Back to Journals » Clinical Epidemiology » Volume 11

Randomized clinical trials with run-in periods: frequency, characteristics and reporting

Authors Laursen DRT, Paludan-Müller AS, Hróbjartsson A

Received 30 September 2018

Accepted for publication 7 December 2018

Published 11 February 2019 Volume 2019:11 Pages 169—184

DOI https://doi.org/10.2147/CLEP.S188752

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Colin Mak

Peer reviewer comments 2

Editor who approved publication: Professor Henrik Toft Sørensen


David Ruben Teindl Laursen,1–4 Asger Sand Paludan-Müller,2 Asbjørn Hróbjartsson1,3,4

1Centre for Evidence-Based Medicine Odense (CEBMO), Odense University Hospital, Odense, Denmark; 2Nordic Cochrane Centre, Rigshospitalet, Copenhagen, Denmark; 3Department of Clinical Research, University of Southern Denmark, Odense, Denmark; 4Odense Patient data Explorative Network (OPEN), Odense University Hospital, Odense, Denmark

Background: Run-in periods are occasionally used in randomized clinical trials to exclude patients after inclusion, but before randomization. In theory, run-in periods increase the probability of detecting a potential treatment effect, at the cost of possibly affecting external and internal validity. Adequate reporting of exclusions during the run-in period is a prerequisite for judging the risk of compromised validity. Our study aims were to assess the proportion of randomized clinical trials with run-in periods, to characterize such trials and the types of run-in periods and to assess their reporting.
Materials and methods: This was an observational study of 470 PubMed-indexed randomized controlled trial publications from 2014. We compared trials with and without run-in periods, described the types of run-in periods and evaluated the completeness of their reporting by noting whether publications stated the number of excluded patients, reasons for exclusion and baseline characteristics of the excluded patients.
Results: Twenty-five trials reported a run-in period (5%). These were larger than other trials (median number of randomized patients 217 vs 90, P=0.01) and more commonly industry trials (11% vs 3%, P<0.01). The run-in procedures varied in design and purpose. In 23 out of 25 trials (88%), the run-in period was incompletely reported, mostly due to missing baseline characteristics.
Conclusion: Approximately 1 in 20 trials used run-in periods, though much more frequently in industry trials. Reporting of the run-in period was often incomplete, precluding a meaningful assessment of the impact of the run-in period on the validity of trial results. We suggest that current trials with run-in periods are interpreted with caution and that updates of reporting guidelines for randomized trials address the issue.

Keywords: run-in periods, lead-in periods, enrichment design, single-blind placebo, washout periods, research methodology


Creative Commons License This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.

Download Article [PDF]  View Full Text [HTML][Machine readable]