Detecting potential safety issues in large clinical or observational trials by Bayesian screening when event counts arise from poisson distributions.
J Biopharm Stat
; 23(4): 829-47, 2013.
Article
in En
| MEDLINE
| ID: mdl-23786257
ABSTRACT
Patients in large clinical trials and in studies employing large observational databases report many different adverse events, most of which will not have been anticipated at the outset. Conventional hypothesis testing of between group differences for each adverse event can be problematic Lack of significance does not mean lack of risk, the tests usually are not adjusted for multiplicity, and the data determine which hypotheses are tested. This article describes a Bayesian screening approach that does not test hypotheses, is self-adjusting for multiplicity, provides a direct assessment of the likelihood of no material drug-event association, and quantifies the strength of the observed association. The criteria for assessing drug-event associations can be determined by clinical or regulatory considerations. In contrast to conventional approaches, the diagnostic properties of this new approach can be evaluated analytically. Application of the method to findings from a vaccine trial yields results similar to those found by methods using a false discovery rate argument or a hierarchical Bayes approach. [Supplemental materials are available for this article. Go to the publisher's online edition of Journal of Biopharmaceutical Statistics for the following free supplemental resource Appendix R Code for calculations.].
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Clinical Trials as Topic
/
Models, Statistical
/
Drug-Related Side Effects and Adverse Reactions
Type of study:
Diagnostic_studies
/
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
/
Screening_studies
Limits:
Humans
Language:
En
Journal:
J Biopharm Stat
Journal subject:
FARMACOLOGIA
Year:
2013
Document type:
Article
Affiliation country:
United States