Health Technology Assessment Submissions Research Articles

HTA206 Use of Real-World Data in Systematic Literature Reviews Conducted for Health Technology Assessment Submissions in Europe

Real-world data (RWD) has become an important source of evidence to support payer decision-making during health technology assessment (HTA). RWD is increasingly reviewed by HTA bodies as supporting evidence for effectiveness and safety of interventions. The aim is to identify and describe the extent published RWD evidence is being reviewed as part of systematic literature reviews (SLRs) for HTA.

HTA76 Clinical Expert Opinion in Health Technology Assessment Submissions to a National HTA Agency in Ireland

HTA76 Clinical Expert Opinion in Health Technology Assessment Submissions to a National HTA Agency in Ireland

Appraisals by Health Technology Assessment Agencies of Economic Evaluations Submitted as Part of Reimbursement Dossiers for Oncology Treatments: Evidence from Canada, the UK, and Australia.

Publicly funded healthcare systems, including those in Canada, the United Kingdom (UK), and Australia, often use health technology assessment (HTA) to inform drug reimbursement decision-making, based on dossiers submitted by manufacturers, and HTA agencies issue publicly available reports to support funding recommendations. However, the level of information reported by HTA agencies in these reports may vary. To provide insights on this issue, we describe and assess the reporting of economic methods in recent oncology HTA recommendations from the Canadian Agency for Drugs and Technologies in Health (CADTH), National Institute for Health and Care Excellence (NICE), and Pharmaceutical Benefits Advisory Committee (PBAC). Publicly available HTA recommendations and reports for oncology drugs issued by CADTH over a 2-year period, 2019–2020, were identified and compared with the corresponding HTA documents from NICE and the PBAC. Reporting of key model characteristics and attributes, survival analysis methods, methodological criticisms, and re-assessment of the economic results were characterized using descriptive statistics. Dichotomous differences in the methodological criticisms observed between the three agencies were assessed using Cochran’s Q tests and substantiated using pairwise McNemar tests. Chi-squared tests were used to assess the dichotomous differences in the reporting of methods and explore the potential relationships between categorical variables, where appropriate. HTAs published by CADTH, NICE, and the PBAC consistently reported a broad spectrum of descriptive information on the economic models submitted by manufacturers. While common economic evaluation attributes were well-reported across the three HTA agencies, significant differences in the reporting of survival analysis methods and methodological criticisms were observed. NICE consistently reported more comprehensive information, compared to either CADTH or PBAC. Despite these differences, broadly similar recommendation rates were observed between CADTH and NICE. The PBAC was found to be more restrictive. Based on our 2-year sample of oncology, the HTAs published by CADTH matched with the corresponding HTAs from NICE and PBAC; we observed important variations in the reporting of economic evidence, especially technical aspects, such as survival analysis, across the three agencies. In addition to guidelines for HTA submissions by manufacturers, the community of HTA agencies should also have common standards for reporting the results of their assessments, though the information and opinions reported may differ.

Novel and existing flexible survival methods for network meta-analyses.

Aim: Technical Support Document 21 discusses trial-based, flexible relative survival models. The authors generalized flexible relative survival models to the network meta-analysis (NMA) setting while accounting for different treatment-effect specifications. Methods: The authors compared the standard parametric model with mixture, mixture cure and nonmixture cure, piecewise, splines and fractional polynomial models. The optimal treatment-effect parametrization was defined in two steps. First, all models were run with treatment effects on all parameters and subsequently the optimal model was defined by removing uncertain treatment effects, for which the parameter was smaller than its standard deviation. The authors used a network in previously treated advanced non-small-cell lung cancer. Results: Flexiblemodel-based NMAs impact fit and incremental mean survivaland they increase corresponding uncertainty. Treatment-effect specification impacts incremental survival, reduces uncertainty and improves the fit statistic. Conclusion: Extrapolation techniques already available for individual trials can now be used for NMAs to ensure that the most plausible extrapolations are being used for health technology assessment submissions.

Challenges and Opportunities for Companies to Build HTA/Payer Perspectives Into Drug Development Through the Use of a Dynamic Target Product Profile.

Background: The target product profile (TPP) outlines the desired profile of a target product aimed at a particular disease and is used by companies to plan clinical development. Considering the increasing importance of health technology assessment (HTA) in informing reimbursement decisions, a robust TPP needs to be built to address HTA needs, to guide an integrated evidence generation plan that will support HTA submissions. This study assessed current practices and experiences of companies in building HTA considerations into TPP development. Methods: An opinion survey was designed and conducted in 2019, as a cross-sectional questionnaire consisting of multiple-choice questions. The questionnaire provided a qualitative assessment of companies’ strategies and experiences in building HTA considerations into the TPP. Eligible survey participants were the senior management of Global HTA/Market Access Departments at 18 top international pharmaceutical companies. Results: 11 companies responded to the survey. All companies included HTA requirements in TPP development, but the timing and process varied. The key focus of HTA input related to health problems and treatment pathways, clinical efficacy/effectiveness, and safety. Variance of HTA methods and different value frameworks were identified as a challenge for development plans. Stakeholder engagement, such as HTA scientific advice, was used to pressure test the TPP. Conclusion: This research provides insight into current practice and potential opportunities for value-based drug development. It demonstrates the evolution of the TPP to encompass HTA requirements and suggests that the TPP could have a role as an iterative communication tool for use with HTA agencies to enhance an integrated evidence generation plan.

A Comparison of 7 Oncology External Control Arm Case Studies: Critiques From Regulatory and Health Technology Assessment Agencies

ObjectivesThe development of accelerated approval programs for high morbidity and unmet need conditions has driven the use of single-arm studies in drug development. Regulatory and health technology assessment (HTA) agencies are recognizing that high-quality external control arms (ECAs), built using real-world data, can reduce uncertainties arising from single-arm studies. This review compared 7 case studies of regulatory and HTA agencies’ evaluations of oncology ECAs. MethodsFood and Drug Administration multidisciplinary reviews for oncology submissions from 2014 to 2021 were screened to identify 7 cases (2 blinatumomab indications, avelumab, and erdafitinib, entrectinib, trastuzumab deruxtecan, and idecabtagene vicleucel) with ECAs to support efficacy claims. Regulatory (Food and Drug Administration, European Medicines Agency, Health Canada) and HTA (pan-Canadian Oncology Drug Review, National Institute for Health and Care Excellence, Federal Joint Committee, Haute Autorité de Santé, and Pharmaceutical Benefits Advisory Committee) submissions for these cases were reviewed. The decision makers’ ECA critiques and the level of influence on the decision were analyzed and categorized. ResultsAcross case studies, selection bias and confounding were the most common ECA critiques. Nevertheless, agreement in critiques between and among regulators and HTA bodies was low. ECA influence on agencies’ decisions also varied. ConclusionsEvaluating the same ECA evidence, agencies focused on methodologic issues (ie, selection bias and confounding), but were often not aligned on their critiques. Further research is needed to fully characterize how agencies evaluate ECAs. This study is a first step in critically evaluating agencies’ critiques of ECAs and highlights the need for future guidance development around ECA design and generation.

MSR7 Evaluating the Impact of Weighted Sample Size on Matching Adjusted Indirect Treatment Comparisons between Trials with Time-to-Event Outcome: A Simulation Study

Matching-adjusted indirect comparisons (MAICs) are a popular method of population-adjusted indirect treatment comparison used to support health technology assessment submissions. MAICs rely on a propensity score approach that rescales the weight of patients in the index trial to a target population. We sought to explore the impact of approaches used to rescale weights on the results of MAICs.

SA3 Utility of Artificial Intelligence in Systematic Literature Reviews for Health Technology Assessment Submissions

The use of artificial intelligence (AI) may alleviate additional time and effort needed to conduct robust, fully comprehensive systematic literature reviews (SLRs) intended for submission to health technology assessment (HTA) bodies. This study aimed to determine the ability of AI to accurately identify relevant studies on costs, healthcare resource use (HCRU), economic evaluations (EE), and patient-reported outcomes (PRO).

P37 The Cure Myth: Experience from Recent Health Technology Assessment (HTA) Submissions in Relapsed/Refractory Diffuse Large B-Cell Lymphoma (R/R DLBCL)

Recent clinical trials testing novel cancer therapies such as CAR-Ts are detecting a plateau in the survival curves, conveying a potential opportunity for cure. Long-term survival data are limited, and clinicians are often cautious to make conclusions on the basis of the trial outcomes. Nevertheless, cure assumptions have appeared in oncology HTA submissions such as those in R/R DLBCL. This study aims to investigate how cure assumptions are applied across different HTA submissions for therapies in R/R DLBCL. Publicly available HTA dossiers in R/R DLBCL submitted to NICE, SMC, CADTH, ICER, PBAC and HAS in the past five years were reviewed. Information related to cure assumptions (methodology, cure time point, cure proportion) and the critiques received by the HTA bodies were reviewed and extracted. Of the twelve HTA documents identified, ten submissions applied cure assumption in overall survival extrapolation. These submissions focused on two CAR-T agents (axicabtagene and tisagenlecleucel) and polatuzumab vedotin. From the ten submissions that reported cure assumptions, six used cure-mixture models and four used simple cure assumptions. Eight models set mortality of cured patients to that of the general population, while two considered an adjustment factor. Cure was considered only for the intervention arm in seven models, while the rest considered it for all treatments. The timepoint and proportion of cure varied across the submissions. Critiques were mainly around the issues caused by immaturity of survival data, such as uncertainty in cure assumptions and the choice of cure timepoint. While cure modelling is frequently used in R/R DLBCL and in oncology, there seems to be no consensus on the implication of cure and its implementation in the economic analyses. Clear guidance must be provided by health authorities on how to approach the cure concept in economic modelling and how to validate the assumptions.

POSB311 Reviewing the Use of Matching Adjusted Indirect Comparisons in Health Technology Assessment Submissions

Matching adjusted indirect comparisons (MAIC) are used to facilitate population-adjusted indirect treatment comparisons (ITCs) to support health technology assessment submissions. A recent publication (Phillippo 2020, Statistics in Medicine) evaluated the performance of MAIC and found that MAIC may be biased in cases of small sample sizes (N<500), large reductions in effective sample size (ESS), and missing effect modifiers. Therefore, we sought to assess MAICs that have been submitted to the Canadian Agency for Drugs and Technologies in Health (CADTH) to identify and summarize features that may impact the validity of the ITC.

POSA305 A Systematic Comparison of the Meta-Analysis Software Landscape and Validation of Metaxact for Meta-Analysis of Sparse Outcomes

While meta-analysis has become a prominent cornerstone of scientific medicine in the domain of therapeutics, there is no consensus on which software has the state-of-the-art features to be used for health technology assessment submissions with high degree of methodological comprehensiveness, flexibility, and usability. Furthermore, no systematic evaluation of meta-analysis software has been conducted since 2007 and since then, the meta-analysis software landscape has changed dramatically. The Objectives: of this study were to systematically compare features, flexibility, and usability of MetaXact, RevMan 5.0, Comprehensive Meta-analysis Software, STATA, and R and to validate MetaXact outputs against other meta-analysis software platforms.

Oncology drugs and added benefit: insights from 3 European health technology assessment agencies on the role of efficacy endpoints

Objective This study aimed to understand the impact of different efficacy endpoints on reimbursement decisions made by health technology assessment (HTA) bodies. Materials and methods European Medicines Agency (EMA) oncology product marketing authorizations were screened to identify products that completed review by 3 HTA bodies during 2016–2019: United Kingdom’s National Institute for Health and Care Excellence, Germany’s Gemeinsamer Bundesausschuss, and France’s Haute Autorité de Santé. Each decision’s endpoint information, including overall survival (OS) and progression-free survival (PFS), was extracted. Each endpoint’s influence on added benefits rating (the degree of added benefit as judged by the HTA agency) and full reimbursement (i.e. reimbursed population to label) decisions was tested using bivariate analyses. Results An increasing trend was observed toward HTA submissions with immature OS data (36.8% and 71.4% in 2016 and 2019, respectively), which was a predictor of limited added benefit (p < .001). Regarding data availability, 63% of submissions provided OS, 2% provided PFS without OS; and 35% provided neither. OS availability significantly influenced added benefit (p < .001) but not full reimbursement (p > .05) decisions, whereas PFS without OS had no significant impact compared with either OS or PFS data for either outcome (p = .99). Conclusions The trend toward fewer products filing mature OS data over time suggests sponsors may be increasingly confident achieving reimbursement with surrogate endpoint data, although mature OS data provided the strongest correlation to positive reimbursement decisions. Notably, in some locally advanced settings, OS data maturity will take a long time to obtain. To expedite patient access to new medicines, payers should consider the acceptance of surrogate endpoints predictive of clinical benefit.

Review and Assessment of Patient-Reported Outcomes (PRO) in Patients with Chemotherapy-Induced Anemia (CIA)

OBJECTIVES: Chemotherapy-induced anemia (CIA) is a common adverse event of cancer treatment and is associated with several symptoms that negatively impact health-related quality of life (HRQoL). Due to the nature of CIA signs and symptoms, the use of fit-for-purpose PRO measures reflecting patients' experience of the disease and its treatment is an important step in drug development and evaluation. In this project, we aimed to review and assess the most commonly used PRO measures to best capture the experiences of patients with non-myeloid malignancies.METHODS: A targeted literature review (TLR), including searches of the OVID database, US FDA/European Medicines Agency (EMA), clinical trial databases, regulatory labelling data and health technology assessment (HTA) reports/payer landscape recommendations, was conducted to identify PRO measures used to capture symptoms and HRQoL outcomes in non-myeloid cancer patients with CIA (2008-2021). PRO measures were identified from published studies, phase 2-4 clinical trials, and categorized according to the concept(s) measured and cancer type. Study outcomes were used to determine the optimal PRO strategy to capture the CIA symptoms of patients with non-myeloid cancer. The concepts captured from PROs identified in the TLR were used to develop a preliminary ‘conceptual model’: a graphical representation of signs and symptoms, and the perceived impact on HRQoL.Selected PRO measures, most relevant to the study objectives, were evaluated for their reliability, validity, responsiveness, and extent to which they cover HRQoL domains of interest and, in relation to the current regulatory environment, industry standards and guidance (e.g., FDA Guidance For Industry: Patient-Reported Outcome Measures, 2009). Reviews of the HTA guidelines and reports were conducted to provide insights into the applicability of PRO data from an HTA perspective.RESULTS: The conceptual model captured fatigue as the most important disease-related symptom experienced by non-myeloid cancer patients with CIA (Figure). The OVID search identified 17 PRO measures, which were then categorized by the key CIA-related concepts they assessed, including: sleep quality; HRQoL; anemia-related symptoms; depression/anxiety; and work productivity/activity impairment. The most frequently used PRO was the Functional Assessment of Cancer Therapy-Fatigue (FACT-F, N=11), followed by the FACT-Anemia (FACT-An, N=6). Ten PRO measures were identified from Phase 2-4 ongoing/completed US clinical trials and 6 PROs from EU clinical trials, with FACT-F (N=13) being the most common instrument used . FDA and EMA HRQoL-related product labelling information included the FACT-An, European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) and Cancer Linear Analogue Scale (CLAS).From the TLR results, 9 PRO measures were selected for further review: FACT-An (An, Anemia); FACT-F; FACT-G (G, General); Functional Assessment of Chronic Illness Therapy-F; Patient-reported Outcomes Measurement Information System-F; Brief Fatigue Inventory; Visual Analogue Scale-F; Fatigue Symptom Inventory; and EORTC QLQ-C30. Of these, FACT-An was the only PRO measure specifically developed to measure fatigue and HRQoL in anemic cancer patients. FACT-An includes four HRQoL domains (assessing physical, social/family, emotional and functional wellbeing) from the FACT-G, plus an anemia subscale that comprises a fatigue subscale (13 items) and 7 anemia-specific questions.Results from the HTA/payer landscape review also indicated that the majority of recent HTA submissions reported findings from EORTC QLQ-C30 alongside the EORTC disease-specific adaptations for oncology-related indications and the EQ-5D. Many of the recent HTAs reported data from 2 or more different PRO measures.CONCLUSIONS: CIA impacts various aspects of patients' HRQoL; however, current PRO measures may only partially capture concepts of interest to patients. Multiple measures may be needed to adequately reflect all domains affected by CIA. Future studies may consider conducting concept elicitation interviews with patients and clinicians, to inform future updates to the conceptual model, and validation work to estimate meaningful change thresholds for these measures if not available. [Display omitted] DisclosuresMorga: Astellas Pharma Europe Ltd.: Current Employment. Atzinger: Astellas Pharma Inc.: Current Employment. Barsdorf: Clinical Outcomes Solutions: Current Employment. New: IQVIA: Current Employment. Alexandre: Astellas Pharma Europe B.V.: Current Employment.

Value drivers for pharmaceutical products in health technology assessment (HTA) in Saudi Arabia: Results from a capacity Building, Multi-Stakeholder workshop

ObjectivesCapacity building exercises are important to increase understanding of healthcare processes by key stakeholders, and to facilitate open discussions to build consensus. This study explored the views of a multi-stakeholder group of local Saudi experts on possible value elements that could be important for health technology assessment (HTA) processes and methods regarding pharmaceutical products in Saudi Arabia (‘value drivers’). MethodsA diversified group of local experts were invited to a two-day capacity building workshop from 18 to 19 December 2019 in Riyadh, Saudi Arabia. Information regarding the participants’ demographic and educational/professional background, along with their self-assessed knowledge and experience of HTAs and the concept of value in the pharmaceutical market was collected. For each of 22 value drivers identified during a targeted literature search, participants were asked either to ‘opt out’ of its consideration for future HTA assessments, or rate it from 1 to 10 (low–high) on feasibility and acceptability. ResultsEfficacy and safety were the highest rated value drivers for acceptability and feasibility. Explicit cost-effectiveness thresholds had the lowest ratings for acceptability and feasibility. Participants highlighted data availability and accuracy as a potential challenge to HTA implementation in Saudi Arabia. ConclusionsParticipants valued a pharmaceutical product’s efficacy and safety alongside the consideration of disease characteristics for HTA processes. Participants also valued a binding HTA recommendation and the use of local real-world evidence, where available, to support HTA submissions.

Non-Price-Related Determinants of Value and Access for Novel Non-small Cell Lung Cancer Treatments: A Cross-Country Review of HTA Decision Making.

IntroductionAccess and funding for newly approved treatments for non-small cell lung cancer (NSCLC) are often dependent on Health Technology Assessment (HTA) involving cost-effectiveness analysis. Whilst methods used by HTA agencies share many similarities, final decisions may differ. This may be the result, not just of price considerations, but also of variation in value judgements by different agencies. The aim of this study was to review international HTA evaluations to identify determinants of value and access for NSCLC treatments.MethodsA targeted review and analysis was undertaken of published HTAs for NSCLC across HTA agencies in six countries (Australia, Canada, England, France, Ireland and Scotland). Analysis of extracted data consisted of three stages: descriptive analysis, bivariate analysis and multivariable analysis.ResultsThe analysis included 163 HTAs that assessed oncological treatments for NSCLC from 2003 to 2019. The majority of HTA decisions (67.5%) were positive. However, some evidence of heterogeneity in HTA decisions and the factors informing them were identified. The most influential factors included in the multivariate model related to the HTA agency conducting the appraisal, the year of market authorisation, treatment type and the line of treatment.ConclusionHeterogenous decision-making frameworks can present a challenge to developing HTA submissions. This research contributes to understanding decision-making factors and why countries make different decisions.Supplementary InformationThe online version contains supplementary material available at 10.1007/s41669-021-00279-2.

The Impact of Digital Therapeutics on Current Health Technology Assessment Frameworks.

Historically healthcare has been delivered offline (e.g., physician consultations, mental health counseling services). It is widely understood that healthcare lags behind other industries (e.g., financial, transportation) whom have already incorporated digital technologies in their workflow. However, this is changing with the recent emergence of digital therapeutics (DTx) helping to bring healthcare services online. To promote adoption, healthcare providers need to be educated regarding the digital therapy to allow for proper prescribing. But of equal importance is affordability and many countries rely on reimbursement support from the government and insurance agencies. Here we briefly explore how national reimbursement agencies or non-profits across six countries (Canada, United States of America, United Kingdom, Germany, France, Australia) handle DTx submissions and describe the potential impact of digital therapeutics on current health technology assessment (HTA) frameworks. A targeted review to identify HTA submissions and guidelines from national reimbursement agencies or non-profits was conducted. We reviewed guidelines from the Institute for Clinical and Economic Review (ICER) in the USA, the Canadian Agency for Drugs and Technologies in Health (CADTH) in Canada, the National Institute for Health and Care Excellence (NICE) in the United Kingdom (UK), the Institute for Quality and Efficiency in Health Care (IQWIG) in Germany, Haute Autorité de Santé (HAS) in France, and the Pharmaceutical Benefits Advisory Committee (PBAC) in Australia. Our review identified one set of guidelines developed by NICE in the UK. The guidelines by NICE outlined an evidence standards framework for digital health technologies (DHT). Depending on the organizational impact, financial commitment, and economic risk for the payer, different economic analyses are required. Economic analyses levels are separated into 3 categories, basic, low financial commitment, and high financial commitment. All economic analyses levels require a budget impact analysis. A cost-utility analysis is recommended for DHTs categorized in the high financial commitment category. Whereas, for DHTs that are in the low financial commitment category, a cost-consequence analysis is typically recommended. No HTA guidelines for DTx submissions were identified for the remaining countries (Canada, USA, Germany, France, and Australia)

Use of External Comparators for Health Technology Assessment Submissions Based on Single-Arm Trials

BackgroundSingle-arm trial (SAT) data is increasingly reviewed for drug approvals by regulators and Health Technology Assessment (HTA) bodies. Supplementary data in the form of external comparators (ECs) can be used to provide clinical context to support these drug evaluations. In this study we characterized HTAs for SAT-based submissions, the use of supplementary EC data and outcomes from HTA review. MethodsHTA Accelerator database was used to describe SAT-based HTA submissions with decisions (2011-2019). ResultsA total of 433 SAT-based HTA submissions were identified between 2011 and 2019 with a 13-fold increase during this period. Around 65%(283/433) were in oncology or hem-oncology. Around 52%(226/433) of submissions contained some type of EC data, including prior clinical trials (24%, 104) and real-world data (RWD) (20%, 87), but 40%(175) contained no EC data. The overall acceptance rate for SAT-based submissions was 48% and with RWD EC data acceptance was 59%. In the latest 5-year period (2015-2019), use of RWD ECs increased 22% as a proportion of submissions per year, whereas, prior trial ECs decreased (–14%) and use of no EC remained stable (–2%). Between 2015 to 2017 and 2018 to 2019, acceptance rate for RWD ECs increased by 20% (41% in 2015-2017 to 61% in 2018-2019) whereas prior trial EC use decreased by 10% and no EC submissions decreased 16%. Of 226 submissions using ECs, only 29%(66) used an adjusted indirect treatment comparison method. ConclusionsSAT-based submissions to HTA bodies are rapidly evolving in terms of composition and acceptance. Types of EC and methodological approach used are important determinants of positive outcomes.

PNS7 Ongoing SLRs When Considering HTA Submissions: Rewards and Avoidable Pitfalls

Systematic literature reviews (SLRs) remain the gold-standard approach for evidence synthesis to inform network meta-analysis (NMA), economic models, and associated health technology assessment (HTA) submissions. However, rigorous methodological expectations and an ever-expanding body of literature present challenges for researchers to produce timely, high-quality SLRs, which remain up to date at the time of HTA submissions, particularly in rapidly evolving therapeutic areas. Living systematic reviews are an emerging approach for performing regular updates, with pilot projects published by Cochrane, and more recently a collaboration with the World Health Organisation on the COVID-NMA initiative. To our knowledge, these methods have not yet been adapted and applied in a non-Cochrane setting assessing the relative efficacy and safety of multiple interventions and informing NMA preceding HTA submissions. This concept poster will describe key methodological considerations when planning an ongoing SLR approach to support HTA submissions. RECOMMENDATIONS:•Researchers should prepare a comprehensive, transparent search protocol covering the duration of the ongoing SLR, including consideration of:oRelevant interventions and comparators, including pipeline therapiesoDate limits and update frequencyoTiming of conference proceedingsoCapturing revisions to trial registry data available on Internet sources and publication of resultsoRecord management and plans for clearly reporting methodology and results•Resource planning should consider any overlaps between searches and potential for increased publications following conferences•Future requirements should be considered to minimize protocol amendments•Efficiency and quality may be improved through research team continuity•NMA should be repeated less frequently, on an as-needed basis, with consideration of the impact on the rate of false-positive results Ongoing SLRs can provide a powerful, efficient tool in preparation for upcoming HTA submissions. However, researchers should take care to plan appropriately to overcome potential challenges as the relevant therapeutic landscape expands.

Health Technology Assessment in Australia: The Pharmaceutical Benefits Advisory Committee and Medical Services Advisory Committee

Health technology assessment (HTA) was introduced in Australia for the reimbursement of pharmaceuticals in 1992 and in the following years for procedures, diagnostic tests, and devices. The Australian health system is largely funded by the government. The Pharmaceutical Benefits Scheme is a national list of prescription pharmaceuticals for which the patient pays a small copayment. HTA submissions to the Pharmaceutical Benefits Scheme are assessed by the Pharmaceutical Benefits Advisory Committee. The Medical Benefits Scheme provides ambulatory medical services and HTA submissions are assessed by the Medical Services Advisory Committee. This article describes the processes of reimbursement in Australia as well as the special case of codependent technologies (eg, diagnostic test and a therapeutic drug) where a combined Medical Services Advisory Committee and Pharmaceutical Benefits Advisory Committee application is required. There are many future challenges for HTA in Australia, with growing pressure to provide early access to promising treatments and high cost personalized medicines looming on the horizon. However, Australia is well placed to deal with these issues as the early adoption of HTA and coexistence between industry, academia and the payer has proven to be a fertile environment for developing capacity to undertake and evaluate HTA.

PMS19 Validation of a Cost-Effectiveness MODEL in Rheumatoid Arthritis

Rheumatoid arthritis (RA) has multiple previous health technology assessment (HTA) appraisals for advanced therapies. Cost-effectiveness models (CEMs) in RA are complex, especially with the increasing use of patient-level simulation, therefore, replicating them is an important step prior to HTA submission. Validation can ensure that models provide consistent representation of the disease and intervention, and a solid basis for decision-making. The objective of this study was to validate our patient-level CEM against a published model that was developed by academic experts in previous NICE appraisals. A patient-level, discrete-event simulation model was developed to evaluate the cost-effectiveness of new treatments for moderate-to-severe RA, following an approach developed by Stevenson et al.1 which estimated cost and health benefits using long-term, non-linear health-assessment questionnaire disability index trajectories. Our model was validated against a cost-effectiveness analysis of sequences of biologics (abatacept, adalimumab, certolizumab pegol, etanercept, golimumab, infliximab, tocilizumab) for RA patients in England published by Stevenson et al. in 2017.2 It was possible to replicate the analysis of Stevenson et al.2 2017 in most respects. Stevenson et al.2 reported lifetime incremental QALY gains of 1.5-2.0 and incremental costs of £60,000-£100,000 for the seven drugs. Our model predicted incremental QALYs of 1.54-1.71 and incremental costs of £69,000-£102,000. Estimated ICERs were £48,800-£52,300 and £44,700-£66,700 for Stevenson et al.2 and our model, respectively. The upper ICERs from our model were considered overestimates due to using list prices where patient access scheme prices were confidential. The results of the model validation demonstrate that it is possible to successfully replicate a complex, patient-level model. This illustrates the importance of validation when developing models for HTA to ensure consistency with previous assessments and provide a reliable basis for decision-making. REFERENCES 1. Stevenson M et al. Health Technology Assessment. 2016;20(35):1-610. 2. Stevenson M et al. J Rheumatol. 2017;44(7):973-80.