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A Framework To Guide The Use Of Real-World Evidence To Support Evaluation Of Relative Effectiveness Of New Medicines
A488
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
of experts in the field of health economics has highlighted areas in which degrees could be modified to make them even more desirable or relevant, however an important matter still remains – who is best placed to determine the content of Masters degrees – academia, industry, or both in collaboration? PHP274 A Framework To Guide The Use Of Real-World Evidence To Support Evaluation Of Relative Effectiveness Of New Medicines Stegenga H1, Chambers M2, Jonsson P3, Thwaites R4, Garner S5 Institute for Health and Care Excellence, London, UK, 2MCHCE, London, UK, 3National Institute for Health and Care Excellence (NICE), Manchester, UK, 4Takeda, London, UK, 5National Institute for Health and Care Excellence (NICE), London, UK 1National
Objectives: Payers and health technology assessors (HTAs) are interested in evidence of effectiveness outside the clinical trial setting. The use of real-world data (RWD) to estimate relative effectiveness before marketing authorisation presents a variety of operational and methodological issues. An objective of the IMI GetReal project (www.imi-getreal.eu) is to develop a decision-making framework to guide the potential use and generation of RWD, and inform the design of strategies to provide better information about relative effectiveness of new medicines. Methods: Work Package 1 of GetReal engaged multiple stakeholders to develop the decisionmaking framework, including patient organisations, clinicians, academic specialists, clinical trialists, pharmaceutical companies, European regulators, HTA bodies and payers. Case study workshops in five disease areas were used to examine different analytical methods and study designs using RWD to provide estimates of relative effectiveness, and to elicit stakeholders’ views on the usefulness and acceptability of each option. Results: The framework consists of five key components: 1) overview of current policies related to real-world evidence (RWE) of effectiveness; 2) comprehensive review of sources of RWE; 3) catalogue of real-world study designs outlining key characteristics; 4) description of state of-the-art analytical approaches making use of RWD; and 5) stakeholder perspectives on the use of RWD for decision making. The core of the framework is a decision-making algorithm taking stakeholders through questions on the potential need for RWE and subsequently the potential RWD analyses and study designs. Conclusions: A wide range of stakeholders provided views on the value and acceptability of different RWD study designs and analyses. The resulting framework will help pharmaceutical R&D to assess options for integrating real-world study designs in medicine development programmes, support engagements between pharmaceutical R&D and decision-makers and drive forward the scientific and policy agenda in this area. PHP275 Japan Health Care Act Reform: Toward Decentralization And Integrated Health Care System Toumi M1, Fukushima A2, Murata K2, Onishi Y2 1Faculté de Médecine, Laboratoire de Santé Publique, Aix-Marseille Université, Marseille, France, 2Creativ-Ceutical, Tokyo, Japan
Objectives: Japanese health care system experienced important changes to cope with population ageing. The government passed a new Health bill in 2015 to complement the 2012 one. The objective of this research is to describe how those two reforms will impact the health care landscape in Japan. Methods: We did a literature review and analysed health care reform acts of 2012 and 2015 Results: Main directions are: Enhanced decentralisation with transfer of power to Prefecture (regional government). Regional governance will be established to accountably manage health plan. Prefectures are responsible for health care plan for cancer, stroke, acute myocardial infarction, diabetes mellitus, psychiatric disease, pediatric care. But also to develop home care delivery. Integrated health care are under Prefecture responsibility with case managers who coordinate health care for chronic and multimorbid patients. More than 300 diseases are eligible to case management. Equity in health care access is high on the agenda to ensure equitable accessibility to health services. the two markers will be: mortality and use of expensive therapies (with special focus on oncology). New incentives to encourage patients to use GP for hospital referral and discourage patients self-decision. At the same time large hospitals will be requested to ensure health care coordination with all community based providers to prevent admission and re-admision. Hospital ensuring postdischarge follow-up in coordination with ambulatory care providers will receive subsidies The unique social security and tax number will be established in 2018 to support the extension of E-health record networks currently piloted in targeted catchment area. Conclusions: The Japanese Health care system is operating a reform toward prefecture accountability, and health care integration supported by development of unique E-Health record, incentive for information sharing, case managers, and strengthening GP’s role. This process is established smoothly but should improve health care quality and cost.
HEALTH CARE USE & POLICY STUDIES – Health Technology Assessment Programs PHP276 Understanding Health Technology Assessment (HTA) Bodies in Major European Markets: Systematic Evaluation in 10 EU Countries Nanavaty M, Gala S, Nyandege A, Ramesh V, Mwamburi M Market Access Solutions LLC, Raritan, NJ, USA
Objectives: Value of new drugs are evaluated through HTAs in at least 48 countries. Their influence on evidence-based healthcare decision-making includes determining level of coverage in Europe. The characteristics, attributes and methodologies employed by HTA bodies vary significantly. Navigation through the HTA application process in multiple countries is a challenging endeavor. The objective was to characterize the different HTA methodologies used in major European markets. Methods: We conducted a systematic review of HTA bodies’ documentation of 10 markets in Europe (England & Wales, France, Germany, Italy, Netherlands,
Poland, Scotland, Spain, Sweden and Switzerland) and on peer-reviewed publications through PubMed. For Italy and Spain, a prominent regional HTA was evaluated, Lombardy and Catalonia respectively. Over 350 HTA characteristics, attributes assessed and methodologies used were assessed. Results: Among 10 HTA systems evaluated, England & Wales (NICE), Netherlands (CVZ) and Poland (AOTM) use explicitly stated incremental cost-effectiveness ratio (ICER) thresholds of £20,000-£30,000/QALY, € 40,000/QALY and € 26,500/QALY respectively. Three markets use implicit ICER thresholds based on the cost-effectiveness studies of previously approved drugs/technologies. Seven HTA bodies involve the general public, 6 publish reports online, 5 review within 2-6 months, and 3 allow for some form of appeal. We describe the various characteristics, attributes, and methodologies by payer architypes across Europe and discuss the associated pros and cons. Numerous HTA bodies provide support during submission process but others lack important information in the public domain. Conclusions: HTA bodies vary significantly and can be categorized as ones using explicit ICER thresholds and ones using implicit ICER thresholds in addition to other factors. Understanding the nuances related to HTA evaluation processes in multiple countries regarding involvement the general public, duration of review process, and ability to appeal, methods of technology assessment, preference on active controls, or availability of submission support will help manufacturers plan accordingly. PHP277 Concordance of Health Technology Assessment Recommendations of Diabetes, Hepatitis, Oncology and Epilepsy Pharmaceutical Products by Five Agencies within Europe: An Interrater Reliability and Association Analysis Abugri I1, Braun D1, Manfred E1, Gerbsch N2 1Cardiff University in collaboration with Hochschule Fresenius, Idstein, Germany, 2Bundesverband der Pharmazeutischen Industrie e.V, Berlin, Germany
Objectives: In recent years, a “fourth hurdle” is increasingly adopted by health care systems within Europe that requires product sponsors to show value for their products, usually at national levels. Thus, the same product is assessed by different national agencies. Therefore, this study seeks to assess the level of agreement HTA recommendations of similar product-indication pairs across five countries, test the association between HTA agencies and HTA recommendations. Methods: HTA recommendations on Diabetes, Hepatitis, Oncology and Epilepsy pharmaceutical products appraised by IQWiG, HAS, NICE, SMC and ZIN between January 2011 and 15th March 2016 were comparatively analyzed. Products were included if at least two HTA agency appraises it within the study timeline. Absolute percent agreement and Kappa statistic were used to measure the level agreements. The null hypothesis of independence between HTA agencies and recommendations they issue were explored using correspondence analysis and the strength of association evaluated. Results: There was a significant discordance in HTA recommendations across study agencies with an average percentage of divergence of 69.2%. The level of agreement varied between agencies and across therapeutic areas. Agreement between IQWiG and other agencies was poor to slight in all therapeutic areas except with HAS in the appraisal of Diabetic products. Between NICE and SMC was moderate to strong agreements. The strength of association between agencies and their HTA decisions, measured in Cramer` V, were moderate for diabetes and hepatitis products (0.639 p< 0.000 and 0.535 p< 0.000) and low for oncology products (0.327 p< 0.000). Conclusions: It was concluded that disparity in HTA recommendations among agencies exists leading to a possible non-uniform market access of pharmaceutical products across study countries. Differences in methodology, value judgment, and preferences were the major drivers of divergence. Thus, appreciation of agency-specific preference and value judgment are important to the MAH in obtaining positive HTA outcomes. PHP278 Cadth’s $50,000 Cost-Effectiveness Threshold: Fact or Fiction? Griffiths EA1, Vadlamudi NK2 1PAREXEL, London, UK, 2PAREXEL, Hyderabad, India
Objectives: The Canadian Agency for Drugs and Technologies in Health (CADTH) does not formally state a cost-effectiveness threshold for new medicines. A threshold of CAD$50,000 per quality-adjusted life-year (QALY) is often cited as a benchmark, but there is limited evidence to confirm the accuracy of this figure. To inform future submissions, CADTH appraisals were reviewed to determine whether a cost-effectiveness threshold can be inferred. Methods: All publicly-available CADTH appraisals (assessed under the common drug review [CDR] or pan-Canadian Oncology Drug Review [pCODR]) from January 2010 to May 2016 were reviewed. The decision, rationale, and economic analysis presented were extracted. Results: Between January 2010 and May 2016, CADTH published 279 drug appraisals: 215 under CDR and 64 under pCODR. 29 submissions (10%) were recommended, 163 (58%) were recommended with restrictions, and 87 (31%) were not recommended. Cost-utility analyses were presented in 63/64 pCODR submissions and 83/215 CDR submissions, with other forms of economic analysis (e.g. cost-minimization, cost comparison) in the remaining submissions. Incremental cost-effectiveness ratios (ICER, expressed in cost per-QALY) were often revised upwards by the review committee, and submissions were commonly recommended with restrictions conditional on improved cost-effectiveness. In several appraisals, CADTH included wording such as “a [X%] price reduction would be required for the ICER to fall to [~$50,000]” or “the ICER was < $50,000 per-QALY in most scenarios”, suggesting that a $50,000 threshold may have been considered. However, the range of ICERs for recommended submissions was dominant to $131,100, with several being accepted with ICERs > $50,000. Conclusions: There is some evidence to suggest that CADTH’s cost-effectiveness threshold is ~$50,000 per-QALY, but this is neither consistently applied nor explicitly stated. Further, CADTH will often make decisions based on alternative forms of economic analysis. Although cost-effectiveness analysis has limitations, formally stating a cost-effectiveness threshold would improve transparency and may improve equitable access to new medicines.
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
of experts in the field of health economics has highlighted areas in which degrees could be modified to make them even more desirable or relevant, however an important matter still remains – who is best placed to determine the content of Masters degrees – academia, industry, or both in collaboration? PHP274 A Framework To Guide The Use Of Real-World Evidence To Support Evaluation Of Relative Effectiveness Of New Medicines Stegenga H1, Chambers M2, Jonsson P3, Thwaites R4, Garner S5 Institute for Health and Care Excellence, London, UK, 2MCHCE, London, UK, 3National Institute for Health and Care Excellence (NICE), Manchester, UK, 4Takeda, London, UK, 5National Institute for Health and Care Excellence (NICE), London, UK 1National
Objectives: Payers and health technology assessors (HTAs) are interested in evidence of effectiveness outside the clinical trial setting. The use of real-world data (RWD) to estimate relative effectiveness before marketing authorisation presents a variety of operational and methodological issues. An objective of the IMI GetReal project (www.imi-getreal.eu) is to develop a decision-making framework to guide the potential use and generation of RWD, and inform the design of strategies to provide better information about relative effectiveness of new medicines. Methods: Work Package 1 of GetReal engaged multiple stakeholders to develop the decisionmaking framework, including patient organisations, clinicians, academic specialists, clinical trialists, pharmaceutical companies, European regulators, HTA bodies and payers. Case study workshops in five disease areas were used to examine different analytical methods and study designs using RWD to provide estimates of relative effectiveness, and to elicit stakeholders’ views on the usefulness and acceptability of each option. Results: The framework consists of five key components: 1) overview of current policies related to real-world evidence (RWE) of effectiveness; 2) comprehensive review of sources of RWE; 3) catalogue of real-world study designs outlining key characteristics; 4) description of state of-the-art analytical approaches making use of RWD; and 5) stakeholder perspectives on the use of RWD for decision making. The core of the framework is a decision-making algorithm taking stakeholders through questions on the potential need for RWE and subsequently the potential RWD analyses and study designs. Conclusions: A wide range of stakeholders provided views on the value and acceptability of different RWD study designs and analyses. The resulting framework will help pharmaceutical R&D to assess options for integrating real-world study designs in medicine development programmes, support engagements between pharmaceutical R&D and decision-makers and drive forward the scientific and policy agenda in this area. PHP275 Japan Health Care Act Reform: Toward Decentralization And Integrated Health Care System Toumi M1, Fukushima A2, Murata K2, Onishi Y2 1Faculté de Médecine, Laboratoire de Santé Publique, Aix-Marseille Université, Marseille, France, 2Creativ-Ceutical, Tokyo, Japan
Objectives: Japanese health care system experienced important changes to cope with population ageing. The government passed a new Health bill in 2015 to complement the 2012 one. The objective of this research is to describe how those two reforms will impact the health care landscape in Japan. Methods: We did a literature review and analysed health care reform acts of 2012 and 2015 Results: Main directions are: Enhanced decentralisation with transfer of power to Prefecture (regional government). Regional governance will be established to accountably manage health plan. Prefectures are responsible for health care plan for cancer, stroke, acute myocardial infarction, diabetes mellitus, psychiatric disease, pediatric care. But also to develop home care delivery. Integrated health care are under Prefecture responsibility with case managers who coordinate health care for chronic and multimorbid patients. More than 300 diseases are eligible to case management. Equity in health care access is high on the agenda to ensure equitable accessibility to health services. the two markers will be: mortality and use of expensive therapies (with special focus on oncology). New incentives to encourage patients to use GP for hospital referral and discourage patients self-decision. At the same time large hospitals will be requested to ensure health care coordination with all community based providers to prevent admission and re-admision. Hospital ensuring postdischarge follow-up in coordination with ambulatory care providers will receive subsidies The unique social security and tax number will be established in 2018 to support the extension of E-health record networks currently piloted in targeted catchment area. Conclusions: The Japanese Health care system is operating a reform toward prefecture accountability, and health care integration supported by development of unique E-Health record, incentive for information sharing, case managers, and strengthening GP’s role. This process is established smoothly but should improve health care quality and cost.
HEALTH CARE USE & POLICY STUDIES – Health Technology Assessment Programs PHP276 Understanding Health Technology Assessment (HTA) Bodies in Major European Markets: Systematic Evaluation in 10 EU Countries Nanavaty M, Gala S, Nyandege A, Ramesh V, Mwamburi M Market Access Solutions LLC, Raritan, NJ, USA
Objectives: Value of new drugs are evaluated through HTAs in at least 48 countries. Their influence on evidence-based healthcare decision-making includes determining level of coverage in Europe. The characteristics, attributes and methodologies employed by HTA bodies vary significantly. Navigation through the HTA application process in multiple countries is a challenging endeavor. The objective was to characterize the different HTA methodologies used in major European markets. Methods: We conducted a systematic review of HTA bodies’ documentation of 10 markets in Europe (England & Wales, France, Germany, Italy, Netherlands,
Poland, Scotland, Spain, Sweden and Switzerland) and on peer-reviewed publications through PubMed. For Italy and Spain, a prominent regional HTA was evaluated, Lombardy and Catalonia respectively. Over 350 HTA characteristics, attributes assessed and methodologies used were assessed. Results: Among 10 HTA systems evaluated, England & Wales (NICE), Netherlands (CVZ) and Poland (AOTM) use explicitly stated incremental cost-effectiveness ratio (ICER) thresholds of £20,000-£30,000/QALY, € 40,000/QALY and € 26,500/QALY respectively. Three markets use implicit ICER thresholds based on the cost-effectiveness studies of previously approved drugs/technologies. Seven HTA bodies involve the general public, 6 publish reports online, 5 review within 2-6 months, and 3 allow for some form of appeal. We describe the various characteristics, attributes, and methodologies by payer architypes across Europe and discuss the associated pros and cons. Numerous HTA bodies provide support during submission process but others lack important information in the public domain. Conclusions: HTA bodies vary significantly and can be categorized as ones using explicit ICER thresholds and ones using implicit ICER thresholds in addition to other factors. Understanding the nuances related to HTA evaluation processes in multiple countries regarding involvement the general public, duration of review process, and ability to appeal, methods of technology assessment, preference on active controls, or availability of submission support will help manufacturers plan accordingly. PHP277 Concordance of Health Technology Assessment Recommendations of Diabetes, Hepatitis, Oncology and Epilepsy Pharmaceutical Products by Five Agencies within Europe: An Interrater Reliability and Association Analysis Abugri I1, Braun D1, Manfred E1, Gerbsch N2 1Cardiff University in collaboration with Hochschule Fresenius, Idstein, Germany, 2Bundesverband der Pharmazeutischen Industrie e.V, Berlin, Germany
Objectives: In recent years, a “fourth hurdle” is increasingly adopted by health care systems within Europe that requires product sponsors to show value for their products, usually at national levels. Thus, the same product is assessed by different national agencies. Therefore, this study seeks to assess the level of agreement HTA recommendations of similar product-indication pairs across five countries, test the association between HTA agencies and HTA recommendations. Methods: HTA recommendations on Diabetes, Hepatitis, Oncology and Epilepsy pharmaceutical products appraised by IQWiG, HAS, NICE, SMC and ZIN between January 2011 and 15th March 2016 were comparatively analyzed. Products were included if at least two HTA agency appraises it within the study timeline. Absolute percent agreement and Kappa statistic were used to measure the level agreements. The null hypothesis of independence between HTA agencies and recommendations they issue were explored using correspondence analysis and the strength of association evaluated. Results: There was a significant discordance in HTA recommendations across study agencies with an average percentage of divergence of 69.2%. The level of agreement varied between agencies and across therapeutic areas. Agreement between IQWiG and other agencies was poor to slight in all therapeutic areas except with HAS in the appraisal of Diabetic products. Between NICE and SMC was moderate to strong agreements. The strength of association between agencies and their HTA decisions, measured in Cramer` V, were moderate for diabetes and hepatitis products (0.639 p< 0.000 and 0.535 p< 0.000) and low for oncology products (0.327 p< 0.000). Conclusions: It was concluded that disparity in HTA recommendations among agencies exists leading to a possible non-uniform market access of pharmaceutical products across study countries. Differences in methodology, value judgment, and preferences were the major drivers of divergence. Thus, appreciation of agency-specific preference and value judgment are important to the MAH in obtaining positive HTA outcomes. PHP278 Cadth’s $50,000 Cost-Effectiveness Threshold: Fact or Fiction? Griffiths EA1, Vadlamudi NK2 1PAREXEL, London, UK, 2PAREXEL, Hyderabad, India
Objectives: The Canadian Agency for Drugs and Technologies in Health (CADTH) does not formally state a cost-effectiveness threshold for new medicines. A threshold of CAD$50,000 per quality-adjusted life-year (QALY) is often cited as a benchmark, but there is limited evidence to confirm the accuracy of this figure. To inform future submissions, CADTH appraisals were reviewed to determine whether a cost-effectiveness threshold can be inferred. Methods: All publicly-available CADTH appraisals (assessed under the common drug review [CDR] or pan-Canadian Oncology Drug Review [pCODR]) from January 2010 to May 2016 were reviewed. The decision, rationale, and economic analysis presented were extracted. Results: Between January 2010 and May 2016, CADTH published 279 drug appraisals: 215 under CDR and 64 under pCODR. 29 submissions (10%) were recommended, 163 (58%) were recommended with restrictions, and 87 (31%) were not recommended. Cost-utility analyses were presented in 63/64 pCODR submissions and 83/215 CDR submissions, with other forms of economic analysis (e.g. cost-minimization, cost comparison) in the remaining submissions. Incremental cost-effectiveness ratios (ICER, expressed in cost per-QALY) were often revised upwards by the review committee, and submissions were commonly recommended with restrictions conditional on improved cost-effectiveness. In several appraisals, CADTH included wording such as “a [X%] price reduction would be required for the ICER to fall to [~$50,000]” or “the ICER was < $50,000 per-QALY in most scenarios”, suggesting that a $50,000 threshold may have been considered. However, the range of ICERs for recommended submissions was dominant to $131,100, with several being accepted with ICERs > $50,000. Conclusions: There is some evidence to suggest that CADTH’s cost-effectiveness threshold is ~$50,000 per-QALY, but this is neither consistently applied nor explicitly stated. Further, CADTH will often make decisions based on alternative forms of economic analysis. Although cost-effectiveness analysis has limitations, formally stating a cost-effectiveness threshold would improve transparency and may improve equitable access to new medicines.