The impact of the war on maintenance of long-term therapies in Ukraine.

Due to the Russian invasion, which started on 24 February 2022, the Ukrainian healthcare system is facing multiple challenges. A great number of healthcare facilities have been destroyed, while availability of other ones is often limited due to a lack of qualified medical staff. Certain services, e.g. cancer therapies, have been seriously disrupted. Moreover, millions of Ukrainians with chronic conditions are also suffering as due to war-related problems with execution of their long-term therapies. Availability of drugs is particularly limited in the occupied regions. According to the national statistics, as of 18 August 2022, about 505 pharmacies were damaged in Eastern Ukraine and 47 completely ruined. Moreover, the invaders have been blocking humanitarian aid provided to these territories by the Ukrainian government or other countries. Fortunately, in the areas controlled by the Government of Ukraine, the acute shortage of medicines, observed at the beginning of the war, has already been eliminated. Nevertheless, not all drugs are now fully available, even in the areas where no military attacks occur. The economic availability of drugs is also profoundly influenced by the significant increase in the cost of medications and the fall in average salaries. The Government of Ukraine is trying to minimise the impact of these war-related challenges by adopting a new legislation. This includes, among others, simplification of procedures for licensing, quality control and import of medicinal products to Ukraine. Other measures involve securing displaced people with the option of benefiting from local healthcare facilities, broadening the scope of the ePrescription system, authorizing primary care doctors to issue prescriptions to refugees, increasing the number of drugs reimbursed for long-term therapies, etc. These solutions, however, cannot balance all the harmful consequences the war in Ukraine brings in terms of maintenance of long-term therapies. Therefore, in order to minimise this negative impact, Ukraine still needs urgent international support in this area.

Core concepts in pharmacoepidemiology: Measures of drug utilization based on individual-level drug dispensing data.

BACKGROUND: Drug utilization studies are essential to facilitate rational drug use in the society. AIM: In this review, we provide an overview of drug utilization measures that can be used with individual-level drug dispensing data, referencing additional reading on the individual analysis. This is intended to serve as a primer for those new to drug utilization research and a shortlist from which researchers can identify useful analytical approaches when designing their drug utilization study. RESULTS AND DISCUSSION: We provide an overview of: (1) basic measures of drug utilization which are used to describe changes in drug use over time or compare drug use in different populations; (2) treatment adherence measures with specific focus on persistence and implementation; (3) how to measure drug combinations which is useful when assessing drug-drug interactions, concomitant treatment, and polypharmacy; (4) prescribing quality indicators and measures to assess variations in drug use which are useful tools to assess appropriate use of drugs; (5) proxies of prescription drug misuse and skewness in drug use; and (6) considerations when describing the characteristics of drug users or prescribers.

Challenges and Opportunities With Routinely Collected Data on the Utilization of Cancer Medicines. Perspectives From Health Authority Personnel Across 18 European Countries.

Background: Rising expenditure for new cancer medicines is accelerating concerns that their costs will become unsustainable for universal healthcare access. Moreover, early market access of new oncology medicines lacking appropriate clinical evaluation generates uncertainty over their cost-effectiveness and increases expenditure for unknown health gain. Patient-level data can complement clinical trials and generate better evidence on the effectiveness, safety and outcomes of these new medicines in routine care. This can support policy decisions including funding. Consequently, there is a need for improving datasets for establishing real-world outcomes of newly launched oncology medicines. Aim: To outline the types of available datasets for collecting patient-level data for oncology among different European countries. Additionally, to highlight concerns regarding the use and availability of such data from a health authority perspective as well as possibilities for cross-national collaboration to improve data collection and inform decision-making. Methods: A mixed methods approach was undertaken through a cross-sectional questionnaire followed-up by a focus group discussion. Participants were selected by purposive sampling to represent stakeholders across different European countries and healthcare settings. Descriptive statistics were used to analyze quantifiable questions, whilst content analysis was employed for open-ended questions. Results: 25 respondents across 18 European countries provided their insights on the types of datasets collecting oncology data, including hospital records, cancer, prescription and medicine registers. The most available is expenditure data whilst data concerning effectiveness, safety and outcomes is less available, and there are concerns with data validity. A major constraint to data collection is the lack of comprehensive registries and limited data on effectiveness, safety and outcomes of new medicines. Data ownership limits data accessibility as well as possibilities for linkage, and data collection is time-consuming, necessitating dedicated staff and better systems to facilitate the process. Cross-national collaboration is challenging but the engagement of multiple stakeholders is a key step to reach common goals through research. Conclusion: This study acts as a starting point for future research on patient-level databases for oncology across Europe. Future recommendations will require continued engagement in research, building on current initiatives and involving multiple stakeholders to establish guidelines and commitments for transparency and data sharing.

Swedish Covid-19 Investigation for Future Insights - A Population Epidemiology Approach Using Register Linkage (SCIFI-PEARL).

BACKGROUND: In response to the Covid-19 pandemic, we designed and initiated a nationwide linked multi-register, regularly updated, observational study for timely response to urgent scientific questions. AIM: To describe the SCIFI-PEARL (Swedish Covid-19 Investigation for Future Insights - a Population Epidemiology Approach using Register Linkage) linked database encompassing essentially all known diagnosed Swedish Covid-19 patients plus a large general population comparison cohort and outline its utility in the current and future phases of the pandemic. METHODS: Individuals with Covid-19 from the entire country are identified on a regularly updated basis, from different sources: all individuals from SmiNet, the national database of notifiable diseases, with positive SARS-CoV-2 polymerase chain reaction (PCR) test results; patients identified in the healthcare system by condition (ICD-10) or procedure codes in the National Patient Register or Cause-of-Death Register; patients identified through several disease-specific national quality registers (NQRs); and in two regions additionally patients identified in primary care. A comparison population was obtained by stratified random sampling from Swedish national population registers. Data from all these registers plus the National Prescribed Drug Register, the Cancer Register, national sociodemographic registers, some additional NQRs, the National Vaccination Register, and further data sources, are then linked to all study subjects (Covid-19 cases and population cohort). New cases in the study population and all data for all subjects are updated every few months, as required. CONCLUSION AND UTILITY: The SCIFI-PEARL study cohort captures Swedish residents with Covid-19 on an ongoing basis, includes a representative general population comparison cohort, and links to a broad range of national and regional healthcare data for a comprehensive longitudinal view of the Covid-19 pandemic. By combining high-quality national registers with short time delay and continuous repeated linkage and updating, the project brings timely and internationally relevant data for epidemiological research on SARS-CoV-2. Our efforts provide an example and important learnings for similar efforts internationally in the future.

Survival of esophageal and gastric cancer patients with adjuvant and palliative chemotherapy-a retrospective analysis of a register-based patient cohort.

PURPOSE: The survival of esophageal and gastric cancer patients treated with chemotherapy is rarely assessed outside of clinical trials. Therefore, we compared the effectiveness of various curative or palliative chemotherapy regimens on the survival of esophageal and gastric cancer patients in a "real world" clinical setting. METHODS: We identified a cohort of 966 incident esophageal and gastric cancer patients in Stockholm/Gotland County (a low-risk Western population) during 2008-2013. Patients who received chemotherapy with curative intention (n = 279) and palliative intention (n = 182) were analyzed separately. Using Cox proportional hazards regression models, we estimated hazard ratios (HRs) with 95% confidence intervals (CIs) and adjusted for the potential confounding factors: age, sex, TNM stage, radiotherapy, comorbidity, marital status, education, income, and country of birth. RESULTS: In esophageal cancer patients with curative treatment intention, we observed a higher hazard for death among patients who received carboplatin-fluorouracil compared to patients who received cisplatin-fluorouracil, corresponding to a HR of 2.18 (95% CI 1.09-4.37). Conversely, in patients with cancer in the gastroesophageal junction who had a curative treatment intention at diagnosis, we observed a reduced hazard for death among those who received fluorouracil-oxaliplatin, compared to patients who received cisplatin-fluorouracil (HR 0.28; 95% CI 0.08-0.96). CONCLUSION: Among patients with esophageal cancer who received treatment with curative intention, cisplatin-fluorouracil was associated with better survival compared to carboplatin-fluorouracil, while patients with gastroesophageal junction cancer who were treated with cisplatin-fluorouracil had worse survival compared to fluorouracil-oxaliplatin.

Electronic assessment of cardiovascular potentially inappropriate medications in an administrative population database.

AIM: To explore the feasibility of the electronic assessment of potentially inappropriate medication (PIM) criteria in a large administrative database and to explore the validity of the cardiovascular subset of PIM criteria, by studying the association with relevant outcome. METHOD: A cohort study using administrative data from Stockholm County, Sweden (VAL database). Eligible for inclusion were community-dwelling older people (≥65 years), alive in Stockholm County on 31 December 2015. We applied PIM criteria pertaining to the cardiovascular medication group (first-level ATC C group), and we assessed the association between PIM use and mortality and hospitalisation. RESULTS: Patients' (n = 315 120) mean age was 74.0 years (range 65-114), and 54.7% were women. There were 111 cardiovascular PIM criteria in the repository, from which 44 were not registered or prescribed in our population. We excluded another 43 requiring information not available in the database, or duplicates, resulting in 24 applicable criteria. The prevalence of polypharmacy (≥ five medications) was 25.5% and the prevalence of at least one PIM use was 8.3%, including 2.8% underuse and 5.3% misuse. Patients with intake of ≥10 medications had 38% increased mortality risk compared to those with 0-4 medications. Unplanned hospitalisation and emergency department visits were positively associated with underuse (12% and 25%, respectively) and misuse (13% and 12%, respectively). CONCLUSION: It was feasible to select a subset of cardiovascular PIM criteria originating from different PIM lists and to apply this subset in an administrative database. Additionally, by applying this subset, we showed significant associations with clinical outcome.

Did we see it Coming? An Evaluation of the Swedish Early Awareness and Alert System.

BACKGROUND: Early awareness and alert systems have been established in many countries but evidence on their ability to accurately prioritize new medicines (for early assessment) is limited. OBJECTIVE: The purpose of this study was to assess whether the Swedish Early Awareness and Alert System identified and prioritized (i.e., produced early assessment reports for) new medicines that would go on to have substantial economic impact. METHODS: We adapted a study design commonly used in the assessment of diagnostic test accuracy. The prioritization made by the Swedish Early Awareness and Alert System prior to marketing authorization comprised the index test and the national drug sales data in the second year post-authorization served as the reference standard. All initial marketing authorization applications for medicinal products processed by the European Medicines Agency between 2010 and 2015 (study population) were classified using the index test and the reference standard. RESULTS: Two hundred and fifty-three new medicinal products processed by the European Medicines Agency comprised the study population. Of these, 71 were prioritized by the Swedish Early Awareness and Alert System and 21 were classified as having substantial economic impact. The sensitivity and positive predictive value were 76.2% and 22.5%, respectively. Subgroup analyses showed that the accuracy of prioritization, in terms of sensitivity, was 100% for antineoplastic/immunomodulating agents. CONCLUSIONS: The Swedish Early Awareness and Alert System identified all new medicines that would go on to have substantial economic impact and prioritized most of these medicines. Our findings provide reassurance to decision makers who rely on the outputs of the Swedish Early Awareness and Alert System to keep informed about new medicines. Moreover, this study also provides valuable insights to stakeholders willing to establish or evaluate their own early awareness and alert activities and systems.

Barriers for Access to New Medicines: Searching for the Balance Between Rising Costs and Limited Budgets.

Introduction: There is continued unmet medical need for new medicines across countries especially for cancer, immunological diseases, and orphan diseases. However, there are growing challenges with funding new medicines at ever increasing prices along with funding increased medicine volumes with the growth in both infectious diseases and non-communicable diseases across countries. This has resulted in the development of new models to better manage the entry of new medicines, new financial models being postulated to finance new medicines as well as strategies to improve prescribing efficiency. However, more needs to be done. Consequently, the primary aim of this paper is to consider potential ways to optimize the use of new medicines balancing rising costs with increasing budgetary pressures to stimulate debate especially from a payer perspective. Methods: A narrative review of pharmaceutical policies and implications, as well as possible developments, based on key publications and initiatives known to the co-authors principally from a health authority perspective. Results: A number of initiatives and approaches have been identified including new models to better manage the entry of new medicines based on three pillars (pre-, peri-, and post-launch activities). Within this, we see the growing role of horizon scanning activities starting up to 36 months before launch, managed entry agreements and post launch follow-up. It is also likely there will be greater scrutiny over the effectiveness and value of new cancer medicines given ever increasing prices. This could include establishing minimum effectiveness targets for premium pricing along with re-evaluating prices as more medicines for cancer lose their patent. There will also be a greater involvement of patients especially with orphan diseases. New initiatives could include a greater role of multicriteria decision analysis, as well as looking at the potential for de-linking research and development from commercial activities to enhance affordability. Conclusion: There are a number of ongoing activities across countries to try and fund new valued medicines whilst attaining or maintaining universal healthcare. Such activities will grow with increasing resource pressures and continued unmet need.

Real-World Use and Outcomes of Olaparib: a Population-Based Cohort Study.

BACKGROUND: Although olaparib, the first poly (adenosine diphosphate [ADP]-ribose) polymerase (PARP) inhibitor approved, has been used in routine clinical practice for over three years, little has been published on its uptake, utilization patterns, and clinical outcomes. OBJECTIVE: To examine real-world use and outcomes of olaparib treatment in Swedish patients during the first three years following regulatory approval. PATIENTS AND METHODS: This is a population-based cohort study using data from the Swedish national registers. All individuals initiating olaparib treatment from regulatory approval to 31 December 2017 were included. The extent of off-label use was assessed based on recorded diagnoses. Ovarian cancer patients were followed until death or the end of the study period. Starting dose and dose adjustments were assessed. Time to olaparib discontinuation and overall survival were plotted using Kaplan-Meier survival curves. RESULTS: We identified 109 patients to whom olaparib was dispensed in Sweden during the study period. Nine of these were prescribed olaparib off-label for either breast or prostate cancer and were excluded from further analyses. Median age among the remaining 100 patients with ovarian cancer was 59 years (range: 42-83). Almost all patients (96%) started on the recommended dose (400 mg [eight capsules] taken twice daily). Dose reductions were explicitly recorded for 14% of patients. Median time to discontinuation was 289 days (95% confidence interval [CI]: 226; 338). Median overall survival from olaparib initiation was 1002 days (95% CI: 676; not calculable). CONCLUSIONS: To our knowledge, this is the first population-based study of olaparib real-world use and outcomes. During the first three years following regulatory approval, olaparib was mainly prescribed to ovarian cancer patients. Ovarian cancer patients stayed on olaparib for a median of 9.5 months and the treatment appeared to be well tolerated.

Trends in medicines procurement by the Brazilian federal government from 2006 to 2013.

The costs of medicines pose a growing burden on healthcare systems worldwide. A comprehensive understanding of current procurement processes provides strong support for the development of effective policies. This study examined Brazilian Federal Government pharmaceutical procurement data provided by the Integrated System for the Administration of General Services (SIASG) database, from 2006 to 2013. Medicine purchases were aggregated by volume and expenditure for each year. Data on expenditure were adjusted for inflation using the Extended National Consumer Price Index (IPCA) for December 31, 2013. Lorenz distribution curves were used to study the cumulative proportion of purchased therapeutic classes. Expenditure variance analysis was performed to determine the impact of each factor, price and/or volume, on total expenditure variation. Annual expenditure on medicines increased 2.72 times, while the purchased volume of drugs increased 1.99 times. A limited number of therapeutic classes dominated expenditure each year. Drugs for infectious diseases drove the increase in expenditures from 2006 to 2009 but were replaced by antineoplastic and immunomodulating agents beginning in 2010. Immunosuppressants (L04), accounted for one third of purchases since 2010, showing the most substantial growth in expenditures during the period (250-fold increase). The overwhelming price-related increase in expenditures caused by these medicines is bound to have a relevant impact on the sustainability of the pharmaceutical supply system. We observed increasing trends in expenditures, especially in specific therapeutic classes. We propose the development and implementation of better medicine procurement systems, and strategies to allow for monitoring of product price, effectiveness, and safety. This must be done with ongoing assessment of pharmaceutical innovations, therapeutic value and budget impact.

Healthcare resource use, comorbidity, treatment and clinical outcomes for patients with primary intracranial tumors: a Swedish population-based register study.

BACKGROUND: Primary intracranial tumors are relatively uncommon and heterogeneous, which make them challenging to study. We coupled data from unique Swedish population-based registries in order to deeper analyze the most common intracranical tumor types. Patient characteristics (e.g. comorbidities), care process measures like adherence to national guidelines, healthcare resource use and clinical outcome was evaluated. MATERIALS AND METHODS: A register-based study including several population-based registries for all patients living in Stockholm-Gotland, diagnosed with primary intracranial tumor between 2001 and 2013 was performed. Patient characteristics were captured and investigated in relation to survival, healthcare resource use (inpatient-, outpatient- and primary care) and treatment process. RESULTS: High-grade glioma and meningioma were the most common tumor types and most patients (76%) were above the age of 40 in the patient population (n = 3664). Older age, comorbidity (Elixhauser comorbidity index) and type of tumor (high-grade glioma) were associated with lower survival rate and increased use of healthcare resources, analyzed for patients living in Stockholm (n = 3031). The analyses of healthcare use and survival showed no differences between males and females, when stratifying by tumor types. Healthcare processes were not always consistent with existing national treatment recommendations for patients with high-grade gliomas (n = 474) with regard to specified lead times, analyzed in the Swedish Brain Tumor Registry, as also observed at the national level. CONCLUSIONS: Age, comorbidity and high-grade gliomas, but not sex, were associated with decreased survival and increased use of healthcare resources. Fewer patients than aimed for in national guidelines received care according to specified lead times. The analysis of comprehensive population-based register data can be used to improve future care processes and outcomes.

Persistence to antihypertensive drug classes: A cohort study using the Swedish Primary Care Cardiovascular Database (SPCCD).

The aim was to study persistence to, and switching between, antihypertensive drug classes and to determine factors associated with poor persistence.This was an observational cohort study. The Swedish Primary Care Cardiovascular Database includes data from medical records, socioeconomic data, filled prescriptions, and hospitalizations from national registries for 75,000 patients with hypertension. Patients included in the study were initiated on antihypertensive drug treatment in primary healthcare in 2006 to 2007. We defined class persistence as the proportion remaining on the initial drug class, including 30 days of gap. Patients with a filled prescription of another antihypertensive drug class after discontinuation of the initial drug, including 30 days of gap, were classified as switchers. Persistence to the various drug classes were compared with that for diuretics.We identified 4997 patients (mean age 60 ±â€Š12 years in men and 63 ±â€Š13 years in women). Out of these, 95 (2%) filled their first prescription for fixed combination therapy and 4902 (98%) for monotherapy, including angiotensin converting enzyme inhibitors (37%), angiotensin receptor blockers (4%), beta blockers (21%), calcium channel blockers (8%), and diuretics (28%). Persistence to the initial drug class was 57% after 1 year and 43% after 2 years. There were no differences in persistence between diuretics and any of the other antihypertensive drug classes, after adjustment for confounders. Discontinuation (all adjusted) was more common in men (P = 0.004), younger patients (P < 0.001), those with mild systolic blood pressure elevation (P < 0.001), and patients born outside the Nordic countries (P < 0.001). Among 1295 patients who switched drug class after their first prescription, only 21% had a blood pressure recorded before the switch occurred; and out them 69% still had high blood pressures.In conclusion, there appears to be no difference in drug class persistence between diuretics and other major antihypertensive drug classes, when factors known to be associated with poor persistence are taken into account.

Healthcare Utilisation and Drug Treatment in a Large Cohort of Patients with Inflammatory Bowel Disease.

BACKGROUND AND AIMS: Crohn's disease [CD] and ulcerative colitis [UC] are chronic diseases associated with a substantial utilisation of healthcare resources. We aimed to estimate the prevalence of inflammatory bowel disease [IBD], CD, and UC and to describe and compare healthcare utilisation and drug treatment in CD and UC patients. METHODS: This was a cross-sectional study of all patients with a recorded IBD diagnosis in Stockholm County, Sweden. Data on outpatient visits, hospitalisations, surgeries, and drug treatment during 2013 were analysed. RESULTS: A total of 13 916 patients with IBD were identified, corresponding to an overall IBD prevalence of 0.65% [CD 0.27%, UC 0.35%, inflammatory bowel disease unclassified 0.04%]; 49% of all IBD patients were treated with IBD-related drugs. Only 3.6% of the patients received high-dose corticosteroids, whereas 32.4% were treated with aminosalicylates [CD 21.2%, UC 41.0%, p < 0.0001]. More CD patients were treated with biologicals compared with UC patients [CD 9.6%, UC 2.9%, p < 0.0001] and surgery was significantly more common among CD patients [CD 3.0%, UC 0.8%, p < 0.0001]. CONCLUSIONS: This study indicates that patients with CD are the group with the highest medical needs. Patients with CD utilised significantly more healthcare resources [including outpatient visits, hospitalisations, and surgeries] than UC patients. Twice as many CD patients received immunomodulators compared with UC patients and CD patients were treated with biologicals three times more often. These results highlight that CD remains a challenge and further efforts are needed to improve care in these patients.

Concomitant use of two or more antipsychotic drugs is common in Sweden.

OBJECTIVES: To assess the prevalence of concomitant use of two or more antipsychotic drugs and other psychotropic drugs in the Swedish population. METHODS: Data for this observational cohort study were collected from the Swedish Prescribed Drug Register including all dispensed drugs to the entire Swedish population (9.4 million inhabitants). We identified all individuals with at least one dispensed prescription of antipsychotic drug during January to June 2008. After 12 months, a second exposure period was chosen. Individuals who were dispensed two or more antipsychotic drugs in both periods were considered long-time users of antipsychotic polypharmacy. RESULTS: In 2008, 1.5% of the Swedish population was dispensed antipsychotic drugs, the majority (75%) using only one antipsychotic drug. Out of individuals who were dispensed 2 or more antipsychotic drugs during the first period, 62% also was also dispensed at least 2 antipsychotic drugs during the second period. A total of 665 different unique combinations were used in 2008. Individuals prescribed two or more antipsychotic drugs during both periods were more often dispensed anxiolytics and sedatives than those who were dispensed only one antipsychotic drug. Elderly were dispensed antipsychotic drugs much more often than younger persons. CONCLUSIONS: In Sweden, 25% of patients dispensed antipsychotic drugs receive a combination of two or more antipsychotic drugs. Individuals who are dispensed antipsychotic polypharmacy are more often dispensed anxiolytics and sedatives than those prescribed only one antipsychotic drug. Long-term observational studies are needed to assess the efficacy and safety of such combinations.

The Swedish Primary Care Cardiovascular Database (SPCCD): 74 751 hypertensive primary care patients.

OBJECTIVE: To describe the Swedish Primary Care Cardiovascular Database, SPCCD. Design. Longitudinal data from electronic medical records, linked to national registers. Setting. 48 primary healthcare centres in urban (south-western Stockholm) and rural (Skaraborg) regions in Sweden. Subjects. Patients diagnosed with hypertension 2001-2008. MAIN OUTCOME MEASURES: Blood pressure (BP) and impact of retrieval of data on BP levels, clinical characteristics, co-morbidity and pharmacological treatment. RESULTS: The SPCCD contains 74 751 individuals, 56% women. Completeness of data ranged from > 99% for drug prescriptions to 34% for smoking habits. BP was recorded in 98% of patients during 2001-2008 and in 63% in 2008. Mean BP based on the last recorded value in 2008 was 142 ± 17/80 ± 13 mmHg. Digit preference in BP measurements differed between the two regions, p < 0.001. Antihypertensive drugs were prescribed in primary healthcare to 88% of the patients in 2008; however, when all prescribers were included 96% purchased their drugs. Cardiovascular co-morbidity and diabetes mellitus were present in 28% and 22%, respectively. CONCLUSION: This large and representative database shows that there is room for improvement of BP control in Sweden. The SPCCD will provide a rich source for further research of hypertension and its complications.

Extraction of electronic health record data in a hospital setting: comparison of automatic and semi-automatic methods using anti-TNF therapy as model.

There is limited experience and methods for extractions of drug therapy data from electronic health records (EHR) in the hospital setting. We have therefore developed and evaluated completeness and consistency of an automatic versus a semi-automatic extraction procedure applied on prescribing and administration of the TNF inhibitor infliximab using a hospital EHR system in Karolinska University Hospital, Sweden. Using two different extraction methods (automatic and semi-automatic), all administered infusions of infliximab between 2007 and 2010 were extracted from a database linked to the EHR system. Extracted data included encrypted personal identity number (PIN), date of birth, sex, time of prescription/administration, healthcare units, prescribed/administered dose and time of admission/discharge. The primary diagnosis (ICD-10) for the treatment with infliximab was extracted by linking infliximab infusions to their corresponding treatment episode. A total of 13,590 infusions of infliximab were administered during the period of 2007 to 2010. Of those were 13,531 (99.6%) possible to link to a corresponding treatment episode, and a primary diagnosis was extracted for 13,530 infusions. Information on encrypted PIN, date of birth, time of prescription/administration, time of admission/discharge and healthcare unit was complete. Information about sex was missing in one patient only. Calculable information about dosage was extracted for 13,300 (98.3%) of all linked infusions. This methodological study showed the potential to extract drug therapy data in a hospital setting. The semi-automatic procedure produced an almost complete pattern of demographics, diagnoses and dosages for the treatment with infliximab.

Forecasting drug utilization and expenditure in a metropolitan health region.

BACKGROUND: New pharmacological therapies are challenging the healthcare systems, and there is an increasing need to assess their therapeutic value in relation to existing alternatives as well as their potential budget impact. Consequently, new models to introduce drugs in healthcare are urgently needed. In the metropolitan health region of Stockholm, Sweden, a model has been developed including early warning (horizon scanning), forecasting of drug utilization and expenditure, critical drug evaluation as well as structured programs for the introduction and follow-up of new drugs. The aim of this paper is to present the forecasting model and the predicted growth in all therapeutic areas in 2010 and 2011. METHODS: Linear regression analysis was applied to aggregate sales data on hospital sales and dispensed drugs in ambulatory care, including both reimbursed expenditure and patient co-payment. The linear regression was applied on each pharmacological group based on four observations 2006-2009, and the crude predictions estimated for the coming two years 2010-2011. The crude predictions were then adjusted for factors likely to increase or decrease future utilization and expenditure, such as patent expiries, new drugs to be launched or new guidelines from national bodies or the regional Drug and Therapeutics Committee. The assessment included a close collaboration with clinical, clinical pharmacological and pharmaceutical experts from the regional Drug and Therapeutics Committee. RESULTS: The annual increase in total expenditure for prescription and hospital drugs was predicted to be 2.0% in 2010 and 4.0% in 2011. Expenditures will increase in most therapeutic areas, but most predominantly for antineoplastic and immune modulating agents as well as drugs for the nervous system, infectious diseases, and blood and blood-forming organs. CONCLUSIONS: The utilisation and expenditure of drugs is difficult to forecast due to uncertainties about the rate of adoption of new medicines and various ongoing healthcare reforms and activities to improve the quality and efficiency of prescribing. Nevertheless, we believe our model will be valuable as an early warning system to start developing guidance for new drugs including systems to monitor their effectiveness, safety and cost-effectiveness in clinical practice.

Nationwide drug-dispensing data reveal important differences in adherence to drug label recommendations on CYP2D6-dependent drug interactions.

AIMS: The study aimed to investigate the clinical adherence to drug label recommendations on important drug-drug interactions (DDIs). Dispensing data on drug combinations involving selective serotonin reuptake inhibitor (SSRI) antidepressants could help to identify areas for intensified medical education. METHODS: This was a retrospective, cross-sectional analysis of individual dispensing data regarding all individuals > or =15 years old in Sweden. The study analysed the prescribing and dispensing of CYP2D6 drugs (metoprolol, donepezil, galantamine, codeine, tamoxifen) together with CYP2D6-blocking SSRIs (paroxetine/fluoxetine) or SSRIs without significant CYP2D6 inhibition (citalopram/escitalopram/sertraline), and the related prescribing of CYP2D6-independent comparator drugs (atenolol, rivastigmine, propoxyphene, anastrozole). Odds were calculated between each CYP2D6 drug and the corresponding comparator drug in patients on fluoxetine/paroxetine and citalopram/escitalopram/sertraline, respectively. The odds ratio (OR) was calculated by dividing the obtained odds in patients on fluoxetine/paroxetine by the corresponding odds in patients on citalopram/escitalopram/sertraline. RESULTS: Compared with patients that were dispensed citalopram/escitalopram/sertraline, patients dispensed fluoxetine/paroxetine had lower prescribing rates of metoprolol (adjusted OR 0.80; 95% confidence interval 0.76, 0.85), donepezil (0.65; 0.49, 0.86) and galantamine (0.58; 0.41, 0.81). In contrast, the use of prodrugs codeine (compared woth propoxyphene) or tamoxifen (compared with anastrozole) was similar among patients on fluoxetine/paroxetine and citalopram/escitalopram/sertraline (adjusted OR 1.03; 0.94, 1.12 and 1.29; 0.96, 1.73, respectively). CONCLUSIONS: Clinically important DDIs that are associated with impaired bioactivation of prodrugs might be more easily neglected in clinical practice compared with DDIs that cause drug accumulation and symptomatic adverse drug reactions.

Initiatives to enhance renin-angiotensin prescribing efficiency in Austria: impact and implications for other countries.

AIM: To assess the utilization of renin-angiotensin drugs, including combinations, in Austria in practice given the limited availability of diuretics, as well as the impact of recent reforms and initiatives on the utilization and expenditure of angiotensin-converting enzyme inhibitors (ACEis) and angiotensin receptor blockers (ARBs), following prescribing restrictions on ARBs immediately after their introduction. METHODS: Utilization of dispensed prescriptions in ambulatory care was captured from 2001 to 2007 using defined daily doses as well as defined daily doses/1000 inhabitants/day for patients covered by the social health-insurance system. The data were provided by the internal data warehouse of Hauptverband der Osterreichischen Sozialversicherungsträger. Total costs in Euros were used for the analysis to facilitate comparisons with earlier studies. RESULTS: There was appreciable utilization of fixed-dose diuretic combinations at between 36 and 38% of all renin-angiotensin products, in line with expectations. The reduction in expenditure/defined daily dose for originator and generic ACEis and their combinations is, again, in line with expectations, mirroring earlier findings for proton pump inhibitors and statins. ARB utilization was just under 27% of all renin-angiotensin products. This is higher than the low utilization rates seen with atorvastatin following its prescribing restrictions, and may reflect the difficulties if restrictions are based on subjective criteria. ARB utilization rates were lower or similar to other countries, who have implemented a different range of demand-side reforms to limit their prescribing with the advent of generic ACEis. CONCLUSION: The results confirm the successful implementation of the latest pricing policies and demand-side measures for generics and originators in Austria. We believe the prescribing restrictions for ARBs reduced their utilization in practice and offer an alternative approach to other demand-side measures.