Supplement 1

The 27th Norwegian Conference on Epidemiology

Persistence of statin treatment – the impact of analytic method when estimating drug survival

Background: There is ample evidence for several pharmaceutical treatments that adherence in terms oftreatment duration and dose is suboptimal. The actual drug intake cannot be observed directly in prescriptiondatabases, which only register drug redeemed and a limited number of patient characteristics. Consequently,the actual dose and duration of treatment must be inferred from observed redemptions. Persistence can thenbe expressed as treatment duration (also referred to as drug survival).Method: We used data from the Norwegian Prescription Database (NorPD) on redemptions of statins (ATCcodeC10AA) for the period 2010-2019 to explore three methods for determining prescription durations andin turn persistence (treatment duration): (i) The DDD-method using the number of DDD redeemed; (ii) Thedose-unit approach using the number of tablets redeemed; (iii) The reverse waiting time distribution method(WTD), which estimates prescription duration as the 90th percentile of the distribution within which patientsin ongoing treatment will have a new subsequent redemption. The three methods for estimating prescriptionduration were then used to estimate treatment duration using Kaplan Meier (KM) survival functions. For theDDD-method and the dose-unit approach we conducted sensitivity analyses assuming that one DDD or onetablet would last for 1.00, 1.25 or 2.00 days. We also tested the impact of grace periods in sensitivity analyses.Results: Treatment duration and drug survival varied substantially for the same patients depending on thechosen method, duration of a DDD or a tablet, and inclusion of grace periods. The 25th percentile of treatmentduration was 100 days for the DDD approach with one DDD per day, 100 days with the dose-unit approachwith one tablet per day and 453 days with the WTD approach.Conclusion: When estimating treatment duration from prescription databases one should be aware that thesemeasures of persistence are highly influenced by the chosen methodology. The choice of method should beinformed by the clinical context with a preference for use of methods based on a formal model.

Medical care contact for infertility and related medication use during pregnancy – a European, cross-sectional web-based study

Aims: The aim of the study was two-fold: i) to determine the prevalence of medical care contact for infertility in European countries; ii) to map overall and long-term/chronic medication use during pregnancy in women who sought medical care due to infertility.Methods: This is a sub-study of the Multinational Medication Use in Pregnancy Study, a cross-sectional, web-based study conducted from October 2011 to February 2012. We included 8097 participants from Europe who were pregnant or new mothers. We collected data on overall and long-term/chronic medication use, medical care seeking due to infertility, and whether women eventually conceived spontaneously or with the aid of infertility treatment.Results: Medical care contact for infertility was lower in Western Europe (prevalence estimate: 10.0-15.3%), compared with Northern (15.2-17.5%) or Eastern (17.4-20.9%), but Poland had the lowest estimate (8.0%). Overall, 660 (8.2%) women sought medical care due to infertility but conceived spontaneously; 548 (6.8%) conceived aided by fertility treatment, and 6889 (85.0%) women did not seek help. Use of any medication was comparable across the three groups (range 80.4-82.5%), but women seeking help for infertility (21.8-24.6%) took more often long-term/chronic medications than women who did not (14.8%).Conclusion: Medical care contacts for infertility varies greatly across European countries. Women who had medical contact due to infertility used more often chronic medications in pregnancy than women who did not, pointing to more co-morbidities and risk pregnancies.

For mye eller for lite medisiner? En nasjonal studie av forskrevne psykofarmaka blant innsatte i norske fengsler

SAMMENDRAGBakgrunn: Legemiddelbruk i den norske befolkningen er økende. Kunnskap om omfang, hvem brukerne er og bruksmønster er en forutsetning for optimalisering av legemiddelbruk i alle grupper av befolkningen. Samtidig finnes det ingen oppdaterte studier som viser bruk av forskrevne legemidler blant innsatte i Norge. Hensikten med denne studien er derfor å beskrive bruk av forskrevne psykofarmaka blant innsatte i fengsel før og under soning, samt undersøke hvilke faktorer som er assosiert med legemiddelbruk.Material og metode: Datamaterialet er fra «The Norwegian Offender Mental Health and Addiction Study», NorMA-studien, som ble gjennomført i perioden 2013-2014 ved 57 fengselsenheter i Norge. Totalt svarte 1495 innsatte (96 kvinner) på spørreskjema. Vi undersøkte selvrapportert bruk av psykofarmaka knyttet til sovemedisin, beroligende legemidler, antidepressiva, LAR-legemidler, smertestillende legemidler og ADHD- legemidler. Vi brukte logistiske regresjoner for å undersøke sammenhenger mellom ulike bakgrunnsfaktorer og bruk av ulike legemidler under soning.Resultater: Sovemedisin var mest brukt, både før og under soning. Tjue prosent av innsatte brukte sove- medisin daglig under soning. Innsatte brukte mer psykofarmaka enn den generelle befolkningen, med unntak av smertestillende legemidler. Under soning var bruk av de fleste undersøkte psykofarmaka assosiert med betydelige psykiske plager, skadelig rusbruk, å motta økonomiske sosiale ytelser samt å ha hatt en oppvekst preget av rus og psykiske problemer.Konklusjon: Våre funn viser at innsattes psykiske helse og russituasjon bør ha høy prioritet under soning. Det er forventet at innsatte bruker mer forskrevne psykofarmaka enn den generelle befolkningen. At den generelle befolkningen bruker mer smertestillende enn innsatte, bør derfor undersøkes nærmere. Lindstad M, Skurtveit S, Bukten A. Too much or too little medication? A national study of prescribedpsychotropic drugs among inmates in Norwegian prisons. Norsk Epidemiologi 2021; 29 (1-2): 85-95.ENGLISH SUMMARYBackground: Prescription drug use in the Norwegian population is increasing. Knowledge of who the usersareand usage patterns is a prerequisite for optimizing prescription drug use in all groups of the population.There are no updated studies describing prescription drug use among prisoners in Norway. The purpose ofthis study is to describe the use of prescribed psychotropic drugs among inmates in prison before and duringimprisonment and to investigate factors associated with prescription drug use while in prison.Material and method: The study is based on self-reported data from "The Norwegian Offender MentalHealth and Addiction Study" (NorMA) which was conducted in the period 2013-2014 at 57 prison units inNorway. A total of 1495 inmates (96 women) responded to the questionnaire. We investigated self-reporteduse of psychotropic drugs related to: hypnotics, anxiolytics, antidepressants, OMT-medications, pain medicationand ADHD-medications. We used logistic regression models to investigate relationships betweendifferent background factors and the use of prescribed drugs during imprisonment.Results: Hypnotics were most commonly used, both before and during imprisonment. Twenty percent ofinmates had used hypnotics daily during imprisonment. Inmates used more psychotropic drugs than the generalpopulation, with the exception of pain medications. During imprisonment, usage of most psychotropicdrugs imprisonment were associated with symptoms of mental illness, harmful drug use before imprisonment,having received social benefits and to have had an upbringing marked by drug use and mental problems.Conclusion: Our findings show that prisoners' mental health and substance use situation should have a highpriority during imprisonment. It is expected that inmates use more prescribed psychotropic drugs than thegeneral population. The fact that the general population uses more pain medication than inmates shouldtherefore be investigated further.

Hormonal contraceptive use in Norway, 2006-2020, by contraceptive type, age and county: A nationwide register-based study

Aim: Our aim was to study hormonal contraceptive use among women in Norway during 2006-2020 according to age groups and geography, including choice of contraceptive method, type of prescriber for long-acting reversible contraceptives, and prescriber’s adherence to the national health authority recommendations.Material and methods: We conducted a nationwide drug utilization study including all women aged 16-49 years in Norway during 2006-2020. The Norwegian Prescription Database (NorPD) includes detailed information about all dispensed prescription medications from Norwegian pharmacies to individuals in ambulatory care, including year of dispensing, patient’s year of birth and county of residence, and the prescriber’s profession.Results: This study shows a slight increase in overall use of hormonal contraceptives among 16-49-year-olds during 2006-2018, increasing from 36% of the population to 40%. Combined oral contraceptives (COCs) was the most commonly used hormonal contraceptive method in all age groups. The use of COCs decreased during the period and the decline was greatest in those below 25 years. From 2016 80% of all new users of COCs received the recommended COC containing levonorgestrel. Use of estrogen-free contraceptives, long-acting reversible contraceptives (LARCs) and gestagen pills, has increased. After 2014 the use of LARCs, especially subdermal implant, increased steeply among younger women. Oslo had the lowest proportion of users of hormonal contraceptives among teenagers and young adults during the whole period, while among 30-49-yearolds Oslo was more in line with the other counties.Conclusion: Combined oral contraceptives (COC) was the most used hormonal contraceptive method in all age groups. However, the use of COCs decreased during the period, especially in those < 25 years, where a corresponding increase in the use of LARC has taken place, mainly from 2014 onwards. Four out of five women who initiated COC received the recommended COC type and the steep increase in use of estrogen-free LARCs in recent years implies that Norwegian prescribers have high compliance with the recommendations from the health authorities.

INSPIRE: A new opportunity for cancer pharmacoepidemiology research

Until recently, there has been limited overview of the hospital administered cancer medications. The Cancer Registry of Norway has the approval to collect data on medical oncology treatment provided to each patient, but the reporting has so far been manual, time consuming and incomplete. Apart from conducting costly chart reviews, it has not been possible to carry out studies on hospital administered cancer medications. Efforts trying to improve manual reporting have not been sufficient and the most effective way of collecting data on cancer medications is through the hospital systems used for ordering/administering medical oncological treatment. The INSPIRE (INcreaSe PharmaceutIcal REporting) project was initiated to automatically and electronically collect data on cancer medication from the hospitals systems to the Cancer Registry. The project is a unique collaboration between 12 pharmaceutical companies, the Association of Pharmaceutical Companies in Norway, the Norwegian Cancer Society, Inven2, the Cancer Registry of Norway and the four Regional Health Trusts. In this article we describe the INSPIRE project, the data collection, and when and what kind of data that will be available. These new medication data at the Cancer Registry provide new opportunities for cancer pharmacoepidemiology research in Norway.

Antibacterial use by birth year and birth season in children 0-2 years in Norway

Introduction: Consumption of antibacterials in children follows seasonal cycles, and time to first treatment depends on birth season. The aim of this study was to describe dispensing rate, one-year periodic prevalence, and age at first prescription in children aged 0-2 years in Norway.Methods: We used data from the Norwegian prescription database and included all dispensed prescriptions on systemic antibacterials in 2008-2017 during the first three years of life to children born 2005-2014. We calculated age by subtracting birth month and birth year from date of collection of prescription. We used multiple linear regression to investigate the effect of birth season on age at first dispensed prescription.Results: We included 714 262 prescriptions to 281 888 individuals (53.1% boys). In 2016, one-year-old boys had the highest periodic prevalence (35.6%) and the highest dispense rate (545/1000 individuals), followed by one-year-old girls (32.6%, 478/1000 individuals). The lowest prevalence and dispense rate in all age groups was found towards the end of the period. Winter months had the highest proportion of dispensed prescriptions, and children born in autumn were significantly younger when collecting their first prescription. On average, boys collected their first prescription 26 days younger compared to girls.Conclusion: One-year-olds have the highest periodic prevalence and the highest dispense rate. This contrast with results from other studies on Norwegian data and is probably attributed to our use of birth month for calculation of age. Children born in autumn were younger when collecting their first prescription compared to other birth seasons. It is unknown whether this has any long-term clinical implications.

A common data model for harmonization in the Nordic Pregnancy Drug Safety Studies (NorPreSS)

It is necessary to carry out large observational studies to generate robust evidence about the safety of drugs used during pregnancy. In the Nordic countries, nationwide population-based health registers that document all births and dispensed prescribed drugs are valuable resources for such studies. A common data model (CDM) is a data harmonization and structuring tool that enables a unified and streamlined analytic approach for studies including data from multiple countries or databases. We describe a CDM developed for the Nordic Pregnancy Drug Safety Studies (NorPreSS), including details on data sources and structure of the data tables. We also provide an overview of the advantages and disadvantages of the approach (e.g. sharing of data analysis programs versus extra initial work to create CDM datasets from raw data).

Antithyroid drug treatment and pregnancy outcomes among women with hyperthyroidism in pregnancy: A Norwegian population-based registry-linkage study

Aims: The aim of this study was two-fold: i) to describe factors associated with antithyroid drug (ATD) treatmentduring gestation among women with hyperthyroidism in pregnancy, ii) to investigate the impact of ATDtreatment during gestation on pregnancy outcomes.Methods: Women with hyperthyroidism in pregnancy and ATD treatments were identified through linkage ofthree national registries (2008-2018): The Medical Birth Registry of Norway, the Norwegian PrescriptionRegistry and the Norwegian Patient Registry. Pregnancies were categorized as ATD treated or untreated basedon filled prescriptions indicating ATD exposure during pregnancy. ATD treatment was examined by trimester(T1, T2/T3) and by substance carbimazole (CMZ), propylthiouracil (PTU) and by both CMZ/PTU. Generalizedestimating equations analysis with a robust variance estimator was used to estimate adjusted odds ratio (aOR)and adjusted standardized mean difference (aSMD) with 95% confidence interval (CI).Results: We identified 1699 pregnancies with hyperthyroidism during gestation. Hyperthyroidism was treatedwith ATD in 44.4% of the pregnancies, while 55.6% were untreated. Pregnant women treated with ATD hadmore often asthma compared to untreated women. Prenatal exposure to CMZ was associated with increased riskof preterm birth (aOR 1.8, 95% CI 1.1-2.8) whereas PTU exposure in the first trimester was associated with anincreased risk of cardiac malformations (aOR 9.0, 95% CI 1.8-44.7). There was no association between ATDtreatment in pregnancy and maternal preeclampsia (aOR 0.8, 95% CI 0.4-1.3) and gestational hypertension (aOR0.9, 95% CI 0.5-1.8).Conclusion: This nationwide registry study found an association between treatment with carbimazole and increasedrisk of preterm birth. Exposure to propylthiouracil in the first trimester was associated with an increasedrisk of cardiac malformations. These findings should be interpreted in light of international findings on the riskof untreated hyperthyroidism and the potential risk of ATD treatment for the mother and child.

Innhold

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