Helle Wallach-Kildemoes

The Nordic prescription databases as a resource for pharmacoepidemiological research—a literature review

All five Nordic countries have nationwide prescription databases covering all dispensed drugs, with potential for linkage to outcomes. The aim of this review is to present an overview of therapeutic areas studied and methods applied in pharmacoepidemiologic studies using data from these databases.

Data Resource Profile: The Danish National Prescription Registry

Data Resource Profile: The Danish National Prescription Registry Anton Pottegård,* Sigrun Alba Johannesdottir Schmidt, Helle Wallach-Kildemoes, Henrik Toft Sørensen, Jesper Hallas and Morten Schmidt Clinical Pharmacology and Pharmacy, University of Southern Denmark, Odense, Denmark, Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark, Social and Clinical Pharmacy, University of Copenhagen, Copenhagen, Denmark and Department of Internal Medicine, Regional Hospital of Randers, Randers, Denmark

Is the high-risk strategy to prevent cardiovascular disease equitable? A pharmacoepidemiological cohort study

AbstractBackgroundStatins are increasingly prescribed to prevent cardiovascular disease (CVD) in asymptomatic individuals. Yet, it is unknown whether those at higher CVD risk – i.e. individuals in lower socio-economic position (SEP) – are adequately reached by this high-risk strategy. We aimed to examine whether the Danish implementation of the strategy to prevent cardiovascular disease (CVD) by initiating statin (HMG-CoA reductase inhibitor) therapy in high-risk individuals is equitable across socioeconomic groups.MethodsDesign: Cohort study.Setting and participants: Applying individual-level nationwide register information on socio-demographics, dispensed prescription drugs and hospital discharges, all Danish citizens aged 20+ without previous register-markers of CVD, diabetes or statin therapy were followed during 2002–2006 for first occurrence of myocardial infarction (MI) and a dispensed statin prescription (N = 3.3 mill). Main outcome measures: Stratified by gender, 5-year age-groups and socioeconomic position (SEP), incidence of MI was applied as a proxy for statin need. Need-standardized statin incidence rates were calculated, applying MI incidence rate ratios (IRR) as need-weights to adjust for unequal needs across SEP.Horizontal equity in initiating statin therapy was tested by means of Poisson regression analysis. Applying the need-standardized statin parameters and the lowest SEP-group as reference, a need-standardized statin IRR > 1 translates into horizontal inequity favouring the higher SEP-groups.ResultsMI incidence decreased with increasing SEP without a parallel trend in incidence of statin therapy. According to the regression analyses, the need-standardized statin incidence increased in men aged 40–64 by 17%, IRR 1.17 (95% CI: 1.14-1.19) with each increase in income quintile. In women the proportion was 23%, IRR 1.23 (1.16-1.29). An analogous pattern was seen applying education as SEP indicator and among subjects aged 65–84.ConclusionThe high-risk strategy to prevent CVD by initiating statin therapy seems to be inequitable, reaching primarily high-risk subjects in lower risk SEP-groups.

Social adversity and regional differences in prescribing of ADHD medication for school-age children

Objectives: To explore whether regional variations in the initiation of attention-deficit hyperactivity disorder (ADHD) medication among school-age children are explained by differences in sociodemographic composition and/or ADHD prescribing practice, especially in children who face social adversity (low parental education and single parenthood). Methods: A cohort of Danish school-age children (ages 5–17) without previous psychiatric conditions (N = 813,416) was followed during 2010–2011 for incident ADHD prescribing in the individual-level Danish registers. Register information was retrieved for both children and their parents. Regional differences were decomposed into contributions from differences in sociodemographic composition and in prescribing practices. Incidence rate ratios (IRR) with 95% confidence interval (CI) of ADHD prescribing were calculated using demographically standardized multivariable Poisson regression models. Results: Compared with the Capital, prescribing rates were significantly higher in regions North and Zealand (IRR, 1.19; 95% CI, 1.08–1.32 and 1.17; 1.08–1.28, respectively) and lower in South (IRR, 0.60; 95% CI, 0.54–0.66). After inclusion of the interaction term (region*social adversity), the multivariable analyses revealed a higher rate for the most disadvantaged children in North (IRR, 2.00; 95% CI, 1.51–2.66) and a lower rate in South (IRR, 0.47; 95% CI, 0.3–0.65). Prescribing rates were the highest for disadvantaged children in all regions, demonstrating the steepest social gradient in North and the smoothest in South. Demographic composition explained little of the variation: 3% for North and 13% for Zealand. Conclusions: Differences in sociodemographic composition explain little of regional variation in incident ADHD prescribing for children. However, large regional differences prevail in prescribing practices for children facing social adversity, indicating that local cultures shape the interpretation and handling of children with ADHD-like behaviors.

A Paradigm Shift Towards Patient Involvement in Medicines Development and Regulatory Science Workshop Proceedings and Commentary

The Copenhagen Centre for Regulatory Science (CORS) and Biopeople at the University of Copenhagen held a workshop in May 2015 titled “Patient Involvement in Medicines Development and Approvals: A Paradigm Shift Towards True Patient Impact in Medicines Development and Regulatory Science” that acknowledged the importance of having patients more involved in the entire process of medicines research and development (R&D) and life cycle management. Four key stakeholders, representing patients, academia, industry, and regulatory authorities, each gave their view and perspective on the status and challenges of current patient involvement. From the 3 breakout sessions, it was concluded that patient-reported outcomes (ie, the report of the status of a patient’s health condition that comes directly from the patient, without interpretation of the patient’s response by a clinician or anyone else), was considered as an important tool when deciding endpoints. It was agreed that professionalization of the patient within medicine R&D to some extent would be necessary for obtaining influence. However, the industry should also seek to accommodate to the patient instead of waiting passively for patients to become educated. A much better organized and stronger involvement of patients was called for. However, this should not only rely on goodwill, but should preferably be implemented by legal requirements, so as to secure compliance by all stakeholders. An independent platform with the purpose of providing access to patient experience was proposed. A research and educational center such as CORS, which was founded on cross-sectorial and cross-disciplinary cooperation, is an example of an institution that could be a good starting point for hosting such a platform.

Statin prescribing according to gender, age and indication: what about the benefit-risk balance?

RATIONALES, AIMS AND OBJECTIVES The increasing dispensing of statins has raised concern about the appropriateness of prescribing to various population groups. We aimed to (1) investigate incident and prevalent statin prescribing according to indication, gender and age and (2) relate prescribing patterns to evidence on beneficial and adverse effects. METHODS A cohort of Danish inhabitants (n = 4 424 818) was followed in nationwide registries for dispensed statin prescriptions and hospital discharge information. We calculated incidence rates (2005-2009), prevalence trends (2000-2010) and absolute numbers of statin users according to register proxies for indication, gender and age. RESULTS In 2010, the prevalence became highest for ages 75-84 and was higher in men than women (37% and 33%, respectively). Indication-specific incidences and prevalences peaked at ages around 65-70, but in myocardial infarction, the prevalence was about 80% at ages 45-80. Particularly, incidences tended to be lower in women until ages of about 60 where after gender differences were negligible. In asymptomatic individuals (hypercholesterolaemia, presumably only indication) aged 50+, dispensing was highest in women. The fraction of statin dispensing for primary prevention decreased with age: higher for incident than prevalent prescribing. Independent of age, this fraction was highest among women, e.g. 60% versus 45% at ages 55-64. The fraction for potential atherosclerotic condition (PAC, e.g. heart failure) increased with age. CONCLUSION Prevalence of statin utilization was highest for ages 75-84, although indication-specific measures were relatively low. Despite inconclusive evidence for a favourable risk-benefit balance, statin prescribing was high among people aged 80+, asymptomatic women and PAC patients.

Pattern of statin use changes following media coverage of its side effects

Background The media plays a role in shaping opinions about medical decisions, for example, whether to initiate or stop treatment. An association between negative media attention and statin discontinuation has been demonstrated, but it may differ depending on the reason for prescription and whether the user is new (incident) or long term (prevalent). Aim The aim of this study is to explore whether a Danish newspaper article featuring the side effects of statins affects statin discontinuation in incident versus prevalent users, with the reason for prescription also taken into account. Methods The study relies on a quasi-experimental design and uses registry data on statin purchases to explore discontinuation and treatment duration. As a proxy for reason for prescription, data on filled prescriptions and hospital diagnoses from a Danish registry were used. We compared statin discontinuation in all statin users in Denmark in 2007 before the media event (n=343,438) and after it in 2008 (n=404,052). Results Compared to 2007, statin discontinuation among prevalent users in 2008 increased by 2.97 percentage points (pp). The change in discontinuation varied with the indication for statin use. Those with myocardial infarction had the smallest increase (1.98 pp) and those with hypercholesterolemia or primary hypertension had the largest increase (3.54 pp). Incident statin users had a higher level of discontinuation and a larger difference in discontinuation between 2007 and 2008. Compared to 2007, more people (5.52 pp) discontinued statin treatment in 2008. Again, those with myocardial infarction had the smallest decrease in statin discontinuation (1.49 pp), while those with a potential atherosclerotic condition (7.05 pp) and hypercholesterolemia or primary hypertension (6.10 pp) had the largest increase. Conclusion Statin discontinuation increased in 2008 following a media event, but especially among individuals prescribed statins for primary prevention and among new statin users.

Adverse events in children and adolescents treated with quetiapine: an analysis of adverse drug reaction reports from the Danish Medicines Agency database

Quetiapine is a low-affinity dopamine D2 receptor antagonist, approved for the treatment of bipolar disorder and schizophrenia in children and adolescents by the Food and Drug Administration, but not by European Medicine Agency. Although knowledge of adverse drug reactions in children and adolescents is scarce, quetiapine is increasingly being used for youth in Denmark. The aim of this case study is to discuss adverse drug events (ADEs) spontaneously reported to the Danish Medicines Agency on quetiapine used in the pediatric population in relation to adversive drug reactions (ADRs) reported in the European Summary of Product Characteristics (SPCs). The ADE report database at Danish Medicines Agency was searched for all quetiapine ADRs involving individuals (<18 years) in the period 1997–2015. Fifteen ADE case reports were retrieved, scrutinized, and categorized. The average age was 14.8 years (range 10–17 years) and six patients were boys. The main reported ADEs were (i) endocrine, for example, hyperprolactinemia and hyperthyroidism, (ii) cardiac, for example, tachycardia and QT prolongation, (iii) neurological, for example, seizures and cerebral hemorrhage, and (iv) psychiatric, for example, hallucinations. As some of the reported ADEs are life threatening and not listed as ADRs in the SPCs, off-label use of quetiapine in children and adolescents gives rise to safety concerns.

The influence of generic substitution on the content of patient-pharmacist communication in Swedish community pharmacies.

The objective was to study the relationship between the length and content of patient–pharmacist communication in community pharmacies, and generic substitution.

Social Pharmacy Research in Copenhagen—Maintaining a Broad Approach

Social Pharmacy (SP) is a multidisciplinary field to promote the adequate use of medicine. The field of SP is increasingly important due to a numbers of new trends all posing challenges to society. The SP group at the University of Copenhagen has for several years used a broad approach to SP teaching and research, often illustrated by the four levels: individual, group, organizational, and societal. In this paper the relevance of maintaining a broad approach to SP research is argued for and examples of the importance of such type of research is presented.