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Are pilot trials useful for predicting randomisation and attrition rates in definitive studies: A review of publicly funded trials

Are pilot trials useful for predicting randomisation and attrition rates in definitive studies: A review of publicly funded trials
Are pilot trials useful for predicting randomisation and attrition rates in definitive studies: A review of publicly funded trials

Background/aims: External pilot trials are recommended for testing the feasibility of main or confirmatory trials. However, there is little evidence that progress in external pilot trials actually predicts randomisation and attrition rates in the main trial. To assess the use of external pilot trials in trial design, we compared randomisation and attrition rates in publicly funded randomised controlled trials with rates in their pilots. 

Methods: Randomised controlled trials for which there was an external pilot trial were identified from reports published between 2004 and 2013 in the Health Technology Assessment Journal. Data were extracted from published papers, protocols and reports. Bland–Altman plots and descriptive statistics were used to investigate the agreement of randomisation and attrition rates between the full and external pilot trials. 

Results: Of 561 reports, 41 were randomised controlled trials with pilot trials and 16 met criteria for a pilot trial with sufficient data. Mean attrition and randomisation rates were 21.1% and 50.4%, respectively, in the pilot trials and 16.8% and 65.2% in the main. There was minimal bias in the pilot trial when predicting the main trial attrition and randomisation rate. However, the variation was large: the mean difference in the attrition rate between the pilot and main trial was −4.4% with limits of agreement of −37.1% to 28.2%. Limits of agreement for randomisation rates were −47.8% to 77.5%. 

Conclusion: Results from external pilot trials to estimate randomisation and attrition rates should be used with caution as comparison of the difference in the rates between pilots and their associated full trial demonstrates high variability. We suggest using internal pilot trials wherever appropriate.

attrition, dropout, feasibility, Pilot trial, randomisation, recruitment, trial design
1740-7745
Cooper, Cindy L.
9b1b9889-535a-4ac1-af21-e4916b2b6eaa
Whitehead, Amy
7bd4e1d1-078b-4f2b-bfc9-ed44ba0a195a
Pottrill, Edward
a5b4af32-60f2-4961-945c-4b86231ff6b7
Julious, Steven A.
e70c3d71-b62d-41a8-8e98-df954f127935
Walters, Stephen J.
aed7a87c-2c83-4a28-a68f-54bfecb3fa53
Cooper, Cindy L.
9b1b9889-535a-4ac1-af21-e4916b2b6eaa
Whitehead, Amy
7bd4e1d1-078b-4f2b-bfc9-ed44ba0a195a
Pottrill, Edward
a5b4af32-60f2-4961-945c-4b86231ff6b7
Julious, Steven A.
e70c3d71-b62d-41a8-8e98-df954f127935
Walters, Stephen J.
aed7a87c-2c83-4a28-a68f-54bfecb3fa53

Cooper, Cindy L., Whitehead, Amy, Pottrill, Edward, Julious, Steven A. and Walters, Stephen J. (2018) Are pilot trials useful for predicting randomisation and attrition rates in definitive studies: A review of publicly funded trials. Clinical Trials. (doi:10.1177/1740774517752113).

Record type: Article

Abstract

Background/aims: External pilot trials are recommended for testing the feasibility of main or confirmatory trials. However, there is little evidence that progress in external pilot trials actually predicts randomisation and attrition rates in the main trial. To assess the use of external pilot trials in trial design, we compared randomisation and attrition rates in publicly funded randomised controlled trials with rates in their pilots. 

Methods: Randomised controlled trials for which there was an external pilot trial were identified from reports published between 2004 and 2013 in the Health Technology Assessment Journal. Data were extracted from published papers, protocols and reports. Bland–Altman plots and descriptive statistics were used to investigate the agreement of randomisation and attrition rates between the full and external pilot trials. 

Results: Of 561 reports, 41 were randomised controlled trials with pilot trials and 16 met criteria for a pilot trial with sufficient data. Mean attrition and randomisation rates were 21.1% and 50.4%, respectively, in the pilot trials and 16.8% and 65.2% in the main. There was minimal bias in the pilot trial when predicting the main trial attrition and randomisation rate. However, the variation was large: the mean difference in the attrition rate between the pilot and main trial was −4.4% with limits of agreement of −37.1% to 28.2%. Limits of agreement for randomisation rates were −47.8% to 77.5%. 

Conclusion: Results from external pilot trials to estimate randomisation and attrition rates should be used with caution as comparison of the difference in the rates between pilots and their associated full trial demonstrates high variability. We suggest using internal pilot trials wherever appropriate.

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More information

Accepted/In Press date: 1 January 2018
e-pub ahead of print date: 23 January 2018
Keywords: attrition, dropout, feasibility, Pilot trial, randomisation, recruitment, trial design

Identifiers

Local EPrints ID: 418448
URI: http://eprints.soton.ac.uk/id/eprint/418448
ISSN: 1740-7745
PURE UUID: 7da40af6-c655-4101-ba94-25a4655082c3

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Date deposited: 08 Mar 2018 17:30
Last modified: 15 Mar 2024 18:36

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Contributors

Author: Cindy L. Cooper
Author: Amy Whitehead
Author: Edward Pottrill
Author: Steven A. Julious
Author: Stephen J. Walters

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