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BMJ Open. 2019 Apr 8;9(4):e028504. doi: 10.1136/bmjopen-2018-028504.

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

Author information

1
Department of Research, Cancer Registry of Norway, Oslo, Norway.
2
Norwegian National Advisory Unit on Women's Health, Women's Clinic, Oslo University Hospital, Oslo, Norway.
3
Cancer Registry of Norway, Oslo, Norway.
4
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
5
Genetic Epidemiology Group, Folkhälsan Research Centerand Faculty of Medicine, Helsinki University, Helsinki, Finland.
6
Department of Community Medicine, University of Tromsø, The Arctic University of Norway, Tromsø, Norway.
7
Department of Pharmacology, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
8
Section for Pharmacology and PharmaceuticalBiosciences, Department of Pharmacy, University of Oslo, Oslo, Norway.
9
Regional Medicines Information and Pharmacovigilance Centre (RELIS), Department of Pharmacology, Oslo University Hospital, Oslo, Norway.
10
Department of Chronic Diseases and Aging, Nasjonalt folkehelseinstitutt, Oslo, Norway.
11
Clinical Pharmacology and Pharmacy, Department ofPublic Health, University of Southern Denmark, Odense, Denmark.
12
Danish Cancer Society Research Center, Danish Cancer Society, Copenhagen, Denmark.

Abstract

INTRODUCTION:

Surveillance 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 ANALYSIS:

The 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 DISSEMINATION:

The 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.

KEYWORDS:

cancer risk; drug safety; pharmacoepidemiology

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