Risto Huupponen’s research while affiliated with University of Turku and other places

The Finnish web-based Meds75+ database supports rational, safe and appropriate prescribing to older adults in primary care. This article describes the content and updating process of Meds75+ and demonstrates its applicability in everyday clinical practice. Meds75+ contains a classification (A–D) and recommendation texts for 450–500 drug substances when used in the treatment of older adults aged 75 years or older. The content of Meds75+ is continually updated. Each assessment of a drug substance begins with a structured collection of available information and research evidence. After that, an interdisciplinary expert panel discusses the classification and recommendation using a consensus method. A rolling 3-year updating cycle guarantees that all drug substances are reviewed regularly. Most drug substances are classified as class A (41%) (suitable, e.g. bisoprolol) or as class C (37%) (suitable with specific precautions, e.g. ibuprofen). One-fifth (20%) of the substances are in class D (avoid use, e.g. diazepam). Most commonly, older adults have purchased substances affecting the alimentary tract and metabolism (17%), the nervous system (16%) and the cardiovascular system (15%). In Finland, the proportion of older adults using class D substances (37%) has not changed between the years 2019 and 2022. Meds75+ has potential to support safer and more effective use of medications for older adults, since it offers up-to-date information on drug substances for healthcare professionals.

Background: Vitamin K antagonists, warfarin in particular, have been the mainstay of anticoagulation therapy, but their use has declined in many countries since direct oral anticoagulants (DOACs) have entered the market. Objective: To examine utilization trends of oral anticoagulants (OACs) in Finland considering the reimbursement of DOACs and changes to national treatment guidelines for the treatment of atrial fibrillation (AF). Methods: Both public, aggregated data on reimbursed OAC dispensations and individual-level data on electronic dis- pensations during 2014–2022 were applied. Data on electronic dispensations during 2015–2016 were used to study OAC initiations. Data on entitlements to reimbursement for DOACs came from public data. Results: In 2014, there were almost 20,000 DOAC users, rising to 214,000 in 2022. The number of warfarin users de- clined since 2015 from over 181,000 to around 59,000 users in 2022, DOACs exceeding warfarin in the number of users in 2019. The total DOAC costs were higher than warfarin costs each year. Rivaroxaban was the most widely used DOAC during 2014–2018, and apixaban during 2019–2022. In 2015, there were more warfarin (56.7%) than DOAC (43.3%) initiators, but the result was opposite for 2016 (warfarin 39.4%, DOACs 60.6%). The number of indi- viduals entitled to reimbursement for DOACs has increased steadily, and in 2022, there were over 196,000 individuals entitled to this reimbursement due to AF. Conclusions: The uptake of DOACs in Finland appears to have been gradual and slower than in many other countries. During the 2010s, the treatment guidelines for AF were more cautious in recommending DOACs than the European guidelines. The use of DOACs increased as their reimbursement became less restrictive.

Background Patient recruitment for clinical trials is challenging—only approximately one third of all trials recruit their participants as planned. The pharmaceutical industry’s views on recruitment success have not been comprehensively investigated, although the industry globally conducts almost one third of all clinical drug trials. This study explored patient recruitment success and failure factors and the role of electronic health records (EHR) in the recruitment of trial participants in the Nordic countries. Methods A descriptive qualitative interview study was conducted with 21 representatives of the pharmaceutical industry or contract research organizations operating in Finland, Sweden, Denmark, and Norway. The interviews covered 34 clinical pre-market drug trials. Qualitative data were analyzed using inductive content analysis. Results Four main categories were derived to represent both success and failure factors, whereas a fifth category represented only failure factors: (1) sponsor-related (protocol and trial preparation and feasibility evaluations), (2) site/investigator-related (access to patients, motivation, commitment and resources), (3) patient-related recruitment factors (medical need, patients’ role in their care and attitudes towards trials), (4) Sponsor—sites—patients collaboration factors, and (5) start-up related factors. EHR was the most important source of recruitment, utilized in 29 out of 34 trials discussed. Revision of the legislation regulating the secondary use of EHR was highlighted as the most effective measure to facilitate the use of EHR in recruitment of trial participants. Conclusions The industry representatives recognized quite well their own role in contributing to the success or failure of the recruitment: to facilitate recruitment of trial participants, many obstacles can be avoided with better trial preparation and proper feasibility evaluations. As access to patients represents one of the key success or failure factors of recruitment, and as the EHR is regarded the main source of searching for and finding patients, the development of EHR utilization appears to represent a powerful tool to improve patient recruitment.

Introduction: Feasibility evaluations are performed to create the best possible starting point for the set-up and execution of a clinical trial, and to identify any obstacles for successful trial conduct. New digital technologies can provide various types of data for use in feasibility evaluations. There is a need to identify and compare such data sources for trial site identification and for evaluating the sites' patient recruitment potential. Especially, information is needed on the use of electronic health records. We investigated how different data sources are used by pharmaceutical companies operating in the Nordic countries for identifying trial sites and for evaluating their potential to recruit trial participants. Methods: This was a semi-structured qualitative interview study with 21 participants from pharmaceutical companies and contract research organizations operating in Finland, Sweden, Denmark and Norway. Qualitative content analysis was applied. Results: For identifying countries and trial sites on a global level, the trial sponsors mostly used databases on previous trial performance. The use of electronic health record data was very limited. Sites' and investigators' visibility in various databases was seen as fundamental for their countries becoming selected into new clinical trials. For estimating the sites' recruitment projections, most sites were seen to base their patient count estimates solely on their previous experience. Some sites had reviewed their electronic health record data, which was considered to increase the accuracy of their recruitment estimates and these sites' attractivity. Along with dialogs with investigators, the sponsors used various data sources to validate the investigators' estimates. Legislative obstacles were seen to hinder the use of electronic health record queries for estimation of patient counts. Conclusion: Visibility in the databases used by trial sponsors is crucial for the countries and sites to be identified. Site selection appears to be based on trust and relationships built from experience, but electronic data provide the support upon which the trust is based. Estimation of the number of potential trial participants is a complex and time-consuming process for both investigators and sponsors. Sponsors seem to favour sites who could support their patient count estimates with electronic health record data as they were quicker in providing the estimates and more reliable than sites with no electronic health record evidence. The patient count evaluation process could be simplified, accelerated and made more reliable with more systematic use of electronic health record evidence in the feasibility evaluation phase. This would increase the accuracy of the patient count estimates and, on its part, contribute to improved recruitment success.

Electronic health records (EHR) are a potential resource for identification of clinical trial participants. We evaluated how accurately a commercially available EHR Research Platform, InSite, is able to identify potential trial participants from the EHR system of a large tertiary care hospital. Patient counts were compared with results obtained in a conventional manual search performed for a reference study that investigated the associations of atrial fibrillation (AF) and cerebrovascular incidents. The Clinical Data Warehouse (CDW) of Turku University Hospital was used to verify the capabilities of the EHR Research Platform. The EHR query resulted in a larger patient count than the manual query (EHR Research Platform 5859 patients, manual selection 2166 patients). This was due to the different search logic and some exclusion criteria that were not addressable in structured digital format. The EHR Research Platform (5859 patients) and the CDW search (5840 patients) employed the same search logic. The temporal relationship between the two diagnoses could be identified when they were available in structured format and the time difference was longer than a single hospital visit. Searching for patients with the EHR Research Platform can help to identify potential trial participants from a hospital's EHR system by limiting the number of records to be manually reviewed. EHR query tools can best be utilized in trials where the selection criteria are expressed in structured digital format.

Background Warfarin is underutilised in frail older people because of the fear of bleeding complications. Drug interactions are an independent bleeding risk factor. However, the extent to which potential drug interactions are taken into account at warfarin therapy initiation in frail patients is not known.Objective The objective of this study was to investigate the use of potentially interacting drugs increasing the bleeding risk before and after warfarin initiation in frail and non-frail patients.Methods We conducted an observational study including inpatients aged ≥ 60 years initiated on warfarin in a tertiary hospital in Adelaide, South Australia. Frailty status was assessed with the Reported Edmonton Frail Scale. Medication charts were reviewed before and after warfarin initiation.ResultsIn total, 151 patients (102 non-frail and 49 frail) were included. Before warfarin initiation, the use of clopidogrel and acetaminophen was more common in frail patients compared with non-frail patients (25.5% vs 10.2%, p = 0.0135, 63.8% vs 35.7% p = 0.0014, respectively). The use of non-steroidal anti-inflammatory drugs, 9.2% in non-frail patients and 6.4% in frail patients before warfarin initiation, was completely stopped after warfarin initiation in both groups. The use of antiplatelet drugs decreased from 56.1% in non-frail patients and 66.0 % in frail patients to 12.2% and 14.9%, respectively. Instead, the use of drugs affecting the metabolism of warfarin or vitamin K increased in both groups. No statistically significant difference was seen in the exposure to interacting drugs between study groups after warfarin initiation. Acetaminophen, senna glycosides and cytochrome P450 2C9 inhibiting drugs were the most common interacting drugs at discharge used in 49.0%, 18.4% and 20.4% of non-frail patients and 53.2%, 29.8% and 19.1% of frail patients, respectively.Conclusions The overall frequency of potential drug interactions was moderate and frail patients were not exposed to warfarin drug interactions more often than non-frail patients. Further studies in larger study populations are required to verify these results.

Background: Since 1994, the Finnish Prescription Register (FPR) has been the main data source for pharmacoepidemiology research in Finland. However, the FPR data are limited to reimbursed dispensations only. Implementation of electronic prescribing started in 2010 and after a stepwise extension, electronic prescribing became mandatory in all healthcare settings in 2017. Prescriptions issued and dispensed electronically are stored in the Prescription Centre of the nationwide Kanta database. Objectives: To describe the contents of the Kanta database and to compare the coverage of Kanta with the FPR, using prescriptions and dispensations of oral anticoagulants (OACs) as an example. Methods: All prescriptions, dispensations, and their cancellations and corrections for OACs recorded in Kanta were retrieved for the period 2012-2016. Results: In 2016, the total number of valid electronic prescriptions for OACs was 249 139 and the number of valid electronic OAC dispensations was 765 745. The number of identified direct oral anticoagulant (DOAC) users was higher in Kanta compared to the FPR since 2014, although more users of all OACs were identified from the FPR during 2012-2015. In 2016, an indication was identified in 44.7% of OAC prescriptions and dosing instructions in 99.5% of DOAC prescriptions. Conclusions: The Kanta database is a promising source of data on medication exposure. Because of reimbursement restrictions, use of DOACs was under-ascertained through the FPR.

Direct oral anticoagulants provide an alternative to vitamin K antagonists for the anticoagulation therapy in atrial fibrillation (AF). The availability of several treatment options with different attributes makes shared decision making appropriate for the choice of anticoagulation therapy. The aim of this study was to understand how physicians choose an oral anticoagulant (OAC) for patients with AF and how physicians view patients’ participation in this decision. Semi‐structured interviews with 17 Finnish physicians (8 general practitioners and 9 specialists) working in the public sector were conducted. An interview guide on experience, prescribing and opinions about oral anticoagulants was developed based on previous literature. The data were thematically analysed using deductive and inductive approaches. Based on the interviews, patient's opinion was the most influential factor in decision making when there were no clinical factors limiting the choice between OACs. Of patient's preferences, the most important was the attitude towards co‐payments of OACs. Patients’ opinions on monitoring of treatment, dosing and antidote availability were also mentioned by the interviewees. The choice of an OAC in AF was patient‐centered as all interviewees expressed that patient's opinion affect the choice. This article is protected by copyright. All rights reserved.

Clinical significance of potential interaction between warfarin and statins is unclear. Our objective was to determine whether use of statins as a class or use of simvastatin modulates the rate of bleeding requiring hospitalisation among new warfarin users. Using Finnish healthcare databases, we identified a cohort of 101,588 warfarin initiators between 1 January 2009 and 30 June 2012. By the end of 2012, these patients accumulated 92,695 person‐years of exposure to warfarin‐only and 60,253 years of exposure to warfarin‐with‐statin. The outcome was a composite of gastrointestinal, intracranial or other bleeding leading to hospitalisation. A Poisson generalised estimating equations model was employed to estimate rate ratios (RR) and their 95% confidence intervals (CI) for exposure to warfarin‐with‐statin compared to warfarin‐only and to allow multiple episodes per patient and time‐dependent covariates. In multivariable models, we found no difference in the bleeding rate in association with exposure to any statin (multivariable‐adjusted RR=0.98, 95% CI 0.89‐1.07) or to simvastatin (RR=1.01, 95% CI 0.91‐1.11) with warfarin compared to exposure to warfarin‐only. We conclude that concomitant use of statins and warfarin was not associated with an increased rate of bleeding requiring hospitalisation. This article is protected by copyright. All rights reserved.