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Screening for carcinogenic or chemopreventive effects of
prescription drugs
Anton Pottegård, MScPharm PhD
University of Southern Denmark
VKA – All cancersBenzodiazepiner – All cancers
Azathioprine – All cancers [Myasthenia]Disulfiram – MM/Breast/Prostate
[Alcoholics]Azathioprine – NMSC [Myasthenia]
Myasthenia – All cancersMetformin – Colon cancer [Diabetics]
Statins – NMSC Lithium – Upper urinary tract cancer
Statins – Renal cancerLithium – Colorectal cancer
PDEIs – Malignant melanomaTCA – Glioma
RACEDRapid Assessment of
Carcinogenic Effects of Drugs
RACED vol. 1
Table of contents:Valproic acid (sub. prostate)
AllopurinolAntidepressants
Antipsychotics (sub. prostate)Ibuprofen (sub. colon)
ThiazidesAce-inhibitors
ATII-antagonistsCalcium-channel-blockers (grp2)
Clopidogrel
DicloxacillinPottegård et al.
JAMA 2015 Jul 21;314(3):296-7.
Proton Pump Inhibitors
Henriksen et al.Pharmacoepidemiol Drug Saf. 2015
Sep 23.
AntidiabeticsStage et al.
J Thromb Haemost (Accepted)
RACED2
Anton PottegårdSøren Friis
René dePont ChristensenLaurel A. HabelJoshua J. GagneJesper Hallas
Design
Multiple case-control study
Outcome
All cancerSingle cancer sitesSingle cancer types
Based on ICD-O topography and morphology codes:
99 cancers and subtypes.
Exposures
Only drug classesOnly single substances
Both!
For each cancer, we included all drugs
that had 10 observed long-term users (defined as ≥8 prescriptions) among
the cases
Analysis
Matching by gender and age… thereby adjusting for gender, age
and calendar time
Adjusting for Charlson-score and education
… as crude confounder adjustment
Material
278,485 incident cancer cases
22,125 drug-cancer pairs
Screening: Step 1
ORs estimated comparing long-term use (≥8 fills) to non-use.
Signals were defined as: OR <0.67 or >1.5, or95%CI >1.2 or <0.83
Intermediary results
4,561 signals
Screening: Step 2
Outcome specificityThe ratio of ORsignal to ORoverall outside
0.83-1.20.
Dose-response patternA significant slope on the dose-response
curve (p<0.10).
Results
77.4% failed to meet dose-response criteria, 1.7% failed test for specificity,
1.4% failed both; thus leaving 1,020 signals.
159 at the second level of the ATC-system,351 at the fourth level of the ATC-system,
and 510 for single agents.
703 signals indicated an increased cancer risk,
317 indicated a chemopreventive effect.
All done?
What about issues of multiple testing?
What about legal issues?
Male pharmacoepidemiologist seeks enthusiastic partner who owns his/her own degree and
grows his/her own hypotheses. Access to cancer-data is a plus,
as is being open-minded!
