Title: Modelling approaches for site-agnostic cancer drugs to inform NICE appraisal
Funder: Department of Health and Social Care

Abstract: In May 2017, the U.S. Food and Drug Administration (FDA) granted the first approval for a cancer treatment based on a common biomarker rather than the location in the body where the tumour originated (i.e. a ‘site agnostic’ indication). There are approximately 18 technologies currently in development for site-agnostic indications and the first marketing authorisation could be granted in Europe within a year. Site-agnostic treatments have the potential for important treatment effects in patient populations who currently have limited or no available treatment options. However, it is also important to ensure that the use of these treatments in in the NHS is supported by systematic and robust assessments of clinical evidence (i.e. how well the medicine or treatment works) and economic evidence (i.e. the medicine’s value for money). These assessments are undertaken by the National Institute for Health and Care Excellence (NICE). However, a site-agnostic marketing authorisation would likely include a large number of tumour sites. It is not possible for NICE to conduct a separate assessment for each tumour site for which the treatment could be beneficial. As a result, NICE needs to consider how to develop an approach that will enable these products to be appropriately assessed without creating unnecessary delays in patient access. The proposed research will explore the level to which NICE’s existing approaches for assessing clinical and economic value can be applied to site-agnostic indications and any changes that might be required. We propose to explore the nature and amount of evidence which is typically available at the point of initial marketing authorisation and to develop guidance to establish the evidence and analyses required to help inform NICE decisions. We will use case studies to highlight possible problems and to explore other ways that these might be addressed. This research will help to inform future NICE policy on how to appraise cancer drugs with site-agnostic indications. It will also inform the development of guidance for those developing these treatments to help their understanding of the clinical- and cost-effectiveness assessments that will be required to inform NICE appraisals.

Lay abstract: Research question To what extent can current modelling approaches for cancer drugs adequately deal with site-agnostic indications given the substantial heterogeneity of the population, limited information on survival outcomes and lack of comparative clinical data? Background In May 2017, the FDA granted accelerated approval to pembrolizumab for treating solid tumours with the microsatellite instability high or mismatch repair deficient biomarker. The first site-agnostic marketing authorisation could be granted by the EMA within a year and will likely include a large number of tumour sites. Due to capacity constraints, it is not feasible for NICE to conduct a separate appraisal for each site. NICE needs to explore how these products can be appraised without creating delays in patient access. Aims and objectives The main aim of this project is to explore modelling approaches to inform NICE appraisals of site-agnostic drugs in oncology. The specific objectives are: • To identify the nature of evidence likely to be available at initial marketing authorisation. • To determine the types of evidence and analyses required to support such NICE appraisals. • To develop a conceptual framework to establish the evidence and cost-effectiveness analyses required to guide NICE decision-making. • To identify and implement one or more case studies to highlight methods and evidence challenges and to explore alternative ways of addressing these. • To identify any changes that might be required to the methods used in the NICE technology appraisal programme. • To make recommendations for further methodological research. Methods Phase 1: Development of formal project protocol We will develop a formal project proposal to ensure that the proposed scope of work and analyses are appropriate to address the policy and methodological questions facing NICE. We propose an initial meeting with NICE to agree the aims and objectives of the project, the key deliverables and timings. We anticipate that the elements of work detailed in Phases 2-5 will be required. Phase 2: Establishing the nature of evidence likely to be available and consideration of the types of evidence and analyses required to support NICE appraisals The designs of clinical trials for site-agnostic drugs are likely to differ significantly from traditional clinical trials designed for specific tumour types. These may pose challenges for conventional modelling approaches. We propose to undertake a series of targeted reviews to determine the type of evidence that is likely to be available at the point of marketing authorisation and to consider the evidence and analyses likely to be required to support a NICE appraisal. Phase 3: Development of conceptual framework for assessing the value of site-agnostic drugs Based on the findings of phase 2, we will develop a conceptual framework to outline the evidence and analyses needed to estimate the value of site-agnostic drugs and to guide NICE appraisal decisions. The conceptual framework will help to clarify the key model parameters and how these can be linked through modelling. Phase 4: Development of case studies The fourth phase of work will involve identifying one or more case studies to illustrate how the types of analyses and evidence necessary to inform NICE decision can be developed. We propose to use case studies to explore those areas of evidence and analyses which are anticipated to be most challenging. Phase 5: Project report and dissemination A report will be drafted for review by NICE. This will provide full details of all phases of research including rationale, methods, results and implications for NICE appraisal. A final report will be produced following this review. Timelines for delivery We propose to start the project in Oct 2018 and to submit the final report in December 2019. Due to the limited capacity due to STA commitments it is proposed that the majority of funding will be during the period April 2019 – December 2019. Anticipated impact and dissemination This research will help inform future NICE policy on how to appraise cancer drugs with site-agnostic indications. The research findings will be published in one or more peer-reviewed journals and presented at suitable conferences.

Research activity codes: 8.4 RESEARCH DESIGN AND METHODOLOGIES (HEALTH SERVICES)
Health categories: CANCER AND NEOPLASMS