigate drug and behavioral therapies. Geographic access to PVD clinical trials within the United States is limited to primarily large metropolitan areas. Conclusions PVD studies represent a small group of trials registered in ClinicalTrials.gov, despite the high prevalence of vascular disease in the general population. This low number, compounded by the decreasing number of PVD trials in the United States, is concerning and may limit the ability to inform current clinical practice of patients with PVD. PMID:25239436

  3. Virtual Reality Job Interview Training and 6-Month Employment Outcomes for Individuals with Schizophrenia Seeking Employment

    PubMed Central

    Smith, Matthew J.; Fleming, Michael F.; Wright, Michael A.; Roberts, Andrea G.; Humm, Laura Boteler; Olsen, Dale; Bell, Morris D.

    2015-01-01

    BACKGROUND Individuals with schizophrenia have low employment rates and the job interview presents a critical barrier for them to obtain employment. Virtual reality training has demonstrated efficacy at improving interview skills and employment outcomes among multiple clinical populations. However, the effects of this training on individuals with schizophrenia are unknown. This study evaluated the efficacy of virtual reality job interview training (VR-JIT) at improving job interview skills and employment outcomes among individuals with schizophrenia in a small randomized controlled trial (n=21 VR-JIT trainees, n=11 waitlist controls). METHODS Trainees completed up to 10 hours of virtual interviews using VR-JIT, while controls received services as usual. Primary outcome measures included two pre-test and two post-test video-recorded role-play interviews scored by blinded human resource experts and self-reported interviewing self-confidence. Six-month follow-up data on employment outcomes were collected. RESULTS Trainees reported the intervention was easy-to-use, helpful, and prepared them for future interviews. Trainees demonstrated increased role-play scores between pre-test and post-test while controls did not (p=0.001). After accounting for neurocognition and months since prior employment, trainees had greater odds of receiving a job offer by 6 month follow-up compared to controls (OR: 8.73, p=0.04) and more training was associated with fewer weeks until receiving a job offer (r=−0.63, p<0.001). CONCLUSIONS Results suggest VR-JIT is acceptable to trainees and may be efficacious for improving job interview skills in individuals with schizophrenia. Moreover, trainees had greater odds of receiving a job offer by 6-month follow-up. Future studies could evaluate the effectiveness of VR-JIT within community-based services. PMID:26032567

  4. OARSI Clinical Trials Recommendations: Design and conduct of clinical trials for hand osteoarthritis.

    PubMed

    Kloppenburg, M; Maheu, E; Kraus, V B; Cicuttini, F; Doherty, M; Dreiser, R-L; Henrotin, Y; Jiang, G-L; Mandl, L; Martel-Pelletier, J; Nelson, A E; Neogi, T; Pelletier, J-P; Punzi, L; Ramonda, R; Simon, L S; Wang, S

    2015-05-01

    Hand osteoarthritis (OA) is a very frequent disease, but yet understudied. However, a lot of works have been published in the past 10 years, and much has been done to better understand its clinical course and structural progression. Despite this new knowledge, few therapeutic trials have been conducted in hand OA. The last OARSI recommendations for the conduct of clinical trials in hand OA dates back to 2006. The present recommendations aimed at updating previous recommendations, by incorporating new data. The purpose of this expert opinion, consensus driven exercise is to provide evidence-based guidance on the design, execution and analysis of clinical trials in hand OA, where published evidence is available, supplemented by expert opinion, where evidence is lacking, to perform clinical trials in hand OA, both for symptom and for structure-modification. They indicate core outcome measurement sets for studies in hand OA, and list the methods and instruments that should be used to measure symptoms or structure. For both symptom- and structure-modification, at least pain, physical function, patient global assessment, HR-QoL, joint activity and hand strength should be assessed. In addition, for structure-modification trials, structural progression should be measured by radiographic changes. We also provide a research agenda listing many unsolved issues that seem to most urgently need to be addressed from the perspective of performing "good" clinical trials in hand OA. These updated OARSI recommendations should allow for better standardizing the conduct of clinical trials in hand OA in the next future.

  5. Effectiveness of core stability exercises and recovery myofascial release massage on fatigue in breast cancer survivors: a randomized controlled clinical trial.

    PubMed

    Cantarero-Villanueva, Irene; Fernández-Lao, Carolina; Del Moral-Avila, Rosario; Fernández-de-Las-Peñas, César; Feriche-Fernández-Castanys, María Belén; Arroyo-Morales, Manuel

    2012-01-01

    The purpose of the present paper was to evaluate the effects of an 8-week multimodal program focused on core stability exercises and recovery massage with DVD support for a 6-month period in physical and psychological outcomes in breast cancer survivors. A randomized controlled clinical trial was performed. Seventy-eight (n = 78) breast cancer survivors were assigned to experimental (core stability exercises plus massage-myofascial release) and control (usual health care) groups. The intervention period was 8 weeks. Mood state, fatigue, trunk curl endurance, and leg strength were determined at baseline, after the last treatment session, and at 6 months of followup. Immediately after treatment and at 6 months, fatigue, mood state, trunk curl endurance, and leg strength exhibited greater improvement within the experimental group compared to placebo group. This paper showed that a multimodal program focused on core stability exercises and massage reduced fatigue, tension, depression, and improved vigor and muscle strength after intervention and 6 months after discharge.

  6. Ten Years after the International Committee of Medical Journal Editors’ Clinical Trial Registration Initiative, One Quarter of Phase 3 Pediatric Epilepsy Clinical Trials Still Remain Unpublished: A Cross Sectional Analysis

    PubMed Central

    Lampert, Anette; Hoffmann, Georg F.; Ries, Markus

    2016-01-01

    Introduction Although selective reporting of clinical trial results introduces bias into evidence based clinical decision making, publication bias in pediatric epilepsy is unknown today. Since there is a considerable ambiguity in the treatment of an important and common clinical problem, pediatric seizures, we assessed the public availability of results of phase 3 clinical trials that evaluated treatments of seizures in children and adolescents as a surrogate for the extent of publication bias in pediatric epilepsy. Methods We determined the proportion of published and unpublished study results of phase 3 clinical trials that were registered as completed on ClinicalTrials.gov. We searched ClinicalTrials.gov, PubMed, and Google Scholar for publications and contacted principal investigators or sponsors. The analysis was performed according to STROBE criteria. Results Considering studies that were completed before 2014 (N = 99), 75 (76%) pediatric phase 3 clinical trials were published but 24 (24%) remained unpublished. The unpublished studies concealed evidence from 4,437 patients. Mean time-to-publication was 25 SD ± 15.6 months, more than twice as long as mandated. Conclusion Ten years after the ICMJE’s clinical trials registration initiative there is still a considerable amount of selective reporting and delay of publication that potentially distorts the body of evidence in the treatment of pediatric seizures. PMID:26735955

  7. Controlled clinical trial of oral and topical diethylcarbamazine in treatment of onchocerciasis.

    PubMed

    Taylor, H R; Greene, B M; Langham, M E

    1980-05-01

    In a double-blind controlled clinical trial comparing the safety and efficacy of oral diethylcarbamazine citrate (DEC) with topical DEC for the treatment of onchocerciasis twenty men with moderate skin-snip microfilarial counts received daily therapy for 1 week, then weekly therapy for the rest of 6 months. The number of microfilariae per skin snip dropped quickly to 2% of initial levels and remained at low levels in those receiving oral DEC, and to 20% of initial levels in patients treated with DEC lotion. Side-effects in both groups included lymphadenopathy, fever, pruritus, rash, proteinuria, and chorioretinitis; they were commoner with topical DEC.

  8. Sufficient trial size to inform clinical practice.

    PubMed

    Manski, Charles F; Tetenov, Aleksey

    2016-09-20

    Medical research has evolved conventions for choosing sample size in randomized clinical trials that rest on the theory of hypothesis testing. Bayesian statisticians have argued that trials should be designed to maximize subjective expected utility in settings of clinical interest. This perspective is compelling given a credible prior distribution on treatment response, but there is rarely consensus on what the subjective prior beliefs should be. We use Wald's frequentist statistical decision theory to study design of trials under ambiguity. We show that ε-optimal rules exist when trials have large enough sample size. An ε-optimal rule has expected welfare within ε of the welfare of the best treatment in every state of nature. Equivalently, it has maximum regret no larger than ε We consider trials that draw predetermined numbers of subjects at random within groups stratified by covariates and treatments. We report exact results for the special case of two treatments and binary outcomes. We give simple sufficient conditions on sample sizes that ensure existence of ε-optimal treatment rules when there are multiple treatments and outcomes are bounded. These conditions are obtained by application of Hoeffding large deviations inequalities to evaluate the performance of empirical success rules. PMID:27601679

  9. Incidental Diagnosis in Healthy Clinical Trial Subjects

    PubMed Central

    Duncan, Christopher JA; Rowland, Rosalind; Lillie, Patrick J; Meyer, Joel; Sheehy, Susanne H; O'Hara, Geraldine A; Hamill, Matthew; Donaldson, Hannah; Dinsmore, Laura; Poulton, Ian D; Gilbert, Sarah C; McShane, Helen; Hill, Adrian VS

    2012-01-01

    Previously unrecognized medical conditions identified in volunteers for early phase clinical studies have significant clinical and ethical implications for the participant. It is therefore crucial that the potential for unexpected diagnosis is addressed during the informed consent process. But the frequency of incidental diagnosis in healthy volunteers who attend for clinical trial screening remains unclear. To assess this we retrospectively analyzed 1,131 independent screening visits for 990 volunteers at a single academic center over a 10-year period to describe the frequency and nature of new clinical findings. Overall 23 of 990 volunteers (2.3%) were excluded at screening for a newly diagnosed medical abnormality. Some clinically important conditions, such as nephrotic syndrome and familial hypercholesterolemia were identified. The frequency of abnormalities was associated with increasing age in males (p = 0.02 χ2 for trend) but not females (p = 0.82). These data will assist those planning and conducting phase I/II vaccine trials in healthy volunteers, and importantly should strengthen the informed consent of future trial participants. Clin Trans Sci 2012; Volume 5: 348–350 PMID:22883613

  10. Information-based monitoring of clinical trials.

    PubMed

    Tsiatis, Anastasios A

    2006-10-15

    When designing a clinical trial to compare the effect of different treatments on response, a key issue facing the statistician is to determine how large a study is necessary to detect a clinically important difference with sufficient power. This is the case whether the study will be analysed only once (single-analysis) or whether it will be monitored periodically with the possibility of early stopping (group-sequential). Standard sample size calculations are based on both the magnitude of difference that is considered clinically important as well as values for the nuisance parameters in the statistical model. For planning purposes, best guesses are made for the value of the nuisance parameters and these are used to determine the sample size. However, if these guesses are incorrect this will affect the subsequent power to detect the clinically important difference. It is argued in this paper that statistical precision is directly related to Statistical Information and that the study should continue until the requisite statistical information is obtained. This is referred to as information-based design and analysis of clinical trials. We also argue that this type of methodology is best suited with group-sequential trials which monitor the data periodically and allow for estimation of the statistical information as the study progresses. PMID:16927248

  11. Seven myths of randomisation in clinical trials.

    PubMed

    Senn, Stephen

    2013-04-30

    I consider seven misunderstandings that may be encountered about the nature, purpose and properties of randomisation in clinical trials. Some concern the practical realities of clinical research on patients. Others are to do with the value and purpose of balance. Still others are to do with a confusion about the role of conditioning in valid statistical inference. I consider a simple game of chance involving two dice to illustrate some points about inference and then consider the seven misunderstandings in turn. I conclude that although one should not make a fetish of randomisation, when proposing alternatives to randomisation in clinical trials, one should be very careful to be precise about the exact nature of the alternative being considered if one is to avoid the danger of underestimating the advantages that randomisation can offer. PMID:23255195

  12. Neuroendocrine cancer vaccines in clinical trials.

    PubMed

    Bridle, Byram W

    2011-06-01

    This article focuses on neuroendocrine cancer vaccines that have been evaluated in human clinical trials within the last 5 years. The definition of what constitutes a neuroendocrine tumor requires clarification. Strategies and barriers common to cancer vaccines are highlighted. In general, neuroendocrine cancer is rare; however, special attention will be paid to neuroblastoma and small-cell-lung cancer owing to their relatively higher prevalence. A variety of other neuroendocrine tumor vaccine trials will also be addressed. The common problem of generating only sporadic tumor-specific immune responses that are of low-magnitude will be discussed in detail, with recommendations for future directions.

  13. Powered toothbrushes: a review of clinical trials.

    PubMed

    Heasman, P A; McCracken, G I

    1999-07-01

    There is now a vast range of powered toothbrushes (PTBs) available on the market and the efficacy of each product is usually determined in one, or a series of controlled clinical trials. This article reviews briefly the design of PTBs, some of the proposed indications for their use, and the principal observations from published studies of these products. The important issues regarding the regulation and design of trials involving PTBs are discussed and some recommendations are proposed with a view to developing a more structured approach to testing these products.

  14. Dialogues on diversifying clinical trials: successful strategies for engaging women and minorities in clinical trials.

    PubMed

    Coakley, Meghan; Fadiran, Emmanuel Olutayo; Parrish, L Jo; Griffith, Rachel A; Weiss, Eleanor; Carter, Christine

    2012-07-01

    There is mounting scientific evidence pointing to genetic or physiologic distinctions between genders and among racial and ethnic groups that influence disease risk and severity and response to treatment. The diverse enrollment of subjects engaged in clinical trials research is, thus, critical to developing safer and more effective drugs and medical devices. However, in the United States, there are striking disparities in clinical trial participation. To address this problem, the Food and Drug Administration (FDA) Office of Women's Health and the Society for Women's Health Research (SWHR) together convened the 2-day meeting, Dialogues on Diversifying Clinical Trials. The conference was held in Washington, DC, on September 22-23, 2011, and brought together a wide range of speakers from clinical research, industry, and regulatory agencies. Here, we present the major findings discussed at this meeting about female and minority patients and physicians and their willingness to participate in clinical trials and the barriers that sponsors face in recruiting a diverse trial population. We also discuss some recommendations for improving trial diversity through new technologies and greater efficiency in trial regulation and review.

  15. 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

  16. Using e-technologies in clinical trials

    PubMed Central

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

    2015-01-01

    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

  17. Desmopressin versus Oxybutynin for Nocturnal Enuresis in Children in Bandar Abbas: A Randomized Clinical Trial

    PubMed Central

    Ghasemi, Kambiz; Esteghamati, Maryam; Mohammadzadeh, Malihe; Zare, Shahram

    2016-01-01

    Background Nocturnal enuresis is among the most common disorders in children. Several pharmacological and non-pharmacological treatments are available for nocturnal enuresis. Studies for reaching the best pharmacological treatment for this disorder are continuing. Objective To compare the effectiveness and safety of Desmopressin and oxybutynin for treatment of nocturnal enuresis in children from Bandar Abbas in 2014. Methods This randomized controlled trial was conducted in 2014 and participants included 66 children with nocturnal enuresis who were more than 5 years old. Patients were randomly assigned into two groups. The first group received 120 microgram Desmopressin daily for 2 months, then 60 microgram daily for 2 months, then 60 microgram every 2 days. The second group received 5 mg oxybutynin twice a day for 6 months. The patients were followed after 1, 3, and 6 months to track treatment response. The study outcomes were frequency of nocturnal enuresis, urinary incontinency, urgency, and frequency. Data were analyzed using SPSS software. Results There were no significant differences between the two groups with respects to sex, age, place of residence, and parents’ education (p<0.05). Nocturnal enuresis, incontinency, urgency, and frequency of nocturnal enuresis was significantly lower with Desmopressin treatment in comparison to the oxybutynin treated group after 1 and 3 months (p<0.05). In addition, constipation and xerostomia were more frequent among the oxybutynin group after 1, 3, and 6 months (p<0.01). Blurred vision was also more frequent among oxybutynin group after 3 months (p<0.01). After 6 months the frequency of nocturnal enuresis and its frequency was higher in oxybutynin group in comparison to the Desmopressin group (p<0.05). Conclusion Desmopressin is more effective and has lower rate of side effects in comparison to oxybutynin for treatment of nocturnal enuresis. We recommend using Desmopressin for treatment of nocturnal enuresis in children

  18. Clinical trial endpoints in acute kidney injury.

    PubMed

    Billings, Frederic T; Shaw, Andrew D

    2014-01-01

    The development and use of consensus criteria for acute kidney injury (AKI) diagnosis and the inclusion of recently identified markers of renal parenchymal damage as endpoints in clinical trials have improved the ability of physicians to compare the incidence and severity of AKI across patient populations, provided targets for testing new treatments, and may increase insight into the mechanisms of AKI. To date, these markers have not consistently translated into important clinical outcomes. Is that because these markers of renal injury/dysfunction are measurements of process of care (and not indicative of persistently impaired renal function), or is it because patients do actually recover from AKI? Physicians currently have limited ability to measure renal function reserve, and the ultimate consequence of a case of AKI on long-term morbidity remains unclear. There is little doubt that groups of patients who develop AKI have worse outcomes than groups of patients who do not, but investigators are now realizing the value of measuring clinically meaningful renal endpoints in all subjects enrolled in AKI clinical trials. Important examples of these outcomes include persistently impaired renal function, new hemodialysis, and death. We propose that these major adverse kidney events (MAKE) be included in all effectiveness clinical trials. Adaptation of the MAKE composite assessed 30, 60, or 90 days following AKI (i.e., MAKE30 or MAKE90) will improve our capacity to understand and treat AKI and may also provide a consensus composite to allow comparison of different interventions. Primary endpoints for phase I and II clinical trials, on the other hand, should continue to use continuous markers of renal injury/dysfunction as well as 'hard' clinical outcomes in order to generate meaningful data with limited subject exposure to untested treatments. By doing so, investigators may assess safety without requiring large sample sizes, demonstrate treatment effect of an unknown

  19. 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.

  20. Clinical trials integrity: a CRO perspective.

    PubMed

    Beach, J E

    2001-01-01

    When contract research organizations (CROs) were first formed, pharmaceutical companies outsourced to them only certain aspects of the conduct of their clinical trials. At first CROs were highly specialized entities, providing, for example, either biostatistical advice, clinical research associates who monitored investigational sites for regulatory compliance, or regulatory support. Gradually, full service CROs emerged, offering a full range of services for clinical trials, including the selection of investigators and investigational sites, assistance with patient recruitment, safety surveillance and reporting, site audits, and data management and biostatistics. This evolving relationship between CROs and the pharmaceutical and medical device industries has resulted in CROs assuming more and more of the regulatory and ethical risks and responsibilities inherent in the conduct of clinical trials. In this full service role, CROs, unlike sponsors, are not interested in the outcome of study, but like sponsors, are subject to heavy regulation by the federal government, must follow applicable state laws, must respect international guidelines, and are obliged to follow their own operating procedures. Moreover, they are judged by the industry on the basis of the scope and quality of services provided, including the degree of adherence to the research protocol, regulatory requirements, and timelines; the quality of the professional working relationships with investigators and institutions, both academic and community-based; and the validity of the data. Further, CROs are subject to comprehensive audits by sponsoring companies, FDA, and other regulatory authorities. For all these reasons, CROs are being tasked with strict vigilance of all stages of the clinical trial process to ensure that the laws, regulations, and industry standards designed for the protection of human subjects and data integrity are maintained.

  1. 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

  2. How do researchers decide early clinical trials?

    PubMed

    Grankvist, Hannah; Kimmelman, Jonathan

    2016-06-01

    Launch of clinical investigation represents a substantial escalation in commitment to a particular clinical translation trajectory; it also exposes human subjects to poorly understood interventions. Despite these high stakes, there is little to guide decision-makers on the scientific and ethical evaluation of early phase trials. In this article, we review policies and consensus statements on human protections, drug regulation, and research design surrounding trial launch, and conclude that decision-making is largely left to the discretion of research teams and sponsors. We then review what is currently understood about how research teams exercise this discretion, and close by laying out a research agenda for characterizing the way investigators, sponsors, and reviewers approach decision-making in early phase research.

  3. ClinicalTrials.gov | NIH MedlinePlus the Magazine

    MedlinePlus

    ... this page please turn Javascript on. Clinical Trials.gov Past Issues / Summer 2011 Table of Contents “...a ... help with a clinical trial: Visit www.clinicaltrials.gov Brought to you by the National Library of ...

  4. 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

  5. Clinical and radiographic comparison of various medicaments used for pulpotomy in primary molars: A randomized clinical trial

    PubMed Central

    Goyal, Prachi; Pandit, I. K.; Gugnani, Neeraj; Gupta, Monica; Goel, Richa; Gambhir, Ramandeep Singh

    2016-01-01

    Objective: To evaluate and compare the efficacy of ferric sulfate, glutaraldehyde, and mineral trioxide aggregate (MTA) as pulpotomy medicaments in primary molars. Materials and Methods: This was a perspective randomized clinical trial. A total of 90 molars from 42 children aged 4–8 years were selected for pulpotomy procedure. Teeth were randomly divided into three equal groups of 30 teeth each. Teeth in Group I were intended to be treated with ferric sulfate, Group II were intended to be treated with buffered glutaraldehyde and Group III with MTA. All the molars were evaluated clinically at 24 h and both clinically and radio graphically at 1, 3, and 6 months. The observations were statistically analyzed using Chi-square test and Fisher's exact test. Results: After 1 month, there was no clinical finding observed in all the three groups. At 3 months postoperative evaluation, 13.3% of teeth in Group I and 12.5% of teeth in Group II had mobility. At 6 months interval, pain and sinus formation each was noted in 9.1% of primary teeth in Group I while periodontal ligament widening was reported in 66.7% of teeth in Group I and 85.7% of teeth in Group II. Conclusion: MTA exhibited overall best results as pulpotomy agent for primary molars followed by 15.5% ferric sulfate, whereas 2% buffered glutaraldehyde was found to be least effective as a pulpotomy agent. PMID:27403046

  6. 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.

  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. OARSI Clinical Trials Recommendations: Soluble biomarker assessments in clinical trials in osteoarthritis.

    PubMed

    Kraus, V B; Blanco, F J; Englund, M; Henrotin, Y; Lohmander, L S; Losina, E; Önnerfjord, P; Persiani, S

    2015-05-01

    The objective of this work was to describe requirements for inclusion of soluble biomarkers in osteoarthritis (OA) clinical trials and progress toward OA-related biomarker qualification. The Guidelines for Biomarkers Working Group, representing experts in the field of OA biomarker research from both academia and industry, convened to discuss issues related to soluble biomarkers and to make recommendations for their use in OA clinical trials based on current knowledge and anticipated benefits. This document summarizes current guidance on use of biomarkers in OA clinical trials and their utility at five stages, including preclinical development and phase I to phase IV trials. As demonstrated by this summary, biomarkers can provide value at all stages of therapeutics development. When resources permit, we recommend collection of biospecimens in all OA clinical trials for a wide variety of reasons but in particular, to determine whether biomarkers are useful in identifying those individuals most likely to receive clinically important benefits from an intervention; and to determine whether biomarkers are useful for identifying individuals at earlier stages of OA in order to institute treatment at a time more amenable to disease modification. PMID:25952342

  9. OARSI Clinical Trials Recommendations: Soluble biomarker assessments in clinical trials in osteoarthritis.

    PubMed

    Kraus, V B; Blanco, F J; Englund, M; Henrotin, Y; Lohmander, L S; Losina, E; Önnerfjord, P; Persiani, S

    2015-05-01

    The objective of this work was to describe requirements for inclusion of soluble biomarkers in osteoarthritis (OA) clinical trials and progress toward OA-related biomarker qualification. The Guidelines for Biomarkers Working Group, representing experts in the field of OA biomarker research from both academia and industry, convened to discuss issues related to soluble biomarkers and to make recommendations for their use in OA clinical trials based on current knowledge and anticipated benefits. This document summarizes current guidance on use of biomarkers in OA clinical trials and their utility at five stages, including preclinical development and phase I to phase IV trials. As demonstrated by this summary, biomarkers can provide value at all stages of therapeutics development. When resources permit, we recommend collection of biospecimens in all OA clinical trials for a wide variety of reasons but in particular, to determine whether biomarkers are useful in identifying those individuals most likely to receive clinically important benefits from an intervention; and to determine whether biomarkers are useful for identifying individuals at earlier stages of OA in order to institute treatment at a time more amenable to disease modification.

  10. Effectiveness of HIV/STD Sexual Risk Reduction Groups for Women in Substance Abuse Treatment Programs: Results of a NIDA Clinical Trials Network Trial

    PubMed Central

    Tross, Susan; Campbell, Aimee N. C.; Cohen, Lisa R.; Calsyn, Donald; Pavlicova, Martina; Miele, Gloria; Hu, Mei-Chen; Haynes, Louise; Nugent, Nancy; Gan, Weijin; Hatch-Maillette, Mary; Mandler, Raul; McLaughlin, Paul; El-Bassel, Nabila; Crits-Christoph, Paul; Nunes, Edward V.

    2009-01-01

    Context Since drug-involved women are among the fastest growing groups with AIDS, sexual risk reduction intervention for them is a public health imperative. Objective Test effectiveness of HIV/STD safer sex skills building (SSB) groups for women in community drug treatment. Design Randomized trial of SSB versus standard HIV/STD Education (HE); assessments at baseline, 3- and 6- months Participants Women recruited from 12 methadone or psychosocial treatment programs in NIDA’s Clinical Trials Network. 515 women with ≥ one unprotected vaginal or anal sex occasion (USO) with a male partner in the past 6 months were randomized. Interventions In SSB, five 90-minute groups used problem-solving and skills rehearsal to increase HIV/STD risk awareness, condom use and partner negotiation skills. In HE, one 60-minute group covered HIV/STD disease, testing, treatment, and prevention information. Main Outcome Number of USOs at follow up. Results A significant difference in mean USOs was obtained between SSB and HE over time (F=67.2, p<.0001). At 3 months, significant decrements were observed in both conditions. At 6 months SSB maintained the decrease, HE returned to baseline (p<.0377). Women in SSB had 29% fewer USOs than those in HE. Conclusions Skills building interventions can produce ongoing sexual risk reduction in women in community drug treatment. PMID:18645513

  11. 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

  12. Mediated Imitation in 6-Month-Olds: Remembering by Association.

    ERIC Educational Resources Information Center

    Barr, Rachel; Vieira, Aurora; Rovee-Collier, Carolyn

    2001-01-01

    Two experiments examined whether associating an imitation task with an operant task affected 6-month-olds' memory for either task. Results indicated that infants successfully imitated a puppet's action for up to 2 weeks only if the associated operant task (pressing a lever to activate a miniature train) was retrieved first. Follow-up study…

  13. Retrieval Protracts Deferred Imitation by 6-Month-Olds

    ERIC Educational Resources Information Center

    Barr, Rachel; Rovee-Collier, Carolyn; Campanella, Jennifer

    2005-01-01

    Past research using a deferred imitation task has shown that 6-month-olds remember a 3-part action sequence for only 1 day. The concept of a time window suggests that there is a limited period within which additional information can be integrated with a prior memory. Its width tracks the forgetting function of the memory. This study asked if…

  14. Maternal Regulation of Infant Reactivity From 2 to 6 Months.

    ERIC Educational Resources Information Center

    Jahromi, Laudan B.; Putnam, Samuel P.; Stifter, Cynthia A.

    2004-01-01

    Previous research has investigated the effect of maternal soothing behaviors on reducing infant reactivity but not the differential effects of specific maternal behaviors on infant stress responses. The present study investigated maternal regulation of 2- and 6-month-olds' responses to an inoculation and found a significant decline with age in…

  15. 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

  16. A model to examine the validity of the 6-month abstinence criterion for liver transplantation.

    PubMed

    Yates, W R; Martin, M; LaBrecque, D; Hillebrand, D; Voigt, M; Pfab, D

    1998-04-01

    Six months of abstinence from alcohol is a commonly used criterion for liver transplantation eligibility for patients with alcoholic cirrhosis. There is limited evidence to document the validity of this criterion with regard to risk of alcoholism relapse. Ninety-one patients with alcoholic cirrhosis were interviewed for relapse risk using the High Risk Alcoholism Relapse (HRAR) Scale. The HRAR model can be used to predict relapse risk independent of duration of sobriety and therefore can be used to examine the validity of the 6 months of abstinence criteria in this clinical population. The two methods demonstrated poor to fair agreement. Agreement was highest with a cutoff allowing a 5% 6-month relapse risk when 79% agreement (c = 0.56) was demonstrated between the two methods. Using the 6-month abstinence criterion alone disallows a significant number of candidates who have a low relapse risk based on their HRAR score. The validity of the 6-month abstinence criterion is supported somewhat by comparison with the HRAR model. However, use of the 6-month abstinence criterion alone forces a significant number of patients with a low relapse risk by HRAR to wait for transplant listing. A relapse risk model based on an estimate of alcoholism severity in addition to duration of sobriety may more accurately select patients who are most likely to benefit from liver transplantation. PMID:9581661

  17. 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

  18. What is the impact of ethics on clinical trials?

    PubMed

    Spielman, Bethany

    2016-01-01

    Ethics has often been ignored or evaded in clinical trials, and the conditions under which global clinical trials are conducted make this problem likely to persist. Ethics can, however, have an impact at any of several stages of a trial when the individuals involved are committed. This editorial provides historical examples of ignoring, evading or, alternatively, using ethical help to improve clinical trials, and suggests that the actual role of ethics depends on the individuals involved.

  19. Advances in clinical research methodology for pain clinical trials.

    PubMed

    Farrar, John T

    2010-11-01

    Pain is a ubiquitous phenomenon, but the experience of pain varies considerably from person to person. Advances in understanding of the growing number of pathophysiologic mechanisms that underlie the generation of pain and the influence of the brain on the experience of pain led to the investigation of numerous compounds for treating pain. Improved knowledge of the subjective nature of pain, the variations in the measurement of pain, the mind-body placebo effect and the impact of differences in the conduct of a clinical trial on the outcome have changed approaches to design and implement studies. Careful consideration of how these concepts affect the choice of study population, the randomization and blinding process, the measurement and collection of data, and the analysis and interpretation of results should improve the quality of clinical trials for potential pain therapies.

  20. 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

  1. 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

  2. 77 FR 35407 - Proposed Collection; Comment Request: Clinical Mythteries: A Video Game About Clinical Trials

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-06-13

    ...: A Video Game About Clinical Trials SUMMARY: In compliance with the requirement of Section 3506(c)(2... Collection: Title: Clinical Mythteries: A Video Game About Clinical Trials. Type of Information...

  3. Advances in kinase targeting: current clinical use and clinical trials.

    PubMed

    Rask-Andersen, Mathias; Zhang, Jin; Fabbro, Doriano; Schiöth, Helgi B

    2014-11-01

    Phosphotransferases, also known as kinases, are the most intensively studied protein drug target category in current pharmacological research, as evidenced by the vast number of kinase-targeting agents enrolled in active clinical trials. This development has emerged following the great success of small-molecule, orally available protein kinase inhibitors for the treatment of cancer, starting with the introduction of imatinib (Gleevec®) in 2003. The pharmacological utility of kinase-targeting has expanded to include treatment of inflammatory diseases, and rapid development is ongoing for kinase-targeted therapies in a broad array of indications in ophthalmology, analgesia, central nervous system (CNS) disorders, and the complications of diabetes, osteoporosis, and otology. In this review we highlight specifically the kinase drug targets and kinase-targeting agents being explored in current clinical trials. This analysis is based on a recent estimate of all established and clinical trial drug mechanisms of action, utilizing private and public databases to create an extensive dataset detailing aspects of more than 3000 approved and experimental drugs. PMID:25312588

  4. Use of crowdsourcing for cancer clinical trial development.

    PubMed

    Leiter, Amanda; Sablinski, Tomasz; Diefenbach, Michael; Foster, Marc; Greenberg, Alex; Holland, John; Oh, William K; Galsky, Matthew D

    2014-10-01

    Patient and physician awareness and acceptance of trials and patient ineligibility are major cancer clinical trial accrual barriers. Yet, trials are typically conceived and designed by small teams of researchers with limited patient input. We hypothesized that through crowdsourcing, the intellectual and creative capacity of a large number of researchers, clinicians, and patients could be harnessed to improve the clinical trial design process. In this study, we evaluated the feasibility and utility of using an internet-based crowdsourcing platform to inform the design of a clinical trial exploring an antidiabetic drug, metformin, in prostate cancer. Over a six-week period, crowd-sourced input was collected from 60 physicians/researchers and 42 patients/advocates leading to several major (eg, eligibility) and minor modifications to the clinical trial protocol as originally designed. Crowdsourcing clinical trial design is feasible, adds value to the protocol development process, and may ultimately improve the efficiency of trial conduct.

  5. Randomized Clinical Trial of a Sustained-Exposure Ciprofloxacin for Intratympanic Injection During Tympanostomy Tube Surgery

    PubMed Central

    Mair, Eric A.; Moss, Jonathan R.; Dohar, Joseph E.; Antonelli, Patrick J.; Bear, Moraye; LeBel, Carl

    2016-01-01

    Objective: This exploratory clinical trial evaluated the safety and clinical activity of a novel, sustained-exposure formulation of ciprofloxacin microparticulates in poloxamer (OTO-201) administered during tympanostomy tube placement in children. Methods: Double-blind, randomized, prospective, placebo- and sham-controlled, multicenter Phase 1b trial in children (6 months to 12 years) with bilateral middle ear effusion requiring tympanostomy tube placement. Patients were randomized to intraoperative OTO-201 (4 mg or 12 mg), placebo, or sham (2:1:1 ratio). Results: Eighty-three patients (52 male/31 female; mean age, 2.80 years) were followed for safety (otoscopic exams, cultures, audiometry, and tympanometry) and clinical activity, defined as treatment failure (physician-documented otorrhea and/or otic or systemic antibiotic use ≥3 days post surgery). At baseline, 14.3% to 36.8% of children showed positive cultures of middle ear effusion samples in at least 1 ear. Through day 15, treatment failures accounted for 14.3%, 15.8%, 45.5%, and 42.9% of patients (OTO-201 4 mg, OTO-201 12 mg, placebo, and sham, respectively); treatment failure reductions for OTO-201 doses were significant compared to pooled control (P values = .023 and .043, respectively). Observed OTO-201 safety profile was indistinguishable from placebo or sham. Conclusions: Results of this first clinical trial suggest that OTO-201 was well tolerated and shows preliminary clinical activity in treating tympanostomy tube otorrhea. PMID:26296929

  6. Globalization of clinical trials - where are we heading?

    PubMed

    George, Melvin; Selvarajan, Sandhiya; S, Suresh-Kumar; Dkhar, Steven A; Chandrasekaran, Adithan

    2013-05-01

    The last decade has witnessed a greater transparency in clinical research with the advent of clinical trial registries. The aim of the study was to describe the trends in the globalization of clinical trials in the last five years. We performed an internet search using the WHO International clinical trials registry platform (WHO ICTRP) to identify the clinical trials conducted from January 2007 to December 31, 2011 among 25 countries. Among the 25 countries, the United States, Japan and Germany occupy the top positions in the total number of clinical trials conducted. Clinical trials in the US (36312) constituted 31.5% of the total number of trials performed during this period. However over a period of five years both US and Western Europe appear to show a decline, while the emerging countries show a rise in clinical trials registered. Among the emerging countries China, India and Republic of Korea are most active regions involved in clinical trials. Cancer, diabetes and respiratory diseases were most widely researched areas overall. Although the study confirms the transition in the clinical trials research towards emerging countries, the developed regions of the world still contribute to more than 70% of the trials registered worldwide.

  7. Whole body vibration for older persons: an open randomized, multicentre, parallel, clinical trial

    PubMed Central

    2011-01-01

    Background Institutionalized older persons have a poor functional capacity. Including physical exercise in their routine activities decreases their frailty and improves their quality of life. Whole-body vibration (WBV) training is a type of exercise that seems beneficial in frail older persons to improve their functional mobility, but the evidence is inconclusive. This trial will compare the results of exercise with WBV and exercise without WBV in improving body balance, muscle performance and fall prevention in institutionalized older persons. Methods/Design An open, multicentre and parallel randomized clinical trial with blinded assessment. 160 nursing home residents aged over 65 years and of both sexes will be identified to participate in the study. Participants will be centrally randomised and allocated to interventions (vibration or exercise group) by telephone. The vibration group will perform static/dynamic exercises (balance and resistance training) on a vibratory platform (Frequency: 30-35 Hz; Amplitude: 2-4 mm) over a six-week training period (3 sessions/week). The exercise group will perform the same exercise protocol but without a vibration stimuli platform. The primary outcome measure is the static/dynamic body balance. Secondary outcomes are muscle strength and, number of new falls. Follow-up measurements will be collected at 6 weeks and at 6 months after randomization. Efficacy will be analysed on an intention-to-treat (ITT) basis and 'per protocol'. The effects of the intervention will be evaluated using the "t" test, Mann-Witney test, or Chi-square test, depending on the type of outcome. The final analysis will be performed 6 weeks and 6 months after randomization. Discussion This study will help to clarify whether WBV training improves body balance, gait mobility and muscle strength in frail older persons living in nursing homes. As far as we know, this will be the first study to evaluate the efficacy of WBV for the prevention of falls. Trial

  8. Safety and efficacy of oral slow release morphine for maintenance treatment in heroin addicts: a 6-month open noncomparative study.

    PubMed

    Vasilev, Georgi N; Alexieva, Daniela Z; Pavlova, Rositsa Z

    2006-01-01

    This open-label, noncomparative, single-center trial evaluated the safety and efficacy of once-daily treatment with slow release oral morphine (SROM) capsules for the maintenance treatment of 20 outpatients with heroin dependency over 6 months at the National Institute for Addictions in Sofia, Bulgaria. Doses were individually titrated up to a mean daily maintenance dose of 760 mg (range 440-1,200 mg). SROM was effective in significantly reducing the signs and symptoms of opioid withdrawal and craving for heroin, with stabilization generally evident within two weeks. Nineteen patients completed 6 months of treatment and illicit opioid use was virtually eliminated. One patient withdrew voluntarily at 22 weeks. Validated questionnaires and tests indicated improvements in patients' well-being from baseline assessments. These included significant improvements with regard to suicidal depression (85%), anxiety and dysphoria (66%), general illness (58%), social dysfunction (54%), sense of hopelessness (34%), attention (25%), and self-reported typical depressive (27%) and disease-related (11%) symptoms. No deaths, serious adverse events, or withdrawals due to adverse events occurred. Five episodes of constipation and one episode of sweating (all nonserious and of mild or moderate severity) were reported. Vital signs were unaffected by SROM and no weight change was evident over the study period. The observations made in this study indicate a promising role for once-daily treatment with SROM in the clinical management of heroin dependency.

  9. [Stem cells in cardiological clinical trials].

    PubMed

    Przybycień, Krzysztof; Kornacewicz Jach, Zdzisława; Machaliński, Bogusław

    2011-01-01

    Stem cell-based therapy is a novel therapeutic strategy introduced into cardiology, although there are not any established standards within the stem/progenitor cell type employed, their preparation, rout of administration as well as methods controlling the pathophysiological and clinical parameters after the cell application. The aim of the present work was a complex meta-analysis of the clinical trials carried out in this field. Over 1000 patients with myocardial infarction as well as circulatory failure have been treated with stem cell-based therapy so far, but the obtained results are not concordant. Progress within cell biology and biotechnology give hopes for development of more effective therapeutic approaches. Identification and isolation of cardiac- -specific stem/progenitor cells may deliver new perspectives for such therapy in the nearest future.

  10. Pharmacotherapy of urolithiasis: evidence from clinical trials.

    PubMed

    Moe, Orson W; Pearle, Margaret S; Sakhaee, Khashayar

    2011-02-01

    Urolithiasis is a worldwide problem with significant health and economic burdens. Medical therapy that alters the course of stone disease has enormous medical and financial impact. Urolithiasis is a final manifestation of a broad range of etiologies and pathogenesis. The modest progress in understanding the pathophysiology has hampered successful development of targeted therapy. Current regimens are based mostly on rational alteration of urinary biochemistry and physical chemistry to lower the risk of precipitation. In terms of pharmacotherapy, there are drugs to successfully improve hypercalciuria, hypocitraturia, aciduria, hyperuricosuria, and hypercystinuria. These agents have been proven to be effective in randomized controlled trials in improving urinary biochemical and physicochemical risk factors, as well as clinical outcomes. Although our current regimens have clearly improved the management and lives of stone formers, there are still clearly identifiable immense voids in the knowledge of pathophysiology of stone disease that can be filled with combined basic science and clinical studies. PMID:20927039

  11. 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....

  12. 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 ...

  13. ClinicalTrials.gov Turns 10! | NIH MedlinePlus the Magazine

    MedlinePlus

    ... please turn Javascript on. Feature: Clinical Trials ClinicalTrials.gov Turns 10! Past Issues / Fall 2010 Table of ... and whom to contact for more information. ClinicalTrials.gov's Helpful Features ClinicalTrials.gov has many helpful consumer ...

  14. Citation Sentiment Analysis in Clinical Trial Papers.

    PubMed

    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.

  15. 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

  16. Congenital Panfollicular Nevus in a 6-Month-Old Girl.

    PubMed

    Duan, Linna; Antaya, Richard J; Ko, Christine J; Narayan, Deepak

    2016-01-01

    A 6-month-old girl presented with an irregular nodule on the right lateral neck. The lesion, which superficially resembled a lymphangioma or mastocytoma, had been present since birth but had recently been growing. The patient was referred for surgical resection. Microscopic findings were compatible with a recently described rare hamartoma termed "panfollicular nevus," which is a well-circumscribed lesion containing aberrantly differentiated, clustered hair follicles in high density. PMID:26822169

  17. SPIRIT 2013 Statement: defining standard protocol items for clinical trials.

    PubMed

    Chan, An-Wen; Tetzlaff, Jennifer M; Altman, Douglas G; Laupacis, Andreas; Gøtzsche, Peter C; Krle A-Jerić, Karmela; Hrobjartsson, Asbjørn; Mann, Howard; Dickersin, Kay; Berlin, Jesse A; Dore, Caroline J; Parulekar, Wendy R; Summerskill, William S M; Groves, Trish; Schulz, Kenneth F; Sox, Harold C; Rockhold, Frank W; Rennie, Drummond; Moher, David

    2015-12-01

    The protocol of a clinical trial serves as the foundation for study planning, conduct, reporting, and appraisal. However, trial protocols and existing protocol guidelines vary greatly in content and quality. This article describes the systematic development and scope of SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) 2013, a guideline for the minimum content of a clinical trial protocol. The 33-item SPIRIT checklist applies to protocols for all clinical trials and focuses on content rather than format. The checklist recommends a full description of what is planned; it does not prescribe how to design or conduct a trial. By providing guidance for key content, the SPIRIT recommendations aim to facilitate the drafting of high-quality protocols. Adherence to SPIRIT would also enhance the transparency and completeness of trial protocols for the benefit of investigators, trial participants, patients, sponsors, funders, research ethics committees or institutional review boards, peer reviewers, journals, trial registries, policymakers, regulators, and other key stakeholders. PMID:27440100

  18. Clinical Research Trials | NIH MedlinePlus the Magazine

    MedlinePlus

    ... of this page please turn Javascript on. Clinical Research Trials Past Issues / Summer 2012 Table of Contents Let the Opportunities to Join A Clinical Study Find You How does clinical research work? Visit our website and click on New ...

  19. Curcumin effects on blood lipid profile in a 6-month human study.

    PubMed

    Baum, Larry; Cheung, Stanley K K; Mok, Vincent C T; Lam, Linda C W; Leung, Vivian P Y; Hui, Elsie; Ng, Chelsia C Y; Chow, Moses; Ho, Ping C; Lam, Sherry; Woo, Jean; Chiu, Helen F K; Goggins, William; Zee, Benny; Wong, Adrian; Mok, Hazel; Cheng, William K F; Fong, Carmen; Lee, Jenny S W; Chan, Ming-Houng; Szeto, Samuel S L; Lui, Victor W C; Tsoh, Joshua; Kwok, Timothy C Y; Chan, Iris H S; Lam, Christopher W K

    2007-12-01

    Studies in animals and a short-term human study have suggested that curcumin, a polyphenolic compound concentrated in the curry spice turmeric, decreases serum cholesterol concentration. However, no controlled human trials have examined the effect of curcumin on cholesterol. This study investigated the effects of consuming curcumin on the serum lipid profile in men and women. Elderly subjects (n=36) consumed 4 g/d curcumin, 1g/d curcumin, or placebo in a 6-month, randomized, double-blind trial. Plasma curcumin and its metabolites were measured at 1 month, and the serum lipid profile was measured at baseline, 1 month, and 6 months. The plasma curcumin concentration reached a mean of 490 nmol/L. The curcumin concentration was greater after capsule than powder administration. Consumption of either dose of curcumin did not significantly affect triacylglycerols, or total, LDL, and HDL cholesterol over 1 month or 6 months. However, the concentrations of plasma curcumin and serum cholesterol were positively and significantly correlated. Curcumin consumption does not appear to have a significant effect on the serum lipid profile, unless the absorbed concentration of curcumin is considered, in which case curcumin may modestly increase cholesterol.

  20. 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

  1. MESHING MOLECULAR SEQUENCES AND CLINICAL TRIALS: A FEASIBILITY STUDY

    PubMed Central

    Chen, Elizabeth S.; Sarkar, Indra Neil

    2009-01-01

    The centralized and public availability of molecular sequence and clinical trial data presents an opportunity to identify potentially valuable linkages across the bench-to-bedside “T1” translational barrier. In this study, we sought to leverage keyword metadata (Medical Subject Heading [MeSH] descriptors) to infer relationships between molecular sequences and clinical trials, as indexed by GenBank and ClinicalTrials.gov. The results of this feasibility study found that approximately 30% of sequences in GenBank could be linked to trials and over 90% of trials in ClinicalTrials.gov could be linked to sequences through MeSH descriptors. In a cursory evaluation, we were able to consistently identify meaningful linkages between molecular sequences and clinical trials. Based on our findings, there may be promise in subsequent studies aiming to identify linkages across the T1 translational barrier using existing large repositories. PMID:19850150

  2. Clinical trials in zirconia: a systematic review.

    PubMed

    Al-Amleh, B; Lyons, K; Swain, M

    2010-08-01

    Zirconia is unique in its polymorphic crystalline makeup, reported to be sensitive to manufacturing and handling processes, and there is debate about which processing method is least harmful to the final product. Currently, zirconia restorations are manufactured by either soft or hard-milling processes, with the manufacturer of each claiming advantages over the other. Chipping of the veneering porcelain is reported as a common problem and has been labelled as its main clinical setback. The objective of this systematic review is to report on the clinical success of zirconia-based restorations fabricated by both milling processes, in regard to framework fractures and veneering porcelain chipping. A comprehensive review of the literature was completed for in vivo trials on zirconia restorations in MEDLINE and PubMed between 1950 and 2009. A manual hand search of relevant dental journals was also completed. Seventeen clinical trials involving zirconia-based restorations were found, 13 were conducted on fixed partial dentures, two on single crowns and two on zirconia implant abutments, of which 11 were based on soft-milled zirconia and six on hard-milled zirconia. Chipping of the veneering porcelain was a common occurrence, and framework fracture was only observed in soft-milled zirconia. Based on the limited number of short-term in vivo studies, zirconia appears to be suitable for the fabrication of single crowns, and fixed partial dentures and implant abutments providing strict protocols during the manufacturing and delivery process are adhered to. Further long-term prospective studies are necessary to establish the best manufacturing process for zirconia-based restorations. PMID:20406352

  3. Short-Term Effects of Kefir-Fermented Milk Consumption on Bone Mineral Density and Bone Metabolism in a Randomized Clinical Trial of Osteoporotic Patients

    PubMed Central

    Tung, Yu-Tang; Kao, Chao-Chih; Hu, Fu-Chang; Chen, Chuan-Mu

    2015-01-01

    Milk products are good sources of calcium that may reduce bone resorption and help prevent bone loss as well as promote bone remodeling and increase bone formation. Kefir is a product made by kefir grains that degrade milk proteins into various peptides with health-promoting effects, including antithrombotic, antimicrobial and calcium-absorption enhancing bioactivities. In a controlled, parallel, double-blind intervention study over 6 months, we investigated the effects of kefir-fermented milk (1,600 mg) supplemented with calcium bicarbonate (CaCO3, 1,500 mg) and bone metabolism in 40 osteoporosis patients, and compared them with CaCO3 alone without kefir supplements. Bone turnover markers were measured in fasting blood samples collected before therapy and at 1, 3, and 6 months. Bone mineral density (BMD) values at the spine, total hip, and hip femoral neck were assessed by dual-energy x-ray absorptiometry (DXA) at baseline and at 6 months. Among patients treated with kefir-fermented milk, the relationships between baseline turnover and 6 months changes in DXA-determined BMD were significantly improved. The serum β C-terminal telopeptide of type I collagen (β-CTX) in those with T-scores > -1 patients significantly decreased after three months treatment. The formation marker serum osteocalcin (OC) turned from negative to positive after 6 months, representing the effect of kefir treatment. Serum parathyroid hormone (PTH) increased significantly after treatment with kefir, but decreased significantly in the control group. PTH may promote bone remodeling after treatment with kefir for 6 months. In this pilot study, we concluded that kefir-fermented milk therapy was associated with short-term changes in turnover and greater 6-month increases in hip BMD among osteoporotic patients. Trial Registration: ClinicalTrials.gov NCT02361372 PMID:26655888

  4. [Features of Clinical Register of Chinese Medicine and Pharmacy Based on ClinicalTrials.gov. (USA)].

    PubMed

    Lu, Peng-fei; Liao, Xing; Xie, Yan-ming; Wang, Zhi-guo

    2015-11-01

    In recent 10 years, clinical trials of Chinese medicine and pharmacy (cMP) at clinicalTrials.gov.(USA) are gradually increasing. In order to analyze features of CMP clinical register, ClinicalTrials.gov register database were comprehensively retrieved in this study. Included clinical trials were input one item after another using EXCEL. A final of 348 CMP clinical trials were included. Results showed that China occupied the first place in CMP clinical register, followed by USA. CMP clinical trials, sponsored mainly by colleges/universities and hospitals, mostly covered interventional studies on evaluating safety/effectiveness of CMP. The proportions of studies, sponsored by mainland China and companies, recruitment trials and multi-center clinical trials in interventional trials were increasing. The proportions of studies sponsored by Hong Kong and Taiwan, research completed trials, unclear research status, phase III clinical trials, and published research trials in interventional trials were decreasing. Published ratios of CMP clinical trials were quite low. There were more missing types and higher proportions in trial register information.

  5. 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

  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. Risk-proportionate clinical trial monitoring: an example approach from a non-commercial trials unit

    PubMed Central

    2014-01-01

    Background Some level of monitoring is usually required during a clinical trial to protect the rights and safety of trial participants and to safeguard the quality and reliability of trial results. Although there is increasing support for the use of risk-proportionate approaches to achieve these aims, the variety of methods and lack of an empirical evidence base can present challenges for clinical trial practitioners. Methods This paper describes the monitoring methods and procedures that are utilised by a non-commercial clinical trials unit which coordinates a range of clinical trials across a variety of clinical areas with different associated risks. Results Monitoring activities and approaches should be selected to be proportionate to the risks identified within a trial. A risk-proportionate approach to monitoring is described giving details of methods that may be considered by clinical trial practitioners during the development of a trial monitoring plan. An example risk assessment and corresponding monitoring plan for a low risk (type A in the Medicines and Healthcare Products Regulatory Agency (MHRA) classification system) pediatric trial is provided for illustration. Conclusion We present ideas for developing a monitoring plan for a clinical trial of an investigational medicinal product based on our experience. Alternative approaches may be relevant or preferable in other settings based on inherent risk. PMID:24739398

  8. The Egyptian clinical trials' registry profile: Analysis of three trial registries (International Clinical Trials Registry Platform, Pan-African Clinical Trials Registry and clinicaltrials.gov).

    PubMed

    Zeeneldin, Ahmed A; Taha, Fatma M

    2016-01-01

    Registering clinical trials (CTs) in public domains enhances transparency, increases trust in research, improves participation and safeguards against publication bias. This work was done to study the profile of clinical research in Egypt in three CT registries with different scopes: the WHO International CT Registry Platform (ICTRP), the continental Pan-African CT Registry (PACTR) and the US clinicaltrials.gov (CTGR). In March 2014, ICTRP, PACTR and CTGR were searched for clinical studies conducted in Egypt. It was found that the number of studies conducted in Egypt (percentage) was 686 (0.30%) in ICTRP, 56 (11.3%) in PACTR and 548 (0.34%) in CTGR. Most studies were performed in universities and sponsored by university/organization, industry or individual researchers. Inclusion of adults from both genders predominated. The median number of participants per study in the three registries ranged between 63 and 155. The conditions researched differed among the three registries and study purpose was mostly treatment followed by prevention. Endpoints were mostly efficacy followed by safety. Observational:Interventional studies (i.e. clinical trials) represented 15.5%:84.5% in ICTRP, 0%:100% in PACTR and 16.4%:83.6% in CTGR. Most interventions were drugs or procedures. Observational studies were mostly prospective and cohort studies. Most CTs were phase 3 and tested drugs or procedures. Parallel group assignment and random allocation predominated. Blinding was implemented in many of trials and was mostly double-blind. We conclude that CTs from Egypt in trial registries are apparently low and do not accurately reflect clinical research conducted in Egypt or its potential. Development of an Egyptian CT registry is eagerly needed. Registering all Egyptian CTs in public domains is highly recommended. PMID:26843968

  9. The Egyptian clinical trials' registry profile: Analysis of three trial registries (International Clinical Trials Registry Platform, Pan-African Clinical Trials Registry and clinicaltrials.gov).

    PubMed

    Zeeneldin, Ahmed A; Taha, Fatma M

    2016-01-01

    Registering clinical trials (CTs) in public domains enhances transparency, increases trust in research, improves participation and safeguards against publication bias. This work was done to study the profile of clinical research in Egypt in three CT registries with different scopes: the WHO International CT Registry Platform (ICTRP), the continental Pan-African CT Registry (PACTR) and the US clinicaltrials.gov (CTGR). In March 2014, ICTRP, PACTR and CTGR were searched for clinical studies conducted in Egypt. It was found that the number of studies conducted in Egypt (percentage) was 686 (0.30%) in ICTRP, 56 (11.3%) in PACTR and 548 (0.34%) in CTGR. Most studies were performed in universities and sponsored by university/organization, industry or individual researchers. Inclusion of adults from both genders predominated. The median number of participants per study in the three registries ranged between 63 and 155. The conditions researched differed among the three registries and study purpose was mostly treatment followed by prevention. Endpoints were mostly efficacy followed by safety. Observational:Interventional studies (i.e. clinical trials) represented 15.5%:84.5% in ICTRP, 0%:100% in PACTR and 16.4%:83.6% in CTGR. Most interventions were drugs or procedures. Observational studies were mostly prospective and cohort studies. Most CTs were phase 3 and tested drugs or procedures. Parallel group assignment and random allocation predominated. Blinding was implemented in many of trials and was mostly double-blind. We conclude that CTs from Egypt in trial registries are apparently low and do not accurately reflect clinical research conducted in Egypt or its potential. Development of an Egyptian CT registry is eagerly needed. Registering all Egyptian CTs in public domains is highly recommended.

  10. New rules for clinical trial-related injury and compensation.

    PubMed

    Choudhury, Khushboo; Ghooi, Ravindra

    2013-01-01

    The rules for compensation for injury and death in clinical trials have recently been notified. These rules clarify that medical management of all injuries in clinical trials is mandatory and in cases in which injury or death is related to the clinical trial, the subject (or nominee) is entitled to compensation over and above the medical management. They also specify procedures and timelines for reporting serious adverse events. These require simplification. The rules will hopefully make clinical trial safer for subjects and investigators alike. However, they suffer from certain inconsistencies that should be reconsidered. They need to be modified so that they do not damage the industry.

  11. Reducing Clinical Trial Monitoring Resource Allocation and Costs Through Remote Access to Electronic Medical Records

    PubMed Central

    Uren, Shannon C.; Kirkman, Mitchell B.; Dalton, Brad S.; Zalcberg, John R.

    2013-01-01

    Purpose: With electronic medical records (eMRs), the option now exists for clinical trial monitors to perform source data verification (SDV) remotely. We report on a feasibility study of remote access to eMRs for SDV and the potential advantages of such a process in terms of resource allocation and cost. Methods: The Clinical Trials Unit at the Peter MacCallum Cancer Centre, in collaboration with Novartis Pharmaceuticals Australia, conducted a 6-month feasibility study of remote SDV. A Novartis monitor was granted dedicated software and restricted remote access to the eMR portal of the cancer center, thereby providing an avenue through which perform SDV. Results: Six monitoring visits were conducted during the study period, four of which were performed remotely. The ability to conduct two thirds of the monitoring visits remotely in this complex phase III study resulted in an overall cost saving to Novartis. Similarly, remote monitoring eased the strain on internal resources, particularly monitoring space and hospital computer terminal access, at the cancer center. Conclusion: Remote access to patient eMRs for SDV is feasible and is potentially an avenue through which resources can be more efficiently used. Although this feasibility study involved limited numbers, there is no limit to scaling these processes to any number of patients enrolled onto large clinical trials. PMID:23633977

  12. Omega 3 Fatty Acids Supplementation and Oxidative Stress in HIV-Seropositive Patients. A Clinical Trial

    PubMed Central

    Amador-Licona, Norma; Díaz-Murillo, Teresa A.; Pereyra-Nobara, Texar A.; Guízar-Mendoza, Juan M.; Barbosa-Sabanero, Gloria; Orozco-Aviña, Gustavo; Moreno-Martínez, Sandra C.; Luna-Montalbán, Rafael; Vázquez-Valls, Eduardo

    2016-01-01

    HIV-seropositive patients show high incidence of coronary heart disease and oxidative stress has been described as relevant key in atherosclerosis development. The aim of this study was to assess the effect of omega 3 fatty acids on different markers of oxidative stress in HIV-seropositive patients. We performed a randomized parallel controlled clinical trial in The Instituto Mexicano del Seguro Social, a public health hospital. 70 HIV-seropositive patients aged 20 to 55 on clinical score A1, A2, B1 or B2 receiving highly active antiretroviral therapy (HAART) were studied. They were randomly assigned to receive omega 3 fatty acids 2.4 g (Zonelabs, Marblehead MA) or placebo for 6 months. At baseline and at the end of the study, anthropometric measurements, lipid profile, glucose and stress oxidative levels [nitric oxide catabolites, lipoperoxides (malondialdehyde plus 4-hydroxialkenals), and glutathione] were evaluated. Principal HAART therapy was EFV/TDF/FTC (55%) and AZT/3TC/EFV (15%) without difference between groups. Treatment with omega 3 fatty acids as compared with placebo decreased triglycerides (-0.32 vs. 0.54 mmol/L; p = 0.04), but oxidative stress markers were not different between groups. Trial Registration ClinicalTrials.gov NCT02041520 PMID:27015634

  13. [Acupuncture clinical trials published in high impact factor journals].

    PubMed

    Hu, Min; Liu, Jian-Ping; Wu, Xiao-Ke

    2014-12-01

    Acupuncture clinical trials are designed to provide reliable evidence of clinical efficacy, and SCI papers is one of the high-quality clinical efficacy of acupuncture research. To analyze these papers published in high impact factor journals on acupuncture clinical trials, we can study clinical trials from design to implementation, the efficacy of prevention and cure, combined with international standard practices to evaluate the effectiveness and safety of acupuncture. That is the core of acupuncture clinical trials, as well as a prerequisite for outstanding academic output. A scientific and complete acupuncture clinical trial should be topically novel, designed innovative, logically clear, linguistically refining, and the most important point lies in a great discovery and solving the pragmatic problem. All of these are critical points of papers to be published in high impact factor journal, and directly affect international evaluation and promotion of acupuncture.

  14. Characteristics of drug combination therapy in oncology by analyzing clinical trial data on ClinicalTrials.gov.

    PubMed

    Wu, Menghua; Sirota, Marina; Butte, Atul J; Chen, Bin

    2015-01-01

    Within the past few decades, drug combination therapy has been intensively studied in oncology and other complex disease areas, especially during the early drug discovery stage, as drug combinations have the potential to improve treatment response, minimize development of resistance or minimize adverse events. In the present, designing combination trials relies mainly on clinical and empirical experience. While empirical experience has indeed crafted efficacious combination therapy clinical trials (combination trials), however, garnering experience with patients can take a lifetime. The preliminary step to eliminating this barrier of time, then, is to understand the current state of combination trials. Thus, we present the first large-scale study of clinical trials (2008-2013) from ClinicalTrials.gov to compare combination trials to non-combination trials, with a focus on oncology. In this work, we developed a classifier to identify combination trials and oncology trials through natural language processing techniques. After clustering trials, we categorized them based on selected characteristics and observed trends present. Among the characteristics studied were primary purpose, funding source, endpoint measurement, allocation, and trial phase. We observe a higher prevalence of combination therapy in oncology (25.6% use combination trials) in comparison to other disease trials (6.9%). However, surprisingly the prevalence of combinations does not increase over the years. In addition, the trials supported by the NIH are significantly more likely to use combinations of drugs than those supported by industry. Our preliminary study of current combination trials may facilitate future trial design and move more preclinical combination studies to the clinical trial stage.

  15. Trial design innovations: Clinical trials for treatment of neuropsychiatric symptoms in Alzheimer's Disease

    PubMed Central

    Zhong, K

    2015-01-01

    Neuropsychiatric symptoms are common in Alzheimer's disease (AD) and other neurodegenerative disorders. Recent progress has been made with clinical trials, advancing new therapies for psychosis in Parkinson's disease (PD), agitation in AD, and apathy in AD. Definitions have emerged for agitation and apathy in patients with cognitive impairment, facilitating recruitment of clinical trial populations. Progress in clinical trial design and the agents being assessed promise to advance therapies for disabling symptoms and improve quality of life for patients and caregivers. PMID:26206713

  16. International clinical trials of HIV vaccines: II. phase I trial of an HIV-1 synthetic peptide vaccine evaluating an accelerated immunization schedule in Yunnan, China.

    PubMed

    Li, D; Forrest, B D; Li, Z; Xue, P; Hanson, C V; Duan, S; Cheng, H; Li, M; Wang, C Y; Koff, W C

    1997-06-01

    A Phase 1, double-blind, placebo controlled trial was conducted in Longchuan County, China, to evaluate the safety and immunogenicity of a prototype HIV-1 synthetic peptide vaccine in a target population at risk for HIV infection, and to establish the infrastructure for future large-scale HIV vaccine efficacy trials. Subjects were randomly assigned to receive 100 microg or 500 microg of vaccine or alum placebo, and were given three injections at an accelerated 0, 1, and 2 month schedule. The vaccine was well tolerated with no significant local or systemic reactions observed in any subjects. Fifty-five percent (100 microg dose) and 64% (500 microg dose) of subjects who received the vaccine produced binding antibody to the immunogen as determined by ELISA. However, HIV-1 (MN) neutralizing antibody was detected in only 23% (3/13) of subjects with detectable HIV-1 specific binding antibody. It was concluded that this prototype HIV-1 synthetic peptide vaccine was well tolerated, safe and immunogenic, and that a 0, 1, 2 month schedule was not as effective in stimulating HIV-1 specific neutralizing antibodies compared with previous trials utilizing a 0, 1, 6 month schedule. Finally, this trial demonstrated that well-designed HIV vaccine trials can be performed at this clinical trials site in Yunnan, China, and that this site should be considered for conducting larger safety, immunogenicity and efficacy trials of candidate HIV vaccines.

  17. [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

  18. Evidence from Clinical Trials: Can We Do Better?

    PubMed Central

    Siderowf, Andrew D.

    2004-01-01

    Summary: Randomized clinical trials provide the most internally valid evidence for medical decision-making. In many areas of neurology, results from clinical trials showing which therapies are and are not effective have had a substantial impact on patient care. Relative to observational methods, the central advantage of clinical trials is control of bias attributable to unmeasured differences between patients. However, trials also have clear limitations, including a historical failure to include a representative cross-section of patients with a given disease, and highly structured treatment regimes that are difficult to replicate in normal practice settings. These limitations tend to reduce the generalizability of results from clinical trials. This article reviews some ways in which the design and application of clinical trials could be improved so that the evidence produced would be more relevant to health-care providers and other decision makers. PMID:15717039

  19. Project Zero Delay: a process for accelerating the activation of cancer clinical trials.

    PubMed

    Kurzrock, Razelle; Pilat, Susan; Bartolazzi, Marcel; Sanders, Dwana; Van Wart Hood, Jill; Tucker, Stanley D; Webster, Kevin; Mallamaci, Michael A; Strand, Steven; Babcock, Eileen; Bast, Robert C

    2009-09-10

    Drug development in cancer research is lengthy and expensive. One of the rate-limiting steps is the initiation of first-in-human (phase I) trials. Three to 6 months can elapse between investigational new drug (IND) approval by the US Food and Drug Administration and the entry of a first patient. Issues related to patient participation have been well analyzed, but the administrative processes relevant to implementing clinical trials have received less attention. While industry and academia often partner for the performance of phase I studies, their administrative processes are generally performed independently, and their timelines driven by different priorities: safety reviews, clinical operations, regulatory submissions, and contracting of clinical delivery vendors for industry; contracts, budgets, and institutional review board approval for academia. Both processes converge on US Food and Drug Administration approval of an IND. In the context of a strategic alliance between M. D. Anderson Cancer Center and AstraZeneca Pharmaceuticals LP, a concerted effort has been made to eliminate delays in implementing clinical trials. These efforts focused on close communications, identifying and matching key timelines, alignment of priorities, and tackling administrative processes in parallel, rather than sequentially. In a recent, first-in-human trial, the study was activated and the first patient identified in 46 days from completion of the final study protocol and about 48 hours after final US Food and Drug Administration IND approval, reducing the overall timeline by about 3 months, while meeting all clinical good practice guidelines. Eliminating administrative delays can accelerate the evaluation of new drugs without compromising patient safety or the quality of clinical research. PMID:19652061

  20. A practice-based trial of blood pressure control in African Americans (TLC-Clinic): study protocol for a randomized controlled trial

    PubMed Central

    2011-01-01

    Background Poorly controlled hypertension (HTN) remains one of the most significant public health problems in the United States, in terms of morbidity, mortality, and economic burden. Despite compelling evidence supporting the beneficial effects of therapeutic lifestyle changes (TLC) for blood pressure (BP) reduction, the effectiveness of these approaches in primary care practices remains untested, especially among African Americans, who share a disproportionately greater burden of HTN-related outcomes. Methods/Design This randomized controlled trial tests the effectiveness of a practice-based comprehensive therapeutic lifestyle intervention, delivered through group-based counseling and motivational interviewing (MINT-TLC) versus Usual Care (UC) in 200 low-income, African Americans with uncontrolled hypertension. MINT-TLC is designed to help patients make appropriate lifestyle changes and develop skills to maintain these changes long-term. Patients in the MINT-TLC group attend 10 weekly group classes focused on healthy lifestyle changes (intensive phase); followed by 3 monthly individual motivational interviewing (MINT) sessions (maintenance phase). The intervention is delivered by trained research personnel with appropriate treatment fidelity procedures. Patients in the UC condition receive a single individual counseling session on healthy lifestyle changes and print versions of the intervention materials. The primary outcome is within-patient change in both systolic and diastolic BP from baseline to 6 months. In addition to BP control at 6 months, other secondary outcomes include changes in the following lifestyle behaviors from baseline to 6 months: a) physical activity, b) weight loss, c) number of daily servings of fruits and vegetables and d) 24-hour urinary sodium excretion. Discussion This vanguard trial will provide information on how to refine MINT-TLC and integrate it into a standard treatment protocol for hypertensive African Americans as a result of

  1. Gesture Performance in Schizophrenia Predicts Functional Outcome After 6 Months

    PubMed Central

    Walther, Sebastian; Eisenhardt, Sarah; Bohlhalter, Stephan; Vanbellingen, Tim; Müri, René; Strik, Werner; Stegmayer, Katharina

    2016-01-01

    The functional outcome of schizophrenia is heterogeneous and markers of the course are missing. Functional outcome is associated with social cognition and negative symptoms. Gesture performance and nonverbal social perception are critically impaired in schizophrenia. Here, we tested whether gesture performance or nonverbal social perception could predict functional outcome and the ability to adequately perform relevant skills of everyday function (functional capacity) after 6 months. In a naturalistic longitudinal study, 28 patients with schizophrenia completed tests of nonverbal communication at baseline and follow-up. In addition, functional outcome, social and occupational functioning, as well as functional capacity at follow-up were assessed. Gesture performance and nonverbal social perception at baseline predicted negative symptoms, functional outcome, and functional capacity at 6-month follow-up. Gesture performance predicted functional outcome beyond the baseline measure of functioning. Patients with gesture deficits at baseline had stable negative symptoms and experienced a decline in social functioning. While in patients without gesture deficits, negative symptom severity decreased and social functioning remained stable. Thus, a simple test of hand gesture performance at baseline may indicate favorable outcomes in short-term follow-up. The results further support the importance of nonverbal communication skills in subjects with schizophrenia. PMID:27566843

  2. Privacy and confidentiality in pragmatic clinical trials

    PubMed Central

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

    2015-01-01

    With pragmatic clinical trials (PCTs) 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 PCTs. In this paper we explore both the ethical foundation and regulatory framework intended to protect privacy in PCTs. 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

  3. Promoting public awareness of randomised clinical trials using the media: the 'Get Randomised' campaign.

    PubMed

    Mackenzie, Isla S; Wei, Li; Rutherford, Daniel; Findlay, Evelyn A; Saywood, Wendy; Campbell, Marion K; Macdonald, Thomas M

    2010-02-01

    WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT * Recruitment is key to the success of clinical trials. * Many clinical trials fail to achieve adequate recruitment. * Public understanding and engagement in clinical research could be improved. WHAT THIS STUDY ADDS * 'Get Randomised' is the first campaign of its kind in the UK. * It is possible to improve public awareness of clinical research using the media. * Further work is needed to determine whether improved public awareness leads to increased participation in clinical research in the future. AIM To increase public awareness and understanding of clinical research in Scotland. METHODS A generic media campaign to raise public awareness of clinical research was launched in 2008. The 'Get Randomised' campaign was a Scotland-wide initiative led by the University of Dundee in collaboration with other Scottish universities. Television, radio and newspaper advertising showed leading clinical researchers, general practitioners and patients informing the public about the importance of randomised clinical trials (RCTs). 'Get Randomised' was the central message and interested individuals were directed to the http://www.getrandomised.org website for more information. To assess the impact of the campaign, cross-sectional surveys were conducted in representative samples of 1040 adults in Scotland prior to campaign launch and again 6 months later. RESULTS There was an improvement in public awareness of clinical trials following the campaign; 56.7% [95% confidence interval (CI) 51.8, 61.6] of the sample recalled seeing or hearing advertising about RCTs following the campaign compared with 14.8% (10.8, 18.9) prior to the campaign launch (difference = 41.4%; 95% CI for difference 35.6, 48.3; P < 0.01). Of those who recalled the advertising, 49% felt that the main message was that people should take part more in medical research. However, on whether they would personally take part in a clinical trial if asked, there was little difference

  4. Promoting public awareness of randomised clinical trials using the media: the ‘Get Randomised’ campaign

    PubMed Central

    Mackenzie, Isla S; Wei, Li; Rutherford, Daniel; Findlay, Evelyn A; Saywood, Wendy; Campbell, Marion K; MacDonald, Thomas M

    2010-01-01

    AIM To increase public awareness and understanding of clinical research in Scotland. METHODS A generic media campaign to raise public awareness of clinical research was launched in 2008. The ‘Get Randomised’ campaign was a Scotland-wide initiative led by the University of Dundee in collaboration with other Scottish universities. Television, radio and newspaper advertising showed leading clinical researchers, general practitioners and patients informing the public about the importance of randomised clinical trials (RCTs). ‘Get Randomised’ was the central message and interested individuals were directed to the http://www.getrandomised.org website for more information. To assess the impact of the campaign, cross-sectional surveys were conducted in representative samples of 1040 adults in Scotland prior to campaign launch and again 6 months later. RESULTS There was an improvement in public awareness of clinical trials following the campaign; 56.7% [95% confidence interval (CI) 51.8, 61.6] of the sample recalled seeing or hearing advertising about RCTs following the campaign compared with 14.8% (10.8, 18.9) prior to the campaign launch (difference = 41.4%; 95% CI for difference 35.6, 48.3; P < 0.01). Of those who recalled the advertising, 49% felt that the main message was that people should take part more in medical research. However, on whether they would personally take part in a clinical trial if asked, there was little difference in response following the campaign [‘yes’ 31.3% (28.4, 34.1) prior; 30.4% (27.6, 33.2) following; difference =−0.9%; 95% CI for difference −4.8, 3.1%; P= 0.92]. CONCLUSIONS It is possible to raise public awareness of clinical research using the media, but further efforts may be required to influence individuals' decisions to take part in clinical research. PMID:20233175

  5. 77 FR 49449 - Food and Drug Administration Clinical Trial Requirements, Compliance, and Good Clinical Practice...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-08-16

    ... HUMAN SERVICES Food and Drug Administration Food and Drug Administration Clinical Trial Requirements... announcing a public workshop. The public workshop on FDA's clinical trial requirements is designed to aid the... FDA and clinical trial staff, investigators, and institutional review boards (IRBs). Individual...

  6. Hypnosis and self-hypnosis, administered and taught by nurses, for the reduction of chronic pain: a controlled clinical trial.

    PubMed

    Buchser, E; Burnand, B; Sprunger, A L; Clémence, A; Lepage, C; Martin, Y; Chédel, D; Guex, P; Sloutskis, D; Rumley, R

    1994-01-01

    Hypnosis is a technique whereby an individual can reach a particular state, quite unrelated to sleep, characterized by aroused, attentive and focused concentration. Although there are numerous clinical applications of hypnosis, there are virtually no controlled clinical trials to support its effectiveness. We propose a controlled randomized clinical trial comparing a "control" group of chronic pain patients treated by a programme including conventional oral medication combined with various nerve blocks and/or spinal administration of drugs, with a "treatment" group having a similar treatment programme plus hypnosis carried out by nurses. Outcome measurements include mainly the variation of pain intensity, the amount of analgesic drug consumption, spontaneous physical activity, and the change in health-related quality of life. The assessment of the outcome variable is done at the initial workup, weekly for the first 3 weeks, and at 6 and 12 weeks. A follow-up survey is conducted at 6 months. PMID:8073244

  7. Hypnosis and self-hypnosis, administered and taught by nurses, for the reduction of chronic pain: a controlled clinical trial.

    PubMed

    Buchser, E; Burnand, B; Sprunger, A L; Clémence, A; Lepage, C; Martin, Y; Chédel, D; Guex, P; Sloutskis, D; Rumley, R

    1994-01-01

    Hypnosis is a technique whereby an individual can reach a particular state, quite unrelated to sleep, characterized by aroused, attentive and focused concentration. Although there are numerous clinical applications of hypnosis, there are virtually no controlled clinical trials to support its effectiveness. We propose a controlled randomized clinical trial comparing a "control" group of chronic pain patients treated by a programme including conventional oral medication combined with various nerve blocks and/or spinal administration of drugs, with a "treatment" group having a similar treatment programme plus hypnosis carried out by nurses. Outcome measurements include mainly the variation of pain intensity, the amount of analgesic drug consumption, spontaneous physical activity, and the change in health-related quality of life. The assessment of the outcome variable is done at the initial workup, weekly for the first 3 weeks, and at 6 and 12 weeks. A follow-up survey is conducted at 6 months.

  8. Effect of a Home-Based Exercise Program on Functional Recovery Following Rehabilitation After Hip Fracture A Randomized Clinical Trial

    PubMed Central

    Latham, Nancy K.; Harris, Bette Ann; Bean, Jonathan F.; Heeren, Timothy; Goodyear, Christine; Zawacki, Stacey; Heislein, Diane M.; Mustafa, Jabed; Pardasaney, Poonam; Giorgetti, Marie; Holt, Nicole; Goehring, Lori; Jette, Alan M.

    2015-01-01

    IMPORTANCE For many older people, long-term functional limitations persist after a hip fracture. The efficacy of a home exercise program with minimal supervision after formal hip fracture rehabilitation ends has not been established. OBJECTIVE To determine whether a home exercise program with minimal contact with a physical therapist improved function after formal hip fracture rehabilitation ended. DESIGN, SETTING, AND PARTICIPANTS Randomized clinical trial conducted from September 2008 to October 2012 in the homes of 232 functionally limited older adults who had completed traditional rehabilitation after a hip fracture. INTERVENTIONS The intervention group (n = 120) received functionally oriented exercises (such as standing from a chair, climbing a step) taught by a physical therapist and performed independently by the participants in their homes for 6 months. The attention control group (n = 112) received in-home and telephone-based cardiovascular nutrition education. MAIN OUTCOMES AND MEASURES Physical function assessed at baseline, 6 months (ie, at completion of the intervention), and 9 months by blinded assessors. The primary outcome was change in function at 6 months measured by the Short Physical Performance Battery (SPPB; range 0-12, higher score indicates better function) and the Activity Measure for Post-Acute Care (AM-PAC) mobility and daily activity (range, 23-85 and 9-101, higher score indicates better function). RESULTS Among the 232 randomized patients, 195 were followed up at 6 months and included in the primary analysis. The intervention group (n=100) showed significant improvement relative to the control group (n=95) in functional mobility (mean SPPB scores for intervention group: 6.2 [SD, 2.7] at baseline, 7.2 [SD, 3] at 6 months; control group: 6.0 [SD, 2.8] at baseline, 6.2 [SD, 3] at 6 months; and between-group differences: 0.8 [95% CI, 0.4 to 1.2], P < .001; mean AM-PAC mobility scores for intervention group: 56.2 [SD, 7.3] at baseline, 58

  9. OARSI Clinical Trials Recommendations: Design, conduct, and reporting of clinical trials for knee osteoarthritis.

    PubMed

    McAlindon, T E; Driban, J B; Henrotin, Y; Hunter, D J; Jiang, G-L; Skou, S T; Wang, S; Schnitzer, T

    2015-05-01

    The goal of this document is to update the original OARSI recommendations specifically for the design, conduct, and reporting of clinical trials that target symptom or structure modification among individuals with knee osteoarthritis (OA). To develop recommendations for the design, conduct, and reporting of clinical trials for knee OA we initially drafted recommendations through an iterative process. Members of the working group included representatives from industry and academia. After the working group members reviewed a final draft, they scored the appropriateness for recommendations. After the members voted we calculated the median score among the nine members of the working group who completed the score. The document includes 25 recommendations regarding randomization, blocking and stratification, blinding, enhancing accuracy of patient-reported outcomes (PRO), selecting a study population and index knee, describing interventions, patient-reported and physical performance measures, structural outcome measures, biochemical biomarkers, and reporting recommendations. In summary, the working group identified 25 recommendations that represent the current best practices regarding clinical trials that target symptom or structure modification among individuals with knee OA. These updated recommendations incorporate novel technologies (e.g., magnetic resonance imaging (MRI)) and strategies to address the heterogeneity of knee OA. PMID:25952346

  10. Clinical Trials: A Crucial Key to Human Health Research

    MedlinePlus

    Skip Navigation Bar Home Current Issue Past Issues Clinical Trials: A Crucial Key to Human Health Research Past ... the forefront of human health research today are clinical trials—studies that use human volunteers to help medical ...

  11. The challenge of comorbidity in clinical trials for multiple sclerosis

    PubMed Central

    Miller, Aaron; Sormani, Maria Pia; Thompson, Alan; Waubant, Emmanuelle; Trojano, Maria; O'Connor, Paul; Reingold, Stephen; Cohen, Jeffrey A.

    2016-01-01

    Objective: We aimed to provide recommendations for addressing comorbidity in clinical trial design and conduct in multiple sclerosis (MS). Methods: We held an international workshop, informed by a systematic review of the incidence and prevalence of comorbidity in MS and an international survey about research priorities for studying comorbidity including their relation to clinical trials in MS. Results: We recommend establishing age- and sex-specific incidence estimates for comorbidities in the MS population, including those that commonly raise concern in clinical trials of immunomodulatory agents; shifting phase III clinical trials of new therapies from explanatory to more pragmatic trials; describing comorbidity status of the enrolled population in publications reporting clinical trials; evaluating treatment response, tolerability, and safety in clinical trials according to comorbidity status; and considering comorbidity status in the design of pharmacovigilance strategies. Conclusion: Our recommendations will help address knowledge gaps regarding comorbidity that interfere with the ability to interpret safety in monitored trials and will enhance the generalizability of findings from clinical trials to “real world” settings where the MS population commonly has comorbid conditions. PMID:26888986

  12. Financial managers' costing expertise is needed in clinical trials.

    PubMed

    West, D A; Balas, E A; West, T D

    2000-01-01

    In addition to providing comparable and verifiable evidence regarding outcomes, clinical trials could also serve as sources of accurate and replicable financial information. Trial reports that identify expenses associated with effective diagnostic and therapeutic interventions enable cost controls. Standardized cost calculations could help clinicians and administrators identify more efficient health care technologies. Unfortunately, relatively few published trials include economic analyses and when they do, data are incomplete. Based on analyses of 97 clinical trial reports, this article proposes a standard costing format. Health care financial managers have the costing expertise necessary to implement and interpret standardized cost calculations for clinical trials. With the active involvement of financial managers, a standard costing format for clinical trials can be achieved. PMID:10961828

  13. Prevention of Traumatic Stress in Mothers of Preterms: 6-Month Outcomes

    PubMed Central

    St John, Nick; Lilo, Emily; Jo, Booil; Benitz, William; Stevenson, David K.; Horwitz, Sarah M.

    2014-01-01

    OBJECTIVE: Symptoms of posttraumatic stress disorder are a well-recognized phenomenon in mothers of preterm infants, with implications for maternal health and infant outcomes. This randomized controlled trial evaluated 6-month outcomes from a skills-based intervention developed to reduce symptoms of posttraumatic stress disorder, anxiety, and depression. METHODS: One hundred five mothers of preterm infants were randomly assigned to (1) a 6- or 9-session intervention based on principles of trauma-focused cognitive behavior therapy with infant redefinition or (2) a 1-session active comparison intervention based on education about the NICU and parenting of the premature infant. Outcome measures included the Davidson Trauma Scale, the Beck Depression Inventory II, and the Beck Anxiety Inventory. Participants were assessed at baseline, 4 to 5 weeks after birth, and 6 months after the birth of the infant. RESULTS: At the 6-month assessment, the differences between the intervention and comparison condition were all significant and sizable and became more pronounced when compared with the 4- to 5-week outcomes: Davidson Trauma Scale (Cohen's d = −0.74, P < .001), Beck Anxiety Inventory (Cohen's d = −0.627, P = .001), Beck Depression Inventory II (Cohen's d = −0.638, P = .002). However, there were no differences in the effect sizes between the 6- and 9-session interventions. CONCLUSIONS: A brief 6-session intervention based on principles of trauma-focused cognitive behavior therapy was effective at reducing symptoms of trauma, anxiety, and depression in mothers of preterm infants. Mothers showed increased benefits at the 6-month follow-up, suggesting that they continue to make use of techniques acquired during the intervention phase. PMID:25049338

  14. Relationship of cravings with weight loss and hunger: results from a 6 month worksite weight loss intervention

    Technology Transfer Automated Retrieval System (TEKTRAN)

    We examined the association of food cravings with weight loss and eating behaviors in a 6 month worksite lifestyle weight loss program. This randomized controlled trial of the intervention versus a wait-listed control was conducted at 4 worksites, and 95 participants completed outcome assessments ...

  15. 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

  16. Implementation of the NCI’s National Clinical Trials Network

    Cancer.gov

    NCI is launching a new clinical trials research network intended to improve treatment for the more than 1.6 million Americans diagnosed with cancer each year. The new system, NCI’s National Clinical Trials Network (NCTN), will facilitate the rapid initia

  17. Critical periods after stroke study: translating animal stroke recovery experiments into a clinical trial

    PubMed Central

    Dromerick, Alexander W.; Edwardson, Matthew A.; Edwards, Dorothy F.; Giannetti, Margot L.; Barth, Jessica; Brady, Kathaleen P.; Chan, Evan; Tan, Ming T.; Tamboli, Irfan; Chia, Ruth; Orquiza, Michael; Padilla, Robert M.; Cheema, Amrita K.; Mapstone, Mark E.; Fiandaca, Massimo S.; Federoff, Howard J.; Newport, Elissa L.

    2015-01-01

    Introduction: Seven hundred ninety-five thousand Americans will have a stroke this year, and half will have a chronic hemiparesis. Substantial animal literature suggests that the mammalian brain has much potential to recover from acute injury using mechanisms of neuroplasticity, and that these mechanisms can be accessed using training paradigms and neurotransmitter manipulation. However, most of these findings have not been tested or confirmed in the rehabilitation setting, in large part because of the challenges in translating a conceptually straightforward laboratory experiment into a meaningful and rigorous clinical trial in humans. Through presentation of methods for a Phase II trial, we discuss these issues and describe our approach. Methods: In rodents there is compelling evidence for timing effects in rehabilitation; motor training delivered at certain times after stroke may be more effective than the same training delivered earlier or later, suggesting that there is a critical or sensitive period for strongest rehabilitation training effects. If analogous critical/sensitive periods can be identified after human stroke, then existing clinical resources can be better utilized to promote recovery. The Critical Periods after Stroke Study (CPASS) is a phase II randomized, controlled trial designed to explore whether such a sensitive period exists. We will randomize 64 persons to receive an additional 20 h of upper extremity therapy either immediately upon rehab admission, 2–3 months after stroke onset, 6 months after onset, or to an observation-only control group. The primary outcome measure will be the Action Research Arm Test (ARAT) at 1 year. Blood will be drawn at up to 3 time points for later biomarker studies. Conclusion: CPASS is an example of the translation of rodent motor recovery experiments into the clinical setting; data obtained from this single site randomized controlled trial will be used to finalize the design of a Phase III trial. PMID

  18. Adult cancer clinical trials that fail to complete: an epidemic?

    PubMed

    Stensland, Kristian D; McBride, Russell B; Latif, Asma; Wisnivesky, Juan; Hendricks, Ryan; Roper, Nitin; Boffetta, Paolo; Hall, Simon J; Oh, William K; Galsky, Matthew D

    2014-09-01

    The number and diversity of cancer therapeutics in the pipeline has increased over the past decade due to an enhanced understanding of cancer biology and the identification of novel therapeutic targets. At the same time, the cost of bringing new drugs to market and the regulatory burdens associated with clinical drug development have progressively increased. The finite number of eligible patients and limited financial resources available to evaluate promising new therapeutics represent rate-limiting factors in the effort to translate preclinical discoveries into the next generation of standard therapeutic approaches. Optimal use of resources requires understanding and ultimately addressing inefficiencies in the cancer clinical trials system. Prior analyses have demonstrated that a large proportion of trials initiated by the National Cancer Institute (NCI) Cooperative Group system are never completed. While NCI Cooperative Group trials are important, they represent only a small proportion of all cancer clinical trials performed. Herein, we explore the problem of cancer clinical trials that fail to complete within the broader cancer clinical trials enterprise. Among 7776 phase II-III adult cancer clinical trials initiated between 2005-2011, we found a seven-year cumulative incidence of failure to complete of approximately 20% (95% confidence interval = 18% to 22%). Nearly 48000 patients were enrolled in trials that failed to complete. These trials likely contribute little to the scientific knowledge base, divert resources and patients from answering other critical questions, and represent a barrier to progress.

  19. [PDCA Applied in Special Rectification of Medical Instrument Clinical Trial].

    PubMed

    Wang, Lei; Qu, Xintao; Yu, Xiuchun

    2015-07-01

    PDCA cycle was applied in special rectification activities for medical instrument clinical trial, with quality criteria of implementation made. Completed medical instrument clinical trial from January 2011 to December 2012 was believed as control group, from January 2013 to December 2014 as PDCA group, the scores of clinical trial and the score rate of items were compared and analyzed. Results show quality scores of clinical trial in PDCA group are higher than that in control group (51 vs. 81, P < 0.001), score rate of items increased except adverse events (P < 0.001). The special rectification activities with PDCA applied in our department are feasible and effective. It significantly improves implement quality of medical instrument clinical trial.

  20. [PDCA Applied in Special Rectification of Medical Instrument Clinical Trial].

    PubMed

    Wang, Lei; Qu, Xintao; Yu, Xiuchun

    2015-09-01

    PDCA cycle was applied in special rectification activities for medical instrument clinical trial, with quality criteria of implementation made. Completed medical instrument clinical trial from January 2011 to December 2012 was believed as control group, from January 2013 to December 2014 as PDCA group, the scores of clinical trial and the score rate of items were compared and analyzed. Results show quality scores of clinical trial in PDCA group are higher than that in control group (51 vs. 81, P < 0.001), score rate of items increased except adverse events (P < 0.001). The special rectification activities with PDCA applied in our department are feasible and effective. It significantly improves implement quality of medical instrument clinical trial.

  1. [Multi-national clinical trial in circulatory disorders].

    PubMed

    Takahashi, Kihito

    2009-02-01

    As Japan becomes more integrated into the global market, pharmaceutical research and development (R&D) in Japan faces considerable challenges. While global simultaneous development including Asian countries has become a common strategy for multi-national pharmaceutical companies, Japan has been frequently set aside because of its provincial regulatory and clinical trial infrastructure. Meanwhile, many improvement programs in pharmaceutical area have been initiated in Japan. With this increased scrutiny, significant improvements in regulatory process, clinical trial costs, and site performance are anticipated over the next few years. RENAAL is the first multi-national clinical trial involving Japanese patients diabetic nephropathy associated with type II diabetes mellitus. In this article, issues which have been observed in the process of conducting multi-national clinical trial were discussed based on the experience with RENAAL. It is hoped that, as we gain more experiences in multi-national clinical trials, solutions for these issues are found in near future.

  2. 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

  3. Culturally-Tailored Smoking Cessation for Adult American Indian Smokers: A Clinical Trial

    PubMed Central

    Smith, Stevens S.; Rouse, Leah M.; Caskey, Mark; Fossum, Jodi; Strickland, Rick; Culhane, J. Kevin; Waukau, Jerry

    2015-01-01

    This collaborative, community-engaged project developed and tested a Culturally-Tailored Treatment (CTT) for American Indian/Alaska Native (AI/AN) smokers in the Menominee tribal community. One hundred three adult AI/AN smokers were randomized to receive either Standard Treatment (n= 53) or CTT (n = 50) for smoking cessation. Both treatment conditions included 12 weeks of varenicline and four individual counseling sessions but differed in terms of cultural tailoring of the counseling. The primary outcome was 7-day biochemically-confirmed point-prevalence abstinence (PPA) at the 6-month end-of-study visit. Both intention-to-treat (ITT) and responder-only analyses were conducted. There were no statistically significant group differences in 7-day PPA. The overall ITT abstinence rate at 6 months was 20%; the responder-only rate was 42%. The current study represents the first randomized smoking cessation clinical trial testing a culturally-tailored smoking cessation intervention designed for a specific AI/AN tribal community that combined FDA-approved cessation medication (varenicline) and innovative cultural intervention components. PMID:26973352

  4. Clinical trial design for endovascular ischemic stroke intervention

    PubMed Central

    Liebeskind, David S.; Edgell, Randall C.; Amlie-Lefond, Catherine M.; Kalia, Junaid S.; Alexandrov, Andrei V.

    2012-01-01

    Background: Randomized, double-blinded, placebo-controlled trials have significant impact on clinical practice. The ultimate goal of a clinical trial of therapy for acute ischemic stroke (AIS) is to compare 2 interventions. Challenges may include interventional therapy standardization, enrollment rate, patient selection, biases, data and safety monitoring, reporting, and financial and logistical support. Method: Selected randomized and single-arm prospective AIS trial designs. Clinical trial elements and their challenges are reviewed. Innovative designs and proposed recommendations to overcome some of the specific challenges and limitations are discussed. Results: AIS therapy trials have specific challenges related to ethical issues, enrollment rate, outcome measures, limited time to treatment, efficacy, safety, and limited or variable operator experience with complex technology in a delicate end organ. Proposed suggestions for improving trial design include the following: incorporation of a lead-in phase; careful patient and outcome measure selection; historical, concurrent, or hybrid controls; open data access; and a Bayesian approach. An open data paradigm may facilitate creation of computerized prediction models for future trials (minimizing cost by decreasing sample size or providing futility analyses and directing resources to other trials). Collaborative, consortium, and network infrastructures may allow more effective and efficient study completion. Self-learning, self-correcting trials with intrinsic flexibility to adapt may help future clinical trial design in AIS. Conclusion: The randomized clinical trial design in AIS endovascular therapy is challenging. Lead-in phases, careful patient selection, use of innovative outcome measures, control groups, and newer clinical trial design may enhance conduct of future trials, their validity, and their results. PMID:23008403

  5. Clinical Trial: Marine Lipid Suppositories as Laxatives

    PubMed Central

    Ormarsson, Orri Thor; Geirsson, Thormodur; Bjornsson, Einar Stefan; Jonsson, Tomas; Moller, Pall; Loftsson, Thorsteinn; Stefansson, Einar

    2012-01-01

    Cod-liver oil and other marine products containing polyunsaturated fatty acids have anti-inflammatory, anti-bacterial and anti-viral effects and may be useful in the treatment of various inflammatory and infectious diseases. We developed suppositories and ointment with 30% free fatty acid (FFA) extract from omega-3 fish oil. Our purpose was to evaluate the safety of marine lipid suppositories and ointment in healthy volunteers and to explore the laxative effect of the suppositories. Thirty healthy volunteers were randomized either to a study group administrating 30% FFA suppositories and applying 30% FFA ointment to the perianal region twice per day for two weeks, or to a control group using placebo suppositories and ointment in a double blinded manner. Results: No serious toxic effects or irritation were observed. In the study group 93% felt the urge to defecate after administration of the suppositories as compared to 37% in the control group (P = 0.001). Subsequently 90% in the study group defecated, compared to 33% in the control group (P = 0.001). Conclusion: The marine lipid suppositories and ointment were well tolerated with no significant toxic side effects observed during the study period. The suppositories have a distinct laxative effect and we aim to explore this effect in further clinical trials. PMID:23118720

  6. An unusual form of localized papulonodular cutaneous histiocytosis in a 6-month-old boy.

    PubMed

    van Haselen, C W; Toonstra, J; den Hengst, C W; van Vloten, W A

    1995-09-01

    We report a 6-month-old boy with an unusual form of cutaneous histiocytosis. The lesions were noticed shortly after birth, and there was no evidence of systemic disease. This histiocytic disorder could not be classified according to the Histiocyte Society classification, and was therefore designated an 'unclassified' group II histiocytic disorder. The clinical picture was characterized by dark-red papulonodules with a tendency to coalesce into plaques. Histologically, the infiltrate was characterized by non-epidermotropic histiocytes showing varying degrees of differentiation, eosinophils and lymphocytes, and by the absence of foamy cells and Touton giant cells. As a most conspicuous feature, electron microscopic examination revealed laminated dense bodies, whereas Birbeck granules and comma-shaped bodies were absent. This further distinguished this uncommon variant from the well-known class II histiocytoses. During a 6-month follow-up period all the lesions showed marked regression.

  7. Power of an effective clinical conversation: improving accrual onto clinical trials.

    PubMed

    Parreco, Linda K; DeJoice, Rhonda W; Massett, Holly A; Padberg, Rose Mary; Thakkar, Sona S

    2012-09-01

    The National Cancer Institute (NCI) is actively transforming clinical trials to revitalize the clinical trials system and improve patient accrual. For more than 30 years, NCI has provided information and communication resources about cancer clinical trials. The Institute supports a clinical trials Web site (www.cancer.gov/clinicaltrials) that receives nearly a half million page views a month. In addition, NCI's Cancer Information Service (800-4-CANCER, chat and e-mail) responds to 1,750 clinical trial inquiries every month. Although these numbers suggest that a high volume of clinical trial information is being exchanged between NCI, the public, and providers, most patients decide whether to participate in clinical trials during the patient-provider interaction. PMID:23277764

  8. Current clinical trials testing the combination of immunotherapy with radiotherapy.

    PubMed

    Kang, Josephine; Demaria, Sandra; Formenti, Silvia

    2016-01-01

    Increasing evidence demonstrates that radiation acts as an immune stimulus, recruiting immune mediators that enable anti-tumor responses within and outside the radiation field. There has been a rapid expansion in the number of clinical trials harnessing radiation to enhance antitumor immunity. If positive, results of these trials will lead to a paradigm shift in the use of radiotherapy. In this review, we discuss the rationale for trials combining radiation with various immunotherapies, provide an update of recent clinical trial results and highlight trials currently in progress. We also address issues pertaining to the optimal incorporation of immunotherapy with radiation, including sequencing of treatment, radiation dosing and evaluation of clinical trial endpoints. PMID:27660705

  9. 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

  10. Clinical Trials Registration and Results Information Submission. Final rule.

    PubMed

    2016-09-21

    This final rule details the requirements for submitting registration and summary results information, including adverse event information, for specified clinical trials of drug products (including biological products) and device products and for pediatric postmarket surveillances of a device product to ClinicalTrials.gov, the clinical trial registry and results data bank operated by the National Library of Medicine (NLM) of the National Institutes of Health (NIH). This rule provides for the expanded registry and results data bank specified in Title VIII of the Food and Drug Administration Amendments Act of 2007 (FDAAA) to help patients find trials for which they might be eligible, enhance the design of clinical trials and prevent duplication of unsuccessful or unsafe trials, improve the evidence base that informs clinical care, increase the efficiency of drug and device development processes, improve clinical research practice, and build public trust in clinical research. The requirements apply to the responsible party (meaning the sponsor or designated principal investigator) for certain clinical trials of drug products (including biological products) and device products that are regulated by the Food and Drug Administration (FDA) and for pediatric postmarket surveillances of a device product that are ordered by FDA. PMID:27658315

  11. Are clinical trial results transferable in the real life?

    PubMed

    Natale, Enrico; Marsocci, Alfiera

    2016-06-22

    Generally in the clinical practice patients are more complex in comparison with those included in the clinical trials. In this article, we discuss three relevant items, which may implement the transferability of the clinical trial results in the real world. The observational studies have fewer restrictions on the number of patients included, due to more relaxed inclusion and exlusion criteria than in randomized clinical trials. The absence of randomization however may lead to potential for bias. The recurrent event analysis may extend the positive results of clinical trials regarding the reductions of the first primary endpoint event to total events, including those beyond the first event. This analysis is of great interest in the clinical practice, where recurrent events are common. Finally the reliability of subgroup analysis is discussed. Pre-specified subgroup analyses are more credible and valuable than post-hoc analyses.

  12. Desiderata for Major Eligibility Criteria in Breast Cancer Clinical Trials

    PubMed Central

    Paulson, Matthew L.; Weng, Chunhua

    2015-01-01

    Use of major eligibility criteria is a popular but unstudied folk practice for improving patient screening efficiency for clinical studies. This mixed-methods research study derived the desiderata for major eligibility criteria in breast cancer clinical trials. We randomly selected thirty interventional breast cancer clinical trials conducted at The New York-Presbyterian Hospital on the Columbia University Medical Center campus to create training (N=20) and testing (N=10) datasets. We utilized the Think-aloud protocol to gauge how clinical researchers identify and use major eligibility criteria to prescreen patients for clinical trials during an audio-recorded interview. A focus group session was held to understand the current prescreening process and investigate how it could be optimized to maximize recruitment rates. Using the grounded theory method, we annotated transcriptions to discover user rationale and desiderata behind major eligibility criteria in breast cancer clinical trials, which were later evaluated in a follow-up survey. PMID:26958302

  13. 77 FR 49448 - Food and Drug Administration Clinical Trial Requirements, Compliance, and Good Clinical Practice...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-08-16

    ... HUMAN SERVICES Food and Drug Administration Food and Drug Administration Clinical Trial Requirements... public workshop on FDA's clinical trial requirements is designed to aid the clinical research... interaction with FDA representatives. The program will focus on the relationships among FDA and clinical...

  14. The Brave New World of clinical cancer research: Adaptive biomarker-driven trials integrating clinical practice with clinical research.

    PubMed

    Berry, Donald A

    2015-05-01

    Clinical trials are the final links in the chains of knowledge and for determining the roles of therapeutic advances. Unfortunately, in an important sense they are the weakest links. This article describes two designs that are being explored today: platform trials and basket trials. Both are attempting to merge clinical research and clinical practice.

  15. Effects of lifestyle education program for type 2 diabetes patients in clinics: a cluster randomized controlled trial

    PubMed Central

    2013-01-01

    Background The prevalence of type 2 diabetes is rising worldwide, as has been the global mean fasting plasma glucose level. This study aimed to evaluate the effectiveness of a structured individual-based lifestyle education (SILE) program to reduce the hemoglobin A1c (HbA1c) level in type 2 diabetes patients delivered by registered dietitians in primary care clinical settings. Methods This was a 6-month prospective cluster randomized controlled trial in a primary care setting with randomization at the practice level. Twenty general practitioners in 20 clinics in Kanagawa prefecture, Japan, were involved. 193 adults (51% men, mean age 61.3 years) with type 2 diabetes and HbA1c ≥6.5% who received treatment in medical clinics were the participants. A SILE program was implemented through 4 sessions with trained registered dietitians during the 6-month study period. Results were compared with those of a control group who received usual care. The primary endpoint was the change in HbA1c levels at 6 months from baseline. Secondary endpoints were the changes at 6 months from baseline in fasting plasma glucose, lipid profile, blood pressure, BMI, energy, and nutrient intakes (whole day and each meal). Intention-to-treat analysis was conducted. Mixed-effects linear models were used to examine the effects of the treatment. Results The mean change at 6 months from baseline in HbA1c was a 0.7% decrease in the intervention group (n = 100) and a 0.2% decrease in the control group (n = 93) (difference −0.5%, 95%CI: -0.2% to −0.8%, p = 0.004). After adjusting for baseline values and other factors, the difference was still significant (p = 0.003 ~ 0.011). The intervention group had a significantly greater decrease in mean energy intake at dinner compared with the control group and a greater increase in mean vegetable intake for the whole day, breakfast, and lunch as shown in crude and adjusted models. A tendency toward improvement was observed in the other

  16. Mitigating the Effects of Nonadherence in Clinical Trials

    PubMed Central

    Bain, Earle E.; McCann, David J.; Skolnick, Phil; Laughren, Thomas; Hanina, Adam; Burch, Daniel

    2016-01-01

    Abstract Accounting for subject nonadherence and eliminating inappropriate subjects in clinical trials are critical elements of a successful study. Nonadherence can increase variance, lower study power, and reduce the magnitude of treatment effects. Inappropriate subjects (including those who do not have the illness under study, fail to report exclusionary conditions, falsely report medication adherence, or participate in concurrent trials) confound safety and efficacy signals. This paper, a product of the International Society for CNS Clinical Trial Methodology (ISCTM) Working Group on Nonadherence in Clinical Trials, explores and models nonadherence in clinical trials and puts forth specific recommendations to identify and mitigate its negative effects. These include statistical analyses of nonadherence data, novel protocol design, and the use of biomarkers, subject registries, and/or medication adherence technologies. PMID:26634893

  17. Rotary instruments in the treatment of chronic periodontitis: A randomized clinical trial

    PubMed Central

    Dahiya, Parveen; Kamal, Reet

    2013-01-01

    Background: The study aimed at comparing the effectiveness of rotary instruments with hand instruments in non-surgical treatment of chronic periodontitis. Materials and Methods: Thirty-eight patients with chronic periodontitis, enrolled to this randomized, controlled clinical trial, were divided into two groups. Patients in the control group received scaling and root planing with hand instruments, whereas patients in the test group received treatment with rotary instruments. Clinical assessment by plaque index, bleeding on probing, probing depth, gingival recession, and clinical attachment level was made prior to and at 6 months after treatment. Differences in the clinical parameters were analyzed using the Wilcoxon signed rank test and Mann–Whitney U test. Results: Both treatments resulted in a significant improvement in all clinical recordings, but no differences in any of the investigated parameters were observed at baseline between the two groups. Conclusion: Non-surgical periodontal therapy with the tested rotary instruments may lead to clinical improvements comparable to those obtained with conventional hand instruments. PMID:24554884

  18. 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.

  19. Differential efficacy of treatment with acetylcholinesterase inhibitors in patients with mild and moderate Alzheimer's disease over a 6-month period.

    PubMed

    López-Pousa, S; Turon-Estrada, A; Garre-Olmo, J; Pericot-Nierga, I; Lozano-Gallego, M; Vilalta-Franch, M; Hernández-Ferràndiz, M; Morante-Muñoz, V; Isern-Vila, A; Gelada-Batlle, E; Majó-Llopart, J

    2005-01-01

    There are various anticholinesterase inhibitors (AChEIs) for the symptomatic treatment of mild to moderate Alzheimer's disease (AD). All AChEIs have shown greater efficacy than placebo in randomized, double-blind, parallel-group clinical trials. No differential studies have yet been made of the efficacy between all AChEIs. The study aims to determine the differential efficacy of the AChEIs with respect to a historical sample of patients with AD that were not treated with AChEIs. An open-label, prospective, observational study with a retrospective control group was undertaken to examine the evolution of the cognitive function over a 6-month period. The patients were assessed with the Mini-Mental State Examination (MMSE) at study entry and at 6 months. A general linear model was applied for repeated measurements with the MMSE score as the dependent variable, treatment type as an independent variable and the severity of the deterioration, age and the MMSE baseline score as covariables. Of the sample of 147 patients, 40 initiated treatment with donepezil, 32 with galantamine, 30 with rivastigmine and 45 were part of a historical sample of the memory clinic patients between 1991 and 1996 that had not been treated with AChEIs. The average age was 73.7 years (SD = 6.9; range = 52-86), 67.3% were women, 78.2% of the cases were mild and the MMSE baseline score was 18.1 points (range = 11-27). No significant intergroup differences were observed in these variables. The average doses of donepezil, galantamine and rivastigmine were 5.87 mg/day (SD = 1.92), 14.81 mg/day (SD = 6.25) and 6.41 mg/day (SD = 1.82), respectively. At 6 months, the difference in the MMSE score with respect to the untreated group was 1.6 points for donepezil (95% CI 0.79-2.37; p < 0.001), 0.99 points for galantamine (95% CI 0.14-1.85; p = 0.01) and 0.90 points for rivastigmine (95% CI 0.05-1.74; p = 0.03). No significant differences were observed in the efficacy among the groups treated with AChEIs (p

  20. Is severe obesity a form of addiction? Rationale, clinical approach, and controlled clinical trial.

    PubMed

    Riva, Giuseppe; Bacchetta, Monica; Cesa, Gianluca; Conti, Sara; Castelnuovo, Gianluca; Mantovani, Fabrizia; Molinari, Enrico

    2006-08-01

    For many, obesity is just a problem of energy input and expenditure: more energy input than expenditure. However, the clinical practice and epidemiological data clearly show that weight control is more complex than expected by this simple equation. This is particularly true in morbid obesity, a form of severe obesity in which a person's Body Mass Index (BMI, kg/m(2)) is over 40. If we compare the definitions and diagnostic criteria for "dependence" and "addiction" with the situation of many severe obese subjects, it is apparent that they match very well. Further, different neurological studies confirm this similarity: both addiction and obesity patients have a deficiency of dopamine receptors. Nevertheless, when we compare many of the actual obesity treatments with the ones used in the area of addictions it is possible to find relevant differences: obesity treatments neither consider different levels of type and intensity of care, nor a multidimensional approach. To overcome these limitations, in this paper we propose a bio-psychosocial approach in which the genetic influence (lack of dopamine receptors) is matched by psychosocial issues (pressure for thinness and diet as main body image dissatisfaction treatment). Further, the paper outlines how this approach may influence the treatment options, by focusing both on the lessons coming from actual addiction treatment and the opportunities offered by virtual reality. Finally, the paper presents and discusses the outcome of a controlled trial, based on the proposed approach, including a 6-month follow-up (211 morbid obese females with a BMI of >40 and a documented history of failures.

  1. 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

  2. Health literacy and usability of clinical trial search engines.

    PubMed

    Utami, Dina; Bickmore, Timothy W; Barry, Barbara; Paasche-Orlow, Michael K

    2014-01-01

    Several web-based search engines have been developed to assist individuals to find clinical trials for which they may be interested in volunteering. However, these search engines may be difficult for individuals with low health and computer literacy to navigate. The authors present findings from a usability evaluation of clinical trial search tools with 41 participants across the health and computer literacy spectrum. The study consisted of 3 parts: (a) a usability study of an existing web-based clinical trial search tool; (b) a usability study of a keyword-based clinical trial search tool; and (c) an exploratory study investigating users' information needs when deciding among 2 or more candidate clinical trials. From the first 2 studies, the authors found that users with low health literacy have difficulty forming queries using keywords and have significantly more difficulty using a standard web-based clinical trial search tool compared with users with adequate health literacy. From the third study, the authors identified the search factors most important to individuals searching for clinical trials and how these varied by health literacy level.

  3. 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.

  4. Comparison of arthroplasty trial publications after registration in ClinicalTrials.gov.

    PubMed

    Smith, Holly N; Bhandari, Mohit; Mahomed, Nizar N; Jan, Meryam; Gandhi, Rajiv

    2012-08-01

    In 2005, the International Committee of Medical Journal Editors established a mandatory trial registration before study enrollment for publication in member journals. Our primary objective was to evaluate the publication rates of arthroplasty trials registered with ClinicalTrials.gov (CTG). We further aimed to examine the consistency of registration summaries with that of final publications. We searched CTG for all trials related to joint arthroplasty and conducted a thorough search for publications resulting from registered closed trials. Of 101 closed and completed trials, we found 23 publications, for an overall publication rate of 22.8%. Registration of arthroplasty trials in CTG does not consistently result in publication or disclosure of results. In addition, changes are frequently made to the final presentation of the data that are not reflected in the trial registry.

  5. Audiovisual temporal fusion in 6-month-old infants.

    PubMed

    Kopp, Franziska

    2014-07-01

    The aim of this study was to investigate neural dynamics of audiovisual temporal fusion processes in 6-month-old infants using event-related brain potentials (ERPs). In a habituation-test paradigm, infants did not show any behavioral signs of discrimination of an audiovisual asynchrony of 200 ms, indicating perceptual fusion. In a subsequent EEG experiment, audiovisual synchronous stimuli and stimuli with a visual delay of 200 ms were presented in random order. In contrast to the behavioral data, brain activity differed significantly between the two conditions. Critically, N1 and P2 latency delays were not observed between synchronous and fused items, contrary to previously observed N1 and P2 latency delays between synchrony and perceived asynchrony. Hence, temporal interaction processes in the infant brain between the two sensory modalities varied as a function of perceptual fusion versus asynchrony perception. The visual recognition components Pb and Nc were modulated prior to sound onset, emphasizing the importance of anticipatory visual events for the prediction of auditory signals. Results suggest mechanisms by which young infants predictively adjust their ongoing neural activity to the temporal synchrony relations to be expected between vision and audition.

  6. Intravitreal Autologous Bone Marrow CD34+ Cell Therapy for Ischemic and Degenerative Retinal Disorders: Preliminary Phase 1 Clinical Trial Findings

    PubMed Central

    Park, Susanna S.; Bauer, Gerhard; Abedi, Mehrdad; Pontow, Suzanne; Panorgias, Athanasios; Jonnal, Ravi; Zawadzki, Robert J.; Werner, John S.; Nolta, Jan

    2015-01-01

    Purpose. Because human bone marrow (BM) CD34+ stem cells home into damaged tissue and may play an important role in tissue repair, this pilot clinical trial explored the safety and feasibility of intravitreal autologous CD34+ BM cells as potential therapy for ischemic or degenerative retinal conditions. Methods. This prospective study enrolled six subjects (six eyes) with irreversible vision loss from retinal vascular occlusion, hereditary or nonexudative age-related macular degeneration, or retinitis pigmentosa. CD34+ cells were isolated under Good Manufacturing Practice conditions from the mononuclear cellular fraction of the BM aspirate using a CliniMACs magnetic cell sorter. After intravitreal CD34+ cell injection, serial ophthalmic examinations, microperimetry/perimetry, fluorescein angiography, electroretinography (ERG), optical coherence tomography (OCT), and adaptive optics OCT were performed during the 6-month follow-up. Results. A mean of 3.4 million (range, 1–7 million) CD34+ cells were isolated and injected per eye. The therapy was well tolerated with no intraocular inflammation or hyperproliferation. Best-corrected visual acuity and full-field ERG showed no worsening after 6 months. Clinical examination also showed no worsening during follow-up except among age-related macular degeneration subjects in whom mild progression of geographic atrophy was noted in both the study eye and contralateral eye at 6-month follow-up, concurrent with some possible decline on multifocal ERG and microperimetry. Cellular in vivo imaging using adaptive optics OCT showed changes suggestive of new cellular incorporation into the macula of the hereditary macular degeneration study eye. Conclusions. Intravitreal autologous BM CD34+ cell therapy appears feasible and well tolerated in eyes with ischemic or degenerative retinal conditions and merits further exploration. (ClinicalTrials.gov number, NCT01736059.) PMID:25491299

  7. Neck strain in car occupants: injury status after 6 months and crash-related factors.

    PubMed

    Ryan, G A; Taylor, G W; Moore, V M; Dolinis, J

    1994-10-01

    In this study, 29 individuals who sustained a neck strain as a result of a car crash were drawn from a group of physiotherapy and general practices and were followed up after 6 months. The aim was to examine relationships between the state of the neck injury at the time of follow up and crash-related factors, notably crash severity and occupant awareness. Crash severity was assessed by measurement of damage to the involved vehicles, while 6-month injury status was established through physical examinations and interviews. No statistically significant associations between crash severity and 6-month injury status were found, but subjects who were unaware of the impending collision had a greatly increased likelihood of experiencing persisting symptoms of and/or signs of neck strain, compared with those who were aware (odds ratio = 15.0; 95 per cent confidence limits: 1.8, 178). While the role of crash severity in the production and duration of neck strains remains unclear, awareness appears to have a strong protective influence and may prove to be a useful prognostic indicator in clinical settings.

  8. Clinical trial registration in oral health journals.

    PubMed

    Smaïl-Faugeron, V; Fron-Chabouis, H; Durieux, P

    2015-03-01

    Prospective registration of randomized controlled trials (RCTs) represents the best solution to reporting bias. The extent to which oral health journals have endorsed and complied with RCT registration is unknown. We identified journals publishing RCTs in dentistry, oral surgery, and medicine in the Journal Citation Reports. We classified journals into 3 groups: journals requiring or recommending trial registration, journals referring indirectly to registration, and journals providing no reference to registration. For the 5 journals with the highest 2012 impact factors in each group, we assessed whether RCTs with results published in 2013 had been registered. Of 78 journals examined, 32 (41%) required or recommended trial registration, 19 (24%) referred indirectly to registration, and 27 (35%) provided no reference to registration. We identified 317 RCTs with results published in the 15 selected journals in 2013. Overall, 73 (23%) were registered in a trial registry. Among those, 91% were registered retrospectively and 32% did not report trial registration in the published article. The proportion of trials registered was not significantly associated with editorial policies: 29% with results in journals that required or recommended registration, 15% in those that referred indirectly to registration, and 21% in those providing no reference to registration (P = 0.05). Less than one-quarter of RCTs with results published in a sample of oral health journals were registered with a public registry. Improvements are needed with respect to how journals inform and require their authors to register their trials.

  9. 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.

  10. '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

    2015-07-29

    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.

  11. '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

  12. Modeling the dissemination and uptake of clinical trials results

    PubMed Central

    Rosas, Scott R.; Schouten, Jeffrey T.; Cope, Marie T.; Kagan, Jonathan M.

    2013-01-01

    A select set of highly cited publications from the National Institutes of Health (NIH) HIV/AIDS Clinical Trials Networks was used to illustrate the integration of time interval and citation data, modeling the progression, dissemination, and uptake of primary research findings. Following a process marker approach, the pace of initial utilization of this research was measured as the time from trial conceptualization, development and implementation, through results dissemination and uptake. Compared to earlier studies of clinical research, findings suggest that select HIV/AIDS trial results are disseminated and utilized relatively rapidly. Time-based modeling of publication results as they meet specific citation milestones enabled the observation of points at which study results were present in the literature summarizing the evidence in the field. Evaluating the pace of clinical research, results dissemination, and knowledge uptake in synthesized literature can help establish realistic expectations for the time course of clinical trials research and their relative impact toward influencing clinical practice. PMID:24808630

  13. Ethical considerations in industry-sponsored multiregional clinical trials.

    PubMed

    Ibia, Ekopimo; Binkowitz, Bruce; Saillot, Jean-Louis; Talerico, Steven; Koerner, Chin; Ferreira, Irene; Agarwal, Anupam; Metz, Craig; Maman, Marianne

    2010-01-01

    During the last several decades, the scientific and ethics communities have addressed important ethical issues in medical research, resulting in the elaboration and adoption of concepts, guidelines, and codes. Ethical issues in the conduct of Multiregional Clinical Trials have attracted significant attention mainly in the last two decades. With the globalization of clinical research and the rapid expansion to countries with a limited tradition of biomedical research, sponsors must proactively address local ethical issues, the adequacy of oversight as well as the applicability and validity of data, and scientific conclusions drawn from diverse patient populations. This paper highlights some core ethical principles and milestones in medical research, and, from an industry perspective, it discusses ethical issues that the clinical trial team may face when conducting Multiregional Clinical Trials (MRCT, clinical trials conducted at sites located across multiple geographic regions of the world). This paper further highlights the areas of consensus and controversies and proposes points to consider.

  14. Challenges in recruitment and retention of clinical trial subjects

    PubMed Central

    Kadam, Rashmi Ashish; Borde, Sanghratna Umakant; Madas, Sapna Amol; Salvi, Sundeep Santosh; Limaye, Sneha Saurabh

    2016-01-01

    Background: Successful recruitment of patients is known to be one of the most challenging aspects in conduct of randomized controlled trials. Inadequate patient retention during conduct of trial affects conclusive results. Objective: To assess the level of challenges faced by Indian investigators in recruitment and retention of trial subjects. Methods: We developed a survey questionnaire on challenges encountered by investigators in subject recruitment and retention which was hosted on a web portal. Results: Seventy-three investigators from India participated in the survey. The frequently encountered challenges in subject recruitment were complexity of study protocol (38%), lack of awareness about clinical trials in patients (37%), and sociocultural issues related to trial participation (37%). About 63% of participants strongly agreed that creating a positive awareness about clinical trials among people through press and media, having a dedicated clinical research coordinator for trial (50.7%), and designing a recruitment strategy prior to study initiation (46.6%) would enhance recruitment. Almost 50.7% of participants agreed that interacting with medical community in vicinity of the study site and educating patients about clinical trials during routine outpatient department visits (46.6%) would enhance recruitment. Experiencing a serious adverse event, subject's fear for study procedures (47%) and side effects (44%) were thought to have a moderate effect on subject retention. Conclusion: Our survey has put forth factors related to negative publicity by media, lack of patient education about clinical trials; complex study designs are barriers to clinical trial recruitment in India. It is essential to devise innovative and effective strategies focusing on education of public and mass media about clinical research in India. PMID:27453831

  15. Challenges in launching multinational oncology clinical trials in India

    PubMed Central

    Saini, Kamal S.; Agarwal, Gaurav; Jagannathan, Ramesh; Metzger-Filho, Otto; Saini, Monika L.; Mistry, Khurshid; Ali, Raghib; Gupta, Sudeep

    2013-01-01

    In the recent past, there has been an impressive growth in the number of clinical trials launched worldwide, including India. Participation in well-designed oncology clinical trials is of advantage to Indian healthcare system in general, and cancer patients in particular. However, the number of clinical trials being run in India is not commensurate with the cancer burden prevailing in the country. In this article, the authors investigate the reasons for this discrepancy, highlight critical bottlenecks, and propose ways to ameliorate the situation. PMID:24455545

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

    PubMed

    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.

  17. 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

  18. Can Lifestyle Modification Improve Neurocognition? Rationale and Design of the ENLIGHTEN Clinical Trial

    PubMed Central

    Blumenthal, James A.; Smith, Patrick J.; Welsh-Bohmer, Kathleen; Babyak, Michael A.; Browndyke, Jeffrey; Lin, Pao-Hwa; Doraiswamy, P. Murali; Burke, James; Kraus, William; Hinderliter, Alan; Sherwood, Andrew

    2013-01-01

    Background Risk factors for cardiovascular disease (CVD) not only increase the risk for clinical CVD events, but also are associated with a cascade of neurophysiologic and neuroanatomic changes that increase the risk of cognitive impairment and dementia. Although epidemiological studies have shown that exercise and diet are associated with lower CVD risk and reduced incidence of dementia, no randomized controlled trial (RCT) has examined the independent effects of exercise and diet on neurocognitive function among individuals at risk for dementia. The ENLIGHTEN trial is a RCT of patients with CVD risk factors who also are characterized by subjective cognitive complaints and objective evidence of neurocognitive impairment without dementia (CIND) Study Design A 2 by 2 design will examine the independent and combined effects of diet and exercise on neurocognition. 160 participants diagnosed with CIND will be randomly assigned to 6 months of aerobic exercise, the DASH diet, or a combination of both exercise and diet; a (control) group will receive health education but otherwise will maintain their usual dietary and activity habits. Participants will complete comprehensive assessments of neurocognitive functioning along with biomarkers of CVD risk including measures of blood pressure, glucose, endothelial function, and arterial stiffness. Conclusion The ENLIGHTEN trial will (a) evaluate the effectiveness of aerobic exercise and the DASH diet in improving neurocognitive functioning in CIND patients with CVD risk factors; (b) examine possible mechanisms by which exercise and diet improve neurocognition; and (c) consider potential moderators of treatment, including subclinical CVD. PMID:23000080

  19. Feasibility of feature-based indexing, clustering, and search of clinical trials: A case study of breast cancer trials from ClinicalTrials.gov

    PubMed Central

    Boland, Mary Regina; Miotto, Riccardo; Gao, Junfeng; Weng, Chunhua

    2013-01-01

    Summary Background When standard therapies fail, clinical trials provide experimental treatment opportunities for patients with drug-resistant illnesses or terminal diseases. Clinical Trials can also provide free treatment and education for individuals who otherwise may not have access to such care. To find relevant clinical trials, patients often search online; however, they often encounter a significant barrier due to the large number of trials and in-effective indexing methods for reducing the trial search space. Objectives This study explores the feasibility of feature-based indexing, clustering, and search of clinical trials and informs designs to automate these processes. Methods We decomposed 80 randomly selected stage III breast cancer clinical trials into a vector of eligibility features, which were organized into a hierarchy. We clustered trials based on their eligibility feature similarities. In a simulated search process, manually selected features were used to generate specific eligibility questions to filter trials iteratively. Results We extracted 1,437 distinct eligibility features and achieved an inter-rater agreement of 0.73 for feature extraction for 37 frequent features occurring in more than 20 trials. Using all the 1,437 features we stratified the 80 trials into six clusters containing trials recruiting similar patients by patient-characteristic features, five clusters by disease-characteristic features, and two clusters by mixed features. Most of the features were mapped to one or more Unified Medical Language System (UMLS) concepts, demonstrating the utility of named entity recognition prior to mapping with the UMLS for automatic feature extraction. Conclusions It is feasible to develop feature-based indexing and clustering methods for clinical trials to identify trials with similar target populations and to improve trial search efficiency. PMID:23666475

  20. Targeting Temporomandibular Disorder Pain Treatment to Hormonal Fluctuations: A Randomized Clinical Trial

    PubMed Central

    Turner, Judith A.; Mancl, Lloyd; Huggins, Kimberly Hanson; Sherman, Jeffrey J.; Lentz, Gretchen; LeResche, Linda

    2011-01-01

    Mounting evidence supports the importance of hormonal fluctuations in temporomandibular disorder (TMD) pain among women. Stabilizing influential hormones or having a plan and skills for coping with hormonally-related increases in TMD pain therefore may be beneficial for women with TMD pain. This randomized clinical trial evaluated the short- and long-term efficacy of three interventions for women with TMD pain: (1) dental hygienist-delivered pain self-management training (SMT; n = 59); (2) the same dental hygienist-delivered pain self-management training, but with a focus on menstrual cycle-related changes in pain and other symptoms (targeted SMT, or TSMT; n = 55); and (3) continuous oral contraceptive therapy (6 month trial), aimed at stabilizing hormones believed to be influential in TMD pain (COCT; n = 57). Study participants completed outcome (pain, activity interference, depression) and process (pain beliefs, catastrophizing, coping effectiveness) measures before randomization, and 6 and 12 months later. Intent-to-treat analyses supported the benefits of the SMT and TSMT interventions relative to COCT. Targeting the self-management treatment to menstrual cycle-related symptoms did not increase the treatment’s efficacy. The benefits of the self-management interventions relative to COCT for pain and activity interference were statistically significant at 12 months, but not at 6 months, whereas the benefits for the process measures generally were apparent at both timepoints. COCT was associated with multiple adverse events (none serious). The study provides further support for long-term benefits of a safe, low intensity (two in-person sessions and six brief telephone contacts), dental hygienist-delivered self-management treatment for TMD pain. PMID:21680092

  1. Using the Internet to search for cancer clinical trials: a comparative audit of clinical trial search tools.

    PubMed

    Atkinson, Nancy L; Saperstein, Sandra L; Massett, Holly A; Leonard, Colleen Ryan; Grama, Lakshmi; Manrow, Rick

    2008-07-01

    Advancing the clinical trial research process to improve cancer treatment necessitates helping people with cancer identify and enroll in studies, and researchers are using the power of the Internet to facilitate this process. This study used a content analysis of online cancer clinical trial search tools to understand what people with cancer might encounter. The content analysis revealed that clinical trial search tools were easy to identify using a popular search engine, but their functionality and content varied greatly. Most required that users be fairly knowledgeable about their medical condition and sophisticated in their web navigation skills. The ability to search by a specific health condition or type of cancer was the most common search strategy. The more complex tools required that users input detailed information about their personal medical history and have knowledge of specific clinical trial terminology. Search tools, however, only occasionally advised users to consult their doctors regarding clinical trial decision-making. This, along with the complexity of the tools suggests that online search tools may not adequately facilitate the clinical trial recruitment process. Findings from this analysis can be used as a framework from which to systematically examine actual consumer experience with online clinical trial search tools.

  2. Perceived stress among a workforce 6 months following hurricane Katrina.

    PubMed

    Leon, Kyla A; Hyre, Amanda D; Ompad, Danielle; Desalvo, Karen B; Muntner, Paul

    2007-12-01

    To determine stress levels among a workforce 6 months after hurricane Katrina made landfall, a web-based survey that included the four-item Perceived Stress Scale was administered to employees of the largest employer in New Orleans. An overall Perceived Stress Scale score was obtained by pooling responses for the four items. Among 1,542 adult respondents, 24.1% stated they felt that they were "fairly often" or "very often" unable to control the important things in their life and 21.4% considered that their difficulties were "fairly often" or "very often" piling up so high that they could not overcome them. Also, 6.1% reported that they "almost never" or "never" felt confident about their ability to handle their personal problems and 15.2% indicated that things were "almost never" or "never" going their way. The overall mean Perceived Stress Scale score was 6.3 (standard deviation = 3.1; range = 0-16). Higher stress scale scores, indicating more stress, were present for women, and for participants with lower income, displaced longer than 3 months, who were more afraid of losing their life during hurricane Katrina and its immediate aftermath, and who knew someone that died during the storm. Additionally, participants who were living in a relative of friend's house or in a temporary trailer at the time of the survey had higher stress scores compared to their counterparts who had returned to live in their pre-hurricane residence. There was a direct association between higher stress scores and symptoms of post-traumatic stress disorder. Employers and health care providers should be apprised of the need for monitoring stress and offering counseling opportunities for returning workforces following future large-scale disasters. PMID:17932611

  3. 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

  4. Reforms speed initiation of NCI-sponsored clinical trials

    Cancer.gov

    The process of opening a cancer clinical trial for patient accrual often takes years, and research has shown that trials which are slow to register patients often fail to finish. Following a thorough review, NCI’s Operational Efficiency Working Group prod

  5. Design and Implementation of Clinical Trials of Ion Beam Therapy

    NASA Astrophysics Data System (ADS)

    Cox, James D.

    Design and implementation of clinical trials are complex even when those trials involve established technologies. Ion beam therapy (IBT) imposes additional requirements including sufficient institutional experience using ions for treatment, credentialing of institutions, formulating hypotheses of interest to investigators and to patients, and securing funding from national and private agencies. The effort, though, is very important to the future of radiation oncology.

  6. Improving function in age-related macular degeneration: design and methods of a randomized clinical trial.

    PubMed

    Rovner, Barry W; Casten, Robin J; Hegel, Mark T; Massof, Robert W; Leiby, Benjamin E; Tasman, William S

    2011-03-01

    Age-Related Macular Degeneration (AMD) is the leading cause of severe vision loss in older adults and impairs the ability to read, drive, and live independently and increases the risk for depression, falls, and earlier mortality. Although new medical treatments have improved AMD's prognosis, vision-related disability remains a major public health problem. Improving Function in AMD (IF-AMD) is a two-group randomized, parallel design, controlled clinical trial that compares the efficacy of Problem-Solving Therapy (PST) with Supportive Therapy (ST) (an attention control treatment) to improve vision function in 240 patients with AMD. PST and ST therapists deliver 6 one-hour respective treatment sessions to subjects in their homes over 2 months. Outcomes are assessed masked to treatment assignment at 3 months (main trial endpoint) and 6 months (maintenance effects). The primary outcome is targeted vision function (TVF), which refers to specific vision-dependent functional goals that subjects highly value but find difficult to achieve. TVF is an innovative outcome measure in that it is targeted and tailored to individual subjects yet is measured in a standardized way. This paper describes the research methods, theoretical and clinical aspects of the study treatments, and the measures used to evaluate functional and psychiatric outcomes in this population.

  7. 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

  8. 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

  9. Clinical Research Trials and You: Questions and Answers

    MedlinePlus

    ... volunteers and to preserve the integrity of the science. Ethical guidelines in place today were primarily a response to past research abuses. Informed Consent Informed consent is the process of learning the key facts about a clinical trial before ...

  10. CliniProteus: A flexible clinical trials information management system

    PubMed Central

    Mathura, Venkatarajan S; Rangareddy, Mahendiranath; Gupta, Pankaj; Mullan, Michael

    2007-01-01

    Clinical trials involve multi-site heterogeneous data generation with complex data input-formats and forms. The data should be captured and queried in an integrated fashion to facilitate further analysis. Electronic case-report forms (eCRF) are gaining popularity since it allows capture of clinical information in a rapid manner. We have designed and developed an XML based flexible clinical trials data management framework in .NET environment that can be used for efficient design and deployment of eCRFs to efficiently collate data and analyze information from multi-site clinical trials. The main components of our system include an XML form designer, a Patient registration eForm, reusable eForms, multiple-visit data capture and consolidated reports. A unique id is used for tracking the trial, site of occurrence, the patient and the year of recruitment. Availability http://www.rfdn.org/bioinfo/CTMS/ctms.html. PMID:21670796

  11. Strategies for dealing with fraud in clinical trials.

    PubMed

    Herson, Jay

    2016-02-01

    Research misconduct and fraud in clinical research is an increasing problem facing the scientific community. This problem is expected to increase due to discoveries in central statistical monitoring and with the increase in first-time clinical trial investigators in the increasingly global reach of oncology clinical trials. This paper explores the most common forms of fraud in clinical trials in order to develop offensive and defensive strategies to deal with fraud. The offensive strategies are used when fraud is detected during a trial and the defensive strategies are those design strategies that seek to minimize or eliminate the effect of fraud. This leads to a proposed fraud recovery plan (FRP) that would be specified before the start of a clinical trial and would indicate actions to be taken upon detecting fraud of different types. Statistical/regulatory issues related to fraud include: dropping all patients from a site that committed fraud, or just the fraudulent data (perhaps replacing the latter through imputation); the role of intent-to-treat analysis; effect on a planned interim analysis; effect on stratified analyses and model adjustment when fraud is detected in covariates; effect on trial-wide randomization, etc. The details of a typical defensive strategy are also presented. It is concluded that it is best to follow a defensive strategy and to have an FRP in place to follow if fraud is detected during the trial.

  12. Review of clinical trials for mitochondrial disorders: 1997-2012.

    PubMed

    Kerr, Douglas S

    2013-04-01

    Over the last 15 years, some 16 open and controlled clinical trials for potential treatments of mitochondrial diseases have been reported or are in progress, and are summarized and reviewed herein. These include trials of administering dichloroacetate (an activator of pyruvate dehydrogenase complex), arginine or citrulline (precursors of nitric oxide), coenzyme Q10 (CoQ10; part of the electron transport chain and an antioxidant), idebenone (a synthetic analogue of CoQ10), EPI-743 (a novel oral potent 2-electron redox cycling agent), creatine (a precursor of phosphocreatine), combined administration (of creatine, α-lipoate, and CoQ10), and exercise training (to increase muscle mitochondria). These trials have included patients with various mitochondrial disorders, a selected subcategory of mitochondrial disorders, or specific mitochondrial disorders (Leber hereditary optic neuropathy or mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes). The trial designs have varied from open-label/uncontrolled, open-label/controlled, or double-blind/placebo-controlled/crossover. Primary outcomes have ranged from single, clinically-relevant scores to multiple measures. Eight of these trials have been well-controlled, completed trials. Of these only 1 (treatment with creatine) showed a significant change in primary outcomes, but this was not reproduced in 2 subsequent trials with creatine with different patients. One trial (idebenone treatment of Leber hereditary optic neuropathy) did not show significant improvement in the primary outcome, but there was significant improvement in a subgroup of patients. Despite the paucity of benefits found so far, well-controlled clinical trials are essential building blocks in the continuing search for more effective treatment of mitochondrial disease, and current trials based on information gained from these prior experiences are in progress. Because of difficulties in recruiting sufficient mitochondrial disease patients

  13. Publicly Funded Clinical Trials and the Future of Cancer Care

    PubMed Central

    2013-01-01

    Publicly sponsored trials, conducted primarily by cooperative groups sponsored by the National Cancer Institute, and commercially sponsored trials are necessary to create new knowledge, improve the care of oncology patients, and develop new drugs and devices. Commercial sponsors launch clinical trials that will result in drug approval, label extension, expansion of market share, and an increase in shareholder value. Conversely, publicly sponsored trials seek to optimize therapy for a particular disease, create new knowledge, and improve public health; these trials can also result in label extension of a drug and even in initial drug approval. Publicly sponsored trials may combine and/or compare drugs developed by different commercial sponsors, develop multimodality therapies (e.g., the combination of chemotherapy and radiation), or develop novel treatment schedules or routes of drug administration (e.g., intraperitoneal chemotherapy). Publicly sponsored trials are more likely to focus on therapies for rare diseases and to study survivorship and quality of life; these areas may not be a priority for commercial entities. Screening and prevention strategies have been developed almost exclusively by the public sector given the large sample size and long follow-up period needed to complete the trial and, therefore, the lack of short-term commercial gain. Finally, given the public nature of the funding, clinical investigators are expected to publish their results even if the outcomes are unfavorable for the investigational therapy. With the ongoing reorganization of the cooperative groups to form a national clinical trials network, opportunities exist to create a robust platform for biomarker discovery and validation through the expanded collection of well-annotated biospecimens obtained from clinical trial participants. Thus, publicly funded trials are vital to developing and refining new cancer treatments and disseminating results to the medical community and the

  14. Clinical trials and oral care R&D.

    PubMed

    Gerlach, Robert W

    2006-01-01

    The introduction of hydrogen peroxide whitening strips in 2000 has contributed to new paradigms for treatment and expanded interest in tooth whitening. Clinical trials played a prominent role in the whitening strip research and development process. Four case studies from the whitening strip development program are used to review the fundamentals of clinical trials design, conduct, analysis, and interpretation as part of new product development in oral care.

  15. Lung-MAP Launches: First Precision Medicine Trial From National Clinical Trials Network

    Cancer.gov

    A unique public-private collaboration today announced the initiation of the Lung Cancer Master Protocol (Lung-MAP) trial, a multi-drug, multi-arm, biomarker-driven clinical trial for patients with advanced squamous cell lung cancer. Squamous cell carcinom

  16. Neuromuscular Evaluation With Single-Leg Squat Test at 6 Months After Anterior Cruciate Ligament Reconstruction

    PubMed Central

    Hall, Michael P.; Paik, Ronald S.; Ware, Anthony J.; Mohr, Karen J.; Limpisvasti, Orr

    2015-01-01

    Background: Criteria for return to unrestricted activity after anterior cruciate ligament (ACL) reconstruction varies, with some using time after surgery as the sole criterion—most often at 6 months. Patients may have residual neuromuscular deficits, which may increase the risk of ACL injury. A single-leg squat test (SLST) can dynamically assess for many of these deficits prior to return to unrestricted activity. Hypothesis: A significant number of patients will continue to exhibit neuromuscular deficits with SLST at 6 months after ACL reconstruction. Study Design: Cross-sectional study; Level of evidence, 3. Methods: Patients using a standardized accelerated rehabilitation protocol at their 6-month follow-up after primary ACL reconstruction were enrolled. Evaluation included bilateral SLST, single-leg hop distance, hip abduction strength, and the subjective International Knee Documentation Committee (IKDC) score. Results: Thirty-three patients were enrolled. Poor performance of the operative leg SLST was found in 15 of 33 patients (45%). Of those 15 patients, 7 (45%) had concomitant poor performance of the nonoperative leg compared with 2 of 18 patients (11%) in those who demonstrated good performance in the operative leg. The poor performers were significantly older (33.6 years) than the good performers (24.2 years) (P = .007). Those with poor performance demonstrated decreased hip abduction strength (17.6 kg operative leg vs 20.5 kg nonoperative leg) (P = .024), decreased single-leg hop distance (83.3 cm operative leg vs 112.3 cm nonoperative leg) (P = .036), and lower IKDC scores (67.9 vs 82.3) (P = .001). Conclusion: Nearly half of patients demonstrated persistent neuromuscular deficits on SLST at 6 months, which is when many patients return to unrestricted activity. Those with poor performance were of a significantly older age, decreased hip abduction strength, decreased single-leg hop distance, and lower IKDC subjective scores. Clinical Relevance: The SLST

  17. Quantitative MR in multi-center clinical trials.

    PubMed

    Ashton, Edward

    2010-02-01

    MRI has a wide variety of applications in the clinical trials process. MR has shown particular utility in the early phases of clinical development, when trial sponsors are interested in demonstrating proof of concept and must make decisions about allocation of resources to a particular compound based on the results from a small number of experimental subjects. This utility is largely due to the many different imaging endpoints that can be measured using MR, ranging from structural (tumor burden, hippocampal volume) to functional (blood flow, vascular permeability) to molecular (hepatic fat fraction, glycosaminoglycan content). The unique flexibility of these systems has proven to be both a blessing and a curse to those attempting to deploy MR in multi-center clinical trials, however, as differences among scanner manufacturers and models in pulse sequence implementation, hardware capabilities, and even terminology make it increasingly difficult to ensure that results obtained at one center are comparable to those at another. These problems are compounded by the differences between the procedures used in clinical trials and those used in routine clinical practice, which make trial-specific training for site technologists and radiologists a necessity in many cases. This article will briefly review the benefits of including quantitative MR imaging in clinical trials, then explore in detail the challenges presented by the need to develop and deploy a detailed MR protocol that is both effective and implementable across many different MR systems and software versions.

  18. Perspectives on clinical trial data transparency and disclosure.

    PubMed

    Alemayehu, Demissie; Anziano, Richard J; Levenstein, Marcia

    2014-09-01

    The increased demand for transparency and disclosure of data from clinical trials sponsored by pharmaceutical companies poses considerable challenges and opportunities from a statistical perspective. A central issue is the need to protect patient privacy and adhere to Good Clinical and Statistical Practices, while ensuring access to patient-level data from clinical trials to the wider research community. This paper offers options to navigate this dilemma and balance competing priorities, with emphasis on the role of good clinical and statistical practices as proven safeguards for scientific integrity, the importance of adopting best practices for reporting of data from secondary analyses, and the need for optimal collaboration among stakeholders to facilitate data sharing.

  19. Meta-analysis of five photodisinfection clinical trials for periodontitis

    NASA Astrophysics Data System (ADS)

    Andersen, Roger C.; Loebel, Nicolas G.; Andersen, Dane M.

    2009-06-01

    Photodynamic therapy(PDT) has been demonstrated to effectively kill human periopathogens in vitro. To evaluate the efficacy of PDT in vivo a series of clinical trials was carried out in multiple centers and populations. Clinical parameters including clinical attachment level, pocket probing depth and bleeding on probing were all evaluated. All groups received the standard of care, scaling and root planing, and the treatment group additionally received a single treatment of PDT. Of the total 309 patients and over 40,000 pockets treated in these 5 trials it was determined that photodynamic therapy provided a statistically significant improvement in clinical parameters over scaling and root planing alone.

  20. Is surgery at progression a prognostic marker for improved 6-month progression-free survival or overall survival for patients with recurrent glioblastoma?

    PubMed

    Clarke, Jennifer L; Ennis, Michele M; Yung, W K Alfred; Chang, Susan M; Wen, Patrick Y; Cloughesy, Timothy F; Deangelis, Lisa M; Robins, H Ian; Lieberman, Frank S; Fine, Howard A; Abrey, Lauren; Gilbert, Mark R; Mehta, Minesh; Kuhn, John G; Aldape, Kenneth D; Lamborn, Kathleen R; Prados, Michael D

    2011-10-01

    Historically, the North American Brain Tumor Consortium used 6-month progression-free survival (PFS6) as the primary outcome for recurrent glioma phase II clinical trials. In some trials, a subset of patients received the trial treatment before surgery to assess tumor uptake and biological activity. We compared PFS6 and overall survival (OS) for patients with glioblastoma undergoing surgery at progression to results for those without surgery to evaluate the impact of surgical intervention on these outcomes. Two data sets were analyzed. The first included 511 patients enrolled during the period 1998-2005, 105 of whom had surgery (excluding biopsies) during the study or ≤ 30 days prior to registration. Analysis was stratified on the basis of whether temozolomide was part of the protocol treatment regimen. The second data set included 247 patients enrolled during 2005-2008, 103 of whom underwent surgery during the clinical trial or immediately prior to study registration. A combined data set consisting of all patients who did not receive temozolomide was also compiled. No statistically significant difference in PFS6 or OS was found between the surgery and nonsurgery groups in either data set alone or in the combined data set (P > .45). We conclude that PFS6 and OS results for patients with and without surgical intervention at the time of progression are similar, allowing data from these patients to be combined in assessing the benefit of new treatments without the need for stratification or other statistical adjustment.

  1. Is surgery at progression a prognostic marker for improved 6-month progression-free survival or overall survival for patients with recurrent glioblastoma?

    PubMed Central

    Clarke†, Jennifer L.; Ennis†, Michele M.; Yung, W. K. Alfred; Chang, Susan M.; Wen, Patrick Y.; Cloughesy, Timothy F.; DeAngelis, Lisa M.; Robins, H. Ian; Lieberman, Frank S.; Fine, Howard A.; Abrey, Lauren; Gilbert, Mark R.; Mehta, Minesh; Kuhn, John G.; Aldape, Kenneth D.; Lamborn, Kathleen R.; Prados, Michael D.

    2011-01-01

    Historically, the North American Brain Tumor Consortium used 6-month progression-free survival (PFS6) as the primary outcome for recurrent glioma phase II clinical trials. In some trials, a subset of patients received the trial treatment before surgery to assess tumor uptake and biological activity. We compared PFS6 and overall survival (OS) for patients with glioblastoma undergoing surgery at progression to results for those without surgery to evaluate the impact of surgical intervention on these outcomes. Two data sets were analyzed. The first included 511 patients enrolled during the period 1998–2005, 105 of whom had surgery (excluding biopsies) during the study or ≤30 days prior to registration. Analysis was stratified on the basis of whether temozolomide was part of the protocol treatment regimen. The second data set included 247 patients enrolled during 2005–2008, 103 of whom underwent surgery during the clinical trial or immediately prior to study registration. A combined data set consisting of all patients who did not receive temozolomide was also compiled. No statistically significant difference in PFS6 or OS was found between the surgery and nonsurgery groups in either data set alone or in the combined data set (P > .45). We conclude that PFS6 and OS results for patients with and without surgical intervention at the time of progression are similar, allowing data from these patients to be combined in assessing the benefit of new treatments without the need for stratification or other statistical adjustment. PMID:21813511

  2. 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

  3. Measurement of quality of life in clinical trials.

    PubMed

    Kaasa, S

    1992-01-01

    Information on patients' quality of life (QOL) will give a more comprehensive evaluation of the treatment outcome than only measures of tumour response and survival. Psychosocial indicators have rarely been used in clinical trials. This may in part be explained by physicians' lack of familiarity with these measures, methodological insufficiency and a basic philosophical reason, i.e., most doctors tend to focus on curative treatment and not on palliative treatment. A series of QOL questionnaires has been validated in the last decade for use in cancer clinical trials. Selection of the optimal method in the given trial is important. The trial ought to be designed so the proportion of missing data is low. QOL should be used as an end point in selective trials with an optimal study design and with a study coordinator who is willing to collect QOL data.

  4. Adherence and the Lie in a HIV Prevention Clinical Trial

    PubMed Central

    Stadler, Jonathan; Scorgie, Fiona; van der Straten, Ariane; Saethre, Eirik

    2016-01-01

    The lie has been presented as a performance that protects identities against moral judgment in the context of power imbalances. We explore this assertion from the perspective of a pre-exposure prophylaxis trial to prevent HIV for African women in South Africa, in which context biological evidence of widespread lying about product adherence was produced, resulting in a moral discourse that opposed altruistic and selfish motivations. In this article, we seek to understand the meaning of the lie from the perspective of women trial participants. Seeing the trial as representing a hopeful future, and perfect adherence as sustaining their investment in this, participants recited scripted accounts of adherence and performed the role of the perfect adherer, while identifying other participants as dishonest. Given that clinical trials create moral orders and adherence is key to this, we argue that women embraced the apparatus of the clinical trial to assert their moral subjectivities. PMID:26575611

  5. 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

  6. A national strategy to develop pragmatic clinical trials infrastructure.

    PubMed

    Concannon, Thomas W; Guise, Jeanne-Marie; Dolor, Rowena J; Meissner, Paul; Tunis, Sean; Krishnan, Jerry A; Pace, Wilson D; Saltz, Joel; Hersh, William R; Michener, Lloyd; Carey, Timothy S

    2014-04-01

    An important challenge in comparative effectiveness research is the lack of infrastructure to support pragmatic clinical trials, which compare interventions in usual practice settings and subjects. These trials present challenges that differ from those of classical efficacy trials, which are conducted under ideal circumstances, in patients selected for their suitability, and with highly controlled protocols. In 2012, we launched a 1-year learning network to identify high-priority pragmatic clinical trials and to deploy research infrastructure through the NIH Clinical and Translational Science Awards Consortium that could be used to launch and sustain them. The network and infrastructure were initiated as a learning ground and shared resource for investigators and communities interested in developing pragmatic clinical trials. We followed a three-stage process of developing the network, prioritizing proposed trials, and implementing learning exercises that culminated in a 1-day network meeting at the end of the year. The year-long project resulted in five recommendations related to developing the network, enhancing community engagement, addressing regulatory challenges, advancing information technology, and developing research methods. The recommendations can be implemented within 24 months and are designed to lead toward a sustained national infrastructure for pragmatic trials.

  7. 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

  8. Design and implementation of clinical trials in rehabilitation research.

    PubMed

    Hart, Tessa; Bagiella, Emilia

    2012-08-01

    The growth of evidence-based medicine means that both researchers and clinicians must grasp the complex issues involved in implementing clinical trials, which are especially challenging for the behavioral (experience-based) treatments that predominate in rehabilitation. In this article we discuss selected issues germane to the design, implementation, and analysis of group-level clinical trials in rehabilitation. We review strengths, weaknesses, and best applications of 1-sample, between-subjects, and within-subjects study designs, including newer models such as practical clinical trials and point-of-care trials. We also discuss the selection of appropriate control conditions against which to test rehabilitation treatments, as well as issues related to trial blinding. In a section on treatment definition, we discuss the challenges of specifying the active ingredients in the complex interventions that are widely used in rehabilitation, and present an illustration of 1 approach to defining treatments via the learning mechanisms that underlie them. Issues related to treatment implementation are also discussed, including therapist allocation and training, and assessment of treatment fidelity. Finally we consider 2 statistical topics of particular importance to many rehabilitation trials: the use of multiple or composite outcomes, and factors that must be weighed in estimating sample size for clinical trials.

  9. 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

  10. Infants, mothers, and dyadic contributions to stability and prediction of social stress response at 6 months.

    PubMed

    Provenzi, Livio; Olson, Karen L; Montirosso, Rosario; Tronick, Ed

    2016-01-01

    The study of infants' interactive style and social stress response to repeated stress exposures is of great interest for developmental and clinical psychologists. Stable maternal and dyadic behavior is critical to sustain infants' development of an adaptive social stress response, but the association between infants' interactive style and social stress response has received scant attention in previous literature. In the present article, overtime stability of infant, maternal, and dyadic behaviors was measured across 2 social stress (i.e., Face-to-Face Still-Face, FFSF) exposures, separated by 15 days. Moreover, infant, maternal, and dyadic behaviors were simultaneously assessed as predictors of infants' social stress to both FFSF exposures. Eighty-one mother-infant dyads underwent the FFSF twice, at 6 months (Exposure 1: the first social stress) and at 6 months and 15 days (Exposure 2: repeated social stress). Infant and mother behavior and dyadic synchrony were microanalytically coded. Overall, individual behavioral stability emerged between FFSF exposures. Infants' response to the first stress was predicted by infant behavior during Exposure 1 Play. Infants' response to the repeated social stress was predicted by infants' response to the first exposure to the Still-Face and by infants' behavior and dyadic synchrony during Exposure 2 Play. Findings reveal stability for individual, but not for dyadic, behavior between 2 social stress exposures at 6 months. Infants' response to repeated social stress was predicted by infants' earlier stress response, infants' own behavior in play, and dyadic synchrony. No predictive effects of maternal behavior were found. Insights for research and clinical work are discussed.

  11. Infants, mothers, and dyadic contributions to stability and prediction of social stress response at 6 months.

    PubMed

    Provenzi, Livio; Olson, Karen L; Montirosso, Rosario; Tronick, Ed

    2016-01-01

    The study of infants' interactive style and social stress response to repeated stress exposures is of great interest for developmental and clinical psychologists. Stable maternal and dyadic behavior is critical to sustain infants' development of an adaptive social stress response, but the association between infants' interactive style and social stress response has received scant attention in previous literature. In the present article, overtime stability of infant, maternal, and dyadic behaviors was measured across 2 social stress (i.e., Face-to-Face Still-Face, FFSF) exposures, separated by 15 days. Moreover, infant, maternal, and dyadic behaviors were simultaneously assessed as predictors of infants' social stress to both FFSF exposures. Eighty-one mother-infant dyads underwent the FFSF twice, at 6 months (Exposure 1: the first social stress) and at 6 months and 15 days (Exposure 2: repeated social stress). Infant and mother behavior and dyadic synchrony were microanalytically coded. Overall, individual behavioral stability emerged between FFSF exposures. Infants' response to the first stress was predicted by infant behavior during Exposure 1 Play. Infants' response to the repeated social stress was predicted by infants' response to the first exposure to the Still-Face and by infants' behavior and dyadic synchrony during Exposure 2 Play. Findings reveal stability for individual, but not for dyadic, behavior between 2 social stress exposures at 6 months. Infants' response to repeated social stress was predicted by infants' earlier stress response, infants' own behavior in play, and dyadic synchrony. No predictive effects of maternal behavior were found. Insights for research and clinical work are discussed. PMID:26569560

  12. Are Parents of Preschool Children Inclined to Give Consent for Participation in Nutritional Clinical Trials?

    PubMed Central

    Patel, Dipen Vasudev; Phatak, Ajay Gajanan

    2016-01-01

    Objective Micronutrient deficiencies can lead to anemia, growth restriction, and poor motor and cognitive development. A clinical trial was planned to assess the impact of nutritional supplementation on cognitive measures in preschool children. Conducting clinical trials in children is difficult due to underlying laws, hesitation of the research community, and difficult enrollment. We carried out a questionnaire-based feasibility survey to assess the interest of parents towards participation in such a nutrition-based study. Methods After approval from the Institutional Human Research Ethics Committee, the principals of four kindergarten schools at Vallabh Vidyanagar, Anand, Gujarat, India consented to participate. Children at the participating schools were distributed a consent form and pre-tested questionnaire, to be taken home for parents to sign, fill and return. Results Out of a total of 1049 consent forms and questionnaires distributed, 602 (57.39%) signed and filled forms were returned. Despite fair awareness regarding the need of research, parents’ willingness to involve their children in a 6 month duration research study, not requiring invasive measures like blood pricks, was 180 (29.9%). Nearly half (250, 41.5%) did not respond and more than a quarter (172, 28.6%) declined participation on behalf of their children. Conclusion The interest level of a pre-school child's parents for participation of the child in a nutrition intervention study evaluating cognitive measures like memory is low. Understanding the study population’s motivating and inhibiting factors leading to decreased participation in clinical trials is necessary to facilitate the creation of a pertinent evidence base. PMID:27732680

  13. Establishing a clinical trials network in nephrology: experience of the Australasian Kidney Trials Network

    PubMed Central

    Morrish, Alicia T; Hawley, Carmel M; Johnson, David W; Badve, Sunil V; Perkovic, Vlado; Reidlinger, Donna M; Cass, Alan

    2014-01-01

    Chronic kidney disease is a major public health problem globally. Despite this, there are fewer high-quality, high-impact clinical trials in nephrology than other internal medicine specialties, which has led to large gaps in evidence. To address this deficiency, the Australasian Kidney Trials Network, a Collaborative Research Group, was formed in 2005. Since then, the Network has provided infrastructure and expertise to conduct patient-focused high-quality, investigator-initiated clinical trials in nephrology. The Network has not only been successful in engaging the nephrology community in Australia and New Zealand but also in forming collaborations with leading researchers from other countries. This article describes the establishment, development, and functions of the Network. The article also discusses the current and future funding strategies to ensure uninterrupted conduct of much needed clinical trials in nephrology to improve the outcomes of patients affected by kidney diseases with cost-effective interventions. PMID:24088955

  14. Next-Generation Sequencing to Guide Clinical Trials

    PubMed Central

    Siu, Lillian L.; Conley, Barbara A.; Boerner, Scott; LoRusso, Patricia M.

    2015-01-01

    Rapidly accruing knowledge of the mutational landscape of malignant neoplasms, the increasing facility of massively parallel genomic sequencing, and the availability of drugs targeting many “driver” molecular abnormalities have spurred the oncologic community to consider how to use these new tools to improve cancer treatment. In order to assure that assignment of patients to a particular targeted treatment is likely to be beneficial to the patient, it will be necessary to conduct appropriate clinical research. It is clear that clinical (histology, stage) eligibility criteria are not sufficient for most clinical trials using agents that target mutations that are present in only a minority of patients. Recently, several clinical trial designs have been suggested to test the benefit of targeted treatment in molecular and/or clinical subgroups of patients. However, challenges remain in the implementation of such trials, including choice of assay, levels of evidence regarding gene variants, tumor heterogeneity, identifying resistance mechanisms, the necessity of screening large numbers of patients, infrastructure needs, and collaboration of investigators and industry. This article reviews current trial designs and discusses some of the considerations, advantages and drawbacks of designing clinical trials that depend on particular molecular variants as eligibility criteria. PMID:26473189

  15. 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

  16. 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.

  17. The placebo response in clinical trials: more questions than answers

    PubMed Central

    Enck, Paul; Klosterhalfen, Sibylle; Weimer, Katja; Horing, Björn; Zipfel, Stephan

    2011-01-01

    Meta-analyses and re-analyses of trial data have not been able to answer some of the essential questions that would allow prediction of placebo responses in clinical trials. We will confront these questions with current empirical evidence. The most important question asks whether the placebo response rates in the drug arm and in the placebo arm are equal. This ‘additive model’ is a general assumption in almost all placebo-controlled drug trials but has rarely been tested. Secondly, we would like to address whether the placebo response is a function of the likelihood of receiving drug/placebo. Evidence suggests that the number of study arms in a trial may determine the size of the placebo and the drug response. Thirdly, we ask what the size of the placebo response is in ‘comparator’ studies with a direct comparison of a (novel) drug against another drug. Meta-analytic and experimental evidence suggests that comparator studies may produce higher placebo response rates when compared with placebo-controlled trials. Finally, we address the placebo response rate outside the laboratory and outside of trials in clinical routine. This question poses a serious challenge whether the drug response in trials can be taken as evidence of drug effects in clinical routine. PMID:21576146

  18. Methodological quality and reporting of ethical requirements in clinical trials

    PubMed Central

    Ruiz-Canela, M.; de Irala-Estevez, J.; Martinez-Gonzalez, M. A.; Gomez-Gracia, E.; Fernandez-Crehuet, J.

    2001-01-01

    Objectives—To assess the relationship between the approval of trials by a research ethics committee (REC) and the fact that informed consent from participants (ICP) was obtained, with the quality of study design and methods. Design—Systematic review using a standardised checklist. Main measures—Methodological and ethical issues of all trials published between 1993 and 1995 in the New England Journal of Medicine, the Lancet, the Journal of the American Medical Association and the British Medical Journal were studied. In addition, clinical trials conducted in Spain and published by at least one Spanish author during the same period in any other journal were also included. Results—We studied the published articles of 767 trials and found the following indicators of lower methodological quality to be independent predictors for failure to disclose REC approval or ICP: absence of concealment of allocation, lack of justification for unblinded trials, not using a treatment for the patients in the control group, absent information on statistical methods, not including sample size estimation, not establishing the rules to stop the trial, and omitting the presentation of a baseline comparison of groups Conclusion—Trials of higher methodological and scientific quality were more likely to provide information about their ethical aspects. Key Words: Clinical trials • informed consent • research ethics committees • research design PMID:11417024

  19. A sequential procedure for monitoring clinical trials against historical controls.

    PubMed

    Xiong, Xiaoping; Tan, Ming; Boyett, James

    2007-03-30

    In this paper, we develop a sequential procedure to monitor clinical trials against historical controls. When there is a strong ethical concern about randomizing patients to existing treatment because biological and medical evidence suggests that the new treatment is potentially superior to the existing one, or when the enrollment is too limited for randomization of subjects into experimental and control groups, one can monitor the trial sequentially against historical controls if the historical data with required quality and sample size are available to form a valid reference for the trial. This design of trial is sometimes the only alternative to a randomized phase III trial design that is intended but not feasible in situations such as above. Monitoring this type of clinical trial leads to a statistical problem of comparing two population means in a situation in which data from one population are sequentially collected and compared with all data from the other population at each interim look. The proposed sequential procedures is based on the sequential conditional probability ratio test (SCPRT) by which the conclusion of the sequential test would be virtually the same as that arrived at by a non-sequential test based on all data at the planned end of the trial. We develop the sequential procedure by proposing a Brownian motion that emulates the test statistic, and then proposing an SCPRT that is adapted to the special properties of the trial. PMID:16900551

  20. 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

  1. An Ongoing Randomized Clinical Trial in Dysphagia

    ERIC Educational Resources Information Center

    Robbins, JoAnne; Hind, Jackie; Logemann, Jerilyn

    2004-01-01

    Most of us who have clinical practices firmly contend that the treatments we provide cause beneficial changes in the lives of our patients. Indeed, our clinical experience engenders strong convictions to the point of believing that withholding treatment creates ethical violations. Intellectually, however, we must recognize that the value of…

  2. Clinical trial design in the neurocritical care unit.

    PubMed

    Hall, C E; Mirski, M; Palesch, Y Y; Diringer, M N; Qureshi, A I; Robertson, C S; Geocadin, R; Wijman, C A C; Le Roux, P D; Suarez, Jose I

    2012-02-01

    Clinical trials provide a robust mechanism to advance science and change clinical practice across the widest possible spectrum. Fundamental in the Neurocritical Care Society's mission is to promote Quality Patient Care by identifying and implementing best medical practices for acute neurological disorders that are consistent with the current scientific knowledge. The next logical step will be to foster rapid growth of our scientific body of evidence, to establish and disseminate these best practices. In this manuscript, five invited experts were impaneled to address questions, identified by the conference organizing committee as fundamental issues for the design of clinical trials in the neurological intensive care unit setting. PMID:21792753

  3. Supporting grid-based clinical trials in Scotland.

    PubMed

    Sinnott, R O; Stell, A J; Ajayi, O

    2008-06-01

    A computational infrastructure to underpin complex clinical trials and medical population studies is highly desirable. This should allow access to a range of distributed clinical data sets; support the efficient processing and analysis of the data obtained; have security at its heart; and ensure that authorized individuals are able to see privileged data and no more. Each clinical trial has its own requirements on data sets and how they are used; hence a reusable and flexible framework offers many advantages. The MRC funded Virtual Organisations for Trials and Epidemiological Studies (VOTES) is a collaborative project involving several UK universities specifically to explore this space. This article presents the experiences of developing the Scottish component of this nationwide infrastructure, by the National e-Science Centre (NeSC) based at the University of Glasgow, and the issues inherent in accessing and using the clinical data sets in a flexible, dynamic and secure manner. PMID:18477596

  4. Supporting grid-based clinical trials in Scotland.

    PubMed

    Sinnott, R O; Stell, A J; Ajayi, O

    2008-06-01

    A computational infrastructure to underpin complex clinical trials and medical population studies is highly desirable. This should allow access to a range of distributed clinical data sets; support the efficient processing and analysis of the data obtained; have security at its heart; and ensure that authorized individuals are able to see privileged data and no more. Each clinical trial has its own requirements on data sets and how they are used; hence a reusable and flexible framework offers many advantages. The MRC funded Virtual Organisations for Trials and Epidemiological Studies (VOTES) is a collaborative project involving several UK universities specifically to explore this space. This article presents the experiences of developing the Scottish component of this nationwide infrastructure, by the National e-Science Centre (NeSC) based at the University of Glasgow, and the issues inherent in accessing and using the clinical data sets in a flexible, dynamic and secure manner.

  5. The Effectiveness of Individualized Acupuncture Protocols in the Treatment of Gulf War Illness: A Pragmatic Randomized Clinical Trial

    PubMed Central

    Conboy, Lisa; Gerke, Travis; Hsu, Kai-Yin; St John, Meredith; Goldstein, Marc; Schnyer, Rosa

    2016-01-01

    Background Gulf War Illness is a Complex Medical Illness characterized by multiple symptoms, including fatigue, sleep and mood disturbances, cognitive dysfunction, and musculoskeletal pain affecting veterans of the first Gulf War. No standard of care treatment exists. Methods This pragmatic Randomized Clinical Trial tested the effects of individualized acupuncture treatments offered in extant acupuncture practices in the community; practitioners had at least 5 years of experience plus additional training provided by the study. Veterans with diagnosed symptoms of Gulf War Illness were randomized to either six months of biweekly acupuncture treatments (group 1, n = 52) or 2 months of waitlist followed by weekly acupuncture treatments (group 2, n = 52). Measurements were taken at baseline, 2, 4 and 6 months. The primary outcome is the SF-36 physical component scale score (SF-36P) and the secondary outcome is the McGill Pain scale. Results Of the 104 subjects who underwent randomization, 85 completed the protocol (82%). A clinically and statistically significant average improvement of 9.4 points (p = 0.03) in the SF-36P was observed for group 1 at month 6 compared to group 2, adjusting for baseline pain. The secondary outcome of McGill pain index produced similar results; at 6 months, group 1 was estimated to experience a reduction of approximately 3.6 points (p = 0.04) compared to group 2. Conclusions Individualized acupuncture treatment of sufficient dose appears to offer significant relief of physical disability and pain for veterans with Gulf War Illness. This work was supported by the Office of the Assistant Secretary of Defense for Health Affairs through the Gulf War Illness Research Program under Award No. W81XWH-09-2-0064. Opinions, interpretations, conclusions and recommendations are those of the author and are not necessarily endorsed by the Department of Defense. Trial Registration ClinicalTrials.gov NCT01305811 PMID:27031099

  6. 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

  7. 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.

  8. Effectiveness of Core Stability Exercises and Recovery Myofascial Release Massage on Fatigue in Breast Cancer Survivors: A Randomized Controlled Clinical Trial

    PubMed Central

    Cantarero-Villanueva, Irene; Fernández-Lao, Carolina; del Moral-Avila, Rosario; Fernández-de-las-Peñas, César; Feriche-Fernández-Castanys, María Belén; Arroyo-Morales, Manuel

    2012-01-01

    The purpose of the present paper was to evaluate the effects of an 8-week multimodal program focused on core stability exercises and recovery massage with DVD support for a 6-month period in physical and psychological outcomes in breast cancer survivors. A randomized controlled clinical trial was performed. Seventy-eight (n = 78) breast cancer survivors were assigned to experimental (core stability exercises plus massage-myofascial release) and control (usual health care) groups. The intervention period was 8 weeks. Mood state, fatigue, trunk curl endurance, and leg strength were determined at baseline, after the last treatment session, and at 6 months of followup. Immediately after treatment and at 6 months, fatigue, mood state, trunk curl endurance, and leg strength exhibited greater improvement within the experimental group compared to placebo group. This paper showed that a multimodal program focused on core stability exercises and massage reduced fatigue, tension, depression, and improved vigor and muscle strength after intervention and 6 months after discharge. PMID:21792370

  9. Effectiveness of core stability exercises and recovery myofascial release massage on fatigue in breast cancer survivors: a randomized controlled clinical trial.

    PubMed

    Cantarero-Villanueva, Irene; Fernández-Lao, Carolina; Del Moral-Avila, Rosario; Fernández-de-Las-Peñas, César; Feriche-Fernández-Castanys, María Belén; Arroyo-Morales, Manuel

    2012-01-01

    The purpose of the present paper was to evaluate the effects of an 8-week multimodal program focused on core stability exercises and recovery massage with DVD support for a 6-month period in physical and psychological outcomes in breast cancer survivors. A randomized controlled clinical trial was performed. Seventy-eight (n = 78) breast cancer survivors were assigned to experimental (core stability exercises plus massage-myofascial release) and control (usual health care) groups. The intervention period was 8 weeks. Mood state, fatigue, trunk curl endurance, and leg strength were determined at baseline, after the last treatment session, and at 6 months of followup. Immediately after treatment and at 6 months, fatigue, mood state, trunk curl endurance, and leg strength exhibited greater improvement within the experimental group compared to placebo group. This paper showed that a multimodal program focused on core stability exercises and massage reduced fatigue, tension, depression, and improved vigor and muscle strength after intervention and 6 months after discharge. PMID:21792370

  10. Quadriceps neural alterations in anterior cruciate ligament reconstructed patients: A 6-month longitudinal investigation.

    PubMed

    Lepley, A S; Gribble, P A; Thomas, A C; Tevald, M A; Sohn, D H; Pietrosimone, B G

    2015-12-01

    The purpose of this investigation was to evaluate differences in quadriceps corticospinal excitability, spinal-reflexive excitability, strength, and voluntary activation before, 2 weeks post and 6 months post-anterior cruciate ligament reconstruction (ACLr). This longitudinal, case-control investigation examined 20 patients scheduled for ACLr (11 females, 9 males; age: 20.9 ± 4.4 years; height:172.4 ± 7.5 cm; weight:76.2 ± 11.8 kg) and 20 healthy controls (11 females, 9 males; age:21.7 ± 3.7 years; height: 173.7 ± 9.9 cm; weight: 76.1 ± 19.7 kg). Maximal voluntary isometric contractions (MVIC), central activation ratio (CAR), normalized Hoffmann spinal reflexes, active motor threshold (AMT), and normalized motor-evoked potential (MEP) amplitudes at 120% of AMT were measured in the quadriceps muscle at the specific time points. ACLr patients demonstrated bilateral reductions in spinal-reflexive excitability compared with controls before surgery (P = 0.02) and 2 weeks post-surgery (P ≤ 0.001). ACLr patients demonstrated higher AMT at 6 months post-surgery (P ≤ 0.001) in both limbs. No MEP differences were detected. Quadriceps MVIC and CAR were lower in both limbs of the ACLr group before surgery and 6 months post-surgery (P ≤ 0.05) compared with controls. Diminished excitability of spinal-reflexive and corticospinal pathways are present at different times following ACLr and occur in combination with clinical deficits in quadriceps strength and activation. Early rehabilitation strategies targeting spinal-reflexive excitability may help improve postoperative outcomes, while later-stage rehabilitation may benefit from therapeutic techniques aimed at improving corticospinal excitability.

  11. 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

  12. Volunteering for Clinical Trials Can Help Improve Health Care for Everyone

    MedlinePlus

    ... Trials Volunteering for Clinical Trials Can Help Improve Health Care for Everyone Past Issues / Fall 2010 Table of ... Research / Volunteering for Clinical Trials Can Help Improve Health Care for Everyone Fall 2010 Issue: Volume 5 Number ...

  13. Beyond the Randomized Controlled Trial: A Review of Alternatives in mHealth Clinical Trial Methods

    PubMed Central

    Wiljer, David; Cafazzo, Joseph A

    2016-01-01

    Background Randomized controlled trials (RCTs) have long been considered the primary research study design capable of eliciting causal relationships between health interventions and consequent outcomes. However, with a prolonged duration from recruitment to publication, high-cost trial implementation, and a rigid trial protocol, RCTs are perceived as an impractical evaluation methodology for most mHealth apps. Objective Given the recent development of alternative evaluation methodologies and tools to automate mHealth research, we sought to determine the breadth of these methods and the extent that they were being used in clinical trials. Methods We conducted a review of the ClinicalTrials.gov registry to identify and examine current clinical trials involving mHealth apps and retrieved relevant trials registered between November 2014 and November 2015. Results Of the 137 trials identified, 71 were found to meet inclusion criteria. The majority used a randomized controlled trial design (80%, 57/71). Study designs included 36 two-group pretest-posttest control group comparisons (51%, 36/71), 16 posttest-only control group comparisons (23%, 16/71), 7 one-group pretest-posttest designs (10%, 7/71), 2 one-shot case study designs (3%, 2/71), and 2 static-group comparisons (3%, 2/71). A total of 17 trials included a qualitative component to their methodology (24%, 17/71). Complete trial data collection required 20 months on average to complete (mean 21, SD 12). For trials with a total duration of 2 years or more (31%, 22/71), the average time from recruitment to complete data collection (mean 35 months, SD 10) was 2 years longer than the average time required to collect primary data (mean 11, SD 8). Trials had a moderate sample size of 112 participants. Two trials were conducted online (3%, 2/71) and 7 trials collected data continuously (10%, 7/68). Onsite study implementation was heavily favored (97%, 69/71). Trials with four data collection points had a longer study

  14. 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.

  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. Brain Connectivity Predicts Placebo Response across Chronic Pain Clinical Trials

    PubMed Central

    Tétreault, Pascal; Mansour, Ali; Vachon-Presseau, Etienne; Schnitzer, Thomas J.; Apkarian, A. Vania

    2016-01-01

    Placebo response in the clinical trial setting is poorly understood and alleged to be driven by statistical confounds, and its biological underpinnings are questioned. Here we identified and validated that clinical placebo response is predictable from resting-state functional magnetic-resonance-imaging (fMRI) brain connectivity. This also led to discovering a brain region predicting active drug response and demonstrating the adverse effect of active drug interfering with placebo analgesia. Chronic knee osteoarthritis (OA) pain patients (n = 56) underwent pretreatment brain scans in two clinical trials. Study 1 (n = 17) was a 2-wk single-blinded placebo pill trial. Study 2 (n = 39) was a 3-mo double-blinded randomized trial comparing placebo pill to duloxetine. Study 3, which was conducted in additional knee OA pain patients (n = 42), was observational. fMRI-derived brain connectivity maps in study 1 were contrasted between placebo responders and nonresponders and compared to healthy controls (n = 20). Study 2 validated the primary biomarker and identified a brain region predicting drug response. In both studies, approximately half of the participants exhibited analgesia with placebo treatment. In study 1, right midfrontal gyrus connectivity best identified placebo responders. In study 2, the same measure identified placebo responders (95% correct) and predicted the magnitude of placebo’s effectiveness. By subtracting away linearly modeled placebo analgesia from duloxetine response, we uncovered in 6/19 participants a tendency of duloxetine enhancing predicted placebo response, while in another 6/19, we uncovered a tendency for duloxetine to diminish it. Moreover, the approach led to discovering that right parahippocampus gyrus connectivity predicts drug analgesia after correcting for modeled placebo-related analgesia. Our evidence is consistent with clinical placebo response having biological underpinnings and shows that the method can also reveal that active

  17. 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

  18. [The management in clinical trials of pharmacological agents].

    PubMed

    Kurmanova, L V

    1995-01-01

    The author analyzes the experience gained by foreign countries in the creation of a new management system in all spheres of public health, including clinical trials and use of drugs. A term "High-Quality Clinical Practice" is used in the European Community, reflecting the standard or the norm of clinical studies and designed as a complex of regulations for the organization and implementation of clinical studies. High-Quality Clinical Practice implies all reasonable measures providing the accuracy of experimental data and guarantees the rights of the participants in the trials. Studies carried out in conformity with the requirements of High-Quality Clinical Practice bring about reliable results and permit the pharmaceutical companies and public health organs use these data.

  19. 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

  20. Real-Time Enrollment Dashboard For Multisite Clinical Trials

    PubMed Central

    Mattingly, William A; Kelley, Robert R; Wiemken, Timothy L; Chariker, Julia H; Peyrani, Paula; Guinn, Brian E; Binford, Laura E; Buckner, Kimberley; Ramirez, Julio

    2015-01-01

    Objective Achieving patient recruitment goals are critical for the successful completion of a clinical trial. We designed and developed a web-based dashboard for assisting in the management of clinical trial screening and enrollment. Materials and Methods We use the dashboard to assist in the management of two observational studies of community-acquired pneumonia. Clinical research associates and managers using the dashboard were surveyed to determine its effectiveness as compared with traditional direct communication. Results The dashboard has been in use since it was first introduced in May of 2014. Of the 23 staff responding to the survey, 77% felt that it was easier or much easier to use the dashboard for communication than to use direct communication. Conclusion We have designed and implemented a visualization dashboard for managing multi-site clinical trial enrollment in two community acquired pneumonia studies. Information dashboards are a useful tool for clinical trial management. They can be used as a standalone trial information tool or included into a larger management system. PMID:26878068

  1. A guide to organizing a multicenter clinical trial.

    PubMed

    Chung, Kevin C; Song, Jae W

    2010-08-01

    Multicenter clinical trials are important research tools. Planning a multicenter clinical trial is a long and arduous task that requires substantial preparation time. In this guide, the authors discuss the steps used to plan a multicenter clinical trial. A preplanning phase, which involves formulating and refining a research question and conducting pilot studies, is detailed, and the planning phase, which involves the acquisition of funding to support the coordination and preparation of a multicenter clinical trial, culminating in the submission of an R01 grant, is described. An essential asset to planning a multicenter clinical trial is the fluidity with which all collaborators work together toward a common vision. The philosophy among collaborators should be consensus and commitment and is emphasized by the development of a consensus assisted study protocol. Most important are the recruitment of centers and co-investigators who are dedicated, collaborative, and selfless in the team effort to achieve goals that cannot be reached by a single-center effort.

  2. Defining, monitoring and combining safety information in clinical trials.

    PubMed

    Enas, G G; Goldstein, D J

    Assessment of clinical trial safety data for industry, regulatory agencies, medical practitioners and patients requires definition and measurement, monitoring, and overall analysis. Prospective 'safety' definitions and reliable measurement tools reduce inefficient data collection and improve the validity of resulting analyses. Statistical tools can help investigators monitor safety data from controlled clinical trials and help improve post-marketing surveillance. Also, when evaluating overall safety, one needs to assess all available information by combining information from many trials and other sources. Planning for this combined assessment, incorporating flexibility to assess unanticipated yet important nuances in individual trials, may be more important than the actual statistical analysis method used. A keen awareness of the future needs of consumers of this information is quite important. Some current proposals to combine safety information will be discussed.

  3. How Have Cancer Clinical Trial Eligibility Criteria Evolved Over Time?

    PubMed Central

    Yaman, Anil; Chakrabarti, Shreya; Sen, Anando; Weng, Chunhua

    2016-01-01

    Knowledge reuse of cancer trial designs may benefit from a temporal understanding of the evolution of the target populations of cancer studies over time. Therefore, we conducted a retrospective analysis of the trends of cancer trial eligibility criteria between 1999 and 2014. The yearly distributions of eligibility concepts for chemicals and drugs, procedures, observations, and medical conditions extracted from free-text eligibility criteria of 32,000 clinical trials for 89 cancer types were analyzed. We identified the concepts that trend upwards or downwards in all or selected cancer types, and the concepts that show anomalous trends for some cancers. Later, concept trends were studied in a disease-specific manner and illustrated for breast cancer. Criteria trends observed in this study are also validated and interpreted using evidence from the existing medical literature. This study contributes a method for concept trend analysis and original knowledge of the trends in cancer clinical trial eligibility criteria. PMID:27570681

  4. Potential of adaptive clinical trial designs in pharmacogenetic research.

    PubMed

    van der Baan, Frederieke H; Knol, Mirjam J; Klungel, Olaf H; Egberts, Antoine Cg; Grobbee, Diederick E; Roes, Kit C B

    2012-04-01

    Adaptive trial designs can be beneficial in pharmacogenetic research when prior uncertainty exists regarding the exact role and clinical relevance of genetic variability in drug response. This type of design enables us to learn about the effect of the genetic variability on drug response and to immediately use this information for the remainder of the study. For different types of adaptive trial designs, we discuss when and how the designs are suitable for pharmacogenetic research: adaptation of randomization, adaptation of patient enrollment and adaptive enrichment. To illustrate the potential benefits of an adaptive design over a fixed design, we simulated an adaptive trial based on the results of the IPASS trial. With a simple model we show that for this example an adaptive enrichment design would have led to a smaller trial, with less EGF receptor mutation-negative patients unnecessarily exposed to the drug, without compromising the α level or reducing power. PMID:22462749

  5. [Facing the unreliability of clinical trials literature].

    PubMed

    Jefferson, Tom

    2016-01-01

    Journal publications of randomized controlled trials ("literature") have so far formed the basis for evidence of the effects of pharmaceuticals and biologicals. In the last decade, progressively accumulating evidence has shown that literature is affected by reporting bias with evident implications for the reliability of any decision based on literature or its derivatives such as research synthesis. Another important factor is the growing body of evidence of the fragility of editorial quality control mechanisms in biomedicine ande their easy exploitation for marketing purposes in the symbiosis between publishing and the pharmaceutical industry. Regulatory documents are probably more reliable than currently accessible other sources but there are many severe limitations to the long-term use of regulatory documents for research synthesis and decision-making. Instead of trying to reform the fields of research, industry, government, regulation and publishing, I propose basing public health decisions and reimbursement of any important interventions on independent trials and studies following the model pioneered by the Mario Negri Institute of Pharmacological Research. PMID:26901365

  6. [The Characteristics and Management of Medical Equipment Clinical Trials in Hospital].

    PubMed

    Zou, Shuaionc; Huang, Xuxia; Li, Yeyu; Huang, Qian; Fang, Hengying

    2015-03-01

    In this paper, we analyse the general information of medical equipment clinical trials by clinical trial process management experience to elaborate the characteristics of the medical equipment clinical trials and the existent problems in our hospital in 10 years. We propose corresponding countermeasures to ensure the quality of medical tests, and improve the management of medical equipment clinical trials in hospital.

  7. Stereotactic Body Radiotherapy for Localized Prostate Cancer: Interim Results of a Prospective Phase II Clinical Trial

    SciTech Connect

    King, Christopher R. Brooks, James D.; Gill, Harcharan; Pawlicki, Todd; Cotrutz, Cristian; Presti, Joseph C.

    2009-03-15

    Purpose: The radiobiology of prostate cancer favors a hypofractionated dose regimen. We report results of a prospective Phase II clinical trial of stereotactic body radiotherapy (SBRT) for localized prostate cancer. Methods and Materials: Forty-one low-risk prostate cancer patients with 6 months' minimum follow-up received 36.25 Gy in five fractions of 7.25 Gy with image-guided SBRT alone using the CyberKnife. The early (<3 months) and late (>6 months) urinary and rectal toxicities were assessed using validated quality of life questionnaires (International Prostate Symptom Score, Expanded Prostate Cancer Index Composite) and the Radiation Therapy Oncology Group (RTOG) toxicity criteria. Patterns of prostate-specific antigen (PSA) response are analyzed. Results: The median follow-up was 33 months. There were no RTOG Grade 4 acute or late rectal/urinary complications. There were 2 patients with RTOG Grade 3 late urinary toxicity and none with RTOG Grade 3 rectal complications. A reduced rate of severe rectal toxicities was observed with every-other-day vs. 5 consecutive days treatment regimen (0% vs. 38%, p = 0.0035). A benign PSA bounce (median, 0.4 ng/mL) was observed in 12 patients (29%) occurring at 18 months (median) after treatment. At last follow-up, no patient has had a PSA failure regardless of biochemical failure definition. Of 32 patients with 12 months minimum follow-up, 25 patients (78%) achieved a PSA nadir {<=}0.4 ng/mL. A PSA decline to progressively lower nadirs up to 3 years after treatment was observed. Conclusions: The early and late toxicity profile and PSA response for prostate SBRT are highly encouraging. Continued accrual and follow-up will be necessary to confirm durable biochemical control rates and low toxicity profiles.

  8. Clinical Trial of Tailored Activity and Eating Newsletters with Older Rural Women

    PubMed Central

    Walker, Susan Noble; Pullen, Carol H.; Boeckner, Linda; Hageman, Patricia A.; Hertzog, Melody; Oberdorfer, Maureen K.; Rutledge, Matthew J.

    2009-01-01

    Background Unhealthy diet and lack of physical activity increase rural midlife and older women’s risk for chronic diseases and premature death, and they are behind urban residents in meeting Healthy People 2010 objectives. Objectives To compare a tailored intervention based on the Health Promotion Model (HPM) and a generic intervention to increase physical activity and healthy eating among rural women. Methods In a randomized by site community-based controlled clinical trial, Wellness for Women, 225 women aged 50 to 69 years were recruited in two similar rural areas. Over 12 months, women received by mail either 18 generic newsletters or 18 newsletters computer-tailored on HPM behavior-specific cognitions (benefits, barriers, self-efficacy, and interpersonal support), activity, and eating. Outcomes at 6 and 12 months included behavioral markers and biomarkers of physical activity and eating. Data were analyzed by repeated measures ANOVA and χ2 tests (α < .05). Results Both groups significantly increased stretching and strengthening exercise and fruit and vegetable servings and decreased % calories from fat, while only the tailored group increased ≥ moderate intensity activity and decreased % calories from saturated fat from baseline to 6 months. Both groups increased stretching and strengthening exercise, while only the tailored group increased ≥ moderate activity and fruit and vegetable servings and decreased % calories from fat from baseline to 12 months. Both groups had several changes in biomarkers over the study. A higher proportion of women receiving tailored newsletters met Healthy People 2010 criteria for ≥ moderate activity, fruit and vegetable servings, and % calories from fat at 12 months. Discussion Mailed computer-tailored and generic print newsletters facilitated the adoption of change in both activity and eating over 6 months. Tailored newsletters were more efficacious in facilitating change over 12 months. PMID:19289928

  9. Effects of growth hormone administration for 6 months on bone turnover and bone marrow fat in obese premenopausal women

    PubMed Central

    Bredella, Miriam A.; Gerweck, Anu V.; Barber, Lauren A.; Breggia, Anne; Rosen, Clifford J.; Torriani, Martin; Miller, Karen K.

    2014-01-01

    Purpose Abdominal adiposity is associated with low BMD and decreased growth hormone (GH) secretion, an important regulator of bone homeostasis. The purpose of our study was to determine the effects of a short course of GH on markers of bone turnover and bone marrow fat in premenopausal women with abdominal adiposity. Materials and Methods In a 6-month, randomized, double-blind, placebo-controlled trial we studied 79 abdominally obese premenopausal women (21–45y) who underwent daily sc injections of GH vs. placebo. Main outcome measures were body composition by DXA and CT, bone marrow fat by proton MR spectroscopy, P1NP, CTX, 25(OH)D, hsCRP, undercarboxylated osteocalcin (ucOC), preadipocyte factor 1 (Pref 1), apolipoprotein B (ApoB), and IGF-1. Results GH increased IGF-1, P1NP, 25(OH)D, ucOC, bone marrow fat and lean mass, and decreased abdominal fat, hsCRP, and ApoB compared with placebo (p<0.05). There was a trend toward an increase in CTX and Pref-1. Among all participants, 6-month increase in IGF-1 correlated with 6-month increase in P1NP (p=0.0005), suggesting that subjects with the greatest increases in IGF-1 experienced the greatest increases in bone formation. Six-month decrease in abdominal fat, hsCRP, and ApoB inversely predicted 6-month change in P1NP, and 6-month increase in lean mass and 25(OH)D positively predicted 6-month change in P1NP (p≤0.05), suggesting that subjects with greatest decreases in abdominal fat, inflammation and ApoB, and the greatest increases in lean mass and 25(OH)D experienced the greatest increases in bone formation. Six-month increase in bone marrow fat correlated with 6-month increase in P1NP (trend), suggesting that subjects with the greatest increases in bone formation experienced the greatest increases in bone marrow fat. Forward stepwise regression analysis indicated that increase in lean mass and decrease in abdominal fat were positive predictors of P1NP. When IGF-1 was added to the model, it became the only predictor

  10. Clinical Trials for Rare Lung Diseases: Lessons from Lymphangioleiomyomatosis

    PubMed Central

    McCormack, Francis X.

    2010-01-01

    Abstract Lymphangioleiomyomatosis (LAM) is a rare, slowly progressive neoplasm that causes gradual but often life-threatening cystic destruction of the lung. Advances in our understanding of the molecular and cellular pathogenesis have LAM have identified a number of promising targets for testing in therapeutic trials. However, the design, prioritization, organization, and implementation of clinical trials in rare lung diseases poses unique challenges, including geographically disperse populations, sluggish enrollment, off- label drug use, burdensome regulations, and paucity of validated surrogate endpoints. PMID:20235889

  11. Incentives to Participate in Clinical Trials: Practical and Ethical Considerations

    PubMed Central

    Bernstein, Steven L.; Feldman, James

    2015-01-01

    Background Clinical trials often offer incentives to encourage individuals to enroll, and to enhance follow-up. The scope and nature of incentives used in ED-based trials is unknown. Objectives To characterize the quantity and quality of incentives and other forms of compensation used in clinical trials of human subjects recruited in U.S. EDs. A secondary goal is to provide an historical and ethical analysis of the use of incentives in clinical trials. Methods We reviewed English-language randomized clinical trials conducted in U.S. emergency departments from 2009-2013. Full text of the studies was reviewed to identify whether incentives were used, their value, and timing. Funding source was noted as well. Data are presented with descriptive statistics. Results Of 1151 papers identified, 76 (6.6%) fit criteria for review. Of these, 7 (9.2%) provided incentive payments. A recently published eighth trial was included as well. The total cash value of incentives offered ranged from $10-195. Four studies offered payment at enrollment only. Incentives included cash, debit cards, and gift cards. Conclusion The use of financial incentives in ED-based trials is uncommon. Studies that employ incentives are generally extramurally funded, usually by a federal agency, and include waves of follow-up that continue after discharge from the ED. Payment size is modest. Incentives may improve recruitment and retention in ED-based trials, but authoritative data are lacking. Investigators need to take care to avoid incentives that may be coercive or unduly influence research participants. PMID:26095131

  12. Generalizability in two clinical trials of Lyme disease

    PubMed Central

    Cameron, Daniel J

    2006-01-01

    Objective To examine the generalizability of two National Institutes of Health (NIH)-funded double-blind randomized placebo-controlled clinical trials in patients with chronic Lyme disease and to determine whether selection factors resulted in the unfavorable outcomes. Design Epidemiologic review of the generalizability of two trials conducted by Klempner et al. This paper considers whether the study group was representative of the general chronic Lyme disease population. Results In their article in The New England Journal of Medicine, Klempner et al. failed to discuss the limitations of their clinical trials. This epidemiologic review argues that their results are not generalizable to the overall Lyme disease population. The treatment failure reported by the authors may be the result of enrolling patients who remained ill after an average of 4.7 years and an average of 3 previous courses of treatment. The poor outcome cited in these trials may be explained by having selected patients who had undergone delayed treatment or multiple treatments unsuccessfully. These selection factors were not addressed by the studies' authors, nor have they been discussed by reviewers. The trials have been over-interpreted by the NIH and widely publicized in a press release. The results have been extrapolated to other groups of Lyme disease patients by commentators, by a case discussant in an influential medical journal, and by health insurance companies to deny antibiotic treatment. Conclusion The Klempner et al. trials are assumed to be internally valid based on a Randomized Control Trial (RCT) design. However, this review argues that the trials have limited generalizability beyond the select group of patients with characteristics like those in the trial. Applying the findings to target populations with characteristics that differ from those included in these trials is inappropriate and may limit options for chronic Lyme disease patients who might benefit from antibiotic treatment

  13. 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.

  14. 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

  15. A novel synthetic material for spinal fusion: a prospective clinical trial of porous bioactive titanium metal for lumbar interbody fusion.

    PubMed

    Fujibayashi, Shunsuke; Takemoto, Mitsuru; Neo, Masashi; Matsushita, Tomiharu; Kokubo, Tadashi; Doi, Kenji; Ito, Tatsuya; Shimizu, Akira; Nakamura, Takashi

    2011-09-01

    The objective of this study was to establish the efficacy and safety of porous bioactive titanium metal for use in a spinal fusion device, based on a prospective human clinical trial. A high-strength spinal interbody fusion device was manufactured from porous titanium metal. A bioactive surface was produced by simple chemical and thermal treatment. Five patients with unstable lumbar spine disease were treated surgically using this device in a clinical trial approved by our Ethics Review Committee and the University Hospital Medical Information Network. Clinical and radiological results were reported at the minimum follow-up period of 1 year. The optimal mechanical strength and interconnected structure of the porous titanium metal were adjusted for the device. The whole surface of porous titanium metal was treated uniformly and its bioactive ability was confirmed before clinical use. Successful bony union was achieved in all cases within 6 months without the need for autologous iliac crest bone grafting. Two specific findings including an anchoring effect and gap filling were evident radiologically. All clinical parameters improved significantly after the operation and no adverse effects were encountered during the follow-up period. Although a larger and longer-term follow-up clinical study is mandatory to reach any firm conclusions, the study results show that this porous bioactive titanium metal is promising material for a spinal fusion device.

  16. Recruitment and Retention of Women for Clinical Leiomyoma Trials

    PubMed Central

    McCarthy-Keith, Desireé; Nurudeen, Sahadat; Armstrong, Alicia; Levens, Eric; Nieman, Lynnette K.

    2010-01-01

    Background Subject recruitment and retention in clinical leiomyoma trials is challenging. We evaluated strategies to increase patient enrollment and completion in leiomyoma trials. Materials and methods Randomized trials for treatment of symptomatic leiomyoma published from 2000 through 2008 were evaluated and thirteen trials were selected. Subject enrollment and completion rates, recruitment methods and reasons for patient drop-out were assessed. Results Recruitment by study personnel or clinic staff during evaluation for symptomatic leiomyoma was the most common strategy for enrollment. Additional methods included local media, internet postings and physician referrals. Seven to 85% of patients enrolled after screening, with a median enrollment of 70%. Sixty-five to 100% of patients completed the study after enrollment with a median completion rate of 89%. Reasons for drop-out at the screening stage included failure to meet inclusion criteria, patient refusal and patient preference for specific treatment. Commonly reported reasons for drop-out after enrollment were refusal of treatment following randomization, adverse reaction to study intervention and non-compliance with study protocol or follow-up visits. Conclusion Women with symptomatic uterine leiomyomas may be attracted to participate in leiomyoma trials, however desire for specific treatment and persistent symptoms following intervention may hinder their participation. Randomization to placebo treatment and stringent inclusion criteria appear to adversely impact accrual. A wide range of recruiting tactics is needed and media sources or direct mailings may prove particularly effective to improve subject recruitment and retention in clinical leiomyoma trials. PMID:19788933

  17. [Clinical trial data validation and user acceptance testing].

    PubMed

    Sun, Hua-long; Dai, Nan

    2015-11-01

    For pharmaceutical industries, clinical data is one of the most valuable deliverables. It is also the basis of analysis, submission, approval, labeling and marketing of a drug product. To ensure the integrity and reliability of clinical data, a scientific standardized quality control (QC) has to be established at each step of a clinical trial. Data validation is conducted to ensure the reasonability and compliance of clinical data by checking data quality before the data is statistically analyzed. This paper focuses on purpose of data validation, creation of data validation plan, rationale of data validation, types of data validation and performance of user acceptance testing on clinical database. PMID:26911047

  18. Alternative clinical trial design in neurocritical care.

    PubMed

    Lazaridis, Christos; Maas, Andrew I R; Souter, Michael J; Martin, Renee H; Chesnut, Randal M; DeSantis, Stacia M; Sung, Gene; Leroux, Peter D; Suarez, Jose I

    2015-06-01

    Neurocritical care involves the care of highly complex patients with combinations of physiologic derangements in the brain and in extracranial organs. The level of evidence underpinning treatment recommendations remains low due to a multitude of reasons including an incomplete understanding of the involved physiology; lack of good quality, prospective, standardized data; and the limited success of conventional randomized controlled trials. Comparative effectiveness research can provide alternative perspectives and methods to enhance knowledge and evidence within the field of neurocritical care; these include large international collaborations for generation and maintenance of high quality data, statistical methods that incorporate heterogeneity and individualize outcome prediction, and finally advanced bioinformatics that integrate large amounts of variable-source data into patient-specific phenotypes and trajectories. PMID:25894451

  19. Alternative clinical trial design in neurocritical care.

    PubMed

    Lazaridis, Christos; Maas, Andrew I R; Souter, Michael J; Martin, Renee H; Chesnut, Randal M; DeSantis, Stacia M; Sung, Gene; Leroux, Peter D; Suarez, Jose I

    2015-06-01

    Neurocritical care involves the care of highly complex patients with combinations of physiologic derangements in the brain and in extracranial organs. The level of evidence underpinning treatment recommendations remains low due to a multitude of reasons including an incomplete understanding of the involved physiology; lack of good quality, prospective, standardized data; and the limited success of conventional randomized controlled trials. Comparative effectiveness research can provide alternative perspectives and methods to enhance knowledge and evidence within the field of neurocritical care; these include large international collaborations for generation and maintenance of high quality data, statistical methods that incorporate heterogeneity and individualize outcome prediction, and finally advanced bioinformatics that integrate large amounts of variable-source data into patient-specific phenotypes and trajectories.

  20. Design of clinical trials in acute kidney injury: report from an NIDDK workshop on trial methodology.

    PubMed

    Palevsky, Paul M; Molitoris, Bruce A; Okusa, Mark D; Levin, Adeera; Waikar, Sushrut S; Wald, Ron; Chertow, Glenn M; Murray, Patrick T; Parikh, Chirag R; Shaw, Andrew D; Go, Alan S; Faubel, Sarah G; Kellum, John A; Chinchilli, Vernon M; Liu, Kathleen D; Cheung, Alfred K; Weisbord, Steven D; Chawla, Lakhmir S; Kaufman, James S; Devarajan, Prasad; Toto, Robert M; Hsu, Chi-yuan; Greene, Tom; Mehta, Ravindra L; Stokes, John B; Thompson, Aliza M; Thompson, B Taylor; Westenfelder, Christof S; Tumlin, James A; Warnock, David G; Shah, Sudhir V; Xie, Yining; Duggan, Emily G; Kimmel, Paul L; Star, Robert A

    2012-05-01

    Acute kidney injury (AKI) remains a complex clinical problem associated with significant short-term morbidity and mortality and lacking effective pharmacologic interventions. Patients with AKI experience longer-term risks for progressive chronic ESRD, which diminish patients' health-related quality of life and create a larger burden on the healthcare system. Although experimental models have yielded numerous promising agents, translation into clinical practice has been unsuccessful, possibly because of issues in clinical trial design, such as delayed drug administration, masking of therapeutic benefit by adverse events, and inadequate sample size. To address issues of clinical trial design, the National Institute of Diabetes and Digestive and Kidney Diseases sponsored a workshop titled "Clinical Trials in Acute Kidney Injury: Current Opportunities and Barriers" in December 2010. Workshop participants included representatives from academia, industry, and government agencies whose areas of expertise spanned basic science, clinical nephrology, critical care medicine, biostatistics, pharmacology, and drug development. This document summarizes the discussions of collaborative workgroups that addressed issues related to patient selection, study endpoints, the role of novel biomarkers, sample size and power calculations, and adverse events and pilot/feasibility studies in prevention and treatment of AKI. Companion articles outline the discussions of workgroups for model trials related to prevention or treatment of established AKI in different clinical settings, such as in patients with sepsis.

  1. The Egyptian clinical trials’ registry profile: Analysis of three trial registries (International Clinical Trials Registry Platform, Pan-African Clinical Trials Registry and clinicaltrials.gov)

    PubMed Central

    Zeeneldin, Ahmed A.; Taha, Fatma M.

    2015-01-01

    Registering clinical trials (CTs) in public domains enhances transparency, increases trust in research, improves participation and safeguards against publication bias. This work was done to study the profile of clinical research in Egypt in three CT registries with different scopes: the WHO International CT Registry Platform (ICTRP), the continental Pan-African CT Registry (PACTR) and the US clinicaltrials.gov (CTGR). In March 2014, ICTRP, PACTR and CTGR were searched for clinical studies conducted in Egypt. It was found that the number of studies conducted in Egypt (percentage) was 686 (0.30%) in ICTRP, 56 (11.3%) in PACTR and 548 (0.34%) in CTGR. Most studies were performed in universities and sponsored by university/organization, industry or individual researchers. Inclusion of adults from both genders predominated. The median number of participants per study in the three registries ranged between 63 and 155. The conditions researched differed among the three registries and study purpose was mostly treatment followed by prevention. Endpoints were mostly efficacy followed by safety. Observational:Interventional studies (i.e. clinical trials) represented 15.5%:84.5% in ICTRP, 0%:100% in PACTR and 16.4%:83.6% in CTGR. Most interventions were drugs or procedures. Observational studies were mostly prospective and cohort studies. Most CTs were phase 3 and tested drugs or procedures. Parallel group assignment and random allocation predominated. Blinding was implemented in many of trials and was mostly double-blind. We conclude that CTs from Egypt in trial registries are apparently low and do not accurately reflect clinical research conducted in Egypt or its potential. Development of an Egyptian CT registry is eagerly needed. Registering all Egyptian CTs in public domains is highly recommended. PMID:26843968

  2. Initial Readability Assessment of Clinical Trial Eligibility Criteria

    PubMed Central

    Kang, Tian; Elhadad, Noémie; Weng, Chunhua

    2015-01-01

    Various search engines are available to clinical trial seekers. However, it remains unknown how comprehensible clinical trial eligibility criteria used for recruitment are to a lay audience. This study initially investigated this problem. Readability of eligibility criteria was assessed according to (i) shallow and lexical characteristics through the use of an established, generic readability metric; (ii) syntactic characteristics through natural language processing techniques; and (iii) health terminological characteristics through an automated comparison to technical and lay health texts. We further stratified clinical trials according to various study characteristics (e.g., source country or study type) to understand potential factors influencing readability. Mainly caused by frequent use of technical jargons, a college reading level was found to be necessary to understand eligibility criteria text, a level much higher than the average literacy level of the general American population. The use of technical jargons should be minimized to simplify eligibility criteria text. PMID:26958204

  3. 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

  4. Strategies and Challenges in Clinical Trials Targeting Human Aging

    PubMed Central

    Newman, John C.; Milman, Sofiya; Hashmi, Shahrukh K.; Austad, Steve N.; Kirkland, James L.; Halter, Jeffrey B.

    2016-01-01

    Interventions that target fundamental aging processes have the potential to transform human health and health care. A variety of candidate drugs have emerged from basic and translational research that may target aging processes. Some of these drugs are already in clinical use for other purposes, such as metformin and rapamycin. However, designing clinical trials to test interventions that target the aging process poses a unique set of challenges. This paper summarizes the outcomes of an international meeting co-ordinated by the NIH-funded Geroscience Network to further the goal of developing a translational pipeline to move candidate compounds through clinical trials and ultimately into use. We review the evidence that some drugs already in clinical use may target fundamental aging processes. We discuss the design principles of clinical trials to test such interventions in humans, including study populations, interventions, and outcomes. As examples, we offer several scenarios for potential clinical trials centered on the concepts of health span (delayed multimorbidity and functional decline) and resilience (response to or recovery from an acute health stress). Finally, we describe how this discussion helped inform the design of the proposed Targeting Aging with Metformin study. PMID:27535968

  5. Effect of 6 months use of a dentifrice and oral rinse containing sanguinaria extract and zinc chloride upon the microflora of the dental plaque and oral soft tissues.

    PubMed

    Harper, D S; Mueller, L J; Fine, J B; Gordon, J; Laster, L L

    1990-06-01

    This study documented the effect upon the oral flora of twice daily brushing with a dentifrice containing 0.075% sanguinaria extract and 2% zinc chloride, followed by use of a mouthrinse containing 0.03% sanguinaria extract and 0.2% zinc chloride. Sixty subjects were randomly assigned to treatment or placebo groups and monitored in a 6-month double-blind clinical trial. Bacteriological samples from the tongue, buccal mucosa, and supra- and subgingival plaque were characterized at 0, 14, and 28 weeks. Microbiological monitoring showed no increases in populations of yeast, staphylococci, coliform organisms, or Pseudomonas. Total Gram-negative counts in supragingival plaque samples decreased 83% in the active group compared to a 232% increase for the control group. Populations of B. intermedius in supragingival plaque were significantly lower in the active group at 3 months and significantly lower counts of Fusobacterium sp. were observed at 3 and 6 months. Results indicate that use of the test products did not promote opportunistic overgrowth of pathogens in the oral flora. Additionally, the alterations in organisms associated with gingivitis may account for reductions in gingivitis seen in the active group.

  6. 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.

  7. Outcome measures for clinical drug trials in autism.

    PubMed

    Aman, Michael G; Novotny, Sherie; Samango-Sprouse, Carole; Lecavalier, Luc; Leonard, Elizabeth; Gadow, Kenneth D; King, Bryan H; Pearson, Deborah A; Gernsbacher, Morton Ann; Chez, Michael

    2004-01-01

    This paper identifies instruments and measures that may be appropriate for randomized clinical trials in participants with autism spectrum disorders (ASDs). The Clinical Global Impressions scale was recommended for all randomized clinical trials. At this point, however, there is no "perfect" choice of outcome measure for core features of autism, although we will discuss five measures of potential utility. Several communication instruments are recommended, based in part on suitability across the age range. In trials where the intention is to alter core features of ASDs, adaptive behavior scales are also worthy of consideration. Several "behavior complexes" common to ASDs are identified, and instruments are recommended for assessment of these. Given the prevalence of cognitive impairment in ASDs, it is important to assess any cognitive effects, although cognitive data from ASD randomized clinical trials, thus far, are minimal. Guidance from trials in related pharmacologic areas and behavioral pharmacology may be helpful. We recommend routine elicitation of side effects, height and weight, vital signs, and (in the case of antipsychotics) extrapyramidal side-effects assessment. It is often appropriate to include laboratory tests and assessments for continence and sleep pattern.

  8. 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

  9. 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

  10. Sustainable development of a GCP-compliant clinical trials platform in Africa: the Malaria Clinical Trials Alliance perspective

    PubMed Central

    2010-01-01

    Background The Malaria Clinical Trials Alliance (MCTA), a programme of INDEPTH network of demographic surveillance centres, was launched in 2006 with two broad objectives: to facilitate the timely development of a network of centres in Africa with the capacity to conduct clinical trials of malaria vaccines and drugs under conditions of good clinical practice (GCP); and to support, strengthen and mentor the centres in the network to facilitate their progression towards self-sustaining clinical research centres. Case description Sixteen research centres in 10 African malaria-endemic countries were selected that were already working with the Malaria Vaccine Initiative (MVI) or the Medicines for Malaria Venture (MMV). All centres were visited to assess their requirements for research capacity development through infrastructure strengthening and training. Support provided by MCTA included: laboratory and facility refurbishment; workshops on GCP, malaria diagnosis, strategic management and media training; and training to support staff to undertake accreditation examinations of the Association of Clinical Research Professionals (ACRP). Short attachments to other network centres were also supported to facilitate sharing practices within the Alliance. MCTA also played a key role in the creation of the African Media & Malaria Research Network (AMMREN), which aims to promote interaction between researchers and the media for appropriate publicity and media reporting of research and developments on malaria, including drug and vaccine trials. Conclusion In three years, MCTA strengthened 13 centres to perform GCP-compliant drug and vaccine trials, including 11 centres that form the backbone of a large phase III malaria vaccine trial. MCTA activities have demonstrated that centres can be brought up to GCP compliance on this time scale, but the costs are substantial and there is a need for further support of other centres to meet the growing demand for clinical trial capacity. The

  11. The Role of Social Media in Recruiting for Clinical Trials in Pregnancy

    PubMed Central

    Shere, Mahvash; Zhao, Xiu Yan; Koren, Gideon

    2014-01-01

    Background Recruitment of women in the periconceptional period to clinical studies using traditional advertising through medical establishments is difficult and slow. Given the widespread use of the internet as a source for medical information and research, we analyze the impact of social media in the second phase of an ongoing randomized, open-label clinical trial among pregnant women. This study aims to assess the effectiveness of social media as a recruitment tool through the comparison of diverse recruitment techniques in two different phases of the trial. Methods Recruitment in Phase 1 of the study consisted solely of traditional healthcare-based sources. This was compared to Phase 2 of the study where traditional recruitment was continued and expanded, while social media was used as a supplementary source. Yearly recruitment and recruitment rates in the two phases were compared using the Mann Whitney U test. The contributions of each recruitment source to overall recruitment were analyzed, and the impact of potential confounders on recruitment rate was evaluated using a multiple regression and Interrupted Time Series Analysis. Results In the first phase of the study, with over 56 months of recruitment using traditional sources, 35 women were enrolled in the study, resulting in a mean rate of ±0.62 recruits/month. In the 6 months implementing recruitment through social media, 45 women were recruited, for a 12-fold higher rate of ±7.5 recruits/month. Attrition rates remained constant, suggesting that social media had a positive impact on recruitment. The Interrupted Time Series Analysis detected a significant difference in recruitment after the intervention of social media (p<0.0001) with an evident increase in the number of recruits observed after the use of social media. Conclusions Clinicians and scientists recruiting for clinical studies should learn how to use online social media platforms to improve recruitment rates, thus increasing recruitment

  12. Coronally Advanced Flap with Different Designs in the Treatment of Gingival Recession: A Comparative Controlled Randomized Clinical Trial.

    PubMed

    Zucchelli, Giovanni; Stefanini, M; Ganz, S; Mazzotti, Claudio; Mounssif, Ilham; Marzadori, Matteo

    2016-01-01

    The aim of this parallel double-blind randomized controlled clinical trial was to describe a modified approach using the coronally advanced flap (CAF) with triangular design and to compare its efficacy, in terms of root coverage and esthetics, with a trapezoidal type of CAF. A sample of 50 isolated Miller Class I and II gingival recessions with at least 1 mm of keratinized tissue apical to the defects were treated with CAF. Of these recessions, 25 were randomly treated with trapezoidal CAF (control group) while the other 25 (test group) were treated with a modified triangular CAF. The clinical and esthetic evaluations, made by the patient and an independent periodontist, were performed 3 months, 6 months, and 1 year after the surgery. No statistically significant difference was demonstrated between the two CAF groups in terms of recession reduction, complete root coverage, or 6-month and 1-year patient esthetic scores. Better 3-month patient esthetic evaluations and better periodontist root coverage, color match, and contiguity assessments were reported after triangular CAF. Trapezoidal CAF was associated with greater incidence of keloid formation. Single-type gingival recessions can be successfully covered with both types of CAF. The triangular CAF should be preferred for esthetically demanding patients. PMID:27100801

  13. 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

  14. Mesenchymal stem cells in multiple sclerosis - translation to clinical trials.

    PubMed

    Dulamea, A

    2015-01-01

    Multiple sclerosis is a chronic inflammatory disease of the central nervous system, characterized by an aberrant activation of the immune system and combining demyelination with neurodegeneration. Studies on experimental models of multiple sclerosis revealed immunomodulatory and immunosuppressive properties of mesenchymal stem cells. Clinical trials using mesenchymal stem cells therapy in multiple sclerosis patients showed tolerability, safety on short term, some immunomodulatory properties reducing the Th1 proinflammatory response and the inflammatory MRI parameters. The author reviews the data about experimental studies and clinical trials using mesenchymal stem cells for the treatment of multiple sclerosis.

  15. A modest proposal for dropping poor arms in clinical trials.

    PubMed

    Proschan, Michael A; Dodd, Lori E

    2014-08-30

    This paper presents a simple procedure for clinical trials comparing several arms with control. Demand for streamlining the evaluation of new treatments has led to phase III clinical trials with more arms than would have been used in the past. In such a setting, it is reasonable that some arms may not perform as well as an active control. We introduce a simple procedure that takes advantage of negative results in some comparisons to lessen the required strength of evidence for other comparisons. We evaluate properties analytically and use them to support claims made about multi-arm multi-stage designs.

  16. Methodologic approach to adverse events applied to bupropion clinical trials.

    PubMed

    Cato, A E; Cook, L; Starbuck, R; Heatherington, D

    1983-05-01

    A strategy for identifying and classifying adverse events and for assessing their relationship to therapy and frequency of occurrence is presented. Data from clinical trials of bupropion (Wellbutrin), a novel antidepressant, are presented as an example. Bupropion was studied in four double-blind, placebo-controlled trials (N = 360) at dosages of 300-750 mg/day. The incidence and frequency of adverse events associated with bupropion were minimal, and correlated well with the known pharmacologic and clinical properties of this new antidepressant. PMID:6406455

  17. Effects of Vitamin D Intake on FEV1 and COPD Exacerbation: A Randomized Clinical Trial Study

    PubMed Central

    Zendedel, Abolfazl; Gholami, Mohammadreza; Anbari, Khatereh; Ghanadi, Kourosh; Bachari, Elham Ceneicel; Azargon, Alireza

    2015-01-01

    Aim: This study aimed to evaluate the effects of vitamin D intake on COPD exacerbation and FEV1 in the patients with severe and very severe COPD. Methods: This double blind placebo control randomized clinical trial study was done in the Ashayer university hospital in Khorramabad in 2012. Eighty eight patients with severe and very severe COPD were randomly selected from those who recoursed to the internal medicine clinic of Ashayer hospital. They were randomly allocated to case and placebo group. The patients received routine treatment for COPD. Along with the routine treatment, placebo group received 100,000 IU of oral vitamin D per month, for 6 months. Data was analyzed using SPSS computer software, paired t-test, independent t-test, non parametric t-test and Pearson correlation coefficients. Results: In each group, there were 44 patients. After the intervention, there were significant differences in FEV1 and the number of COPD exacerbation between the case and control group patients. Also, after the study, in the case group, FEV1 was increased and the number of COPD exacerbation was decreased significantly. Conclusion: Vitamin D intake decreased COPD exacerbation and improved FEV1 in the patients with severe and very severe COPD. It is suggested that baseline serum vitamin D levels will recorded in similar studies and the effect of vitamin D intake will evaluated regarding the baseline serum vitamin D levels. PMID:25946929

  18. Effectiveness of dry needling for chronic nonspecific neck pain: a randomized, single-blinded, clinical trial.

    PubMed

    Cerezo-Téllez, Ester; Torres-Lacomba, María; Fuentes-Gallardo, Isabel; Perez-Muñoz, Milagros; Mayoral-Del-Moral, Orlando; Lluch-Girbés, Enrique; Prieto-Valiente, Luis; Falla, Deborah

    2016-09-01

    Chronic neck pain attributed to a myofascial pain syndrome is characterized by the presence of muscle contractures referred to as myofascial trigger points. In this randomized, parallel-group, blinded, controlled clinical trial, we examined the effectiveness of deep dry needling (DDN) of myofascial trigger points in people with chronic nonspecific neck pain. The study was conducted at a public Primary Health Care Centre in Madrid, Spain, from January 2010 to December 2014. A total of 130 participants with nonspecific neck pain presenting with active myofascial trigger points in their cervical muscles were included. These participants were randomly allocated to receive: DDN plus stretching (n = 65) or stretching only (control group [n = 65]). Four sessions of treatment were applied over 2 weeks with a 6-month follow-up after treatment. Pain intensity, mechanical hyperalgesia, neck active range of motion, neck muscle strength, and perceived neck disability were measured at baseline, after 2 sessions of intervention, after the intervention period, and 15, 30, 90, and 180 days after the intervention. Significant and clinically relevant differences were found in favour of dry needling in all the outcomes (all P < 0.001) at both short and long follow-ups. Deep dry needling and passive stretching is more effective than passive stretching alone in people with nonspecific neck pain. The results support the use of DDN in the management of myofascial pain syndrome in people with chronic nonspecific neck pain. PMID:27537209

  19. Omega 3 Fatty Acids Supplementation and Oxidative Stress in HIV-Seropositive Patients. A Clinical Trial.

    PubMed

    Amador-Licona, Norma; Díaz-Murillo, Teresa A; Gabriel-Ortiz, Genaro; Pacheco-Moises, Fermín P; Pereyra-Nobara, Texar A; Guízar-Mendoza, Juan M; Barbosa-Sabanero, Gloria; Orozco-Aviña, Gustavo; Moreno-Martínez, Sandra C; Luna-Montalbán, Rafael; Vázquez-Valls, Eduardo

    2016-01-01

    HIV-seropositive patients show high incidence of coronary heart disease and oxidative stress has been described as relevant key in atherosclerosis development. The aim of this study was to assess the effect of omega 3 fatty acids on different markers of oxidative stress in HIV-seropositive patients. We performed a randomized parallel controlled clinical trial in The Instituto Mexicano del Seguro Social, a public health hospital. 70 HIV-seropositive patients aged 20 to 55 on clinical score A1, A2, B1 or B2 receiving highly active antiretroviral therapy (HAART) were studied. They were randomly assigned to receive omega 3 fatty acids 2.4 g (Zonelabs, Marblehead MA) or placebo for 6 months. At baseline and at the end of the study, anthropometric measurements, lipid profile, glucose and stress oxidative levels [nitric oxide catabolites, lipoperoxides (malondialdehyde plus 4-hydroxialkenals), and glutathione] were evaluated. Principal HAART therapy was EFV/TDF/FTC (55%) and AZT/3TC/EFV (15%) without difference between groups. Treatment with omega 3 fatty acids as compared with placebo decreased triglycerides (-0.32 vs. 0.54 mmol/L; p = 0.04), but oxidative stress markers were not different between groups.

  20. Omega 3 Fatty Acids Supplementation and Oxidative Stress in HIV-Seropositive Patients. A Clinical Trial.

    PubMed

    Amador-Licona, Norma; Díaz-Murillo, Teresa A; Gabriel-Ortiz, Genaro; Pacheco-Moises, Fermín P; Pereyra-Nobara, Texar A; Guízar-Mendoza, Juan M; Barbosa-Sabanero, Gloria; Orozco-Aviña, Gustavo; Moreno-Martínez, Sandra C; Luna-Montalbán, Rafael; Vázquez-Valls, Eduardo

    2016-01-01

    HIV-seropositive patients show high incidence of coronary heart disease and oxidative stress has been described as relevant key in atherosclerosis development. The aim of this study was to assess the effect of omega 3 fatty acids on different markers of oxidative stress in HIV-seropositive patients. We performed a randomized parallel controlled clinical trial in The Instituto Mexicano del Seguro Social, a public health hospital. 70 HIV-seropositive patients aged 20 to 55 on clinical score A1, A2, B1 or B2 receiving highly active antiretroviral therapy (HAART) were studied. They were randomly assigned to receive omega 3 fatty acids 2.4 g (Zonelabs, Marblehead MA) or placebo for 6 months. At baseline and at the end of the study, anthropometric measurements, lipid profile, glucose and stress oxidative levels [nitric oxide catabolites, lipoperoxides (malondialdehyde plus 4-hydroxialkenals), and glutathione] were evaluated. Principal HAART therapy was EFV/TDF/FTC (55%) and AZT/3TC/EFV (15%) without difference between groups. Treatment with omega 3 fatty acids as compared with placebo decreased triglycerides (-0.32 vs. 0.54 mmol/L; p = 0.04), but oxidative stress markers were not different between groups. PMID:27015634

  1. Effectiveness of dry needling for chronic nonspecific neck pain: a randomized, single-blinded, clinical trial.

    PubMed

    Cerezo-Téllez, Ester; Torres-Lacomba, María; Fuentes-Gallardo, Isabel; Perez-Muñoz, Milagros; Mayoral-Del-Moral, Orlando; Lluch-Girbés, Enrique; Prieto-Valiente, Luis; Falla, Deborah

    2016-09-01

    Chronic neck pain attributed to a myofascial pain syndrome is characterized by the presence of muscle contractures referred to as myofascial trigger points. In this randomized, parallel-group, blinded, controlled clinical trial, we examined the effectiveness of deep dry needling (DDN) of myofascial trigger points in people with chronic nonspecific neck pain. The study was conducted at a public Primary Health Care Centre in Madrid, Spain, from January 2010 to December 2014. A total of 130 participants with nonspecific neck pain presenting with active myofascial trigger points in their cervical muscles were included. These participants were randomly allocated to receive: DDN plus stretching (n = 65) or stretching only (control group [n = 65]). Four sessions of treatment were applied over 2 weeks with a 6-month follow-up after treatment. Pain intensity, mechanical hyperalgesia, neck active range of motion, neck muscle strength, and perceived neck disability were measured at baseline, after 2 sessions of intervention, after the intervention period, and 15, 30, 90, and 180 days after the intervention. Significant and clinically relevant differences were found in favour of dry needling in all the outcomes (all P < 0.001) at both short and long follow-ups. Deep dry needling and passive stretching is more effective than passive stretching alone in people with nonspecific neck pain. The results support the use of DDN in the management of myofascial pain syndrome in people with chronic nonspecific neck pain.

  2. Investigating fatigue of less than 6 months' duration. Guidelines for family physicians.

    PubMed Central

    Godwin, M.; Delva, D.; Miller, K.; Molson, J.; Hobbs, N.; MacDonald, S.; MacLeod, C.

    1999-01-01

    OBJECTIVE: To develop an evidence-based systematic approach to assessment of adult patients who present to family physicians complaining of fatigue of less than 6 months' duration. The guidelines present investigative options, making explicit what should be considered in all cases and what should be considered only in specific situations. They aim to provide physicians with an approach that, to the extent possible, is based on evidence so that time and cost are minimized and detection and management of the cause of the fatigue are optimized. QUALITY OF EVIDENCE: MEDLINE was searched from 1966 to 1997 using the key words "family practice" and "fatigue." Articles about chronic fatigue syndrome were excluded. Articles with level 3 evidence were found, but no randomized trials, cohort studies, or case-control studies were found. Articles looking specifically at the epidemiology, demographics, investigations, and diagnoses of patients with fatigue were chosen. Articles based on studies at referral and specialty centres were given less weight than those based on studies in family physicians' offices. MAIN MESSAGE: Adherence to these guidelines will decrease the cost of investigating the symptom of fatigue and optimize diagnosis and management. This needs to be proved in practice, however, and with research that produces level 1 and 2 evidence. CONCLUSIONS: Adults presenting with fatigue of less than 6 months' duration should be assessed for psychosocial causes and should have a focused history and physical examination to determine whether further investigations should be done. The guidelines outline investigations to be considered. The elderly require special consideration. These guidelines have group validation, but they need to be tested by more physicians in various locations and types of practices. PMID:10065311

  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.

  4. Updates on the Clinical Trials in Diabetic Macular Edema.

    PubMed

    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.

  5. [Key aspects in interpreting clinical trials in radiology].

    PubMed

    Díaz Gómez, L; García Villar, C; Seguro Fernández, Á

    2015-01-01

    A clinical trial is an experimental study to evaluate the efficacy and safety of a treatment or diagnostic technique in human beings. To ensure the methodological quality of a clinical trial and the validity of its results, various checklists have been elaborated to identify biases that could invalidate its conclusions. This article focuses on the points we need to consider in the critical evaluation of a clinical trial. We can usually find this information in the "materials and methods" and "results" sections of articles. Randomization, follow-up (or analysis of losses), blinding, and equivalence between groups (apart from the intervention itself) are some key aspects related to design. In the "results" section, we need to consider what measures of clinical efficacy were used (relative risk, odds ratio, or number needed to treat, among others) and the precision of the results (confidence intervals). Once we have confirmed that the clinical trial fulfills these criteria, we need to determine whether the results can be applied in our environment and whether the benefits obtained justify the risks and costs involved.

  6. 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

  7. Comparing the effectiveness of a clinical registry and a clinical data warehouse for supporting clinical trial recruitment: a case study.

    PubMed

    Weng, Chunhua; Bigger, J Thomas; Busacca, Linda; Wilcox, Adam; Getaneh, Asqual

    2010-11-13

    This paper reports a case study comparing the relative efficiency of using a Diabetes Registry or a Clinical Data Warehouse to recruit participants for a diabetes clinical trial, TECOS. The Clinical Data Warehouse generated higher positive predictive accuracy (31% vs. 6.6%) and higher participant recruitment than the Registry (30 vs. 14 participants) in a shorter time period (59 vs. 74 working days). We identify important factors that increase clinical trial recruitment efficiency and lower cost.

  8. 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.

  9. 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

  10. Conducting qualitative research within Clinical Trials Units: avoiding potential pitfalls.

    PubMed

    Cooper, Cindy; O'Cathain, Alicia; Hind, Danny; Adamson, Joy; Lawton, Julia; Baird, Wendy

    2014-07-01

    The value of using qualitative research within or alongside randomised controlled trials (RCTs) is becoming more widely accepted. Qualitative research may be conducted concurrently with pilot or full RCTs to understand the feasibility and acceptability of the interventions being tested, or to improve trial conduct. Clinical Trials Units (CTUs) in the United Kingdom (UK) manage large numbers of RCTs and, increasingly, manage the qualitative research or collaborate with qualitative researchers external to the CTU. CTUs are beginning to explicitly manage the process, for example, through the use of standard operating procedures for designing and implementing qualitative research with trials. We reviewed the experiences of two UK Clinical Research Collaboration (UKCRC) registered CTUs of conducting qualitative research concurrently with RCTs. Drawing on experiences gained from 15 studies, we identify the potential for the qualitative research to undermine the successful completion or scientific integrity of RCTs. We show that potential problems can arise from feedback of interim or final qualitative findings to members of the trial team or beyond, in particular reporting qualitative findings whilst the trial is on-going. The problems include: We make recommendations for improving the management of qualitative research within CTUs.

  11. An ontology-based architecture for integration of clinical trials management applications.

    PubMed

    Shankar, Ravi D; Martins, Susana B; O'Connor, Martin; Parrish, David B; Das, Amar K

    2007-10-11

    Management of complex clinical trials involves coordinated-use of a myriad of software applications by trial personnel. The applications typically use distinct knowledge representations and generate enormous amount of information during the course of a trial. It becomes vital that the applications exchange trial semantics in order for efficient management of the trials and subsequent analysis of clinical trial data. Existing model-based frameworks do not address the requirements of semantic integration of heterogeneous applications. We have built an ontology-based architecture to support interoperation of clinical trial software applications. Central to our approach is a suite of clinical trial ontologies, which we call Epoch, that define the vocabulary and semantics necessary to represent information on clinical trials. We are continuing to demonstrate and validate our approach with different clinical trials management applications and with growing number of clinical trials.

  12. An Ontology-based Architecture for Integration of Clinical Trials Management Applications

    PubMed Central

    Shankar, Ravi D.; Martins, Susana B.; O’Connor, Martin; Parrish, David B.; Das, Amar K.

    2007-01-01

    Management of complex clinical trials involves coordinated-use of a myriad of software applications by trial personnel. The applications typically use distinct knowledge representations and generate enormous amount of information during the course of a trial. It becomes vital that the applications exchange trial semantics in order for efficient management of the trials and subsequent analysis of clinical trial data. Existing model-based frameworks do not address the requirements of semantic integration of heterogeneous applications. We have built an ontology-based architecture to support interoperation of clinical trial software applications. Central to our approach is a suite of clinical trial ontologies, which we call Epoch, that define the vocabulary and semantics necessary to represent information on clinical trials. We are continuing to demonstrate and validate our approach with different clinical trials management applications and with growing number of clinical trials. PMID:18693919

  13. Cross-system evaluation of clinical trial search engines.

    PubMed

    Jiang, Silis Y; Weng, Chunhua

    2014-01-01

    Clinical trials are fundamental to the advancement of medicine but constantly face recruitment difficulties. Various clinical trial search engines have been designed to help health consumers identify trials for which they may be eligible. Unfortunately, knowledge of the usefulness and usability of their designs remains scarce. In this study, we used mixed methods, including time-motion analysis, think-aloud protocol, and survey, to evaluate five popular clinical trial search engines with 11 users. Differences in user preferences and time spent on each system were observed and correlated with user characteristics. In general, searching for applicable trials using these systems is a cognitively demanding task. Our results show that user perceptions of these systems are multifactorial. The survey indicated eTACTS being the generally preferred system, but this finding did not persist among all mixed methods. This study confirms the value of mixed-methods for a comprehensive system evaluation. Future system designers must be aware that different users groups expect different functionalities.

  14. Safety and tolerability review of lorcaserin in clinical trials.

    PubMed

    Greenway, F L; Shanahan, W; Fain, R; Ma, T; Rubino, D

    2016-10-01

    Lorcaserin is a novel selective serotonin 2C receptor agonist indicated by the US Food and Drug Administration for chronic weight management in adults with obesity or overweight with ≥1 comorbidity. The safety and efficacy of lorcaserin were established during two Phase III clinical trials in patients without diabetes (BLOOM and BLOSSOM) and one Phase III clinical trial in patients with type 2 diabetes (BLOOM-DM). Headache was the most common adverse event experienced by patients during all Phase III trials. Additional adverse events occurring in >5% of patients receiving lorcaserin included dizziness, fatigue, nausea, dry mouth and constipation in patients without diabetes, and hypoglycaemia, back pain, cough and fatigue in patients with diabetes. In a pooled analysis of echocardiographic data collected during the three lorcaserin Phase III trials, the incidence of FDA-defined valvulopathy was similar in patients taking lorcaserin and the placebo. Here, the safety profile of lorcaserin at the FDA-approved dose of 10 mg twice daily is reviewed using data from the lorcaserin Phase III programme, with a focus on theoretical adverse events commonly associated with agonists of the serotonin receptor family. Based on the lorcaserin Phase III clinical trial data, lorcaserin is safe and well tolerated in the indicated patient populations. PMID:27627785

  15. Current Immunotherapies for Sarcoma: Clinical Trials and Rationale

    PubMed Central

    Mitsis, Demytra; Francescutti, Valerie

    2016-01-01

    Sarcoma tumors are rare and heterogeneous, yet they possess many characteristics that may facilitate immunotherapeutic responses. Both active strategies including vaccines and passive strategies involving cellular adoptive immunotherapy have been applied clinically. Results of these clinical trials indicate a distinct benefit for select patients. The recent breakthrough of immunologic checkpoint inhibition is being rapidly introduced to a variety of tumor types including sarcoma. It is anticipated that these emerging immunotherapies will exhibit clinical efficacy for a variety of sarcomas. The increasing ability to tailor immunologic therapies to sarcoma patients will undoubtedly generate further enthusiasm and clinical research for this treatment modality. PMID:27703409

  16. The Importance of Children in Clinical Trials | NIH MedlinePlus the Magazine

    MedlinePlus

    ... Medicines for Children The Importance of Children in Clinical Trials Past Issues / Winter 2012 Table of Contents Dr. ... to a parent who asks you why children’s clinical trials are important? Clinical research is critically important to ...

  17. The therapeutic effect of clinical trials: understanding placebo response rates in clinical trials – A secondary analysis

    PubMed Central

    Walach, Harald; Sadaghiani, Catarina; Dehm, Cornelia; Bierman, Dick

    2005-01-01

    Background and purpose Placebo response rates in clinical trials vary considerably and are observed frequently. For new drugs it can be difficult to prove effectiveness superior to placebo. It is unclear what contributes to improvement in the placebo groups. We wanted to clarify, what elements of clinical trials determine placebo variability. Methods We analysed a representative sample of 141 published long-term trials (randomized, double-blind, placebo-controlled; duration > 12 weeks) to find out what study characteristics predict placebo response rates in various diseases. Correlational and regression analyses with study characteristics and placebo response rates were carried out. Results We found a high and significant correlation between placebo and treatment response rate across diseases (r = .78; p < .001). A multiple regression model explained 79% of the variance in placebo variability (F = 59.7; p < 0.0001). Significant predictors are, among others, the duration of the study (beta = .31), the quality of the study (beta = .18), the fact whether a study is a prevention trial (beta = .44), whether dropouts have been documented (beta = -.20), or whether additional treatments have been documented (beta = -.17). Healing rates with placebo are lower in the following diagnoses; neoplasms (beta = -.21), nervous diseases (beta = -.10), substance abuse (beta = -.14). Without prevention trials the amount of variance explained is 42%. Conclusion Medication response rates and placebo response rates in clinical trials are highly correlated. Trial characteristics can explain some portion of the variance in placebo healing rates in RCTs. Placebo response in trials is only partially due to methodological artefacts and only partially dependent on the diagnoses treated. PMID:16109176

  18. ADCOMS: a composite clinical outcome for prodromal Alzheimer's disease trials

    PubMed Central

    Wang, Jinping; Logovinsky, Veronika; Hendrix, Suzanne B; Stanworth, Stephanie H; Perdomo, Carlos; Xu, Lu; Dhadda, Shobha; Do, Ira; Rabe, Martin; Luthman, Johan; Cummings, Jeffrey; Satlin, Andrew

    2016-01-01

    Background Development of new therapies for Alzheimer's disease (AD) is increasingly focused on more mildly affected populations, and requires new assessment and outcome strategies. Patients in early stages of AD have mild cognitive decline and no, or limited, functional impairment. To respond to these assessment challenges, we developed a measurement approach based on established scale items that exhibited change in previous amnestic Mild Cognitive Impairment (aMCI) trials. Methods Partial least squares regression with a longitudinal clinical decline model identified items from commonly used clinical scales with the highest combined sensitivity to change over time in aMCI and weighted these items according to their relative contribution to detecting clinical progression in patients’ early stages of AD. The resultant AD Composite Score (ADCOMS) was assessed for its ability to detect treatment effect in aMCI/prodromal AD (pAD) clinical trial populations. Results ADCOMS consists of 4 Alzheimer's Disease Assessment Scale–cognitive subscale items, 2 Mini-Mental State Examination items, and all 6 Clinical Dementia Rating—Sum of Boxes items. ADCOMS demonstrated improved sensitivity to clinical decline over individual scales in pAD, aMCI and in mild AD dementia. ADCOMS also detected treatment effects associated with the use of cholinesterase inhibitors in these populations. Improved sensitivity predicts smaller sample size requirements when ADCOMS is used in early AD trials. Conclusions ADCOMS is proposed as new standard outcome for pAD and mild AD dementia trials, and is progressing in a CAMD-sponsored qualification process for use in registration trials of pAD. PMID:27010616

  19. Clinical Trials: Spline Modeling is Wonderful for Nonlinear Effects.

    PubMed

    Cleophas, Ton J

    2016-01-01

    Traditionally, nonlinear relationships like the smooth shapes of airplanes, boats, and motor cars were constructed from scale models using stretched thin wooden strips, otherwise called splines. In the past decades, mechanical spline methods have been replaced with their mathematical counterparts. The objective of the study was to study whether spline modeling can adequately assess the relationships between exposure and outcome variables in a clinical trial and also to study whether it can detect patterns in a trial that are relevant but go unobserved with simpler regression models. A clinical trial assessing the effect of quantity of care on quality of care was used as an example. Spline curves consistent of 4 or 5 cubic functions were applied. SPSS statistical software was used for analysis. The spline curves of our data outperformed the traditional curves because (1) unlike the traditional curves, they did not miss the top quality of care given in either subgroup, (2) unlike the traditional curves, they, rightly, did not produce sinusoidal patterns, and (3) unlike the traditional curves, they provided a virtually 100% match of the original values. We conclude that (1) spline modeling can adequately assess the relationships between exposure and outcome variables in a clinical trial; (2) spline modeling can detect patterns in a trial that are relevant but may go unobserved with simpler regression models; (3) in clinical research, spline modeling has great potential given the presence of many nonlinear effects in this field of research and given its sophisticated mathematical refinement to fit any nonlinear effect in the mostly accurate way; and (4) spline modeling should enable to improve making predictions from clinical research for the benefit of health decisions and health care. We hope that this brief introduction to spline modeling will stimulate clinical investigators to start using this wonderful method.

  20. 78 FR 58318 - Clinical Trial Design for Intravenous Fat Emulsion Products; Public Workshop

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-09-23

    ... HUMAN SERVICES Food and Drug Administration Clinical Trial Design for Intravenous Fat Emulsion Products... ``Clinical Trial Design for Intravenous Fat Emulsion Products.'' This workshop will provide a forum to discuss trial design of clinical trials intended to support registration of intravenous fat...

  1. Clinical Trials in Rare Disease: Challenges and Opportunities

    PubMed Central

    Augustine, Erika F.; Adams, Heather R.; Mink, Jonathan W.

    2014-01-01

    The neuronal ceroid lipofuscinoses constitute one of many groups of rare childhood diseases for which disease-modifying treatments are non-existent. Disease-specific barriers to therapeutic success include incomplete understanding of disease pathophysiology and limitations of treatments that cannot adequately cross the blood-brain barrier to access the central nervous system. Therapeutic development in the neuronal ceroid lipofuscinoses shares many challenges with other rare diseases, such as incomplete understanding of natural history to inform trial design, need for alternatives to the randomized controlled clinical trial, requirement for more sensitive outcome measures to quantify disease, limited access to resources required to mount a clinical trial (including funding), and difficulties of recruiting a small sample to participation. Solutions to these barriers will require multicenter collaboration, partnership with patient organizations, training a new generation of researchers interested in rare diseases, and leveraging existing resources. PMID:24014509

  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. Statistical considerations for stopping systemic lupus erythematosus clinical trials earlier.

    PubMed

    Lew, Robert A; Liang, Matthew H; Doros, Gheorghe

    2015-12-04

    Group sequential designs are used to potentially shorten randomized clinical trials and thereby reduce subject burden, improve safety, and save time and resources. Clinical trials comparing treatments for systemic lupus erythematosus (SLE) might adopt such designs if the ordinal outcome scales for SLE, such as the Systemic Lupus Activity Measure and Systemic Lupus Erythematosus Disease Activity Index, were more like continuous outcome scales with interval properties. After describing the basic features of sequential trials and highlighting some major issues in their design, we propose approaches that mitigate these issues. In particular, high-speed computing has accelerated advances in sequential design, making available a variety of designs that can be implemented with minimal technical support. The challenge now is to understand the concepts behind such flexible designs and then to apply them to improve studies of SLE.

  4. Litigation seeking access to data from ongoing clinical trials: a threat to clinical research.

    PubMed

    Kernan, Walter N; Viscoli, Catherine M; Varughese, Mathew C

    2014-09-01

    Researchers conducting randomized clinical trials may find themselves subject to legal subpoenas for interim data. When a subpoena demands premature disclosure of unblinded data, there is potential for damage to the scientific integrity and reputation of the on-going trial. We describe herein general issues raised by subpoenas for trial data and the particular case of a 2012 subpoena served on investigators from Yale University who were successful in winning reprieve from Connecticut Superior Court.

  5. Rare disease clinical trials: Power in numbers.

    PubMed

    Wicklund, Matthew P

    2016-08-01

    The limb-girdle muscular dystrophies (LGMDs) encompass a collection of genetic muscle diseases with proximal-predominant weakness of the limbs. Thirty-two of these disorders are named via the common nomenclature, including 8 autosomal-dominant (LGMD1A-H) and 24 autosomal-recessive (LGMD2A-X) disorders.(1) In addition, numerous other genetic muscle diseases, including Bethlem myopathy, dystrophinopathies, ryanodine receptor-associated myopathies, and many more, may clinically present with similar proximal-predominant weakness.(2) Therefore, current genetic testing panels targeting neuromuscular weakness frequently encompass >75 genes. These disorders are quite rare, each with minimum prevalence estimates of 0.01-0.60 cases per 100,000 persons.(3) LGMD2A (attributable to mutations in the gene for calpain-3) and LGMD2B (attributable to mutations in the gene for dysferlin) consistently are the 2 most prevalent LGMD subtypes in a variety of ethnic cohorts. PMID:27540592

  6. Clinical trial of cancer therapy with heavy ions at heavy ion research facility in lanzhou

    NASA Astrophysics Data System (ADS)

    Zhang, Hong

    With collaborative efforts of scientists from the Institute of Modern Physics (IMP), Chinese Academy of Sciences and hospitals in Gansu, initial clinical trial on cancer therapy with heavy ions has been successfully carried out in China. From November 2006 to December 2007, 51 patients with superficially-placed tumors were treated with carbon ions at Heavy Ion Research Facility in Lanzhou (HIRFL) within four beam time blocks of 6-11 days, collaborating with the General Hospital of Lanzhou Command and the Tumor Hospital of Gansu Province. Patients and Methods: There were 51 patients (31 males and 20 females) with superficially-placed tumors (squamous cell carcinoma of the skin, basal cell carcinoma of the skin, malignant skin melanoma, sarcoma, lymphoma, breast cancer, metastatic lymph nodes of carcinomas and other skin lesions). The tumors were less than 2.1 cm deep to the skin surface. All patients had histological confirmation of their tumors. Karnofsky Performance Scale (KPS) of all patients was more than 70. The majority of patients were with failures or recurrences of conventional therapies. Median age at the time of radiotherapy (RT) was 55.5 years (range 5-85 years). Patients were immobilized with a vacuum cushion or a head mask and irradiated by carbon ion beams with energy 80-100 MeV/u at spread-out Bragg peak field generated from HIRFL, with two and three-dimensional conformal irradiation methods. Target volume was defined by physical palpation [ultrasonography and Computerized tomography (CT), for some cases]. The clinical target volume (CTV) was defined as the gross total volume GTV with a 0.5-1.0cm margin axially. Field placement for radiation treatment planning was done based on the surface markings. RBE of 2.5-3 within the target volume, and 40-75 GyE with a weekly fractionation of 7 × 3-15 GyE/fraction were used in the trial. Patients had follow-up examinations performed 1 month after treatment, in 1 or 2 months for the first 6 months, and 3-6

  7. A guide to clinical trials. Part II: interpreting medical research.

    PubMed

    Highleyman, Liz

    2006-01-01

    Part I of this two-part article, which appeared in the Summer 2005 issue of BETA, provided an overview of the clinical trial process. Part II covers features of clinical trials and interpretation of study results. Clinical trials provide the foundation for evidence-based medicine, or medical decision-making guided by data from formal research. Medical professionals keep up with the latest information by reading peer-reviewed medical journals and attending conferences. Likewise, HIV positive people can keep abreast of the state of the art by following the medical literature and community publications like BETA. Trials offer important information about a therapy's benefits and risks in a population, but they cannot predict how well a given treatment will work for a specific person. Healthcare providers, therefore, must still rely heavily on clinical experience, intuition, and a careful evaluation of the various factors unique to each individual case--the practice of medicine remains an art as well as a science. PMID:16610119

  8. 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

  9. 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…

  10. Good manufacturing practice production of adenoviral vectors for clinical trials.

    PubMed

    Lusky, Monika

    2005-03-01

    The increasing importance of recombinant adenoviral vectors for gene therapy, cancer therapy, and the development of prophylactic and therapeutic vaccines has led to worldwide efforts toward scalable process development suitable for commercial manufacturing of replication-deficient adenoviral vectors. This review focuses on the manufacturing of adenovirus for clinical trials in the context of good manufacturing practice conditions and regulations. PMID:15812223

  11. Optimizing Educational Video through Comparative Trials in Clinical Environments

    ERIC Educational Resources Information Center

    Aronson, Ian David; Plass, Jan L.; Bania, Theodore C.

    2012-01-01

    Although video is increasingly used in public health education, studies generally do not implement randomized trials of multiple video segments in clinical environments. Therefore, the specific configurations of educational videos that will have the greatest impact on outcome measures ranging from increased knowledge of important public health…

  12. Current clinical trials testing combinations of immunotherapy and radiation.

    PubMed

    Crittenden, Marka; Kohrt, Holbrook; Levy, Ronald; Jones, Jennifer; Camphausen, Kevin; Dicker, Adam; Demaria, Sandra; Formenti, Silvia

    2015-01-01

    Preclinical evidence of successful combinations of ionizing radiation with immunotherapy has inspired testing the translation of these results to the clinic. Interestingly, the preclinical work has consistently predicted the responses encountered in clinical trials. The first example came from a proof-of-principle trial started in 2001 that tested the concept that growth factors acting on antigen-presenting cells improve presentation of tumor antigens released by radiation and induce an abscopal effect. Granulocyte-macrophage colony-stimulating factor was administered during radiotherapy to a metastatic site in patients with metastatic solid tumors to translate evidence obtained in a murine model of syngeneic mammary carcinoma treated with cytokine FLT-3L and radiation. Subsequent clinical availability of vaccines and immune checkpoint inhibitors has triggered a wave of enthusiasm for testing them in combination with radiotherapy. Examples of ongoing clinical trials are described in this report. Importantly, most of these trials include careful immune monitoring of the patients enrolled and will generate important data about the proimmunogenic effects of radiation in combination with a variety of immune modulators, in different disease settings. Results of these studies are building a platform of evidence for radiotherapy as an adjuvant to immunotherapy and encourage the growth of this novel field of radiation oncology.

  13. What can we do about exploratory analyses in clinical trials?

    PubMed

    Moyé, Lem

    2015-11-01

    The research community has alternatively embraced then repudiated exploratory analyses since the inception of clinical trials in the middle of the twentieth century. After a series of important but ultimately unreproducible findings, these non-prospectively declared evaluations were relegated to hypothesis generating. Since the majority of evaluations conducted in clinical trials with their rich data sets are exploratory, the absence of their persuasive power adds to the inefficiency of clinical trial analyses in an atmosphere of fiscal frugality. However, the principle argument against exploratory analyses is not based in statistical theory, but pragmatism and observation. The absence of any theoretical treatment of exploratory analyses postpones the day when their statistical weaknesses might be repaired. Here, we introduce examination of the characteristics of exploratory analyses from a probabilistic and statistical framework. Setting the obvious logistical concerns aside (i.e., the absence of planning produces poor precision), exploratory analyses do not appear to suffer from estimation theory weaknesses. The problem appears to be a difficulty in what is actually reported as the p-value. The use of Bayes Theorem provides p-values that are more in line with confirmatory analyses. This development may inaugurate a body of work that would lead to the readmission of exploratory analyses to a position of persuasive power in clinical trials.

  14. Drug Development and Challenges for Neuromuscular Clinical Trials.

    PubMed

    El Mouelhi, Mohamed

    2016-03-01

    Drug development process faces many challenges, including those encountered in clinical trials for neuromuscular diseases. Drug development is a lengthy and highly costly process. Out of 10 compounds entering first study in man (phase 1), only one compound reaches the market after an average of 14 years with a cost of $2.7 billion. Nevertheless, according to the Centers for Medicare and Medicaid services, prescription drugs constituted only 9 % of each health care dollar spent in USA in 2013. Examples of challenges encountered in neuromuscular clinical trials include lack of validated patient-reported outcome tools, blinding issues, and the use of placebo in addition to lack of health authority guidance for orphan diseases. Patient enrollment challenge is the leading cause of missed clinical trial deadlines observed in about 80 % of clinical trials, resulting in delayed availability of potentially life-saving therapies. Another specific challenge introduced by recent technology is the use of social media and risk of bias. Sharing personal experiences while in the study could easily introduce bias among patients that would interfere with accurate interpretation of collected data. To minimize this risk, recent neuromuscular studies incorporate as an inclusion criterion the patient's agreement not to share any of study experiences through social media with other patients during the study conduct. Consideration of these challenges will allow timely response to the high unmet medical needs for many neuromuscular diseases. PMID:26691331

  15. Considerations for Managing Large-Scale Clinical Trials.

    ERIC Educational Resources Information Center

    Tuttle, Waneta C.; And Others

    1989-01-01

    Research management strategies used effectively in a large-scale clinical trial to determine the health effects of exposure to Agent Orange in Vietnam are discussed, including pre-project planning, organization according to strategy, attention to scheduling, a team approach, emphasis on guest relations, cross-training of personnel, and preparing…

  16. Franklin, Lavoisier, and Mesmer: origin of the controlled clinical trial.

    PubMed

    Herr, Harry W

    2005-01-01

    In 1784, a Royal Commission headed by Benjamin Franklin and Antoine Lavoisier designed a series of ingenious experiments to debunk France's greatest medical rogue, Anton Mesmer, and his bizarre healing of illnesses based on his bogus theory of animal magnetism. Using intentional subject ignorance and sham interventions to investigate mesmerism, Franklin's commission provided a model for the controlled clinical trial. PMID:16144669

  17. Franklin, Lavoisier, and Mesmer: origin of the controlled clinical trial.

    PubMed

    Herr, Harry W

    2005-01-01

    In 1784, a Royal Commission headed by Benjamin Franklin and Antoine Lavoisier designed a series of ingenious experiments to debunk France's greatest medical rogue, Anton Mesmer, and his bizarre healing of illnesses based on his bogus theory of animal magnetism. Using intentional subject ignorance and sham interventions to investigate mesmerism, Franklin's commission provided a model for the controlled clinical trial.

  18. Pragmatic clinical trials: Emerging challenges and new roles for statisticians.

    PubMed

    Califf, Robert M

    2016-10-01

    Patients, clinicians, and policymakers alike need access to high-quality scientific evidence in order to make informed choices about health and healthcare, but the current national clinical trials enterprise is not yet optimally configured for the efficient creation and dissemination of such evidence. However, new technologies and methods hold significant potential for accelerating the rate at which we are able to translate raw findings gathered from both patient care and clinical research into actionable knowledge. We are now entering a period in which the quantitative sciences are emerging as the critical disciplines for advancing knowledge about health and healthcare, and statisticians will increasingly serve as critical mediators in transforming data into evidence. In this new, data-centric era, biostatisticians not only need to be expert at analyzing data but should also be involved directly in diverse efforts, including the review and analysis of research portfolios in order to optimize the relevance of research questions, the use of "quality by design" principles to improve reliability and validity of each individual trial, and the mining of aggregate knowledge derived from the clinical research enterprise as a whole. In order to meet these challenges, it is imperative that we (1) nurture and build the biostatistical workforce, (2) develop a deeper understanding of the biological and clinical context among statisticians, (3) facilitate collaboration among biostatisticians and other members of the clinical trials enterprise, (4) focus on communication skills in training and education programs, and (5) enhance the quantitative capacity of the research and clinical practice worlds.

  19. Pragmatic clinical trials: Emerging challenges and new roles for statisticians.

    PubMed

    Califf, Robert M

    2016-10-01

    Patients, clinicians, and policymakers alike need access to high-quality scientific evidence in order to make informed choices about health and healthcare, but the current national clinical trials enterprise is not yet optimally configured for the efficient creation and dissemination of such evidence. However, new technologies and methods hold significant potential for accelerating the rate at which we are able to translate raw findings gathered from both patient care and clinical research into actionable knowledge. We are now entering a period in which the quantitative sciences are emerging as the critical disciplines for advancing knowledge about health and healthcare, and statisticians will increasingly serve as critical mediators in transforming data into evidence. In this new, data-centric era, biostatisticians not only need to be expert at analyzing data but should also be involved directly in diverse efforts, including the review and analysis of research portfolios in order to optimize the relevance of research questions, the use of "quality by design" principles to improve reliability and validity of each individual trial, and the mining of aggregate knowledge derived from the clinical research enterprise as a whole. In order to meet these challenges, it is imperative that we (1) nurture and build the biostatistical workforce, (2) develop a deeper understanding of the biological and clinical context among statisticians, (3) facilitate collaboration among biostatisticians and other members of the clinical trials enterprise, (4) focus on communication skills in training and education programs, and (5) enhance the quantitative capacity of the research and clinical practice worlds. PMID:27378791

  20. Results of clinical trials with SPEM

    NASA Astrophysics Data System (ADS)

    De Vincentis, G.; Scopinaro, F.; Pani, R.; Pellegrini, R.; Soluri, A.; Scafè, R.; Massa, R.; Cinti, M. N.; Weinberg, I. N.; Khalkhali, I.; Betti, M.

    2003-01-01

    X-ray mammography represents the principal tool for breast cancer screening, but has several limitations. Due to the low specificity of X-ray mammography, many more biopsies are performed than are necessary. More than 60% of breast biopsies performed because of suspicious X-ray mammograms yield a diagnosis other than cancer. In women with X-ray dense breast tissue, X-ray mammography can miss as many as 20% of cancers. Several studies suggest that combining 99mTc Sestamibi Scintimammography (SM) with X-ray mammography can increase the accuracy of breast imaging in selected populations. The principal limitation of prone-position scintimammography (PSM) using a standard Anger gamma camera is low sensitivity for subcentimeter cancers (i.e., stages T1a and T1b). Detecting these small cancers is extremely important clinically, since removal of the cancers at these early stages is thought to represent the best opportunity for cure. Our group constructed a high spatial resolution detector specifically dedicated to SM, the Single Photon Emission Mammography (SPEM) camera. Unlike conventional Anger gamma cameras, the SPEM camera incorporates a high spatial resolution position-sensitive photomultiplier tube, coupled to an array of scintillating crystals. The compactness of the SPEM camera allows breast compression to be implemented in a cranio-caudal view, facilitating comparison to X-ray mammograms taken in the same position. Clinical results so obtained have demonstrated increased diagnostic sensitivity in sub-centimeter tumors (80% for SPEM vs 50% with PSM). Factors contributing to this increased sensitivity include improved signal-to-noise ratio (SNR). For sub-centimeter cancers, SPEM SNR values were consistently much higher than those of PSM. Classic detectability studies have demonstrated that an SNR value >5 is required for reliable detection of cancers. For subcentimeter cancers, only the SPEM attained or exceeded this minimum threshold. The results showed that

  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.

  2. Spirulina platensis versus silymarin in the treatment of chronic hepatitis C virus infection. A pilot randomized, comparative clinical trial

    PubMed Central

    2012-01-01

    Background Spirulina platensis, a cynobacterium used frequently as a dietary supplement had been found to exhibit many immune-stimulating and antiviral activities. It had been found to activate macrophages, NK cells, T cells, B cells, and to stimulate the production of Interferon gamma (IFN-γ) and other cytokines. Natural substances isolated from Spirulina platensis had been found to be potent inhibitors against several enveloped viruses by blocking viral absorption/penetration and some replication stages of progeny viruses after penetration into cells. We aimed to study whether this dietary supplement possesses any therapeutically feasible activity worthy of further larger controlled clinical evaluation. Methods Sixty six patients with chronic hepatitis C virus infection and eligible for inclusion had been randomized to either Spirulina or Silymarin treated groups for a period of six months treatment. The two groups were followed up and blindly compared for early (after 3 months) and end of 6 months treatment virological response. The effects of both treatments on each of alanine aminotransferase (ALT), Chronic Liver Disease Questionnaire scores (CLDQ), Arizona Sexual Experience Scale scores (ASEX) and the occurrence of any attributable adverse events were also compared. Results Among the 30 patients who had been treated with Spirulina and completed the 6 months protocol, 4 patients (13.3%) had a complete end of treatment virological response and 2 patients (6.7%) had a partial end of treatment response defined as significant decrease of virus load of at least 2-logs10. Though the proportion of responders in Spirulina group was greater than in the Silymarin group, the difference was not statistically significant at the end of both 6 months (p = 0.12) and 3 months treatment (p = 0.22) by Exact test. Alanine aminotransferase as well as CLDQ and ASEX scores were found to be more significantly improved in Spirulina than in Silymarin treated group. Conclusions Our

  3. Opioids in Preclinical and Clinical Trials

    NASA Astrophysics Data System (ADS)

    Nagase, Hiroshi; Fujii, Hideaki

    Since 1952, when Gates determined the stereo structure of morphine, numerous groups have focused on discovering a nonnarcotic opioid drug [1]. Although several natural, semisynthetic, and synthetic opioid ligands (alkaloids and peptides) have been developed in clinical studies, very few were nonnarcotic opioid drugs [2]. One of the most important studies in the opioid field appeared in 1976, when Martin and colleagues [3] established types of opioid receptors (these are now classified into μ, δ, and κ types). Later, Portoghese discovered a highly selective μ type opioid receptor antagonist, β-funaltrexamine [4]. This led to the finding that the μ type opioid receptor was correlated to drug dependence [5]. Consequently, δ, and particularly κ, opioid agonists were expected to lead to ideal opioid drugs. Moreover, opioid antagonists were evaluated for the treatment of symptoms related to undesirable opioid system activation. In this chapter, we provide a short survey of opioid ligands in development and describe the discovery of the two most promising drugs, TRK-851 [6] and TRK-820 (nalfurafine hydrochloride) [7].

  4. 78 FR 13351 - Submission for OMB Review; Comment Request: Clinical Mythteries: A Video Game About Clinical Trials

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-02-27

    ... Mythteries: A Video Game About Clinical Trials SUMMARY: Under the provisions of Section 3507(a)(1)(D) of the... Clinical Trials. Type of Information Collection Request: NEW. Need and Use of Information Collection:...

  5. Challenges and guidelines for clinical trial of herbal drugs.

    PubMed

    Parveen, Abida; Parveen, Bushra; Parveen, Rabea; Ahmad, Sayeed

    2015-01-01

    World Health Organization (WHO) has defined herbal medicines as finished labeled medicinal product that contain an active ingredient, aerial, or underground parts of the plant or other plant material or combinations. According to a report of WHO, about 80% of the world population is reported to rely on traditional medicine for their primary health care needs. Even in the developed countries, complementary or alternative medicine is gaining popularity. A report of a global survey on national policy on traditional medicine and regulation of herbal medicines indicated that about 50 countries including China, Japan, and Germany already have their national policy and laws on regulations of traditional medicines. Herbal drugs possess a long history of its use and better patient tolerance. These are cheaper and easily available in countries like India due to rich agro culture conditions. However, reckless utilization of resources threatens the sustainability of several plant species. Traditional medicines are governed by the Drugs and Cosmetics Act of 1940 and the Drugs and Cosmetics Rules of 1945. In 1959, the Government of India amended the Drugs and Cosmetics Act to include drugs that are derived from traditional Indian medicine. In 1993, the guidelines for the safety and efficacy of herbal medicines developed by an expert committee directed that the procedures laid down by the office of the Drug Controller General of India for allopathic drugs should be followed for all traditional and herbal products to enter into clinical trials for any therapeutic condition. However, there are certain loop holes in the clinical trials of herbal drugs as the lack of stringent bylaws and regulations. Hence, a deep insight of important challenges and major regulatory guidelines for clinical trial of herbal drugs and botanicals is discussed in the present communication. There is lack of scientific evidence to evaluate safety and efficacy of herbal drugs. The quality of the trial drug

  6. Challenges and guidelines for clinical trial of herbal drugs.

    PubMed

    Parveen, Abida; Parveen, Bushra; Parveen, Rabea; Ahmad, Sayeed

    2015-01-01

    World Health Organization (WHO) has defined herbal medicines as finished labeled medicinal product that contain an active ingredient, aerial, or underground parts of the plant or other plant material or combinations. According to a report of WHO, about 80% of the world population is reported to rely on traditional medicine for their primary health care needs. Even in the developed countries, complementary or alternative medicine is gaining popularity. A report of a global survey on national policy on traditional medicine and regulation of herbal medicines indicated that about 50 countries including China, Japan, and Germany already have their national policy and laws on regulations of traditional medicines. Herbal drugs possess a long history of its use and better patient tolerance. These are cheaper and easily available in countries like India due to rich agro culture conditions. However, reckless utilization of resources threatens the sustainability of several plant species. Traditional medicines are governed by the Drugs and Cosmetics Act of 1940 and the Drugs and Cosmetics Rules of 1945. In 1959, the Government of India amended the Drugs and Cosmetics Act to include drugs that are derived from traditional Indian medicine. In 1993, the guidelines for the safety and efficacy of herbal medicines developed by an expert committee directed that the procedures laid down by the office of the Drug Controller General of India for allopathic drugs should be followed for all traditional and herbal products to enter into clinical trials for any therapeutic condition. However, there are certain loop holes in the clinical trials of herbal drugs as the lack of stringent bylaws and regulations. Hence, a deep insight of important challenges and major regulatory guidelines for clinical trial of herbal drugs and botanicals is discussed in the present communication. There is lack of scientific evidence to evaluate safety and efficacy of herbal drugs. The quality of the trial drug

  7. D-Cycloserine Augmentation of Exposure Therapy for Post-Traumatic Stress Disorder: A Pilot Randomized Clinical Trial

    PubMed Central

    Difede, JoAnn; Cukor, Judith; Wyka, Katarzyna; Olden, Megan; Hoffman, Hunter; Lee, Francis S; Altemus, Margaret

    2014-01-01

    Viewing post-traumatic stress disorder (PTSD) as a disorder of emotional learning, this study used a cognitive enhancer synergistically with virtual reality exposure (VRE) therapy for the treatment of PTSD. The main objective was to determine if a novel pharmacotherapy, D-cycloserine (DCS), enhanced the efficacy of the psychotherapy. Pre-clinical studies suggest that when fear extinction occurs during DCS administration, neuroplasticity may be enhanced. VRE therapy is a particularly promising format to test the hypothesis that DCS enhances extinction learning, as sensory fear cues are standardized across patients. In a pilot randomized, double-blind, placebo-controlled trial, 100 mg of DCS or placebo was administered 90 min before each weekly VRE session, to ensure peak plasma concentrations during the sessions in 25 patients with chronic PTSD. The primary outcome measure was the Clinician Administered PTSD Scale (CAPS). Secondary outcome measures included the Beck Depression Inventory-II and the State-Trait Anger Expression Inventory-2. Assessments occurred at pre-treatment, following sessions 3, 6, 10, post-treatment, and at 6 months. The difference in CAPS between the VRE-DCS (n=13) and VRE-placebo (n=12) groups increased over time beginning at 6 weeks, with medium to large between-group effect sizes immediately post-treatment and 6 months later (d=0.68 and d=1.13, respectively). A similar pattern was observed for depression, anger expression, and sleep. PTSD remission rates were significantly greater for the VRE-DCS group (46% vs 8% at post-treatment; 69% vs 17% at 6 months). Patients in the VRE-DCS group showed earlier and greater improvement in PTSD symptoms compared with the VRE-placebo group. These results suggest a promising new treatment for PTSD. PMID:24217129

  8. Clinical trials of xenotransplantation: waiver of the right to withdraw from a clinical trial should be required.

    PubMed

    Spillman, Monique A; Sade, Robert M

    2007-01-01

    Xenotransplantation pits clinical research ethics against public health needs because recipients must undergo long-term, perhaps life-long, surveillance for infectious diseases. This surveillance requirement is effectively an abrogation of the right to withdraw from a clinical trial. Ulysses contracts, which are advance directives for future care, may be an ethical mechanism by which to balance public health needs against limitation of individual rights. PMID:17518852

  9. Clinical trials of xenotransplantation: waiver of the right to withdraw from a clinical trial should be required.

    PubMed

    Spillman, Monique A; Sade, Robert M

    2007-01-01

    Xenotransplantation pits clinical research ethics against public health needs because recipients must undergo long-term, perhaps life-long, surveillance for infectious diseases. This surveillance requirement is effectively an abrogation of the right to withdraw from a clinical trial. Ulysses contracts, which are advance directives for future care, may be an ethical mechanism by which to balance public health needs against limitation of individual rights.

  10. Clinical trials of vitamin and mineral supplements for cancer prevention.

    PubMed

    Greenwald, Peter; Anderson, Darrell; Nelson, Stefanie A; Taylor, Philip R

    2007-01-01

    Approximately 20-30% of Americans consume multivitamin supplements daily, indicating high public interest in the prevention of cancer and other chronic diseases through a nutrition-based approach. Although several bioactive food components, including vitamins and minerals, have been investigated for their ability to affect cancer risk, few large, randomized, placebo-controlled clinical trials of multivitamins with cancer as the primary endpoint have been performed. The results of most large-scale trials of multivitamin supplements (combinations of > or = 2 vitamins and minerals) to prevent cancer have been mixed. The Linxian General Population and Dysplasia trials found a decreased risk of cancer, particularly stomach cancer, for participants taking a multivitamin supplement, but this was in a borderline-deficient population in China. Two trials, the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study and the beta-Carotene and Retinol Efficacy Trial, found an increased risk of lung cancer among male cigarette smoke