Dataset Information

Overrunning in clinical trials: some thoughts from a methodological review.

ABSTRACT:

Background

In sequential and adaptive trials, the delay that happens after the trial is stopped, by a predetermined stopping criterion, takes the name of overrunning. Overrunning consists of extra data, collected by investigators while awaiting results of the interim analysis (IA). The inclusion of such extra data in the analyses is scientifically appropriate and follows regulatory advice. Nevertheless, its effect from a broader perspective is unclear.

Methods

This article aims at clarifying the overall impact of including such overrunning data, providing first a revision, and then a comparison of the several approaches proposed in the literature for treating such data. A simulation study is performed based on two real-life examples.

Results

The paper shows that overrunning inclusion could seriously change the decision of an early conclusion of the study. It also shows that some of the methods proposed in the literature to include overrunning data are more conservative than others.

Conclusion

The choice of a more or a less conservative method could be considered more appropriate depending on the endpoint type or the design type.

SUBMITTER: Baldi I

PROVIDER: S-EPMC7374901 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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Publications

Overrunning in clinical trials: some thoughts from a methodological review.

Baldi Ileana I Azzolina Danila D Soriani Nicola N Barbetta Beatrice B Vaghi Paola P Giacovelli Giampaolo G Berchialla Paola P Gregori Dario D

Trials 20200721 1

<h4>Background</h4>In sequential and adaptive trials, the delay that happens after the trial is stopped, by a predetermined stopping criterion, takes the name of overrunning. Overrunning consists of extra data, collected by investigators while awaiting results of the interim analysis (IA). The inclusion of such extra data in the analyses is scientifically appropriate and follows regulatory advice. Nevertheless, its effect from a broader perspective is unclear.<h4>Methods</h4>This article aims at ...[more]

PMID: 32693832

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Project description:BackgroundRecent years have seen publication of a considerable number of clinical trials of preventive interventions against clinical malaria in children. There has been variability in the specification of end-points, case definitions, analysis methods and reporting and the relative lack of standardization complicates the ability to make comparative evaluations between trials.MethodsTo prepare for a WHO consultation on design issues in malaria vaccine trials, controlled trials of preventive interventions against malaria in children in endemic countries were identified in which clinical malaria, or death, had been one of the main end-points. Trials were included that evaluated the impact of vaccines, insecticide-treated bed nets (ITN), intermittent presumptive or preventive therapy in infants (IPTi) or, in one instance, vitamin A supplementation. Methods that had been used in these trials were summarized and compared in order to identify issues that were directly relevant to the design of malaria vaccine trials.Results29 controlled trials of preventive malaria interventions were identified, of which eight were vaccine trials. Vaccine trials that were designed to detect an effect on clinical malaria all reported the incidence rate of first episodes of clinical malaria as their primary endpoint. Only one trial of a preventive intervention (of ITN) was identified that was designed to detect an effect on severe malaria. A group of larger trials were designed to detect an effect of impregnated bed nets or curtains on all-cause mortality as the primary end-point. Key methodological and reporting differences between trials are noted in the text. Two issues have been identified that are of some concern. Firstly, the choice of primary endpoint is not stated in the reports of a number of the trials and, secondly, the relationship between pre-specified analysis plans and trial reports is rarely made clear.ConclusionThis article reports an investigation into the ways in which trial design and reporting could be improved and standardized to enable comparative evaluation of the relative merits of malaria control measures, and specifically with respect to the design of malaria vaccine trials. The need for standardization of clinical trial design, conduct, analysis and reporting has been also affirmed as a priority area by the Malaria Vaccine Technology Roadmap.

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Dataset Information

Overrunning in clinical trials: some thoughts from a methodological review.

Background

Methods

Results

Conclusion

Publications

Overrunning in clinical trials: some thoughts from a methodological review.

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