Bridging the gap: Can International Consortium of Health Outcomes Measurement standard sets align outcomes accepted for regulatory and health technology assessment decision-making of oncology medicines.

Standard outcome sets developed by the International Consortium for Health Outcomes Measurement (ICHOM) facilitate value-based health care in healthcare practice and have gained traction from regulators and Health Technology Assessment (HTA) agencies that regularly assess the value of new medicines. We aimed to assess the extent to which the outcomes used by regulators and HTA agencies are patient-relevant, by comparing these to ICHOM standard sets. We conducted a cross-sectional comparative analysis of ICHOM standard sets, and publicly available regulatory and HTA assessment guidelines. We focused on oncology due to many new medicines being developed, which are accompanied by substantial uncertainty regarding the relevance of these treatments for patients. A comparison of regulatory and HTA assessment guidelines, and ICHOM standard sets showed that both ICHOM and regulators stress the importance of disease-specific outcomes. On the other hand, HTA agencies have a stronger focus on generic outcomes in order to allow comparisons across disease areas. Overall, similar outcomes are relevant for market access, reimbursement, and in ICHOM standard sets. However, some differences are apparent, such as the acceptability of intermediate outcomes. These are recommended in ICHOM standard sets, but regulators are more likely to accept intermediate outcomes than HTA agencies. A greater level of alignment in outcomes accepted may enhance the efficiency of regulatory and HTA processes, and increase timely access to new medicines. ICHOM standard sets may help align these outcomes. However, some differences in outcomes used may remain due to the different purposes of regulatory and HTA decision-making.

Implantable Devices for Single-Sided Deafness and Conductive or Mixed Hearing Loss: A Health Technology Assessment.

BACKGROUND: Single-sided deafness refers to profound sensorineural hearing loss or non-functional hearing in one ear, with normal or near-normal hearing in the other ear. Its hallmark is the inability to localize sound and hear in noisy environments. Conductive hearing loss occurs when there is a mechanical problem with the conduction of sound vibrations. Mixed hearing loss is a combination of sensorineural and conductive hearing loss. Conductive and mixed hearing loss, which frequently affect both ears, create additional challenges in learning, employment, and quality of life. Cochlear implants and bone-conduction implants may offer objective and subjective benefits of hearing for people with these conditions who are deemed inappropriate candidates for standard hearing aids and do not meet the current indication (i.e., bilateral deafness) for publicly funded cochlear implants in Canada. METHODS: We conducted a health technology assessment, which included an evaluation of clinical benefits and harms, cost-effectiveness, budget impact, and patient preferences and values related to implantable devices for single-sided deafness and conductive or mixed hearing loss. We performed a systematic literature search for systematic reviews and cost-effectiveness studies of cochlear implants and bone-conduction implants, compared to no interventions, for these conditions in adults and children. We conducted cost-utility analyses and budget impact analyses from the perspective of the Ontario Ministry of Health to examine the impact of publicly funding both types of hearing implants for the defined populations. We also interviewed 22 patients and parents of children about their experience with hearing loss and hearing implants. RESULTS: We included 20 publications in the clinical evidence review. For adults and children with single-sided deafness, cochlear implantation when compared with no treatment improves speech perception in noise (% correct responses: 43% vs. 15%, P < .01; GRADE: Moderate), sound localization (localization error: 14° vs. 41°, P < .01; GRADE: Moderate), tinnitus (Visual Analog Scale, loudness: 3.5 vs. 8.5, P < .01; GRADE: Moderate), and hearing-specific quality of life (Speech Spatial and Qualities of Hearing Scale, speech: 5.8 vs. 2.6, P = .01; spatial: 5.7 vs. 2.3, P < .01; GRADE: Moderate); for children, speech and language development also improve (GRADE: Moderate). For those with single-sided deafness in whom cochlear implantation is contraindicated, bone-conduction implants when compared with no intervention provide clinically important functional gains in hearing thresholds (36-41 dB improvement in pure tone audiometry and 38-56 dB improvement in speech reception threshold, P < .05; GRADE: Moderate) and improve speech perception in noise (signal-to-noise ratio -2.0 vs. 0.6, P < .05 for active percutaneous devices; signal-to-noise ratio improved by 1.3-2.5 dB, P < .05 for active transcutaneous devices; GRADE: Moderate) and hearing-specific quality of life (Abbreviated Profile for Hearing Aid Benefit, ease of communication: 12%-53% vs. 24%-59%; background noise: 18%-48% vs. 33%-79%; listening in reverberant condition: 26%-55% vs. 41%-65%, P < .05 [active percutaneous devices]; ease of communication: 7% vs. 20%; background noise: 46% vs. 69%; listening in reverberant condition: 27% vs. 43%; P < .05 [active transcutaneous devices]; Children's Home Inventory for Listening Difficulties score 7.3 vs. 3.4; P < .05 [passive transcutaneous devices]; GRADE: Moderate). For those with conductive or mixed hearing loss, bone-conduction implants when compared with no intervention improve hearing thresholds (improved 19-45 dB [active percutaneous devices], improved 24-37 dB [active transcutaneous devices], improved 31 dB [passive transcutaneous devices], and improved 21-49 dB [active transcutaneous middle-ear implants]; GRADE: Moderate), speech perception (% correct: 77%-93% vs. < 25%; P < .05 [active transcutaneous devices], % speech recognition: 55%-98% vs. 0-72%; P < .05 [active transcutaneous middle-ear implants]; GRADE: Moderate), and hearing-specific quality of life and subjective benefits of hearing (GRADE: Moderate).In the cost-utility analyses, cochlear implants for adults and children with single-sided deafness provided greater health gains for an incremental cost, compared with no intervention. On average, the incremental cost-effectiveness ratio (ICER) was between $17,783 and $18,148 per quality-adjusted life-year (QALY). At a willingness-to-pay of $100,000 per QALY, 70% of the simulations were considered cost-effective. For the same population, bone-conduction implants were not likely to be cost-effective compared with no intervention (ICER: $402,899-$408,350/QALY). Only 38% of simulations were considered cost-effective at a willingness-to-pay of $100,000 per QALY. For adults and children with conductive or mixed hearing loss, bone-conduction implants may be cost-effective compared with no intervention (ICER: $74,155-$87,580/QALY). However, there was considerable uncertainty in the results. At a willingness-to-pay of $100,000 per QALY, only 50% to 55% of simulations were cost-effective. In sensitivity analyses, results were most sensitive to changes in health-related utilities (measured using generic quality-of-life tools), highlighting the limitations of currently published data (i.e., small sample sizes and short follow-up).For people with single-sided deafness, publicly funding cochlear implants in Ontario would result in an estimated additional cost of $2.8 million to $3.6 million in total over the next 5 years, and an additional $0.8 million would be required for bone-conduction implants for this population. For people with conductive or mixed hearing loss, publicly funding bone-conduction implants would cost an estimated additional $3.1 million to $3.3 million in total over the next 5 years.In interviews, people with single-sided deafness and conductive or mixed hearing loss reported that standard hearing aids did not meet their expectations; therefore, they chose to undergo surgery for an implantable device. Most participants with experience of a cochlear implant or bone-conduction implant spoke positively about being able to hear better and enjoy a better quality of life. People with a cochlear implant reported additional benefits: binaural hearing, better sound localization, and better hearing in noisy areas. Cost and access were barriers to receiving an implantable device. CONCLUSIONS: Based on evidence of moderate quality, cochlear implantation and bone-conduction implants improve functional and patient-important outcomes in adults and children with single-sided deafness and conductive or mixed hearing loss. Qualitative results of interviews with patients are consistent with the findings of the systematic reviews we examined.Among people with single-sided deafness, cochlear implants may be cost-effective compared with no intervention, but bone-conduction implants are unlikely to be. Among people with conductive or mixed hearing loss, bone-conduction implants may be cost-effective compared with no intervention. Results and uncertainty are mainly driven by changes in health utilities associated with having a hearing implant. Hence, further research on utility values in this population is warranted with larger sample sizes and longer follow-up.The 5-year cost of publicly funding both types of hearing implant for single-sided deafness and conductive or mixed hearing loss in Ontario is estimated to be $6.7 million to $7.8 million.

Intercepting Endometrial Cancer: Opportunities to Expand Access Using New Technology.

Although endometrial cancer is often diagnosed at an early curable stage, the incidence and mortality from endometrial cancer is rising and minority women are particularly at risk. We hypothesize that delays in clinical presentation contribute to racial disparities in endometrial cancer mortality and treatment-related morbidity. Improved methods for endometrial cancer risk assessment and distinguishing abnormal uterine bleeding and postmenopausal bleeding from physiologic variation are needed. Accordingly, we propose a multipronged strategy that combines innovative patient education with novel early detection strategies to reduce health impacts of endometrial cancer and its precursors, especially among Black women. Futuristic approaches using gamification, smartphone apps, artificial intelligence, and health promotion outside of the physical clinic hold promise in preventing endometrial cancer and reducing morbidity and mortality related to the disease, but they also raise a number of questions that will need to be addressed by future research.

The South African Guidelines for Pharmacoeconomic Submissions' Evidence Requirements Compared with Other African Countries and The National Institute for Health and Care Excellence in England.

Objectives: The South African Guidelines for Pharmacoeconomic Submissions (SAGPS) were compared with other African pharmacoeconomic guidelines and the National Institute of Health and Care Excellence Methods Guide (NICE MG) to make recommendations for evidence generation and further development thereof.Methods: The European Network for HTA Core Model (version 3.0) (the Model) provided the comparative framework, using three criteria: completely, partly, or not completely requiring the same/similar information.Results: Of 45 African countries reviewed, only Egypt had a publicly accessible pharmacoeconomic guideline (EPG). The guidelines were different in respect to their intended audience, size, and content but for all the main focus are the economic evaluation, and health problem and current treatment domains. The SAGPS and EPG had few requirements for a medicine's safety, organizational, ethical, and legal aspects. The SAGPS completely or partly required the same/similar information as the Model for 41.2% of total issues, the EPG 33.3%, and the NICE MG 63.2%.Conclusions: The SAGPS was similar to the EPG, but not as comprehensive as the NICE MG and could be strengthened for decision-making and priority setting. Evidence generation should focus on describing the medicine's targeted disease and current treatment options, and associated cost and outcomes data.

Autologous Serum-Based Eye Drops for Treatment of Ocular Surface Disease: A Report by the American Academy of Ophthalmology.

PURPOSE: To describe the safety and effectiveness of using autologous serum-based eye drops for the treatment of severe dry eye and persistent corneal epithelial defect. METHODS: Literature searches of the PubMed and Cochrane Library databases were conducted most recently in March 2019. The searches identified 281 citations, which were reviewed in abstract form. Of these, 48 were selected for a full-text review, and 13 met the inclusion criteria and were assigned a quality-of-evidence rating by the panel methodologist. Eight of these studies were rated level II and 5 were rated level III; there were no level I studies. RESULTS: This analysis included 10 studies of the use of autologous serum-based eye drops for severe dry eye disease and 4 studies of persistent epithelial defect. Several studies showed good effectiveness, with some improvement in symptoms, signs, or both. Eight of the studies reported improved symptoms for severe dry eye disease, and all noted improvement in at least 1 clinical sign. For persistent epithelial defects, all of the studies showed improvement, with 3 of the 4 demonstrating an improvement rate of more than 90%. Adverse events were rare. CONCLUSIONS: Although autologous serum-based tears may be effective in the treatment of severe dry eye and persistent epithelial defect, conclusions are limited owing to the absence of controlled trials.

Critical review and quality-assessment of cost analyses in radiotherapy: How reliable are the data?

PURPOSE/OBJECTIVE: Health economic evaluations (HEE) are increasingly having an impact on policymakers, although the results greatly depend on the quality of the methodology used and on transparent reporting. The two main objectives of this study were to evaluate the quality of cost analyses of external beam radiotherapy (EBRT) and to assess the comprehensiveness and relevance of cost criteria defined in three validated quality-assessment instruments. MATERIALS AND METHODS: The selection of articles was based on a previous systematic literature review of EBRT-costing studies retrieved from January 2004 to January 2015 (Period 1) in MEDLINE, Embase, and NHS-EED databases and completed in a second time period from January 2015 to November 2018 (Period 2). Three validated instruments to assess the methodology quality with the CHEC and the QHES, and the methodology with the CHEERS checklists were used. The quality was evaluated by both quantitative and qualitative analyses. The scoring robustness was examined with the Kendall coefficient of concordance and inter-class correlation coefficients. RESULTS: In total, twenty-three articles were selected. The main geographic areas of cost analyses were Canada (n = 5), France (n = 4), and the USA (n = 4). The most commonly studied pathologies and technologies were prostate (n = 7) and head and neck cancer (n = 5) and IMRT (n = 8) and IGRT (n = 2), respectively. The mean instrument scores demonstrated a fair degree of methodological quality, with 69.7% for the CHEC, 73.6% for the QHES, as well as for the reporting quality, with 59.4% for CHEERS for Period 1 (74.4%, 71.5%, and 66.1%, respectively, for Period 2). An additional qualitative analysis per criterion revealed that certain items, essential for understanding the costing methodology and the results (e.g., the time horizon, discount rate, sensitivity analysis) were often only partially completed. Statistical analysis confirmed that the reviewers' scoring was consistent. The instruments identified the same top three articles, albeit with a degree of variation in the ranking. CONCLUSION: Qualitative and quantitative assessment of cost analyses in EBRT exhibits a fair level of study quality in terms of the methodology and reporting transparency. The impact of cost calculations on the final HEE result appears to be underestimated, and increased transparency of the data sources and the methodologies is needed.

Stories of Patient Involvement Impact in Health Technology Assessments: A Discussion Paper.

OBJECTIVES: As more health technology assessment (HTA) bodies seek to implement patient involvement, there is a desire to learn from other HTA bodies about their experiences and understand what approaches can be used and which ones make a real difference to HTA. This is difficult, as the impact of patient involvement in HTA is not well documented. This study aims to promote further discussion about the ways in which patient involvement can impact HTAs by studying stories of impact. METHODS: In a multi-stakeholder workshop, experts leading patient involvement in four HTA bodies shared examples of HTAs where they believed patient involvement made a difference, then they reflected on these impact stories within the wider context of impact evaluation. RESULTS: The HTA bodies drew on patient input and patient-based evidence to inform their HTAs. The patient involvement was observed to elucidate patients' experiences, needs and preferences which, in turn, was observed to influence the HTA recommendations about optimal use of technologies, including taking account of issues for sub-groups, outcomes that matter to patients and educational needs. CONCLUSIONS: Personal stories of patient involvement may enable a wider understanding of different approaches to and impact of patient involvement. The examples relate to both patient input and patient-based evidence and highlight the role that patient involvement can play in reducing uncertainties and complementing the clinical and economic evidence in HTA. They suggest that impact can be seen in recommendations about how and when a technology is used.

How Do Pharmaceutical Companies Model Survival of Cancer Patients? A Review of NICE Single Technology Appraisals in 2017.

OBJECTIVES: Before an intervention is publicly funded within the United Kingdom, the cost-effectiveness is assessed by the National Institute of Health and Care Excellence (NICE). The efficacy of an intervention across the patients' lifetime is often influential of the cost-effectiveness analyses, but is associated with large uncertainties. We reviewed committee documents containing company submissions and evidence review group (ERG) reports to establish the methods used when extrapolating survival data, whether these adhered to NICE Technical Support Document (TSD) 14, and how uncertainty was addressed. METHODS: A systematic search was completed on the NHS Evidence Search webpage limited to single technology appraisals of cancer interventions published in 2017, with information obtained from the NICE Web site. RESULTS: Twenty-eight appraisals were identified, covering twenty-two interventions across eighteen diseases. Every economic model used parametric curves to model survival. All submissions used goodness-of-fit statistics and plausibility of extrapolations when selecting a parametric curve. Twenty-five submissions considered alternate parametric curves in scenario analyses. Six submissions reported including the parameters of the survival curves in the probabilistic sensitivity analysis. ERGs agreed with the company's choice of parametric curve in nine appraisals, and agreed with all major survival-related assumptions in two appraisals. CONCLUSIONS: TSD 14 on survival extrapolation was followed in all appraisals. Despite this, the choice of parametric curve remains subjective. Recent developments in Bayesian approaches to extrapolation are not implemented. More precise guidance on the selection of curves and modelling of uncertainty may reduce subjectivity, accelerating the appraisal process.

A review and validation of overall survival extrapolation in health technology assessments of cancer immunotherapy by the National Institute for Health and Care Excellence: how did the initial best estimate compare to trial data subsequently made available?

BACKGROUND: Validation of overall survival (OS) extrapolations of immune-checkpoint inhibitors (ICIs) during the National Institute for Health and Care Excellence (NICE) Single Technology Assessment (STA) process is limited due to data still maturing at the time of submission. Inaccurate extrapolation may lead to inappropriate decision-making. The availability of more mature trial data facilitates a retrospective analysis of the plausibility and validity of initial extrapolations. This study compares these extrapolations to subsequently available longer-term data. METHODS: A systematic search of completed NICE appraisals of ICIs from March 2000 to December 2017 was performed. A targeted search was also undertaken to procure published OS data from the pivotal clinical trials for each identified STA made available post-submission to NICE. Initial Kaplan-Meier curves and associated extrapolations from NICE documentation were extracted to compare the accuracy of OS projections versus the most mature data. RESULTS: The review identified 11 STAs, of which 10 provided OS data upon submission to NICE. The extrapolations undertaken considered parametric or piecewise survival models. Additional data cut-offs provided a mean of 18 months of OS beyond the end of the original data. Initial extrapolations typically under-estimated OS from the most mature data cut-off by 0.4-2.7%, depending on the choice of assessment method and use of the manufacturer- or ERG-preferred extrapolation. CONCLUSION: Long-term extrapolation of OS is required for NICE STAs based on initial immature OS data. The results of this study demonstrate that the initial OS extrapolations employed by manufacturers and ERGs generally predicted OS reasonably well when compared to more mature data (when available), although on average they appeared to underestimate OS. This review and validation shows that, while the choice of OS extrapolation is uncertain, the methods adopted are generally aligned with later-published follow-up data and appear appropriate for informing HTA decisions.

EVIDENCE REQUIRED BY HEALTH TECHNOLGY ASSESSMENT AND REIMBURSEMENT BODIES EVALUATING DIAGNOSTIC OR PROGNOSTIC ALGORITHMS THAT INCLUDE OMICS DATA.

OBJECTIVES: Multi-analyte assays with algorithmic analyses (MAAAs) use combinations of circulating and clinical markers including omics-based sources for diagnostic and/or prognostic purposes. Assessing MAAAs is challenging under existing health technology assessment (HTA) methods or practices. We undertook a scoping review to explore the HTA methods used for MAAAs to identify the criteria used for clinical research and reimbursement purposes. METHODS: This review included only non-companion (stand-alone) tests that are actionable and that have been evaluated by leading HTA or insurer/reimbursement bodies up to September 2017. RESULTS: Twenty-five reports and articles evaluating seventeen MAAAs were examined, most of which have been developed in oncology. The two main models used were the EUnetHTA Core model and the Evaluation of Genomic Applications in Practice and Prevention ACCE framework. Clinical validity and utility criteria were used, as were economic, ethical, legal, and social aspects. Economic evidence on MAAAs was scarce, and there is no consensus on whether the perspectives used are sufficiently broad to include all relevant stakeholders. CONCLUSIONS: Clinical utility and efficiency were the most used criteria, with stronger evidence needed linking the use of the algorithm with the clinical outcomes in real-life practice. HTA bodies must as well consider questions related to the analytical validity of MAAAs or with organizational aspects. The two main models, the EUnetHTA Core model and the ACCE framework, could be adapted to the assessment of MAAAs.

ENVIRONMENTAL IMPACT ASSESSMENT OF A HEALTH TECHNOLOGY: A SCOPING REVIEW.

INTRODUCTION: The Health Technology Expert Review Panel is an advisory body to Canadian Agency for Drugs and Technologies in Health (CADTH) that develops recommendations on health technology assessments (HTAs) for nondrug health technologies using a deliberative framework. The framework spans several domains, including the environmental impact of the health technology(ies). Our research objective was to identify articles on frameworks, methods or case studies on the environmental impact assessment of health technologies. METHODS: A literature search in major databases and a focused gray literature search were conducted. The main search concepts were HTA and environmental impact/sustainability. Eligible articles were those that described a conceptual framework or methods used to conduct an environmental assessment of health technologies, and case studies on the application of an environmental assessment. RESULTS: From the 1,710 citations identified, thirteen publications were included. Two articles presented a framework to incorporate environmental assessment in HTAs. Other approaches described weight of evidence practices and comprehensive and integrated environmental impact assessments. Central themes derived include transparency and repeatability, integration of components in a framework or of evidence into a single outcome, data availability to ensure the accuracy of findings, and familiarity with the approach used. CONCLUSIONS: Each framework and methods presented have different foci related to the ecosystem, health economics, or engineering practices. Their descriptions suggested transparency, repeatability, and the integration of components or of evidence into a single outcome as their main strengths. Our review is an initial step of a larger initiative by CADTH to develop the methods and processes to address the environmental impact question in an HTA.

[Theoretical grounds of a structural and functional model for quality assurance of radiation diagnostics under conditions of development of the modern health care system in Ukraine].

OBJECTIVE: Introduction: Modern changes in the health care system of Ukraine are focused on financial support in providing medical and diagnostic care to the population and are based on deep and consistent structural and functional transformations. They are aimed at providing adequate quality care, which is the main target function and a principal criterion for operation of health care system. The urgency of this problem is increasing in the context of reforming the health care system and global changes in the governmental financial guarantees for the provision of medical services to the population. The aim of the work is to provide theoretical grounds for a structural and functional model of quality assurance of radiation diagnostics at all levels of medical care given to the population under the current health care reform in Ukraine. PATIENTS AND METHODS: Materials and methods: The object of the study is organizing the operation of the radiation diagnostic service; the information is based on the actual data on the characteristics of radiation diagnosis at different levels of medical care provision. Methods of systematic approach, system analysis and structural and functional analysis of the operating system of radiation diagnostics are used. RESULTS: Review: The basis of the quality assurance model is the cyclical process, which includes the stages of the problem identifition, planning of its solution, organization of the system for implementation of decisions, monitoring the quality management process of the radiation diagnostics, and factors influencing the quality of the radiation diagnostics service. These factors include the quality of the structure, process, results, organization of management and control of current processes and the results of radiation diagnostics management. CONCLUSION: Conclusions: The advantages of the proposed model for ensuring the quality of the radiation diagnostics service are its systemacy and complexity, elimination of identified defects and deficiencies, and achievement of profitability through modern redistribution and use of existing resources of the health care system. The results of adequate service quality management activities in radiation diagnostics are the improvement of organizational and economic principles along with legislative regulation, the implementation of a modern system of radiation diagnostics in the state health care at the national and regional levels, the increase of the accessibility, quality and efficiency of the radiation diagnostics service.

Drug Policy in Estonia.

The aim of this article was to present a general overview of the health care system as well as pricing and reimbursement environment in Estonia. In Estonia the main stakeholders in the pharmaceutical sector are the Ministry of Social Affairs, the State Agency of Medicine, and the Estonian Health Insurance Fund. The national health insurance scheme is public, and approximately 95% of the population is covered by it. It is a social insurance, and universal and equal access to health care based on national health insurance is granted. The Estonian Health Insurance Fund is financed from social taxes and state budget and is responsible for the reimbursement of pharmaceuticals in the hospital setting. It acts as an advisory body to the Ministry of Social Affairs on the process of reimbursement regarding cost effectiveness. Pharmaceutical products' reimbursement dossiers submission and decisions are dealt with on the state level. Health technology assessment analyses are required by the authorities and the Baltic Guidelines for Economic Evaluations of Pharmaceuticals have to be followed. The reimbursement lists are positive lists only, and the criteria upon which reimbursement decisions are based are officially defined. Revisions of reimbursement are performed depending on the need and they are based on the prices of reference countries.

Impact assessment of Iran's health technology assessment programme.

BACKGROUND: Following approximately 10 years from the beginning of Iran's national Health Technology Assessment (HTA) programme, the present study aims to evaluate its success by examining the impact of HTA and identifying the determinant factors leading to the implementation of HTA report results. METHODS: The triangulation method was employed herein. HTA reports were initially identified and their impact and determinant factors were then examined from the perspectives of both researchers (by preparing a questionnaire according to the Payback model and sending it to HTA principle investigators) and stakeholders (semi-structured interviews held with each HTA stakeholder). Simultaneously, the quality of the HTA reports was examined with relevant critical appraisal checklists. RESULTS: The impact of 19 equipment technologies and four pharmaceutical technologies were assessed in this study. Twenty researchers replied (response rate, 86.96%) to the questionnaire on the impact of HTA reports from the researcher's perspective. To assess the impact of HTA reports from the stakeholder's perspective, seven policy-makers were chosen and interviewed as the main target audience. The most common step taken to disseminate the results of the HTA projects was publication. Conducting the HTA had taught researchers and their colleagues' new skills and had facilitated the securing of research grants from other organisations. Most reports had used the systematic review method but the relevant details had been scarcely presented regarding outcomes, costs and analysis. The greatest impact of HTA reports on decision-making had been on policy-makers providing and allocating finances. Barriers in stewardship, identification and prioritisation of topics, performance and dissemination of HTA results were the main barriers of implementing HTAs. CONCLUSIONS: In most aspects, the status of HTA impact reports need improvement. Thus far, the barriers and facilitators of the HTA programme in Iran have been investigated in other studies. These findings should be pooled to reach a solution that can be actively applied to the health system to improve the status quo of HTA in Iran.

Desarrollo de la evaluación de tecnologías en salud en algunos países de Latinoamérica / The development of health technology assessment in some Latin American countries

La evaluación de las tecnologías tiene una serie de definiciones que terminan precisando de un análisis multidisciplinario que sirven para tomar decisiones. La evolución de la evaluación de tecnologías sanitarias se manifiesta a través de la Oficina de evaluación de tecnologías del congreso de Estados Unidos, la sociedad internacional para la evaluación de tecnologías en salud, la red internacional de agencias de evaluación de tecnologías en salud y las distintas organizaciones mundiales y regionales que siguen impulsando su desarrollo en el mundo y la Región Latinoamericana. La evaluación de las tecnologías sanitarias es una herramienta para la toma de decisiones que, según el apoyo político, que reciba, su crecimiento está asegurado(AU)

The technology assessment has a number of definitions that require a multidisciplinary analysis for decision-making. The evolution of the health technology assessment becomes evident through the Office of Technology Assessment of the US Congress, the International Society for Health Technology Assessment, the international network of health technology assessment and the global and regional organizations that continue to drive its development agencies and the various regional and world organizations that continue advancing its development in Latin America and the world. The health technology assessment is a tool for decision-making and, depending on the political support, its growth is assured(AU)

HOW TO AVOID GIVING THE RIGHT ANSWERS TO THE WRONG QUESTIONS: THE NEED FOR INTEGRATED ASSESSMENTS OF COMPLEX HEALTH TECHNOLOGIES.

Health technologies are becoming increasingly complex and contemporary health technology assessment (HTA) is only partly equipped to address this complexity. The project "Integrated assessments of complex health technologies" (INTEGRATE-HTA), funded by the European Commission, was initiated with the overall objective to develop concepts and methods to enable patient-centered, integrated assessments of the effectiveness, and the economic, social, cultural, and ethical issues of complex technologies that take context and implementation issues into account. The project resulted in a series of guidances that should support the work of HTA scientists and decision makers alike.

ARTHROSCOPIC SURGERY FOR KNEE OSTEOARTHRITIS: IMPACT OF HEALTH TECHNOLOGY ASSESSMENT IN GERMANY.

OBJECTIVES: This study aims to describe how a negative reimbursement decision-based on the health technology assessment (HTA) report of a nondrug intervention-affects healthcare providers in Germany. METHODS: Knee arthroscopy was chosen as an example, because as of April 2016 this procedure is no longer reimbursed for osteoarthritis, but is still covered for other indications, including meniscal lesions. The exclusion followed an HTA report prepared by the Institute for Quality and Efficiency in Health Care (IQWiG). Here, we examine how the decision to revoke reimbursement for arthroscopy was perceived by the surgical community. Information was collected from official hospital statistics, the internet, and informal interviews with orthopedic surgeons. RESULTS: In 2015, a total of 37,920 arthroscopic procedures were performed for knee osteoarthritis in Germany. Several surgical societies were unhappy with the negative decision, which was issued as a directive in November 2015, and they challenged the decision-making process as well as the underlying scientific evidence. In March 2016, fifteen societies issued joint recommendations on how to differentiate osteoarthritis from other knee diseases and how to document other diseases in a way that inspections by representatives of health insurance funds would not detect any deficiencies. In informal interviews, orthopedic surgeons indicated that miscoding of the principal diagnosis (meniscal tear rather than knee osteoarthritis) is to be expected, especially in the hospital sector. CONCLUSIONS: HTA can have a significant impact on the provision of health services, but various loopholes allow physicians to undermine policy decisions. Therefore, it is important to involve all stakeholders in HTA and to convince them of the benefits of evidence-based medicine.

The correlation between HTA recommendations and reimbursement status of orphan drugs in Europe.

BACKGROUND: The aim of this study was to review and compare types of reimbursement recommendations for orphan drugs issued by eight European health technology assessment (HTA) agencies and the reimbursement status of these drugs in the corresponding countries. Separate calculations were also performed for three sub-groups: ultra-orphan drugs, oncology orphan drugs and other (non-ultra, non-oncology) orphan drugs. RESULTS: We reviewed drugs authorized by the European Medicine Agency (EMA) between 1 November 2002 and 30 September 2015. Among these, we identified 101 orphan drugs. Seventy-nine of them were assessed by eight European HTA agencies. The average rates of positive, conditional and negative reimbursement recommendations issued by these agencies were 55.7 %, 15.3 % and 29.0 %, respectively. On average, 21.2 % of EMA-authorized orphan drugs were reimbursed in the eight European countries studied: 49.0 % of those with positive, 53.6 % of those with conditional, and 16.0 % of those with negative reimbursement recommendations. In addition, 5.4 % of orphan drugs that had not been assessed by any of the eight HTA agencies were also reimbursed. The shares of oncology, ultra, and other orphan drugs that were assessed by HTA agencies were similar, with the lowest share observed in ultra-orphan drugs (72 %) and the highest in other orphan drugs (80 %). In terms of reimbursement, 20 % of oncology orphan drugs, 25 % of ultra-orphan drugs and 21 % of other orphan drugs were reimbursed. CONCLUSIONS: Reimbursement of orphan drugs does not always correspond to the type of HTA recommendation. While the highest rate of reimbursement is observed (unsurprisingly) among drugs with positive or conditional recommendation, a high rate of reimbursement (11 %) is also observed among ultra-orphan drugs that had never been assessed by any HTA agency.

Health Technology Assessment for Molecular Diagnostics: Practices, Challenges, and Recommendations from the Medical Devices and Diagnostics Special Interest Group.

BACKGROUND: Health technology assessments (HTAs) are increasingly used to inform coverage, access, and utilization of medical technologies including molecular diagnostics (MDx). Although MDx are used to screen patients and inform disease management and treatment decisions, there is no uniform approach to their evaluation by HTA organizations. OBJECTIVES: The International Society for Pharmacoeconomics and Outcomes Research Devices and Diagnostics Special Interest Group reviewed diagnostic-specific HTA programs and identified elements representing common and best practices. METHODS: MDx-specific HTA programs in Europe, Australia, and North America were characterized by methodology, evaluation framework, and impact. Published MDx HTAs were reviewed, and five representative case studies of test evaluations were developed: United Kingdom (National Institute for Health and Care Excellence's Diagnostics Assessment Programme, epidermal growth factor receptor tyrosine kinase mutation), United States (Palmetto's Molecular Diagnostic Services Program, OncotypeDx prostate cancer test), Germany (Institute for Quality and Efficiency in Healthcare, human papillomavirus testing), Australia (Medical Services Advisory Committee, anaplastic lymphoma kinase testing for non-small cell lung cancer), and Canada (Canadian Agency for Drugs and Technologies in Health, Rapid Response: Non-invasive Prenatal Testing). RESULTS: Overall, the few HTA programs that have MDx-specific methods do not provide clear parameters of acceptability related to clinical and analytic performance, clinical utility, and economic impact. The case studies highlight similarities and differences in evaluation approaches across HTAs in the performance metrics used (analytic and clinical validity, clinical utility), evidence requirements, and how value is measured. Not all HTAs are directly linked to reimbursement outcomes. CONCLUSIONS: To improve MDx HTAs, organizations should provide greater transparency, better communication and collaboration between industry and HTA stakeholders, clearer links between HTA and funding decisions, explicit recognition of and rationale for differential approaches to laboratory-developed versus regulatory-approved test, and clear evidence requirements.

A comparison of two methods for expert elicitation in health technology assessments.

BACKGROUND: When data needed to inform parameters in decision models are lacking, formal elicitation of expert judgement can be used to characterise parameter uncertainty. Although numerous methods for eliciting expert opinion as probability distributions exist, there is little research to suggest whether one method is more useful than any other method. This study had three objectives: (i) to obtain subjective probability distributions characterising parameter uncertainty in the context of a health technology assessment; (ii) to compare two elicitation methods by eliciting the same parameters in different ways; (iii) to collect subjective preferences of the experts for the different elicitation methods used. METHODS: Twenty-seven clinical experts were invited to participate in an elicitation exercise to inform a published model-based cost-effectiveness analysis of alternative treatments for prostate cancer. Participants were individually asked to express their judgements as probability distributions using two different methods - the histogram and hybrid elicitation methods - presented in a random order. Individual distributions were mathematically aggregated across experts with and without weighting. The resulting combined distributions were used in the probabilistic analysis of the decision model and mean incremental cost-effectiveness ratios and the expected values of perfect information (EVPI) were calculated for each method, and compared with the original cost-effectiveness analysis. Scores on the ease of use of the two methods and the extent to which the probability distributions obtained from each method accurately reflected the expert's opinion were also recorded. RESULTS: Six experts completed the task. Mean ICERs from the probabilistic analysis ranged between £162,600-£175,500 per quality-adjusted life year (QALY) depending on the elicitation and weighting methods used. Compared to having no information, use of expert opinion decreased decision uncertainty: the EVPI value at the £30,000 per QALY threshold decreased by 74-86 % from the original cost-effectiveness analysis. Experts indicated that the histogram method was easier to use, but attributed a perception of more accuracy to the hybrid method. CONCLUSIONS: Inclusion of expert elicitation can decrease decision uncertainty. Here, choice of method did not affect the overall cost-effectiveness conclusions, but researchers intending to use expert elicitation need to be aware of the impact different methods could have.