Differential losses to follow-up that are outcome-dependent can vitiate a clinical trial: Simulation results.

TitleDifferential losses to follow-up that are outcome-dependent can vitiate a clinical trial: Simulation results.
Publication TypeJournal Article
Year of Publication2018
AuthorsPotthoff, Richard F.
JournalJ Biopharm Stat
Volume28
Issue4
Pagination633-644
Date Published2018
ISSN1520-5711
KeywordsComputer Simulation, Follow-Up Studies, Humans, Lost to Follow-Up, Randomized Controlled Trials as Topic, Treatment Outcome
Abstract

Loss to follow-up (LTFU) in clinical trials represents a potential threat to their soundness that may not be adequately recognized. We consider a log-rank test in a trial with two arms, experimental and control, and with a single unfavorable binary endpoint such as death. Commonly, one applies censoring to patients with LTFU. That approach is valid if LTFU is independent of outcome, but can lead to bias otherwise. Unfortunately, there is no statistical test for independence, so the legitimacy of the approach rests on unverifiable assumptions. For two cases, we evaluate the impact of the approach based on simulations that use reasonable models for outcome-dependent LTFU. In each case, LTFU in one arm disproportionately suppresses recognition of relatively early deaths or other outcomes, thus producing bias favoring that arm. The first case has extra LTFU in the experimental arm and the treatment has no benefit. The second case has extra LTFU in the control arm and the treatment is effective. The simulation results show severe inflation of Type I error in the first case and major loss of power in the second case. Remedies for LTFU are scarce but include avoiding it in the first place where possible.

DOI10.1080/10543406.2017.1372773
Alternate JournalJ Biopharm Stat
Original PublicationDifferential losses to follow-up that are outcome-dependent can vitiate a clinical trial: Simulation results.
PubMed ID28858561
PubMed Central IDPMC6145451
Grant ListP01 CA142538 / CA / NCI NIH HHS / United States