Semi-automated risk estimation using large databases: quinolones and Clostridium difficile associated diarrhea.
OBJECTIVE
The availability of large databases with person time information and appropriate statistical methods allow for relatively rapid pharmacovigilance analyses. A semi-automated method was used to investigate the effect of fluoroquinolones on the incidence of C. difficile associated diarrhea (CDAD).


METHODS
Two US databases, an electronic medical record (EMR) and a large medical claims database for the period 2006-2007 were evaluated using a semi-automated methodology. The raw EMR and claims datasets were subject to a normalization procedure that aligns the drug exposures and conditions using ontologies; Snowmed for medications and MedDRA for conditions. A retrospective cohort design was used together with matching by means of the propensity score. The association between exposure and outcome was evaluated using a Poisson regression model after taking into account potential confounders.


RESULTS
A comparison between quinolones as the target cohort and macrolides as the comparison cohort produced a total of 564,797 subjects exposed to a quinolone in the claims data and 233,090 subjects in the EMR. They were matched with replacement within six strata of the propensity score. Among the matched cohorts there were a total of 488 and 158 outcomes in the claims and the EMR respectively. Quinolones were found to be twice more likely to be significantly associated with CDAD than macrolides adjusting for risk factors (IRR 2.75, 95%CI 2.18-3.48).


CONCLUSIONS
Use of a semi-automated method was successfully applied to two observational databases and was able to rapidly identify a potential for increased risk of developing CDAD with quinolones.
GlaxoSmithKline, Research Triangle Park, NC 27709, USA. robertino.mera@gsk.com
Robertino M
RM
Mera
Kathleen J
KJ
Beach
Gregory E
GE
Powell
Edward N
EN
Pattishall
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016360:Clostridioides difficile / Q000302:isolation & purification*; D003015:Clostridium Infections / Q000453:epidemiology / Q000209:etiology* / Q000382:microbiology; D015331:Cohort Studies; D016208:Databases, Factual; D003967:Diarrhea / Q000453:epidemiology / Q000209:etiology* / Q000382:microbiology; D057286:Electronic Health Records / Q000706:statistics & numerical data; D005260:Female; D024841:Fluoroquinolones / Q000009:adverse effects*; D006801:Humans; D015994:Incidence; D018942:Macrolides / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D016012:Poisson Distribution; D012189:Retrospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D014481:United States / Q000453:epidemiology; D055815:Young Adult
D024841:Fluoroquinolones; D018942:Macrolides