Controlled clinical trials最新文献

This study was performed to evaluate randomized cancer trials resulting negative regarding inadequate accrual, unsupported assumptions of equivalence and factors implied in such assumptions. A search in PubMed electronic data base was done for a sample of 800 most recently entered studies by March 2003 indexed with MESH term “neoplasms” and categorized according to design, intervention, outcome and conclusion. Minimal detectable differences with optimized power were calculated in each comparison according to number of patients accrued. Factors related with inadequate claim for equivalence in negative comparisons were also searched. Among the papers located, 194 met requirements and 188 were analyzed leading to 392 valid comparisons addressing survival, anti cancer effect or major toxicity, 235 of which resulted “negative”. According to accrual, only 15.2% (ci95%, 9.9% to 20.3%) of negative comparisons would detect a 10% absolute difference between arms with 80% of chance. 53.6% (ci95%, 47.0% to 60.1%) of negative comparisons inadequately claimed equivalence. However, equivalence was supported by data in only 20.5% (ci95%, 12.6% to 28.4%) of negative comparisons that claimed for it. Negative comparisons based on new drugs had higher likelihood to be inadequately presented as supporting equivalence than those based in older drugs (66.7% vs. 43.5%, chi-square p=0.024). We concluded that most cancer clinical comparisons resulting negative are affected by poor accrual. They often inadequately claim for equivalence without supporting data. Comparisons involving new drugs are specially affected by this problem. Authors, editors and readers must be more rigorous regarding adequate assumptions of equivalence.

SEARCH for Diabetes in Youth is an observational, multicenter study focusing on physician-diagnosed diabetes in individuals <20 years old. The study will estimate the population prevalence and incidence of diabetes by type, age, gender, and ethnicity and develop practical approaches to diabetes classification in 5 million children (∼6% of the <20 U.S. population) with wide ethnic and socioeconomic representation from four geographically defined populations and two health plans. An estimated 6000 prevalent and 800 incident diabetes cases per year will be identified with annual follow-up. Cases will be ascertained through clinical and nonclinical resources or partnerships at each site. Data collection involves patient interviews, physical examinations, laboratory measurements (diabetes autoantibodies, fasting/stimulating C-peptide, hemoglobin A1c, blood glucose, lipids, urine albumin, creatinine), medical records reviews, and documentation of risk factors for complications and processes of care.

Purpose: We present the rationale and design of the Zambian Exclusive Breast-feeding Study (ZEBS), a randomized trial evaluating the efficacy of short-duration exclusive breast-feeding (EBF) as a strategy to reduce postnatal human immunodeficiency virus (HIV) transmission while preserving the other health benefits of this important mode of infant feeding. Methods: One thousand two hundred HIV-positive pregnant women were recruited in Lusaka, Zambia, and followed with their infants for 24 months. In addition to Nevirapine (NVP), all women received intensive and frequent clinic- and home-based counseling to support exclusive breast-feeding. When the infant was 1 week of age, half of the women were randomly assigned to a group encouraged to abruptly (<24 h) cease all breast-feeding at 4 months. The primary outcome of the experimental (randomized) comparison is HIV-free survival at 24 months. The design is also observational and will compare HIV transmission rates between those who do and do not adhere to the counseling intervention promoting exclusive breast-feeding. Conclusion: Our study aims to quantify the benefit–risk ratio of early cessation of exclusive breast-feeding to interrupt mother-to-child transmission of HIV with an intensive behavioral intervention and has both observational and experimental analytic approaches. Our study design assesses efficacy and also has a prominent applied component that if the intervention is effective, it will permit rapid and sustainable adoption within low-resource communities.

While randomised controlled trials remain the accepted ‘gold standard’ in medical research, participant recruitment is often problematic, particularly with primary care trials or those requiring healthy volunteers. Such difficulties can jeopardise the trial, leading to early abandonment, reduced statistical power or timetable and budget overruns. Substantial changes in recruitment plans may reduce the generalisability of the research. In order to overcome some of the more common recruitment difficulties, it is important that researchers share their recruitment strategy successes and failures. We report our experience of recruiting healthy volunteers to a condom trial, based within primary care and community populations. This was an RCT of the effect that using an additional spermicidal lubricant has on condom failure. We originally aimed to recruit entirely from Family Planning Clinics, but eventually required a wide variety of strategies. Targeted mailings, newspaper coverage and electronic ‘posters’ were among the most successful we used to bolster clinic recruitment. Concerned at our slow recruitment rates, we conducted a questionnaire survey investigating the reasons for participation and non-participation in the research completed by 101 trial participants, 112 decliners and 90 controls (total 303). The most important reasons given for taking part included ‘considering the research to be important’ (85%), ‘wanting to help the researchers’ (70%), ‘having time to help’ (62%) and ‘getting free condoms and lubricant’ (56%). The most popular reasons for declining were ‘not wanting to use condoms’ (38%), ‘partner's unwillingness to take part’ (29%), ‘not wanting to alter usual contraceptive practice’ (27%), ‘not having time’ (21%). Contrary to expectations, embarrassment and fears about confidentiality were relatively unimportant factors in this decision. In conclusion, the key to attaining recruitment targets was the core research team taking an active part, working closely with clinic staff and maintaining tight control of the process. Altruism remains a powerful motivation for participants, supported by incentives and procedural details to minimise personal inconvenience. Even for intimate research topics, these general factors outweigh specific issues.

During the design stage of a study to assess the population sensitivity (P_S) (or specificity) of a diagnostic test, the number of subjects (N) who will be administered both a gold standard test and a new test needs to be calculated. A common approach is to calculate the number of cases (n) with a specific disease or condition as diagnosed by the gold standard test first, and then to determine N based on the prevalence or incidence rate of the disease (P_P) in the population, calculated as N=n/P_P. Due to sampling variation, given the sample size N, the number of cases having the disease identified by the gold standard test could be less than N×P_P. In this case, the study would be under-powered and may fail to produce an unbiased and precise estimate. In this study, we investigated this possibility for a situation where the required sample size is calculated using the confidence interval approach. When the sampling variation is considered, the variance of the sample sensitivity is slightly inflated, but its confidence interval width becomes widely dispersed. In order to reach the originally designed precision, adjustment in the sample size, N, is needed and suggested in this paper.

Purpose: To report the protocol for surveillance of the eye and vision in a clinical trial of MART1-transduced dendritic cells for metastatic melanoma. Methods: In a phase I/II clinical trial of dendritic cell-based genetic immunotherapy for metastatic cutaneous melanoma, ophthalmic evaluation is performed prior to immunization (Baseline Evaluation), 56±7 days after first vaccination (mid-study evaluation), when dendritic cell injections are complete 112±7 days after first vaccination (end-study evaluation) and 168±7 days after first vaccination (post-study evaluation). Results: The protocol for baseline, mid-study and end-study evaluations of the eye and vision includes ophthalmic history, comprehensive ophthalmic examination, psychophysical and electrophysiological visual function assessment, fundus photography and fluorescein angiography. Post-study evaluation consists of the 25-item visual functioning questionnaire augmented to elicit autoimmune manifestation with complete ophthalmic evaluation if vision-related symptoms or abnormalities are noted during or after the vaccination. Conclusion: Limited adverse effects on the eye and vision have been reported in melanoma immunotherapy trials, although this novel mode of therapy has the potential to induce melanoma paraneoplastic syndromes known to severely impair vision. Therefore, surveillance of the eye and vision should be considered in melanoma immunotherapy trials.

The optimum site and investigator selection process remains a closely guarded confidential matter and an essential part of development expertise of big pharmaceutical companies and CROs. The right and careful selection and evaluation of investigators and site is critical for successful completion of the trial within budget, timelines and generation of high quality data. The criteria for site and investigator selection in India for Good Clinical Practices (GCP) clinical trials are described for a start up company/CRO and can be applied to any country in Asia and Africa. Foreign sponsors doing clinical studies in India should pay close attention to site and investigator selection. The first GCP study in India was done only in 1995. At the dawn of 21st century, India is at the take off stage in clinical trials now. GCP studies can be done in India, as the quality of data is good, costs are lower and patient enrolment is much faster resulting in early completion of studies.

Background: Racial distribution of clinical trial participants is important because results from these studies serve to define evidence-based practice. This report summarizes the experience of the VA Cooperative Studies Program (CSP) in enrolling white, black and Hispanic patients. Methods: An analysis of enrollment in randomized controlled trials conducted by VA CSP between 1975 and 2000. A standardized enrollment ratio for each trial was calculated by dividing the observed number of enrolled white patients in the trial by the expected number of eligible white patients based on the proportion of white patients hospitalized at the enrolling VA Medical Centers. Results: 138 VA CSP clinical trials were initiated between 1975 and 2000, 83 contained information on race for 71,463 patients. Overall, 76% of enrolled patients were white, 20% were black, and 4% were Hispanic. Based on standardized enrollment ratios, 60 of the 83 trials had 95% confidence intervals that excluded 1.0. Of these, 32 studies enrolled more white patients than expected and 28 enrolled more Black and/or Hispanic patients than expected based on the racial distribution of patients hospitalized at sites involved in the trials. When trials were separated by intervention type, 13 of the 19 trials that had an invasive arm enrolled fewer minority patients than expected. In trials that targeted diseases that affect minority populations to a greater degree than whites (diabetes, hypertension and end stage renal disease), 11 of the 14 trials enrolled more minority patients than expected. Conclusions: There were several trials that enrolled either more or less minority patients than expected based on patients hospitalized at study sites. Trials that included an invasive arm enrolled fewer minority participants than expected. Trials that involve invasive therapies may wish to adopt special recruitment strategies to reach minority populations.

The Women's Health Initiative (WHI) is a study designed to examine the major causes of death and disability in women. This multi-arm, randomized, controlled trial of over 160,000 post-menopausal women of varying ethnic and socioeconomic backgrounds and a goal of 20% of the study participants from minority populations is perhaps one of the most challenging recruitment efforts ever undertaken. Of the two main study arms, the Clinical Trial (CT) and the Observational Study (OS), the CT arm recruitment goal was to randomize 64,500 postmenopausal women 50–79 years of age. Women enrolled in the study will be followed for a period of 8–12 years. Ten clinical centers, out of a total of 40 throughout the United States, were selected as minority recruitment centers on the basis of their history of interaction with and access to large numbers of women from certain population subgroups. WHI enrollment began in September 1993 and ended in December 1998, resulting in the randomization and enrollment of a total of 161,856 (17.5% minority) women participants (68,135 (18.5% minority) in the CT and 93,721 (16.7%) in the OS). Within the CT arm, WHI achieved 101.7% of the goal of 48,000 participants in the Dietary Modification (DM) component, and 99.4% of the goal of 27,500 in the hormone-replacement component (HRT), with 11.8% overlap between DM and HRT. Of those who expressed initial interest in WHI, African Americans had the highest randomization yields in the DM component and Hispanics had the highest in the HRT component (15.2% and 10.2%, respectively). Overall, mass mailing was the greatest source of randomized participants. In addition, minority clinics found community outreach, personal referrals, and culturally appropriate recruitment materials particularly effective recruitment tools. For minority recruitment, our findings suggest that the key to high yield is reaching the target population through appropriate recruitment strategies and study information that get their attention. Also, once minority subjects are reached, they tend to participate.