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Sample records for 6-month clinical trial

  1. 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

  2. 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…

  3. 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...

  4. 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…

  5. 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

  6. 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

  7. 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…

  8. 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 ...

  9. Clinical Trials

    MedlinePlus

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

  10. 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

  11. 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

  12. 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

  13. 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 ...

  14. 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

  15. 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

  16. 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

  17. 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

  18. 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

  19. 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

  20. ClinicalTrials.gov

    MedlinePlus

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

  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. 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 ...

  3. 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.

  4. 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.

  5. Transcranial magnetic stimulation at 1 Hertz improves clinical symptoms in children with Tourette syndrome for at least 6 months.

    PubMed

    Le, Kai; Liu, Ling; Sun, Manli; Hu, Ling; Xiao, Nong

    2013-02-01

    Tourette syndrome (TS) is characterized by multiple motor and phonic tics. Repetitive transcranial magnetic stimulation (rTMS) targeting the supplemental motor area (SMA) can reduce tic severity. Here, we investigated whether 1 Hz rTMS targeted to the SMA could improve symptoms in children with TS. Twenty-five children with TS (aged under 16 years) received 20 daily sessions of rTMS to the SMA at a frequency of 1 Hz, 110% of resting motor threshold (RMT). Clinical assessment and physiological measures of the left and right RMT were conducted at different times during treatment and follow-up. After four weeks of treatment we observed statistically significant reductions on the Yale Global Tic Severity Scale, Clinical Global Impression Scale, Swanson, Nolan and Pelham Rating Scale, version IV for attention-deficit hyperactivity disorder, Children's Depression Inventory, Spence Children's Anxiety Scale and a novel Attention Test. In addition, symptom improvement correlated with an increase of both right and left RMT and was stable at six months follow-up. Therefore, we found that 1 Hz rTMS to the SMA can improve clinical symptoms in children with TS for at least six months. PMID:23238046

  6. 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

  7. Clinical Trials in Vision Research

    MedlinePlus

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

  8. 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

    2016-01-01

    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

  9. 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

  10. The 'natural' history of active rheumatoid arthritis over 3-6 months--an analysis of patients enrolled into trials of potential disease-modifying anti-rheumatic drugs, and treated with placebo.

    PubMed

    Porter, D R; Capell, H A

    1993-06-01

    The natural history of RA over a period of 6 months is not known, but this is of central importance to the design and interpretation of drug trials of possible DMARDs. We analysed the disease activity of 142 rheumatoid patients who were randomized to receive placebo in five double blind, placebo-controlled trials of possible disease-modifying drugs conducted in a single unit. There was no significant change in ESR, duration of morning stiffness or platelet count over a period of 6 months; the mean change in ESR at 3 months was an increase of 2 mm/h (99% C.I. -3, +7), and only 5% of patients more than halved their ESR over 6 months. There was a small significant fall in articular index over 6 months of placebo treatment. There is no measurable placebo effect on ESR, morning stiffness or platelet count when these are used as measures of disease activity in trials of drug therapy in RA. ESR is an informative, stable measure of disease activity; the duration of morning stiffness may be more useful than the articular index. The use of these results as the basis of a historical cohort to help design future placebo-controlled trials, and to interpret uncontrolled trials of putative anti-rheumatic drugs is discussed. PMID:8508282

  11. 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 ...

  12. Managing clinical trials.

    PubMed

    Farrell, Barbara; Kenyon, Sara; Shakur, Haleema

    2010-01-01

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

  13. 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

  14. CLINICAL TRIALS.GOV

    EPA Science Inventory

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

  15. 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

  16. Clinical trials of homoeopathy.

    PubMed Central

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

    1991-01-01

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

  17. AIDS Clinical Trials Group Network

    MedlinePlus

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

  18. The Perfect Clinical Trial.

    PubMed

    Bril, V

    2016-01-01

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

  19. 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 ...

  20. Participating in Clinical Trials

    MedlinePlus Videos and Cool Tools

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

  1. Shuffling Adaptive Clinical Trials.

    PubMed

    Gokhale, Sanjay G; Gokhale, Sankalp

    2016-01-01

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

  2. 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

  3. Continence and Quality-of-Life Outcomes 6 Months Following an Intensive Pelvic-Floor Muscle Exercise Program for Female Stress Urinary Incontinence: A Randomized Trial Comparing Low- and High-Frequency Maintenance Exercise

    PubMed Central

    Borello-France, Diane F; Downey, Patricia A; Zyczynski, Halina M; Rause, Christine R

    2008-01-01

    Background and Objectives: Few studies have examined the effectiveness of pelvic-floor muscle (PFM) exercises to reduce female stress urinary incontinence (SUI) over the long term. This study: (1) evaluated continence and quality-of-life outcomes of women 6 months following formalized therapy and (2) determined whether low- and high-frequency maintenance exercise programs were equivalent in sustaining outcomes. Subjects and Methods: Thirty-six women with SUI who completed an intensive PFM exercise intervention trial were randomly assigned to perform a maintenance exercise program either 1 or 4 times per week. Urine leaks per week, volume of urine loss, quality of life (Incontinence Impact Questionnaire [IIQ] score), PFM strength (Brink score), and prevalence of urodynamic stress incontinence (USI) were measured at a 6-month follow-up for comparison with postintervention status. Parametric and nonparametric statistics were used to determine differences in outcome status over time and between exercise frequency groups. Results: Twenty-eight women provided follow-up data. Postintervention status was sustained at 6 months for all outcomes (mean [SD] urine leaks per week=1.2±2.1 versus 1.4±3.1; mean [SD] urine loss=0.2±0.5 g versus 0.2±0.8 g; mean [SD] IIQ score=17±20 versus 22±30; mean [SD] Brink score=11±1 versus 11±1; and prevalence of USI=48% versus 35%). Women assigned to perform exercises once or 4 times per week similarly sustained their postintervention status. Discussion and Conclusions: Benefits of an initial intensive intervention program for SUI were sustained over 6 months. However, only 15 of the 28 women provided documentation of their exercise adherence, limiting conclusions regarding the need for continued PFM exercise during follow-up intervals of ≤6 months. PMID:18820095

  4. Gateways to clinical trials.

    PubMed

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

    2005-11-01

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

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

    ERIC Educational Resources Information Center

    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, Young, Ozonoff & Rogers, 2007). Using eye-tracking data and behavioral data recorded during a live mother-infant interaction…

  6. Gaze behavior and affect at 6 months: predicting clinical outcomes and language development in typically developing infants and infants at risk for autism.

    PubMed

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

    2009-09-01

    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, Young, Ozonoff & Rogers, 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

  7. 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…

  8. Efficacy of cranial electrotherapy stimulation for neuropathic pain following spinal cord injury: a multi-site randomized controlled trial with a secondary 6-month open-label phase

    PubMed Central

    Tan, Gabriel; Rintala, Diana H.; Jensen, Mark P.; Richards, J. Scott; Holmes, Sally Ann; Parachuri, Rama; Lashgari-Saegh, Shamsi; Price, Larry R.

    2011-01-01

    Background Chronic pain is a significant problem for many individuals following spinal cord injury (SCI). Unfortunately, SCI-related neuropathic pain has proven to be largely refractory to analgesic medications and other available treatments. Cranial electrotherapy stimulation (CES) has been effective in managing some types of pain. It involves the application of a small amount of current through the head via ear clip electrodes. Objective Explore the effectiveness of CES for neuropathic pain in persons with SCI and chronic pain. Study design Multi-site, double-blind, sham-controlled study. Participants Adults with SCI and chronic neuropathic pain at or below the level of injury were randomized to receive active or sham CES. Intervention Application of active CES or sham CES 1 hour daily for 21 days. Six-month open-label phase to assess ‘as-needed’ CES use. Outcome measures Change in pre- to post-session pain ratings as well as change in pain intensity, pain interference, pain quality, pain beliefs and coping strategies, general physical and mental health status, depressive symptomatology, perceived stress, and anxiety pre- to post-treatment. Results The active group reported a significantly greater average decrease in pain during daily treatments than the sham group (Kruskal–Wallis chi-square = 4.70, P < 0.05). During the 21-day trial, there was a significant group × time interaction for only one outcome variable; the active group showed larger pre- to post-treatment decreases in pain interference than the sham group did (F = 8.50, P < 0.01, d = 0.59). Conclusions On average, CES appears to have provided a small but statistically significant improvement in pain intensity and pain interference with few troublesome side effects. Individual results varied from no pain relief to a great deal of relief. PMID:21756567

  9. Gateways to clinical trials.

    PubMed

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

    2005-09-01

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

  10. 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

  11. 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

  12. 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

  13. Efficacy and safety of duloxetine for treatment of fibromyalgia in patients with or without major depressive disorder: Results from a 6-month, randomized, double-blind, placebo-controlled, fixed-dose trial.

    PubMed

    Russell, I Jon; Mease, Philip J; Smith, Timothy R; Kajdasz, Daniel K; Wohlreich, Madelaine M; Detke, Michael J; Walker, Daniel J; Chappell, Amy S; Arnold, Lesley M

    2008-06-01

    The primary objectives of this study were to assess the efficacy and safety of duloxetine for reducing pain severity in fibromyalgia patients with or without current major depressive disorder. This was a 6-month, multicenter, randomized, double-blind, placebo-controlled study. In total, 520 patients meeting American College of Rheumatology criteria for fibromyalgia were randomly assigned to duloxetine (20 mg/day, 60 mg/day, or 120 mg/day) or placebo, administered once daily, for 6 months (after 3 months, the duloxetine 20-mg/day group titrated to 60 mg/day). The co-primary outcome measures were the Brief Pain Inventory (BPI) average pain severity score and Patient Global Impressions of Improvement (PGI-I) score. Safety was assessed via treatment-emergent adverse events, and changes in vital sign, laboratory, and ECG measures. Compared with placebo-treated patients, those patients treated with duloxetine 120 mg/day improved significantly more on the co-primary outcome measures at 3 months (change in BPI score [-2.31 vs -1.39, P<0.001] and PGI-I [2.89 vs 3.39, P=0.004]) and at 6 months (change in BPI [-2.26 vs -1.43, P=0.003] and PGI-I [2.93 vs 3.37, P=0.012]). Compared with placebo, treatment with duloxetine 60 mg/day also significantly improved the co-primary measures at 3 months and BPI at 6 months. Duloxetine was efficacious in patients both with and without major depressive disorder. There were no clinically significant differences between treatment groups in changes in vital signs, laboratory measures, or ECG measures. Study results demonstrated that duloxetine at doses of 60 mg/day and 120 mg/day appears to be safe and efficacious in patients with fibromyalgia. PMID:18395345

  14. 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.

  15. Gateways to clinical trials.

    PubMed

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

    2002-11-01

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

  16. 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

  17. 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

  18. 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

  19. 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

  20. Gateways to clinical trials.

    PubMed

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

    2003-12-01

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

  1. 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

  2. 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

  3. 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

  4. 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

  5. Gateways to clinical trials.

    PubMed

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

    2006-05-01

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

  6. Gateways to clinical trials.

    PubMed

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

    2006-01-01

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

  7. 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

  8. Gateways to clinical trials.

    PubMed

    Moral, M A; Tomillero, A

    2008-03-01

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

  9. Gateways to clinical trials.

    PubMed

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

    2006-09-01

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

  10. Gateways to clinical trials.

    PubMed

    Tomillero, A; Moral, M A

    2010-12-01

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

  11. Gateways to clinical trials.

    PubMed

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

    2004-01-01

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

  12. Gateways to clinical trials.

    PubMed

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

    2004-09-01

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

  13. Gateways to clinical trials.

    PubMed

    Tomillero, A; Moral, M A

    2009-09-01

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

  14. Gateways to clinical trials.

    PubMed

    Bayés, M; Rabasseda, X

    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

  15. 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

  16. 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

  17. 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

  18. 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

  19. 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.

  20. 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

  1. 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

  2. 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

  3. Gateways to clinical trials.

    PubMed

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

    2003-01-01

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

  4. Gateways to clinical trials.

    PubMed

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

    2004-06-01

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

  5. 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

  6. 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

  7. Gateways to clinical trials.

    PubMed

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

    2004-01-01

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

  8. 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

  9. 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

  10. 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

  11. 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

  12. [Critical reading of clinical trials].

    PubMed

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

    2011-12-01

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

  13. 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 ...

  14. 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

  15. 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.)

  16. Social media in clinical trials.

    PubMed

    Thompson, Michael A

    2014-01-01

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

  17. 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

  18. 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

  19. 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

  20. Inept media trials of clinical trials

    PubMed Central

    Ramamurthy, N. V.

    2012-01-01

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

  1. Clinical Trials and Older People

    MedlinePlus

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

  2. 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

  3. Malaria diagnostics in clinical trials.

    PubMed

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

    2013-11-01

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

  4. Malaria Diagnostics in Clinical Trials

    PubMed Central

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

    2013-01-01

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

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

    PubMed

    Heerlein, Andrés

    2009-01-01

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

  6. 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

  7. [Quality control in clinical trials].

    PubMed

    Fukushima, M

    1996-01-01

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

  8. Randomized controlled trial of primary care physician motivational interviewing versus brief advice to engage adolescents with an Internet-based depression prevention intervention: 6-month outcomes and predictors of improvement.

    PubMed

    Hoek, Willemijn; Marko, Monika; Fogel, Joshua; Schuurmans, Josien; Gladstone, Tracy; Bradford, Nathan; Domanico, Rocco; Fagan, Blake; Bell, Carl; Reinecke, Mark A; Van Voorhees, Benjamin W

    2011-12-01

    We believe that primary care physicians could play a key role in engaging youth with a depression prevention intervention. We developed CATCH-IT (Competent Adulthood Transition with Cognitive Behavioral and Interpersonal Training), which is an adolescent Internet-based behavior change model. We conducted a randomized comparison of two approaches in engaging adolescents with the Internet intervention: primary care physician (PCP) motivational interview + CATCH-IT Internet program (MI) vs PCP brief advice + CATCH-IT Internet program (BA). The participants (N = 84) were recruited by screening for risk of depression in 13 primary care practices. We compared depressive disorder outcomes between groups and within groups over 6 months and examined the potential predictors and moderators of outcomes across both study arms. Depressive symptom scores declined from baseline to 6 weeks with these statistically significant reductions sustained at the 6 months follow-up in both groups. No significant interactions with treatment condition were found. However, by 6 months, the MI group demonstrated significantly fewer depressive episodes and reported less hopelessness as compared with the BA group. Hierarchical linear modeling regressions showed higher ratings of ease of use of the Internet program predicting lower depressive symptom levels over 6 months. In conclusion, a primary care/Internet-based intervention model among adolescents demonstrated reductions in depressed mood over 6 months and may result in fewer depressive episodes. PMID:22061038

  9. 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. |

  10. 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 ...

  11. Cancer nanotherapeutics in clinical trials.

    PubMed

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

    2015-01-01

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

  12. 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 ...

  13. 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 ...

  14. Reliability of gait in multiple sclerosis over 6 months.

    PubMed

    Sosnoff, Jacob J; Klaren, Rachel E; Pilutti, Lara A; Dlugonski, Deirdre; Motl, Robert W

    2015-03-01

    Gait impairment is ubiquitous in multiple sclerosis (MS) and is often characterized by alterations in spatiotemporal parameters of gait. There is limited information concerning reliability of spatiotemporal gait parameters over clinical timescales (e.g. 6 months). The current report provides novel evidence that gait parameters of 74 ambulatory persons with MS with mild-to-moderate disability are reliable over 6-months (ICC's for overall sample range from 0.56 to 0.91) in the absence of any intervention above and beyond standard care. Such data can inform clinical decision-making and power analyses for designing RCTs (i.e., sample size estimates) involving persons with MS. PMID:25772669

  15. [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

  16. 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

  17. 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

  18. 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 ...

  19. Gatekeepers for pragmatic clinical trials.

    PubMed

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

    2015-10-01

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

  20. 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

  1. Guttural pouch mycosis in a 6-month-old filly

    PubMed Central

    2006-01-01

    Abstract A 6-month-old filly was presented with unilateral epistaxis. Based on clinical signs, endoscopic examination, and postmortem examination, guttural pouch mycosis was diagnosed. The young age of the filly and the fact that this was the 2nd diagnosis of guttural pouch mycosis on this farm was unusual. PMID:16604984

  2. [Internet use in clinical trials].

    PubMed

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

    2014-01-01

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

  3. 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.

  4. MindTrial: An Intelligent System for Clinical Trials

    PubMed Central

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

    2010-01-01

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

  5. Target population for clinical trials

    PubMed Central

    Studenski, S

    2016-01-01

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

  6. Pharmacogenomics in cardiovascular clinical trials.

    PubMed

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

    2004-12-01

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

  7. Culturally Adapted Motivational Interviewing for Latino Heavy Drinkers: Results from a Randomized Clinical Trial

    PubMed Central

    Lee, Christina S.; López, Steven R.; Colby, Suzanne M.; Rohsenow, Damaris; Hernández, Lynn; Borrelli, Belinda; Caetano, Raul

    2014-01-01

    A randomized clinical trial of culturally adapted (CAMI) and un-adapted motivational interviewing (MI) to reduce drinking and related problems among heavy drinking Latinos randomized and assessed 58 participants at baseline, at 2 (86% retention) and 6 months (84% retention). Significant declines across both were found in heavy drinking days/month and drinking consequences (p < .001), with greater reductions for drinking consequences for CAMI at 2 months (p = .009) and continuing reductions in CAMI at 6 months. Findings provide preliminary support for the value of culturally adaptation to enhance the efficacy of motivational interviewing with Latino heavy drinkers. PMID:24215227

  8. Clinical trials and gender medicine.

    PubMed

    Cassese, Mariarita; Zuber, Veronica

    2011-01-01

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

  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. What Are Clinical Trials? | NIH MedlinePlus the Magazine

    MedlinePlus

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

  11. 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

  12. 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

  13. 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

  14. Contraceptive development and clinical trials.

    PubMed

    Fraser, I S

    1986-02-01

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

  15. Genomic sequencing in clinical trials

    PubMed Central

    2011-01-01

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

  16. 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

  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. Ethics of clinical trials in Nigeria

    PubMed Central

    Okonta, Patrick I.

    2014-01-01

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

  19. Why are clinical trials necessary in India?

    PubMed Central

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

    2014-01-01

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

  20. The unintended consequences of clinical trials regulations.

    PubMed

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

    2009-11-01

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

  1. Effect of 6-month caloric restriction on Cu bound to ceruloplasmin in adult overweight subjects.

    PubMed

    Piacenza, Francesco; Malavolta, Marco; Basso, Andrea; Costarelli, Laura; Giacconi, Robertina; Ravussin, Eric; Redman, Leanne M; Mocchegiani, Eugenio

    2015-08-01

    In a randomized clinical trial of calorie restriction (CR), we demonstrated that important cardiovascular disease (CVD) biomarkers were favorably influenced by CR alone and in conjunction with physical exercise. The aim of this study was to examine the effects of CR with or without exercise on copper bound to ceruloplasmin (CuCp), a well-known biomarker for CVD, in overweight men and women enrolled in the CALERIE phase 1 study. Forty-six individuals were randomized to one of four groups for 6 months: control, healthy weight maintenance; CR, 25% CR from baseline energy requirements; CR+exercise, 12.5% CR and 12.5% through aerobic exercise; and low-calorie diet, low-calorie diet until 15% reduction in body weight followed by weight maintenance diet. CuCp was determined in fasting blood samples by a high-performance liquid chromatography-inductively coupled plasma mass spectrometry methodology and compared with changes in body composition and markers of CVD. After 6 months, CR combined with exercise induced a decrease in plasma concentration of CuCp. CuCp was inversely correlated with insulin sensitivity at baseline and after 6 months of intervention. A cluster analysis showed that the percent change of weight after 6 months of intervention was the most important variable that could discriminate the intervention groups. The percent change of CuCp was the only other variable selected by the analysis. Decreased CuCp in overweight subjects by CR combined with exercise suggests a positive effect of this intervention on metabolic health. Further studies to explain the relationship between weight loss and CuCp and its relevance for cardiovascular health are needed. PMID:26001545

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

    PubMed Central

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

    2016-01-01

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

  3. 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

  4. Prudent precaution in clinical trials of nanomedicines.

    PubMed

    Marchant, Gary E; Lindor, Rachel A

    2012-01-01

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

  5. The Cooperative Landscape of Multinational Clinical Trials

    PubMed Central

    Hsiehchen, David; Espinoza, Magdalena; Hsieh, Antony

    2015-01-01

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

  6. Lessons learned from radiation oncology clinical trials.

    PubMed

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

    2013-11-15

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

  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. Methodology Series Module 4: Clinical Trials.

    PubMed

    Setia, Maninder Singh

    2016-01-01

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

  9. Personalized medicine: ethics for clinical trials.

    PubMed

    Sharrer, G Terry

    2012-01-01

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

  10. Paperless clinical trials: Myth or reality?

    PubMed

    Gupta, Sandeep K

    2015-01-01

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

  11. The Clinical Trials Transformation Initiative (CTTI).

    PubMed

    Grignolo, Alberto

    2011-01-01

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

  12. Microbicide clinical trial adherence: insights for introduction.

    PubMed

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

    2013-01-01

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

  13. Multiple comparisons in complex clinical trial designs.

    PubMed

    Hung, H M James; Wang, Sue-Jane

    2013-05-01

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

  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. 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

  16. Vaporization of the Prostate with 150-W Thulium Laser: Complications with 6-Month Follow-Up

    PubMed Central

    García-Larrosa, Alejandro; Capdevila, Santiago; Laborda, Ainhoa

    2014-01-01

    Abstract Purpose: To analyze the efficacy and safety of vaporization of the prostate (VP) with the 150-W thulium:yttrium-aluminum-garnet (Tm:YAG) laser. Patients and Methods: In a prospective series of 55 patients with small- and medium-size prostates undergoing major outpatient surgery (MOS), the primary objectives were to analyze changes in maximum flow (Qmax) and International Prostate Symptom Score (IPSS) after 6 months. Immediate (<30 days) and late (>30 days) complications were subsequently recorded. Results: An increase in mean Qmax of 9.33 mL/s (95% confidence interval [CI] of the mean difference 6.73–11.93; P<0.001) was recorded, and mean IPSS was reduced by 16.88 points (95% CI 14.22–19.54; P<0.001). The immediate complications recorded were acute urinary retention (one patient), urinary tract infection without fever (two patients), and macroscopic hematuria (two patients). The only late complication observed was bladder neck sclerosis (one patient). Conclusion: After 6 months, VP with 150-W Tm:YAG presents promising results in the clinical improvement of patients with small- and medium-size prostates. Its complication rate is low and it offers excellent hemostasis. The data from our study provide the basis for the design of clinical trials to compare this technique with other procedures. PMID:24521152

  17. Prognostic Utility of Routine Chimerism Testing at 2 – 6 Months after Allogeneic Hematopoietic Cell Transplantation

    PubMed Central

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

    2009-01-01

    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 – 6 months after HCT with myeloablative conditioning regimens were evaluated for association with subsequent risks of chronic graft versus host disease (GVHD), non-relapse mortality (NRM), relapse and overall mortality. Only 70 (5%) of 1304 patients had <95% donor-derived cells in the marrow. Low donor chimerism in the marrow occurred predominantly among patients with low risk disease as compared to higher risk diseases and was significantly associated with a reduced risk of chronic GVHD. Among 673 patients tested, 164 (24%) had <85% donor-derived T cells in the blood. Low donor T cell chimerism occurred predominantly among patients with low risk disease as compared to higher risk diseases, among those who had conditioning with busulfan as compared to TBI, and among those with lower grades of acute GVHD. Low donor T cell chimerism in the blood was significantly associated with a reduced risk of chronic GVHD, but not with the risks of relapse, NRM or overall mortality. Routine testing of chimerism in the marrow and blood at 2 – 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. PMID:19203726

  18. Marketing and clinical trials: a case study

    PubMed Central

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

    2007-01-01

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

  19. 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

  20. 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

  1. Monitoring recruitment effectiveness and cost in a clinical trial.

    PubMed

    Bjornson-Benson, W M; Stibolt, T B; Manske, K A; Zavela, K J; Youtsey, D J; Buist, A S

    1993-04-01

    Recruitment effort and costs in clinical trials are very often underestimated. As funding constraints increase, more precise estimates of costs as well as methods to monitor effectiveness are needed. However, few studies exist that report recruitment cost effectiveness and costs. The study reported here was developed in Portland, Oregon as an ancillary study to the Lung Health Study. The authors developed a monitoring and evaluation system to track response rates and costs associated with each of five recruitment methods. These methods include (1) media (TV, radio, newspapers), (2) neighborhood promotion, (3) direct mail, (4) worksite promotion, and (5) referral by other study participants. The analysis is limited to a 6-month period (April 1-September 30, 1987) or the middle phase of recruitment. During the study period, 46% were recruited from media, 30% from neighborhood promotion, 1.5% from direct mail, 11% from worksites, and 12% from referrals. Neighborhood promotion and direct mail were least cost-effective, media most cost-effective, with worksite and referral moderately cost-effective. The cost-effectiveness of media promotion is explained in part by the limited number of media sources in Portland, making it possible to reach a large audience with less effort, as well as the ability to provide rapid feedback to media sources. We conclude that the effectiveness of recruitment in a clinical trial is maximized by using multiple overlapping recruitment strategies coupled with a monitoring system that can provide rapid feedback regarding the effectiveness and costs of each strategy. PMID:8500313

  2. 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

  3. A guide to clinical trials for cancer

    MedlinePlus

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

  4. 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

  5. Swiss regulations for controlling clinical trials.

    PubMed

    Zanini, G M

    1998-04-01

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

  6. Are clinical trials really the answer?

    PubMed

    Block, G

    1995-12-01

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

  7. 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

  8. 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

  9. Special article: 2014 Pediatric Clinical Trials Forum.

    PubMed

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

    2016-04-01

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

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

    PubMed

    Grill, Joshua D; Monsell, Sarah E

    2014-03-01

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

  11. Social Media Ups Clinical Trial Enrollment.

    PubMed

    2016-08-01

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

  12. 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

  13. Biomarkers and Surrogate Endpoints In Clinical Trials

    PubMed Central

    Fleming, Thomas R.; Powers, John H

    2012-01-01

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

  14. Quality of clinical trials: A moving target

    PubMed Central

    Bhatt, Arun

    2011-01-01

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

  15. Clinical trial designs incorporating predictive biomarkers.

    PubMed

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

    2016-02-01

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

  16. Elderly patients’ participation in clinical trials

    PubMed Central

    Shenoy, Premnath; Harugeri, Anand

    2015-01-01

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

  17. RECENT CLINICAL TRIALS IN LUPUS NEPHRITIS

    PubMed Central

    Ward, Michael M.

    2014-01-01

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

  18. Clinical Trials in Retinal Dystrophies

    PubMed Central

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

    2016-01-01

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

  19. Advances in cardiology: clinical trial update.

    PubMed

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

    2011-05-01

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

  20. Disease-mongering through clinical trials.

    PubMed

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

    2015-06-01

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

  1. Ethical Issues in Clinical Trials Involving Nanomedicine

    PubMed Central

    Resnik, David B.; Tinkle, Sally S.

    2009-01-01

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

  2. 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

  3. A centralized informatics infrastructure for the National Institute on Drug Abuse Clinical Trials Network

    PubMed Central

    Pan, Jeng-Jong; Nahm, Meredith; Wakim, Paul; Cushing, Carol; Poole, Lori; Tai, Betty; Pieper, Carl F.

    2009-01-01

    Background Clinical trial networks were created to provide a sustaining infrastructure for the conduct of multisite clinical trials. As such, they must withstand changes in membership. Centralization of infrastructure including knowledge management, portfolio management, information management, process automation, work policies, and procedures in clinical research networks facilitates consistency and ultimately research. Purpose In 2005, the National Institute on Drug Abuse (NIDA) Clinical Trials Network (CTN) transitioned from a distributed data management model to a centralized informatics infrastructure to support the network’s trial activities and administration. We describe the centralized informatics infrastructure and discuss our challenges to inform others considering such an endeavor. Methods During the migration of a clinical trial network from a decentralized to a centralized data center model, descriptive data were captured and are presented here to assess the impact of centralization. Results We present the framework for the informatics infrastructure and evaluative metrics. The network has decreased the time from last patient-last visit to database lock from an average of 7.6 months to 2.8 months. The average database error rate decreased from 0.8% to 0.2%, with a corresponding decrease in the interquartile range from 0.04%–1.0% before centralization to 0.01%–0.27% after centralization. Centralization has provided the CTN with integrated trial status reporting and the first standards-based public data share. A preliminary cost-benefit analysis showed a 50% reduction in data management cost per study participant over the life of a trial. Limitations A single clinical trial network comprising addiction researchers and community treatment programs was assessed. The findings may not be applicable to other research settings. Conclusions The identified informatics components provide the information and infrastructure needed for our clinical trial

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

    PubMed Central

    Wing, Rena R.

    2014-01-01

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

  5. VOICES: the value of 6-month clinical evaluation in stroke. The protocol for a planned qualitative study to ascertain the value of stroke follow-up to people affected by stroke

    PubMed Central

    Jenkins, Colin; Price, Fiona

    2014-01-01

    Introduction The National Clinical Guidelines for Stroke recommend ‘routine follow-up of patients 6 months post discharge’. The Sentinel Stroke National Audit Programme sets a standard of 6 months postadmission follow-up, capturing data on process and outcomes. There appears to be no convincing model of stroke follow-up at 6 months, and despite evidence of unmet need in almost 50% of stroke survivors 1–5 years after their stroke, little work focuses on the first 12 months of recovery. By listening to the living experiences of stroke, the research aims to tailor the stroke care pathway to the needs of those affected. Methods and analysis A focus group of six stroke survivors and carers will be invited to identify appropriate interview questions about the value of follow-up at 6 months, ensuring that this study has its genesis in the participant experience. A pilot study of four stroke survivors will ascertain the feasibility of the method. Thirty stroke survivors from the follow-up clinic will be invited to take part in semistructured interviews. Raw data, in the form of digital recordings of the interviews, will be transcribed. Interview transcriptions will be checked by the participant for accuracy prior to analysis using NVivo software. Literal and reflective narrative analysis will be used to code transcribed text to examine shared themes and reflect on content. Ethics and dissemination Study documentation has been reviewed by the Coventry and Warwickshire Research Ethics Committee; the chief investigator met with the committee to scrutinise the study and justify its methodology. The committee has approved this study. A copy of the final report will be given to participants, the Stroke Association, the local Clinical Commissioning Group and participants’ general practitioners. It is intended to disseminate the results locally by presentation to the Trust board, at academic conferences and by publication in a peer-reviewed scientific journal

  6. Biomarkers in T cell therapy clinical trials

    PubMed Central

    2011-01-01

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

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

    PubMed

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

    2002-12-01

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

  8. Building data quality into clinical trials.

    PubMed

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

    2002-01-01

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

  9. 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

  10. Consent to clinical trials in anaesthesia.

    PubMed

    Montgomery, J E; Sneyd, J R

    1998-03-01

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

  11. Feeding patterns and diet - children 6 months to 2 years

    MedlinePlus

    ... You can start to introduce solid foods at age 6 months. Most of your baby's calories should still come from breast milk or formula. Breast milk is not a good source of iron. So after 6 months, your baby will start ...

  12. Optimizing biologically targeted clinical trials for neurofibromatosis

    PubMed Central

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

    2014-01-01

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

  13. Regulatory aspects of clinical trials in children.

    PubMed

    Mentzer, Dirk

    2009-01-01

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

  14. 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

  15. Surgeons: A Future Role in Clinical Trials?

    PubMed

    Rusch

    1997-01-01

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

  16. 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

  17. Economic Return of Clinical Trials Performed Under the Pediatric Exclusivity Program

    PubMed Central

    Li, Jennifer S.; Eisenstein, Eric L.; Grabowski, Henry G.; Reid, Elizabeth D.; Mangum, Barry; Schulman, Kevin A.; Goldsmith, John V.; Murphy, M. Dianne; Califf, Robert M.; Benjamin, Daniel K.

    2009-01-01

    Context In 1997, Congress authorized the Food and Drug Administration (FDA) to grant 6 month extensions of marketing rights through the Pediatric Exclusivity program if industry sponsors complete FDA-requested pediatric trials. The program has been praised for creating incentives for studies in children; it has been criticized as a “windfall” to the innovator drug industry. This critique has been a substantial part of Congressional debate on the program, which is due to sunset in 2007. Objective To quantify the economic return to industry for completing Pediatric Exclusivity. Design Cohort study of programs conducted for Pediatric Exclusivity. We selected 9 drugs that were granted Pediatric Exclusivity. From the final study reports submitted to FDA, we obtained key elements of the clinical trial design and study operations. We estimated the cost of performing each study and converted these into estimates of after-tax cash outflows. We obtained 3-year market sales and converted these into estimates of after-tax cash inflows based upon 6 months of additional market protection. We then calculated the net economic return (cash inflows less outflows) and ratio net return to costs (net economic return divided by cash outflows) for each product. Main Outcome Measures Net economic return and ratio of net return to cost. Results The indications studied reflected a broad representation of the program: asthma, tumors, attention deficit disorder, hypertension, depression/generalized anxiety disorder, diabetes, gastroesophageal reflux, bacterial infection, and bone mineralization. The distribution of net economic return for 6 months of exclusivity varied substantially among products [net return ranged from (−)$8.9 million to (+)$507.9 million; ratio of return to cost ranged from −0.68 to 73.6] Conclusions The economic return for pediatric exclusivity is highly variable. Pediatric Exclusivity, as an incentive to complete much-needed clinical trials in children, can

  18. 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

  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. PMID:26374682

  20. Management of acute malnutrition in infants aged under 6 months (MAMI): Current issues and future directions in policy and research

    PubMed Central

    Kerac, Marko; Mwangome, Martha; McGrath, Marie; Haider, Rukhsana; Berkley, James A.

    2016-01-01

    Background Globally, some 4.7 million infants aged under 6 months are moderately wasted and 3.8 million are severely wasted. Traditionally, they have been overlooked by clinicians, nutritionists, and policy makers. Objective To present evidence and arguments for why treating acute malnutrition in infants under 6 months of age is important and outline some of the key debates and research questions needed to advance their care. Methods Narrative review. Results and conclusions Treating malnourished infants under 6 months of age is important to avoid malnutrition-associated mortality in the short term and adverse health and development outcomes in the long term. Physiological and pathological differences demand a different approach from that in older children; key among these is a focus on exclusive breastfeeding wherever possible. New World Health Organization guidelines for the management of severe acute malnutrition (SAM) include this age group for the first time and are also applicable to management of moderate acute malnutrition (MAM). Community-based breastfeeding support is the core, but not the sole, treatment. The mother–infant dyad is at the heart of approaches, but wider family and community relationships are also important. An urgent priority is to develop better case definitions; criteria based on mid-upper-arm circumference (MUAC) are promising but need further research. To effectively move forward, clinical trials of assessment and treatment are needed to bolster the currently sparse evidence base. In the meantime, nutrition surveys and screening at health facilities should routinely include infants under 6 months of age in order to better define the burden and outcomes of acute malnutrition in this age group. PMID:25993754

  1. One-year sustained glycaemic control and less hypoglycaemia with new insulin glargine 300 U/ml compared with 100 U/ml in people with type 2 diabetes using basal plus meal-time insulin: the EDITION 1 12-month randomized trial, including 6-month extension

    PubMed Central

    Riddle, M C; Yki-Järvinen, H; Bolli, G B; Ziemen, M; Muehlen-Bartmer, I; Cissokho, S; Home, P D

    2015-01-01

    Aims To evaluate the maintenance of efficacy and safety of insulin glargine 300 U/ml (Gla-300) versus glargine 100 U/ml (Gla-100) in people with type 2 diabetes mellitus (T2DM) using basal plus meal-time insulin for 12 months in the EDITION 1 trial. Methods EDITION 1 was a multicentre, randomized, open-label, two-arm, phase IIIa study. Participants completing the initial 6-month treatment period continued to receive Gla-300 or Gla-100, as previously randomized, once daily for a further 6-month open-label extension phase. Changes in glycated haemoglobin (HbA1c) and fasting plasma glucose concentrations, insulin dose, hypoglycaemic events and body weight were assessed. Results Of 807 participants enrolled in the initial phase, 89% (359/404) assigned to Gla-300 and 88% (355/403) assigned to Gla-100 completed 12 months. Glycaemic control was sustained in both groups (mean HbA1c: Gla-300, 7.24%; Gla-100, 7.42%), with more sustained HbA1c reduction for Gla-300 at 12 months: least squares mean difference Gla-300 vs Gla-100: HbA1c −0.17 [95% confidence interval (CI) −0.30 to −0.05]%. The mean daily basal insulin dose at 12 months was 1.03 U/kg for Gla-300 and 0.90 U/kg for Gla-100. Lower percentages of participants had ≥1 confirmed [≤3.9 mmol/l (≤70 mg/dl)] or severe hypoglycaemic event with Gla-300 than Gla-100 at any time of day [24 h; 86 vs 92%; relative risk 0.94 (95% CI 0.89–0.99)] and during the night [54 vs 65%; relative risk 0.84 (95% CI 0.75–0.94)], while the annualized rates of such hypoglycaemic events were similar. No between-treatment differences in adverse events were apparent. Conclusion During 12 months of treatment of T2DM requiring basal and meal-time insulin, glycaemic control was better sustained and fewer individuals reported hypoglycaemia with Gla-300 than with Gla-100. The mean basal insulin dose was higher with Gla-300 compared with Gla-100, but total numbers of hypoglycaemic events and overall tolerability did not differ between

  2. [Dental calculus-inhibiting tooth pastes and mouthwashes. A review of the literature of clinical trials].

    PubMed

    Barbakow, F; Imfeld, T

    1989-01-01

    Several brands of anticalculus dentifrices and mouthrinses claim to reduce the formation of supragingival calculus. These products contain soluble pyrophosphates (with or without Gantrez), zinc citrate trihydrate or zinc chloride which reduce the amount of supragingival but not subgingival calculus after a scaling. Most of the clinical anticalculus trials ran for 3 or 6 months and the calculus reductions were assessed using the Volpe-Manhold Index. This index assesses the coronal extension of supragingival calculus. Calculus reductions varied from 9% to 50% but no plaque scores were quantitated. However, the ADA has stipulated that dentifrices claiming anticalculus effects must clearly state that the products have not therapeutic effect on periodontal diseases. Some of the placebo dentifrices used in the clinical trials also reduced the calculus scores although they are not as yet advertised as anticalculus dentifrices. PMID:2678454

  3. 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

  4. Rett Syndrome: Reaching for Clinical Trials.

    PubMed

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

    2015-07-01

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

  5. 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

  6. 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

  7. How ethical is your clinical trial?

    PubMed Central

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

    2010-01-01

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

  8. Automatic Selection of Clinical Trials Based on A Semantic Web Approach.

    PubMed

    Cuggia, Marc; Campillo-Gimenez, Boris; Bouzille, Guillaume; Besana, Paolo; Jouini, Wassim; Dufour, Jean-Charles; Zekri, Oussama; Gibaud, Isabelle; Garde, Cyril; Duvauferier, Regis

    2015-01-01

    Recruitment of patients in clinical trials is nowadays preoccupying, as the inclusion rate is particularly low. The main identified factors are the multiplicity of open clinical trials, the high number and complexity of eligibility criteria, and the additional workload that a systematic search of the clinical trials a patient could be enrolled in for a physician. The principal objective of the ASTEC project is to automate the prescreening phase during multidisciplinary meetings (MDM). This paper presents the evaluation of a computerized recruitment support systems (CRSS) based on semantic web approach. The evaluation of the system was based on data collected retrospectively from a 6 month period of MDM in Urology and on 4 clinical trials of prostate cancer. The classification performance of the ASTEC system had a precision of 21%, recall of 93%, and an error rate equal to 37%. Missing data was the main issue encountered. The system was designed to be both scalable to other clinical domains and usable during MDM process. PMID:26262114

  9. Gateways to clinical trials. December 2008.

    PubMed

    Tomillero, A; Moral, M A

    2008-12-01

    Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables have been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: AAV1/SERCA2a; Abatacept, ABT-263, Adalimumab, Aflibercept, Afobazole, Aliskiren fumarate, Anakinra, Atazanavir/ritonavir, Aviscumine, Axitinib, Azacitidine; Bevacizumab, Biphasic insulin aspart, Bortezomib, Briobacept; Carmoterol hydrochloride, CCX-282, Ceftobiprole medocaril, Certolizumab pegol, Cetuximab; Darifenacin hydrobromide, Dasatinib, Denosumab, Doripenem, Duloxetine hydrochloride; E-7080, Epratuzumab, Erlotinib hydrochloride, Everolimus, Exenatide, Ezetimibe/simvastatin; Gefitinib, Golimumab; gamma-Hydroxybutyrate sodium; Imatinib mesylate, Insulin detemir, Insulin glulisine, IVX-0142; Laquinimod sodium, Linezolid, Lopinavir/ritonavir; Ocrelizumab, Omalizumab; Parecoxib sodium, Pemetrexed disodium, Pregabalin; Rosuvastatin calcium, Rotigotine; Sorafenib, Sugammadex sodium; Tapentadol hydrochloride, Tenofovir disoproxil fumarate/emtricitabine, Tocilizumab; Ularitide, Ustekinumab; Valsartan/amlodipine besylate, Varenicline tartrate, Vatalanib succinate, Vildagliptin, Vorinostat. PMID:19271026

  10. Women’s health and clinical trials

    PubMed Central

    Schiebinger, Londa

    2003-01-01

    Women have traditionally been underrepresented in clinical trials. In order to translate recent advances in our understanding of the molecular and physiological bases of sex differences into new therapeutics and health practices, sound sex-specific clinical data are imperative. Since the founding of the Office of Research on Women’s Health within the Office of the Director at the NIH in 1990, inequities in federally funded biomedical research, diagnosis, and treatment of diseases affecting women in the US have been reviewed. Discussed herein is the evolution of gender-related research innovations, primarily within the last decade, and strategies and challenges involved in the success of this recent development. PMID:14523031

  11. Remote ischemic conditioning: a clinical trial's update.

    PubMed

    Candilio, Luciano; Hausenloy, Derek J; Yellon, Derek M

    2011-01-01

    Coronary artery disease (CAD) is the leading cause of death and disability worldwide, and early and successful restoration of myocardial reperfusion following an ischemic event is the most effective strategy to reduce final infarct size and improve clinical outcome. This process can, however, induce further myocardial damage, namely acute myocardial ischemia-reperfusion injury (IRI) and worsen clinical outcome. Therefore, novel therapeutic strategies are required to protect the myocardium against IRI in patients with CAD. In this regard, the endogenous cardioprotective phenomenon of "ischemic conditioning," in which the heart is put into a protected state by subjecting it to one or more brief nonlethal episodes of ischemia and reperfusion, has the potential to attenuate myocardial injury during acute IRI. Intriguingly, the heart can be protected in this manner by applying the "ischemic conditioning" stimulus to an organ or tissue remote from the heart (termed remote ischemic conditioning or RIC). Furthermore, the discovery that RIC can be noninvasively applied using a blood pressure cuff on the upper arm to induce brief episodes of nonlethal ischemia and reperfusion in the forearm has greatly facilitated the translation of RIC into the clinical arena. Several recently published proof-of-concept clinical studies have reported encouraging results with RIC, and large multicenter randomized clinical trials are now underway to investigate whether this simple noninvasive and virtually cost-free intervention has the potential to improve clinical outcomes in patients with CAD. In this review article, we provide an update of recently published and ongoing clinical trials in the field of RIC. PMID:21821533

  12. Cytomegalovirus vaccine: phase II clinical trial results.

    PubMed

    Rieder, F; Steininger, C

    2014-05-01

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

  13. 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

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

    PubMed

    Zannad, F; Plétan, Y

    2001-01-01

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

  15. The Joys of Clinical Trials: A Case Study of a Multicenter Pharmaceutical Trial.

    ERIC Educational Resources Information Center

    Soronson, Bryan M.; Shaw, Diana V.

    1994-01-01

    A discussion of clinical trials in the pharmaceutical industry describes typical processes and administrative issues, then presents a case in which a foreign pharmaceutical company negotiated with a university for sponsorship of a multicenter clinical trial of a new drug therapy. Problems and important considerations in clinical trials are…

  16. Tyranny of the randomised clinical trial.

    PubMed

    Rosenbek, John C

    2016-06-01

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

  17. 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

  18. 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

  19. 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

  20. Integrated safety in tocilizumab clinical trials

    PubMed Central

    2011-01-01

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

  1. Validity and reliability of patient reported outcomes used in Psoriasis: results from two randomized clinical trials

    PubMed Central

    Shikiar, Richard; Bresnahan, Brian W; Stone, Stephen P; Thompson, Christine; Koo, John; Revicki, Dennis A

    2003-01-01

    Background Two Phase III randomized controlled clinical trials were conducted to assess the efficacy, safety, and tolerability of weekly subcutaneous administration of efalizumab for the treatment of psoriasis. Patient reported measures of psoriasis-related functionality and health-related quality of life and of psoriasis-related symptom assessments were included as part of the trials. Objective To assess the reliability, validity, and responsiveness of the patient reported outcome measures that were used in the trials – the Dermatology Life Quality Index (DLQI), the Psoriasis Symptom Assessment (PSA) Scale, and two itch measures, a Visual Analog Scale (VAS) and the National Psoriasis Foundation (NPF) itch measure. Methods Subjects aged 18 to 70 years with moderate to severe psoriasis for at least 6 months were recruited into the two clinical trials (n = 1095). Internal consistency reliability was evaluated for all patient reported outcomes at baseline and at 12 weeks. Construct validity was evaluated by relations among the different patient reported outcomes and between the patient reported outcomes and the clinical assessments (Psoriasis Area and Severity Index; Overall Lesion Severity Scale; Physician's Global Assessment of Change) assessed at baseline and at 12 weeks, as was the change over the course of the 12 week portion of the trial. Results Internal consistency reliability ranged from 0.86 to 0.95 for the patient reported outcome measures. The patient reported outcome measures were all shown to have significant construct validity with respect to each other and with respect to the clinical assessments. The four measures also demonstrated significant responsiveness to change in underlying clinical status of the patients over the course of the trial, as measured by the independently assessed clinical outcomes. Conclusions The DLQI, the PSA, VAS, and the NPF are considered useful tools for the measurement of dermatology-related limitations of functional

  2. Gateways to clinical trials. March 2003.

    PubMed

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

    2003-03-01

    Gateways to clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Studies knowledge area of Prous Science Integrity, the drug discovery and devlopment protal, http://integrity.prous.com. This issue focuses on the following selection of drugs: AAV-CF, adalimumab, ademetionine, afeletecan hydrochloride, agomelatine, alemtuzumab, almotriptan, amdoxovir, aplidine, aranose, arsenic sulfide, atazanavir, atlizumab; Bimatoprost, BMS-181176, BMS-188667, bortezomib, bryostatin 1; Combretastatin A-4 phosphate; Darbepoetin alfa, darusentan, deferasirox, desloratadine, DTaP-HBV-IPV/Hib-vaccine, DTI-0009; Eculizumab, edodekin alfa, emtricitabine, enfuvirtide, epoetin, esomeprazole magnesium etoricoxib; Fampridine, fenretinide, FR-146687; Galiximab, gamma-Hydroxybutyrate sodium, ganirelix acetate, gefitinib, Gemtuzumab ozogamicin, gimatecan; HEA125xOKT3, hIL-13-PE38QQR, HSV-2 theracine, Hu14.18-IL-2, human gammaglobulin; Idraparinux sodium, imatinib mesylate, IMiD3, insulin detemir, interleukin-4, irofulven, ISAtx-247; JT-1001; Levetiracetam, levosimendan, liposomal doxorubicin, liposomal vincristine sulfate, lixivaptan, lopinavir, lumiracoxib; Maxacalcitol, melatonin, midostaurin, MLN-518; Neridronic acid, nesiritide, nitronaproxen; Oblimersen sodium, oregovomab; PEG-filgrastim polyglutamate paclitaxel, prasterone, pregabalin; Rosuvastatin calcium, rotigotine hydrochloride; SGN-30; T-1249, tenofovir disoproxil fumarate, teriparatide, tiotropium bromide, tipranavir, TMC-114, trabectedin, transdermal selegiline; UK-427857; Valdecoxib, valganciclovir hydrochloride, vardenafil, vatalanib succinate, vincristine sulfate TCS; Zofenopril calcium. PMID:12731460

  3. 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

  4. 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

  5. A survey of clinical trials with fenbufen.

    PubMed

    Mawdsley, P

    1980-01-01

    To date, the efficacy and safety of gamma-oxo(1,1'-biphenyl)-4-butanoic acid (fenbufen) have been evaluated in over 200 clinical trials involving several thousand patients. The program of clinical investigation consisted of open dose ranging studies in patients; short-term, double-blind controlled studies of both cross-over and parallel group design to evaluate efficacy and safety compared to placebo and active reference drugs; long-term, double-blind controlled studies of parallel group design versus an active reference agent; open studies to evaluate the long-term efficacy and safety of fenbufen; and special studies to investigate possible effects on eyes, ears and heart. The overall experience with fenbufen in 60 US and 37 foreign clinical trials is summarized in this report with respect to the following: therapeutic efficacy and safety in rheumatoid arthritis, osteoarthritis, ankylosing spondylitis, analgesia and gout. The age range covered in these studies was 13 to 87 years, and included 206 patients over the age of 70. 3457 patients received fenbufen in all phases of these clinical trials, including short-term and long-term studies. The patient total includes: 1462 patients (664 US, 798 foreign) with rheumatoid arthritis, 1225 (420 US, 805 foreign) with osteoarthritis, 55 (19 US, 36 foreign) with ankylosing spondylitis, 39 (foreign) with gout, and 676 patients (103 US, 573 (foreign) who participated in analgesia studies. The worldwide clinical studies have demonstrated very good clinical efficacy of fenbufen in comparison to other non-steroidal antirheumatic (nsa) drugs. The tolerance was much better in many cases compared with tolerance levels of other nsa-drugs. The good results were confirmed by new papers presented during IX International Congress of Rheumatology, Wiesbaden/FR Germany, September 1979. Fenbufen is currently marketed in Brazil, Columbia, Costa Rica, Dominican Republic, Ecuador, El Salvador, Great Britain, Greece, Guatemala, Honduras

  6. 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

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

    PubMed

    Van Pham, Phuc

    2016-01-01

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

  8. 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....

  9. 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 ...

  10. Statistical properties of randomization in clinical trials.

    PubMed

    Lachin, J M

    1988-12-01

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

  11. 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

  12. Clinical Research Trials | NIH MedlinePlus the Magazine

    MedlinePlus

    ... version 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? ...

  13. 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

  14. 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

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

    PubMed

    Liu, Katherine A; Mager, Natalie A Dipietro

    2016-01-01

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

  16. Gateways to Clinical Trials. June 2002.

    PubMed

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

    2002-06-01

    Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Studies knowledge area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: Abacavir sulfate, abarelix, abciximab, alicaforsen sodium, almotriptan, alteplase, amlodipine, amoxicillin trihydrate, amprenavir, argatroban monohydrate, aspirin, atorvastatin calcium, azathioprine; Baclofen, benidipine hydrochloride, benserazide, BMS-214662, bosentan, botulinum toxin type B; Candesartan cilexetil, carbamazepine, carbidopa, carboplatin, ceftriaxone sodium, celecoxib, cetirizine hydrochloride, clarithromycin, clavulanate potassium, clopidogrel hydrogensulfate, clozapine, CPI-1189, cyclophosphamide, cytarabine; Darbepoetin alfa, denileukin diftitox, dexamethasone, dipyridamole, droperidol, DW-166HC; Ebastine, efalizumab, efavirenz, eletriptan, enalapril maleate, enfuvirtide, enoxaparin sodium, enrasentan, entacapone, epoetin, eprosartan mesilate, etanercept, etoricoxib; Fenofibratefexofenadine hydrochloride, filgrastim, fludarabine phosphate, fluoxetine hydrochloride fluvoxamine maleate, frovatriptan, furosemide; Gabapentin, galantamine hydrobromide, gatifloxacin, gefitinib, ghrelin (human), glatiramer acetate; Haloperidol; Ibuprofen, ibuprofen, guaiacol ester, idarubicin hydrochloride, imipramine hydrochloride, imiquimod, interferon beta, interferon beta-1a, interferon beta-1b, interferon omega, irbesartan, itraconazole; Ketorolac, ketorolac tromethamine; Lamifiban, lamotrigine, lanoteplase, lansoprazole, leflunomide, leuprorelin acetate, levetiracetam, levocetirizine, levodopa, lisinopril, loratadine; Manidipine, methylprednisolone, metronidazole, mirtazapine, mizolastine, modafinil, morphine sulfate; Naproxen sodium, naratriptan hydrochloride, nifedipine, NSC-683864; Ofloxacin, olanzapine

  17. 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

  18. 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

  19. Issues and perspectives in designing clinical trials for negative symptoms in schizophrenia.

    PubMed

    Marder, Stephen R; Alphs, Larry; Anghelescu, Ion-George; Arango, Celso; Barnes, Thomas R E; Caers, Ivo; Daniel, David G; Dunayevich, Eduardo; Fleischhacker, W Wolfgang; Garibaldi, George; Green, Michael F; Harvey, Philip D; Kahn, René S; Kane, John M; Keefe, Richard S E; Kinon, Bruce; Leucht, Stefan; Lindenmayer, Jean-Pierre; Malhotra, Anil K; Stauffer, Virginia; Umbricht, Daniel; Wesnes, Keith; Kapur, Shitij; Rabinowitz, Jonathan

    2013-11-01

    A number of pharmacological agents for treating negative symptoms in schizophrenia are currently in development. Unresolved questions regarding the design of clinical trials in this area were discussed at an international meeting in Florence, Italy in April 2012. Participants included representatives from academia, the pharmaceutical industry, and the European Medicines Agency (EMA). Prior to the meeting, participants submitted key questions for debate and discussion. Responses to the questions guided the discussion during the meeting. The group reached agreement on a number of issues: (1) study subjects should be under the age of 65; (2) subjects should be excluded for symptoms of depression that do not overlap with negative symptoms; (3) functional measures should not be required as a co-primary in negative symptom trials; (4) information from informants should be included for ratings when available; (5) Phase 2 negative symptom trials should be 12weeks and 26weeks is preferred for Phase 3 trials; (6) prior to entry into a negative symptom study, subjects should demonstrate clinical stability for a period of 4 to 6months by collection of retrospective information; and (7) prior to entry, the stability of negative and positive symptoms should be confirmed prospectively for four weeks or longer. The participants could not reach agreement on whether predominant or prominent negative symptoms should be required for study subjects. PMID:24028744

  20. Development and Implementation of a Double-Blind Corticosteroid-Tapering Regimen for a Clinical Trial

    PubMed Central

    Collinson, Neil; Tuckwell, Katie; Habeck, Frank; Chapman, Monique; Klearman, Micki; Stone, John H.

    2015-01-01

    We describe the design and operationalization of a blinded corticosteroid-tapering regimen for a randomized trial of tocilizumab in giant cell arteritis (GCA). To our knowledge, no clinical trial in any disease has ever employed a blinded corticosteroid-tapering regimen, but this was necessary to the design of our trial which is likely to be relevant to other investigations of steroid-sparing regimens. Two standardized corticosteroid-tapering regimens are required for this GCA trial: a 6-month regimen in 3 arms (taken with tocilizumab 162 mg subcutaneously weekly or every other week or with placebo) and a 12-month regimen with placebo (fourth arm). Investigators select initial prednisone doses, tapered in an open-label fashion until 20 mg/day. Doses <20 mg/day are blinded. At least 27 blinded blister packs are required to ensure blinding and encourage compliance. This permits all possible daily doses but requires ≤5 capsules/day. The number of capsules taken at any point during tapering is identical across groups. Our approach may be extrapolated to trials beyond GCA. PMID:25878667

  1. Clinical trial demonstrates exercise following bariatric surgery improves insulin sensitivity

    PubMed Central

    Coen, Paul M.; Tanner, Charles J.; Helbling, Nicole L.; Dubis, Gabriel S.; Hames, Kazanna C.; Xie, Hui; Eid, George M.; Stefanovic-Racic, Maja; Toledo, Frederico G.S.; Jakicic, John M.; Houmard, Joseph A.; Goodpaster, Bret H.

    2014-01-01

    BACKGROUND. Roux-en-Y gastric bypass (RYGB) surgery causes profound weight loss and improves insulin sensitivity (SI) in obese patients. Regular exercise can also improve SI in obese individuals; however, it is unknown whether exercise and RYGB surgery–induced weight loss would additively improve SI and other cardiometabolic factors. METHODS. We conducted a single-blind, prospective, randomized trial with 128 men and women who recently underwent RYGB surgery (within 1–3 months). Participants were randomized to either a 6-month semi-supervised moderate exercise protocol (EX, n = 66) or a health education control (CON; n = 62) intervention. Main outcomes measured included SI and glucose effectiveness (SG), which were determined from an intravenous glucose tolerance test and minimal modeling. Secondary outcomes measured were cardiorespiratory fitness (VO2 peak) and body composition. Data were analyzed using an intention-to-treat (ITT) and per-protocol (PP) approach to assess the efficacy of the exercise intervention (>120 min of exercise/week). RESULTS. 119 (93%) participants completed the interventions, 95% for CON and 91% for EX. There was a significant decrease in body weight and fat mass for both groups (P < 0.001 for time effect). SI improved in both groups following the intervention (ITT: CON vs. EX; +1.64 vs. +2.24 min–1/μU/ml, P = 0.18 for Δ, P < 0.001 for time effect). A PP analysis revealed that exercise produced an additive SI improvement (PP: CON vs. EX; +1.57 vs. +2.69 min–1/μU/ml, P = 0.019) above that of surgery. Exercise also improved SG (ITT: CON vs. EX; +0.0023 vs. +0.0063 min–1, P = 0.009) compared with the CON group. Exercise improved cardiorespiratory fitness (VO2 peak) compared with the CON group. CONCLUSION. Moderate exercise following RYGB surgery provides additional improvements in SI, SG, and cardiorespiratory fitness compared with a sedentary lifestyle during similar weight loss. TRIAL REGISTRATION. clinicaltrials.gov identifier

  2. A data grid for imaging-based clinical trials

    NASA Astrophysics Data System (ADS)

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

    2007-03-01

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

  3. Analyzing acute procedural pain in clinical trials.

    PubMed

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

    2014-07-01

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

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

    PubMed Central

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

    2013-01-01

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

  5. 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

  6. Using Clinical Trial Simulators to Analyse the Sources of Variance in Clinical Trials of Novel Therapies for Acute Viral Infections

    PubMed Central

    Weverling, Gerrit-Jan; de Wolf, Frank; Anderson, Roy M.

    2016-01-01

    Background About 90% of drugs fail in clinical development. The question is whether trials fail because of insufficient efficacy of the new treatment, or rather because of poor trial design that is unable to detect the true efficacy. The variance of the measured endpoints is a major, largely underestimated source of uncertainty in clinical trial design, particularly in acute viral infections. We use a clinical trial simulator to demonstrate how a thorough consideration of the variability inherent in clinical trials of novel therapies for acute viral infections can improve trial design. Methods and Findings We developed a clinical trial simulator to analyse the impact of three different types of variation on the outcome of a challenge study of influenza treatments for infected patients, including individual patient variability in the response to the drug, the variance of the measurement procedure, and the variance of the lower limit of quantification of endpoint measurements. In addition, we investigated the impact of protocol variation on clinical trial outcome. We found that the greatest source of variance was inter-individual variability in the natural course of infection. Running a larger phase II study can save up to $38 million, if an unlikely to succeed phase III trial is avoided. In addition, low-sensitivity viral load assays can lead to falsely negative trial outcomes. Conclusions Due to high inter-individual variability in natural infection, the most important variable in clinical trial design for challenge studies of potential novel influenza treatments is the number of participants. 100 participants are preferable over 50. Using more sensitive viral load assays increases the probability of a positive trial outcome, but may in some circumstances lead to false positive outcomes. Clinical trial simulations are powerful tools to identify the most important sources of variance in clinical trials and thereby help improve trial design. PMID:27332704

  7. Perceptions of Reimbursement for Clinical Trial Participation

    PubMed Central

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

    2012-01-01

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

  8. Ergocalciferol Supplementation in Hemodialysis Patients With Vitamin D Deficiency: A Randomized Clinical Trial.

    PubMed

    Miskulin, Dana C; Majchrzak, Karen; Tighiouart, Hocine; Muther, Richard S; Kapoian, Toros; Johnson, Doug S; Weiner, Daniel E

    2016-06-01

    Locally produced 1,25-dihydroxyvitamin D3 may have pleiotropic effects outside of bone. Experimental and observational studies suggest that nutritional vitamin D may enhance erythropoiesis in settings of 25-hydroxy vitamin D (25(OH)D) deficiency. We conducted a double-blind, placebo-controlled, randomized clinical trial to assess the effects of supplementation with ergocalciferol on epoetin utilization and other secondary outcomes in patients on hemodialysis with serum 25(OH)D <30 ng/ml. In all, 276 patients were randomized to 6 months of ergocalciferol or placebo. Mean±SD serum 25(OH)D increased from 16.0±5.9 ng/ml at baseline to 39.2±14.9 ng/ml in the ergocalciferol arm and did not change (16.9±6.4 ng/ml and 17.5±7.4 ng/ml, respectively) in the placebo arm. There was no significant change in epoetin dose over 6 months in the ergocalciferol or placebo arms (geometric mean rate 0.98 [95% confidence interval (95% CI), 0.94 to 1.02] versus 0.99 [95% CI, 0.95 to 1.03], respectively) and no difference across arms (P=0.78). No change occurred in serum calcium, phosphorus, intact parathyroid hormone, or C-reactive protein levels, cinacalcet use, or phosphate binder or calcitriol dose in either study arm. Rates of all-cause, cardiovascular, and infection-related hospitalizations did not differ by study arm, although statistical power was limited for these outcomes. In conclusion, 6 months of supplementation with ergocalciferol increased serum 25(OH)D levels in patients on hemodialysis with vitamin D insufficiency or deficiency, but had no effect on epoetin utilization or secondary biochemical and clinical outcomes. PMID:26677862

  9. Recruitment and Retention of Patients into Emergency Medicine Clinical Trials

    PubMed Central

    Cofield, Stacey; Conwit, Robin; Barsan, William; Quinn, James

    2010-01-01

    The emergency medicine and pre-hospital environments are unlike any other clinical environments and require special consideration to allow the successful implementation of clinical trials. This article reviews the specific issues involved in Emergency Medicine Clinical Trials (EMCT), and provides strategies from emergency medicine and non-emergency medicine trials to maximize recruitment and retention. While the evidence supporting some of these strategies is deficient, addressing recruitment and retention issues with specific strategies will help researchers deal with these issues in their funding applications and in turn develop the necessary infrastructure to participate in emergency medicine clinical trials. PMID:21040112

  10. 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

  11. [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

  12. 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

  13. The mPED randomized controlled clinical trial: applying mobile persuasive technologies to increase physical activity in sedentary women protocol

    PubMed Central

    2011-01-01

    Background Despite the significant health benefits of regular physical activity, approximately half of American adults, particularly women and minorities, do not meet the current physical activity recommendations. Mobile phone technologies are readily available, easily accessible and may provide a potentially powerful tool for delivering physical activity interventions. However, we need to understand how to effectively apply these mobile technologies to increase and maintain physical activity in physically inactive women. The purpose of this paper is to describe the study design and protocol of the mPED (mobile phone based physical activity education) randomized controlled clinical trial that examines the efficacy of a 3-month mobile phone and pedometer based physical activity intervention and compares two different 6-month maintenance interventions. Methods A randomized controlled trial (RCT) with three arms; 1) PLUS (3-month mobile phone and pedometer based physical activity intervention and 6-month mobile phone diary maintenance intervention), 2) REGULAR (3-month mobile phone and pedometer based physical activity intervention and 6-month pedometer maintenance intervention), and 3) CONTROL (pedometer only, but no intervention will be conducted). A total of 192 physically inactive women who meet all inclusion criteria and successfully complete a 3-week run-in will be randomized into one of the three groups. The mobile phone serves as a means of delivering the physical activity intervention, setting individualized weekly physical activity goals, and providing self-monitoring (activity diary), immediate feedback and social support. The mobile phone also functions as a tool for communication and real-time data capture. The primary outcome is objectively measured physical activity. Discussion If efficacy of the intervention with a mobile phone is demonstrated, the results of this RCT will be able to provide new insights for current behavioral sciences and m

  14. 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...

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

    PubMed

    Cummings, J; Zhong, K

    2015-11-01

    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. Maternal regulation of infant reactivity from 2 to 6 months.

    PubMed

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

    2004-07-01

    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 both the intensity and duration of infants' crying. Maternal affection and touching decreased from 2 to 6 months, whereas maternal vocalizing and distraction behaviors increased. At both ages, the combination of maternal holding/rocking and vocalizing was associated with decreases in all levels of infant reactivity. Neither strategy alone, however, was found to be effective. Feeding/ pacifying behaviors were effective only when initial distress was at a low or moderate level, which suggests that the effectiveness of maternal regulatory behaviors may depend on the intensity of infants' crying. PMID:15238037

  17. 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

  18. 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

  19. 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

  20. Two randomized controlled clinical trials to study the effectiveness of prednisolone treatment in preventing and restoring clinical nerve function loss in leprosy: the TENLEP study protocols

    PubMed Central

    2012-01-01

    Background Nerve damage in leprosy often causes disabilities and deformities. Prednisolone is used to treat nerve function impairment (NFI). However, optimal dose and duration of prednisolone treatment has not been established yet. Besides treating existing NFI it would be desirable to prevent NFI. Studies show that before NFI is clinically detectable, nerves often show subclinical damage. Within the ‘Treatment of Early Neuropathy in LEProsy’ (TENLEP) study two double blind randomized controlled trials (RCT) will be carried out: a trial to establish whether prednisolone treatment of 32 weeks duration is more effective than 20 weeks in restoring nerve function in leprosy patients with clinical NFI (Clinical trial) and a trial to determine whether prednisolone treatment of early sub-clinical NFI can prevent clinical NFI (Subclinical trial). Methods Two RCTs with a follow up of 18 months will be conducted in six centers in Asia. In the Clinical trial leprosy patients with recent (< 6 months) clinical NFI, as determined by Monofilament Test and Voluntary Muscle Test, are included. The primary outcomes are the proportion of patients with restored or improved nerve function. In the Subclinical trial leprosy patients with subclinical neuropathy, as determined by Nerve Conduction Studies (NCS) and/or Warm Detection Threshold (WDT), and without any clinical signs of NFI are randomly allocated to a placebo group or treatment group receiving 20 weeks prednisolone. The primary outcome is the proportion of patients developing clinical NFI. Reliability and normative studies are carried out before the start of the trial. Discussion This study is the first RCT testing a prednisolone regimen with a duration longer than 24 weeks. Also it is the first RCT assessing the effect of prednisolone in the prevention of clinical NFI in patients with established subclinical neuropathy. The TENLEP study will add to the current understanding of neuropathy due to leprosy and provide insight

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

    PubMed Central

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

    2013-01-01

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

  2. 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

  3. Improved Squat and Gait Biomechanics 6-Months Post-Arthroscopic Surgery for Femoroacetabular Impingement

    PubMed Central

    Cvetanovich, Gregory; Farkas, Gary Jordan; Rajan, Kumar; Espinoza, Alejandro; Nho, Shane Jay

    2016-01-01

    Objectives: This study aimed to assess gait and squat biomechanics 6-months following arthroscopic surgery for femoroacetabular impingement. Methods: Symptomatic patients with clinical and radiographic diagnosis of FAI who had failed non-operative treatment underwent gait and squat analysis preoperatively and at 6-months postoperatively following arthroscopic surgery for FAI. Age- and BMI-matched controls without radiographic FAI or other lumbar or lower extremity pathology underwent a single analysis for comparison. Comparisons between preoperative and 6-month postoperative gait and squat parameters as well as comparison to the control group were performed using paired and independent sample t-tests. Statistical significance was set at p<0.05. Results: Fifteen FAI patients and 9 controls were analyzed. Age for the patients vs. controls was 28.7±9.6 y vs. 27.8±6.5 y (p>0.05), respectively; while BMI was 23.5±5.1 kg/m2 vs. 22.8±3.5 kg/m2 (p>0.05). All gait parameters were unchanged between preoperative and 6-month postoperative testing (p>0.05), with a trend toward significance for hip external rotation moment (p=0.056) (Table 1). Squat testing revealed that FAI arthroscopic surgery increased maximum hip extension (p=0.011), with a trend toward significance for hip adduction moment (p=0.059). All other squat parameters did not differ from preoperative to 6-month follow-up (p>0.05). Compared to the control group, preoperative FAI patients had reduced hip external rotation moment during gait (p=0.024), with a trend toward significance for hip abduction moment (p=0.082). No other gait or squat differences were detected between FAI patients preoperatively or 6-months postoperatively compared to controls (p>0.05). Conclusion: Biomechanical gait and squat analysis at 6-month follow-up from arthroscopic FAI surgery revealed a tendency to improve external hip rotation during gait and maximum hip extension and hip adduction during squat. Arthroscopic surgery for FAI may

  4. 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

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

    PubMed

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

    2016-07-01

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

  6. A randomized clinical trial evaluating the success rate of ethanol wet bonding technique and two adhesives

    PubMed Central

    Mortazavi, Vajihesadat; Samimi, Pouran; Rafizadeh, Mojgan; Kazemi, Shantia

    2012-01-01

    Background: Composite resin restorations may have a short lifespan due to the degradation of resin–dentin interface. Ethanol wet bonding technique may extend the longevity of resin–dentin bond. The purpose of this one year randomized clinical trial was to compare clinical performance of two adhesives with ethanol wet bonding technique. Materials and Methods: This randomized clinical trial was performed on 36 non-carious cervical lesions in 12 patients restored with composite resin using one of the following approaches: 1. OptiBond FL (Kerr, USA); 2. Clearfil SE Bond (Kuraray, Japan) with enamel etching and 3. Ethanol wet bonding technique with the part of adhesive of OptiBond FL. The clinical success rate was assessed after 24 h, 6, 9 and 12 months according to the United States Public Health Service (USPHS) criteria: Marginal discoloration, marginal defect, retention rate, caries occurrence, and postoperative sensitivity. The tooth vitality was also assessed. Results: The retention rate was 100% at baseline and at 6 months follow up for all types of bonding protocols and was 91.67% at 9 and 12 months follow up for ethanol wet bonding group. None of the restorations in three groups showed marginal defects, marginal discoloration or caries occurrence and were vital after 12 months. There was no statistically significant difference between three groups after 12 months follow up (p value = 0.358). Conclusions: Composite restorations placed using ethanol wet bonding technique presented equal performance to the other groups. PMID:23559924

  7. 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

  8. 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

  9. [Reporting adverse reactions and events in randomised clinical trials].

    PubMed

    Hemmingsen, Bianca; Støy, Lina; Wetterslev, Jørn; Tarnow, Lise; Friis, Karin Bach; Christensen, Louise Lundby; Sales, Nader; Gluud, Christian

    2010-08-30

    "Good clinical practice" (GCP) is an international guideline on how to conduct clinical trials on medical products involving human participants. Danish statute follows the EU trial directive (2001/20/EF) including the GCP guidelines. This article summarises the practical implementation of reporting adverse events and adverse reactions to the Danish Medicines Agency and the regional ethics committee based on the protocol of the ongoing Copenhagen Insulin and Metformin Therapy (CIMT) trial. PMID:20825743

  10. 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

  11. 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 ... very emotional." Should You Be Interested in a Clinical Trial People volunteer to take part in clinical ...

  12. Randomized clinical trial for treatment of chronic nightmares in trauma-exposed adults.

    PubMed

    Davis, Joanne L; Wright, David C

    2007-04-01

    Nightmares and sleep disturbance are fundamental concerns for victims of trauma. This study examined the efficacy of a manualized cognitive-behavioral treatment (CBT) for chronic nightmares in trauma-exposed individuals via a randomized clinical trial. Participants were randomly assigned to a treatment group or wait-list control group, with 27 participants completing the treatment. At the 6-month follow-up assessment, 84% of treated participants reported an absence of nightmares in the previous week. Significant decreases were also reported in symptoms of depression and posttraumatic stress, fear of sleep, and number of sleep problems, while sleep quality and quantity improved. The present study adds to the growing literature indicating this brief CBT as a first-line treatment for trauma-exposed individuals with chronic nightmares. PMID:17427914

  13. Placebos used in clinical trials for Chinese herbal medicine.

    PubMed

    Qi, Guan D; We, Ding A; Chung, Leung P; Fai, Cheng K

    2008-06-01

    One of the important components in randomized Controlled Trial (RCT) is blinding. The gold standard of clinical trials is to achieve a double blind design. However, only a small number of randomized controlled trials in traditional Chinese medicine have been reported, most of them are of poor quality in methodology including placebo preparation and verification. The purpose of the article is to review the validity of placebo used in blinded clinical trials for Chinese herbal medicine (CHM) in recent years and related patents. We searched the Wanfang Database (total of 827 Chinese journals of medicine and/or pharmacy, from 1999 to 2005) and 598 full-length articles related to placebo clinical trials were found. 77 placebo blinded clinical trials for Chinese medicine were extracted by manual search from the 598 articles. After reviewing the 77 full-length articles, we found that nearly half of the clinical trials did not pay attention to the physical quality of the testing drug and placebo and whether they were of comparable physical quality. The rest provided very limited placebo information so that blinding assurance could not be assumed. Only 2 articles (2.6%) specifically validated the comparability between the testing drug and the placebo. Researchers in Chinese medicine commonly ignored the quality of the placebo in comparison to the test drug. This may be causing bias in the clinical trials. Quality specifications and evaluation of the placebo should deserve special attention to reduce bias in randomized controlled trials in TCM study. PMID:19076001

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

    PubMed

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

    2009-04-01

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

  15. The duty to disclose adverse clinical trial results.

    PubMed

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

    2009-08-01

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

  16. 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

  17. BE-ACTIV for Depression in Nursing Homes: Primary Outcomes of a Randomized Clinical Trial

    PubMed Central

    Van Haitsma, Kimberly; Schoenbachler, Ben; Looney, Stephen W.

    2015-01-01

    Objectives. To report the primary outcomes of a cluster randomized clinical trial of Behavioral Activities Intervention (BE-ACTIV), a behavioral intervention for depression in nursing homes. Method. Twenty-three nursing homes randomized to BE-ACTIV or treatment as usual (TAU); 82 depressed long-term care residents recruited from these nursing homes. BE-ACTIV participants received 10 weeks of individual therapy after a 2-week baseline. TAU participants received weekly research visits. Follow-up assessments occurred at 3- and 6-month posttreatment. Results. BE-ACTIV group participants showed better diagnostic recovery at posttreatment in intent-to-treat analyses adjusted for clustering. They were more likely to be remitted than TAU participants at posttreatment and at 3-month posttreatment but not at 6 months. Self-reported depressive symptoms and functioning improved in both groups, but there were no significant treatment by time interactions in these variables. Discussion. BE-ACTIV was superior to TAU in moving residents to full remission from depression. The treatment was well received by nursing home staff and accepted by residents. A large proportion of participants remained symptomatic at posttreatment, despite taking one or more antidepressants. The results illustrate the potential power of an attentional intervention to improve self-reported mood and functioning, but also the difficulties related to both studying and implementing effective treatments in nursing homes. PMID:24691156

  18. 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

  19. Integrating pain metrics into oncology clinical trials.

    PubMed

    Cleeland, Charles S; O'Mara, Ann; Zagari, Martin; Baas, Carole

    2011-11-01

    Cancer-related pain is highly prevalent and often severe, and as a result is often one of the defining experiences for patients with malignancy. Patients and patients' families almost always live with the ever-present reality that cancer treatment and progression may be accompanied by pain. For patients nearing the end of life, most fear that their final days will be spent living with the terrible effects of the disease, the most important of which is pain. Despite this, there is far less systematic research on the mechanisms of cancer-related pain or on the development of new agents to reduce or eliminate pain in cancer patients compared with research to combat the disease itself. Further, even when the focus of research is treatment of the tumor, the effects of anticancer treatments on pain are often underreported in publications and other forums. To illustrate the relative drought in the cancer pain control area, there have been no new drugs approved for cancer-related pain in recent years. A number of methodologic and logistical challenges that hinder the ability to assess pain response in clinical trials are discussed in this article. Possible ways to address these challenges are also discussed. PMID:22046026

  20. Improving Alzheimer's disease phase II clinical trials.

    PubMed

    Greenberg, Barry D; Carrillo, Maria C; Ryan, J Michael; Gold, Michael; Gallagher, Kim; Grundman, Michael; Berman, Robert M; Ashwood, Timothy; Siemers, Eric R

    2013-01-01

    Over the past 30 years, many drugs have been studied as possible treatments for Alzheimer's disease, but only four have demonstrated sufficient efficacy to be approved as treatments, of which three are in the same class. This lack of success has raised questions both in the pharmaceutical industry and academia about the future of Alzheimer's disease therapy. The high cost and low success rate of drug development across many disease areas can be attributed, in large part, to late-stage clinical failures (Schachter and Ramoni, Nat Rev Drug Discov 2007;6:107-8). Thus, identifying in phase II, or preferably phase I, drugs that are likely to fail would have a dramatic impact on the costs associated with developing new drugs. With this in mind, the Alzheimer's Association convened a Research Roundtable on June 23 and 24, 2011, in Washington, DC, bringing together scientists from academia, industry, and government regulatory agencies to discuss strategies for improving the probability of phase II trial results predicting success when considering the go/no-go decision-making process leading to the initiation of phase III. PMID:23164548

  1. The Clinical Trials Involvement of Latino and White Physicians

    PubMed Central

    Ramirez, Amelie G.; Wildes, Kimberly; Talavera, Greg; Nápoles-Springer, Anna; Gallion, Kipling; Pérez-Stable, Eliseo J.

    2008-01-01

    Background Ethnic differences in physicians’ attitudes and behaviors related to clinical trials might partially account for disparities in clinical trial participation among Latino patients. Literature regarding Latino physicians’ involvement in clinical trials, in comparison to White physicians, could not be found. Methods Cross-sectional data from randomly selected physicians (N=695), stratified by ethnicity, were analyzed to test associations of ethnicity with physicians’ participation in and attitudes toward referral of patients to clinical trials. Results Chi-square analyses showed significant (p<0.05) associations of physician race/ethnicity and clinical trials involvement, type of trial for which the physician is likely to recommend a patient, belief in scientific value, and factors that would influence recommendation for a patient to participate. Multivariate analyses resulted in several significant (p<0.05) predictors of clinical trials outcomes, including physician race/ethnicity. Conclusions Latino physicians were significantly less involved in clinical trials than White physicians and found less scientific value in them, highlighting areas for future education and intervention. PMID:18155966

  2. A prospective study of atopic dermatitis managed without topical corticosteroids for a 6-month period

    PubMed Central

    Fukaya, Mototsugu; Sato, Kenji; Yamada, Takahiro; Sato, Mitsuko; Fujisawa, Shigeki; Minaguchi, Satoko; Kimata, Hajime; Dozono, Haruhiko

    2016-01-01

    Topical corticosteroids (TCS) are regarded as the mainstay treatment for atopic dermatitis (AD). As AD has a tendency to heal naturally, the long-term efficacy of TCS in AD management should be compared with the outcomes seen in patients with AD not using TCS. However, there are few long-term studies that consider patients with AD not using TCS. We designed a prospective multicenter cohort study to assess the clinical outcomes in patients with AD who did not use TCS for 6 months and then compared our results with an earlier study by Furue et al which considered AD patients using TCS over 6 months. Our patients’ clinical improvement was comparable with the patients described in Furue’s research. In light of this, it is reasonable for physicians to manage AD patients who decline TCS, as the expected long-term prognosis is similar whether they use TCS or not. PMID:27445501

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

    PubMed

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

    2014-10-01

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

  4. Preventive treatment of chronic bronchitis: a meta-analysis of clinical trials with a bacterial extract (OM-85 BV) and a cost-effectiveness analysis.

    PubMed

    Bergemann, R; Brandt, A; Zoellner, U; Donner, C F

    1994-09-01

    Chronic bronchitis is a lifelong disease with significant effects on the patient and on the costs to health insurance institutions. Acute exacerbations in chronic bronchitic patients may have a negative impact on patients' quality of life and on the progression of the disease, particularly in more severe patients. The clinical efficacy of the immunoactive bacterial extract OM-85 BV has been shown in several clinical trials, a cost-effectiveness evaluation (CEA) of its use in chronic bronchitic patients has not been fulfilled so far. In this study a meta-analysis on the preventive treatment of acute exacerbations with OM-85 BV and a CEA, focusing on direct costs only, was performed. The meta-analysis showed a mean value of 0.6 prevented acute exacerbations per 6 months per patient, and a reduction of 9 days in antibiotic treatment per 6 months per patient. CEA evaluated the different cost elements. The mean direct cost (consultations, antibiotics, etc.) for the treatment of 1 acute exacerbation in chronic bronchitic patients was calculated as 143, 459 Lira. Thus for 0.6 prevented acute exacerbations per 6 months per patient a reduction in cost of 86,075 Lira (0.6-143,459) could be expected. The additional costs for the preventive treatment with OM-85 BV, based on prices for Italy, are 34,980 Lira per patient per 6 months. In conclusion, the effective cost savings per patient per 6 months are 51, 095 Lira. The sensitivity analysis revealed only one critical parameter, i.e. the clinical effectiveness of OM-85 BV. Even assuming 0.3 prevented exacerbations per 6 months per patient, the preventive treatment still proved to be cost effective. PMID:8000415

  5. 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...

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

    PubMed

    Oba, Koji

    2016-02-01

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

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

    PubMed

    Aotani, Eriko

    2007-02-01

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

  8. 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

  9. Key Concepts of Clinical Trials: A Narrative Review

    PubMed Central

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

    2012-01-01

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

  10. 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

  11. Money and morals: ending clinical trials for financial reasons.

    PubMed

    Eaton, Margaret L; Kwon, Brian K; Scott, Christopher Thomas

    2015-01-01

    Too often, biopharmaceutical companies stop their clinical trials solely for financial reasons. In this chapter, we discuss this phenomenon against the backdrop of a 2011 decision by Geron Corporation to abandon its stem cell clinical trial for spinal cord injury (SCI), the preliminary results of which were released in May 2014. We argue that the resultant harms are widespread and are different in nature from the consequences of stopping trials for scientific or medical reasons. We examine the ethical and social effects that arise from such decisions and discuss them in light of ethical frameworks, including duties of individual stakeholders and corporate sponsors. We offer ways that sponsors and clinical sites can ensure that trials are responsibly started, and once started adequately protect the interests of participants. We conclude with recommendations that industry sponsors of clinical trials should adopt in order to advance a collective and patient-centered research ethic. PMID:25062706

  12. Mitigating the Effects of Nonadherence in Clinical Trials.

    PubMed

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

    2016-09-01

    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

  13. Do 6-month-olds understand that speech can communicate?

    PubMed

    Vouloumanos, Athena; Martin, Alia; Onishi, Kristine H

    2014-11-01

    Adults and 12-month-old infants recognize that even unfamiliar speech can communicate information between third parties, suggesting that they can separate the communicative function of speech from its lexical content. But do infants recognize that speech can communicate due to their experience understanding and producing language, or do they appreciate that speech is communicative earlier, with little such experience? We examined whether 6-month-olds recognize that speech can communicate information about an object. Infants watched a Communicator selectively grasp one of two objects (target). During test, the Communicator could no longer reach the objects; she turned to a Recipient and produced speech (a nonsense word) or non-speech (coughing). Infants looked longer when the Recipient selected the non-target than the target object when the Communicator spoke but not when she coughed - unless the Recipient had previously witnessed the Communicator's selective grasping of the target object. Our results suggest that at 6 months, with a receptive vocabulary of no more than a handful of commonly used words, infants possess some abstract understanding of the communicative function of speech. This understanding may provide an early mechanism for language and knowledge acquisition. PMID:24835877

  14. DICOM Structured Reporting and Cancer Clinical Trials Results

    PubMed Central

    Clunie, David A

    2007-01-01

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

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

    PubMed

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

    2012-05-01

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

  16. Clinical Trial Design Issues in Mild to Moderate Alzheimer Disease

    PubMed Central

    Knopman, David S.

    2009-01-01

    The field of clinical trials and therapeutics in Alzheimer Disease (AD) is little more than 20 years old. Considerable progress has been made in crafting appropriate designs for clinical trials of promising therapeutic agents for AD. This article reviews basic issues in diagnostic criteria, choice of outcome measures, duration of trials and analytic strategies. Through trial and error, a general set of strategies has evolved for the assessment of putative therapies for mild to moderate AD. The experience of the past two decades has set the stage for discovering the next generation of anti-AD drugs and introducing those therapies at milder stages of the disease. PMID:19057167

  17. Randomization in clinical trials: conclusions and recommendations.

    PubMed

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

    1988-12-01

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

  18. 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

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

    PubMed

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

    2015-06-01

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

  20. 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. PMID:25315593

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

    PubMed

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

    2016-03-01

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

  2. 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 ...

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

    PubMed

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

    2004-06-01

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

  4. 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

  5. Clinical Trials For Cytoprotection In Stroke

    PubMed Central

    Labiche, Lise A.; Grotta, James C.

    2004-01-01

    Summary: To date, many cytoprotective drugs have reached the stage of pivotal phase 3 efficacy trials in acute stroke patients. (Table 1) Unfortunately, throughout the neuroprotective literature, the phrase “failure to demonstrate efficacy” prevails as a common thread among the many neutral or negative trials, despite the largely encouraging results encountered in preclinical studies. The reasons for this discrepancy are multiple, and have been discussed by Dr. Zivin in his review. Many of the recent trials have addressed deficiencies of the previous ones with more rigorous trial design, including more specific patient selection criteria (ensure homogeneity of stroke location and severity), stratified randomization algorithms (time-to-treat), narrowed therapeutic time-window and pharmacokinetic monitoring. Current trials have also incorporated biologic surrogate markers of toxicity and outcome such as drug levels and neuroimaging. Lastly, multi-modal therapies and coupled cytoprotection/reperfusion strategies are being investigated to optimize tissue salvage. This review will focus on individual therapeutic strategies and we will emphasize what we have learned from these trials both in terms of trial design and the biologic effect (or lack thereof) of these agents. PMID:15717007

  6. '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

  7. 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

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

    PubMed Central

    Geifman, Nophar; Butte, Atul J.

    2016-01-01

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

  9. Clinical Trial of Erythropoietin in Young Children With Cerebral Palsy.

    PubMed

    Cho, Kye Hee; Min, Kyunghoon; Lee, Seung Hoon; Lee, SunHee; An, SeongSoo A; Kim, MinYoung

    2016-09-01

    This study was conducted to assess the safety and efficacy of recombinant human erythropoietin in young children with cerebral palsy aged between 6 months and 3 years. All participants received subcutaneous recombinant human erythropoietin and 8 weeks of rehabilitation therapy. Adverse events, changes of vital signs, and hematologic tests were monitored up to 8 weeks postinjection. Functional measures of development at 4 and 8 weeks postinjection were compared with baseline values, and improvements were compared with those of an age-matched historical control group. Nine participants completed the trial from June 2012 to February 2015. No adverse events were related to recombinant human erythropoietin. Erythropoiesis was noted, although within normal range. Functional improvements were observed in all participants (P < .05) and increases in motor function were higher in recombinant human erythropoietin group than the control group. Accordingly, recombinant human erythropoietin administration was safe without any significant adverse events and improved the functional outcomes in young children with cerebral palsy. PMID:27233796

  10. 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

  11. Robot-assisted upper-limb therapy in acute rehabilitation setting following stroke: Department of Veterans Affairs multisite clinical trial.

    PubMed

    Burgar, Charles G; Lum, Peter S; Scremin, A M Erika; Garber, Susan L; Van der Loos, H F Machiel; Kenney, Deborah; Shor, Peggy

    2011-01-01

    This randomized, controlled, multisite Department of Veterans Affairs clinical trial assessed robot-assisted (RA) upper-limb therapy with the Mirror Image Movement Enabler (MIME) in the acute stroke rehabilitation setting. Hemiparetic subjects (n = 54) received RA therapy using MIME for either up to 15 hours (low-dose) or 30 hours (high-dose) or received up to 15 hours of additional conventional therapy in addition to usual care (control). The primary outcome measure was the Fugl-Meyer Assessment (FMA). The secondary outcome measures were the Functional Independence Measure (FIM), Wolf Motor Function Test, Motor Power, and Ashworth scores at intake, discharge, and 6-month follow-up. Mean duration of study treatment was 8.6, 15.8, and 9.4 hours for the low-dose, high-dose, and control groups, respectively. Gains in the primary outcome measure were not significantly different between groups at follow-up. Significant correlations were found at discharge between FMA gains and the dose and intensity of RA. Intensity also correlated with FMA gain at 6 months. The high-dose group had greater FIM gains than controls at discharge and greater tone but no difference in FIM changes compared with low-dose subjects at 6 months. As used during acute rehabilitation, motor-control changes at follow-up were no less with MIME than with additional conventional therapy. Intensity of training with MIME was positively correlated with motor-control gains. PMID:21674393

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

    PubMed Central

    Goodarzynejad, Hamidreza; Babamahmoodi, Abdolreza

    2015-01-01

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

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

    PubMed

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

    2015-01-01

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

  14. Factors associated to breastfeeding cessation before 6 months.

    PubMed

    Roig, Antoni Oliver; Martínez, Miguel Richart; García, Julio Cabrero; Hoyos, Santiago Pérez; Navidad, Ginesa Laguna; Alvarez, Juan Carlos Flores; Pujalte, María Del Mar Calatayud; De León González, Ricardo García

    2010-01-01

    This research aimed to identify the determinants of full breastfeeding (FBF) and any breastfeeding (ABF) cessation before 6 months, through a six-month follow-up of 248 mothers going a postpartum visit. Data were collected by personal interview during the first month and telephone interviews at four and six months postpartum. Coxs proportional hazards model was used. Not having previous ABF experience, previous ABF duration

  15. 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

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

    PubMed Central

    Cummings, Jeffrey; Gould, Heath; Zhong, Kate

    2012-01-01

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

  17. Targeting temporomandibular disorder pain treatment to hormonal fluctuations: a randomized clinical trial.

    PubMed

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

    2011-09-01

    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 3 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 12months 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 time points. COCT was associated with multiple adverse events (none serious). The study provides further support for long-term benefits of a safe, low-intensity (2 in-person sessions and 6 brief telephone contacts), dental hygienist-delivered self-management treatment for TMD pain. PMID:21680092

  18. 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

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

    PubMed

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

    2014-10-01

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

  20. 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

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

    MedlinePlus

    ... other federal agencies, pharmaceutical companies, universities and nonprofit organizations. Here's how it works. After you enter the ClinicalTrials.gov Web site, you can search for a trial by the name of the disease, the location of the study, the type of treatment or the sponsoring institution. ...

  2. 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

  3. 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

  4. Textual inference for eligibility criteria resolution in clinical trials.

    PubMed

    Shivade, Chaitanya; Hebert, Courtney; Lopetegui, Marcelo; de Marneffe, Marie-Catherine; Fosler-Lussier, Eric; Lai, Albert M

    2015-12-01

    Clinical trials are essential for determining whether new interventions are effective. In order to determine the eligibility of patients to enroll into these trials, clinical trial coordinators often perform a manual review of clinical notes in the electronic health record of patients. This is a very time-consuming and exhausting task. Efforts in this process can be expedited if these coordinators are directed toward specific parts of the text that are relevant for eligibility determination. In this study, we describe the creation of a dataset that can be used to evaluate automated methods capable of identifying sentences in a note that are relevant for screening a patient's eligibility in clinical trials. Using this dataset, we also present results for four simple methods in natural language processing that can be used to automate this task. We found that this is a challenging task (maximum F-score=26.25), but it is a promising direction for further research. PMID:26376462

  5. Temporal knowledge representation for scheduling tasks in clinical trial protocols.

    PubMed Central

    Weng, Chunhua; Kahn, Michael; Gennari, John

    2002-01-01

    Clinical trial protocols include detailed temporal constraints on treatment and associated tasks. Unlike health-care guidelines, protocols are highly prescriptive. Therefore, informatics applications that enforce such temporal constraints are more directly useful with protocols than with guidelines. Although there are some temporal knowledge representation efforts for health-care guidelines, we find these to be insufficiently expressive for clinical trial protocols. In this paper, we focus on temporal knowledge representation for clinical trial protocols and the task of patient-specific scheduling in protocols. We define a temporal ontology, use it to encode clinical trial protocols, and describe a prototype tool to carry out patient-specific scheduling for the tasks in protocols. We predict that an expressive temporal knowledge representation can support a number of scheduling and management tasks for protocol-based care. PMID:12463951

  6. 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 ...

  7. What Are the Possible Benefits and Risks of Clinical Trials?

    MedlinePlus

    ... of questions to ask your doctor and the research staff, go to "How Do Clinical Trials Protect Participants?" Featured Video ... children and their own motivations for pursuing research in this field. Learn more at http://www. ...

  8. 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

  9. ClinicalTrials.gov | NIH MedlinePlus the Magazine

    MedlinePlus

    ... of Contents “...a powerful tool for the healthcare consumer” Clinical trials are research studies that use volunteers to help medical professionals test new treatments for a wide array of diseases and ...

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

    PubMed

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

    2008-01-01

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

  11. NIH-Supported Clinical Trial Finds Antidepressant Reduces Alzheimer's Agitation

    MedlinePlus

    ... Plan National Alzheimer's Project Act (NAPA) About ADEAR NIH-supported clinical trial finds antidepressant reduces Alzheimer’s agitation February 25, 2014 NIH-funded researchers are testing interventions to alleviate psychiatric ...

  12. 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

  13. 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. PMID:26194810

  14. 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

  15. Immunotherapy for pancreatic ductal adenocarcinoma: an overview of clinical trials

    PubMed Central

    Paniccia, Alessandro; Merkow, Justin; Edil, Barish H.

    2015-01-01

    Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer-related death and current therapeutic strategies are often unsatisfactory. Identification and development of more efficacious therapies is urgently needed. Immunotherapy offered encouraging results in preclinical models during the last decades, and several clinical trials have explored its therapeutic application in PDAC. The aim of this review is to summarize the results of clinical trials conducted to evaluate the future perspective of immunotherapy in the treatment of PDAC. PMID:26361407

  16. Unconventional Anticancer Agents: A Systematic Review of Clinical Trials

    PubMed Central

    Vickers, Andrew J.; Kuo, Joyce; Cassileth, Barrie R.

    2006-01-01

    Purpose A substantial number of cancer patients turn to treatments other than those recommended by mainstream oncologists in an effort to sustain tumor remission or halt the spread of cancer. These unconventional approaches include botanicals, high-dose nutritional supplementation, off-label pharmaceuticals, and animal products. The objective of this study was to review systematically the methodologies applied in clinical trials of unconventional treatments specifically for cancer. Methods MEDLINE 1966 to 2005 was searched using approximately 200 different medical subject heading terms (eg, alternative medicine) and free text words (eg, laetrile). We sought prospective clinical trials of unconventional treatments in cancer patients, excluding studies with only symptom control or nonclinical (eg, immune) end points. Trial data were extracted by two reviewers using a standardized protocol. Results We identified 14,735 articles, of which 214, describing 198 different clinical trials, were included. Twenty trials were phase I, three were phase I and II, 70 were phase II, and 105 were phase III. Approximately half of the trials investigated fungal products, 20% investigated other botanicals, 10% investigated vitamins and supplements, and 10% investigated off-label pharmaceuticals. Only eight of the phase I trials were dose-finding trials, and a mere 20% of phase II trials reported a statistical design. Of the 27 different agents tested in phase III, only one agent had a prior dose-finding trial, and only for three agents was the definitive study initiated after the publication of phase II data. Conclusion Unconventional cancer treatments have not been subject to appropriate early-phase trial development. Future research on unconventional therapies should involve dose-finding and phase II studies to determine the suitability of definitive trials. PMID:16382123

  17. 78 FR 7437 - Proposed Collection; Comment Request (60-Day FRN); The Clinical Trials Reporting Program (CTRP...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-02-01

    ... Clinical Trials Reporting Program (CTRP) Database (NCI) SUMMARY: In compliance with the requirement of... publication. Proposed Collection: The Clinical Trials Reporting Program (CTRP) Database, 0925-0600,...

  18. Using Registries to Recruit Subjects for Clinical Trials

    PubMed Central

    Tan, Meng H; Thomas, Matthew; MacEachern, Mark P

    2015-01-01

    Aim We studied the use of patient/disease registries to recruit potential subjects for prospective clinical trials - describing the number, types and major benefits of using this approach. Methods In December 2013, we conducted a focused database search in PubMed, EMBASE, and Web of Science for studies (English language only) that used registries to recruit subjects for clinical trials published in 2004-2013. Of the 233 unique citations identified, 21 used registries to recruit subjects - 10 papers and 11 abstracts. Pearling and search for subsequent full papers of the abstracts identified 4 more papers. Results Our analysis, based on these 25 citations, showed 14 are related to cancer, 3 to diabetes mellitus, 1 each to stroke, asthma, and celiac disease and 5 are disease neutral. Many types of registries (population-based cancer, quality improvement, disease-specific, web-based disease-neutral registries, local general practice registers, and national health database) are used to recruit subjects for clinical trials and uncover new knowledge. Overall, 16 registries are in the US, 4 in UK, 1 each in Canada, Spain, Australia and I in many countries. Registries can identify very large number of subjects for screening for eligibility for clinical trials, especially in very large trials, rare disease trials, and trials involving minority patients. Conclusions Registries can retrospectively identify very large numbers of potential subjects for screening for eligibility and enrollment in prospective clinical trials. This matching can lead to more timely recruitment and help solve a major problem in conducting clinical trials. PMID:25545027

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  1. 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

  2. A Randomized Trial of Family Focused Therapy With Populations at Clinical High Risk for Psychosis: Effects on Interactional Behavior

    PubMed Central

    O’Brien, Mary P.; Miklowitz, David J.; Candan, Kristin A.; Marshall, Catherine; Domingues, Isabel; Walsh, Barbara C.; Zinberg, Jamie L.; De Silva, Sandra D.; Woodberry, Kristen A.; Cannon, Tyrone D.

    2013-01-01

    Objective This study investigated whether family focused therapy (FFT-CHR), an 18-session intervention that consisted of psychoeducation and training in communication and problem solving, brought about greater improvements in family communication than enhanced care (EC), a 3-session psychoeducational intervention, among individuals at clinical high risk for developing psychosis. Method This study was conducted within a randomized controlled trial across 8 sites. We examined 10-min problem-solving discussions at baseline and 6-month reassessment among 66 adolescents and young adults and their parents. Trained coders who were blind to treatment and time of assessment achieved high levels of interrater reliability when evaluating family discussions on categories of calm–constructive and critical– conflictual behavior. Results Individuals at high risk and their family members who participated in FFT-CHR demonstrated greater improvement from baseline to 6-month reassessment in constructive communication and decreases in conflictual behaviors during family interactions than those in EC. Participants in FFT-CHR showed greater increases from baseline to 6 months in active listening and calm communication and greater decreases in irritability and anger, complaints and criticism, and off-task comments compared to participants in EC. These changes occurred equally in high-risk participants and their family members. Conclusions A 6-month family skills training treatment can bring about significant improvement in family communication among individuals at high risk for psychosis and their parents. Future studies should examine the association between enhancements in family communication and reduced risk for the onset of psychosis among individuals at high risk. PMID:24188511

  3. Bach flower remedies: a systematic review of randomised clinical trials.

    PubMed

    Ernst, Edzard

    2010-01-01

    Bach flower remedies continue to be popular and its proponents make a range of medicinal claims for them. The aim of this systematic review was to critically evaluate the evidence for these claims. Five electronic databases were searched without restrictions on time or language. All randomised clinical trials of flower remedies were included. Seven such studies were located. All but one were placebo-controlled. All placebo-controlled trials failed to demonstrate efficacy. It is concluded that the most reliable clinical trials do not show any differences between flower remedies and placebos. PMID:20734279

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

    PubMed

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

    2015-03-01

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

  5. 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

  6. 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. PMID:7960072

  7. 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

  8. 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

  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. Building clinical trial priorities at the University of Rwanda.

    PubMed

    Condo, Jeanine; Kateera, Brenda; Mutimura, Eugene; Birungi, Francine; Ndagijimana, Albert; Jansen, Stefan; Kamwesiga, Julius; Forrest, Jamie I; Mills, Edward J; Binagwaho, Agnes

    2014-01-01

    After the genocide in Rwanda, the country's healthcare system collapsed. Remarkable gains have since been made by the state to provide greater clinical service capacity and expand health policies that are grounded on locally relevant evidence. This commentary explores the challenges faced by Rwanda in building an infrastructure for clinical trials. Through local examples, we discuss how a clinical trial infrastructure can be constructed by (1) building educational capacity; (2) encouraging the testing of relevant interventions using appropriate and cost-effective designs; and, (3) promoting ethical and regulatory standards. The future is bright for clinical research in Rwanda and with a renewed appetite for locally generated evidence it is necessary that we discuss the challenges and opportunities in drawing up a clinical trials agenda. PMID:25429819

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

    PubMed

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

    2016-06-01

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

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

    PubMed

    Scott, Christopher Thomas; Magnus, David

    2014-12-01

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

  13. 77 FR 74670 - Draft Guidance for Industry on Enrichment Strategies for Clinical Trials to Support Approval of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-12-17

    ... potential clinical trial designs, and discusses potential regulatory considerations when using enrichment... discusses general clinical trial design considerations, provides examples of potential clinical trial..., will represent the Agency's current thinking on clinical trial designs employing enrichment...

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

    PubMed

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

    2016-08-01

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

  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. PMID:26853346

  17. 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

  18. 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…

  19. 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

  20. Clinical Trial Design Issues in Systemic Sclerosis: an Update.

    PubMed

    Gordon, Jessica K; Domsic, Robyn T

    2016-06-01

    Systemic sclerosis (scleroderma, SSc) is a multisystem disease characterized by vasculopathy, autoimmunity, and fibrosis. SSc has the highest disease-related mortality rate among the rheumatologic illnesses. In the USA, there remains no FDA-approved therapy. As our understanding of SSc pathogenesis improves, targeted therapies interrupting key pathways and mediators will be studied in clinical trials. However, clinical trials in SSc are fraught with challenges. Validated clinical outcome measures do not exist for all disease manifestations. It can be difficult to discern disease activity from damage. SSc is highly heterogeneous, with multiple different phenotypes, and predicting who will have progressive disease is not currently well understood. Biomarkers are in early stages of development and do not represent surrogate outcomes at this time. Given that SSc is uncommon, studies of similar disease aspects or populations can lead to competition for patients. This review will focus on current issues in SSc clinical trial design. PMID:27146381

  1. Reporting, access, and transparency: better infrastructure of clinical trials.

    PubMed

    Antonelli, Massimo; Mercurio, Giovanna

    2009-01-01

    Open access to information in medical science and adequate reporting of clinical trials may allow investigators and editors to recognize bias in study designs and avoid unnecessary duplication of efforts. Unfortunately, most of clinical trials are very expensive and are often supported by industries that may have financial reasons to hide or partially disclose results. However, investigators and editors have a greater interest in publishing results that can immediately change clinical practice rather than negative results, thus contributing to facilitate publication biases. Several years ago, legislation in several countries mandated the registration of clinical trials as an effective means of promoting information access and full transparency in medical research. However, comprehensive registers have not been adequately supported by law, particularly in Europe, where legislation has ironically contributed to fragmented research, and dampened its competitiveness and productivity. In this context, appropriate strategies help to protect the independence of academic research and ensure full transparency in medical science. PMID:19104221

  2. Clinical trials transparency and the Trial and Experimental Studies Transparency (TEST) act.

    PubMed

    Logvinov, Ilana

    2014-03-01

    Clinical trial research is the cornerstone for successful advancement of medicine that provides hope for millions of people in the future. Full transparency in clinical trials may allow independent investigators to evaluate study designs, perform additional analysis of data, and potentially eliminate duplicate studies. Current regulatory system and publishers rely on investigators and pharmaceutical industries for complete and accurate reporting of results from completed clinical trials. Legislation seems to be the only way to enforce mandatory disclosure of results. The Trial and Experimental Studies Transparency (TEST) Act of 2012 was introduced to the legislators in the United States to promote greater transparency in research industry. Public safety and advancement of science are the driving forces for the proposed policy change. The TEST Act may benefit the society and researchers; however, there are major concerns with participants' privacy and intellectual property protection. PMID:24440100

  3. 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

  4. 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

  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. 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

  7. 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. PMID:21813511

  8. 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

  9. Results of a preliminary clinical trial on a multiple channel cochlear prosthesis.

    PubMed

    Dowell, R C; Martin, L F; Clark, G M; Brown, A M

    1985-01-01

    Speech discrimination testing was carried out under clinical trial conditions for eight profoundly postlingually deaf adults to assess the efficacy of a newly developed 22-channel cochlear prosthesis and speech processor. Three months postoperatively, these patients showed significantly better results with the cochlear prosthesis than for preoperative testing with a conventional hearing aid or vibrotactile aid (following a 6-month trial with the aid) on each of a series of tests from the Minimal Auditory Capabilities battery. Assessment of lipreading enhancement using standard speech tests, consonant recognition studies, and speech tracking showed significant improvements for each patient when using the cochlear prosthesis. Six patients showed a significant amount of open set speech discrimination without lipreading at levels which have not been reported for single electrode cochlear prostheses. The two patients who performed poorly on these tests both had restricted multiple channel systems due to their disease, one patient being restricted to virtually a single channel system and the other to only ten of the 22 electrodes. These results indicate that this multiple channel cochlear prosthesis has potential as a treatment for profound postlingual deafness over a wide range of etiologies and ages. PMID:3160295

  10. 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

  11. Night Waking in 6-Month-Old Infants and Maternal Depressive Symptoms

    PubMed Central

    Karraker, Katherine Hildebrandt; Young, Marion

    2008-01-01

    Relations between night waking in infants and depressive symptoms in their mothers at 6 months postpartum were examined using the data from the National Institute for Child Health and Human Development Study of Early Child Care. Although more depressive symptoms were only weakly correlated with a higher frequency of infant waking, longer wake times, and more total time awake, the rate of clinically significant depression scores was about double in mothers of chronically waking infants in comparison with mothers whose infants did not awaken during the night. The value of comparing subgroups to elucidate relations identified through correlations is discussed. PMID:19050747

  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. 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

  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. PMID:26374676

  15. 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

  16. Designing clinical trials in trauma surgery

    PubMed Central

    Perry, D. C.; Griffin, X. L.; Parsons, N.; Costa, M. L.

    2014-01-01

    The surgical community is plagued with a reputation for both failing to engage and to deliver on clinical research. This is in part due to the absence of a strong research culture, however it is also due to a multitude of barriers encountered in clinical research; particularly those involving surgical interventions. ‘Trauma’ amplifies these barriers, owing to the unplanned nature of care, unpredictable work patterns, the emergent nature of treatment and complexities in the consent process. This review discusses the barriers to clinical research in surgery, with a particular emphasis on trauma. It considers how barriers may be overcome, with the aim to facilitate future successful clinical research. Cite this article: Bone Joint Res 2014;3:123–9. PMID:24764547

  17. Recommendations for Soluble Biomarker Assessments in Osteoarthritis Clinical Trials

    PubMed Central

    Kraus, Virginia Byers; Blanco, Francisco J; Englund, Martin; Henrotin, Yves; Lohmander, L Stefan; Losina, Elena; Önnerfjord, Patrik; Persiani, Stefano

    2015-01-01

    Objective To describe requirements for inclusion of soluble biomarkers in osteoarthritis (OA) clinical trials and progress toward OA-related biomarker qualification. Methods 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. Results This document summarizes current guidance on use of biomarkers in OA clinical trials and their utility at 5 stages, including preclinical development and phase I to phase IV trials. Conclusions 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

  18. The protection of patients' rights in clinical trials.

    PubMed

    Czarkowski, Marek

    2006-01-01

    The Helsinki Declaration is a very important document regarding the protection of patients' rights in clinical trials and one of the fundamental sources of operational principles for every ethics committee. Although they have been updated, the international guidelines for ethics committees continually fail to address certain issues pertaining to the protection of patients' rights in clinical trials. These issues include, most significantly, the method of electing ethics committees (a free, secret ballot should be preferred to direct appointment), the avoidance of conflict of interest during the election of ethics committee members, and the necessary insurance coverage for the participants of clinical trials. Polish law should, on the other hand, be developed in such way as to not limit the effectiveness of ethics committees in protecting patients' rights in clinical trials. The ideal solution would be to draft a uniform law concerning not only clinical trials, but all medical experiments. The opinions of experts who have been reviewing medical research projects for several years may prove to be especially valuable in this setting. PMID:16501654

  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. 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.

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

    PubMed

    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

  2. Clinical trials in palliative care: an ethical evaluation.

    PubMed

    Janssens, R; Gordijn, B

    2000-08-01

    On first sight, clinical trials do not seem to fit well within the concept of palliative care. In palliative care, the needs and wishes of the patient set the norm while participation in experimental trials is potentially harmful for the patient. The dilemma seems hard to solve as optimal care for the dying and improvement of treatment for future patients are both imperative. Yet, the one seems to exclude the other. However, on closer examination it becomes less evident that clinical trials in palliative care confront us with an unsolvable dilemma. Some patients' lives may gain meaning through participation in trials out of solidarity with future patients. In order to clarify this, the notions of authenticity and hope can be illuminative. PMID:10900367

  3. The FDA and designing clinical trials for chronic cutaneous ulcers.

    PubMed

    Maderal, Andrea D; Vivas, Alejandra C; Eaglstein, William H; Kirsner, Robert S

    2012-12-01

    Treatment of chronic wounds can present a challenge, with many patients remaining refractory to available advanced therapies. As such, there is a strong need for the development of new products. Unfortunately, despite this demand, few new wound-related drugs have been approved over the past decade. This is in part due to unsuccessful clinical trials and subsequent lack of Food and Drug Administration (FDA) approval. In this article, we discuss the FDA approval process, how it relates to chronic wound trials, common issues that arise, and how best to manage them. Additionally, problems encountered specific to diabetic foot ulcers (DFU) and venous leg ulcers (VLU) are addressed. Careful construction of a clinical trial is necessary in order to achieve the best possible efficacy outcomes and thereby, gain FDA approval. How to design an optimal trial is outlined. PMID:23063664

  4. A Randomized Clinical Trial on Preventing Pressure Ulcers with Wheelchair Seat Cushions

    PubMed Central

    Brienza, David; Kelsey, Sheryl; Karg, Patricia; Allegretti, Ana; Olson, Marian; Schmeler, Mark; Zanca, Jeanne; Geyer, Mary Jo; Kusturiss, Marybeth; Holm, Margo

    2010-01-01

    Objectives To determine the efficacy of skin protection wheelchair seat cushions in preventing pressure ulcers in the elderly, nursing home population Design Clinical trial with participants assigned at random to either a skin protection or segmented foam cushion. Two hundred thirty two participants were recruited between June 2004 and May 2008 and followed for 6 months or until pressure ulcer incidence. Setting Twelve nursing homes Participants Nursing home residents’ age ≥ 65, using wheelchairs ≥6 hours/day, Braden score ≤ 18, and combined Braden activity and mobility score ≤ 5. Participants were recruited from a referred sample. Intervention All participants were provided a fitted wheelchair and randomized into skin protection (SPC) or segmented foam (SFC) cushion groups. The SPC group received an air, viscous fluid/foam, or gel/foam cushion. The SFC group received a 7.6 cm crosscut foam cushion. Measurements Pressure ulcer incidence over 6 months for wounds near the ischial tuberosities (IT ulcers) were measured. Secondary analysis was performed on combined IT and sacral/coccyx ulcers. Results One hundred eighty participants reached a study endpoint and 42 were lost to follow-up. Ten did not receive the intervention. There were 8/119 (6.7%) IT ulcers in the SFC group and 1/113 (0.9%) in the SPC group (p<0.04). In the group of combined IT and sacral/coccyx ulcers, there were 21/119 pressure ulcers (17.6%) in the SFC group and 12/113 (10.6%) in the SPC group (p=0.14). Conclusion Skin protection cushions used with fitted wheelchairs lower pressure ulcer incidence for elderly, nursing home residents and should be used to help prevent pressure ulcers. PMID:21070197

  5. 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.

  6. 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

  7. Progesterone neuroprotection: The background of clinical trial failure.

    PubMed

    Schumacher, Michael; Denier, Christian; Oudinet, Jean-Paul; Adams, David; Guennoun, Rachida

    2016-06-01

    Since the first pioneering studies in the 1990s, a large number of experimental animal studies have demonstrated the neuroprotective efficacy of progesterone for brain disorders, including traumatic brain injury (TBI). In addition, this steroid has major assets: it easily crosses the blood-brain-barrier, rapidly diffuses throughout the brain and exerts multiple beneficial effects by acting on many molecular and cellular targets. Moreover, progesterone therapies are well tolerated. Notably, increased brain levels of progesterone are part of endogenous neuroprotective responses to injury. The hormone thus emerged as a particularly promising protective candidate for TBI and stroke patients. The positive outcomes of small Phase 2 trials aimed at testing the safety and potential protective efficacy of progesterone in TBI patients then provided support and guidance for two large, multicenter, randomized and placebo-controlled Phase 3 trials, with more than 2000 TBI patients enrolled. The negative outcomes of both trials, named ProTECT III and SyNAPSE, came as a big disappointment. If these trials were successful, progesterone would have become the first efficient neuroprotective drug for brain-injured patients. Thus, progesterone has joined the numerous neuroprotective candidates that have failed in clinical trials. The aim of this review is a reappraisal of the preclinical animal studies, which provided the proof of concept for the clinical trials, and we critically examine the design of the clinical studies. We made efforts to present a balanced view of the strengths and limitations of the translational studies and of some serious issues with the clinical trials. We place particular emphasis on the translational value of animal studies and the relevance of TBI biomarkers. The probability of failure of ProTECT III and SyNAPSE was very high, and we present them within the broader context of other unsuccessful trials. PMID:26598278

  8. The Myth of Equipoise in Phase 1 Clinical Trials

    PubMed Central

    Shamoo, Adil E.

    2008-01-01

    Phase 1 clinical research trials using healthy volunteers are conducted for the sole purpose of serving the public good (a utilitarian concept). The literature on equipoise analysis does not exclude phase 1 trials with controls or healthy volunteers from the claim of being in “equipoise.” The continued perpetuation of this ethically and scientifically invalid concept undermines the ethics of research with human subjects. PMID:19099004

  9. Aspects of vulnerable patients and informed consent in clinical trials

    PubMed Central

    Kuthning, Maria; Hundt, Ferdinand

    2013-01-01

    Scope: To discuss the rationale behind informed consent in clinical trials focusing on vulnerable patients from a European and German viewpoint. Methods: Scientific literature search via PubMed, Medline, Google. Results: Voluntary informed consent is the cornerstone of policies regulating clinical trials. To enroll a patient into a clinical trial without having obtained written and signed consent is to be considered as a serious issue in the conduct of a clinical trial. Development of ethical guidance for physicians started before Christ Era with the Hippocratic Oath. Main function of consent, as articulated in all guidelines developed for clinical research, is to facilitate an individual’s freedom of choice, respect autonomy, and thus to ensure welfare of the participants in clinical trials. Minors are unable to provide legally binding informed consent, this issue is addressed through a combination of parental permission and minor’s assent. Illiteracy is a critical problem that affects all corners of our earth; it has no boundaries and exists among every race and ethnicity, age group, and economic class. New strategies to improve communication with patients including the use of videotapes or animated cartoon illustrations could be taught. Finally the time with the potential participant seems to be the best way to improve understanding. Conclusion: Discovery of life saving and life enhancing new treatments requires partnership that is based on good communication and trust between patients and researchers, sponsors, ethics committees, authorities, lawyers and politicians so that vulnerable patients can benefit from the results of well controlled clinical trials. PMID:23346043

  10. Immunological monitoring of anticancer vaccines in clinical trials

    PubMed Central

    Ogi, Chizuru; Aruga, Atsushi

    2013-01-01

    Therapeutic anticancer vaccines operate by eliciting or enhancing an immune response that specifically targets tumor-associated antigens. Although intense efforts have been made for developing clinically useful anticancer vaccines, only a few Phase III clinical trials testing this immunotherapeutic strategy have achieved their primary endpoint. Here, we report the results of a retrospective research aimed at clarifying the design of previously completed Phase II/III clinical trials testing therapeutic anticancer vaccines and at assessing the value of immunological monitoring in this setting. We identified 17 anticancer vaccines that have been investigated in the context of a completed Phase II/III clinical trial. The immune response of patients receiving anticancer vaccination was assessed for only 8 of these products (in 15 distinct studies) in the attempt to identify a correlation with clinical outcome. Of these studies, 13 were supported by a statistical correlation study (Log-rank test), and no less than 12 identified a positive correlation between vaccine-elicited immune responses and disease outcome. Six trials also performed a Cox proportional hazards analysis, invariably demonstrating that vaccine-elicited immune responses have a positive prognostic value. However, despite these positive results in the course of early clinical development, most therapeutic vaccines tested so far failed to provide any clinical benefit to cancer patients in Phase II/III studies. Our research indicates that evaluating the immunological profile of patients at enrollment might constitute a key approach often neglected in these studies. Such an immunological monitoring should be based not only on peripheral blood samples but also on bioptic specimens, whenever possible. The evaluation of the immunological profile of cancer patients enrolled in early clinical trials will allow for the identification of individuals who have the highest chances to benefit from anticancer vaccination

  11. 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

  12. 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

  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. PMID:25832350

  14. New clinical trials for nonmotor manifestations of Parkinson's disease.

    PubMed

    Schrag, Anette; Sauerbier, Anna; Chaudhuri, Kallol Ray

    2015-09-15

    Nonmotor manifestations in Parkinson's disease (PD) encompass a range of clinical features, including neuropsychiatric problems, autonomic dysfunction, sleep disorders, fatigue, and pain. Despite their importance for patients' quality of life, the evidence base for their treatment is relatively sparse. Nevertheless, the last few years have seen a number of new trials starting that specifically address nonmotor features as an outcome measure in clinical trials. Large randomized, controlled trials in the last 3 years reported improvement of psychosis with the new selective serotonin 5-HT2A inverse agonist pimavanserin and of postural hypotension with the oral norepinephrine precursor droxidopa. Smaller new randomized, controlled trials support the effectiveness of Deep Brain Stimulation and opiates for pain, of rivastigmine for apathy and piribedil for apathy post-DBS, group cognitive behavioral therapy for depression and/or anxiety, continuous positive airway pressure for sleep apnea in PD and doxepin for insomnia, and of solifenacin succinate and transcutaneous tibial nerve stimulation for urinary symptoms. A number of new smaller or open trials as well as post-hoc analyses of randomized, controlled trials have suggested usefulness of other treatments, and new randomized, controlled trials are currently ongoing. PMID:26371623

  15. [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

  16. 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

  17. Twenty questions about multiple sclerosis clinical trials methodologies.

    PubMed

    Pryse-Phillips, W

    2001-04-01

    The heterogeneity of methods used in multiple sclerosis (MS) clinical trials prevents fair comparison of trials and reduces confidence in the validity of the therapeutic claims made. The validity of recent clinical trials is lessened by the following factors: MS shows variability in type and in rates of disease progression; primary progressive MS may not be the same disease as typical MS, and inclusion of subjects with this condition may have skewed results of trials to date. Using a new model, "relapsing-remitting" and "secondary progressive" MS are considered to represent earlier and later stages of the same disease. The variety of endpoints used in clinical trials impairs comparisons. The differences between EDSS stages vary at different levels and it is concluded that this is no longer the most appropriate tool, although it could be improved by modifying the scoring or scales to assess certain focused items. The clinical significance of a reduction in relapse rate is questioned, as are the inclusion criteria employed in recent trials. Drug doses based upon body mass differ from those based on surface area, making it hard to compare the effects of trial agents. The definitions of "sustained worsening" are not uniform and the concept is complicated by regression to the mean. Trials should continue for long enough to be sure that any beneficial effects noted are permanent. Although extensions provide better long-term data, they are usually statistically underpowered and clinically and demographically imbalanced. Ethically, if benefit is determined to be present, a trial should be stopped so that all subjects may be offered the beneficial agent, but determination of benefit may be imperfect. The "intention to treat" paradigm is a shibboleth, providing data on effectiveness rather than efficacy. The simple listing and addition of unwanted effects (UEs) is unproductive. Trivial UEs detract little from quality of life and are unimportant. The remainder should be

  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. Clinical Trial and Research Study Recruiters' Verbal Communication Behaviors.

    PubMed

    Morgan, Susan E; Mouton, Ashton; Occa, Aurora; Potter, Jonell

    2016-07-01

    The lack of accrual to research studies and clinical trials is a persistent problem with serious consequences: Advances in medical science depend on the participation of large numbers of people, including members of minority and underserved populations. The current study examines a critical determinant of accrual: the approach of patients by professional recruiters who request participation in research studies and clinical trials. Findings indicate that recruiters use a number of verbal strategies in the communication process, including translating study information (such as simplifying, using examples, and substituting specific difficult or problematic words), using linguistic reframing or metaphors, balancing discussions of research participation risks with benefits, and encouraging potential participants to ask questions. The identification of these verbal strategies can form the basis of new communication protocols that will help medical and nonmedical professionals communicate more clearly and effectively with patients and other potential participants about research studies and clinical trials, which should lead to increased accrual in the future. PMID:27259754

  20. Patient-reported outcomes in lupus clinical trials with biologics.

    PubMed

    Annapureddy, N; Devilliers, H; Jolly, M

    2016-09-01

    Therapeutic advances in systemic lupus erythematosus (SLE) are greatly needed. Despite advances in our knowledge of pathogenesis of the disease and targets, treatment remains a significant challenge. Finding effective and relatively safe medications remains one of the top priorities. SLE significantly impairs quality of life (QoL), and patient-reported outcomes (PROs) measure a unique aspect of the disease not captured by disease activity. Inclusion of PRO measurements is encouraged in SLE clinical trials, as they allow capturing benefits of a proposed intervention in language patients can relate to and in areas deemed pertinent and important to and by patients. Availability of patient-reported and patient-centric clinical trials data may facilitate patients in informed and shared decision making, and allow for comparative cost-effectiveness evaluation for future resource allocation and reimbursements. Herein we review clinical trials with biologic therapies wherein PRO tools were included in the study design. PMID:27497256

  1. 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

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

    PubMed

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

    2016-08-01

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

  4. Wrongful Termination: Lessons From the Geron Clinical Trial

    PubMed Central

    Magnus, David

    2014-01-01

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

  5. Importance of placebo effect in cough clinical trials.

    PubMed

    Eccles, Ron

    2010-01-01

    Cough is a unique symptom because, unlike sneeze and other symptoms, it can be under voluntary control and this complicates clinical trials on cough medicines. All over-the-counter cough medicines (OTC) are very effective treatments because of their placebo effect. The placebo effect is enhanced by expectancy related to advertising, brand, packaging, and formulation. This placebo effect creates a problem for the conduct of clinical trials on OTC cough medicines that attempt to demonstrate the efficacy of a pharmacological agent above that of any placebo effect. Up to 85% of the efficacy of some cough medicines can be attributed to a placebo effect. The placebo effect apparent in clinical trials consists of several components: natural recovery, regression of cough response toward mean, demulcent effect, effect of sweetness, voluntary control, and effects related to expectancy and meaning of the treatment. The placebo effect has been studied most in the pain model, and placebo analgesia is reported to depend on the activation of endogenous opioid systems in the brain; this model may be applicable to cough. A balanced placebo design may help to control for the placebo effect, but this trial design may not be acceptable due to deception of patients. The placebo effect in clinical trials may be controlled by use of a crossover design, where feasible, and the changes in the magnitude of the placebo effect in this study design are discussed. PMID:19760296

  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. PMID:22566003

  7. 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

  8. Prospective clinical trial of a human tumor cloning system.

    PubMed

    Von Hoff, D D; Clark, G M; Stogdill, B J; Sarosdy, M F; O'Brien, M T; Casper, J T; Mattox, D E; Page, C P; Cruz, A B; Sandbach, J F

    1983-04-01

    A prospective clinical trial was performed to evaluate the usefulness of a human tumor cloning system for selecting single-agent chemotherapy for patients with advanced cancers. Six hundred four single-agent trials were performed in the 470 patients whose tumors were submitted for drug sensitivity testing. Only 246 of these 604 trials (41%) could be directed by the cloning system results because of inadequate tumor growth and other difficulties. In these 246 prospective trials, there was a 60% true positive and an 85% true negative rate for predicting for response or lack of response of an individual patient's tumor to the single agent. There was also a relationship between the percentage of decrease in survival of tumor colony-forming units and the probability of a clinical response of the patient's tumor to the same drug used in vivo. Despite these encouraging findings, work to improve tumor growth and additional prospective clinical trials of the system are needed before the system can be recommended for routine clinical use. PMID:6339044

  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. Prolonged-release melatonin versus placebo for benzodiazepine discontinuation in patients with schizophrenia: a randomized clinical trial - the SMART trial protocol

    PubMed Central

    2011-01-01

    Background Treatment of schizophrenia frequently includes prolonged benzodiazepine administration despite a lack of evidence of its use. It is often difficult to discontinue benzodiazepines because of the development of dependence. We aim to assess if melatonin can facilitate the withdrawal of prolonged benzodiazepine administration in patients with schizophrenia. Furthermore, we aim to investigate the association of benzodiazepine dose reduction with the following clinically important variables: sleep, psychophysiology, cognition, social function, and quality of life. Methods/Design Randomized, blinded, two-armed, parallel superiority trial. We plan to include 80 consenting outpatients diagnosed with schizophrenia or schizoaffective disorder, 18-55 years of age, treated with antipsychotic drug(s) and at least one benzodiazepine derivative for the last three months before inclusion. Exclusion criteria: currently under treatment for alcohol or drug abuse, aggressive or violent behavior, known mental retardation, pervasive developmental disorder, dementia, epilepsy, terminal illness, severe co morbidity, inability to understand Danish, allergy to melatonin, lactose, starch, gelatin, or talc, hepatic impairment, pregnancy or nursing, or lack of informed consent. After being randomized to prolonged-release melatonin (Circadin®) 2 mg daily or matching placebo, participants are required to slowly taper off their benzodiazepine dose. The primary outcome measure is benzodiazepine dose at 6 months follow-up. Secondary outcome measures include sleep, psychophysiological, and neurocognitive measures. Data are collected at baseline and at 6 months follow-up regarding medical treatment, cognition, psychophysiology, sleep, laboratory tests, adverse events, psychopathology, social function, and quality of life. Data on medical treatment, cognition, psychophysiology, adverse events, social function, and quality of life are also collected at 2 and 4 months follow-up. Discussion

  11. 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

  12. Lidocaine for systemic sclerosis: a double-blind randomized clinical trial

    PubMed Central

    2011-01-01

    Background Systemic sclerosis (scleroderma; SSc) is an orphan disease with the highest case-specific mortality of any connective-tissue disease. Excessive collagen deposit in affected tissues is a key for the disease's pathogenesis and comprises most of the clinical manifestations. Lidocaine seems to be an alternative treatment for scleroderma considering that: a) the patient's having excessive collagen deposits in tissues affected by scleroderma; b) the patient's demonstrating increased activity of the enzyme prolyl hydroxylase, an essential enzyme for the biosynthesis of collagen; and c) lidocaine's reducing the activity of prolyl hydroxylase. The aim of this study was to evaluate the efficacy and safety of lidocaine in treating scleroderma. Methods A randomized double-blind clinical trial included 24 patients with scleroderma randomized to receive lidocaine or placebo intravenously in three cycles of ten days each, with a one-month interval between them. Outcomes: cutaneous (modified Rodnan skin score), oesophageal (manometry) and microvascular improvement (nailfold capillaroscopy); improvement in subjective self-assessment and in quality of life (HAQ). Results There was no statistically significant difference between the groups for any outcome after the treatment and after 6-months follow-up. Improvement in modified Rodnan skin score occurred in 66.7% and 50% of placebo and lidocaine group, respectively (p = 0.408). Both groups showed an improvement in subjective self-assessment, with no difference between them. Conclusions Despite the findings of a previous cohort study favouring the use of lidocaine, this study demonstrated that lidocaine at this dosage and means of administration showed a lack of efficacy for treating scleroderma despite the absence of significant adverse effects. However, further similar clinical trials are needed to evaluate the efficacy of lidocaine when administered in different dosages and by other means. PMID:21299861

  13. 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

  14. 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

  15. Six-month freedom from treatment failure is an important end point for acute GVHD clinical trials.

    PubMed

    Sengsayadeth, S; Savani, B N; Jagasia, M; Goodman, S; Greer, J P; Chen, H; Chinratanalab, W; Kassim, A A; Engelhardt, B G

    2014-02-01

    We studied the American Society for Blood and Marrow Transplantation (ASBMT) 6-month (m) freedom from treatment failure (FFTF) as a predictor of survival for patients with acute GVHD (aGVHD) requiring treatment. Adult patients undergoing allogeneic hematopoietic cell transplant (HCT) from February 2007 to March 2009 who were enrolled in a prospective biomarker clinical trial and developed aGVHD requiring systemic corticosteroids by day +100 were included (N=44). Six-month FFTF was defined as per the ASBMT guidelines (absence of death, malignancy relapse/progression or systemic immunosuppression change within 6 months of starting steroids and before chronic GVHD development). aGVHD was treated with systemic corticosteroids in 44 patients. Day 28 response after steroid initiation (complete response+very good partial response+partial response) occurred in 38 (87%) patients, but only 28 (64%) HCT recipients met the 6-m FFTF end point. Day 28 response predicted 6-m FFTF. Achieving 6-m FFTF was associated with improved 2-year (y) OS (81% vs 48%; P=0.03) and decreased 2-y non-relapse mortality (8% vs 49%; P=0.01). In multivariate analysis, 6-m FFTF continued to predict improved OS (hazard ratio, 0.27; P=0.03). The 6-m FFTF end point measures fixed outcomes, predicts long-term therapeutic success and could be less prone to measurement error than aGVHD clinical response at day 28. PMID:24096824

  16. Six Month Freedom from Treatment Failure is an Important Endpoint for Acute Graft-Versus-Host Disease Clinical Trials

    PubMed Central

    Sengsayadeth, Salyka; Savani, Bipin N.; Jagasia, Madan; Goodman, Stacey; Greer, John P.; Chen, Heidi; Chinratanalab, Wichai; Kassim, Adetola A.; Engelhardt, Brian G.

    2013-01-01

    We studied the ASBMT 6 month (m) freedom from treatment failure (FFTF) as a predictor of survival for patients with acute graft-versus-host disease (aGVHD) requiring treatment. Adult patients undergoing allogeneic hematopoietic cell transplant (HCT) from February 2007 to March 2009 who were enrolled in a prospective biomarker clinical trial and developed aGVHD requiring systemic corticosteroids by day +100 were included (N=44). Six month FFTF was defined per ASBMT guidelines [absence of death, malignancy relapse/progression, or systemic immunosuppression change within 6 months of starting steroids and before chronic GVHD development]. aGVHD was treated with systemic corticosteroids in 44 patients. Day 28 response after steroid initiation (CR+VGPR+PR) occurred in 38 (87%) patients, but only 28 (64%) HCT recipients met the 6 m FFTF endpoint. Day 28 response predicted 6 m FFTF. Achieving 6 m FFTF was associated with improved 2 year (y) overall survival (OS) [81% vs. 48%, P= 0.03)] and decreased 2 y non-relapse mortality [8% vs. 49% (P= 0.01)]. In multivariate analysis, 6 m FFTF continued to predict improved OS (HR, 0.27; P=0.03). The 6 m FFTF endpoint measures fixed outcomes, predicts long-term therapeutic success, and could be less prone to measurement error than aGVHD clinical response at day 28. PMID:24096824

  17. 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

  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. PMID:27015634

  20. 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

  1. Differences in trial knowledge and motives for participation among cancer patients in phase 3 clinical trials.

    PubMed

    Godskesen, T M; Kihlbom, U; Nordin, K; Silén, M; Nygren, P

    2016-05-01

    While participants in clinical oncology trials are essential for the advancement of cancer therapies, factors decisive for patient participation have been described but need further investigation, particularly in the case of phase 3 studies. The aim of this study was to investigate differences in trial knowledge and motives for participation in phase 3 clinical cancer trials in relation to gender, age, education levels and former trial experience. The results of a questionnaire returned from 88 of 96 patients (92%) were analysed using the Mann-Whitney U-test. There were small, barely relevant differences in trial knowledge among patients when stratified by gender, age or education. Participants with former trial experience were less aware about the right to withdraw. Male participants and those aged ≥65 years were significantly more motivated by a feeling of duty, or by the opinions of close ones. Men seem more motivated than women by external factors. With the awareness that elderly and single male participants might be a vulnerable group and participants with former trial experience are less likely to be sufficiently informed, the information consent process should focus more on these patients. We conclude that the informed consent process seems to work well, with good results within most subgroups. PMID:25904313

  2. 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

  3. [Clinical trial data management and quality metrics system].

    PubMed

    Chen, Zhao-hua; Huang, Qin; Deng, Ya-zhong; Zhang, Yue; Xu, Yu; Yu, Hao; Liu, Zong-fan

    2015-11-01

    Data quality management system is essential to ensure accurate, complete, consistent, and reliable data collection in clinical research. This paper is devoted to various choices of data quality metrics. They are categorized by study status, e.g. study start up, conduct, and close-out. In each category, metrics for different purposes are listed according to ALCOA+ principles such us completeness, accuracy, timeliness, traceability, etc. Some general quality metrics frequently used are also introduced. This paper contains detail information as much as possible to each metric by providing definition, purpose, evaluation, referenced benchmark, and recommended targets in favor of real practice. It is important that sponsors and data management service providers establish a robust integrated clinical trial data quality management system to ensure sustainable high quality of clinical trial deliverables. It will also support enterprise level of data evaluation and bench marking the quality of data across projects, sponsors, data management service providers by using objective metrics from the real clinical trials. We hope this will be a significant input to accelerate the improvement of clinical trial data quality in the industry. PMID:26911027

  4. Current status of quality in Japanese clinical trials.

    PubMed

    Saito, Kazuyuki; Kodama, Yasuo; Ono, Shunsuke; Mutoh, Mizue; Kawashima, Susumu; Fujimura, Akio

    2005-08-01

    The changes in the quality of Japanese clinical trials were evaluated by comparing the results of Good Clinical Practice (GCP) audits conducted from April 1997 to March 2000 (fiscal year (FY) 1997-1999) with those from April 2001 to March 2002 (FY2001). During both of the periods inspections were undertaken by the Organization for Pharmaceutical Safety and Research (OPSR). The audit findings in the former period were based on the audits that covered 331 hospitals and 775 trials conducted under the old GCP guideline. The audits in the latter period targeted 147 hospitals and 238 trials conducted under the old or new GCP guideline. The total number of deficiencies detected by GCP audits in the former three-year period (FY 1997-1999) was 1529, and the corresponding number in the latter single year (FY 2001) was 912. Two remarkable changes in OPSR's findings were observed between FY 1997-1999 and FY 2001 as follows; the proportion of protocol deviations increased from 14.7% (225/1529) to 53.1% (484/912), while the proportion of errors in case report forms (CRFs) decreased from 43.6% (666/1529) to 15.4% (140/912). The new GCP guideline sets very high standards for a hospital's qualification: to have sufficient equipment and hospital resources, to have capacity for promptly responding to urgent trial-related problems, to have an IRB, and to have appropriate staff including clinical research coordinators (CRCs) assigned to the clinical trial. Our results suggest that the impact of the regulatory changes of applicable standard is large for a hospital's qualification for conducting clinical trials in Japan. PMID:16054582

  5. 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.

  6. Application of the verbal autopsy during a clinical trial.

    PubMed

    Pacqué-Margolis, S; Pacqué, M; Dukuly, Z; Boateng, J; Taylor, H R

    1990-01-01

    During a community-based treatment trial of onchocerciasis with ivermectin, verbal autopsies were employed as one method to assess the safety of the drug. The verbal autopsy questionnaire was designed to determine causes of death and mortality differentials in the treated population. During the 8 months of surveillance here reported, 25 individuals died, yet only 9 of these deaths were certified. Seven of the deaths occurred to individuals who had been treated with ivermectin and the majority of the deaths occurred to children under 5, who were excluded from treatment. The verbal autopsy method was evaluated and validated by comparing the verbal autopsy diagnosis of cause of death to death certificate diagnosis, when available. In addition, verbal autopsies were retrospectively performed for all deaths which had occurred at the hospital during the 6 months preceding the start of the study, if these deaths were traceable to households in the surveillance population. We found that in 80% of the adult deaths, the verbal autopsy and death certificate diagnoses of underlying cause of death agreed. The verbal autopsy was less accurate in diagnosing child deaths which we attribute to the design of the verbal autopsy (being to detect potential drug related deaths in adults) and to the delay between death and interview. We conclude that verbal autopsies are an important addition to surveillance systems in remote areas where the absence or inadequacy of health information systems does not allow a thorough follow-up of all subjects in drug studies. PMID:2218641

  7. 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

  8. Flexible design clinical trial methodology in regulatory applications.

    PubMed

    Hung, H M James; Wang, Sue-Jane; O'Neill, Robert

    2011-06-15

    Adaptive designs or flexible designs in a broader sense have increasingly been considered in planning pivotal registration clinical trials. Sample size reassessment design and adaptive selection design are two of such designs that appear in regulatory applications. At the design stage, consideration of sample size reassessment at an interim time of the trial should lead to extensive discussion about how to appropriately size the trial. Additionally, careful attention needs to be paid to the issue of how the size of the trial is impacted by the requirement that the final p-value of the trial meets the specific threshold of a clinically meaningful effect. These issues are not straightforward and will be discussed in this work. In a trial design that allows selection between a pre-specified patient subgroup and the initially planned overall patient population based on the accumulating data, there is an issue of what the 'overall' population means. In addition, it is critically important to know how such selection influences the validity of statistical inferences on the potentially modified overall population. This work presents the biases that may incur under adaptive patient selection designs. PMID:21344470

  9. Strategies for clinical trials in type 1 diabetes.

    PubMed

    Ehlers, Mario R

    2016-07-01

    During the past one to two decades, substantial progress has been made in our understanding of the immunopathology of type 1 diabetes (T1D) and the potential for immune interventions that can alter the natural history of the disease. This progress has resulted from the use of standardized study designs, endpoints, and, to a certain extent, mechanistic analyses in intervention trials in the setting of new-onset T1D. To date, most of these trials have involved single-agent interventions but, increasingly, future trials will test therapeutic combinations that are based on a compelling scientific rationale and testable mechanistic hypotheses. These increasingly complex trials will benefit from novel trial designs (such as factorial or adaptive designs), enhanced clinical endpoints that more directly assess islet pathology (such as β-cell death assays and islet or pancreatic imaging), improved responder analyses, and sophisticated mechanistic assays that provide deep phenotyping of lymphocyte subsets, gene expression profiling, in vitro T cell functional assessments, and antigen-specific responses. With this developing armamentarium of enhanced trial designs, endpoints, and clinical and mechanistic response analyses, we can expect substantial progress in better understanding the breakdown in immunologic tolerance in T1D and how to restore it to achieve significant and long-lasting preservation of islet function. PMID:27068279

  10. Functional Outcome at 6 Months in Surgical Treatment of Spontaneous Supratentorial Intracerebral Haemorrhage

    PubMed Central

    Ghani, Abdul Rahman Izaini; John, John Tharakan Kalappurakkal; Idris, Zamzuri; Ghazali, Mazira Mohamad; Murshid, Nur-Leem; Musa, Kamarul Imran

    2008-01-01

    A prospective cohort study was done to evaluate the role of surgery in patients with spontaneous supratentorial intracerebral haemorrhage (SICH) and to identify predictors of outcome including the use of invasive regional cortical cerebral blood flow (rCoBF) and microdialysis. Surgery consisted of craniotomy or decompressive craniectomy. The ventriculostomy for intracranial pressure (ICP) monitoring and drainage and regional cortical cerebral blood flow (rCoBF) and microdialysis were performed in all subjects. Pre and post operative information on subjects were collected. The study end points was functional outcome at 6 months based on a dichotomised Glasgow Outcome Scale (GOS).The selected clinical, radiological, biochemical and treatment factors that may influence the functional outcome were analysed for their significance. A total of 36 patients were recruited with 27(75%) patients had Glasgow Coma Score (GCS) between 5 to 8 on admission and 9(25%) were admitted with GCS of 9. At 6 months, 86 % had a poor or unfavourable outcome (GOS I–III) and 14% had good or favourable outcome (GOS IV–V). The mortality rate at 6 months was 55%. Univariate analysis for the functional outcome identified 2 significant variables, the midline shift (p=0.013) and mean lactate:pyruvate ratio (p=0.038). Multivariate analysis identified midline shift as the single significant independent predictor of functional outcome (p=0.013).Despite aggressive regional cortical cerebral blood flow (rCoBF) and microdialysis study for detection of early ischemia, surgical treatment for spontaneous intracerebral haemorrhage only benefited a small number of patients in terms of favourable outcome (14%) and in the majority of patients (86%), the outcome was unfavourable. Patients with midline shift > 5mm has almost 21 times higher chances (adj) OR 20.8 of being associated with poor outcome (GOS I–III). PMID:22589638

  11. 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

  12. Existing data sources for clinical epidemiology: Aarhus University Clinical Trial Candidate Database, Denmark.

    PubMed

    Nørrelund, Helene; Mazin, Wiktor; Pedersen, Lars

    2014-01-01

    Denmark is facing a reduction in clinical trial activity as the pharmaceutical industry has moved trials to low-cost emerging economies. Competitiveness in industry-sponsored clinical research depends on speed, quality, and cost. Because Denmark is widely recognized as a region that generates high quality data, an enhanced ability to attract future trials could be achieved if speed can be improved by taking advantage of the comprehensive national and regional registries. A "single point-of-entry" system has been established to support collaboration between hospitals and industry. When assisting industry in early-stage feasibility assessments, potential trial participants are identified by use of registries to shorten the clinical trial startup times. The Aarhus University Clinical Trial Candidate Database consists of encrypted data from the Danish National Registry of Patients allowing an immediate estimation of the number of patients with a specific discharge diagnosis in each hospital department or outpatient specialist clinic in the Central Denmark Region. The free access to health care, thorough monitoring of patients who are in contact with the health service, completeness of registration at the hospital level, and ability to link all databases are competitive advantages in an increasingly complex clinical trial environment. PMID:24748818

  13. Existing data sources for clinical epidemiology: Aarhus University Clinical Trial Candidate Database, Denmark

    PubMed Central

    Nørrelund, Helene; Mazin, Wiktor; Pedersen, Lars

    2014-01-01

    Denmark is facing a reduction in clinical trial activity as the pharmaceutical industry has moved trials to low-cost emerging economies. Competitiveness in industry-sponsored clinical research depends on speed, quality, and cost. Because Denmark is widely recognized as a region that generates high quality data, an enhanced ability to attract future trials could be achieved if speed can be improved by taking advantage of the comprehensive national and regional registries. A “single point-of-entry” system has been established to support collaboration between hospitals and industry. When assisting industry in early-stage feasibility assessments, potential trial participants are identified by use of registries to shorten the clinical trial startup times. The Aarhus University Clinical Trial Candidate Database consists of encrypted data from the Danish National Registry of Patients allowing an immediate estimation of the number of patients with a specific discharge diagnosis in each hospital department or outpatient specialist clinic in the Central Denmark Region. The free access to health care, thorough monitoring of patients who are in contact with the health service, completeness of registration at the hospital level, and ability to link all databases are competitive advantages in an increasingly complex clinical trial environment. PMID:24748818

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

    MedlinePlus

    ... page please turn Javascript on. Feature: Medicines for Children The Importance of Children in Clinical Trials Past Issues / Winter 2012 Table ... say to a parent who asks you why children’s clinical trials are important? Clinical research is critically ...

  15. Cross-System Evaluation of Clinical Trial Search Engines

    PubMed Central

    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. PMID:25954590

  16. 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. PMID:25954590

  17. Designing Clinical Trials of Intervention for Mobility Disability: Results from the Lifestyle Interventions and Independence for Elders (LIFE) Pilot Trial

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Clinical trials to assess interventions for mobility disability are critically needed, however data for efficiently designing such trials are lacking. Our results are described from the LIFE pilot clinical trial, in which 424 volunteers aged 70-89 years were randomly assigned to one of two intervent...

  18. Perspectives on the Design of Clinical Trials Combining Transarterial Chemoembolization and Molecular Targeted Therapy

    PubMed Central

    Hsu, Chiun; Po-Ching-Liang; Morita, Satoshi; Hu, Fu-Chang; Cheng, Ann-Lii

    2012-01-01

    (TTP) or overall survival (OS) [9, 10]. However, specific subgroups of patients who received treatment for more than 6 months exhibited significantly better survival (table 2). Because median survival can be greater than 2 years in patients with intermediate-stage HCC, it is likely that an extended exposure period is necessary for MTA effects to reach the biological threshold at which survival benefit becomes measurable. Therefore, early discontinuation of study drug treatment may significantly undermine the statistical power of efficacy analysis in randomized trials (fig. 1). Clinical trials should be designed to minimize confounding factors that could lead to early discontinuation of study drug [1, 2, 3, 11, 12]. Factors that are crucial in this regard can be categorized into five domains: (1) selection of primary endpoints, (2) selection of patient population, (3) selection of TACE procedures, (4) timing of randomization, and (5) study drug administration. In this review we discuss the confounding effects potentially associated with each domain and the possible interactions among domains in trials combining TACE and MTA. We also discuss strategies that can help improve sensitivity and accuracy measurements of MTA efficacy. PMID:24159581

  19. Matching Patient Records to Clinical Trials Using Ontologies

    NASA Astrophysics Data System (ADS)

    Patel, Chintan; Cimino, James; Dolby, Julian; Fokoue, Achille; Kalyanpur, Aditya; Kershenbaum, Aaron; Ma, Li; Schonberg, Edith; Srinivas, Kavitha

    This paper describes a large case study that explores the applicability of ontology reasoning to problems in the medical domain. We investigate whether it is possible to use such reasoning to automate common clinical tasks that are currently labor intensive and error prone, and focus our case study on improving cohort selection for clinical trials. An obstacle to automating such clinical tasks is the need to bridge the semantic gulf between raw patient data, such as laboratory tests or specific medications, and the way a clinician interprets this data. Our key insight is that matching patients to clinical trials can be formulated as a problem of semantic retrieval. We describe the technical challenges to building a realistic case study, which include problems related to scalability, the integration of large ontologies, and dealing with noisy, inconsistent data. Our solution is based on the SNOMED CT® ontology, and scales to one year of patient records (approx. 240,000 patients).

  20. Operation of a radiopharmacy for a clinical trial.

    PubMed

    Norenberg, Jeffrey P; Petry, Neil A; Schwarz, Sally

    2010-09-01

    Clinical investigations of radiopharmaceuticals are undertaken to advance promising compounds toward approval by the Food and Drug Administration (FDA) as "legend drugs." This FDA approval requires that the safety and efficacy of the investigational drug (ID) be demonstrated through clinical trials. The investigational radiopharmaceutical drug service (IRDS) is a pharmacy service that plays a critical role in the acquisition, preparation, accountability, and distribution of radiopharmaceuticals used in clinical research. Due to their radioactive and other unique properties, and their potential role as biomarkers or tools in clinical trials of other therapeutic drugs, radiopharmaceutical drugs must be managed by a qualified IRDS rather than by a typical pharmacy-based investigational drug service (IDS). The IRDS is responsible for establishing study-specific procedures for appropriate radiopharmaceutical drug accountability, billing, procurement, storage, preparation, dispensing and destruction of investigational drugs within the hospital. All drugs, and particularly parenteral drug products, must be safe for administration to human subjects enrolled in clinical trials regardless of their FDA regulatory status as approved or investigational new drug products. The United States Pharmacopeia (USP) <797> sterile compounding requirements provides enforceable minimum practice and quality standards for compounded sterile preparations of drug products based on current scientific information and best sterile compounding practices. Consequently, they apply equally to facilities dedicated to IDS and IRDS operations. The FDA also regulates drug manufacturing through current Good Manufacturing Practices (cGMP). This rule (21CFR Part 212) establishes cGMP regulations specific to positron emission tomography radiopharmaceuticals, separate from the regular drug cGMP rule (Parts 210 and 211). Compliance with regulatory, statutory, and sponsor requirements is a major consideration

  1. 76 FR 22404 - Analgesic Clinical Trials Innovation, Opportunities, and Networks (ACTION) Initiative

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-04-21

    ... the design of the clinical trials that is at fault in this situation and that better trial designs... of FDA's clinical trial databases and development of novel and alternative means of analyzing various... HUMAN SERVICES Food and Drug Administration Analgesic Clinical Trials Innovation, Opportunities,...

  2. 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...

  3. Clinical trials involving cats: What factors affect owner 1 participation?

    PubMed Central

    Gruen, Margaret E; Jiamachello, Katrina N; Thomson, Andrea; Lascelles, BDX

    2014-01-01

    Clinical trials are frequently hindered by difficulty recruiting eligible participants, increasing the timeline and limiting generalizability of results. In veterinary medicine, where proxy enrollment is required, no studies have detailed what factors influence owner participation in studies involving cats. We aimed to investigate these factors through a survey of owners at first opinion practices. The survey was designed using feedback from a pilot study and input from clinical researchers. Owners were asked demographic questions and whether they would, would not, or were unsure about participating in a clinical trial with their cat. They then ranked the importance and influence of various factors on participation using a 5-point Likert-type scale, and incentives from most to least encouraging. A total of 413 surveys were distributed to cat owners at four hospitals, two feline-only and two multi-species; 88.6% were completed. Data for importance and influence factors as well as incentive rankings were analyzed overall, by hospital type, location and whether owners would consider participating. The most influential factors were trust in the organization, benefit to the cat and veterinarian recommendation. Importance and influence factors varied by willingness to participate. Ranked incentives were not significantly different across groups, with “Free Services” ranked highest. This study provides a first look at what factors influence participation in clinical trials with cats. Given the importance placed in the recommendation of veterinarians, continued work is needed to determine veterinarian related factors affecting clinical trial participation. The results provide guidance towards improved clinical trial design, promotion and education. PMID:24938313

  4. 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. PMID:23689089

  5. 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

  6. 77 FR 13513 - Modernizing the Regulation of Clinical Trials and Approaches to Good Clinical Practice; Public...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-03-07

    ... FR 55052); 3. Oversight of Clinical Investigations: A Risk-Based Approach to Monitoring--Draft Guidance, published August 29, 2011 (76 FR 53683); 4. Electronic Source Documentation in Clinical... human subjects are protected and resulting clinical trial data are credible and accurate. FDA is...

  7. 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

  8. Placebo Effect in Clinical Trial Design for Irritable Bowel Syndrome

    PubMed Central

    Shah, Eric; Pimentel, Mark

    2014-01-01

    Ongoing efforts to improve clinical trial design in irritable bowel syndrome have been hindered by high placebo response rates and ineffective outcome measures. We assessed established strategies to minimize placebo effect as well as the various approaches to placebo effect which can affect trial design. These include genetic markers such as catechol-O-methyltransferase, opioidergic and dopaminergic neurobiologic theory, pre-cebo effect centered on expectancy theory, and side effect unblinding grounded on conditioning theory. We reviewed endpoints used in the study of IBS over the past decade including adequate relief and subjective global relief, emphasizing their weaknesses in fully evaluating the IBS condition, specifically their motility effects based on functional net value and relative benefit-harm based on dropouts due to adverse events. The focus of this review is to highlight ongoing efforts to improve clinical trial design which can lead to better outcomes in a real-world setting. PMID:24840369

  9. Dominantly Inherited Alzheimer Network: facilitating research and clinical trials

    PubMed Central

    2013-01-01

    The Dominantly Inherited Alzheimer Network (DIAN) is an international registry of individuals at risk for developing autosomal dominant Alzheimer’s disease (AD). Its primary aims are to investigate the temporal ordering of AD pathophysiological changes that occur in asymptomatic mutation carriers and to identify those markers that herald the transition from cognitive normality to symptomatic AD. DIAN participants undergo longitudinal evaluations, including clinical and cognitive assessments and measurements of molecular and imaging AD biomarkers. This review details the unique attributes of DIAN as a model AD biomarker study and how it provides the infrastructure for innovative research projects, including clinical trials. The recent design and launch of the first anti-amyloid-beta secondary prevention trial in AD, led by the related DIAN Trials Unit, also are discussed. PMID:24131566

  10. Radiation Therapy Oncology Group clinical trials with misonidazole

    SciTech Connect

    Wasserman, T.H.; Stetz, J.; Phillips, T.L.

    1981-05-15

    This paper presents a review of the progressive clinical trials of the hypoxic cell radiosensitizer, misonidazole, in the Radiation Therapy Oncology Group (RTOG). Presentation is made of all the schemas of the recently completed and currently active RTOG Phase II and Phase III studies. Detailed information is provided on the clinical toxicity of the Phase II trials, specifically regarding neurotoxicity. With limitations in drug total dose, a variety of dose schedules have proven to be tolerable, with a moderate incidence of nausea and vomiting and mild peripheral neuropathy or central neuropathy. No other organ toxicity has been seen, specifically no liver, renal or bone marrow toxicities. An additional Phase III malignant glioma trial in the Brain Tumor Study Group is described.

  11. 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

  12. Dominantly Inherited Alzheimer Network: facilitating research and clinical trials.

    PubMed

    Moulder, Krista L; Snider, B Joy; Mills, Susan L; Buckles, Virginia D; Santacruz, Anna M; Bateman, Randall J; Morris, John C

    2013-01-01

    The Dominantly Inherited Alzheimer Network (DIAN) is an international registry of individuals at risk for developing autosomal dominant Alzheimer's disease (AD). Its primary aims are to investigate the temporal ordering of AD pathophysiological changes that occur in asymptomatic mutation carriers and to identify those markers that herald the transition from cognitive normality to symptomatic AD. DIAN participants undergo longitudinal evaluations, including clinical and cognitive assessments and measurements of molecular and imaging AD biomarkers. This review details the unique attributes of DIAN as a model AD biomarker study and how it provides the infrastructure for innovative research projects, including clinical trials. The recent design and launch of the first anti-amyloid-beta secondary prevention trial in AD, led by the related DIAN Trials Unit, also are discussed. PMID:24131566

  13. 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

  14. Effects of Normobaric Hyperoxia in Traumatic Brain Injury: A Randomized Controlled Clinical Trial

    PubMed Central

    Taher, Abbas; Pilehvari, Zahra; Poorolajal, Jalal; Aghajanloo, Mashhood

    2016-01-01

    Background Traumatic brain injury (TBI) is one of the important causes of morbidity and mortality throughout the world, especially in young people. In recent years normobaric hyperoxia has become an important and useful step for recovery and improvement of outcome in TBI. Objectives The purpose of this study was to evaluate the effects of normobaric hyperoxia on clinical neurological outcomes of patients with severe traumatic brain injuries. We used the Glasgow outcome scale (GOS), barthel index, and modified rankin scale (mRS) to measure the outcomes of patients with TBI. Patients and Methods Sixty-eight consecutive patients with severe TBI (mean Glasgow coma scale [GCS] score: 7.4) who met the inclusion criteria were entered in this randomized controlled clinical trial. The patients were randomized into two groups, as follows: 1) experimental: received 80% oxygen via mechanical ventilator in the first 6 hours of admission, 2) control: received 50% oxygen by mechanical ventilator in the first 6 hours of admission and then standard medical care. We measured the GOS, Barthel Index, and mRS at the time of discharge from hospital and reassessed these measurements at the 6-month follow-up after injury. Results According to our study, there were no significant sex or age differences between the two groups (P = 0.595 and 0.074). The number of days in the intensive care unit (ICU) in the control group and experimental group were 11.4 and 9.4 days, respectively (P = 0.28), while the numbers of days of general ward admission were 13.9 and 11.4 days (P = 0.137) respectively. The status of GOS at time of discharge were severe = 13 and 10, moderate = 16 and 19, and low = 5 and 5 in the control and experimental groups, respectively (P = 0.723); 6 months after injury, the scores were as follows: moderate = 16 and 9, low = 15 and 25, and severe = 3 and 0 (P = 0.024). The Barthel index scores in the control and experimental groups were 59.7 and 63.9 at time of discharge (P = 0

  15. Clinical trials in Huntington's disease: Interventions in early clinical development and newer methodological approaches.

    PubMed

    Sampaio, Cristina; Borowsky, Beth; Reilmann, Ralf

    2014-09-15

    Since the identification of the Huntington's disease (HD) gene, knowledge has accumulated about mechanisms directly or indirectly affected by the mutated Huntingtin protein. Transgenic and knock-in animal models of HD facilitate the preclinical evaluation of these targets. Several treatment approaches with varying, but growing, preclinical evidence have been translated into clinical trials. We review major landmarks in clinical development and report on the main clinical trials that are ongoing or have been recently completed. We also review clinical trial settings and designs that influence drug-development decisions, particularly given that HD is an orphan disease. In addition, we provide a critical analysis of the evolution of the methodology of HD clinical trials to identify trends toward new processes and endpoints. Biomarker studies, such as TRACK-HD and PREDICT-HD, have generated evidence for the potential usefulness of novel outcome measures for HD clinical trials, such as volumetric imaging, quantitative motor (Q-Motor) measures, and novel cognitive endpoints. All of these endpoints are currently applied in ongoing clinical trials, which will provide insight into their reliability, sensitivity, and validity, and their use may expedite proof-of-concept studies. We also outline the specific opportunities that could provide a framework for a successful avenue toward identifying and efficiently testing and translating novel mechanisms of action in the HD field. PMID:25216371

  16. Outcome Markers for Clinical Trials in Cerebral Amyloid Angiopathy

    PubMed Central

    Greenberg, Steven M.; Rustam Al-Shahi, Salman; Biessels, Geert Jan; van Buchem, Mark; Cordonnier, Charlotte; Lee, Jin-Moo; Montaner, Joan; Schneider, Julie A.; Smith, Eric E; Vernooij, Meike; Werring, David J.

    2014-01-01

    Efforts are underway for early-phase trials of candidate therapies for cerebral amyloid angiopathy (CAA), an untreatable cause of hemorrhagic stroke and vascular cognitive impairment. A major barrier to these trials is the lack of consensus on measuring treatment effectiveness. We review a range of potential outcome markers for CAA against the ideal criteria of being clinically meaningful, closely reflective of biological progression, efficient for smaller/shorter trials, reliably measurable, and cost effective. In practice, outcomes tend either to have high clinical salience but relatively low statistical efficiency and thus more applicability for later phase studies, or greater statistical efficiency but more limited clinical meaning. The most statistically efficient outcomes are those that are potentially reversible with treatment, though their clinical significance remains unproven. Many of the candidate outcomes for CAA trials are likely to be applicable to other small vessel brain diseases as well. Considerations emerging from this review outline a path towards rapid and efficient testing of emerging candidate therapies for CAA and other small vessel diseases. PMID:24581702

  17. 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. PMID:26390962

  18. Current Clinical Trials Testing Combinations of Immunotherapy and Radiation

    PubMed Central

    Crittenden, M.; Kohrt, H.; Levy, R.; Jones, J.; Camphausen, K.; Dicker, A.; Demaria, S.; Formenti, S.

    2014-01-01

    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, 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. PMID:25481267

  19. 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…

  20. 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

  1. Recent NIMH Clinical Trials and Implications for Practice

    ERIC Educational Resources Information Center

    Vitiello, Benedetto; Kratochvil, Christopher J.

    2008-01-01

    Optimal treatment of adolescent depression requires the use of antidepressants such as fluoxetine, and the addition of cognitive-behavioral therapy (CBT) offers better potential. Second-step pharmacological treatment of the disorder offers a success rate of around 50%. Clinical trial for the use of sertraline and CBT in treating…

  2. 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…

  3. 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. PMID:25481267

  4. 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

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

    PubMed

    Chevret, Sylvie

    2012-05-20

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

  6. 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

  7. 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

  8. Anxiety and depression in patients with head and neck cancer: 6-month follow-up study

    PubMed Central

    Wu, Yi-Shan; Lin, Pao-Yen; Chien, Chih-Yen; Fang, Fu-Min; Chiu, Nien-Mu; Hung, Chi-Fa; Lee, Yu; Chong, Mian-Yoon

    2016-01-01

    Objective We aimed to assess psychiatric morbidities of patients with head and neck cancer (HNC) in a prospective study at pretreatment, and 3 and 6 months after treatment, and to compare their health-related quality of life (HRQL) between those with and without depressive disorders (depression). Materials and methods Patients with newly diagnosed HNC from a tertiary hospital were recruited into the study. They were assessed for psychiatric morbidities using the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders, fourth edition. Their HRQL was simultaneously evaluated using the quality of life questionnaire of the European Organisation for Research and Treatment of Cancer with a specific module for head and neck cancer; and depressed and nondepressed HNC patients were compared by using the generalized mixed-effect model for repeated measurements. Results A total of 106 patients were recruited into this study. High rates of anxiety were found at pretreatment, but steadily declined over time (from 27.3% to 6.4%, and later 3.3%). A skew pattern of depression was observed, with prevalence rates from 8.5% at pretreatment to 24.5% and 14% at 3 and 6 months, respectively, after treatment. We found that loss of sense (P=0.001), loss of speech (P<0.001), low libido (P=0.001), dry mouth (P<0.001), and weight loss (P=0.001) were related to depression over time. The depressed patients had a higher consumption of painkillers (P=0.001) and nutrition supplements (P<0.001). The results showed that depression was predicted by sticky saliva (P<0.001) and trouble with social contact (P<0.001) at 3 months, and trouble with social eating (P<0.001) at 6 months. Conclusion Patients with HNC experienced different changes in anxiety and depression in the first 6 months of treatment. Dysfunction in salivation, problems with eating, and problems with social contacts were major risk factors for depression. PMID:27175080

  9. 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

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

    PubMed Central

    Kabbara, Karim; Clark, Rachael; McAlindon, Tim

    2004-01-01

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

  11. 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].

  12. 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

  13. Clinical trial of an inhibitor of RAGE-Aβ interactions in Alzheimer disease

    PubMed Central

    Bell, Joanne; Mancuso, Jessica Y.; Kupiec, James W.; Sabbagh, Marwan N.; van Dyck, Christopher; Thomas, Ronald G.; Aisen, Paul S.

    2014-01-01

    Objective: To examine safety, tolerability, and efficacy of PF-04494700, an inhibitor of the receptor for advanced glycation end products (RAGE), in mild to moderate Alzheimer disease (AD). Methods: Double-blind, placebo-controlled trial at 40 academic centers (United States). Subjects with AD and Mini-Mental State Examination score 14–26 were randomized to PF-04494700 60 mg/day × 6 days, then 20 mg daily (high dose); 15 mg/day × 6 days, then 5 mg daily (low dose); or placebo, for 18 months. Clinical and laboratory measures were used to evaluate safety and tolerability. The primary efficacy measure was the Alzheimer's Disease Assessment Scale–cognitive (ADAS-cog). Secondary measures assessed clinical stage, function, behavior, MRI, and CSF biomarkers. Results: A total of 399 subjects were randomized. In a prespecified interim analysis, when 50% of subjects had completed the 6-month visit, the high dose was associated with confusion, falls, and greater ADAS-cog decline and was discontinued. A second prespecified analysis compared low-dose and placebo groups for futility and safety approximately 12 months after all subjects were randomized. This analysis met criteria for futility, and treatment was discontinued. There were no safety concerns in the low-dose group. Analyses including post-futility data showed decreased decline on the ADAS-cog in the low-dose group at month 18. Other clinical and biomarker measures showed no differences between low-dose treatment and placebo. Conclusions: PF-04494700 at 20 mg/d was associated with increased adverse events and cognitive decline. At 5 mg/d, PF-04494700 had a good safety profile. A potential benefit for this low dose on the ADAS-cog is not conclusive, because of high dropout and discontinuation rates subsequent to the interim analyses. Classification of evidence: This study provides Class I evidence that in patients with AD high-dose PF-04494700 increased cognitive decline at 6 months and Class IV evidence that low

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

    PubMed Central

    Viergever, Roderik F; Li, Keyang

    2015-01-01

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

  15. Serious adverse event reporting in investigator-initiated clinical trials.

    PubMed

    Wallace, Sophie; Myles, Paul S; Zeps, Nikolajs; Zalcberg, John R

    2016-04-01

    Reporting adverse events (AEs) and serious AEs (SAEs) are practical steps to ensure safety for volunteers and patients in medical research involving medications, treatments and devices. However, the burden and cost of reporting should be proportionate with the public health benefit of this information. Unfortunately, in Australia there is clear evidence of ever-increasing requirements from sponsors and ethics committees to report AEs and SAEs unnecessarily, leading to a decrease in the uptake of research, particularly less well funded investigator-initiated trials. We believe that individual AE reports to ethics committees serve no useful purpose, because in most cases the study group identity (drug exposure) is not known in studies with blinded treatment arms and their value is limited. Pragmatic, investigator-initiated Phase IV clinical trials of post-marketed drugs or devices are needed to understand their role in everyday clinical practice. In this setting, the workload and costs of systematic, complete reporting of all AEs and SAEs (independent of whether these are treatment-related) is wasteful, and mostly unnecessary. A trial data safety and monitoring committee is in the unique position of being able to review safety information according to the blinded treatment arms of the study. This enables safety data to be analysed appropriately and a summary report provided to the trial steering committee, principal investigators and the relevant ethics committees in a meaningful way. Defined trial endpoints do not need to be reported as safety events (because they are being properly monitored and analysed). PMID:27031396

  16. Challenges and guidelines for clinical trial of herbal drugs

    PubMed Central

    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

  17. 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 med