- Email: [email protected]
Perspectives of Implementation And Development of HTA System In Ukraine: Use In Decision Making
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on simple event diaries (e.g. seizures) or measures developed prior to the release of the FDA PRO guidance. Importantly, 27.5% of all approved drugs were for an oncology-related condition (versus 15.5% between 2006 and 2010). The proportion of claims granted is lower than what was reported between 2006 and 2010 (24.1%), and prior to the release of the PRO guidance (30%, 1997-2002). Conclusions: PRO claims continue to be approved by FDA, although at a lower rate than previously reported. This may be partly explained by the increase in the number of oncology products with study designs that may not support PRO labeling as per regulatory guidance. The lack of PRO labeling based on secondary endpoints only may be a reflection of sponsors’ reluctance to capture PRO related value messages to regulatory standards when PROs are not required to support the indication. The acceptance of PRO measures developed prior to the release of the PRO guidance for the purpose of labeling reflects ‘regulatory flexibility’ adopted by the FDA reviewers. PHP165 IMPROVING PATIENT SAFETY THROUGH COMMUNICATION: A BRAZILIAN PERSPECTIVE Bueno C C , Almeida P R , Clark L G , Clark O A Evidencias - Kantar Health, Campinas, Brazil .
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Objectives: Ineffective communication among healthcare professionals is one of the leading causes of medical errors and patient harm. Several studies have shown that communication failures were implicated at the root of over 70% of sentinel events. Also, in the acute care setting, communication failures lead to increases in patient harm, length of stay, and resource use. The objective of this study is to analyze how communication problems can directly affect patient safety (PS) in Brazilian hospitals, as well as the government initiatives to deal with this issue. Methods: We assessed PS data in organs such as the Ministry of Health (MOH), National Agency of Sanitary Surveillance (ANVISA) and National Health Confederation (CNS), as well as Brazilian regulations on patient safety. Additionally, a literature review was performed in Medline and SciELO databases using the mesh terms “patient safety” and “communication”, among others. Results: ANVISA and MOH have instituted a series of activities focused on PS and quality in health services. In 2013, they launched the National Program for Patient Safety, which establishes communication as one of the essential factors for PS. However, failures still occur frequently in Brazilian hospitals. In Brazil, the incidence of adverse events in hospital setting is 7.6%, and 66.7% of them are preventable. Studies indicate that communication problems occur in up to 70% of reported cases of adverse events in hospitals. Furthermore, communication failures are responsible for 32% of errors in ICU. Extended data on the literature review will appear on the poster. Conclusions: Communication breakdown is a key factor contributing to most cases of patient harm, and this harm continues to occur at very high levels. Improving communication for safety in healthcare is an imperative, especially in Brazil, where adverse events in hospitals have high rates and PS still has a long way to go to become really effective. PHP166 PATTERNS OF BIOEQUIVALENCE RECOMMENDATIONS AND TRENDS OF ABBREVIATED NEW DRUG APPLICATIONS APPROVAL OVER TIME Wittayanukorn S 1, Babiskin A 1, Dutcher S 1, Pu X1, Hu M 1, Zhao L 1, Lionberger R 2 of Quantitative Methods and Modeling, Office of Research Standards, Office of Generic Drugs, Center of Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD, USA, 2Office of Research Standards, Office of Generic Drugs, Center of Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD, USA .
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Objectives: The Office of Generic Drugs (OGD) began publishing bioequivalence (BE) recommendations for specific (complex/non-complex) products in 2007 to support generic drug development. Nevertheless, little is known about patterns of BE recommendations. The purpose of this study was to describe patterns of BE recommendations published by the OGD and trends of abbreviated new drug application (ANDA) approvals over time. Methods: An analysis of approved ANDAs was conducted at the time of approval from 2007-June 2015(n= 4,028), using data from the publically available product-specific BE guidance website, Drugs@FDA, and National Drug Code (NDC) directory databases. Guidance patterns, trends, and the distribution of ANDAs approved that have BE recommendations compared to those ANDAs approved that did not have BE recommendations were examined using descriptive statistics and chi-squared tests. Results: A total of 1,439 published BE recommendations between 2007-September 2015 were identified. Number of recommendations was highest in 2008(n= 316) but the trend was inconsistent (P< 0.05). Corticosteroids had the highest proportion of BE recommendations (3.68%), followed by opioid agonists (3.51%), and nonsteroidal anti-inflammatory drugs (3.08%). Compared with BE recommendations, opioid agonists (4.31%), antiepileptics (4.25%), and angiotensin II receptor blockers (3.43%) were pharmacologic classes with a high proportion of approved ANDAs(P< 0.05). Overall, 66.68% of ANDAs approved referenced drug products associated with a BE recommendation and the average ANDA numbers(±SD), excluding solutions/injectables, per recommendation was 2.58(±4.35). An analysis of ANDAs approved over time demonstrated the share of ANDAs approved with recommendations was consistently higher than the share of ANDAs approved without recommendations(P < 0.05). Conclusions: Numbers of published BE recommendations varied over time. BE recommendations cover a wide range of pharmacologic classes and the proportion of ANDAs approved with recommendations was high. Non-complex products may not require recommendations and findings support the continuing need for BE recommendations for more complex products that may further facilitate ANDA approvals.
HEALTH CARE USE & POLICY STUDIES – Health Technology Assessment Programs PHP167 Analysis of Real-World Evidence And Real-World Data By Conitec, Brazilian Hta Agency
Nita M E 1, Riveros B S 2, Vaz P 3, Mussolino F 3 1FIPE - Fundaçã Institute de Pesquisas Econômicas, Sao Paulo, Brazil, 2University of Glascow, Glascow, UK, 3HEADS, Sao Paulo, Brazil .
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Objectives: Very little information is available about the demand from CONITEC, the Brazilian HTA agency, for real-world evidence (RWE), moreover, few real-world data (RWD) sources are available. The objective of this study was to examine reports from CONITEC to identify patters of RWE and sources being used. Methods: The reports from CONITEC are publicly available at the Ministry of Health (MoH). All reports from January to September of 2015 were reviewed for RWE and RWD information. In total, 37 seven reports were analyzed in this research. The assessed variables included type of technology, therapeutic area (TA), source of demand, final decision, RWE and RWD sources. Results: In total, there were 33 inclusion demand and 4 were exclusion. The most frequently technology requested were drugs, 31 out of 37. Infectious disease (8), immunobiologics (6), and cancer (4) were the most frequent TAs. A total of 24 demands were from organizations within MoH. Among external demands the majority were from pharmaceutical industries. Brazilian Unified Health System (SUS) database, the DATASUS, was the RWD source most frequently quoted in the final reports (19), and epidemiology, resources used and treatment patterns were the most used RWE. Drug costs were more frequently quoted (17) from the official MoH Journal (DOU). Observational studies were quoted in 12 reports, including chart reviews, and non-randomized interventional trials were used to support the decisions. Surveys were used in two reports to identify treatment patterns. Conclusions: CONITEC is increasingly demanding RWE in the reports. By expanding the use of existing RWD, as DATASUS, a new concern arises with the way RWE are being retrieved and statistically adjusted in the reports. It is noticeable the concentration of RWE in MoH demands compared to other claimants. From demands without RWE, estimations and assumptions were taken into account. PHP168 Not ready for the real world? The role of non-RCT evidence in health technology assessment Griffiths E A 1, Vadlamudi N K 2 1PAREXEL, London, UK, 2PAREXEL International, Hyderabad, India .
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Objectives: The ‘evidence hierarchy’ of randomized controlled trial (RCT) over nonRCT evidence is well-established, and RCTs remain the ‘gold standard’ for regulatory and health technology assessment (HTA) submissions. However, adaptive pathways will likely necessitate the future use of non-RCT evidence in the HTA-decisionmaking process. To inform future submissions, we assessed acceptance based on non-RCT evidence across four HTA agencies, and explored agencies’ reactions to such study designs. Methods: All single HTA appraisals in 2015 from NICE, CADTH, PBAC, and IQWiG were included in the analysis, including resubmissions. Multiple technology appraisals, vaccines, and requests for advice were excluded. The recommendation, reasoning behind the recommendation, and whether or not a non-RCT design trial (e.g. single-arm or observational) was included in the submission, were extracted. Results: A total of 189 appraisals were extracted: 49 for CADTH, 59 for PBAC, 36 for NICE, and 45 for IQWiG. Non-RCT evidence was considered in 5 CADTH appraisals (10%), 12 PBAC appraisals (20%), 13 NICE appraisals (36%), and no IQWiG appraisals. Only three treatments were given a positive recommendation solely on the basis on non-RCT evidence in 2015: daclatasvir for HCV GT3 infection (CADTH, PBAC), ponatinib for chronic myeloid leukemia (PBAC), and darunavir/cobicistat for HIV infection (CADTH). The remaining submissions included additional RCT evidence or were rejected due to high uncertainty about treatment effect. Non-RCT evidence did, however, contribute to a favorable outcome in some submissions, e.g. idelalisib for CLL and tolvaptan for PKD (NICE). Conclusions: NICE, CADTH, and PBAC will consider non-RCT studies such as real-world data and single-arm trials in certain circumstances, but are critical of the lower certainty of the evidence. The contribution of non-RCT evidence to the HTA-decision-making process is currently minor; however, as adaptive pathways and personalized treatment strategies gain momentum, HTA bodies will need to become more flexible in their approach to assessing non-RCT evidence. PHP169 Perspectives of Implementation And Development of HTA System In Ukraine: Use In Decision Making Zaliska O 1, Piniazhko O 1, Kosyachenko K 2, Tolubaiev V 1 1Danylo Halytsky Lviv National Medical University, Lviv, Ukraine, 2UA HTA, Kyiv, Ukraine .
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Objectives: In Ukraine there is an urgent need for rational allocation of scarce resources and priority settings in health care in the current economic situation. The study aims to examine and outline actual issues of HTA system implementation in Ukraine. Methods: A review and expert interviews were conducted towards the key stages of implementation of HTA system in the recent years in Ukraine. Results: There is no central national HTA agency currently functioning in Ukraine. Simultaneously, some HTA-related procedures are applied for the development of State Drug Formulary and national treatment protocols. Nongovernmental organization (NGO) UA HTA and representatives of academia are facilitating the process of HTA implementation in real-life practice for the decision making process. In the recent years, the articles on HTA introduction, methodical recommendations for postgraduate studies were published by Ukrainian scientists. In 2013-2014 the capacity building and training courses on HTA were carried out by NGO UA HTA in collaboration with foreign colleagues. The Commission on development of HTA system of the MOH works on the introduction of HTA since 2014. We propose the implementation of “light” model of HTA in Ukraine: HTA reports have to be prepared by applicant for reimbursement, minimal use of public funds will provide high performance of HTA reports and high value of HTA in health care policy, national HTA agency have to become a “goalkeeper” while providing critical appraisal of HTA reports. National HTA Guidelines have to be approved within legal framework. Adaptation of international HTA reports to local environment is of high importance. Conclusions: Importantly, in the next years there is a necessity to implement international requirements to HTA in order to prioritize procurements of medicines, their financing by government, reimbursement decisions in order to
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improve the market access, medicines prescription and patients’ health outcomes according to the developed scientific methodology in Ukraine. PHP170 From Talk To Action: Emerging Pharmaceutical Value Frameworks In The United States Capuano C 1, Divi B 2, Singhania A 3, Suponcic S 4 1Navigant Life Sciences, Boston, MA, USA, 2Navigant Life Sciences, Chicago, IL, USA, 3Navigant Life Sciences, Los Angeles, CA, USA, 4Navigant Life Sciences, Lawrenceville, NJ, USA .
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Objectives: There is an acceleration and proliferation of new pharmaceutical innovation that is being introduced at premium prices. At the same time, payers and providers in the United States face unprecedented pressure to manage healthcare budgets and value-based decision-making is top-of-mind. A group of policy entrepreneurs have recently proposed several novel frameworks for assessing and comparing therapeutic value. This research reviews these frameworks and ways in which they are being used to manage access to new pharmaceutical innovation. Methods: Secondary research on recently introduced value frameworks with US origin was conducted (ACA-AHA, ASCO, Drug Abacus, ICER, NCCN). Each tool was characterized based on inputs considered and key similarities/differences were summarized. Primary research was conducted with ten managed care pharmacy executives to assess the extent to which these frameworks are being considered in decision-making or adopted as a standard assessment technique. Results: Existing value frameworks were found to differ with regards to consideration of: patient-centric metrics; indirect benefits; unmet need; and burden of illness. Interviewed managed care executives have increasing awareness of emerging value frameworks and a subset have begun to reference their findings in product dossiers for formulary review. Managed care faces challenges in operationalizing these tools especially in sensitive categories such as oncology; but several are piloting benefit designs and other programs which incentivize or reward use of therapies with superior value determinations. Conclusions: Given the current environment, healthcare stakeholders are eager for tools that inform and lend credibility to value-based decision-making. There is growing appetite to adopt emerging value frameworks by those managing access to high-cost therapeutics. For manufacturers that seek to achieve and protect patient access to pharmaceutical innovation, a clear imperative exists to ensure that evidence generation programs and messaging optimally position the product for assessment by emerging value frameworks. PHP171 Inclusion of real-world evidence in submission packages to health technology assessment bodies: What do current guidelines indicate? Wang S , Goring S M , Lozano-Ortega G ICON, Vancouver, BC, Canada .
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Objectives: To describe and assess current recommendations by health technology assessment (HTA) bodies for incorporating real-world evidence (RWE) in submission packages. Methods: We reviewed the most recent pharmacoeconomic (PE) and submission guidelines and technical documentation, for HTA bodies identified through the ISPOR website. We limited the review to documents written in English. Within each document, we searched for explicit or implicit recommendations for incorporating RWE to inform PE models and submission packages. We defined RWE as evidence used for decision making that is not collected in randomized controlled trials (RCTs). Results: We reviewed 18 PE and submission guidelines (3 American; 13 European; 2 Oceanian). In 13 guidelines, inclusion of RWE was recommended or considered. Among those, descriptions were provided regarding the relevance and suitability of RWE for: assessing the technology’s clinical effect and potential risks, inclusion as parameters in PE models, and external validation of such models. For guidance relating specifically to the description of clinical effect, eight deemed RWE acceptable under specific circumstances, with proper quality assessment, or as supplements to RCTs. Technical support documents from the United Kingdom provided guidance on RWE study design hierarchy, types of RWE to include in PE models, and on methods for estimating treatment effectiveness using RWE; such guidance was scarce in other submission guidelines. The remaining five guidelines were of limited scope and did not state their position regarding the inclusion of RWE. Conclusions: RWE can help capture the full value of a new technology and inform decision makers of the anticipated impact of being incorporated into real clinical practice. While the inclusion of RWE within HTA submission packages is addressed by most HTA bodies, the scope of the guidance is often limited or incomplete. Further work to clarify standards for generating and selecting relevant and robust RWE to be incorporated in submission packages is needed. PHP172 Why are there differences in HTA recommendations across countries? An In-depth case study analysis exploring the interface between the macro and micro-level factors influencing these decisions Nicod E 1, Maynou Pujolras L 2, Visintin E 3, Cairns J 4 1London School of Economics and Political Science, London, UK, 2CRES, Universitat Pompeu Fabra, Barcelona, Spain, 3London School of Economics and Political Sciences, London, UK, 4London School of Hygiene and Tropical Medicine, London, UK .
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Objectives: Health technology assessment (HTA) is an evidence-based tool used to inform resource allocation decisions to ensure value for money and best possible care to patients. Despite the systematic nature of this approach, the application and outcomes of HTA vary extensively. The objective of this research was to explore the interface between micro- and macro-level variables that explain differences in HTA recommendations across countries through case study analyses. Methods: The analysis focused on drug reimbursement decisions in four countries (England, Sweden, Scotland, France). Four drug and indication pairs were selected according to the following criteria: representative of the different therapy areas analysed and with diverging HTA recommendations across countries. In-depth case study analyses
were conducted. Results: Mifamurtide, gefitinib, natalizumab and tocilizumab were included in the study. Results depict how micro-level variables influenced these decision processes. These include: managed entry agreements, ICER levels, orphan, type of evidence appraised and how it was interpreted (dealing with uncertainty). Their interface with macro-level variables was explored. These included, among others, the advisory or regulatory nature of the HTA bodies, the ability to carry out external reviews of the evidence, stakeholder involvement processes or the initiator of the HTA process. For example, patient input contributed to addressing uncertainty in countries with formal processes for patient involvement, but not in those without a formal process. Conclusions: Results demonstrate the close association between the micro and macro-level factors. Nevertheless, there were instances where no clear pattern or relationship between these two levels arose. These may relate to micro-level variables, such as the subjective interpretation of the committees making the decision, or to contextual elements, such as a country’s industrial policy. We conclude that although these processes are systematic and rely on evidence-based medicine, a component of these decisions rely on judgments made during the deliberative process. PHP173 The Potential Methods of ICER Threshold Estimation In Taiwan Lee N C , Li Y , Wu G H , Gau C Center for Drug Evaluation, Taipei, Taiwan .
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Objectives: The current healthcare system in Taiwan, National Health Insurance (NHI), is a single-payer compulsory social insurance plan with the global budgeting system. The national health insurance administration (NHIA) makes decisions on listing new health technologies based on clinical benefits, budget impacts, costeffectiveness ( e.g. Incremental Cost Effectiveness Ratios (ICER)), orphan drugs, stakeholder perspectives etc. However, ICER thresholds are still not available in Taiwan at present. This study aims to identify potential approaches to evaluate ICER thresholds in Taiwan and further facilitate the application of ICER thresholds to help better healthcare resource allocation. Methods: A focused literature review was carried out using the following search terms: 1. (willingness to pay OR contingent valuation OR discrete choice experiment) AND (quality adjusted life year or QALY); 2. Willingness to pay for (per) quality adjusted life year. Results: A total of 2 systematic review articles and 20 evidence-based research articles published in 2013-2015 were included in this study. Methods of estimating ICER threshold were identified and classified as supply and demand aspects. From the supply side, ICER thresholds could be interpreted as the most optimal price per QALY within limited resources and budget. Therefore, ICER thresholds could be estimated by using opportunity cost strategies such as rule-based approaches, the league table approach or the revealed preference method. On the other hand, from the demand side, ICER thresholds could be seen as the societal willingness-to-pay (WTP). On the basis of present healthcare system in Taiwan, using the league table approach to estimate ICER thresholds would be recommended. However, further modifications of the league table approach are required to fit into NHI’s global budgeting system. Conclusions: With limited healthcare resources and NHI’s global budgeting system, the league table approach would be suitable to estimate ICER thresholds in Taiwan. Furthermore, the methods of estimating ICER thresholds based on the global budgeting system are urgently needed. PHP174 Differences In HTA Acceptance Rates Across Disease Areas: A Comparison Between Four HTA Agencies Vadlamudi N K 1, Griffiths E A 2 1Parexel International, Hyderabad, India, 2PAREXEL, London, UK .
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Objectives: Different health technology assessment (HTA) agencies have differing criteria for acceptance, leading to divergent appraisal outcomes even when the same clinical study base is presented. To inform future submissions, we compared acceptance rates across four HTA agencies and explored consistency between decisions, including any differences between disease areas. Methods: All single HTA appraisals in 2015 from NICE, CADTH, PBAC, and IQWiG were included in the analysis, including resubmissions. Multiple technology appraisals, vaccines, and requests for advice were excluded. The recommendation, reasoning behind the recommendation, and disease area (classified by ICD10 code) were extracted. Results: A total of 189 appraisals met the inclusion criteria: 49 for CADTH (80% with a favorable outcome), 59 for PBAC (61% favorable), 36 for NICE (83% favorable), and 45 for IQWiG (40% favorable). The greatest proportion of submissions were for neoplasms (n= 39, 59% with a favorable outcome), endocrine/metabolic disorders (n= 29, 52% favorable), infections (n= 23, 96% favorable), and respiratory system disorders (n= 16, 69% favorable). The highest consistency between agencies was observed for infectious disease drugs (reflecting positive reactions to new highly-effective HCV drugs), while the most inconsistency was observed between IQWiG and the other agencies for endocrine/metabolic disease drugs (reflecting IQWiG’s unfavorable assessments of new diabetes drugs due to failure to demonstrate benefit over the appropriate comparator). Only five treatments were compared within the same indication across all four agencies in 2015: 1 consistently unfavorable (apremilast for psorasis), 3 consistently favorable (though with variations in the restrictions placed – all for HCV medicines), and 1 inconsistent (secukinumab for psoriasis). Conclusions: Acceptance rates vary considerably between HTA agencies, and divergence in decisions appears to be influenced by disease area. Acceptance rates for IQWiG are on average lower than for other HTA agencies, most notably for diabetes drugs, reflecting the agency’s strict evidence-based medicine approach to assessments. PHP175 Cases And Meaning of Multiple Criteria Decision Analyses In The Real World: Overview Real Cases And Speculations For Korean Settings Kim H J 1, Kim Y 1, Liew D 2, Rhee Y J 3 1Pfizer Pharmaceuticals Korea Ltd., Seoul, The Republic of Korea, 2Monash University, Melbourne, Australia, 3Dongduk Women’s University, Seoul, The Republic of Korea .
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on simple event diaries (e.g. seizures) or measures developed prior to the release of the FDA PRO guidance. Importantly, 27.5% of all approved drugs were for an oncology-related condition (versus 15.5% between 2006 and 2010). The proportion of claims granted is lower than what was reported between 2006 and 2010 (24.1%), and prior to the release of the PRO guidance (30%, 1997-2002). Conclusions: PRO claims continue to be approved by FDA, although at a lower rate than previously reported. This may be partly explained by the increase in the number of oncology products with study designs that may not support PRO labeling as per regulatory guidance. The lack of PRO labeling based on secondary endpoints only may be a reflection of sponsors’ reluctance to capture PRO related value messages to regulatory standards when PROs are not required to support the indication. The acceptance of PRO measures developed prior to the release of the PRO guidance for the purpose of labeling reflects ‘regulatory flexibility’ adopted by the FDA reviewers. PHP165 IMPROVING PATIENT SAFETY THROUGH COMMUNICATION: A BRAZILIAN PERSPECTIVE Bueno C C , Almeida P R , Clark L G , Clark O A Evidencias - Kantar Health, Campinas, Brazil .
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Objectives: Ineffective communication among healthcare professionals is one of the leading causes of medical errors and patient harm. Several studies have shown that communication failures were implicated at the root of over 70% of sentinel events. Also, in the acute care setting, communication failures lead to increases in patient harm, length of stay, and resource use. The objective of this study is to analyze how communication problems can directly affect patient safety (PS) in Brazilian hospitals, as well as the government initiatives to deal with this issue. Methods: We assessed PS data in organs such as the Ministry of Health (MOH), National Agency of Sanitary Surveillance (ANVISA) and National Health Confederation (CNS), as well as Brazilian regulations on patient safety. Additionally, a literature review was performed in Medline and SciELO databases using the mesh terms “patient safety” and “communication”, among others. Results: ANVISA and MOH have instituted a series of activities focused on PS and quality in health services. In 2013, they launched the National Program for Patient Safety, which establishes communication as one of the essential factors for PS. However, failures still occur frequently in Brazilian hospitals. In Brazil, the incidence of adverse events in hospital setting is 7.6%, and 66.7% of them are preventable. Studies indicate that communication problems occur in up to 70% of reported cases of adverse events in hospitals. Furthermore, communication failures are responsible for 32% of errors in ICU. Extended data on the literature review will appear on the poster. Conclusions: Communication breakdown is a key factor contributing to most cases of patient harm, and this harm continues to occur at very high levels. Improving communication for safety in healthcare is an imperative, especially in Brazil, where adverse events in hospitals have high rates and PS still has a long way to go to become really effective. PHP166 PATTERNS OF BIOEQUIVALENCE RECOMMENDATIONS AND TRENDS OF ABBREVIATED NEW DRUG APPLICATIONS APPROVAL OVER TIME Wittayanukorn S 1, Babiskin A 1, Dutcher S 1, Pu X1, Hu M 1, Zhao L 1, Lionberger R 2 of Quantitative Methods and Modeling, Office of Research Standards, Office of Generic Drugs, Center of Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD, USA, 2Office of Research Standards, Office of Generic Drugs, Center of Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD, USA .
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Objectives: The Office of Generic Drugs (OGD) began publishing bioequivalence (BE) recommendations for specific (complex/non-complex) products in 2007 to support generic drug development. Nevertheless, little is known about patterns of BE recommendations. The purpose of this study was to describe patterns of BE recommendations published by the OGD and trends of abbreviated new drug application (ANDA) approvals over time. Methods: An analysis of approved ANDAs was conducted at the time of approval from 2007-June 2015(n= 4,028), using data from the publically available product-specific BE guidance website, Drugs@FDA, and National Drug Code (NDC) directory databases. Guidance patterns, trends, and the distribution of ANDAs approved that have BE recommendations compared to those ANDAs approved that did not have BE recommendations were examined using descriptive statistics and chi-squared tests. Results: A total of 1,439 published BE recommendations between 2007-September 2015 were identified. Number of recommendations was highest in 2008(n= 316) but the trend was inconsistent (P< 0.05). Corticosteroids had the highest proportion of BE recommendations (3.68%), followed by opioid agonists (3.51%), and nonsteroidal anti-inflammatory drugs (3.08%). Compared with BE recommendations, opioid agonists (4.31%), antiepileptics (4.25%), and angiotensin II receptor blockers (3.43%) were pharmacologic classes with a high proportion of approved ANDAs(P< 0.05). Overall, 66.68% of ANDAs approved referenced drug products associated with a BE recommendation and the average ANDA numbers(±SD), excluding solutions/injectables, per recommendation was 2.58(±4.35). An analysis of ANDAs approved over time demonstrated the share of ANDAs approved with recommendations was consistently higher than the share of ANDAs approved without recommendations(P < 0.05). Conclusions: Numbers of published BE recommendations varied over time. BE recommendations cover a wide range of pharmacologic classes and the proportion of ANDAs approved with recommendations was high. Non-complex products may not require recommendations and findings support the continuing need for BE recommendations for more complex products that may further facilitate ANDA approvals.
HEALTH CARE USE & POLICY STUDIES – Health Technology Assessment Programs PHP167 Analysis of Real-World Evidence And Real-World Data By Conitec, Brazilian Hta Agency
Nita M E 1, Riveros B S 2, Vaz P 3, Mussolino F 3 1FIPE - Fundaçã Institute de Pesquisas Econômicas, Sao Paulo, Brazil, 2University of Glascow, Glascow, UK, 3HEADS, Sao Paulo, Brazil .
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Objectives: Very little information is available about the demand from CONITEC, the Brazilian HTA agency, for real-world evidence (RWE), moreover, few real-world data (RWD) sources are available. The objective of this study was to examine reports from CONITEC to identify patters of RWE and sources being used. Methods: The reports from CONITEC are publicly available at the Ministry of Health (MoH). All reports from January to September of 2015 were reviewed for RWE and RWD information. In total, 37 seven reports were analyzed in this research. The assessed variables included type of technology, therapeutic area (TA), source of demand, final decision, RWE and RWD sources. Results: In total, there were 33 inclusion demand and 4 were exclusion. The most frequently technology requested were drugs, 31 out of 37. Infectious disease (8), immunobiologics (6), and cancer (4) were the most frequent TAs. A total of 24 demands were from organizations within MoH. Among external demands the majority were from pharmaceutical industries. Brazilian Unified Health System (SUS) database, the DATASUS, was the RWD source most frequently quoted in the final reports (19), and epidemiology, resources used and treatment patterns were the most used RWE. Drug costs were more frequently quoted (17) from the official MoH Journal (DOU). Observational studies were quoted in 12 reports, including chart reviews, and non-randomized interventional trials were used to support the decisions. Surveys were used in two reports to identify treatment patterns. Conclusions: CONITEC is increasingly demanding RWE in the reports. By expanding the use of existing RWD, as DATASUS, a new concern arises with the way RWE are being retrieved and statistically adjusted in the reports. It is noticeable the concentration of RWE in MoH demands compared to other claimants. From demands without RWE, estimations and assumptions were taken into account. PHP168 Not ready for the real world? The role of non-RCT evidence in health technology assessment Griffiths E A 1, Vadlamudi N K 2 1PAREXEL, London, UK, 2PAREXEL International, Hyderabad, India .
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Objectives: The ‘evidence hierarchy’ of randomized controlled trial (RCT) over nonRCT evidence is well-established, and RCTs remain the ‘gold standard’ for regulatory and health technology assessment (HTA) submissions. However, adaptive pathways will likely necessitate the future use of non-RCT evidence in the HTA-decisionmaking process. To inform future submissions, we assessed acceptance based on non-RCT evidence across four HTA agencies, and explored agencies’ reactions to such study designs. Methods: All single HTA appraisals in 2015 from NICE, CADTH, PBAC, and IQWiG were included in the analysis, including resubmissions. Multiple technology appraisals, vaccines, and requests for advice were excluded. The recommendation, reasoning behind the recommendation, and whether or not a non-RCT design trial (e.g. single-arm or observational) was included in the submission, were extracted. Results: A total of 189 appraisals were extracted: 49 for CADTH, 59 for PBAC, 36 for NICE, and 45 for IQWiG. Non-RCT evidence was considered in 5 CADTH appraisals (10%), 12 PBAC appraisals (20%), 13 NICE appraisals (36%), and no IQWiG appraisals. Only three treatments were given a positive recommendation solely on the basis on non-RCT evidence in 2015: daclatasvir for HCV GT3 infection (CADTH, PBAC), ponatinib for chronic myeloid leukemia (PBAC), and darunavir/cobicistat for HIV infection (CADTH). The remaining submissions included additional RCT evidence or were rejected due to high uncertainty about treatment effect. Non-RCT evidence did, however, contribute to a favorable outcome in some submissions, e.g. idelalisib for CLL and tolvaptan for PKD (NICE). Conclusions: NICE, CADTH, and PBAC will consider non-RCT studies such as real-world data and single-arm trials in certain circumstances, but are critical of the lower certainty of the evidence. The contribution of non-RCT evidence to the HTA-decision-making process is currently minor; however, as adaptive pathways and personalized treatment strategies gain momentum, HTA bodies will need to become more flexible in their approach to assessing non-RCT evidence. PHP169 Perspectives of Implementation And Development of HTA System In Ukraine: Use In Decision Making Zaliska O 1, Piniazhko O 1, Kosyachenko K 2, Tolubaiev V 1 1Danylo Halytsky Lviv National Medical University, Lviv, Ukraine, 2UA HTA, Kyiv, Ukraine .
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Objectives: In Ukraine there is an urgent need for rational allocation of scarce resources and priority settings in health care in the current economic situation. The study aims to examine and outline actual issues of HTA system implementation in Ukraine. Methods: A review and expert interviews were conducted towards the key stages of implementation of HTA system in the recent years in Ukraine. Results: There is no central national HTA agency currently functioning in Ukraine. Simultaneously, some HTA-related procedures are applied for the development of State Drug Formulary and national treatment protocols. Nongovernmental organization (NGO) UA HTA and representatives of academia are facilitating the process of HTA implementation in real-life practice for the decision making process. In the recent years, the articles on HTA introduction, methodical recommendations for postgraduate studies were published by Ukrainian scientists. In 2013-2014 the capacity building and training courses on HTA were carried out by NGO UA HTA in collaboration with foreign colleagues. The Commission on development of HTA system of the MOH works on the introduction of HTA since 2014. We propose the implementation of “light” model of HTA in Ukraine: HTA reports have to be prepared by applicant for reimbursement, minimal use of public funds will provide high performance of HTA reports and high value of HTA in health care policy, national HTA agency have to become a “goalkeeper” while providing critical appraisal of HTA reports. National HTA Guidelines have to be approved within legal framework. Adaptation of international HTA reports to local environment is of high importance. Conclusions: Importantly, in the next years there is a necessity to implement international requirements to HTA in order to prioritize procurements of medicines, their financing by government, reimbursement decisions in order to
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improve the market access, medicines prescription and patients’ health outcomes according to the developed scientific methodology in Ukraine. PHP170 From Talk To Action: Emerging Pharmaceutical Value Frameworks In The United States Capuano C 1, Divi B 2, Singhania A 3, Suponcic S 4 1Navigant Life Sciences, Boston, MA, USA, 2Navigant Life Sciences, Chicago, IL, USA, 3Navigant Life Sciences, Los Angeles, CA, USA, 4Navigant Life Sciences, Lawrenceville, NJ, USA .
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Objectives: There is an acceleration and proliferation of new pharmaceutical innovation that is being introduced at premium prices. At the same time, payers and providers in the United States face unprecedented pressure to manage healthcare budgets and value-based decision-making is top-of-mind. A group of policy entrepreneurs have recently proposed several novel frameworks for assessing and comparing therapeutic value. This research reviews these frameworks and ways in which they are being used to manage access to new pharmaceutical innovation. Methods: Secondary research on recently introduced value frameworks with US origin was conducted (ACA-AHA, ASCO, Drug Abacus, ICER, NCCN). Each tool was characterized based on inputs considered and key similarities/differences were summarized. Primary research was conducted with ten managed care pharmacy executives to assess the extent to which these frameworks are being considered in decision-making or adopted as a standard assessment technique. Results: Existing value frameworks were found to differ with regards to consideration of: patient-centric metrics; indirect benefits; unmet need; and burden of illness. Interviewed managed care executives have increasing awareness of emerging value frameworks and a subset have begun to reference their findings in product dossiers for formulary review. Managed care faces challenges in operationalizing these tools especially in sensitive categories such as oncology; but several are piloting benefit designs and other programs which incentivize or reward use of therapies with superior value determinations. Conclusions: Given the current environment, healthcare stakeholders are eager for tools that inform and lend credibility to value-based decision-making. There is growing appetite to adopt emerging value frameworks by those managing access to high-cost therapeutics. For manufacturers that seek to achieve and protect patient access to pharmaceutical innovation, a clear imperative exists to ensure that evidence generation programs and messaging optimally position the product for assessment by emerging value frameworks. PHP171 Inclusion of real-world evidence in submission packages to health technology assessment bodies: What do current guidelines indicate? Wang S , Goring S M , Lozano-Ortega G ICON, Vancouver, BC, Canada .
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Objectives: To describe and assess current recommendations by health technology assessment (HTA) bodies for incorporating real-world evidence (RWE) in submission packages. Methods: We reviewed the most recent pharmacoeconomic (PE) and submission guidelines and technical documentation, for HTA bodies identified through the ISPOR website. We limited the review to documents written in English. Within each document, we searched for explicit or implicit recommendations for incorporating RWE to inform PE models and submission packages. We defined RWE as evidence used for decision making that is not collected in randomized controlled trials (RCTs). Results: We reviewed 18 PE and submission guidelines (3 American; 13 European; 2 Oceanian). In 13 guidelines, inclusion of RWE was recommended or considered. Among those, descriptions were provided regarding the relevance and suitability of RWE for: assessing the technology’s clinical effect and potential risks, inclusion as parameters in PE models, and external validation of such models. For guidance relating specifically to the description of clinical effect, eight deemed RWE acceptable under specific circumstances, with proper quality assessment, or as supplements to RCTs. Technical support documents from the United Kingdom provided guidance on RWE study design hierarchy, types of RWE to include in PE models, and on methods for estimating treatment effectiveness using RWE; such guidance was scarce in other submission guidelines. The remaining five guidelines were of limited scope and did not state their position regarding the inclusion of RWE. Conclusions: RWE can help capture the full value of a new technology and inform decision makers of the anticipated impact of being incorporated into real clinical practice. While the inclusion of RWE within HTA submission packages is addressed by most HTA bodies, the scope of the guidance is often limited or incomplete. Further work to clarify standards for generating and selecting relevant and robust RWE to be incorporated in submission packages is needed. PHP172 Why are there differences in HTA recommendations across countries? An In-depth case study analysis exploring the interface between the macro and micro-level factors influencing these decisions Nicod E 1, Maynou Pujolras L 2, Visintin E 3, Cairns J 4 1London School of Economics and Political Science, London, UK, 2CRES, Universitat Pompeu Fabra, Barcelona, Spain, 3London School of Economics and Political Sciences, London, UK, 4London School of Hygiene and Tropical Medicine, London, UK .
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Objectives: Health technology assessment (HTA) is an evidence-based tool used to inform resource allocation decisions to ensure value for money and best possible care to patients. Despite the systematic nature of this approach, the application and outcomes of HTA vary extensively. The objective of this research was to explore the interface between micro- and macro-level variables that explain differences in HTA recommendations across countries through case study analyses. Methods: The analysis focused on drug reimbursement decisions in four countries (England, Sweden, Scotland, France). Four drug and indication pairs were selected according to the following criteria: representative of the different therapy areas analysed and with diverging HTA recommendations across countries. In-depth case study analyses
were conducted. Results: Mifamurtide, gefitinib, natalizumab and tocilizumab were included in the study. Results depict how micro-level variables influenced these decision processes. These include: managed entry agreements, ICER levels, orphan, type of evidence appraised and how it was interpreted (dealing with uncertainty). Their interface with macro-level variables was explored. These included, among others, the advisory or regulatory nature of the HTA bodies, the ability to carry out external reviews of the evidence, stakeholder involvement processes or the initiator of the HTA process. For example, patient input contributed to addressing uncertainty in countries with formal processes for patient involvement, but not in those without a formal process. Conclusions: Results demonstrate the close association between the micro and macro-level factors. Nevertheless, there were instances where no clear pattern or relationship between these two levels arose. These may relate to micro-level variables, such as the subjective interpretation of the committees making the decision, or to contextual elements, such as a country’s industrial policy. We conclude that although these processes are systematic and rely on evidence-based medicine, a component of these decisions rely on judgments made during the deliberative process. PHP173 The Potential Methods of ICER Threshold Estimation In Taiwan Lee N C , Li Y , Wu G H , Gau C Center for Drug Evaluation, Taipei, Taiwan .
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Objectives: The current healthcare system in Taiwan, National Health Insurance (NHI), is a single-payer compulsory social insurance plan with the global budgeting system. The national health insurance administration (NHIA) makes decisions on listing new health technologies based on clinical benefits, budget impacts, costeffectiveness ( e.g. Incremental Cost Effectiveness Ratios (ICER)), orphan drugs, stakeholder perspectives etc. However, ICER thresholds are still not available in Taiwan at present. This study aims to identify potential approaches to evaluate ICER thresholds in Taiwan and further facilitate the application of ICER thresholds to help better healthcare resource allocation. Methods: A focused literature review was carried out using the following search terms: 1. (willingness to pay OR contingent valuation OR discrete choice experiment) AND (quality adjusted life year or QALY); 2. Willingness to pay for (per) quality adjusted life year. Results: A total of 2 systematic review articles and 20 evidence-based research articles published in 2013-2015 were included in this study. Methods of estimating ICER threshold were identified and classified as supply and demand aspects. From the supply side, ICER thresholds could be interpreted as the most optimal price per QALY within limited resources and budget. Therefore, ICER thresholds could be estimated by using opportunity cost strategies such as rule-based approaches, the league table approach or the revealed preference method. On the other hand, from the demand side, ICER thresholds could be seen as the societal willingness-to-pay (WTP). On the basis of present healthcare system in Taiwan, using the league table approach to estimate ICER thresholds would be recommended. However, further modifications of the league table approach are required to fit into NHI’s global budgeting system. Conclusions: With limited healthcare resources and NHI’s global budgeting system, the league table approach would be suitable to estimate ICER thresholds in Taiwan. Furthermore, the methods of estimating ICER thresholds based on the global budgeting system are urgently needed. PHP174 Differences In HTA Acceptance Rates Across Disease Areas: A Comparison Between Four HTA Agencies Vadlamudi N K 1, Griffiths E A 2 1Parexel International, Hyderabad, India, 2PAREXEL, London, UK .
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Objectives: Different health technology assessment (HTA) agencies have differing criteria for acceptance, leading to divergent appraisal outcomes even when the same clinical study base is presented. To inform future submissions, we compared acceptance rates across four HTA agencies and explored consistency between decisions, including any differences between disease areas. Methods: All single HTA appraisals in 2015 from NICE, CADTH, PBAC, and IQWiG were included in the analysis, including resubmissions. Multiple technology appraisals, vaccines, and requests for advice were excluded. The recommendation, reasoning behind the recommendation, and disease area (classified by ICD10 code) were extracted. Results: A total of 189 appraisals met the inclusion criteria: 49 for CADTH (80% with a favorable outcome), 59 for PBAC (61% favorable), 36 for NICE (83% favorable), and 45 for IQWiG (40% favorable). The greatest proportion of submissions were for neoplasms (n= 39, 59% with a favorable outcome), endocrine/metabolic disorders (n= 29, 52% favorable), infections (n= 23, 96% favorable), and respiratory system disorders (n= 16, 69% favorable). The highest consistency between agencies was observed for infectious disease drugs (reflecting positive reactions to new highly-effective HCV drugs), while the most inconsistency was observed between IQWiG and the other agencies for endocrine/metabolic disease drugs (reflecting IQWiG’s unfavorable assessments of new diabetes drugs due to failure to demonstrate benefit over the appropriate comparator). Only five treatments were compared within the same indication across all four agencies in 2015: 1 consistently unfavorable (apremilast for psorasis), 3 consistently favorable (though with variations in the restrictions placed – all for HCV medicines), and 1 inconsistent (secukinumab for psoriasis). Conclusions: Acceptance rates vary considerably between HTA agencies, and divergence in decisions appears to be influenced by disease area. Acceptance rates for IQWiG are on average lower than for other HTA agencies, most notably for diabetes drugs, reflecting the agency’s strict evidence-based medicine approach to assessments. PHP175 Cases And Meaning of Multiple Criteria Decision Analyses In The Real World: Overview Real Cases And Speculations For Korean Settings Kim H J 1, Kim Y 1, Liew D 2, Rhee Y J 3 1Pfizer Pharmaceuticals Korea Ltd., Seoul, The Republic of Korea, 2Monash University, Melbourne, Australia, 3Dongduk Women’s University, Seoul, The Republic of Korea .
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