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Drugs for Rare (And Ultra-Rare) Diseases in Europe: Analysis of Budget Impact and Cost Drivers
A598
VA L U E I N H E A LT H 1 9 ( 2 0 1 6 ) A 3 4 7 – A 7 6 6
Double Helix Consulting, London, UK
Objectives: The National Institute of Health and Care Excellence (NICE) publishes guidance on new and existing highly specialised medicines within the NHS in England. The highly specialised technologies (HST) programme considers rare disease treatments in development pre-marketing authorisation (20 months) as well as new indications (15 months). This research sets out to assess the recommendations and explore limitations and requests imposed by NICE. Methods: A literature review assessing guidance published on the NICE HST website from inception date until 15 June 2016 was conducted. Information on the approval decision and restrictions or recommendations imposed were extracted and analysed. Results: Two products have been assessed by the NICE HST review committee since inception. These included eculizumab for atypical haemolytic uraemic syndrome (HST1) and elosulfase alfa for mucopolysaccharidosis type IVa. A further five products were noted as guidance ‘under development’; due to be published between July and December 2016. Both products were approved for funding in the UK but a range of restrictions and arrangements were imposed. Of particular note were the requests for coordination of eculizumab through an expert centre, monitoring systems to record the number of patients, treatment dose and duration and development of a research programme to evaluate treatment termination or dose adjustment. In the case of elosulfase alfa, within the managed access agreement (MAA), a protocol was set out for price setting following data collection (in addition to the patient access scheme) in order to manage potential financial risk. Conclusions: The HST route provides a relatively new route to market for high value, low volume products in the rare disease space. Introduction of stringent monitoring criteria and methods for data collection are being introduced. It will be important to assess how these are implemented and provide precedent for future products in development. PSY129 Utilisation and Expenditure Beyond HTA: A Case Study of Lidocaine 5% Medicated Plaster Finnigan K1, Daly M1, Clarke S1, Geraghty N2, Barry M2 Medicines Management Programme, Dublin, Ireland, 2National Centre for Pharmacoeconomics, Dublin, Ireland
1HSE
Objectives: Lidocaine 5% medicated plaster was licensed in Ireland in Oct 2010 for the symptomatic relief of neuropathic pain associated with previous herpes zoster infection (post-herpetic neuralgia, PHN) in adults and reimbursed since January 2011. The Medicines Management Programme (MMP) was established in 2013 to promote safe, effective and cost-effective prescribing. It monitors the utilisation of high cost drugs. The aim of this study is to review the increasing utilisation and expenditure on lidocaine 5% medicated plasters in Ireland. Methods: Pharmacy claims data from the General Medical Services (GMS) scheme, which covers 60% of public drug expenditure in Ireland, was analysed using Microsoft Excel® and JMP® 8. The number of patients and expenditure on lidocaine 5% medicated plasters was reviewed from January 2012 to December 2015. Results: Monthly GMS expenditure increased from approximately € 0.4million to € 2million with a corresponding increase in patient numbers from 2,994 to 16,412 from January 2012 to December 2015. Total expenditure in 2015 was € 24.2million, a € 16.7million increase from 2012. The MMP advised the Health Service Executive (HSE) in accordance with the Health Act 2013 (section 18(4)), to examine its cost-effectiveness and this analysis was completed by the National Centre for Pharmacoeconomics (NCPE) in September 2015. The NCPE concluded that this product did not demonstrate costeffectiveness and only approximately 5-10% of patients receive the product for the licensed indication of PHN. The HSE negotiated a price reduction from € 93.96 to € 77.52 per pack in March 2016. The MMP has issued prescribing guidance to highlight the inappropriate prescribing of this medication as there is a lack of clinical evidence to support unlicensed use. Conclusions: This study demonstrates the potential for higher drug utilisation and increased budget impact when prescribing is not restricted to the licensed indication post evaluation. It also highlights the importance of medicines management post Health Technology Assessment (HTA).
PSY130 Choice of First Opioid Prescription and the Transitions from Acute to Long Term Opioid Use – Findings from Big Data Shah AB1, Hayes C1, Martin BC2 1University of Arkansas for Medical Sciences, Little Rock, AR, USA, 2University of Arkansas for Medical Sciences College of Pharmacy, Little Rock, AR, USA
Objectives: We sought to determine the relationship between the choice of the first opioid prescription and the likelihood of continued opioid use at 1 and 3 years. Methods: We identified cancer-free persons with new opioid use episodes in a nationally representative commercially insured database from 20062015. The first opioid prescription was categorized into 5 mutually exclusive types: Long Acting Opioids, Low Potency Opioids, Hydrocodone Short Acting, Oxycodone Short Acting and Other Short Acting. Persons were followed until they discontinued opioids (a gap of at least 180 days without opioid use), lost eligibility, or study end (September 2015). Kaplan Meier survival curves were used to estimate the median days of opioid use and the probability of continuing opioid use at 1 and 3 years for each type first opioid prescription group. Results: A total of 1,316,061 patients, with an average age and duration of enrollment of 44.54 years (±14.56 years) and 2.48 years (±2.04 years) were included. The highest probability of one and three year continued opioid use was found among those initiated on a long-acting opioid (28.08% and 19.26%), followed by patients initiated on a low potency opioid (13.73% and 6.84%). Among patients initiated with low potency opioids, over 60% of the patients who continued opioid use beyond one or three years were still on short acting low potency opioids. The probability of long term use for those starting on hydrocodone, oxycodone or other short acting opioids was similar with three year probabilities of continued use between 2.98% and 2.50%. Conclusions: When physicians consider long term opioid therapy for pain, they may be selecting low potency opioids such as tramadol or a long acting opioid. Further research evaluating
the long term efficacy and safety of low potency opioids must be conducted before physicians use them for chronic pain management. PSY131 Prescribing Patterns of Opioids Dispensed by Pharmacies in South Africa Truter I Nelson Mandela Metropolitan University, Port Elizabeth, South Africa
Objectives: Tramadol was the most often prescribed opioid in a South African study conducted on 2011 data of a medical insurance scheme database. The primary aim of this study was to analyse the prescribing patterns of opioids dispensed by community pharmacies to determine if opioid prescribing patterns were similar if a different prescriber and dispensing database was used. Methods: A retrospective, cross-sectional drug utilisation study was conducted on a 2013 pharmacy dispensing database in South Africa. All records for ATC subgroup N02A were extracted and analysed. Results: A total of 212 527 opioids were dispensed to 105 118 patients at a total cost of R30 227 819.83 (average cost of R142.23 per product). Twelve different active ingredients or active ingredient combinations were prescribed. Tramadol, an atypical opioid, in combination with paracetamol accounted for 71.90% of products, followed by tramadol alone (22.74% of products). These two products therefore accounted for 94.64% of all the products dispensed in ATC subgroup N02A. The originator product of the combination of tramadol and paracetamol accounted for 90.08% of products dispensed, with only 2.00% generic prescribing. Oxycodone (N02AA05, 1.99%) and fentanyl (N02AB03, 1.10%) were the only other opioids dispensed that accounted for more than 1% of the total number of opioids dispensed. In the 2013 study, all the prescriptions were dispensed by community pharmacies. In the 2011 study on a medical insurance scheme database, most prescriptions for opioids were issued by private hospitals (62.89%), followed by pharmacies (24.42%) and general medical practices (12.16%). If only pharmacies are considered, 94.54% of prescriptions were for tramadol or the combination of tramadol and paracetamol (67.59% for tramadol in combination with paracetamol, and 26.95% for tramadol alone). Conclusions: The dispensing patterns of opioids by community pharmacies were nearly identical in the community pharmacy and medical insurance scheme studies, with tramadol clearly dominating opioid prescribing. PSY132 Drugs for Rare (And Ultra-Rare) Diseases in Europe: Analysis of Budget Impact and Cost Drivers Schlander M1, Stenner K2, Gandjour A3 for Innovation & Valuation in Health Care (InnoVal-HC), Wiesbaden, Germany, 2Frankfurt School of Finance and Management, Frankfurt am Main, Germany, 3Frankfurt School of Finance & Management, Frankfurt, Germany
1Institute
Objectives: The objective of the present study was (1) to review recent studies reporting health care expenditures for (or budgetary impact of) drugs for rare diseases in Europe, and (2) to contribute to our understanding of the cost drivers of drugs for non-oncological ultra-rare diseases (URDs) by means of an empirical analysis in Germany. Methods: A systematic search for relevant studies was conducted in PubMed (1966 – December 2014) and in abstracts in congress proceedings. In addition, annual treatment costs of drugs for non-oncological URDs in Germany were analyzed with respect to five explanatory variables: availability of other treatment indications, availability of alternative treatments for the same indication, oral administration, prevalence of the disease, and evidence for a health benefit. Results: A total of seven studies with specific estimates of the budget impact of drugs for rare diseases for a total of nine countries were identified. Annual per-capita spending for orphan drugs ranges from € 0.48 in Russia to € 16 in France. Only one study on URDs was identified. In Germany, annual treatment costs per patient for drugs for non-oncological URDs varies between € 1,175 and € 726,890. In all regression specifications, a significant inverse relationship between availability of alternative treatments for the same indication and annual treatment costs was found. In addition, log prevalence was found to have a significant inverse relationship with log annual treatment cost. Conclusions: Despite annual treatment costs in the range of several hundreds of thousands of euros for some of the URD drugs, per-capita spending for URD drugs is relatively small. In this study, using German market data, an inverse relationship between prevalence and annual treatment costs was found specifically for drugs for non-oncological URDs. PSY133 Status of Orphan Drugs and Reimbursement Recommendations and Decisions in Analysed European Countries Kawalec P, Malinowski K Jagiellonian University Medical College, Krakow, Poland
Objectives: The aim was to investigate a connection between reimbursement recommendations and decisions in case of drugs with orphan status. We examined if the rare or ultra-rare status of the disease could influence the reimbursement recommendations and decisions in considered countries. Methods: We analysed the Orphanet database to collect data on all drugs with orphan status authorized by the European Medicines Agency. The following HTA Agencies were considered: NICE (England), G-BA (Germany), AOTMiT (Poland), ZIN (Netherlands), TLV (Sweden), SMC (Scotland), AWMSG (Wales), HAS (France) and data on HTA recommendations and reimbursement status for these drugs were collected. Descriptive statistics using counts and percentages were employed to analyse data, then we calculated odds for gaining positive or negative recommendations in each agency. Agreement between type of recommendation and final reimbursement decision was also investigated for each analysed country for orphan as well as ultra-orphan drugs using kappa coefficient of agreement. Results: We analysed data on 101 drugs with orphan status; 87 of drugs were used for rare diseases and 14 for ultra rare diseases. Statistical analysis revealed that odds for positive recommendations for drugs for ultra rare disease varied from 0.4 to 0.8 compared to drugs for rare diseases only, although no statistical significance was observed. The agreement between
VA L U E I N H E A LT H 1 9 ( 2 0 1 6 ) A 3 4 7 – A 7 6 6
Double Helix Consulting, London, UK
Objectives: The National Institute of Health and Care Excellence (NICE) publishes guidance on new and existing highly specialised medicines within the NHS in England. The highly specialised technologies (HST) programme considers rare disease treatments in development pre-marketing authorisation (20 months) as well as new indications (15 months). This research sets out to assess the recommendations and explore limitations and requests imposed by NICE. Methods: A literature review assessing guidance published on the NICE HST website from inception date until 15 June 2016 was conducted. Information on the approval decision and restrictions or recommendations imposed were extracted and analysed. Results: Two products have been assessed by the NICE HST review committee since inception. These included eculizumab for atypical haemolytic uraemic syndrome (HST1) and elosulfase alfa for mucopolysaccharidosis type IVa. A further five products were noted as guidance ‘under development’; due to be published between July and December 2016. Both products were approved for funding in the UK but a range of restrictions and arrangements were imposed. Of particular note were the requests for coordination of eculizumab through an expert centre, monitoring systems to record the number of patients, treatment dose and duration and development of a research programme to evaluate treatment termination or dose adjustment. In the case of elosulfase alfa, within the managed access agreement (MAA), a protocol was set out for price setting following data collection (in addition to the patient access scheme) in order to manage potential financial risk. Conclusions: The HST route provides a relatively new route to market for high value, low volume products in the rare disease space. Introduction of stringent monitoring criteria and methods for data collection are being introduced. It will be important to assess how these are implemented and provide precedent for future products in development. PSY129 Utilisation and Expenditure Beyond HTA: A Case Study of Lidocaine 5% Medicated Plaster Finnigan K1, Daly M1, Clarke S1, Geraghty N2, Barry M2 Medicines Management Programme, Dublin, Ireland, 2National Centre for Pharmacoeconomics, Dublin, Ireland
1HSE
Objectives: Lidocaine 5% medicated plaster was licensed in Ireland in Oct 2010 for the symptomatic relief of neuropathic pain associated with previous herpes zoster infection (post-herpetic neuralgia, PHN) in adults and reimbursed since January 2011. The Medicines Management Programme (MMP) was established in 2013 to promote safe, effective and cost-effective prescribing. It monitors the utilisation of high cost drugs. The aim of this study is to review the increasing utilisation and expenditure on lidocaine 5% medicated plasters in Ireland. Methods: Pharmacy claims data from the General Medical Services (GMS) scheme, which covers 60% of public drug expenditure in Ireland, was analysed using Microsoft Excel® and JMP® 8. The number of patients and expenditure on lidocaine 5% medicated plasters was reviewed from January 2012 to December 2015. Results: Monthly GMS expenditure increased from approximately € 0.4million to € 2million with a corresponding increase in patient numbers from 2,994 to 16,412 from January 2012 to December 2015. Total expenditure in 2015 was € 24.2million, a € 16.7million increase from 2012. The MMP advised the Health Service Executive (HSE) in accordance with the Health Act 2013 (section 18(4)), to examine its cost-effectiveness and this analysis was completed by the National Centre for Pharmacoeconomics (NCPE) in September 2015. The NCPE concluded that this product did not demonstrate costeffectiveness and only approximately 5-10% of patients receive the product for the licensed indication of PHN. The HSE negotiated a price reduction from € 93.96 to € 77.52 per pack in March 2016. The MMP has issued prescribing guidance to highlight the inappropriate prescribing of this medication as there is a lack of clinical evidence to support unlicensed use. Conclusions: This study demonstrates the potential for higher drug utilisation and increased budget impact when prescribing is not restricted to the licensed indication post evaluation. It also highlights the importance of medicines management post Health Technology Assessment (HTA).
PSY130 Choice of First Opioid Prescription and the Transitions from Acute to Long Term Opioid Use – Findings from Big Data Shah AB1, Hayes C1, Martin BC2 1University of Arkansas for Medical Sciences, Little Rock, AR, USA, 2University of Arkansas for Medical Sciences College of Pharmacy, Little Rock, AR, USA
Objectives: We sought to determine the relationship between the choice of the first opioid prescription and the likelihood of continued opioid use at 1 and 3 years. Methods: We identified cancer-free persons with new opioid use episodes in a nationally representative commercially insured database from 20062015. The first opioid prescription was categorized into 5 mutually exclusive types: Long Acting Opioids, Low Potency Opioids, Hydrocodone Short Acting, Oxycodone Short Acting and Other Short Acting. Persons were followed until they discontinued opioids (a gap of at least 180 days without opioid use), lost eligibility, or study end (September 2015). Kaplan Meier survival curves were used to estimate the median days of opioid use and the probability of continuing opioid use at 1 and 3 years for each type first opioid prescription group. Results: A total of 1,316,061 patients, with an average age and duration of enrollment of 44.54 years (±14.56 years) and 2.48 years (±2.04 years) were included. The highest probability of one and three year continued opioid use was found among those initiated on a long-acting opioid (28.08% and 19.26%), followed by patients initiated on a low potency opioid (13.73% and 6.84%). Among patients initiated with low potency opioids, over 60% of the patients who continued opioid use beyond one or three years were still on short acting low potency opioids. The probability of long term use for those starting on hydrocodone, oxycodone or other short acting opioids was similar with three year probabilities of continued use between 2.98% and 2.50%. Conclusions: When physicians consider long term opioid therapy for pain, they may be selecting low potency opioids such as tramadol or a long acting opioid. Further research evaluating
the long term efficacy and safety of low potency opioids must be conducted before physicians use them for chronic pain management. PSY131 Prescribing Patterns of Opioids Dispensed by Pharmacies in South Africa Truter I Nelson Mandela Metropolitan University, Port Elizabeth, South Africa
Objectives: Tramadol was the most often prescribed opioid in a South African study conducted on 2011 data of a medical insurance scheme database. The primary aim of this study was to analyse the prescribing patterns of opioids dispensed by community pharmacies to determine if opioid prescribing patterns were similar if a different prescriber and dispensing database was used. Methods: A retrospective, cross-sectional drug utilisation study was conducted on a 2013 pharmacy dispensing database in South Africa. All records for ATC subgroup N02A were extracted and analysed. Results: A total of 212 527 opioids were dispensed to 105 118 patients at a total cost of R30 227 819.83 (average cost of R142.23 per product). Twelve different active ingredients or active ingredient combinations were prescribed. Tramadol, an atypical opioid, in combination with paracetamol accounted for 71.90% of products, followed by tramadol alone (22.74% of products). These two products therefore accounted for 94.64% of all the products dispensed in ATC subgroup N02A. The originator product of the combination of tramadol and paracetamol accounted for 90.08% of products dispensed, with only 2.00% generic prescribing. Oxycodone (N02AA05, 1.99%) and fentanyl (N02AB03, 1.10%) were the only other opioids dispensed that accounted for more than 1% of the total number of opioids dispensed. In the 2013 study, all the prescriptions were dispensed by community pharmacies. In the 2011 study on a medical insurance scheme database, most prescriptions for opioids were issued by private hospitals (62.89%), followed by pharmacies (24.42%) and general medical practices (12.16%). If only pharmacies are considered, 94.54% of prescriptions were for tramadol or the combination of tramadol and paracetamol (67.59% for tramadol in combination with paracetamol, and 26.95% for tramadol alone). Conclusions: The dispensing patterns of opioids by community pharmacies were nearly identical in the community pharmacy and medical insurance scheme studies, with tramadol clearly dominating opioid prescribing. PSY132 Drugs for Rare (And Ultra-Rare) Diseases in Europe: Analysis of Budget Impact and Cost Drivers Schlander M1, Stenner K2, Gandjour A3 for Innovation & Valuation in Health Care (InnoVal-HC), Wiesbaden, Germany, 2Frankfurt School of Finance and Management, Frankfurt am Main, Germany, 3Frankfurt School of Finance & Management, Frankfurt, Germany
1Institute
Objectives: The objective of the present study was (1) to review recent studies reporting health care expenditures for (or budgetary impact of) drugs for rare diseases in Europe, and (2) to contribute to our understanding of the cost drivers of drugs for non-oncological ultra-rare diseases (URDs) by means of an empirical analysis in Germany. Methods: A systematic search for relevant studies was conducted in PubMed (1966 – December 2014) and in abstracts in congress proceedings. In addition, annual treatment costs of drugs for non-oncological URDs in Germany were analyzed with respect to five explanatory variables: availability of other treatment indications, availability of alternative treatments for the same indication, oral administration, prevalence of the disease, and evidence for a health benefit. Results: A total of seven studies with specific estimates of the budget impact of drugs for rare diseases for a total of nine countries were identified. Annual per-capita spending for orphan drugs ranges from € 0.48 in Russia to € 16 in France. Only one study on URDs was identified. In Germany, annual treatment costs per patient for drugs for non-oncological URDs varies between € 1,175 and € 726,890. In all regression specifications, a significant inverse relationship between availability of alternative treatments for the same indication and annual treatment costs was found. In addition, log prevalence was found to have a significant inverse relationship with log annual treatment cost. Conclusions: Despite annual treatment costs in the range of several hundreds of thousands of euros for some of the URD drugs, per-capita spending for URD drugs is relatively small. In this study, using German market data, an inverse relationship between prevalence and annual treatment costs was found specifically for drugs for non-oncological URDs. PSY133 Status of Orphan Drugs and Reimbursement Recommendations and Decisions in Analysed European Countries Kawalec P, Malinowski K Jagiellonian University Medical College, Krakow, Poland
Objectives: The aim was to investigate a connection between reimbursement recommendations and decisions in case of drugs with orphan status. We examined if the rare or ultra-rare status of the disease could influence the reimbursement recommendations and decisions in considered countries. Methods: We analysed the Orphanet database to collect data on all drugs with orphan status authorized by the European Medicines Agency. The following HTA Agencies were considered: NICE (England), G-BA (Germany), AOTMiT (Poland), ZIN (Netherlands), TLV (Sweden), SMC (Scotland), AWMSG (Wales), HAS (France) and data on HTA recommendations and reimbursement status for these drugs were collected. Descriptive statistics using counts and percentages were employed to analyse data, then we calculated odds for gaining positive or negative recommendations in each agency. Agreement between type of recommendation and final reimbursement decision was also investigated for each analysed country for orphan as well as ultra-orphan drugs using kappa coefficient of agreement. Results: We analysed data on 101 drugs with orphan status; 87 of drugs were used for rare diseases and 14 for ultra rare diseases. Statistical analysis revealed that odds for positive recommendations for drugs for ultra rare disease varied from 0.4 to 0.8 compared to drugs for rare diseases only, although no statistical significance was observed. The agreement between