Trials
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The pace of novel medical treatments and approaches to therapy has accelerated in recent years. Unfortunately, many potential therapeutic advances do not fulfil their promise when subjected to randomized controlled trials. It is therefore highly desirable to speed up the process of evaluating new treatment options, particularly in phase II and phase III trials. To help realize such an aim, in 2003, Royston and colleagues proposed a class of multi-arm, two-stage trial designs intended to eliminate poorly performing contenders at a first stage (point in time). Only treatments showing a predefined degree of advantage against a control treatment were allowed through to a second stage. Arms that survived the first-stage comparison on an intermediate outcome measure entered a second stage of patient accrual, culminating in comparisons against control on the definitive outcome measure. The intermediate outcome is typically on the causal pathway to the definitive outcome (i.e. the features that cause an intermediate event also tend to cause a definitive event), an example in cancer being progression-free and overall survival. Although the 2003 paper alluded to multi-arm trials, most of the essential design features concerned only two-arm trials. Here, we extend the two-arm designs to allow an arbitrary number of stages, thereby increasing flexibility by building in several 'looks' at the accumulating data. Such trials can terminate at any of the intermediate stages or the final stage. ⋯ The new designs are practical and are supported by theory. They hold considerable promise for speeding up the evaluation of new treatments in phase II and III trials.
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Randomized Controlled Trial
The effectiveness of simple psychological and exercise interventions for high prevalence mental health problems in young people: a factorial randomised controlled trial.
The prevalence of mental illness in young people is the highest of any age group, with the onset of depression, anxiety and substance use peaking between 18 and 24 years. Effective treatments that target sub-threshold or mild to moderate levels of disorder in young people are required to reduce the risk of persistence and recurrence. The aims of this study are to evaluate whether treatments that are less intensive than cognitive-behaviour therapy, such as problem solving therapy and exercise treatments, are acceptable and effective in managing depression and anxiety symptoms in young people and to identify possible attributes in those who are likely to respond to these treatments. ⋯ The effectiveness of less complex psychological and exercise interventions in young help-seekers with sub-threshold or mild to moderate presentations of high prevalence disorders is yet to be explored. This study has been designed to examine the effectiveness of these interventions delivered alone, or in combination, in a youth-specific service. If effective, the interventions have the potential to prevent the progression of early symptoms and distress to later and potentially more serious stages of mental disorder and reduce the likelihood of ongoing problems associated with the risk of persistence and recurrence.
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Randomized Controlled Trial Multicenter Study Comparative Study
Pancreatitis, very early compared with normal start of enteral feeding (PYTHON trial): design and rationale of a randomised controlled multicenter trial.
In predicted severe acute pancreatitis, infections have a negative effect on clinical outcome. A start of enteral nutrition (EN) within 24 hours of onset may reduce the number of infections as compared to the current practice of starting an oral diet and EN if necessary at 3-4 days after admission. ⋯ The PYTHON trial is designed to show that a very early (< 24 h) start of EN reduces the combined endpoint of mortality or infections as compared to the current practice of an oral diet and EN if necessary at around 72 hours after admission for predicted severe acute pancreatitis.