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. 2019 Feb 11:11:169-184.
doi: 10.2147/CLEP.S188752. eCollection 2019.

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

David Ruben Teindl Laursen  1   2   3   4 , Asger Sand Paludan-Müller  2 , Asbjørn Hróbjartsson  1   3   4
Affiliations

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

David Ruben Teindl Laursen et al. Clin Epidemiol. .

Abstract

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: enrichment design; lead-in periods; research methodology; run-in periods; single-blind placebo; washout periods.

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Conflict of interest statement

Disclosure The authors report no conflicts of interest in this work.

Figures

Figure 1
Figure 1
Flowchart of screening for randomized clinical trials and for run-in periods.a Notes: aWe screened PubMed publications from 2014 one by one in random order until we had obtained 25 randomized clinical trials reporting a run-in period. The PubMed query used was: “(randomized controlled trial[Publication Type]) AND (“2014/01/01”[Date - Publication]: “2014/12/31”[Date - Publication])”.
See this image and copyright information in PMC

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