title: Bias in a placebo-controlled study due to mismeasurement of disease status and the regression effect.
abstract: We raise the concern of whether the use of a placebo group in a randomized clinical trial is sufficient to eliminate bias in the assessment of the effectiveness of a drug when enrollment into the trial prior to intervention requires diagnosis of a dichotomous disease, and the diagnostic test is subject to uncertainty. Due to misclassification and the regression effect, the observed difference in the proportions of diseased individuals between the treatment and placebo groups at follow-up will be equal to the true difference multiplied by the positive predictive value at screening and the difference between the sensitivity and the false-positive value at follow-up. Thus, measurement error of disease status before and after administering the intervention attenuates the intervention effect. Validation data corresponding to both the screening and follow-up conditions are necessary to provide additional information on the validity of the diagnostic test. Proper statistical analysis should include such data for an accurate portrayal of the effectiveness of the treatment.
authors.affiliation: Department of Health Evaluation Sciences, Penn State University College of Medicine, Hershey, PA 17033, USA. hlin@hes.hmc.psu.edu
authors.forename: Hung-Mo
authors.initials: HM
authors.lastname: Lin
authors.forename: Robert H
authors.initials: RH
authors.lastname: Lyles
authors.forename: John M
authors.initials: JM
authors.lastname: Williamson
mesh_terms: D019980:Amoxicillin-Potassium Clavulanate Combination / Q000627:therapeutic use; D015982:Bias; D015897:Comorbidity; D003625:Data Collection / Q000706:statistics & numerical data; D004311:Double-Blind Method; D004359:Drug Therapy, Combination / Q000627:therapeutic use; D006304:Health Status; D006801:Humans; D010034:Otitis Media with Effusion / Q000188:drug therapy; D016032:Randomized Controlled Trials as Topic / Q000706:statistics & numerical data*; D012044:Regression Analysis; D015203:Reproducibility of Results; D016896:Treatment Outcome
chemical_list: D019980:Amoxicillin-Potassium Clavulanate Combination