Transferability of HTA between countries Zoltán Kaló Professor of Health Economics Eötvös Loránd University (ELTE) Syreon Research Institute Transferability of HTA between countries kalo@tatk.elte.hu

Pragmatic approach to evidence based health policy Too complicated and time-consuming to rank all available health care technologies according to their cost-effectiveness  cost-effectiveness criteria are assessed mainly for new and expensive therapies For innovative pharmaceuticals, the mandatory economic evaluation represents the fourth hurdle to market access, as registration already includes assessment of the efficacy, safety and quality. In addition to considering the health gain, the risk-benefit ratio and cost- effectiveness, public payers take into account several other factors in their decisions, including unmet medical need, budget impact, equity, incidence and prevalence of the disease. All these factors are incorporated into a formal health technology assessment process in several countries, prior to the reimbursement and formulary listing of new pharmaceutical therapies

Importance of NICE National Institute for Health and Clinical Excellence (NICE) in England and Wales is one of the most prominent public institutions to incorporate economic evaluation and health technology assessment into its recommendations As NICE publishes health technology assessment reports that are considered to be unbiased references, public decision- makers in many other countries implicitly take into account the NICE recommendations in their own decisions (O’Donnel et al., 2009)

Central-Eastern European situation Presentation Information Central-Eastern European situation HTA capacity is limited in CEE countries Public payers and policymakers have a greater need to rely on NICE recommendations in their own decisions, often without understanding the limitations of the transferability of health technology assessment reports. Reliance on NICE recommendations is especially common for new technologies with significant budget impact. Malignancies the public health burden of malignancies in CEE is huge innovative pharmaceutical therapies are very expensive NICE recommendations in oncology may receive even greater attention in CEE than in any other therapeutic areas. CONFIDENTIAL 4

Welte’s knock-out criteria for HTA transferability “General knock-out” criteria preclude transferability of cost- effectiveness results when either the investigated technology or the comparator are irrelevant, or the methodological quality of the cost-effectiveness study does not meet local standards, meaning that the starting points of the study are irrelevant to local decision-makers. “Specific knock-out criteria” apply when cost-effectiveness results are only transferable after adjustment for differences in treatment patterns, in unit costs, or other aspects for which adjustment may be required. Ref: Welte et al. Pharmacoeconomics, 2004. 22, 857–876.

Policy vs data driven HTA determinants Policy-driven determinants: If the local policy is similar to the NICE policy, there is no need for local adjustment of that particular determinant If the local policy is different from the NICE policy, the transferability of recommendations becomes more limited. Data-driven determinants: require local adjustment, when the data is different.

Determinants of health technology assessment HTA section Determinant Policy driven Measure burden of disease number of patients no prevalence; incidence health status of the target population; disease progression life expectancy; healthy life expectancy; comorbidities; standardized mortality subgroup of patients age; proportion of patients in different disease stages; pharmacogenomic status unmet medical need added innovation availability of effective therapeutic alternatives; first in class; mechanism of action public health need priority setting yes local public health program special regulation orphan drug status; end of life therapy comparator positioning of new therapy in local therapeutic guidelines first line, second line, etc. relevance of the comparator reimbursement status; local practice for standard therapy

Determinants of health technology assessment HTA section Determinant Policy driven Measure health gain baseline risk no mortality; risk of clinical endpoints efficacy or relative effectiveness absolute risk reduction, relative risk reduction real world benefit adherence / compliance health state valuation partly utility estimates cost- effectiveness unit cost production function of health care services; relative prices of medical technologies resource utilization local treatment practices and patient routes methodology of economic evaluation time horizon yes projection of health gain and cost (in years) discount factor % perspective health care or societal perspective; inclusion of indirect costs CE threshold explicit or implicit threshold opportunity cost budget impact expected costs in local currency equity accessibility access and utilization according to geographical and socioeconomic status

Incidence of malignant neoplasms per 100,000 persons (2008) Incidence & mortality Incidence of malignant neoplasms per 100,000 persons (2008) Standardized death rate of malignant neoplasms per 100,000 persons (2009 or nearest year) Czech Republic 288.5 254 Estonia 230.1 275 Hungary 286.6 316 Poland 225.1 272 Slovak Republic 260.6 263 Slovenia 264.8 266 United Kingdom 269.4 199 Source: OECD (2011), Health at a Glance 2011

Mortality burden of malignancies 2005 Source: WHO Health for All, 2010

5-year survival probability, Disease progression Colorectal cancer 5-year survival and standardized mortality 5-year survival probability, (2002-07 or nearest period) Colorectal cancer age standardized mortality / 100,000, (2005 or nearest year) male female Czech Republic 45.6% 48.5% 31.0 Hungary - 31.9 Poland 34.7% 39.3% 20.8 Slovak Republic 29.8 United Kingdom 50.4% 53.1% 17.6 Source: OECD, Health at a Glance, 2009

Unmet medical need Cervical cancer screening, percentage of women screened aged 20-69 Standardized death rate cervix carcinoma (<70 year/100,000 women) Czech Republic 47.7 4.0 Estonia 52.0 5.4 Hungary 23.7 5.2 Poland - 6.5 Slovak Republic 22.9 5.9 Slovenia 72.3 3.3 United Kingdom 78.7 2.1 Source: OECD (2011), Health at a Glance 2011

Unmet medical need Until 2010 NICE reviewed 5 innovative drug therapies to treat renal cell carcinoma (bevacizumab, sorafenib, sunitinib, temsirolimus and everolimus). NICE recommended only one first-line therapy (sunitinib) within a special patient access scheme (2009) and refused all second-line sequential treatments (2009). Despite sorafenib and temsirolimus are orphan drugs in this indication, NICE guidance quotes that survival data is immature and questions the robustness of life extension and sub-group analyses. It is not surprising that overall survival data is immature and non-robust for orphan drugs. The moral question is why an accelerated registration process should be granted for oncology drugs if later patient access to those medicines is denied by the lack of reimbursement.

Unit cost Annual remuneration of employed health professionals (latest available years between 2006-2009; US$ exchange rate) 2007 General practitioners Specialist physicians Hospital nurses Czech Republic (35 167*) 30 859 15 987 Estonia 24 488 31 191 14 749 Hungary 23 410 26 086 12 603 Slovak Republic 25 984 - 12 095 Slovenia 65 447 75 487 28 207 United Kingdom 111 580 (212 144*) 124 453 51 673 Source: OECD Health Data 2010, June

Differential pharmaceutical pricing in the European Union: mission impossible? Parallel trade International price referencing Transparent pricing strategy Price convergence Launch sequence

Impact of European Union: narrow pricing corridor for new medicines

Resource utilisation The ratio of practising nurses to physicians is 3.6 to 1 in the United Kingdom and less than 2.4 to 1 in Central-Eastern European countries (OECD, 2011). The system of health service providers is different in the NHS, e.g. gatekeeping function of general practitioners. Mammography (OECD, 2011) and cervical cancer screening rates are higher in the United Kingdom. There are more acute care beds in Central-Eastern European countries and the number of hospital discharges for cancer cases is 2-3 times higher than in the United Kingdom (OECD, 2011). Greater inequity in the accessibility of health care services in CEE than in the UK (OECD, 2011).

Survey of HTA agencies in LatAm / CEE / Asia: In what ways are results from studies conducted in other jurisdictions used? Ref: Drummond M, Augustovski F, Kaló Z, Yang BM, Pichon-Riviere A, Bae EY, Kamal-Bahl S. Challenges faced in transferring economic evaluations to middle income countries. Manuscript in submission, 2014

Survey of HTA agencies in LatAm / CEE / Asia: Which categories of data from foreign studies are most often used in submissions you receive? Ref: Drummond M, Augustovski F, Kaló Z, Yang BM, Pichon-Riviere A, Bae EY, Kamal-Bahl S. Challenges faced in transferring economic evaluations to middle income countries. Manuscript in submission, 2014

Survey of HTA agencies in LatAm / CEE / Asia: Obstacles to transferring economic evaluationss from other jurisdictions Ref: Drummond M, Augustovski F, Kaló Z, Yang BM, Pichon-Riviere A, Bae EY, Kamal-Bahl S. Challenges faced in transferring economic evaluations to middle income countries. Manuscript in submission, 2014

Number of times mentioned Survey of HTA agencies in LatAm / CEE / Asia: Which categories of foreign data do you consider to be transferable? OBSTACLE Number of times mentioned Other practice patterns, or the availability of facilities, are often different in my jurisdiction 10 The current standard of care/ relevant comparator is often different in my jurisdiction 9 Studies are often conducted in countries with a higher GDP, so results do not apply in my jurisdiction 8 Studies are often badly reported, or not enough details are given It is often difficult or impossible to obtain an electronic copy of the model 7 The patient population is often different in my jurisdiction 6 Often, it is not possible to find local data to re-populate the model Studies often have methodological deficiencies 5 Decision-makers in my jurisdiction much prefer a locally designed study Studies often use methods that are too advanced for decision-makers in my jurisdiction 4 Other obstacles (please list and rank) 3 Lack of local technical capability 1 Decision-makers in my jurisdiction much prefer non-data driven arguments Different resources & costs used in other jurisdictions Ref: Drummond M, Augustovski F, Kaló Z, Yang BM, Pichon-Riviere A, Bae EY, Kamal-Bahl S. Challenges faced in transferring economic evaluations to middle income countries. Manuscript in submission, 2014

Conclusion Transferability of good quality HTA reports could be beneficial to prevent duplication of efforts and save resources for local HTAs. Certain elements of HTA reports are transferable, but adjustment to local data is absolutely necessary. Copying recommendations based on international HTA without local adjustment may do more harm than good.