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Evaluation of the US Food and Drug Administration sentinel analysis tools in confirming previously observed drug‐outcome associations: The case of clindamycin and Clostridium difficile infection
Author(s) -
Carnahan Ryan M.,
Kuntz Jennifer L.,
Wang Shirley V.,
Fuller Candace,
Gagne Joshua J.,
Leonard Charles E.,
Hennessy Sean,
Meyer Tamra,
Archdeacon Patrick,
Chen ChihYing,
Panozzo Catherine A.,
Toh Sengwee,
Katcoff Hannah,
Woodworth Tiffany,
Iyer Aarthi,
Axtman Sophia,
Chrischilles Elizabeth A.
Publication year - 2018
Publication title -
pharmacoepidemiology and drug safety
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.023
H-Index - 96
eISSN - 1099-1557
pISSN - 1053-8569
DOI - 10.1002/pds.4420
Subject(s) - medicine , clindamycin , propensity score matching , confidence interval , hazard ratio , penicillin , emergency medicine , antibiotics , microbiology and biotechnology , biology
Purpose The Food and Drug Administration's Sentinel System developed parameterized, reusable analytic programs for evaluation of medical product safety. Research on outpatient antibiotic exposures, and Clostridium difficile infection (CDI) with non‐user reference groups led us to expect a higher rate of CDI among outpatient clindamycin users vs penicillin users. We evaluated the ability of the Cohort Identification and Descriptive Analysis and Propensity Score Matching tools to identify a higher rate of CDI among clindamycin users. Methods We matched new users of outpatient dispensings of oral clindamycin or penicillin from 13 Data Partners 1:1 on propensity score and followed them for up to 60 days for development of CDI. We used Cox proportional hazards regression stratified by Data Partner and matched pair to compare CDI incidence. Results Propensity score models at 3 Data Partners had convergence warnings and a limited range of predicted values. We excluded these Data Partners despite adequate covariate balance after matching. From the 10 Data Partners where these models converged without warnings, we identified 807 919 new clindamycin users and 8 815 441 new penicillin users eligible for the analysis. The stratified analysis of 807 769 matched pairs included 840 events among clindamycin users and 290 among penicillin users (hazard ratio 2.90, 95% confidence interval 2.53, 3.31). Conclusions This evaluation produced an expected result and identified several potential enhancements to the Propensity Score Matching tool. This study has important limitations. CDI risk may have been related to factors other than the inherent properties of the drugs, such as duration of use or subsequent exposures.