Clinical trials : journal of the Society for Clinical Trials
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Traditionally, phase I clinical trial designs are based upon one predefined course of treatment while varying among patients the dose given at each administration. In actual medical practice, patients receive a schedule comprised of several courses of treatment, and some patients may receive one or more dose reductions or delays during treatment. Consequently, the overall risk of toxicity for each patient is a function of both actual schedule of treatment and the differing doses used at each adminstration. ⋯ Our design is the first for phase I clinical trials that is sufficiently flexible and practical to truly reflect clinical practice by varying both dose and the timing and number of administrations given to each patient.
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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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In analysing clinical trials designed to show superiority of one treatment compared to another, it is standard to use an intention to treat analytic approach. In active-controlled noninferiority studies, this is not standard, due to concerns that such an analysis will inflate the chance of falsely rejecting the null hypothesis, accepting therapeutic noninferiority when it is not justified. ⋯ In this commentary, we argue that these same justifications carry over to noninferiority studies, and that for those and other reasons it should be the preferred analytic approach. We review regulatory guidelines, and propose a number of approaches to minimizing the potential disadvantages of the ITT approach in the noninferiority setting.
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Sample size decisions for clinical trials should be taken in such a way as to maximize informed choice by reducing scientific uncertainty about the consequences of an intervention. ⋯ The approach is a pragmatic aid to trial design in settings where patient preference drives the choice between alternative treatments.
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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.