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May 20, 1998

Concerns About Run-in Periods in Randomized Trials—Reply

Author Affiliations

Margaret A.WinkerMD, Senior EditorIndividualAuthorPhil B.FontanarosaMD, Senior EditorIndividualAuthor

JAMA. 1998;279(19):1526-1527. doi:10-1001/pubs.JAMA-ISSN-0098-7484-279-19-jbk0520

In Reply.—Dr Glynn and colleagues point out that including nonadherers in a clinical trial may compromise the validity of an efficacy study; we would not take issue with this point of view. Our article was meant to call attention to the complexities of applying estimates of treatment effects derived from such studies directly to clinical practice, difficulties that are compounded when considering alternative interventions tested in trials without a run-in period. We agree that it is difficult to know whether using a placebo drug run-in period to exclude nonadherers will lead to underestimation or overestimation of the adverse effects of a drug in the randomized phase of a trial. However, the use of an active drug run-in period to exclude nonadherers will selectively exclude those who are nonadherent because of adverse effects. The result will be underestimation of the rate of adverse effects in the randomized phase compared with the unselected population expected in clinical practice.