Workshop From petri dish to population - and back again Chairman: Anne Broe, Danish Society for Pharmacoepidemiology DSF Annual meeting 17-01-2019

15.00-16.15 From petri dish to population - and back 17-01-2019

Options and possibilities with Danish register research – On its own or as a supplement Dansk Selskab for FarmakoEpidemiologi 17-01-2019

Pharmacoepidemiology Pharmacology – the study of medicines and drugs, including their action, use, and effect on the body Epidemiology – the scientific study of disease and how they are found, spread, and controlled in groups of people The study of drugs on a population level 17-01-2019

Pharmacoepi studies Observational studies Limitations of drug safety data from clinical trials Increased focus on pharmacovigilance Target population for medicines Safety endpoints (post-authorization) Pitfalls Random variation Systematic error (bias) Selection bias Information bias Confounding Billedet er lånt fra Jesper 17-01-2019

Pharmacovigilance (‘drug watch’/drug safety) Monitoring the safety of drugs after authorization Adverse drug effects (noxious and unintended) Medication errors (overdose, misuse, abuse) Collection, Detection, Assessment, Understanding, and prevention of adverse effects 17-01-2019

FALSE ADVERSE EFFECTS Tak til Jesper for humoristisk slide  17-01-2019

Thalidomide 17-01-2019

Advantages Incidence rates Prevalence proportion Use of single substances Persistence (‘drug survival’) Co-medication Prescriber types Regional differences 17-01-2019

Confounding Users and non-users are not comparable Confounding by indication/disease severity Methods to control for confounding Design Analysis Randomization Stratification Cross-over Multivariate analysis Restrictions Propensity score (PS) Matching Self-controlled studies 17-01-2019

Evidence Hierarchy 17-01-2019

Limitations of clinical trials Short follow-up Selected study populations Off label use Random outcome in small trials (but no confounding in big trials) Billedet er lånt fra Jesper 17-01-2019

Conclusion Clinical trials are not suitable for long term follow-up Does not reflect real-life patients (only the selected study group) 17-01-2019

Danish data – so what? 17-01-2019

Danish data are pretty unique! Long register lifetime Population based Government funded health care High coverage and validity 17-01-2019

MEDSTAT.DK     17-01-2019

Medstat.dk Freely available source of aggregated prescription drug statistics Annual national aggregated sales data Cannot describe level of individual exposure Covers ALL sales including in hospital treatments and over the counter sales 17-01-2019

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Drug utilization How much drug X is used per Danish citizen? Among women? In the reproductive age? Are there differences between regions? Estimates can be generated from aggregated sales data Historic trend in sale Comparison with other countries 17-01-2019

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Adelborg K et al. Sixteen-year nationwide trends in antithrombotic drug use in Denmark and its correlation with landmark studies. Heart (2016) Heart impact factor 5 17-01-2019

Nonaspirin Nonsteroidal Antiinflammatory Drug Use in the Nordic Countries from a Cardiovascular Risk Perspective, 2000–2016: A Drug Utilization Study Kasper Bruun Kristensen, Øystein Karlstad, Jaana E. Martikainen, Anton Pottegård, Jonas W. Wastesson, Helga Zoega & Morten Schmidt kaskristensen@health.sdu.dk 17-01-2019

n=26.800.000 The nordic countries consist of Iceland, Norway, Sweden, Finland and Denmark. Although relatively smalle individually, the importance of the nordic countries as a group is considerable. In total 27 million inhabitants, and the domestic product combined makes it the worlds 12th largest economy. In our nordic countries we share a common history and we do have other features that are characteristic, that is our welfare systems. We have practically universal health care to all residents and health care registries of good quality and coverage. Even though we are alike, there are differences so it may be a good idea to pair up with collaborators who know each country. As you may be able to see from the names of people involved in this work all countries are represented and I found this really useful. These are the countries we studied and we studied the use of NSAIDs

Individual level data Statistics Denmark (DST) Danish Health Data Authority (SDS) Unique Person Identification (CPR) - National Patient Registry - National Prescription Registry - Medical Birth Registry - Cancer Registry - Registry of Cause of Death Schmidt et al. Eur J Epidemiol 2014 17-01-2019

http://www.dsfe.dk/danish-registries/ 17-01-2019