David Collister1, Jennifer C Rodrigues2, Lawrence Mbuagbaw2, P J Devereaux3, Gordon Guyatt2, William Herrington4, Michael Walsh3. 1. Department of Health Research Methods, Evidence and Impact, McMaster University, 1280 Main Street West, Hamilton, Ontario, Canada; Population Health Research Institute, 237 Barton Street East, Hamilton, Ontario, Canada. Electronic address: dtcollister@gmail.com. 2. Department of Health Research Methods, Evidence and Impact, McMaster University, 1280 Main Street West, Hamilton, Ontario, Canada. 3. Department of Health Research Methods, Evidence and Impact, McMaster University, 1280 Main Street West, Hamilton, Ontario, Canada; Population Health Research Institute, 237 Barton Street East, Hamilton, Ontario, Canada. 4. Medical Research Council Population Health Research Unit at the University of Oxford, Clinical Trial Service Unit and Epidemiological Studies Unit, Richard Doll Building, Old Road Campus, Oxford OX3 7LF, UK.
Abstract
OBJECTIVE: To systematically review the epidemiology of prerandomized run-in periods in randomized controlled trials (RCTs) of chronic diseases. STUDY DESIGN AND SETTING: Meta-epidemiologic study of all RCTs from the four highest impact medical journals from 2011 to 2016. Eligible trials included parallel RCTs that evaluated pharmacologic therapies in adults with chronic diseases with a minimum follow-up of 24 weeks. RESULTS: Of 262 eligible manuscripts, 48 (18.3%), representing 42 unique RCTs, included run-in periods. Run-in periods were most common in cardiovascular disease and diabetes trials. Of the 42 RCTs, in 22 patients received the experimental therapy, 15 placebo, 4 both (either sequentially or in combination), and one did not report the run-in period drug. The median run-in period duration was 28 days (Q1: Q3 14: 66 days). Reasons for including a run-in period included ensuring eligibility criteria were met (18, 42.9%), excluding participants with nonadherence (18, 42.9%) and intolerances to therapy (15, 35.7%), and to standardize therapy prior to randomization (8, 19.0%). The median run-in completion rate was 77.4% (Q1: Q3 62.2:87.8%). CONCLUSIONS: Run-in periods are uncommon in RCTs of chronic drug treatments and when used, their reporting is heterogeneous. Further research to improve the design, use, and reporting of run-in periods is necessary.
OBJECTIVE: To systematically review the epidemiology of prerandomized run-in periods in randomized controlled trials (RCTs) of chronic diseases. STUDY DESIGN AND SETTING: Meta-epidemiologic study of all RCTs from the four highest impact medical journals from 2011 to 2016. Eligible trials included parallel RCTs that evaluated pharmacologic therapies in adults with chronic diseases with a minimum follow-up of 24 weeks. RESULTS: Of 262 eligible manuscripts, 48 (18.3%), representing 42 unique RCTs, included run-in periods. Run-in periods were most common in cardiovascular disease and diabetes trials. Of the 42 RCTs, in 22 patients received the experimental therapy, 15 placebo, 4 both (either sequentially or in combination), and one did not report the run-in period drug. The median run-in period duration was 28 days (Q1: Q3 14: 66 days). Reasons for including a run-in period included ensuring eligibility criteria were met (18, 42.9%), excluding participants with nonadherence (18, 42.9%) and intolerances to therapy (15, 35.7%), and to standardize therapy prior to randomization (8, 19.0%). The median run-in completion rate was 77.4% (Q1: Q3 62.2:87.8%). CONCLUSIONS: Run-in periods are uncommon in RCTs of chronic drug treatments and when used, their reporting is heterogeneous. Further research to improve the design, use, and reporting of run-in periods is necessary.