Donor Safety in Haemapheresis: Development of an Internet-Based Registry for Comprehensive Assessment of Adverse Events from Healthy Donors.

BACKGROUND: Currently, there is an extensive but highly inconsistent body of literature regarding donor adverse events (AEs) in haemapheresis. As the reports diverge with respect to types and grading of AEs, apheresis procedures and machines, the range of haemapheresis-related AEs varies widely from about 0.03% to 6.6%. METHODS: The German Society for Transfusion Medicine and Immunohaematology (DGTI) formed a 'Haemapheresis Vigilance Working Party' (Arbeitsgemeinschaft Hämapheresevigilanz; AGHV) to create an on-line registry for comprehensive and comparable AE assessment with all available apheresis devices in all types of preparative haemapheresis: plasmapheresis (PLS), plateletpheresis (PLT), red blood cell apheresis, all kind of leukaphereses (autologous/allogeneic blood stem cell apheresis, granulocyte apheresis, lymphocyte/monocyte apheresis) and all possible types of multi-component apheresis. To ensure the comparability of the data, the AGHV adopted the 'Standard for Surveillance of Complications Related to Blood Donation' from the International Society for Blood Transfusion in cooperation with the International Haemovigilance Network (IHN) and the American Association of Blood Banks for AE acquisition and automated evaluation. The registry is embedded in a prospective observational multi-centre study with a study period of 7 years. RESULTS: A preliminary evaluation encompassed the time period from January, 2012 to December, 2015. During this time, the system proved to be safe and stable. Out of approximately 345,000 haemaphereses 16,477 AEs were reported (4.9%) from 20 participating centres. The majority of AEs occurred in PLSs (63%), followed by PLT (34.5%) and SC (2.2%). Blood access injuries (BAI) accounted for about 55% of the supplied AEs, whereas citrate toxicity symptoms, vasovagal reactions and technical events (e.g. disposable leakages, software failures) rather equally affected haemaphereses at 8-15%. Out of 12,348 finalized AEs, 8,759 (70.1%) were associated with a procedure-related break-off, with BAI being the prevailing cause (5,463/8,759; 62.4%). An automated centre- and procedure-specific AE evaluation according to the latest IHN standard and AGHV pre-settings is available within a few minutes. CONCLUSIONS: An on-line electronic platform for comprehensive assessment and centre-specific automated evaluation of AEs in haemaphereses has been developed and proved to be stable and safe over a period of 4 years.

Influence of lifting prescribing restrictions for losartan on subsequent sartan utilization patterns in Austria: implications for other countries.

INTRODUCTION: Prescribing restrictions for angiotensin receptor blockers (ARBs) limited their utilization in Austria. Recently, generic losartan became available with its prescribing restrictions lifted while still in place for patented ARBs. OBJECTIVES: The main aim of this study is to assess the impact of the lifting of the prescribing restriction on utilization of losartan in ambulatory care versus other single ARBs, expenditure per defined daily dose (DDD) of losartan as well as total ARB expenditure and utilization of ARB combinations. Finally, to suggest potential measures that could be introduced to further enhance ARB-prescribing efficiency. METHODOLOGY: A quasi-experimental study of the utilization of different ARBs alone or in fixed dose combinations using a segmented time series. Utilization measured in DDDs, defined as 'the average maintenance dose of a drug when used in its major indication in adults'. Costs measured as total expenditure for different ARBs as well as their expenditure/DDD. RESULTS: Losartan utilization increased significantly following the withdrawal of prescribing restrictions (p > 0.001). Utilization of single-sourced ARBs also increased , but the growth rate was appreciably reduced once restrictions were lifted for losartan (p > 0.01). As a result, total expenditure of single ARBs increased but at an appreciably lower rate than utilization, helped by total expenditure/DDD for losartan declining by 78% over the study period. There was continuing appreciable utilization of fixed-dose combinations. CONCLUSION: Lifting of prescribing restrictions for losartan significantly enhanced its utilization, increasing ARB-prescribing efficiency, providing direction to other European authorities. Additional reforms are being considered to further switch utilization away from single-sourced ARBs to additionally improve prescribing efficiency as more multiple sourced ARBs become available.

Comparing policies to enhance prescribing efficiency in Europe through increasing generic utilization: changes seen and global implications.

AIM: The aim of this article was to evaluate the influence of different demand-side measures to enhance the prescribing of generics in ambulatory care based on cross-national comparisons. METHODS: An observational retrospective study was conducted using administrative databases from across Europe, documenting changes in reimbursed utilization and expenditure of different proton pump inhibitors (PPIs) and statins between 2001 and 2007, alongside different reforms to enhance prescribing efficiency. Utilization was converted to defined daily doses (DDDs) and expenditures were converted to euros. Demand-side measures were collated under the '4 Es'--education, engineering, economics and enforcement--to enable comparisons on the nature and intensity of reforms between countries. RESULTS: There were considerable differences in the utilization of generics and patent-protected PPIs and statins among Western European countries. Decreased utilization of omeprazole and simvastatin, alongside increased utilization of esomeprazole, atorvastatin and rosuvastatin, was seen in countries with limited demand-side measures to counteract commercial pressures. Prescribing restrictions, or a combination of education, prescribing targets and financial incentives, had the greatest influence on enhancing the utilization of omeprazole and simvastatin. For example, there was a threefold reduction in the utilization of atorvastatin in Austria following prescribing restrictions. Multiple demand-side interventions generally had a greater influence than single interventions, with the impact appearing additive. Multiple interventions coupled with initiatives to lower prices of generics considerably enhanced prescribing efficiency. CONCLUSION: This cross-national study has demonstrated considerable variation in the utilization and expenditure of PPIs and statins across Europe, providing opportunities to further improve prescribing efficiency. The '4 Es' do provide an understandable methodology to document and compare the influence of different demand-side measures, with the influence varying by their extent and intensity. Further reforms are essential given current financial pressures. Consequently, further research will concentrate on the potential to develop a scoring system to help predict the possible impact of different demand-side measures on future utilization patterns.

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.

Impact of reimbursement changes on statin use among patients with diabetes in Austria.

BACKGROUND: Statins have evolved as cornerstones of cardiovascular prevention in patients with diabetes. They are effective and can be cost-effective therapies, but increased use imposes a sizeable short-term burden on payors of health care. These have used various instruments to steer appropriate use of such treatment. It was the purpose of this study to examine the effect of two reimbursement policy changes of statin therapy in patients with diabetes in Austria. METHODS: Retrospective cohort study; time-series analysis. From Austrian sickness funds claims, we identified a closed cohort of 68,953 patients receiving treatment for diabetes in the first quarter of 2004. From April 2004 - December 2005, we ascertained use of statins for each monthly interval. Patients were censored at death. We used pseudo-experimental time-series regression to evaluate the effect of two policy changes on statin use and cost overall, as well as on the use of preferred versus non-preferred statins. RESULTS: Statin use among Austrian patients with diabetes increased from 20.6% to 24.9% during the time period. A policy change essentially expanding reimbursement for statins from secondary to primary prevention among patients with diabetes had no discernible effect on the observed trends in statin use. Another policy change that imposed random chart review for appropriateness of prescription of non-preferred statins including atorvastatin 10 mg yielded a marked drop in use of atorvastatin 10 mg and increase in the use of preferred statins, while leaving overall trends in statin use unaffected. CONCLUSIONS: Quantitative evaluation of new policies can provide important insights into the effectiveness und utility of such changes.

Use of Generics-A Critical Cost Containment Measure for All Healthcare Professionals in Europe?

Pharmaceutical expenditures in ambulatory care rose rapidly in Europe in the 1990s and early 2000s. This was typically faster than other components of healthcare spending, leading to reforms to moderate future growth. A number of these centered on generic medicines with measures to lower reimbursed prices as well as enhance their prescribing and dispensing. The principal objective of this paper is to review additional measures that some European countries can adopt to further reduce reimbursed prices for generics. Secondly, potential approaches to address concerns with generics when they arise to maximize savings. Measures to enhance the prescribing of generics will also briefly be discussed. A narrative review of the extensive number of publications and associated references from the co-authors was conducted supplemented with known internal or web-based articles. In addition, health authority and health insurance databases, principally from 2001 to 2007, were analyzed to assess the impact of the various measures on price reductions for generic omeprazole and generic simvastatin vs. pre-patent loss prices, as well as overall efficiency in Proton Pump Inhibitor (PPI) and statin prescribing. The various initiatives generally resulted in considerable lowering of the prices of generics as well as specifically for generic omeprazole and generic simvastatin vs. pre-patent loss prices. At one stage in the UK, generic simvastatin was just 2% of the originator price. These measures also led to increased efficiency for PPI and statin prescribing with reimbursed expenditure for the PPIs and statins either falling or increasing at appreciably lower rates than increases in utilization. A number of strategies have also been introduced to address patient and physician concerns with generics to maximize savings. In conclusion, whilst recent reforms have been successful, European countries must continue learning from each other to fund increased volumes and new innovative drugs as resource pressures grow. Policies regarding generics and their subsequent impact on reimbursement and utilization of single sourced products will continue to play a key role to release valuable resources. However, there must continue to be strategies to address concerns with generics when they exist.

Impact of recent reforms in Austria on utilization and expenditure of PPIs and lipid-lowering drugs: implications for the future.

AIM: To assess the impact of a plethora of reforms and initiatives introduced in Austria since 2002 on the actual utilization and expenditure of proton pump inhibitors and statins. METHODS: Utilization of dispensed prescriptions in ambulatory care was captured from 2001 to 2007 using defined daily doses (DDD) as well as DDDs/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 from the payer's perspective. RESULTS: The reduction in the expenditure per DDD for both generic PPIs and statins was generally in line with expectations at over 60% of originator prices before multiple sources became available. There was also increased utilization of generics following the range of demand-side initiatives. This was 89.5% for generic omeprazole versus total omeprazole and 95.1% for generic simvastatin versus total simvastatin by the end of 2007. The utilization of atorvastatin fell substantially from 36.5% of all statins in 2002 to 10.7% by the end of 2007 following restrictions on its prescribing to patients not achieving target lipid levels with, for instance, generic simvastatin. The combined initiatives reduced expenditure per DDD for the PPIs and the statins by 41 and 60%, respectively, in 2007 versus 2001 levels. This reduction translated into lower expenditure for the statins in 2007 versus 2001 despite substantially increased utilization. CONCLUSION: The results provide examples to other European countries, especially the restrictions on atorvastatin utilization. Nevertheless, further initiatives will be needed to conserve resources as utilization rates grow in chronic disease areas. This includes potential lessons from other European countries.

Assessment of complement activation during membrane-based plasmapheresis procedures.

Previous studies have suggested that plasmapheresis procedures using a separation membrane may activate the complement system and release anaphylatoxins. This study determines the content in C3a/C3a(des Arg) and C5a/C5a(des Arg) in plasma donations obtained by the new Haemonetics Filter Core (FC) procedure and compares it to Baxter Autopheresis C (Auto-C). FC performs sequential blood centrifugation and plasma filtration on a microporous polyethersulfone membrane, while Auto-C removes blood cells by simultaneous gravitation and filtration on a rotating nylon membrane. One group of 34 donors donated on FC and two groups of 30 and 10 donors on Auto-C. Plasma aliquots were taken from the plasma units within 30 min of the end of the collection procedures, frozen at < -30 degrees C and assessed for C3a and C5a at various time points of storage. Mean C3a/C3a(des Arg) in FC plasma (N = 34) was 1,151 (range: 526-2,991), 1,092 (range: 349-3498), and 507 (range: 307-815) ng/ml at time of collection and after 6 and 12 months of storage, respectively. Respective C5a/C5a(des Arg) was 26.6 (range 4.9-74), 18.9 (9.5-42.6), and 30.9 (range: 10.7-62.3) ng/ml. Mean C3a/C3a(des Arg) was higher in Auto-C (P < 0.001): 4,724 ng/ml (N = 10; range: 2,400-7 ,360) and > 4,149 ng/ml (N = 30; 2,408- > 6,430) after 3 and 18 months storage, respectively. Mean C5a/C5a(des Arg) was 32.1 ng/ml (N = 30; range: 10.6-57.2) after 18 months of storage. Complement activation in FC plasmas appears limited compared to Auto-C, suggesting better biocompatibility of this collection device and/or a favourable impact of the sequential cell centrifugation/filtration technology used. Further studies are needed to explain differences in complement activation between apheresis procedures and to assess clinical impacts, if any.