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. 2021 Sep 20;40(21):4714-4731.
doi: 10.1002/sim.9091. Epub 2021 Jun 14.

A hypothesis test of feasibility for external pilot trials assessing recruitment, follow-up, and adherence rates

Duncan T Wilson  1 , Julia Brown  1 , Amanda J Farrin  1 , Rebecca E A Walwyn  1
Affiliations

A hypothesis test of feasibility for external pilot trials assessing recruitment, follow-up, and adherence rates

Duncan T Wilson et al. Stat Med. .

Abstract

The power of a large clinical trial can be adversely affected by low recruitment, follow-up, and adherence rates. External pilot trials estimate these rates and use them, via prespecified decision rules, to determine if the definitive trial is feasible and should go ahead. There is little methodological research underpinning how these decision rules, or the sample size of the pilot, should be chosen. In this article we propose a hypothesis test of the feasibility of a definitive trial, to be applied to the external pilot data and used to make progression decisions. We quantify feasibility by the power of the planned trial, as a function of recruitment, follow-up, and adherence rates. We use this measure to define hypotheses to test in the pilot, propose a test statistic, and show how the error rates of this test can be calculated for the common scenario of a two-arm parallel group definitive trial with a single normally distributed primary endpoint. We use our method to redesign TIGA-CUB, an external pilot trial comparing a psychotherapy with treatment as usual for children with conduct disorders. We then extend our formulation to include using the pilot data to estimate the standard deviation of the primary endpoint and incorporate this into the progression decision.

Keywords: external pilot; feasibility; pilot trial; progression criteria; sample size.

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References

REFERENCES

    1. Sully BGO, Julious SA, Nicholl J. A reinvestigation of recruitment to randomised, controlled, multicenter trials: a review of trials funded by two UK funding agencies. Trials. 2013;14(1):166. https://doi.org/10.1186/1745-6215-14-166.
    1. Fay MP, Halloran ME, Follmann DA. Accounting for variability in sample size estimation with applications to nonadherence and estimation of variance and effect size. Biometrics. 2006;63(2):465-474. https://doi.org/10.1111/j.1541-0420.2006.00703.x.
    1. Teare M, Dimairo M, Shephard N, Hayman A, Whitehead A, Walters S. Sample size requirements to estimate key design parameters from external pilot randomised controlled trials: a simulation study. Trials. 2014;15(1):264. https://doi.org/10.1186/1745-6215-15-264.
    1. Craig P, Dieppe P, Macintyre S, Michie S, Nazareth I, Petticrew M. Developing and evaluating complex interventions: the new medical research council guidance. BMJ Br Med J. 2008;337:a1655. https://doi.org/10.1136/bmj.a1655.
    1. Eldridge SM, Lancaster GA, Campbell MJ, et al. Defining feasibility and pilot studies in preparation for randomised controlled trials: development of a conceptual framework. PLoS One. 2016;11(3):e0150205. https://doi.org/10.1371/journal.pone.0150205.

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