Identifying signals of interest when screening for drug‐outcome associations in health care data

Pottegård, Anton; Hallas, Jesper; Wang, Shirley; Gagne, Joshua J.

doi:10.1111/bcp.13634

Cited by 8 publications

(11 citation statements)

References 20 publications

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“…This does not necessarily imply that the corresponding associations are more likely to be causal. It rather means that even though there are many country-and dataset specific differences, several associations are robust, as suggested elsewhere [38].…”

Section: Discussion Of Methodsmentioning

confidence: 82%

“…However, in all types of statistical screening attempts, the challenge is to separate signals worth following up from irrelevant signals. The p-value can be used to quantify the strength of the association between a certain drug (or groups of drugs) and cancer risk [38]. Thus, we show the p-values together with the underlying effect estimates, the hazard ratio and the corresponding confidence intervals.…”

Section: Discussion Of Methodsmentioning

confidence: 99%

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Drug Use and Cancer Risk: A Drug-Wide Association Study (DWAS) in Norway

Støer

Botteri

Thoresen

et al. 2020

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Background Population-based pharmacoepidemiological studies are used to assess post-marketing drug safety and discover beneficial effects of off-label drug use. We conducted a drug-wide association study (DWAS) to screen for associations between prescription drugs and cancer risk. Methods This registry-based nested case-control study, 1:10 matched on age, sex and date of diagnosis of cases comprises approximately 2 million Norwegian residents including their drug history from 2004-2014. We evaluated the association between prescribed drugs, categorized according to the Anatomical Therapeutic Chemical (ATC) classification system, and the risk of the 15 most common cancer types, overall and by histology. We used stratified Cox regression, adjusted for other drug use, comorbidity, county and parity, and explored dose-response trends. Results We found 145 associations among 1230 drug-cancer combinations on the ATC2-level and 77 of 8130 on the ATC4-level. Results for all drug-cancer combinations are presented in this paper and an online tool (https://pharmacoepi.shinyapps.io/drugwas/). Some associations have been previously reported, i.e. menopausal hormones and breast cancer risk, or are likely confounded, i.e. chronic obstructive pulmonary diseases and lung cancer risk. Other associations were novel, i.e. inverse association between proton pump inhibitors and melanoma risk, and carcinogenic association of propulsives and lung cancer risk. Association for Cancer Research. Conclusions This study confirmed previously reported associations and generated new hypotheses on possible carcinogenic or chemopreventive effects of prescription drugs. Results from this type of explorative approach need to be validated in tailored epidemiological and preclinical studies. Impact DWAS studies are robust and important tools to define new drug-cancer hypotheses.

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Section: Discussion Of Methodsmentioning

confidence: 82%

Section: Discussion Of Methodsmentioning

confidence: 99%

Drug Use and Cancer Risk: A Drug-Wide Association Study (DWAS) in Norway

Støer

Botteri

Thoresen

et al. 2020

Cancer Epidemiology, Biomarkers &Amp; Prevention

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“…In a subsequent internal validation step, we will filter the interesting signals to separate out those signals, which qualify for further investigation. In order to achieve this, we will combine biological, pharmacological and epidemiological knowledge with several approaches as explained by Pottegård et al 28. Thus, robustness against the choice of study design, the assessment of dose-response patterns and the distribution of the cancer risk over time as well as considerations of biological plausibility and possible uncontrolled confounding will be evaluated.…”

Section: Methods and Analysismentioning

confidence: 99%

Identification of potential carcinogenic and chemopreventive effects of prescription drugs: a protocol for a Norwegian registry-based study

et al. 2019

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IntroductionSurveillance of unintended effects of pharmaceuticals (pharmacovigilance or drug safety) is crucial, as knowledge of rare or late side effects is limited at the time of the introduction of new medications into the market. Side effects of drugs may involve increased or decreased risk of cancer, but these typically appear after a long induction period. This fact, together with low incidences of many cancer types, limits the usefulness of traditional pharmacovigilance strategies, primarily based on spontaneous reporting of adverse events, to identify associations between drug use and cancer risk. Postmarketing observational pharmacoepidemiological studies are therefore crucial in the evaluation of drug-cancer associations.Methods and analysisThe main data sources in this project will be the Norwegian Prescription Database and the Cancer Registry of Norway. The underlying statistical model will be based on a multiple nested case–control design including all adult (~200 000) incident cancer cases within the age-range 18–85 years from 2007 through 2015 in Norway as cases. 10 cancer-free population controls will be individually matched to these cases with respect to birth year, sex and index date (date of cancer diagnosis). Drug exposure will be modelled as chronic user/non-user by counting prescriptions, and cumulative use by summarising all dispensions’ daily defined doses over time. Conditional logistic regression models adjusted for comorbidity (National Patient Register), socioeconomic parameters (Statistics Norway), concomitant drug use and, for female cancers, reproduction data (Medical Birth Registry), will be applied to identify drug-use–cancer-risk associations.Ethics and disseminationThe study is approved by the regional ethical committee and the Norwegian data protection authority. Results of the initial screening step and analysis pipeline will be described in a key paper. Subsequent papers will report the evaluation of identified signals in replication studies. Results will be published in peer-reviewed journals, at scientific conferences and through press releases.

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“…Three papers using different approaches (eg, controlling for potential bias and different populations) are described—resulted in different associations of the newer direct acting anticoagulants (DOACs), and the vitamin K antagonists with bleeding and thrombotic events. Further newer methods such as sequence symmetry analysis recently published in the Journal are promising, but still have limitations …”

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confidence: 99%

Spotlight—Introducing a new Commentary series for the BJCP

Webb

2019

Brit J Clinical Pharma

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We are launching a new series of Commentaries, which aim to identify emerging themes-pulling together related content that has recently been published in the Journal for Readers, Authors and Editors and placing this in the context of contemporaneous work in other Journals.Outside of the formal themed issues, currently, our readers may experience papers presented somewhat in isolation to other potentially related work. This could be partly because Authors submit their papers, not always entirely familiar with recent relevant works in the Journal. In parallel, much of the Editor's role involves handling submitted manuscripts, with each paper being handled in isolation to what might be related content that has been published in the Journal.

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Identifying signals of interest when screening for drug‐outcome associations in health care data

Cited by 8 publications

References 20 publications

Drug Use and Cancer Risk: A Drug-Wide Association Study (DWAS) in Norway

Drug Use and Cancer Risk: A Drug-Wide Association Study (DWAS) in Norway

Identification of potential carcinogenic and chemopreventive effects of prescription drugs: a protocol for a Norwegian registry-based study

Spotlight—Introducing a new Commentary series for the BJCP

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