Screening for carcinogenic or chemopreventive effects of prescription drugs Anton Pottegård,...
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Transcript of Screening for carcinogenic or chemopreventive effects of prescription drugs Anton Pottegård,...
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!
Anton Pottegå[email protected]
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