Title: A methodological framework to guide the development and use of economic evaluations of oncology treatments in informing decision-making
Funder: Department of Health and Social Care

Abstract: Background Decision-makers often use economic evaluation to evaluate health care technologies. Because evidence is always imperfect and uncertain, mathematical models are required. It is, however, essential that economic evaluations are designed and implemented appropriately, and that a consistent and robust approach is adopted to allow a fair comparison between treatments. Oncology is a disease area with an increasing incidence of innovative drugs requiring assessment. In addition, the National Institute for health and Care Excellence (NICE) recently decided to re-evaluate cancer therapies previously funded through the cancer drugs fund. Economic evaluations of cancer typically share the same structure articulated around three health states, (i) pre-progression; (ii) progressed disease, and; (iii) death. The time spent in the first two health states is typically estimated using progression-free survival (PFS) and overall survival (OS) Kaplan-Meier curves reported in clinical trials which are then weighted according to the quality of life associated with each state to estimate overall health gains (QALYs). There is growing evidence that different analytic approaches may provide different estimates of total health gains and costs. Identifying when particular approaches may perform better than others subject to the nature of the data available is required. Aims The aim of this research is to develop a methodological framework to inform the choice of analytic approaches for modelling cancer therapies subject to the nature of the data available and to guide decision-making based on these models. Research question Is it possible to identify when particular analytical approaches may perform better than others subject to the nature of the data available? Plan of investigation The study consists of six phases of research. The first phase involves a systematic review of economic evaluations of cancer therapies to identify approaches that are currently used in cancer models to estimate health state durations and total QALYs gained. The second phase involves a systematic review of methods that are used outside economic evaluations to model the dependence between intermediate and final outcomes such as PFS and OS. The third phase involves generating simulated datasets to test and assess the performance of the methods used within and outside the field of health economics. The Fourth phase consists of validating results from the simulation study using real clinical-trial data. As a result of this process, a draft methodological framework will be produced describing the advantages and disadvantages of each approach followed by recommendations on the most appropriate modelling approach subject to the nature of the data available. The last phase of research consists of identifying barriers and facilitators to the implementation of the framework through facilitated group discussion with analysts and decision-makers. Patients and public involvement Five cancer survivors and carers will be part a steering group who will meet on a 6-monthly basis and contribute to all phases of the proposed research to ensure that their views is continually included.Potential benefits to patients and the wider NHS The proposed research study will have several important implications for future economic evaluation of oncology treatments. Improving the quality and consistency of methods used to evaluate oncology treatments is of value for patients; this allows both prescribers and patients to be more confident about treatment choices. In addition, improving the quality and consistency of economic evaluations is of value to the wider NHS context, promoting better resource allocation and avoiding inappropriate displacement, which could result in a net loss of health for NHS patients. Finally, improving the consistency and quality of methods used to evaluate cancer therapies will improve the transparency in health economic models and increase confidence in decisions.

Lay abstract: Background The National Institute for Health and Care Excellence (NICE) makes recommendations about which new and existing treatments are good value for money for the NHS. They use evidence from clinical trials, and a mathematical tool (called a model) is developed to predict patients' quality of life, how long they are likely to live and the cost to the NHS if they receive the new treatment. These models are needed because clinical trials do not always provide enough information about all of these issues. However, different models may result in different predictions, and some models may not be reliable. In cancer treatment (oncology) there is an increasing number of new drugs being developed and it is important that the models used to assess these new cancer drugs are reliable and suitable for use in this process. Models which are unreliable or inappropriate may lead to the wrong decisions being made and poor outcomes for patients with cancer. Aims of the research The aim of this project is to produce a summary document to guide the development of the models used to assess cancer treatments and assess whether the models are the right ones. Design and methods used The study is divided into six phases. In the first phase, the researcher will look at the different approaches that have been used when developing cancer models and create a comprehensive summary. In the second phase, the researcher will look at novel approaches used in the broader literature that could be used to improve predictions of patients' quality of life and how long they are likely to live. In the third and fourth phase, the researcher will examine whether it is possible to identify the right mathematical methods subject to the nature of the data available in the trials. In the fifth phase, the researcher will produce a summary document of approaches identified, highlighting advantages and disadvantages and will formulate recommendations on the best methods to use. In the final phase, the researcher will have discussions with analysts and the people who choose which treatments to recommend about how easy the recommendations can be implemented. Value for patients and public This research aims to include issues that are relevant to patients and the public and ensure the right and most consistent models are used. It will also aim to help the people who make decisions about which are the most effective and cost effective treatments to make better decisions. This will lead to better outcomes for cancer patients, non-cancer patients and the wider NHS. Patient and public involvement Five cancer survivors and carers will be part of the project and contribute to all phases of the proposed research. This contribution from patients and carers will ensure that the project is focussed and relevant to people that will be the most affected by the output from this research. This will also ensure that their views are continually included. What happens to the results? Each phase of the research will be written up in an academic journal and the researcher will present the research findings at national and international conferences. These are attended by many of the people who decide on which treatments are funded, health care professionals and people at a national and international level who make policy decisions. Our experience of patient and public involvement in methodological research will also be presented at a conference. This part of research is essential to make sure good practice is shared by everyone.

Research activity codes: 7.3 MANAGEMENT AND DECISION MAKING
Health categories: CANCER AND NEOPLASMS