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

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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.

OriginalsprogEngelsk
TidsskriftClinical Epidemiology
Vol/bind11
Sider (fra-til)169—184
ISSN1179-1349
DOI
StatusUdgivet - feb. 2019

Fingeraftryk

Randomized Controlled Trials
Publications
Random Allocation
PubMed
Reproducibility of Results
Guidelines

Citer dette

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title = "Randomized clinical trials with run-in periods: frequency, characteristics and reporting",
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",
author = "Laursen, {David Ruben Teindl} and Paludan-M{\"u}ller, {Asger Sand} and Asbj{\o}rn Hr{\~o}bjartsson",
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language = "English",
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pages = "169—184",
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Randomized clinical trials with run-in periods: frequency, characteristics and reporting. / Laursen, David Ruben Teindl; Paludan-Müller, Asger Sand; Hrõbjartsson, Asbjørn.

I: Clinical Epidemiology, Bind 11, 02.2019, s. 169—184.

Publikation: Bidrag til tidsskriftReviewForskningpeer review

TY - JOUR

T1 - Randomized clinical trials with run-in periods: frequency, characteristics and reporting

AU - Laursen, David Ruben Teindl

AU - Paludan-Müller, Asger Sand

AU - Hrõbjartsson, Asbjørn

PY - 2019/2

Y1 - 2019/2

N2 - 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.

AB - 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.

KW - Enrichment design

KW - Lead-in periods

KW - Research methodology

KW - Run-in periods

KW - Single-blind placebo

KW - Washout periods

U2 - 10.2147/CLEP.S188752

DO - 10.2147/CLEP.S188752

M3 - Review

C2 - 30809104

VL - 11

SP - 169—184

JO - Clinical Epidemiology

JF - Clinical Epidemiology

SN - 1179-1349

ER -