Journal of Clinical Oncology, Vol 4, 1529-1541, Copyright © 1986 by American Society of Clinical Oncology
Publication bias: the case for an international registry of clinical trials
RJ Simes
A problem in evaluating different therapies from a review of clinical
trials is that the published clinical trial literature may be biased in
favor of positive or promising results. In this report, a model is proposed
for reviewing clinical trial results which is free from publication bias
based on the selection of trials registered in advance in a registry. The
value of a registry is illustrated by comparing a review of published
clinical trials located by a literature search with a review of registered
trials contained in a cancer trials registry. Two therapeutic questions are
examined: the survival impact of initial alkylating agent (AA) v
combination chemotherapy (CC) in advanced ovarian cancer, and the survival
impact of AA/prednisone v CC in multiple myeloma. In advanced ovarian
cancer, a pooled analysis of published clinical trials demonstrates a
significant survival advantage for combination chemotherapy (median
survival ratio of CC to AA, 1.16; P = .02). However, no significant
difference in survival is demonstrated based on a pooled analysis of
registered trials (median survival ratio, 1.05; P = .25). For multiple
myeloma, a pooled analysis of published trials also demonstrates a
significant survival advantage for CC (median survival ratio, 1.26; P =
04), especially for poor risk patients (ratio, 1.66; P = .002). A pooled
analysis of registered trials also shows a survival benefit for patients
receiving combination chemotherapy (all patients, P = .06; poor risk, P =
.03), but the estimated magnitude of the benefit is reduced (all patients:
ratio, 1.11; poor risk: ratio, 1.22). These examples illustrate an approach
to reviewing the clinical trial literature, which is free from publication
bias, and demonstrate the value and importance of an international registry
of all clinical trials.
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