Clinical trials : journal of the Society for Clinical Trials
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The Women's Health Initiative (WHI) randomized trial of estrogen plus progestin (E + P) was terminated early based on an assessment of harms exceeding benefits for disease prevention. The results contravened prevailing wisdom and a large body of literature regarding benefits of menopausal hormone therapy. The results and their interpretation have been the subject of considerable debate. ⋯ Developing a formal trial monitoring plan with a view towards influencing clinical practice is useful for creating consensus among DSMB members regarding the evidence that would justify stopping a trial and the framework to be used to address statistical complexities. Departures from design assumptions typically occur. These reinforce the role of the DSMB in exercising their judgment, and the judicious adaptation of these statistical guidelines in monitoring and reporting trials. In communicating the results in such circumstances, priority should be given to presenting as fair, accurate and transparent a view of the data and findings as current methods and technology allow.
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The analysis of clinical trials with dropout usually assumes the missing data are ;missing at random', i.e. given an individual's past observed data, their probability of dropout does not depend on their present outcome. However, in many settings this assumption is implausible, so it is sensible to assess the robustness of conclusions to departures from missing at random. ⋯ Our proposed approach allows for the greater uncertainty introduced by missing data that are potentially informatively missing. It can therefore claim to be a truly conservative method, unlike methods such as ;last observation carried forward'. It is practical and accessible to non-statisticians. It should be considered as part of the design and analysis of future clinical trials.
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Intention-to-treat (ITT) is an approach to the analysis of randomized controlled trials (RCT) in which patients are analyzed as randomized regardless of the treatment actually received. ⋯ This study emphasizes that authors use the label ;intention-to-treat' quite differently. The most common use refers to the analysis of all available subjects as randomized regardless of the missing data aspect.
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Innovative approaches are needed to allow for research in the emergency setting while not compromising either the rights or the interests of the subjects enrolled in such research. The emergency consent exception was developed to meet this need. ⋯ Careful attention should be paid by investigators and IRBs as to whether the emergency consent exception is really required for a particular study, or whether the study could proceed using only prospective consent with a longer recruitment period, more research sites, and a higher yield of available family members giving prospective consent. Measures that could shorten the time between initial contact and obtaining informed consent (for example, allowing consent over the phone rather than requiring written consent) might decrease the need for the emergency consent exception.
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Randomized Controlled Trial Multicenter Study
A study design to assess the safety and efficacy of on-pump versus off-pump coronary bypass grafting: the ROOBY trial.
Since the late 1960s, coronary artery bypass graft (CABG-only) procedures were traditionally performed using a heart-lung machine on an arrested heart (on-pump). Over the past decade, an increasing number CABG-only procedures were performed on a beating heart (off-pump). Advocates of the off-pump approach expect to reduce many of the adverse side effects related to using the heart-lung machine, while advocates for the on-pump procedure raise concerns related to graft patency rates and long-term event-free survival for the off-pump technique. ⋯ The study design presented allows for a balanced and fair assessment of the on-pump and off-pump CABG procedures across a diversity of clinical outcomes and resource use metrics. Its results have the potential to influence clinical cardiac surgical practice in the future.