Clinical trials : journal of the Society for Clinical Trials
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Randomized Controlled Trial
Addressing methodological challenges in implementing the nursing home pain management algorithm randomized controlled trial.
Unrelieved pain among nursing home (NH) residents is a well-documented problem. Attempts have been made to enhance pain management for older adults, including those in NHs. Several evidence-based clinical guidelines have been published to assist providers in assessing and managing acute and chronic pain in older adults. Despite the proliferation and dissemination of these practice guidelines, research has shown that intensive systems-level implementation strategies are necessary to change clinical practice and patient outcomes within a health-care setting. One promising approach is the embedding of guidelines into explicit protocols and algorithms to enhance decision making. ⋯ Methodological challenges are inevitable in the conduct of an RCT. The need to optimize internal validity by adhering to the study protocol is compromised by the emergent logistical issues that arise during the course of the study.
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The objective of a non-inferiority trial is to determine whether a new or existing treatment is not less effective than another existing or current treatment by more than a pre-specified margin, Δ, usually with the requirement that the new treatment has some other advantage such as reduced cost or lower toxicity. A possible but unusual result in a non-inferiority trial is for the confidence interval for the treatment effect to lie between zero and Δ, implying that the new treatment is both inferior and non-inferior to the control. Such a result could occur in non-inferiority trials with large sample sizes or large non-inferiority margins. The possibility of this scenario occurring has implications for interim analyses. In standard superiority trials, stopping guidelines are often based on the p value obtained from testing whether treatments are equally effective. In non-inferiority trials, however, even if a new treatment is found to be inferior to the control at an interim analysis, there may still be a reasonable chance of demonstrating non-inferiority in the final analysis. ⋯ Conditional power is an appropriate tool for defining stopping guidelines for futility in non-inferiority trials, particularly those with large non-inferiority margins.
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Historical Article
Parental consent to participation in a randomised trial in children: associated child, family, and physician factors.
Low participation rates in randomised controlled trials involving children are almost a universal problem, leading to high cost and low statistical power. Trial, parent/family, child, and physician factors have been reported to influence parental willingness to consent for paediatric trials. ⋯ Parent, child, and physician factors are associated with consent for trial participation, with most not being modifiable. Having a member of the research study team approach the parent for consent appears to be the only feasible strategy for increasing recruitment to randomised trials in this setting.
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Intention-to-treat (ITT) analysis requires all randomised individuals to be included in the analysis in the groups to which they were randomised. However, there is confusion about how ITT analysis should be performed in the presence of missing outcome data. ⋯ Clinical trials should employ an ITT analysis strategy, comprising a design that attempts to follow up all randomised individuals, a main analysis that is valid under a stated plausible assumption about the missing data, and sensitivity analyses that include all randomised individuals in order to explore the impact of departures from the assumption underlying the main analysis. Following this strategy recognises the extra uncertainty arising from missing outcomes and increases the incentive for researchers to minimise the extent of missing data.
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The Institute of Medicine (IOM) has recommended that each person with cancer should have access to clinical trials, which have been associated with improving care quality and disparities. With no effective enrollment monitoring system, patterns of trial enrollment remain unclear. ⋯ Model stability and consistency suggest that this system is effective for population-based enrollment surveillance. For North Carolina, it suggests a worsening disparity in minority trial enrollment, though our analyses elucidate targets for intervention. Regional enrollment variation suggests the importance of access to clinical research networks and infrastructure. Substantial gender differences merit further examination.