Value Added Medicines: Adjustements of HTA Decision Frameworks To Capture Their Full Value

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financial benefits of the budget impact test are evident, it ultimately fails to maintain the patient’s interest at the heart of decision making. Budget impact analysis essentially represents multiplication of the cost per patient by the number of patients likely to be treated. Therefore patients in more prevalent disease areas are likely to be discriminated against given larger budget impacts these calculations would result in. This results in larger patient groups being used as a bargaining chip by the NHS to drive down drug prices. The test could also be contradictory to the NHSs Constitution, which states patient access to interventions should not be limited on the basis of net acquisition and administration costs. Furthermore, the test may disproportionally impact first to market drugs who often represent a considerably cost-effective alternative to current standards of care but may also be costly to introduce due to existing unmet need.  Conclusion: Whilst the Budget Impact Test provides the NHS opportunity to contain future costs, it pushes the patient further into the back seat in terms of service commissioning, allowing financial interest to increasingly drive decision making. PHP304 Challenges and Future Perspectives on The Reimbursement of Advanced Therapy Medicinal Products Rothwell S1, January D2, Duda M3, Gardner K1, Michel S1 1Evidera, London, UK, 2Evidera, Bethesda, MD, USA, 3Evidera, San Francisco, CA, USA

Objectives: Advanced therapy medicinal products (ATMPs) are a new class of therapeutic interventions, based on gene, cell and tissue manipulations, offering potentially curative treatment options for a range of diseases. While the ATMP classification system is solely a European phenomenon, gene and cell-based therapies (ATMP-like therapies) are emerging across markets and so the question of how these innovative, yet costly, treatments are to be reimbursed is pertinent worldwide. The aim of our research is to: review the current situation surrounding ATMP HTA and reimbursement in Europe, Canada and the US; identify specific challenges to ATMP market access; ascertain if and how assessment procedures are likely to change over the next 3 years.  Methods: Targeted literatures searches and payer interviews (n= 10) were carried out focussing on ATMPs and ATMP-like therapies awarded centralised marketing authorisation by the EMA, FDA or CADTH.  Results: The national systems for HTA and reimbursement of ATMPs, like those for conventional drugs, vary country-by-country. While regulatory agencies have ATMP, or gene- and celltherapy specific policies, HTA and reimbursement bodies do not; hence in many cases, the assessment of ATMPs for reimbursement is largely in line with that for conventional therapies. For ATMPs offering long-term curative effects, the majority of payers identified uncertainty over long-term efficacy as the greatest challenge to optimal reimbursement. Payers discussed, among others, pay-for-performance contracts, rebate contracts, and real-world evidence collection as strategies that can be utilised by manufacturers to mitigate the uncertainty and high costs associated with ATMPs.  Conclusion: The high cost of ATMPs coupled with the uncertainty of long-term efficacy is the greatest challenge to ATMPs gaining market access. Overall, the key concern for payers is how to mitigate the risks of reimbursing a treatment with uncertain long-term outcomes. PHP305 Health Technologies’ Taxonomy and Challenges To Apply The Assessment Araja D Riga Stradins University, Riga, Latvia

The international professional organizations, academies and national competent authorities currently use different approaches for covering the health technologies’ taxonomy and therefore different scope of health technology assessment (HTA). Theoretically is defined that the health technologies include pharmaceuticals, medical devices, diagnostic and treatment methods, rehabilitation and prevention methods; as well as organizational, financial, delivery and support systems. At the same time the HTA is defined as a multidisciplinary field of policy analysis, which studies medical, social, ethical and economic implications of development, diffusion and use of health technology. Practically, by international surveys results, can be observed that HTA is applied mostly for pharmaceuticals and medical devices, and it is specified as a comprehensive national HTA systems. However these systems demonstrate the lack of methods and policy analysis of medical, social, ethical and economic implications of specific health care financing and managerial models, as well as the impact of health technologies interactions. To develop the common approach and avoid misunderstandings could be recommended, firstly, to consider possibility to define the medical technologies as a subgroup of health technologies, which are directly used in treatment process (pharmaceuticals, medical devices, diagnostic and treatment methods) and for which full HTA are applied; secondly, to clarify the separation of diagnostic, medical and surgical procedures from pharmaceuticals and medical devices, as there is not a common approach for their assessment separately or as a part of medical procedure (for pharmaceuticals) or diagnostic and surgical procedure (for medical devices); thirdly, to continue the development of specific HTA methodologies for assessment of health care financing, delivery, and managerial models, prevention activities and complementary medicine, rehabilitation programs and long-term care, and for other health technologies’ subgroups. The common approach for health technologies’ taxonomy and appropriate assessment methods could soften HTA challenges and improve the credibility and value of its results. PHP306 Tissue/Site Agnostic Regulatory Approval of Oncology Drugs: Are Htas Ready For A New Era In Personalised Medicine? Sammon C, Mbanya Z, Sen Nikitas F PHMR Ltd, London, UK

The recent FDA approval of pembrolizumab (Keytruda) for the treatment of all MSI-H and dMMR unresectable and metastatic solid tumors is believed to signal a more general move towards the regulatory approval of oncology drugs for the treatment of genetically defined tumours across multiple locations in the body (tissue/site

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agnostic approvals). We sought to review clinical data available on drugs likely to be considered for tissue/site agnostic approvals with a view to considering the likely hurdles that manufacturers and HTA bodies will encounter in ensuring patients can access these drugs. Publically available clinical data on pembrolizumab (for the treatment of MSI-H and dMMR solid tumors) and larotrectinib (for the treatment of TRK fusion cancers) were extracted and reviewed. Pembrolizumab received FDA approval based on data from 149 patients with MSI-H or dMMR solid tumours enrolled across five uncontrolled, single-arm clinical trials. 90 patients had colorectal cancer and 59 patients were diagnosed with one of 14 other cancer types. Loxo Oncology are expected to submit for tissue/site agnostic FDA approval of larotrectinib for TRK fusion cancer based on data from TRK fusion patients recruited across 3 trials. Interim data indicates that 13 discrete TRK fusion tumour types have been treated across 55 patients: salivary (12), sarcoma (10), infantile fibrosarcoma (7), lung (5), thyroid (5), colon (4), melanoma (4), cholangio (2), GIST (2), and other (4). HTAs of oncology drugs that receive tissue/site agnostic approvals are likely to prove problematic as the grouped efficacy data that regulators may be willing to accept are unlikely to be fit for the purpose of assessing drugs for reimbursement for specific indications within the current HTA frameworks. Reconsideration of the HTA framework for such drugs may be necessary to avoid withholding patient access to drugs for licenced indications. PHP307 An Analysis of The Current Jordanian Pricing System and Developing Recommendations for Its Enhancemnet Batarseh S1, El Khoury AC2, Ashraf RM2 food and Drug Association, Amman, Jordan, 2University of Arkansas for Medical Sciences College of Pharmacy, Little Rock, AR, USA

1Jordan

Objectives: The current list pricing system in Jordan is based on international price referencing. The system has been delivering effective outcomes since 2003. Within a dynamic healthcare and economic environment it is essential to assess periodically the robustness and effectiveness of the system in delivering its objectives.  Methods: A workshop of 28 participants followed by a focus group of decision makers that included experts in health economics, healthcare policy, pricing and reimbursement systems in Jordan was conducted. The group reviewed the Jordanian pricing system and compared it to other systems in UK, Germany, France and Turkey. Based on that, the group ran a comparative analysis to identify the major considerations in developing recommendations for the Jordanian pricing system.  Results: The Jordanian system’s major strengths lie in being a well-structured and cohesive system. For brand products; the price is set to match the lowest outcome of requested price by the manufacturer, price in country of origin, price in Saudi and median among prices in 16 pre identified countries. The system allows for appeals and exceptions according to patient centric criteria. Areas of development in the Jordanian pricing system include; developing specific considerations for pricing of biologic products and the evolution of the system towards value based pricing. Availability of data remains a challenge towards value based pricing.  Conclusion: An effective and cohesive pricing approach is a corner stone of patient focused healthcare system. This is ideally done by continuously improving and advancing the regulations to meet that objective while ensuring that patients still have access to innovative drugs. The focus group agreed on a set of recommendations adopting good pricing practice that provides a support of a cohesive and uniform process in the evaluation of innovative healthcare technologies. PHP308 Effect of Health System, Financing, and Macro-Economic Characteristics on The Migration of Foreign Physicians To Oecd Countries Aydin S University of South Carolina, Columbia, SC, USA

This study specifically focuses on ‘pull’ factors affecting physician migration to OECD countries. The demand on human resource in healthcare is rapidly growing worldwide, and there is a chronic need for some 2.4 million more physicians. These shortages provide that many countries have insufficient numbers of healthcare workforce to deliver necessary interventions producing health. The global migration of physicians is increasingly playing a key role in compensating for an inadequate domestic supply in many countries of the Organization for Economic Cooperation and Development (OECD). Physician flows that is the way for the countries to solve the shortage of medical professionals is receiving increased attention. For example, on average in the OECD, there are around 20% of foreign born employed physicians. In total, 243,000 foreign trained physicians registered to practice in the United States while 91,000 in the United Kingdom (in 2011), 18,000 in Australia (in 2009), and 18,000 in Canada (in 2012) registered to practice. In general, the OECD countries that have more migrated physicians tend to have more professional health workforce to use them as a “quick fix” to address the needs, because training extra physicians takes many years to have an effect.  Based on the previous studies and widely accepted literatures, three main categories have been found crucial on the migration physicians to OECD countries; Healthcare Resources Characteristics (Physicians, Medical graduations, and Medical Technology density), Healthcare System Characteristics and Financing (Health expenditures, Financing of expenditure, Social Protection, healthcare utilization, Health Status), and Macro-Economic Characteristics (GDP, PPP, NCU, GNP, GNI, wages, and unemployment rate). Overall, the migration flows to OECD counties are expected to grow in coming decades due to increasing demand in the aging population as well as technological changes anticipated to increase the demand for health care services. PHP309 Value Added Medicines: Adjustements of HTA Decision Frameworks To Capture Their Full Value Rémuzat C1, Toumi M2 1Creativ-Ceutical, Paris, France, 2Aix-Marseille University, Marseille, France

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Value added medicines (VAMs) are medicines based on known molecules that follow 3 drug repurposing models, i.e., reformulation, repositioning and combination, which deliver substantial value for patients and society. However, current European health technology assessment (HTA) decision frameworks, depending on country, represent various challenges for full value recognition of VAMs. Several challenges have been identified for VAMs in current HTA decision frameworks: 1) May not be eligible for HTA, 2) May not be eligible for early HTA dialogues, 3) May not be eligible for coverage with evidence development, 4) Their benefits, e.g. improvements in patient preference, adherence, and convenience of use, may not be adequately captured, as they can be complex to demonstrate through RCTs or not readily captured via QALYs, 5) Are usually perceived as generic-like products and therefore penalised in the deliberative process. The recommended HTA policy changes should include: 1) Promoting alternative methods, such as multiple criteria decision analysis techniques and constraint optimisation modelling; 2) Adjusting current HTA decision frameworks. Whenever requested, all medicines should be eligible for HTA and early HTA dialogue. HTA decision frameworks should encompass all attributes recommended by the EUnetHTA Core Model®, integrated in a standardised and explicit way through a transparent and reproducible deliberative process. Attributes not already included, or included informally, should be used as appraisal modifiers. HTA decision frameworks should be patient-centric, including patient-reported outcomes, patient-centered outcomes and patient preferences, consider alternative study designs beyond RCTs, and allow coverage with evidence development to capture the benefits that are complex to demonstrate pre-launch. The societal perspective should be adopted, and a broad range of stakeholders – including patients – should take part in the decision-making process. HTA policy changes and robust research support are recommended to enhance VAM value recognition and encourage industry investment in medicines with high potential value to society. PHP310 Estimation of Prevalence In Rare Disease Irwin J1, Auvin S2, Abi-Aad P3, Gibson E3, Battersby A3 International Limited, Maidenhead, UK, 2Université Paris Diderot, Paris, France, 3Wickenstones Ltd, Oxfordshire, UK

1Zogenix

Objectives: Overestimation of real-world prevalence in rare diseases can be a significant issue for policy makers and the pharmaceutical industry. This work explores reasons for the overestimation and develops an outline methodology for the application of drag factors when calculating prevalence based on reported incidence. Two rare epileptic encephalopathies Dravet syndrome (DS) and LennoxGastaut syndrome(LGS) were used as illustrative examples.  Methods: For both rare diseases, a targeted literature review without restriction on publication date was performed to (1) identify all reports of incidence, prevalence and mortality rates and (2) develop a detailed description of how diagnostic practice has evolved over time. The themes considered included time from syndrome identification, developments in disease definition/diagnostic criteria and inclusion (or lack of) in clinical guidelines, availability of any or improved therapies and the development of diagnostic tools. A conceptual model was developed to calculate prevalence based on reported incidence (traditional approach) versus adjusted incidence (according to factors that cause a diagnostic drag).  Results: For DS patients, calculated prevalence based on diagnostic incidence data matches the real-world prevalence for patients under 18 years old, but overestimates the 18 years and older real-world prevalent population. In the case of LGS, the available epidemiological data are heterogeneous and we were not able to reliably compare calculated with real-world prevalence. The proposed conceptual model incorporating diagnostic drag reflects predicted realworld prevalence of adults with DS in Sweden (104 individuals) more accurately than traditional calculated prevalence (191 for the conceptual model vs 257 for the traditional model).  Conclusions: Methodological challenges in measuring epidemiology, coupled with advances in rare disease discovery may cause discrepancies between real-world and calculated prevalence. Care should be taken with calculated prevalence figures to not overstate the real-world prevalence in rare diseases. PHP311 A Healthcare Policy Study To Build A Roadmap for Rare Disease Management Under The Egyptian Healthcare System Soliman NA1, Sallam R2, Anan I2 University, Cairo, Egypt, 2Accsight, Cairo, Egypt

1Cairo

Objectives: This policy study aims to identify the gaps alongside the patient journey of rare disease (RD) patients in Egypt, and to build a roadmap for the enhancement of RD management, as well as to maximize the access of RD patients to treatment and support.  Methodology: An Expert panel meeting was conducted with RD physicians, Key decision makers, Non-Governmental Organizations, payers, patients and their families. The meeting was moderated by an external facilitator to gather all insights and opinions about the objectives as well as building the roadmap milestones, focusing on 3 RDs: myelofibrosis, cystinosis, and tuberous-sclerosis-complex (TSC).  Results: A consensus on the following call to action milestones was established: 1- Create a list of RDs in Egypt estimating their respective prevalence. 2- Create a central hub of data and a research center connecting RD units allover Egypt. 3- Apply unique patient ID in all RD units to avoid duplications. 4- Initiate a national registry program that connects the RD units. 5- Initiate a screening program for patients at risk (focused screening) starting with programs for pregnant mothers / high risk mothers/ mothers with family history. As well as prenatal diagnosis program. 6- Build National Egyptian guidelines for RD with special focus on multidisciplinary management 7- Add the necessary RD drugs to the public-sector formulary. 8- Build a national office for RDs responsible for implementing all the above-mentioned points.  Conclusion: Achieving the milestones of the RD roadmap needs more compelling actions from policy makers, public authorities, industry representatives, and health professionals about the seriousness and importance of treating RDs in Egypt. Great efforts are still needed from the governmental sector to alleviate the obstacles across the entire patients’

journey mainly the financial burden aspect, the availability of medications and most importantly the creation of the RD committee. PHP312 Adapting Pharmacoeconomics To Shape Efficient Health Systems En Route To Uhc - A Conceptual Framework Thiede MH1, Miot J2 1Scenarium Group GmbH, Berlin, Germany, 2University of the Witwatersrand, Johannesburg, South Africa

Today, many countries are in some stage of implementing or using pharmacoeconomics to improve patient and health system outcomes. This conceptual paper aims at identifying the factors that determine the design and applications of the pharmacoeconomic toolkit in different health systems internationally. With a focus on methodological alternatives and different approaches towards integrating and institutionalising pharmacoeconomics within health systems, the paper seeks to provide guidance on processes for the design, implementation and optimisation of pharmacoeconomics as a steering tool within a health system under the universal health coverage (UHC) paradigm. The design of the underlying conceptual framework is based on a review of international literature as well as on policy observations and case studies. The paper analyses ways in which the choice of pharmacoeconomic instruments, their mode and timing of introduction and embedding in an overarching regulatory framework have been shaped by factors that fall into two spheres: health systems characteristics on the one hand and specific contextual factors on the other. The very distinct case studies of South Africa and Germany inform the identification of these determinants and guide the analysis of their influence on forming pharmacoeconomic policy and practice in different contexts. The case studies also serve to illustrate the relevance of particular policy decisions by highlighting the dynamic dimension of decisions made in the case study countries, e.g. regarding certain elements of the General Methods of the German Institute for Quality and Efficiency in Health Care and of the South African National Department of Health’s pharmacoeconomic guidelines. The paper concludes with a structured analytical overview of determinants, designs and implications. The findings are used to spell out clear recommendations for a context-sensitive process towards optimising pharmacoeconomic policy and practice in specific country contexts with a view to UHC. PHP313 Specificities of Cancer Immunotherapy – Challenges From Market Access Perspective Lach K1, Chouaid C2, Rémuzat C3, Toumi M4 Hospitalier Intercommunal, DHU-ATVB, Département de Pneumologie et Pathologie Professionnelle, Créteil, France, 3Creativ-Ceutical, Paris, France, 4Aix-Marseille University, Marseille, France

1Creativ-Ceutical, Krakow, Poland, 2Centre

Background: By targeting immune cells rather than tumour cells, immunooncology therapies (IOs) have shifted the cancer treatment landscape offering the potential for long-term quality survival to many patients for whom treatment options were previously limited. Since the approval of immune checkpoint modulators in metastatic melanoma in 2011, a great deal of knowledge was generated on specificities of IO and many thereof remain challenging from market access perspective. Discussion: Pricing and reimbursement of IO therapies remain a key challenge for decision-makers due to immature evidence at time of market launch. IO therapies showed a delayed tumor response and potential long-term survival in some patients limiting use of standard endpoints (e.g. median overall survival, surrogate endpoints, such as progression-free survival) and raising much uncertainty on long-term efficacy data. Assessment of relative efficacy of IO therapies poses substantial challenges while fast evolving treatment patterns make evidence on successive lines becoming rapidly obsolete. IO response was reported as heterogeneous between patients; lacking predictive biomarkers precludes from selecting proper target populations. Immune-related side effects make long-term safety uncertain. IO response kinetic and heterogeneous populations in terms of survival are problematic vis-à-vis standard methods used to extrapolate survival data. Anticipation of potential budget impact is more complex by uncertainty in dose selection, unclear rules for treatment hold/discontinuation and increasing number of potential drug combinations. Finally, given IO potential for long-term quality survival, decisionmakers should consider a societal perspective to fully capture indirect costs, such as work productivity and caregiver time.  Conclusions: Recognition of entire benefits of IO therapies depends largely upon addressing the discussed challenges. Mature and long-term clinical data are needed to quantify additional benefits and to support decision-making. On-going research and debates on new clinical endpoints, specific survival extrapolation methods, research on biomarkers, drug value frameworks should contribute to addressing gaps in IO assessment. PHP314 Will 2017 Updates To The Highly Specialised Technologies Programme Benefit or Harm Vulnerable Patients? Boodhna T, Hendrich J WG Access, London, UK

Background: The Highly Specialised Technologies programme (HST) assesses drugs for people who suffer rare conditions and whose indicated population is sufficiently small that treatment has to be concentrated in a few centres only. Changes to the National Institute of Health and Care Excellence (NICE) decision making process have recently been announced adding a cost-effectiveness assessment and there is therefore need to examine the impact this change will have for these underserviced and typically vulnerable patients.  Analysis: NICE had previously based decision making upon 1) the epidemiology of the disease, disease morbidity and existing treatment options, 2) The robustness of clinical efficacy arguments, 3) budgetary impact to the NHS and 4) impacts beyond health such as the benefits of research and innovation. These considerations are then communicated through a consultation process after which a decision is made on whether to nationally commission