No difference in between-country variability in use of newly approved orphan and non- orphan medicinal products - a pilot study

<p>Abstract</p> <p>Background</p> <p>Regulators and payers have to strike a balance between the needs of the patient and the optimal allocation of resources. Drugs indicated for rare diseases (orphan medicines) are a special group in this context because of their often high per unit costs. Our objective in this pilot study was to determine, for drugs used in an outpatient setting, how utilisation of centrally authorised drugs varies between countries across a selection of EU member states.</p> <p>Methods</p> <p>We randomly selected five orphan medicines and nine other drugs that were centrally authorised in the European Union between January 2000 and November 2006. We compared utilisation of these drugs in six European Union member states: Austria, Denmark, Finland, Portugal, The Netherlands, and Sweden. Utilisation data were expressed as Defined Daily Doses per 1000 persons per year. Variability in use across countries was determined by calculating the relative standard deviation for the utilisation rates of individual drugs across countries.</p> <p>Results</p> <p>No association between orphan medicine status and variability in use across countries was found (P = 0.52). Drugs with an orphan medicine status were more expensive and had a higher innovation score than drugs without an orphan medicine status.</p> <p>Conclusions</p> <p>The results show that the variability in use of orphan medicines in the different health care systems of the European Union appears to be comparable to the other newly authorised drugs that were included in the analysis. This means that, although strong heterogeneity in access may exist, this heterogeneity is not specific for drugs with an orphan status.</p

Predictors of orphan drug approval in the European Union

Objective: To encourage the development of drugs for rare diseases, orphan drug legislation has been introduced in the USA (1983) and in the EU (2000). Recent literature discusses factors that may influence the development of new orphan medicinal products in the EU. This study aims to identify predictors for successful marketing authorisation of potential orphan drugs in the EU. Methods: A comparison between randomly selected authorised and a matched sample of not-yet-authorised orphan drug designations has been performed. Determinants in the study included characteristics of the indication, of the product and of the sponsor. Data were collected from the public domain only. Results: Orphan drug approval was strongly associated with previous experience of the sponsor in obtaining approval for another orphan drug (OR=17.3, 95% CI=5.6-53.1). Furthermore, existing synthetic entities compared to biotechnology products tended to have a higher likelihood of reaching approval status (OR=3.9, 95% CI=0.9-16.6). Conclusion: This study showed that experience of a company in developing orphan drugs is an important predictor for subsequent authorisation of other orphan drugs. The same applies for existing (synthetic) molecules, for which much knowledge is available. Further research should be directed towards studying the quality of the clinical development program of those designated orphan medicinal products not reaching approval status

Cost-effectiveness analysis of rivaroxaban for treatment and secondary prevention of venous thromboembolism in the Netherlands

Background: Until recently, standard treatment of venous thromboembolism (VTE) concerned a combination of short-term low-molecular-weight heparin (LMWH) and long-term vitamin-K antagonist (VKA). Risk of bleeding and the requirement for regular anticoagulation monitoring are, however, limiting their use. Rivaroxaban is a novel oral anticoagulant associated with a significantly lower risk of major bleeds (hazard ratio=0.54, 95% confidence interval=0.37-0.79) compared to LMWH/VKA therapy, and does not require regular anticoagulation monitoring. Aims: To evaluate the health economic consequences of treating acute VTE patients with rivaroxaban compared to treatment with LMWH/VKA, viewed from the Dutch societal perspective. Methods: A life-time Markov model was populated with the findings of the EINSTEIN phase III clinical trial to analyze cost-effectiveness of rivaroxaban therapy in treatment and prevention of VTE from a Dutch societal perspective. Primary model outcomes were total and incremental quality-adjusted life years (QALYs), as well as life expectancy and costs. Results: Over a patient's lifetime, rivaroxaban was shown to be dominant, with health gains of 0.047 QALYs and cost savings of Euro304 compared to LMWH/VKA therapy. Dominance was robustly present in all sensitivity analyses. Major drivers of the differences between the two treatment arms were related to anticoagulation monitoring (medical costs, travel costs, and loss of productivity) and the occurrence of major bleeds. Conclusion: Rivaroxaban treatment of patients with venous thromboembolism results in health gains and cost savings compared to LMWH/VKA therapy. This conclusion holds for the Dutch setting, both for the societal perspective, as well as the healthcare perspective

Veiligheidswaarschuwingen voor weesgeneesmiddelen in de Europese Unie en de Verenigde Staten

Objective: To determine the frequency and nature of safety-related regulatory actions for orphan drugs in the United States and the European Union. Orphan drugs are often intended for serious or chronically debilitating diseases. None of the studies that have been conducted on safety-related regulatory actions for drugs focused on orphan drugs. Design: Cohort study. Methods: Orphan drugs approved in the United States and/or the European Union between January 2000 and December 2007 were identified (75 US, 44 EU, of which 24 in both regions). Nature, frequency and timing of safety-related regulatory actions were determined for each orphan drug, defined as safety withdrawals, black box warnings, and written communications to healthcare professionals issued by the FDA or the EMA between January 2000 and June 2008. Results: Of the 95 identified orphan drugs 10 (11%) received at least one safety-related regulatory action. No safety withdrawals, 4 black box warnings and 12 written orphan drugs were identified. Probability of a first safety-related regulatory action for orphan drugs was 20% after 8 years of follow-up. Orphan drugs approved by accelerated approval [relative risk (RR) 3.3; 95% CI 1.1 to 10.4), oncologic products (RR 7.8; 95% CI 1.0-63.8) and products for gastrointestinal and metabolism indications (RR 10.4; 95% CI 1.3-87.3) may have a higher risk for a safety-related regulatory action. Conclusion: The probability of a first safety-related regulatory action of an orphan drug was slightly lower than reported for biologicals and new molecular entities. However, detection of safety issues may be complicated by the limited experience with orphan drugs in practical use. Copyright Adis Data Information 2010. All rights reserved

Veiligheidswaarschuwingen voor weesgeneesmiddelen in de Europese Unie en de Verenigde Staten

Objective: To determine the frequency and nature of safety-related regulatory actions for orphan drugs in the United States and the European Union. Orphan drugs are often intended for serious or chronically debilitating diseases. None of the studies that have been conducted on safety-related regulatory actions for drugs focused on orphan drugs. Design: Cohort study. Methods: Orphan drugs approved in the United States and/or the European Union between January 2000 and December 2007 were identified (75 US, 44 EU, of which 24 in both regions). Nature, frequency and timing of safety-related regulatory actions were determined for each orphan drug, defined as safety withdrawals, black box warnings, and written communications to healthcare professionals issued by the FDA or the EMA between January 2000 and June 2008. Results: Of the 95 identified orphan drugs 10 (11%) received at least one safety-related regulatory action. No safety withdrawals, 4 black box warnings and 12 written orphan drugs were identified. Probability of a first safety-related regulatory action for orphan drugs was 20% after 8 years of follow-up. Orphan drugs approved by accelerated approval [relative risk (RR) 3.3; 95% CI 1.1 to 10.4), oncologic products (RR 7.8; 95% CI 1.0-63.8) and products for gastrointestinal and metabolism indications (RR 10.4; 95% CI 1.3-87.3) may have a higher risk for a safety-related regulatory action. Conclusion: The probability of a first safety-related regulatory action of an orphan drug was slightly lower than reported for biologicals and new molecular entities. However, detection of safety issues may be complicated by the limited experience with orphan drugs in practical use. Copyright Adis Data Information 2010. All rights reserved

Cost-effectiveness analysis of rivaroxaban for treatment and secondary prevention of venous thromboembolism in the Netherlands

Background: Until recently, standard treatment of venous thromboembolism (VTE) concerned a combination of short-term low-molecular-weight heparin (LMWH) and long-term vitamin-K antagonist (VKA). Risk of bleeding and the requirement for regular anticoagulation monitoring are, however, limiting their use. Rivaroxaban is a novel oral anticoagulant associated with a significantly lower risk of major bleeds (hazard ratio = 0.54, 95% confidence interval = 0.37–0.79) compared to LMWH/VKA therapy, and does not require regular anticoagulation monitoring. Aims: To evaluate the health economic consequences of treating acute VTE patients with rivaroxaban compared to treatment with LMWH/VKA, viewed from the Dutch societal perspective. Methods: A life-time Markov model was populated with the findings of the EINSTEIN phase III clinical trial to analyze cost-effectiveness of rivaroxaban therapy in treatment and prevention of VTE from a Dutch societal perspective. Primary model outcomes were total and incremental quality-adjusted life years (QALYs), as well as life expectancy and costs. Results: Over a patient’s lifetime, rivaroxaban was shown to be dominant, with health gains of 0.047 QALYs and cost savings of €304 compared to LMWH/VKA therapy. Dominance was robustly present in all sensitivity analyses. Major drivers of the differences between the two treatment arms were related to anticoagulation monitoring (medical costs, travel costs, and loss of productivity) and the occurrence of major bleeds. Conclusion: Rivaroxaban treatment of patients with venous thromboembolism results in health gains and cost savings compared to LMWH/VKA therapy. This conclusion holds for the Dutch setting, both for the societal perspective, as well as the healthcare perspective

Cost-effectiveness analysis of rivaroxaban for treatment and secondary prevention of venous thromboembolism in the Netherlands

Background: Until recently, standard treatment of venous thromboembolism (VTE) concerned a combination of short-term low-molecular-weight heparin (LMWH) and long-term vitamin-K antagonist (VKA). Risk of bleeding and the requirement for regular anticoagulation monitoring are, however, limiting their use. Rivaroxaban is a novel oral anticoagulant associated with a significantly lower risk of major bleeds (hazard ratio = 0.54, 95% confidence interval = 0.37–0.79) compared to LMWH/VKA therapy, and does not require regular anticoagulation monitoring. Aims: To evaluate the health economic consequences of treating acute VTE patients with rivaroxaban compared to treatment with LMWH/VKA, viewed from the Dutch societal perspective. Methods: A life-time Markov model was populated with the findings of the EINSTEIN phase III clinical trial to analyze cost-effectiveness of rivaroxaban therapy in treatment and prevention of VTE from a Dutch societal perspective. Primary model outcomes were total and incremental quality-adjusted life years (QALYs), as well as life expectancy and costs. Results: Over a patient’s lifetime, rivaroxaban was shown to be dominant, with health gains of 0.047 QALYs and cost savings of €304 compared to LMWH/VKA therapy. Dominance was robustly present in all sensitivity analyses. Major drivers of the differences between the two treatment arms were related to anticoagulation monitoring (medical costs, travel costs, and loss of productivity) and the occurrence of major bleeds. Conclusion: Rivaroxaban treatment of patients with venous thromboembolism results in health gains and cost savings compared to LMWH/VKA therapy. This conclusion holds for the Dutch setting, both for the societal perspective, as well as the healthcare perspective