title: An empirical evaluation of the placebo run-in.
abstract: A prerandomization placebo run-in period is often used in an attempt to exclude potential clinical trial participants who are likely to be poor adheres. It is assumed that potential participants who are poor adherers during the run-in will be less likely to take medication during the trial. This assumption was tested in the Cholesterol Reduction in Seniors Program (CRISP), by prescribing placebo for a 3-week period, but not using the results of the run-in as an entry criterion. The CRISP study was a pilot study designed to compare the effects on lipids and the safety of two doses of lovastatin and placebo in persons 65 years of age and older. After general entry criteria were satisfied, each participant was prescribed placebo for a 3-week period. At the end of the 3-week period, all participants were randomized to one of the three treatment groups, regardless of their adherence to the placebo. Of the 431 participants in the study, 66 (15%) who took less than 80% of the prescribed placebo or who failed to return their unused placebo pills were classified as poor run-in adherers. Poor run-in adherence was associated with lower educational attainment. At 3 and 6 months of follow-up mean adherence was 89.3% and 83.4% among all participants. Exclusion of poor run-in adherers would have increased these means to 90.9% and 85.5%, respectively. Treatment effect as measured by fall in LDL cholesterol would have increased by 2.9 mg/dl in the 40 mg/day dose group at 3 months of follow-up with the addition of a placebo run-in. We conclude that a placebo run-in would have had little effect on the outcome of the CRISP study and would have substantially increased recruitment difficulties. Lower educated persons were more likely to be excluded by a placebo run-in, but the effect of the run-in on follow-up adherence was stronger in less educated participants. More research about the role of a placebo run-in is needed in order to determine the appropriate role of this method in clinical trials.
authors.affiliation: School of Public Health, Department of Biostatistics, University of North Carolina, Chapel Hill 27514, USA.
authors.forename: C E
authors.initials: CE
authors.lastname: Davis
authors.forename: W B
authors.initials: WB
authors.lastname: Applegate
authors.forename: D J
authors.initials: DJ
authors.lastname: Gordon
authors.forename: R C
authors.initials: RC
authors.lastname: Curtis
authors.forename: M
authors.initials: M
authors.lastname: McCormick
mesh_terms: D000368:Aged; D002784:Cholesterol / Q000097:blood*; D008078:Cholesterol, LDL / Q000097:blood; D004522:Educational Status; D005240:Feasibility Studies; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D006937:Hypercholesterolemia / Q000188:drug therapy; D008148:Lovastatin / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D010349:Patient Compliance; D018579:Patient Selection; D010865:Pilot Projects; D010919:Placebos; D012107:Research Design; D016896:Treatment Outcome
chemical_list: D008078:Cholesterol, LDL; D010919:Placebos; D002784:Cholesterol; D008148:Lovastatin