Inpatient Drug Utilization in Europe: Nationwide Data Sources and a Review of Publications on a Selected Group of Medicines (PROTECT Project)

Drug utilization (DU) studies in inpatient settings at a national level are rarely conducted. The main objective of this study was to review the general information on hospital medicine management in Europe and to report on the availability and characteristics of nationwide administrative drug consumption databases. A secondary objective was to perform a review of published studies on hospital DU of a group of selected drugs, focusing on methodological characteristics (ATC/DDD). General information on hospital drug management was retrieved from several websites, nationwide administrative drug consumption databases and reports published by governmental organizations. A PubMed search was conducted using keywords related to the selected group of drugs AND ‘hospital drug utilization’. The data sources for hospital DU information varied widely and included 14 databases from 25 reviewed countries. Bulgaria, Croatia, Denmark, Estonia, Finland, France, Hungary, Iceland, Latvia, Norway and Sweden obtain information on inpatient DU at a national level from wholesalers/manufacturers. In Belgium, Italy and Portugal, drugs dispensed to patients in hospitals are registered at a national level. Data are freely available online only for Denmark and Iceland. From the PubMed search, of a total of 868 retrieved studies, only 13 studies used the ATC/DDD methodology. Although the number of DDD/100 bed‐days was used in four studies, other units of measure were also used. The type of information provided for the inpatient sector allowed primarily for conducting DU research at an aggregated data level. The existence of national administrative structures to monitor hospital DU would contribute to promoting the rational use of medicines and improving the safety and quality of prescribing.     

Non-antiarrhythmic drugs prolonging the QT interval: considerable use in seven countries

AIMS: Many drugs belonging to different therapeutic classes appear to share a potentially fatal side-effect: ventricular tachyarrhythmias associated with QT prolongation. The aim of this study was to assess the relevance and the magnitude of the problem in seven countries by grouping all nonantiarrhythmic drugs according to the type of evidence on QT prolongation and analysing their sales data. METHODS: We divided all nonantiarrhythmic QT-prolonging agents into the following categories (in increasing order of clinical relevance): group A, drugs with published clinical or preclinical evidence on QT prolongation or with relevant official warnings; group B, drugs with published clinical or preclinical evidence; group C, drugs with published clinical evidence; group D, drug with published clinical evidence on torsades de pointes or ventricular arrhythmias associated with QT prolongation; group E, drugs belonging to group D with official warnings. We retrieved 1998 sales data from community pharmacies in seven countries (Australia, Denmark, England, Germany, Greece, Italy and Sweden). Data for individual agents were expressed as defined daily doses per 1000 inhabitants per day (DDD/1000/day). Overall use in each country was calculated for each drug group. Groups D and E were considered as the most clinically relevant. RESULTS: Among the 102 nonantiarrhythmic agents meeting at least one of the inclusion criteria, 33 drugs had sales data > or =1 DDD/1000/day and 71 drugs had a use > or =0.1 DDD/1000/day in at least one country. Among the 37 nonantiarrhythmic agents with published reports of ventricular arrhythmias associated with QT prolongation, 12 compounds had sales data > or =1 DDD/1000/day. Total consumption in each country ranged: from 51.9 to 94.7 DDD/1000/day for group A; from 51.6 to 92.7 DDD/1000/day for group B; from 37.1 to 76.6 DDD/1000/day for group C; from 12.9 to 29.1 DDD/1000/day for group D; and from 5.8 to 15.3 DDD/1000/day for group E. CONCLUSIONS: In spite of wide variations in the sales of individual agents, the overall extent of use of nonantiarrhythmic QT-prolonging drugs was of the same order of magnitude in all countries. The significant use of drugs belonging to categories D and E should prompt careful risk/benefit assessment of each agent.     

Trends in consumption of calcium channel blockers in the Czech Republic during 1993-1999 and comparison with selected countries: drug utilization study

OBJECTIVE: To determine the patterns of consumption in calcium channel blockers (CCB) groups in the Czech Republic between 1992 and 1999 and make a comparison with selected countries. METHODS: This was part of a drug utilization study using WHO methodology [Anatomical Therapeutic Chemical classification/defined daily doses (ATC/DDD)]. The wholesale data collected by drug distributors were used. Utilization was calculated as the DDDs for 1000 inhabitants per day. In focus was the consumption of short-acting nifedipine. Comparison with wholesale data from Finland, Norway, Germany and Australia was made. RESULTS: There was a decreasing tendency to use short-acting nifedipine in the Czech Republic over the period 1993-1999. Four years after publication of warning evidence, short-acting nifedipine still accounted for 23% of all calcium channel blockers in our country. The abundance of second-generation CCBs increased from less than 1% in 1993 to 43% in 1999. The consumption of short-acting nifedipine in the Czech Republic and Germany is probably three times more frequent than in Nordic countries and Australia. CONCLUSIONS: Consumption of short-acting nifedipine in the Czech Republic 4 years after recognition of its risks still remains very high. This suggests that implementation of clinical trial results to clinical practice is very slow and ineffective.     

Problems in collecting comparable national drug use data in Europe: the example of antibacterials

OBJECTIVE: To describe the methodological problems in collecting retrospectively comparable data on drug use and to compare the use of antibacterials in some European countries. METHODS: A spreadsheet was distributed in 2000 through the European Drug Utilisation Research Group (EuroDURG) network, requesting 1994-1999 data on use of antibacterials for systemic use (ATC group J01), from ambulatory, hospital, or total care, aggregated at ATC 4th level, and presented in defined daily doses per 1000 inhabitants per day (in the 1999 ATC/DDD version or specified other version). RESULTS: The network was able to provide national utilization data for two or more years in the requested period from 16 countries (4 only from primary care, 3 both from primary care and total use, and 9 only total use data). The main methodological problems identified were: use of divergent ATC/DDD versions, divergent assignment of DDDs for combination products and the use of unofficial or national DDDs. It was possible to correct for the different ATC/DDD versions to some extent, except for the cephalosporin group (not included in the analysis), as the collection of data at the ATC 4th level precluded recalculation of DDDs. In the seven countries with primary care data the total J01 antibacterials use varied by a factor of 2.5 (Belgium 23.4 and The Netherlands 9.5 DDDs per 1000inhabitants per day). The use of J01A tetracyclines varied fourfold, and the use of J01C penicillins and J01F macrolides and lincosamides approximately threefold. Significant reduction over time was seen in J01A and an increase in J01F. CONCLUSIONS: In the scientific and regulatory community it is still difficult to perform a valid and comprehensive cross-national collection of utilization data on antibacterials. White spots on the European map persist for ambulatory care data, and data are missing for the hospital sector in most countries. For a thorough explanation of the considerable intercountry variability (especially in antibacterial subgroups and time trends analysis) a sustained and concerted effort is necessary to implement a validation process of the ATC/DDD use in the various countries and to adopt a common methodological approach to the collection of utilization data at the substance level (ATC 5th level).     

Different versions of the anatomical therapeutic chemical classification system and the defined daily dose – are drug utilisation data comparable?

OBJECTIVE: To investigate whether published drug utilisation studies contain satisfactory references to the ATC/DDD version applied and thus are usable for comparative purposes. METHODS AND RESULTS: A literature survey of drug utilisation studies was made. Seventy-three articles were identified by two Medline searches, one in 1996 and another in 1998. The articles were classified into four different groups. Groups 1 and 2 give proper references to the defined daily doses (DDDs) used in the studies, either by full reference to the version of the ATC Index with DDDs or by listing the actual DDDs used. The articles in groups 1 and 2 represent 46% of the articles in the survey. The articles classified in groups 3 and 4 give references only to general articles about the anatomical therapeutic chemical classification (ATC)/DDD system or no references at all. Fifty-four percent of the articles in the survey were classified in these groups. In these articles it is not possible to identify which DDDs have been used in the presentation of drug consumption data. CONCLUSIONS: According to the results from our literature survey, it is not common practice to include the ATC codes and the DDD values used or to make reference to the versions of the ATC/DDD index used when results from drug utilisation studies are published. One possible reason for this might be little or no knowledge about the ATC/DDD system as a dynamic system in which alterations are made annually. The lack of references to the actual DDDs used in the studies make comparisons between different data sets difficult and misleading.     

Review of the cost of diabetes complications in Australia,Canada, France,Germany, Italy and Spain

ABSTRACT

Objectives: To provide a comprehensive source document on previously published cost data for diabetic complications in Australia, Canada, France, Germany, Italy and Spain for use in a peer-reviewed, validated diabetes model.

Methods: A search for published cost of diabetes complications data was performed in peer-reviewed journals listed in PubMed and health economic conference proceedings from 1994 to March 2005. Where country specific data were not available, we referred to government websites and local cost experts. All costs were inflated to 2003 Euros (€). Major complication costs are presented.

Results: First year costs of non-fatal myocardial infarction varied between €19?277 in Spain and €12?292 in Australia. In subsequent years of treatment, this range was €1226 (France) to €203 (Australia). Angina costs were similar across all four countries: €1716 in Australia; €2218 in Canada; €2613 in France; €3342 in Germany; €2297 in Italy; and €2207 in Spain. Event costs of non-fatal stroke were higher in Canada (€23?173) than in other countries (Australia €13?443; France €11?754; Germany €19?399; Italy €6583; Spain €4638). Event costs of end-stage renal disease varied depending on the type of dialysis: in Australia (€17?188–27?552); Canada (€33?811–58?159); France (€24?608–56?487); Germany (€46?296–68?175); Italy (€43?075–56?717); and Spain (€28?370–32?706). Lower extremity amputation costs were: €18?547 (Australia); €17?130 (Canada); €31?998 (France); €22?096 (Germany); €10?177 (Italy); and €14?787 (Spain).

Conclusions: Overall, our search showed costs are well documented in Australia, Canada, France and Germany, but revealed a paucity of data for Spain and Italy. Spanish costs, collected by contacting local experts and from government reports, generally appeared to be lower for treating cardiovascular complications than in other countries. Italian costs reported in the literature were primarily hospitalization costs derived from diagnosis-related groups, and therefore likely to misrepresent the cost of specific complications. Additional research is required to document complication costs in Spain and Italy. Australian and German values were collected primarily by referring to diagnostic related group (DRG) tariffs and, as a result, there may be a need for future economic evaluations measuring the accuracy of the costs and resource utilization in the reported values. These cost data are essential to create models of diabetes that are able to accurately simulate the cumulative costs associated with the progression of the disease and its complications.     

Use of benzodiazepines and benzodiazepine-related drugs in the Nordic countries between 2000 and 2020

Use of benzodiazepines (BZ) and related drugs is subject to considerable debate due to problems with dependency and adverse events. We aimed to describe and compare their use across the Nordic countries. Data on the use of clonazepam, BZ-sedatives, BZ-hypnotics, and benzodiazepine-related drugs (BZRD) in adults (≥20 years) were obtained from nationwide registers in Denmark, Finland, Iceland, Norway, and Sweden, 2000–2020. Main measures were therapeutic intensity (TI:DDD/1000 inhabitants [inhab.]/day) and annual prevalence (users/1000 inhab./year). Overall, TI of BZ and related drugs decreased in all Nordic countries from 2004 to 2020. However, there were considerable differences between countries in TI. In 2020, the TI of BZ and related drugs ranged from 17 DDD/1000 inhab./day in Denmark to 93 DDD/1000 inhab./day in Iceland. BZRD accounted for 55–78% of BZ use in 2020, followed by BZ sedatives at 20–44%, BZ-hypnotics at <1–5%, and clonazepam at <1–2%. Annual prevalence of BZ use increased with age in all countries, and the highest annual prevalence was observed among people ≥80 years. Overall, the use of BZ and related drugs has decreased in all Nordic countries from 2004 to 2020, however, with considerable differences in their use between countries. The highest prevalence was observed among the oldest age groups—despite warnings against their use in this population.     

The history of the Drug Utilization Research Group in Europe

Following the recommendations from a World Health Organization (WHO)/Euro symposium Consumption of drugs in 1969, a common classification system for drugs was developed, the Anatomical Therapeutic Chemical (ATC), and a technical unit of comparison, the Defined Daily Dose (DDD), as a comparative unit of drug use. This was found to be robust across therapeutic classifications, dosing forms and diverse populations. To maintain and develop the ATC/DDD system a WHO-Collaborating Centre was established in Oslo. As this was found to be of global interest the centre now reports to the WHO headquarters in Geneva.An informal WHO Drug Utilization Research Group (WHO-DURG), later the EuroDURG, has by now met 28 times in Europe. Since 1994 in Stockholm all these meetings have been with ISPE (International Society for Pharmacoepidemiology) when meeting in Europe.The main focus was initially to improve drug utilization through cross-national drug utilization studies based on the ATC/DDD methodology as they revealed large differences between and within countries that could not easily be explained by morbidity differences alone. These observed differences have led to the expansion of the area to include social, economic and qualitative methods with a more generalized public health focus. One of the most recent contributions was the development of drug use quality indicators.     

Therapeutic traditions in type 2 diabetes — are they changing?

The utilisation of antidiabetic drugs reflects both the prevalence of diabetes and the different therapeutic traditions of physicians. A questionnaire survey to study attitudes to the use of oral antidiabetic drugs amongst physicians and possible changes in treatment habits was carried out in a representative sample of Finnish physicians (n=454) in 1992 and the results were compared with those of a similar survey carried out in 1985, and with drug utilisation statistics.The mean fasting blood glucose level at which a physician would start pharmacological treatment was 8.7 mmol·l^–1, which was significantly lower than in the 1985 survey. The responses to various case histories suggested a more active approach to pharmacological treatment compared to the 1985 survey. Insulin treatment especially seems to have gained in popularity. This change in attitude was paralled by an increase in the consumption of antidiabetic drugs in Finland during the observation period. The increase in use of oral drugs was steeper in Finland than in Norway and Sweden.Whether this active approach will improve the metabolic control and prognosis of patients with Type 2 diabetes, remains to be demonstrated.     

Review of the cost of diabetes complications in Australia, Canada, France, Germany, Italy and Spain

OBJECTIVES: To provide a comprehensive source document on previously published cost data for diabetic complications in Australia, Canada, France, Germany, Italy and Spain for use in a peer-reviewed, validated diabetes model. METHODS: A search for published cost of diabetes complications data was performed in peer-reviewed journals listed in PubMed and health economic conference proceedings from 1994 to March 2005. Where country specific data were not available, we referred to government websites and local cost experts. All costs were inflated to 2003 Euros (E). Major complication costs are presented. RESULTS: First year costs of non-fatal myocardial infarction varied between E19277 in Spain and E12292 in Australia. In subsequent years of treatment, this range was E1226 (France) to E203 (Australia). Angina costs were similar across all four countries: E1716 in Australia; E2218 in Canada; E2613 in France; E3342 in Germany; E2297 in Italy; and E2207 in Spain. Event costs of non-fatal stroke were higher in Canada (E23173) than in other countries (Australia E13443; France E11754; Germany E19399; Italy E6583; Spain E4638). Event costs of end-stage renal disease varied depending on the type of dialysis: in Australia (E17188-27552); Canada (E33811-58159); France (E24608-56487); Germany (E46296-68175); Italy (E43075-56717); and Spain (E28370-32706). Lower extremity amputation costs were: E18547 (Australia); E17130 (Canada); E31998 (France); E22096 (Germany); E10177 (Italy); and E14787 (Spain).CONCLUSIONS: Overall, our search showed costs are well documented in Australia, Canada, France and Germany, but revealed a paucity of data for Spain and Italy. Spanish costs, collected by contacting local experts and from government reports, generally appeared to be lower for treating cardiovascular complications than in other countries. Italian costs reported in the literature were primarily hospitalization costs derived from diagnosis-related groups, and therefore likely to misrepresent the cost of specific complications. Additional research is required to document complication costs in Spain and Italy. Australian and German values were collected primarily by referring to diagnostic related group (DRG) tariffs and, as a result, there may be a need for future economic evaluations measuring the accuracy of the costs and resource utilization in the reported values. These cost data are essential to create models of diabetes that are able to accurately simulate the cumulative costs associated with the progression of the disease and its complications.     

Antidiabetic Drug Utilization in Hungary

Objective: To evaluate the utilization trends of antidiabetics in Hungary.Method: The analysis includes the drugs of antidiabetic therapy which were registered between 1998 and 2002 in Hungary. The consumption of antidiabetic drugs was analyzed by the ATC/Defined Daily Dose (DDD) method. The data used in this study were derived from the National Health Insurance and from MIS Consulting Company.Results: Between 1998 and 2002, the total consumption of antidiabetics increased by 41.8%, and reached 47.59 DDD/1000 inhabitants/day in 2002. The consumption of oral antidiabetics (OAD) increased by 33.41% (33.86 DDD/1000 inhabitants/d ay in 2002), while in the case of insulin the increase was 67.8% (13.74 DDD/1000 inhabitants/day). Sulphonylureas were the most frequently used class (21.11 DDD/1000 inhabitants/day in 2002). Glibenclamide was the most frequently used antidiabetic drug (12.63 DDD/1000 inhabitants/day in 2002).Conclusion: The insulin class had greater emphasis in therapy. Among OAD, the consumption rate of sulphonylureas decreased and the consumption rate of Biguanides and acarbose increased. By 2002 metformin replaced 90% of the buformin in use. The limited effect of therapeutic recommendations could explain these changes, although the out-of-date buformin and the non-micronized glibenclamide were still in use in 2002.     

Utilisation of antibiotics in young children: opposite relationships to adult educational levels in Danish and Swedish counties

Background Antibiotic utilisation varies profoundly among and within countries, and the extent of antibiotic utilisation correlates with the frequency of bacterial resistance, particularly among children. Hence, it is important to assess which factors may influence prescribing. In addition to variations in morbidity, health-care organisation, drug regulatory and supply systems, prescriber's attitudes, parents' behaviour, attitudes and socio-economic positions seem important. We compared socio-economic position (educational level of adults) and antibiotic utilisation in children in the municipalities within a Danish and a Swedish county which are geographically close, have similar social and economic development, and similar drug regulatory and supply systems.Methods Data on antibiotic utilisation (1998), expressed in defined daily doses per 1000 inhabitants per day (DDD/TID), were obtained from the Copenhagen County Health Insurance register and from the National Corporation of Swedish Pharmacies. Data on municipal educational levels were obtained from Statistics Denmark and Statistics Sweden.Results The utilisation of antibiotics in 0- to 6-year-old children was higher in the Swedish than in the Danish county but varied between the municipalities within both the Swedish (9.6–17.7 DDD/TID) and the Danish (8.0–12.9 DDD/TID) counties. Most notably, utilisation rates correlated negatively with the education levels in the Danish (r=–0.539, P=0.021) but positively in the Swedish (r=+0.390, P=0.025) municipalities.Conclusion The observed variations in antibiotic prescribing may reflect different parental and/or prescriber attitudes towards use of antibiotics and they emphasise that antibiotic prescribing is influenced by factors other than the prevalence of bacterial infections. Relationships between socio-economic position (educational level) and drug utilisation should not be generalised from one area to another.     

Therapeutic traditions in Northern Ireland,Norway and Sweden: II. Hypertension

Summary A questionnaire survey based on hypertension case histories was performed among a representative sample of 400 GP's and hospital doctors in Northern Ireland, Norway and Sweden, countries having markedly different utilization of antihypertensive drugs. We found a greater propensity to start antihypertensive drug treatment in Northern Ireland than in Norway and Sweden. This was true both in mild diastolic and isolated systolic hypertension. Yet the utilization of antihypertensive drugs in Sweden is about 60% higher than in Northern Ireland and 30% higher than in Norway. Swedish physicians preferred beta-blockers as their first choice to a greater extent than physicians in Northern Ireland and Norway who selected thiazides more often. In general, the choice of drugs agreed with the sales and prescribing patterns in the three countries.Besides providing more insight in therapeutic traditions the study indicates that the lower prescribing of antihypertensive drugs in Northern Ireland, and to some extent in Norway, compared to Sweden, might be due to differences in true or apparent morbidity.     

The impact of migraine on work,family, and leisure among young women – a multinational study

SUMMARY

Objective: To assess the impact of migraine on work, family, and leisure among young women who were employed full or part time, or as a full-time student.

Research design and methods: This cross-sectional telephone survey with 6-month recall was conducted in Israel and eight European countries (Finland, Germany, Greece, Italy, Norway, Spain, Sweden, and The Netherlands). Random-digit dialing was used to identify study participants: women 18–35 years of age with migraine, who used medication to treat their migraine, and who were employed or full-time students.

Results: Of 1810 participants, 42% self-reported having a physician diagnosis of migraine. During the prior 6 months, 46% of participants missed at least 1 day of work or school and 74% were prevented from functioning fully at work or school because of migraine. Mean work/school absenteeism due to migraine was 1.9 days over 6 months (range, 0.8 days in Sweden to 2.8 days in Norway). Over half of participants reported one or more occurrences of being unable to spend time with family or friends (62%) or being unable to enjoy recreational or leisure activities (67%) because of migraine. The percentage of study participants using triptans was lowest in southern Europe and highest in the Nordic countries, ranging from 1% in Greece to 50% in Sweden. Country, age, marital status, physician diagnosis of migraine, and number of migraines or severe headaches in the prior year were independent predictors of the mean number of days of migraine-related work loss. Migraine-related work loss was lowest in Sweden and greatest in Greece, Israel, and The Netherlands. Higher work loss was recorded for those 18–24 years of age; those who were separated, widowed, or divorced; those with migraine diagnosed by a physician; and those with more frequent migraines or severe headaches (≥ 24/year). The 6-month recall period used when estimating patient-reported work loss, and identifying participants with migraine based on self-reported migraine or severe headache, were the most important limitations of the study.

Conclusions: We found substantial migraine-related impairment of productivity at work and school as well as of family and leisure time among young women in Israel and eight European countries.