Clinical trials : journal of the Society for Clinical Trials
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Randomized Controlled Trial
Conducting the ACTIVE randomized trial in hospice care: keys to success.
Untreated pain is common for patients at the end of life. Informal caregivers, often family or friends of patients, are responsible for working with hospice staff to provide pain management. Interdisciplinary team meetings conducted in hospices every 2 weeks provide an opportunity for hospice staff to communicate about pain management with informal caregivers of hospice patients. ⋯ The challenges of conducting randomized trials with hospice patients and caregivers can be addressed with appropriate study design, well-tested research methods, and proactive monitoring of any issues or problems.
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Randomized Controlled Trial
Moving a randomized clinical trial into an observational cohort.
The Selenium and Vitamin E Cancer Prevention Trial (SELECT) was a randomized, double-blind, placebo-controlled prostate cancer prevention study funded by the National Cancer Institute (NCI) and conducted by the Southwest Oncology Group (SWOG). A total of 35,533 men were assigned randomly to one of the four treatment groups (vitamin E + placebo, selenium + placebo, vitamin E + selenium, and placebo + placebo). The independent Data and Safety Monitoring Committee (DSMC) recommended the discontinuation of study supplements because of the lack of efficacy for risk reduction and because futility analyses demonstrated no possibility of benefit of the supplements to the anticipated degree (25% reduction in prostate cancer incidence) with additional follow-up. Study leadership agreed that the randomized trial should be terminated but believed that the cohort should be maintained and followed as the additional follow-up would contribute important information to the understanding of the biologic consequences of the intervention. Since the participants no longer needed to be seen in person to assess acute toxicities or to be given study supplements, it was determined that the most efficient and cost-effective way to follow them was via a central coordinated effort. ⋯ Extended follow-up of participants in prevention research is important to study the long-term effects of the interventions, such as those used in SELECT. The approach taken by SELECT investigators was to continue to follow participants centrally via an annual questionnaire and with a web-based option. The participants enrolled in the CFU study represent a large, well-characterized, generally healthy cohort. The CFU has enabled us to collect additional prostate and other cancer endpoints and longer follow-up on the almost 18,000 participants enrolled. The utility of the extensive biorepository that was developed during the course of the SELECT is enhanced by longer follow-up.
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Obtaining surrogate consent for clinical research studies conducted in the intensive care unit (ICU) setting is logistically challenging. ⋯ Surrogate and self-consent rates were similar. Surrogate unavailability was a major barrier to enrollment; overlap of staffing with usual visiting hours should be considered when planning trials in the ICU.
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Many randomized controlled trials (RCTs) collect cost-effectiveness data. Without appropriate sample size calculations, patient recruitment may cease before the cost-effectiveness of the intervention can be established or continue after the cost-effectiveness of the intervention is established beyond doubt. ⋯ Economic evaluations conducted alongside RCTs are valuable, but often present inconclusive evidence. Trial results may lead to discordant messages when the most effective intervention is probably not the most cost-effective. Despite methodological advances, trialists rarely assessed the extent to which their trial might resolve the key uncertainties about the cost-effectiveness of interventions. We recommend that grant funders should do more to encourage trialists to include economic end points in sample size calculations, particularly when the majority of costs and benefits of the intervention occur within the time frame of the trial.
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Due to the sparse nature of serious drug-related adverse events (AEs), meta-analyses combining data from several randomized controlled trials (RCTs) to evaluate drug safety issues are increasingly being conducted and published, influencing clinical and regulatory decision making. Evaluation of meta-analyses involves the assessment of both the individual constituent trials and the approaches used to combine them. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting framework is designed to enhance the reporting of systematic reviews and meta-analyses. However, PRISMA may not cover all critical elements useful in the evaluation of meta-analyses with a focus on drug safety particularly in the regulatory-public health setting. ⋯ While the majority of PRISMA elements were addressed by most studies reviewed, the majority of studies did not address most of the additional safety-related elements. These findings highlight the need for the development and validation of a drug safety reporting framework and the importance of the current initiative by the Council for International Organizations of Medical Sciences (CIOMS) to create a guidance document for drug safety information synthesis/meta-analysis, which may improve reporting, conduct, and evaluation of meta-analyses of drug safety and inform clinical and regulatory decision making.