Home About us Contact
|
Home About us Contact | ||
|
|
||
Trial Participants (trial + participant)
Selected AbstractsEnhancing the Growth of Natural Eyelashes: The Mechanism of Bimatoprost-Induced Eyelash GrowthDERMATOLOGIC SURGERY, Issue 9 20102Article first published online: 2 APR 2010, JOEL L. COHEN MD BACKGROUND Many women desire prominent eyelashes. In December 2008, bimatoprost ophthalmic solution 0.03% was approved for the treatment of hypotrichosis of the eyelashes in the United States. OBJECTIVE To review eyelash physiology and the proposed mechanisms by which the topical pros-tamide product bimatoprost enhances eyelash growth. METHODS AND MATERIALS Clinical and preclinical studies pertaining to the efficacy, safety, and mechanisms of action of bimatoprost are presented. RESULTS Treatment with bimatoprost increases the percentage of eyelash follicles in anagen at any one time. This probably accounts for its ability to lengthen lashes. Bimatoprost-induced stimulation of melanogenesis appears to result in darker lashes and, at the same time, appears to increase the size of the dermal papilla and hair bulb, affecting lash thickness and fullness. Such effects, largely demonstrated in animal studies, are consistent with the results of a recent Food and Drug Administration phase III clinical trial. The favorable safety profile of bimatoprost in human subjects is probably secondary to the limited exposure of ocular tissues resulting from topical application at the base of the upper lashes. CONCLUSION By influencing the eyelash hair cycle and follicles, bimatoprost ophthalmic solution 0.03% is a safe and effective means of enhancing eyelash growth. Dr. Cohen has served as a consultant and clinical trial participant for Allergan, Inc. [source] BENEFITS TO RESEARCH SUBJECTS IN INTERNATIONAL TRIALS: DO THEY REDUCE EXPLOITATION OR INCREASE UNDUE INDUCEMENT?DEVELOPING WORLD BIOETHICS, Issue 3 2008ANGELA BALLANTYNE ABSTRACT There is an alleged tension between undue inducement and exploitation in research trials. This paper considers claims that increasing the benefits to research subjects enrolled in international, externally-sponsored clinical trials should be avoided on the grounds that it may result in the undue inducement of research subjects. It proceeds from the premise that there are good grounds for thinking that, at least some, international research sponsors exploit trial participants because they do not provide the research population with a fair share of the benefits of research. This provides a prima facie argument for increasing the benefits for research participants. Concern over undue inducement is a legitimate moral concern; however, if this concern is to prevent research populations from receiving their fair share of benefits from research there must be sufficient evidence that these benefits will unduly influence patients' decision-making regarding trial participation. This article contributes to the debate about exploitation versus undue inducement by introducing an analysis of the available empirical research into research participants' motivations and the influence of payments on research subjects' behaviour and risk assessment. Admittedly, the available research in this field is limited, but the research that has been conducted suggests that financial rewards do not distort research subjects' behaviour or blind them to the risks involved with research. Therefore, I conclude that research sponsors should prioritise the prevention of exploitation in international research by providing greater benefits to research participants. [source] A randomized trial of the effects of two novel nicotine replacement therapies on tobacco withdrawal symptoms and user satisfactionADDICTION, Issue 7 2010Hayden McRobbie ABSTRACT Aims To determine effects on craving, user satisfaction, and consumption patterns of two new nicotine replacement therapies (NRT) used for eight hours after overnight tobacco abstinence. Design In a within-subject, cross-over trial participants were randomly assigned Zonnic® nicotine mouth spray (1 mg/spray), Zonnic® nicotine lozenge (2.5 mg), Nicorette® gum (4 mg) and placebo lozenge on each of four study days. Setting University research unit. Participants Forty-seven dependent adult smokers. Measurements Participants rated their urges to smoke, irritability, concentration and restlessness before and during the first hour of product use on a 100-point scale. A subsample of 11 participants provided blood samples for nicotine analysis. Findings All active products reduced craving significantly more than placebo (mean reductions of 28.6, 25.8, 24.7 and 8.9 points for mouth spray, gum, lozenge and placebo). Mouth spray relieved craving faster than placebo and gum with significant reductions within five minutes of use (mean differences of ,14.5 (95% CI: ,23.0 to ,6.0) and ,10.6 (95% CI: ,19.1 to ,2.1) with placebo and gum respectively. Mouth spray produced a faster time to maximum plasma nicotine concentration (14.5 minutes, 95% CI: 8.0 to 21.0) compared to the lozenge (30.3 minutes, 95% CI: 21.1 to 39.5) and gum (45.8 minutes, 95% CI: 36.2 to 55.4). Maximum concentrations of blood nicotine were higher with mouth spray (10.0 ng/ml) and lozenge (10.8 ng/ml) compared to gum (7.8 ng/ml). Both lozenge and mouth spray were well tolerated. Conclusions The mouth spray and lozenge are at least as effective as 4 mg nicotine gum in relieving craving suggesting that they are likely to be effective in aiding smoking cessation. The mouth spray may be particularly useful for acute craving relief. [source] The management of dyslipidaemias in antiretroviral-treated HIV infection: a systematic reviewHIV MEDICINE, Issue 6 2007C McGoldrick Objectives The aim of the study was to assess the currently available evidence concerning the management of dyslipidaemias in HIV-infected individuals treated with antiretroviral therapy. Methods Randomized trials, published within the 5 years preceding 5 October 2005, were identified in PubMed Medline, Embase, and The Cochrane Central Register of Controlled Trials. Studies were then included or excluded, dependent on their meeting inclusion/exclusion criteria. The evidence obtained in the studies that were included was assessed using methods employed by the Scottish Intercollegiate Guidelines Network (SIGN). Results Thirteen relevant trials were identified, concerning the use of statins, fibrates, antiretroviral drug switches and insulin-sensitizing drugs. Most contained small numbers of trial participants. Conclusions Most studies suggested beneficial effects and satisfactory safety profiles for the interventions studied. However, the insulin-sensitizing drug rosiglitazone appeared to have some detrimental effects on lipid profiles. With the small numbers of participants in the majority of studies, these studies were likely to have been inadequately powered to assess the effects of the interventions examined. Larger trials are therefore necessary. [source] Meta-analysis: the effects of proton pump inhibitors on cardiovascular events and mortality in patients receiving clopidogrelALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 8 2010C. S. KWOK Summary Background, Recent studies have suggested an adverse interaction between proton pump inhibitors (PPI) and clopidogrel. Aim, To perform a meta-analysis of cardiovascular outcomes and mortality in patients taking clopidogrel, with and without concomitant PPI. Methods, We searched MEDLINE, EMBASE, Cochrane Controlled Trials Register in October 2009, and checked conference abstracts for randomized and nonrandomized studies that reported the risk of cardiovascular events and mortality with PPI exposure in patients taking clopidogrel. We performed random effects meta-analysis, stratified by study design and assessed heterogeneity using the I2 statistic. Results, Our review included 23 studies covering 93 278 patients. There was substantial heterogeneity in the meta-analyses of major cardiovascular events (19 studies, I2 = 79%) or myocardial infarction (12 studies, I2 = 77%). Analysis of propensity-matched or randomized trial participants showed no associated cardiovascular risk with PPIs, whereas other observational studies generally showed a significant association. Meta-analysis of 13 studies showed no significant association between PPI use and overall mortality (RR 1.09, 95% CI: 0.94,1.26, P = 0.23, I2 = 60%). Conclusion, As there are conflicting and inconsistent data regarding the adverse clopidogrel,PPI interaction, clinicians should focus on potential harm from ulcers/haemorrhage before deciding to omit PPIs in patients taking clopidogrel. [source] Strengthening the understanding of the relationship between survival designs and test statisticsPHARMACEUTICAL STATISTICS: THE JOURNAL OF APPLIED STATISTICS IN THE PHARMACEUTICAL INDUSTRY, Issue 2 2010Guoguang Ma Abstract In the planning of randomized survival trials, the role of follow-up time of trial participants introduces a level of complexity not encountered in non-survival trials. Of the two commonly used survival designs, one design fixes the follow-up time whereas the other allows it to vary. When the follow-up time is fixed the number of events varies. Conversely, when the number of events is fixed, the follow-up time varies. These two designs influence test statistics in ways that have not been fully explored resulting in a misunderstanding of the design,test statistic relationship. We use examples from the literature to strengthen the understanding of this relationship. Group sequential trials are briefly discussed. When the number of events is fixed, we demonstrate why a two-sample risk difference test statistic reduces to a one-sample test statistic which is nearly equal to the risk ratio test statistic. Some aspects of fixed event designs that need further consideration are also discussed. Copyright © 2009 John Wiley & Sons, Ltd. [source] Effectiveness of Increasing Emergency Department Patients' Self-perceived Risk for Being Human Immunodeficiency Virus (HIV) Infected Through Audio Computer Self-interview,based Feedback About Reported HIV Risk BehaviorsACADEMIC EMERGENCY MEDICINE, Issue 11 2009Roland C. Merchant MD Abstract Objectives:, Prior research has demonstrated that emergency department (ED) patient acceptance of human immunodeficiency virus (HIV) screening is partially dependent on patients' self-perceived risk of infection. The primary objective of this study was to determine the effectiveness of audio computer-assisted self-interview (ACASI)-based feedback. The intervention aimed to increase patient's self-perceived risk of being HIV infected by providing immediate feedback on their risk behaviors. Methods:, This 1-year, randomized, controlled trial at a U.S. ED enrolled a random sample of 18- to 64-year-old subcritically ill or injured adult patients who were not known to be HIV infected. All participants completed an anonymous, ACASI-based questionnaire about their HIV risk behaviors related to injection drug use and sex, as well as their self-perceived risk for being HIV infected. Participants were randomly assigned to one of two study groups: an intervention group in which participants received immediate ACASI-based feedback in response to each of their reported risk behaviors or a no-intervention group without feedback. Participants were asked to indicate their level of HIV risk on a five-point scale before and after they answered the questions. Change in level of self-perceived HIV risk was calculated and compared by study group using Pearson's chi-square test. An HIV risk behavior score that summarized reported HIV risk behavior was devised. Because HIV risk behaviors differ by sex, scores were calculated separately for each sex. Linear regression models that adjusted for study group and same subject covariance were employed to determine if higher HIV risk behavior scores were associated with an increase in self-perceived HIV risk. Results:, Of the 566 trial participants, the median age was 29 years (interquartile range [IQR] = 22,43 years), 62.2% were females, and 66.9% had been tested previously for HIV. After answering the reported HIV risk behavior questions, 12.6% of participants had an increase, 79.9% had no change, and 7.5% had a decrease in self-perceived HIV risk. Of the 46.6% of participants who initially indicated that they were not at risk for HIV, 11.4% had an increase in self-perceived HIV risk after answering the reported HIV risk behavior questions. Change in self-perceived HIV risk did not differ by study group (p = 0.77). There were no differences in reported HIV risk scores between the intervention and no-intervention groups for females (p = 0.78) or males (p = 0.86). In the linear regression models, a greater increase in self-perceived HIV risk was associated with higher reported HIV risk behavior scores for females (, = 0.59, 95% confidence interval [CI] = 0.15, 1.04) but not for males (, = 1.00, 95% CI = ,0.13 to 2.14). Conclusions:, Some ED patients can be moved, although modestly, to recognize their risk for being HIV infected by asking about their HIV risk behaviors. However, ACASI-based feedback messages about HIV risk behaviors do not increase subjects' self-perceived HIV risk. Female ED patients appear to increase their self-perceived HIV risk more than males when queried about their HIV risk behaviors. [source] Pivotal studies of orphan drugs approved for neurological diseases,ANNALS OF NEUROLOGY, Issue 2 2009Jun Mitsumoto MPH Objective To identify design elements of clinical trials leading to US Food and Drug Administration approval of drugs for neurological diseases with and without orphan indications. Methods We used publicly available information to identify approvals for drugs for neurological diseases with an orphan indication (n = 19) and compared them with recent approvals for drugs for neurological diseases without an orphan indication (n = 20). We identified "pivotal trials" from drug labels and drug approval packages, and assessed them on four elements of clinical trial design: control, blinding, randomization, and size. Results All drugs for neurological diseases (100%) approved without an orphan indication included at least two randomized, double-blind, placebo-controlled trials. In comparison, 32% of drugs with an orphan indication had at least two such trials (p < 0.001) and 74% had at least one (p = 0.02). Thirty-three pivotal trials were conducted for the 19 drugs approved with an orphan indication. Of the 33 trials, 11 (33%) did not use a placebo control, 9 (27%) were not double blind, and 4 (12%) were not randomized. Drugs approved without an orphan indication had more pivotal trials per drug (3.8 vs 1.7 trials; p < 0.001) and a larger mean trial size (506 vs 164 trial participants; p < 0.001). Interpretation The US Food and Drug Administration has approved orphan drugs for neurological diseases without randomized, doubled-blind, placebo-controlled pivotal trials. As orphan drug development grows, demand will likely increase for alternative designs for conducting adequate and well-controlled studies to demonstrate drug efficacy. Ann Neurol 2009;66:184,190 [source] A randomised controlled trial to evaluate the effect of self-administered analgesia on women's experience of outpatient treatment at colposcopyBJOG : AN INTERNATIONAL JOURNAL OF OBSTETRICS & GYNAECOLOGY, Issue 12 2005M.E. Cruickshank Objective To evaluate the effect of self-administered isoflurane and desflurane on women's experience of outpatient treatment at colposcopy. Design A prospective double-blinded randomised controlled trial. Setting A colposcopy clinic serving a regional population. Population Three hundred and ninety-six women scheduled for treatment of cervical intraepithelial neoplasia (CIN) by large loop excision of the transformation zone (LLETZ). Methods Self-administration of trial gas during a LLETZ procedure. One hundred and ninety-eight women were randomised to use isoflurane and desflurane and 198 to use placebo. Main outcome measures Patient satisfaction, pain and anxiety. Results The mean pain score for cervical surgery was significantly lower for women using isoflurane and desflurane (22.4) than the placebo arm (29.6) (P= 0.003). There was no significant difference between arms in anxiety levels before or after treatment. More women using isoflurane and desflurane (78%) reported ,total helpfulness' of the trial gas than those using placebo (67%) (P= 0.012). A subgroup analysis of trial participants classified as anxious by Hospital Anxiety and Depression Scale (HADS) score at recruitment showed that using isoflurane and desflurane significantly increased total treatment acceptability, helpfulness of the gas and willingness to undergo a similar procedure at six-month follow up. Conclusion Satisfaction with outpatient treatment at colposcopy is generally high. The main effect of isoflurane and desflurane evaluated in this trial was to reduce pain. It appeared to be effective for women with clinically significant anxiety and could be offered as an alternative to general anaesthesia. [source] Analyses of mortality risk in patients with dementia treated with galantamineACTA NEUROLOGICA SCANDINAVICA, Issue 1 2009H. H. Feldman Objective,,, To analyze mortality data from patients with Alzheimer's disease (AD), Alzheimer's plus cerebrovascular disease (AD + CVD) or vascular dementia (VaD). Methods,,, (1) Meta-analysis of mortality data from double-blind, placebo-controlled, randomized trials; and (2) recontact study to collect additional longer term mortality data from previous galantamine trial participants. Results (meta-analysis),,, Across 12 trials (,6 months duration), there was no increased risk of mortality associated with the use of galantamine (n = 4116) compared with that of placebo (n = 2386) (OR galantamine/placebo: 0.67, 95% CI 0.41,1.10). Results (recontact study),,, Median survival was 79 months for patients with AD (n = 478) and 59 months for patients with AD + CVD (n = 180) or VaD (n = 145). Prolonged galantamine treatment (> vs ,6 months) was not associated with decreased survival time (75 vs 61 months respectively; P = 0.02). Cox regression analyses were consistent with the Kaplan,Meier analyses. Conclusions,,, We found no short-term or longer term evidence of increased risk of mortality associated with the use of galantamine in patients with AD, AD + CVD or VaD. [source] Estimating breast cancer-specific and other-cause mortality in clinical trial and population-based cancer registry cohortsCANCER, Issue 22 2009James J. Dignam PhD Abstract BACKGROUND: To compute net cancer-specific survival rates using population data sources (eg, the National Cancer Institute's Surveillance, Epidemiology, and End Results [SEER] Program), 2 approaches primarily are used: relative survival (observed survival adjusted for life expectancy) and cause-specific survival based on death certificates. The authors of this report evaluated the performance of these estimates relative to a third approach based on detailed clinical follow-up history. METHODS: By using data from Cancer Cooperative Group clinical trials in breast cancer, the authors estimated 1) relative survival, 2) breast cancer-specific survival (BCSS) determined from death certificates, and 3) BCSS obtained by attributing cause according to clinical events after diagnosis, which, for this analysis was considered the benchmark "true" estimate. Noncancer life expectancy also was compared between trial participants, SEER registry patients, and the general population. RESULTS: Among trial patients, relative survival overestimated true BCSS in patients with lymph node-negative breast cancer; whereas, in patients with lymph node-positive breast cancer, the 2 estimates were similar. For higher risk patients (younger age, larger tumors), relative survival accurately estimated true BCSS. In lower risk patients, death certificate BCSS was more accurate than relative survival. Noncancer life expectancy was more favorable among trial participants than in the general population and among SEER patients. Tumor size at diagnosis, which is a potential surrogate for screening use, partially accounted for this difference. CONCLUSIONS: In the clinical trials, relative survival accurately estimated BCSS in patients who had higher risk disease despite more favorable other-cause mortality than the population at large. In patients with lower risk disease, the estimate using death certificate information was more accurate. For SEER data and other data sources where detailed postdiagnosis clinical history was unavailable, death certificate-based estimates of cause-specific survival may be a superior choice. Cancer 2009. © 2009 American Cancer Society. [source] Do phase 1 patients have greater needs for palliative care compared with other cancer patients?CANCER, Issue 2 2009Esmé Finlay MD Abstract BACKGROUND: Phase 1 oncology trial participants often are excluded from hospice. However, it is not known whether they would benefit from hospice services. The objectives of the current study were to define the palliative care needs of these patients and to determine whether their needs are greater than those of other cancer patients. METHODS: Two hundred ninety-seven patients who were undergoing cancer therapy and 69 patients who were enrolled in phase 1 trials at 7 oncology clinics in an urban cancer network were recruited and consented to participate in interviews. Interviewers assessed the prevalence and severity of 10 symptoms using the Global Distress Index of the Memorial Symptom Assessment Scale and patients' perceived need for 4 services typically provided through hospice: a chaplain, counselor, home health aide, and visiting nurse. RESULTS: Patients in the 2 groups had a similar symptom burden. However, after adjusting for Eastern Cooperative Oncology Group performance status scores, phase 1 patients were more likely to have 5 of the 10 symptoms and reported greater severity for 6 of the 10 symptoms. Compared with other patients, phase 1 patients were less likely to say they needed a home health aide (4 of 69 patients [6%] vs 198 of 297 patients [67%]), a chaplain (7 of 69 patients [10%] vs 134 of 297 patients [45%]), or a counselor (11 of 69 patients [16%] vs 160 of 297 patients [54%]; chi-square test: P < .001 for all). They were equally likely to say they needed a visiting nurse (30 of 69 patients [44%] vs 142 of 297 patients [48%]; chi-square test: P = .516). CONCLUSIONS: Compared with other patients who had cancer, patients who were participating in phase 1 trials were less likely to want several home care services, although they experienced a greater symptom burden. Further research will be needed to define the palliative care needs of this population. Cancer 2009. © 2009 American Cancer Society. [source] RTVue Fourier-domain OCT: reproducibility of RNFLT and macular thickness measurementsACTA OPHTHALMOLOGICA, Issue 2009A GARAS Purpose To evaluate the reproducibility of peripapillary retinal nerve fiber layer thickness (RNFLT) and macular thickness (MT) measurements with the RTVue-100 Fourier-domain optical coherence tomography, and to determine the influence of pupil dilation, patients' experience in examinations and severity of glaucoma. Methods One eye of 14 normal subjects, 11 patients with moderate, 12 patients with severe glaucoma and 40 screening trial participants were imaged 5 times on the same day. For the hospital-based patients, the measurement series was repeated after pupil dilation and 3 months later. Results For the RNFLT and the MT parameters, intrasession intraclass correlation coefficient (ICC) varied between 93.9 and 99.0%, intrasession coefficient of variation (CV) between 1.95 and 5.69 %, and intratest variability between 3.11 and 9.13 µm. Most thickness values, all intrasession CV and intratest variability values and the signal strength index remained unchanged after pupil dilation. Most intrasession CV values increased significantly with increasing disease severity. Patients' experience in imaging examinations had no influence on intrasession CV. Intratest variability and intrasession CV represented 79.1 to 98.6 % and 77.1 to 95.0 % of test-retest variability and intervisit CV, respectively. Conclusion Reproducibility of RNFLT and MT measurement with the RTVue-100 OCT are satisfactory for clinical purposes both in normals and glaucoma patients. Pupil dilation and patients' experience in imaging examinations do not influence the reproducibility of the measurements clinically significantly. Commercial interest [source] Pitfalls in the design and analysis of paediatric clinical trials: a case of a ,failed' multi-centre study, and potential solutionsACTA PAEDIATRICA, Issue 2 2009Johanna H Van Der Lee Abstract Aim: To increase awareness of possible pitfalls in the design and analysis of a multi-centre randomized clinical trial and to give an overview of alternative study designs and their consequences for power analyses in case of limited availability of trial participants. Methods: Investigation of the assumptions in the power calculation and re-analysis of the original data of a ,failed' trial on the effect of dexamethasone on the duration of mechanical ventilation in young children with respiratory syncytial virus infection. Use of ,boundaries approach' is explored using the data from this trial. A comprehensive overview of the various modern solutions for the design of a subsequent trial in this field is given. Results: Two frequent major deficiencies of trial design and data analysis are reviewed in depth, i.e. too optimistic assumptions for the sample size calculation and failure to adjust for centre effects. Conclusion: Critical review of trial assumptions and if necessary sample size recalculation based on an internal pilot by a data monitoring committee is recommended to maximize the probability of obtaining conclusive results. [source] | ||||||||||