Jaana E. Martikainen

The Nordic countries as a cohort for pharmacoepidemiological research.

The Nordic countries have a long tradition of registry-based epidemiological research. Many population-based health registries were established in the 1960s, with use of unique personal identifiers facilitating linkage between registries. In recent years, each country has established a national database to track prescription drugs dispensed to individuals in ambulatory care. The objectives were to present an overview of the prescription databases established in the Nordic countries, as well as to elaborate on their unique potential for record linkage and cross-national comparison of drug utilization. Five Nordic countries collect drug exposure data based on drugs dispensed at pharmacies and have the potential to link these data to health outcomes. The databases together cover 25 million inhabitants (Denmark: 5.5 million; Finland: 5.3 million; Iceland: 0.3 million; Norway: 4.8 million; and Sweden: 9.2 million). In 2007, the registries encompassed 17 million prescription drug users (68% of the total population). We provide examples of how these databases have been used for descriptive drug utilization studies and analytical pharmacoepidemiological studies linking drug exposure to other health registries. Comparisons are facilitated by many similarities among the databases, including data source, content, coverage and methods used for drug utilization studies and record linkage. There are, however, some differences in coding systems and validity, as well as in some access and technical issues. To perform cross-national pharmacoepidemiological studies, resources, networks and time are needed, as well as methods for pooling data. Interpretation of results needs to account for inter-country heterogeneity and the possibility of spurious relationships. The Nordic countries have a unique potential for collaborative high-quality cross-national pharmacoepidemiological studies with large populations. This research may assist in resolving safety issues of international interest, thus minimizing the risk of either over-reacting on possible signals or underestimating drug safety issues.

Use of ADHD drugs in the Nordic countries: a population-based comparison study.

Zoëga H, Furu K, Halldórsson M, Thomsen PH, Sourander A, Martikainen JE. Use of ADHD drugs in the Nordic countries: a population‐based comparison study.

Policies to enhance prescribing efficiency in europe: findings and future implications.

Introduction: European countries need to learn from each other to address unsustainable increases in pharmaceutical expenditures. Objective: To assess the influence of the many supply and demand-side initiatives introduced across Europe to enhance prescribing efficiency in ambulatory care. As a result provide future guidance to countries. Methods: Cross national retrospective observational study of utilization (DDDs – defined daily doses) and expenditure (Euros and local currency) of proton pump inhibitors (PPIs) and statins among 19 European countries and regions principally from 2001 to 2007. Demand-side measures categorized under the “4Es” – education engineering, economics, and enforcement. Results: Instigating supply side initiatives to lower the price of generics combined with demand-side measures to enhance their prescribing is important to maximize prescribing efficiency. Just addressing one component will limit potential efficiency gains. The influence of demand-side reforms appears additive, with multiple initiatives typically having a greater influence on increasing prescribing efficiency than single measures apart from potentially “enforcement.” There are also appreciable differences in expenditure (€/1000 inhabitants/year) between countries. Countries that have not introduced multiple demand side measures to counteract commercial pressures to enhance the prescribing of generics have seen considerably higher expenditures than those that have instigated a range of measures. Conclusions: There are considerable opportunities for European countries to enhance their prescribing efficiency, with countries already learning from each other. The 4E methodology allows European countries to concisely capture the range of current demand-side measures and plan for the future knowing that initiatives can be additive to further enhance their prescribing efficiency.

Frequency of daily over-the-counter drug use and potential clinically significant over-the-counter-prescription drug interactions in the Finnish adult population.

AbstractObjective: To explore the frequency of continuous use of over-the-counter (OTC) drugs among the Finnish adult population and the potential for harmful interactions between OTC drugs and prescribed (Rx) drugs. Methods: Data were extracted from a 1995–1996 population-based interview survey on health care (n=10,477, response rate 86%). The drug interaction classification system from the Swedish Drug Compendium FASS 1997 was used to identify OTC drugs likely to have clinically significant interactions with prescription drugs. Logistic regression was used to study factors related to continuous use and risks for interactions. Results: Seventeen percent of the population had used OTC drugs and 15% had used OTC vitamins during the 2 days prior to the interview. Daily use of OTC drugs and of vitamins was reported by 7% and 9%, respectively. Continuous use of OTC drugs was related to older age, female gender, higher education, poor health status, long-term morbidity, psychosomatic symptoms (fatigue) and use of prescription drugs, but not to poor lifestyle. Four percent of the OTC drug users had taken drug combinations with potential for clinically significant interactions. Interactions were most common for ketoprofen (15% of ketoprofen users), ibuprofen (10%), and acetylsalicylic acid (ASA) (6%). The number of prescription drugs, long-term illness and lower education best explained the risk for interactions. Conclusion: Continuous use and potentially harmful Rx/OTC drug interactions occur among OTC drug users. Further studies should be done to investigate whether potential combinations will actually lead to clinical problems. The possible interactions of non-steroidal anti-inflammatory drugs (NSAIDs) and analgesics with prescription drugs should especially be taken into account in drug information.

Long-Term Persistence with Statin Therapy: A Nationwide Register Study in Finland

BACKGROUND Preventive statin therapy is often recommended as lifelong treatment. OBJECTIVE The aim of this study was to analyze persistence with statin therapy over a decade of use and to identify factors associated with its discontinuation. METHODS Persistence with therapy among new users of statins in 1995 was followed up until December 31, 2005, in Finland using the nationwide drug reimbursement register. Cumulative persistence was analyzed using Kaplan-Meier analysis. A Cox regression model was applied to analyze associations of various baseline covariates with discontinuation. We further modeled the association of time-specific covariates by stratifying the duration of therapy in years and using a logistic regression in which those continuing therapy until the end of follow-up (persistent users) formed the reference group. Adherence, defined as the proportion of days covered by statins, stratified by the timing of discontinuation, was computed for the respective groups. RESULTS Of the 18,072 new statin users, 73.3% (n =13,254) were aged >54 years and 54.8% (n =9908) were men. Of this cohort, 43.9% (n = 7926) were using statins throughout and at the end of the tenth year. Sex was not associated with persistence at any point. In the Cox model, persons aged 45 to 74 years at initiation were more likely to continue statin use than younger or older age groups. Among those who still used statins after the fifth year of observation, the age difference was not observed in the logistic regression model. The use of 1, 2, 3, or > or =4 cardiovascular drugs before the initiation predicted continuation relative to no cardiovascular drug use (hazard ratio for discontinuation significantly <1.00 in all comparisons). Adherence was best (median 93.9%) among the persistent users. CONCLUSIONS The 10-year persistence with statin use in this general population was approximately 44%. Persons aged 45 to 74 years at initiation and those with at least 1 prescription for another cardiovascular medication were the most likely to continue statin therapy up to the fifth year.

Prescription of Hazardous Drugs During Pregnancy

AbstractBackground: Prescribing drugs to pregnant women requires the balancing of benefits and risks. Only a small proportion of drugs are known to be harmful to the fetus, but for the vast majority of drugs little evidence of fetal safety exists. Aim: To determine the prescription pattern of potentially and clearly harmful prescription drugs during pregnancy with reference to drug safety categorisation, and to define the drug groups primarily responsible for multiple drug use during pregnancy. Study design: A retrospective, register-based cohort study. Methods: Linkage of three nationwide registers in Finland. Data collection included prescription drugs purchased during the preconception period and each trimester in the pregnant cohort, and the corresponding time periods in the non-pregnant controls.The pregnancy safety categorisation was determined for each drug (Anatomic Therapeutic Chemical [ATC] code) by using the Swedish classification of approved medicinal products (Farmaceutiska Specialiteter i Sverige [FASS]) and if not available, the corresponding Australian (Australian Drug Evaluation Committee [ADEC]) or US categorisation (FDA). Groups studied: Women applying for maternity support (maternal grants) during the year 1999 (n = 43 470) plus non-pregnant control women matched by age and hospital district (n = 43 470). Results: In the pregnant cohort, 20.4% of women purchased at least one drug classified as potentially harmful during pregnancy, and 3.4% purchased at least one drug classified as clearly harmful. A significant decline occurred in the number of pregnant women purchasing potentially and clearly harmful drugs during the first trimester when compared with the preconception period, and the decline continued from the first to the second trimester. In the pregnant cohort, 107 (0.2%) women purchased at least ten different drugs during pregnancy. The drugs most commonly purchased in this group were topical corticosteroids and nasal preparations. Conclusion: The use of hazardous prescription drugs declines during pregnancy but prescriptions of known teratogens and the relatively frequent practice of polypharmacy in epilepsy place emphasis on the need for careful pre-pregnancy counselling. However, drug safety classifications give a very crude estimation of risk and should only be used as general guidelines when planning treatment. Risk assessment must always be made on an individual basis, and pregnant women with illnesses requiring treatment must be treated adequately.

Impact of restricted reimbursement on the use of statins in Finland: a register-based study.

Objectives:New and expensive medicines are a driving force behind growth in medicine costs, and policies promoting use of less expensive products have been widely introduced. This study investigated the short-term consequences of the restricted reimbursement of expensive statins (atorvastatin and rosuvastatin) on the use of statins in Finland. Methods:Data on patients purchasing atorvastatin, rosuvastatin, or simvastatin in 2002–2007 were retrieved from the nationwide Prescription Register. Outcome measures included the time trend in the numbers of purchasers and initiators of different statins, the morbidities of new users before and after the new policy, and the proportion of users of expensive statins switching to other statins. Results:After the restriction, the numbers of purchasers of atorvastatin and rosuvastatin dropped, and atorvastatin and rosuvastatin were seldom prescribed as first-line therapy. Before the restriction, 20.9% of new users of atorvastatin and 18.4% of those of rosuvastatin had either coronary artery disease or familial hyperlipidemia. After the restriction the corresponding figures were 28.7% and 26.8%. After the restriction new users of atorvastatin and rosuvastatin were also more likely to use other cardiovascular medicines or antidiabetics or to have previous statin purchases. A total of 57.6% of those using atorvastatin and 49.2% of those using rosuvastatin before the restriction switched to a less expensive statin. Conclusions:Restricted reimbursement of expensive statins decreased their use. It seems that after the policy new statin treatments have channeled appropriately. Although it is likely that the cost-containment aim of the policy was reached, health and long-term effects are not known.

Follow-up of the Finnish Asthma Programme 2000–2010: reduction of hospital burden needs risk group rethinking

The Finnish Asthma Programme 1994–2004 focused on early intervention and disease control, thereby resulting in a significant reduction of asthma morbidity. During the follow-up period from 2000 to 2010, the number of hospital days continued to fall by 54%. Patients ≥65 years, especially women, accounted for 39% of the hospital days, and they need attention if the hospital burden is to be reduced further.

Why has the utilization of antiasthmatics increased in Finland

The sales of antiasthmatics have increased rapidly in the Nordic countries during the 1980s. The causes for this growth in Finland were studied. Four nationwide population surveys show that the prevalence of self-reported asthma has risen, a larger proportion of asthmatic patients are under medication, the number of antiasthmatics per patient has increased, and the dosage recommendations of inhalation glucocorticoids and beta-agonists have grown. The average cost of medical treatment of an asthmatic patient was FIM 1848 (approximately U.S.

Multiuse of medicines in Finland.

510.00) in 1990. The highest average expenses in the 21 districts studied were FIM 2171 and the lowest FIM 1535. To identify the consequences of these variations, the frequency of symptomatic periods as well as the quality of life of the asthmatic patients should be studied.