Insufficient use of menopausal hormone therapy in Swedish women with early or premature menopause caused by bilateral oophorectomy: a register-based study.

OBJECTIVE: To investigate the use of menopausal hormone therapy (MHT) in premenopausal women after bilateral oophorectomy. DESIGN: Retrospective register-based cohort study. SETTING: Sweden. POPULATION: Swedish women aged 35-44 years without malignancy who underwent bilateral oophorectomy in 2005-2020 were identified using The Swedish National Quality Register of Gynaecological Surgery (GynOp). METHODS: Data from GynOp were cross-linked with data on dispensed drugs extracted from the Swedish Prescribed Drug Register. MAIN OUTCOME MEASURES: Proportion of women dispensed MHT at least once within 1 year after surgery. Repeated treatment episodes were defined, and the proportion of 'person time' covered by dispensations was analysed. RESULTS: In total, 1231 of all women (n = 1706) were dispensed MHT at some point after surgery, with 1177 women dispensed MHT within 1 year. This proportion increased from 64% in 2005 to 84% in 2019 (p < 0.001). In the total population, 4537 'treatment years' transpired, corresponding to 43% of the mean time covered. In women dispensed MHT within 1 year, the proportion of time covered was 63%. CONCLUSIONS: Only 69% of all women without malignancy of any kind who underwent bilateral oophorectomy were dispensed MHT within 1 year after surgery, and the duration of treatment was limited. It is important to study further the reasons behind the low dispensation rate in this group to increase adherence to current treatment guidelines, improve quality of life, and avoid increased morbidity and mortality.

Reliability and validity of the Swedish indicator 'Drugs that should be avoided in older people'-an appraisal of a set of potentially inappropriate medications.

PURPOSE: To analyse the reliability and validity of the Swedish indicator 'Drugs that should be avoided in older people'. METHODS: From a previous study that included consecutive primary care patients ≥ 65 years of age, all patients ≥ 75 years of age were analysed. Two physicians independently screened their medication lists and medical records, applying the Swedish indicator which includes potentially inappropriate medications (PIMs): long-acting benzodiazepines, drugs with anticholinergic action, tramadol, propiomazine, codeine, and glibenclamide. The clinical relevance of identified PIMs was independently assessed. Thereafter, the physicians determined in consensus whether some medical action related to the drug treatment was medically justified and prioritised before the next regular visit. If so, the drug treatment was considered inadequate, and if not, adequate. RESULTS: A total of 1,146 drugs were assessed in 149 patients (75‒99 years, 62% female, 0‒20 drugs per patient). In 29 (19%) patients, at least one physician identified ≥ 1 PIM according to the indicator at issue; 24 (16%) patients were concordantly identified with ≥ 1 such PIM (kappa: 0.89). Of 26 PIMs concordantly identified, the physicians concordantly assessed four as clinically relevant and 12 as not clinically relevant (kappa: 0.17). After the consensus discussion, six (4%) patients had ≥ 1 PIM according to the studied indicator that merited action. Using the area under the receiver operating characteristic (ROC) curve, the indicator did not outperform chance in identifying inadequate drug treatment: 0.56 (95% confidence interval: 0.46 to 0.66). CONCLUSION: The Swedish indicator has strong reliability regarding PIM detection but does not validly reflect the adequacy of drug treatment.

Methodological issues in research on drug-related admissions: A meta-epidemiological review with focus on causality assessments.

AIM: To investigate methodological aspects potentially related to the diverging scientific literature on the prevalence of drug-related hospitalisations, focusing on causality assessments. METHODS: Original studies contributing data to a recent meta-analysis were reviewed. Methodological aspects, in particular those related to causality assessments, were extracted and compiled. RESULTS: Thirteen studies provided data on the prevalence of drug-related admissions. Seven studies focused on adverse drug reactions (prevalences 1.3-10%), and six studies used the broader concept of drug-related problems (prevalences 4.5-41%). In 10 out of 13 studies, causality between the drug and the specified problem was assessed. One study required a probable causal relationship; the remaining studies merely required a possible causal relationship. Five studies assessed the association between the problem assumed to be related to drug therapy and the admission, at one end requiring the former to be demonstrated as the underlying cause and, at the other, merely requiring a temporal relationship between drug intake and admission. Three out of eight studies involving multiple assessors for all/some cases reported the inter-rater agreement, ranging from none to almost perfect. Physicians were involved in the assessments in five studies, reporting prevalences of 3.2% to 4.5%, while studies without such medical input reported prevalences of 8.8% to 41%. CONCLUSIONS: This review illustrates that methodological issues contribute to the diverse literature on drug-related admissions. We provide suggestions for harmonisation of research, including explicitly assessing the drug-problem-admission relationships from a medical perspective, focusing on problems where the drug treatment is the probable culprit.

PERson-centredness in hypertension management using information technology (PERHIT): a protocol for a randomised controlled trial in primary health care.

Purpose: For primary health care (PHC), hypertension is the number one diagnosis for planned health care visits. The treatment of high blood pressure (BP) and its consequences constitutes a substantial economic burden. In spite of efficient antihypertensive medications, a low percentage of patients reach a well-controlled BP. The PERson-centredness in Hypertension management using Information Technology (PERHIT) Study is a multicentre randomised controlled trial. PERHIT is designed to evaluate the effect of supporting self-management on systolic blood pressure by the use of information technology in Swedish primary health care.Materials and Methods: After inclusion, 900 patients from 36 PHC centres are randomised to two groups. In the intervention group, patients are provided with a self-management support system including a home-BP monitor and further requested to perform self-reports and measure BP every evening for eight consecutive weeks. In the control group, patients receive treatment as usual.Results: The primary outcome will be the change in systolic blood pressure in patients with hypertension. In addition, person-centredness, daily life activities, awareness of risk and health care costs will also be evaluated.Conclusion: The results of this randomised controlled trial with assessment of blood pressure and same-day self-reports will provide patients a tool to understand the interplay between blood pressure and lifestyle applicable to primary health care. The self-management support system may be of importance for improved adherence to treatment and persistence to treatment recommendations.

Do patients or their physicians more accurately assess long-term risk associated with hypertension? A population-based study.

Objective: To compare the assessments of 10-year probability by patients and their physicians of cardiovascular complications of hypertension with actual outcomes.Design: Patients with uncomplicated hypertension treated with at least one antihypertensive drug at inclusion were followed for 10 years through mandatory national health registers.Setting: 55 primary health care centres, 11 hospital outpatient clinics in SwedenPatients: 848 patient, 212 physicians.Main outcome measures: Patients and physicians estimated the probability of hypertension-related complications with treatment (death, heart failure, acute myocardial infarction/AMI, and stroke) for each patient in 848 pairs. Estimates were compared with the clinical outcomes 10 years later using data from the Mortality Register and the National Patient Register.Results: Patients were significantly better (p < 0.001) than their physicians in estimating the average probability of heart failure compared with actual outcome data (14% vs. 24%, outcome 15%), AMI (16% vs. 26%, outcome 8%), and stroke (15% vs. 25%, outcome 11%). Patients were significantly worse (p < 0.001) at estimating the average probability of death (10% vs. 18%, actual outcome 20%). Neither the patients nor the physicians were able to distinguish reliably between low-risk and high-risk patients after adjustment for age and sex.Conclusions: Patients were better than their physicians in estimating the average probability of morbidity due to hypertension. Both the patients and their attending physicians had difficulty in estimating the individual patient's risk of complications. The results support the use of evidence-based tools in consultations for assessing the risk of cardiovascular complications associated with hypertension.Key points • Shared decision making relies on a common understanding of risks and benefits. Tools for risk assessment of hypertension have been introduced in the last two decades. • Without tools for risk assessment, both patients and physicians had difficulties in estimating the individual patient's risk of cardiovascular morbidity. • Patients were better than physicians in estimating actual average cardiovascular morbidity due to hypertension during a follow-up of 10 years. • The results support the use of evidence-based tools in consultations for assessing the risk of cardiovascular complications associated with hypertension.

Evidence synthesis based on non-randomised studies-a critical review of studies leading to conclusions on fall risk properties of loop diuretics/beta-blockers.

PURPOSE: To describe methodological and reporting issues in non-randomised comparative drug safety studies pooled in meta-analyses, with focus on confounding by indication. METHODS: All studies included in statistically significant meta-analyses in a recent publication investigating fall risk properties of cardiovascular drugs were reviewed. Study characteristics were extracted and assessed. RESULTS: Nine studies, including between 498 and 321,995 individuals, contributed data to the significant meta-analyses in which loop diuretics and beta-blockers were associated with falls, five published in 2015. Five individual studies reported a statistically significant association. In the five cohort studies, characteristics of exposed vs unexposed individuals were either not reported (n = 3) or differed substantially regarding morbidity (n = 2). Drug treatment was determined at baseline, and data on falls were collected for up to 2 years thereafter. Out of the four case-control studies, the cases and controls in only one study were matched for morbidity. Morbidity characteristics of fallers compared with non-fallers were either not reported (n = 2) or they differed (n = 1) or were reported according to the matched-for diseases (n = 1). Confounding by indication was explicitly discussed in two studies. None of the abstract conclusions considered causality issues or the possibility of confounding by indication. CONCLUSIONS: Confounding by indication is a major issue in non-randomised comparative drug safety studies, a problem which may be concealed in meta-analyses. To enhance such research, compared groups need to be balanced regarding relevant factors including morbidities and characteristics adequately reported. Confounding by indication needs to be explicitly discussed and highlighted in the abstract conclusion.

Evaluating beneficial drug effects in a non-interventional setting: a review of effectiveness studies based on Swedish Prescribed Drug Register data.

AIMS: To describe and assess current effectiveness studies published up to 2014 using Swedish Prescribed Drug Register (SPDR) data. METHODS: Study characteristics were extracted. Each study was assessed concerning the clinical relevance of the research question, the risk of bias according to a structured checklist, and as to whether its findings contributed to new knowledge. The biases encountered and ways of handling these were retrieved. RESULTS: A total of 24 effectiveness studies were included in the review, the majority on cardiovascular or psychiatric disease (n = 17; 71%). The articles linked data from four (interquartile range: three to four) registers, and were published in 21 different journals with an impact factor ranging from 1.58 to 51.66. All articles had a clinically relevant research question. According to the systematic quality assessments, the overall risk of bias was low in one (4%), moderate in eight (33%) and high in 15 (62%) studies. Overall, two (8%) studies were assessed as contributing to new knowledge. Frequently occurring problems were selection bias making the comparison groups incomparable, treatment bias with suboptimal handling of drug exposure and an intention-to-treat approach, and assessment bias including immortal time bias. Good examples of how to handle bias problems included propensity score matching and sensitivity analyses. CONCLUSION: Although this review illustrates that effectiveness studies based on dispensed drug register data can contribute to new evidence of intended effects of drug treatment in clinical practice, the expectations of such data to provide valuable information need to be tempered due to methodological issues.

The right drug, but from whose perspective? A framework for analysing the structure and activities of drug and therapeutics committees.

PURPOSE: During the last five decades drug and therapeutics committees (DTCs), have evolved from mainly hospital-based groups of experts in pharmacotherapy and drug logistics into an arena for healthcare professionals employing evidence-based methods of promoting rational drug use. The purpose of this study was to suggest a framework for analysing the structure and activities of DTCs. METHODS: A literature search was carried out in the Medline, Cinahl and Web of Sciences databases for the period 1993-2012. RESULTS: A total of 207 articles were included. Based on these articles a framework for the analysis of the DTCs based on the role of the DTC, target groups, budget perspective and type of economic decisions could be suggested. CONCLUSIONS: In order to respond to future demands the DTCs will have to develop their skill in pharmacoeconomics. Their processes will have to be standardised and made more transparent in order to be better adapted to evidence-based decision-making. They will also have to embrace the possibilities created by electronic health records in both influencing the decisions of physicians, and in improving quality assurance programmes and longitudinal follow-up of drug therapy and outcomes. They will have to find new ways of interacting with the public and policy makers in order to get the resources needed for their work. Finally, they will have to handle the conflict among national, regional and local decision-making processes and the relationship between formularies and therapeutic guidelines.

Timeline of and Expectations for the National Medication List in Sweden.

It is important to separate the continuous chains of medications orders (or decisions by the prescriber) in modern electronic health records from the one-way communication of prescriptions from healthcare to pharmacies. To support the self-administration of prescribed drugs the patient needs a continuously updated list of medication orders. For the NLL to function as a safe resource for the patient, it is necessary to have the information updated, curated, and documented by prescribers in a one-step process within the electronic health record. Four of the Nordic countries have chosen separate ways trying to achieve this. The experiences and obstacles during the introduction of the mandatory National Medication List (NLL) in Sweden and the resulting delays are described. The planned integration for 2022 is now delayed to 2025 and will probably only be achieved in 2028 or even 2030 in some regions.

Incidence in pharmacoepidemiology: A conceptual framework for incidence of a single substance or group of substances with statins as an example.

A framework for analysing incidence in pharmacoepidemiology and drug statistics is suggested using statins as an example. A new case of statin use (first-ever use or recurrence of treatment) can be defined as new on the group (NoG), new on substance whether new on the group or not (NoS), new on substance and new on the group (NoS_and_NoG), new on substance and not new on the group (NoS_not_NoG). METHOD: Individual-level dispensations of statins 2006-2019 for 1 017 058 individuals with at least one dispensation 2019 in Sweden. RESULTS: With 12-month run-in, corresponding to at least 8 months without treatment, the incidence proportion of NoG was 13.39 new cases per 1000 inhabitants and 8.40 with 10-year run-in. Thus, 37% had first been treated with any statin between 12 months and 10 years before the index date. For atorvastatin, NoS was 10.69, NoS_and_NoG 9.99, and NoS_not_NoG 0.70 per 1000 inhabitants. 0.70 per 1000 inhabitants or 6.6% of new cases of atorvastatin represented a change from another statin during the run-in. CONCLUSION: It is essential to separate new cases that are new both on the substance and on the group from those that represent a change of therapy during the run-in.

Challenges with Medication Management and the National Medication List in Sweden: An Interview Study from a Human, Organizational, and Technology Perspective.

Sweden is in the process of implementing the National Medication List (NLL). The aim of this study was to explore the challenges with the medication management process, as well as expectation for NLL, from a human, organizational, and technology perspective. This study included interviews with prescribers, nurses, pharmacists, patients, and their relatives and was conducted during March to June 2020, before the implementation of NLL. Challenges were (1) feeling lost with several different medication lists, (2) spending time searching for information, (3) being frustrated at parallel information systems, (4) patients being the carriers of information, and (5) the feeling of being responsible in an indistinct process. The expectations for NLL in Sweden were high, but there were several fears.

Trends in the incidence, prevalence and sales volume of menopausal hormone therapy in Sweden from 2000 to 2021.

OBJECTIVES: To describe the trends in the prevalence of use menopausal hormone therapy (MHT) in Sweden over the period 2000-2021 and to analyse the impact of different lengths of run-in on the calculated incident use. STUDY DESIGN: Individual-level data on MHT dispensations for 2.5 million women aged 45-69 years for the period 2006-2021 were analysed. Aggregated sales volumes in defined daily dose (DDD) were available for the whole study period (2000-2021). MAIN OUTCOME MEASURES: One-year prevalence and one-year incidence (18-month run-in) per 1000 women and DDD per 1000 women per day of MHT were the main outcome measures. The predictive values for incidence representing first-ever use of MHT were calculated for different run-in periods, which is a defined period without dispensations. RESULTS: Both the DDD, from 2000, and the prevalence, from 2006, decreased by over 80 % in women aged 50-54 years, until 2010, when the use of MHT stabilised. The predictive value for incident users to be first-ever users was 88 % in women aged 50-54 years, with a run-in of 18 months, in 2021. The incidence was stable between 2007 and 2016. From 2017 the incidence increased, being most pronounced for women close to menopause. CONCLUSIONS: MHT use decreased significantly after the turn of the century, but has increased since 2017. A run-in period of 18 months was found suitable and reliable for defining incident users of MHT in the age intervals closest to menopause. Incidence seems to be a more sensitive measure than prevalence or DDD for the early detection of changes in trends in prescriptions of MHT.

PERson-centredness in Hypertension management using Information Technology: a randomized controlled trial in primary care.

OBJECTIVES: To increase the proportion of individuals with hypertension obtaining a blood pressure (BP) of less than 140/90 mmHg by improving the management of hypertension in daily life from a person-centred perspective. METHODS: In this unblinded randomized controlled trial, we tested an interactive web-based self-management system for hypertension. A total of 949 patients with hypertension from 31 primary healthcare centres (PHCCs) in Sweden were randomized 1 : 1 to either the intervention or usual care group. The intervention included daily measurement - via the participant's mobile phone - of BP and pulse and reports of well being, symptoms, lifestyle, medication intake and side effects for eight consecutive weeks. It also included reminders and optional motivational messages. The primary outcome was the proportion of participants obtaining BP of less than 140/90 mmHg at 8 weeks and 12 months. Significance was tested by Pearson's chi 2 -test. RESULTS: A total of 862 patients completed the trial, 442 in the intervention group and 420 in the control group. The primary outcome (BP <140/90 mmHg) at 8 weeks was achieved by 48.8% in the intervention group and 39.9% in the control group ( P  = 0.006). At 12 months, 47.1% (intervention) and 41.0% (control group) had a BP less than 140/90 mmHg ( P  = 0.071). CONCLUSION: The proportion of participants with a controlled BP of less than 140/90 mmHg increased after using the interactive system for self-management of hypertension for 8 weeks compared with usual care. Although the trend continued, there was no significant difference after 12 months. The results indicate that the effect of the intervention is significant, but the long-term effect is uncertain. TRIAL REGISTRATION: The study was registered with ClinicalTrials.gov (NCT03554382).

Corrigendum to "Utilisation Trend of Long-Acting Insulin Analogues including Biosimilars across Europe: Findings and Implications".

[This corrects the article DOI: 10.1155/2021/9996193.].

Incidence in pharmacoepidemiology-Basic definitions and types of misclassification.

The definition of a new case is a vital step in incidence studies in both epidemiology and pharmacoepidemiology, although with significant differences in methodology between the fields. We define and apply a framework for two different types of new cases of drug use, first-ever and recurrent, and show how the associated misclassifications related to length of run-in period can be expressed by the positive predictive value (PPV). In the study, we consider individual-level dispensations of statins 2006-2019 for 1,017,058 individuals with at least one dispensation in 2019 in Sweden. The incidence proportion for statins for both sexes of all ages in Sweden 2019 varied from 17.4/1000 with a run-in of 8 months, 9.45/1000 with 5 years and 8.4/1000 with 10 years. The PPV was 49% with 8 months and 89% for 5 years using 10 years as gold standard. We conclude that the interpretation of incidence and thus the selection of an appropriate run-in period, in pharmacoepidemiology, depends on whether first-ever use, recurrent treatment or both together (new cases) is the focus of the research question studied. At least five different misclassifications can be introduced depending on how incidence is defined.

[Pharmacological knowledge bases in Sweden: successes and future in a time of information overflow]. / Låt Sil bli kärnan i framtidens kunskaps- och beslutsstöd.

Skewed information about medicines in social media influence the healthcare-patient contact. Healthcare staff need situation adapted evidence that can be linked to patient data. For 20 years Sweden has provided praised Pharmacological Knowledge Bases (PKB). They include ¼Janusmed drug-drug interactions«, ¼Janusmed drugs and birth defects« and ¼e-Ped (electronic pediatric) instructions and drug dosage control«. PKBs need to be better integrated into digital tools adhering to a national guide for optimal interface presentation of information. They should be produced by medical editors and delivered through a national digital highway. Experts need to adhere to a policy for handling conflicts of interest and evaluate that information is appreciated and used. PKBs should be accessible as a public good for healthcare staff, students and the public to support personalized medical care.

Performance of 3 Sets of Criteria for Potentially Inappropriate Prescribing in Older People to Identify Inadequate Drug Treatment.

Importance: Potentially inappropriate medications (PIMs) and potential prescribing omissions (PPOs) are used in research to reflect the quality of drug treatment in older people and have been suggested for inclusion in core outcome sets for evaluation of interventions for improved prescribing. Their validation so far, however, is primarily restricted to expert opinion-based processes. Objective: To evaluate the performance of 3 explicit PIM/PPO criteria sets as diagnostic tools to identify inadequate drug treatment in older patients. Design, Setting, and Participants: This diagnostic study analyzed patients aged 65 years or older consecutively included from 2 primary health care centers from October to November 2017. Data were analyzed from February to August 2022. Exposures: The PIMs/PPOs were concordantly identified by 2 specialist physicians (2018-2019) retrospectively after a planned physician visit, using 3 European PIM/PPO criteria sets and without knowledge of this diagnostic study. Main Outcomes and Measures: Area under the receiver operating characteristic (ROC) curve, reflecting the ability of PIM/PPO criteria sets to identify the reference standard of inadequate drug treatment, determined by 2 specialist physicians in consensus. Inadequate drug treatment implied that additional action related to the medication could be medically justified before the next regular visit. Results: A total of 302 patients were analyzed (median age, 74 [IQR, 69-81] years; 178 women [59%]; median number of drugs in the medication list, 6 [IQR, 3-9]); 98 patients (32%) had inadequate drug treatment. A total of 0 to 8 PIMs/PPOs per patient were identified using the Screening Tool of Older Persons' Prescriptions (STOPP)/Screening Tool to Alert to Right Treatment (START) criteria, 0 to 6 with the European EU(7)-PIM list, and 0 to 12 with the Swedish set of indicators of prescribing quality. The areas under the ROC curve for the 3 sets to identify the reference standard for inadequate drug treatment were 0.60 (95% CI, 0.53-0.66) for the STOPP/START criteria, 0.69 (95% CI, 0.63-0.75) for the EU(7)-PIM list, and 0.73 (95% CI, 0.67-0.80) for the Swedish set. For comparison, the area under the ROC curve was 0.71 (95% CI, 0.65-0.78) using the number of drugs in the medication list. Conclusions and Relevance: In this diagnostic study, the evaluated PIM/PPO sets had poor to fair performance as diagnostic tools to identify inadequate drug treatment, comparable with a simple count of the number of drugs in the medication list. These findings suggest that use of PIMs/PPOs as indicators of drug treatment quality in core outcome sets for the evaluation of interventions for improved prescribing may need reconsideration.

Opioid availability statistics from the International Narcotics Control Board do not reflect the medical use of opioids: comparison with sales data from Scandinavia.

OBJECTIVES: Opioid analgesics are essential in clinical practice, but their excessive use is associated with addiction risk. Increases in opioid prescription rates have fuelled an epidemic of opioid addiction in the USA, making statistics on medical opioid use a critical warning signal. A dramatic 150% increase in Swedish opioid access 2001-2013 was recently reported based on data from the International Narcotics Control Board (INCB; Berterame et al. 2016) in conflict with other studies of opioid use in the Nordic countries. This article aims to analyse to what degree published INCB statistics on opioids in Scandinavia (Denmark, Norway and Sweden) reflect actual medical use and study the methodological reasons for putative discrepancies. METHODS: Data on aggregated total national sales of opioids for the whole population, including hospitals, were collected from the Swedish e-Health Authority. Total sales data for Denmark and drugs dispensed at pharmacies in Norway are publicly available through the relevant authorities' websites. RESULTS: INCB opioid statistics during the period 2001-2013 were markedly inconsistent with sales data from Scandinavia, calling the reliability of INCB data into question. INCB-data were flawed by (a) over-representing the volume of fentanyl, (b) under-reporting of codeine, and (c) by not including tramadol. CONCLUSIONS: Opioid availability, as expressed by INCB statistics, does not reflect medical opioid use. It is crucial to underline that INCB statistics are based on the manual compilation of national production, import and export data from manufacturers and drug companies. This is not the same amount that is prescribed and consumed within the health care system. Moreover, there are methodological problems in the INCB reports, in particular concerning fentanyl, codeine and tramadol. We suggest that INCB should carefully review the quality of their data on medical opioids.

Utilisation Trend of Long-Acting Insulin Analogues including Biosimilars across Europe: Findings and Implications.

BACKGROUND: Diabetes mellitus rates and associated costs continue to rise across Europe enhancing health authority focus on its management. The risk of complications is enhanced by poor glycaemic control, with long-acting insulin analogues developed to reduce hypoglycaemia and improve patient convenience. There are concerns though with their considerably higher costs, but moderated by reductions in complications and associated costs. Biosimilars can help further reduce costs. However, to date, price reductions for biosimilar insulin glargine appear limited. In addition, the originator company has switched promotional efforts to more concentrated patented formulations to reduce the impact of biosimilars. There are also concerns with different devices between the manufacturers. As a result, there is a need to assess current utilisation rates for insulins, especially long-acting insulin analogues and biosimilars, and the rationale for patterns seen, among multiple European countries to provide future direction. Methodology. Health authority databases are examined to assess utilisation and expenditure patterns for insulins, including biosimilar insulin glargine. Explanations for patterns seen were provided by senior-level personnel. RESULTS: Typically increasing use of long-acting insulin analogues across Europe including both Western and Central and Eastern European countries reflects perceived patient benefits despite higher prices. However, activities by the originator company to switch patients to more concentrated insulin glargine coupled with lowering prices towards biosimilars have limited biosimilar uptake, with biosimilars not currently launched in a minority of European countries. A number of activities were identified to address this. Enhancing the attractiveness of the biosimilar insulin market is essential to encourage other biosimilar manufacturers to enter the market as more long-acting insulin analogues lose their patents to benefit all key stakeholder groups. CONCLUSIONS: There are concerns with the availability and use of insulin glargine biosimilars among European countries despite lower costs. This can be addressed.

Guiding principles for the use of knowledge bases and real-world data in clinical decision support systems: report by an international expert workshop at Karolinska Institutet.

INTRODUCTION: Technical and logical breakthroughs have provided new opportunities in medicine to use knowledge bases and large-scale clinical data (real-world) at point-of-care as part of a learning healthcare system to diminish the knowledge-practice gap. AREAS COVERED: The article is based on presentations, discussions and recommendations from an international scientific workshop. Value, research needs and funding avenues of knowledge bases and access to real-world data as well as transparency and incorporation of patient perspectives are discussed. EXPERT OPINION: Evidence-based, publicly funded, well-structured and curated knowledge bases are of global importance. They ought to be considered as a public responsibility requiring transparency and handling of conflicts of interest. Information has to be made accessible for clinical decision support systems (CDSS) for healthcare staff and patients. Access to rich and real-world data is essential for a learning health care ecosystem and can be augmented by data on patient-reported outcomes and preferences. This field can progress by the establishment of an international policy group for developing a best practice guideline on the development, maintenance, governance, evaluation principles and financing of open-source knowledge bases and handling of real-world data.