Title: Accounting for the impact of fluctuating health states on quality of life measures included in economic evaluation
Funder: Department of Health and Social Care

Abstract: BACKGROUND One in two people in the UK will get cancer and approximately 331,000 people are diagnosed each year. Although chemotherapy can be effective at treating cancer, it causes significant pharmacological side effects. Patients receive treatment in cycles. One cycle typically lasts 3 to 4 weeks. Each cycle has a treatment and rest period to allow the body to recover. Approximately 4-8 cycles of chemotherapy are used. Therefore a course of chemotherapy leads to significant cyclical fluctuations in quality of life.The use of recommended economic measures, EQ-5D and SF-6D (derived from SF-12/SF-36), may not be appropriate to capture cyclical fluctuating health states. This is due to: (1) the recall periods (health today' and past 4 weeks'), (2) the timing of assessment, (3) a lack of understanding about how these instruments are completed, and (4) the valuation methods employed to generate the quality of life values. If appropriate methods are not used, quality of life results could be spurious and economic recommendations to decision-makers misleading.AIM: To account for the impact of cyclical fluctuating health states in economic evaluation.The research has two parts: the measurement study involves patients and the feasibility valuation study involves the general public.Using predictable fluctuations caused by side effects of chemotherapy treatment for cancer as a case study, the objectives of the measurement study are to: i. Understand how patients with fluctuating symptoms answer questions on EQ-5D and SF-12 ii. Explore the influence of the recall period used in the questionnairesiii. Determine when and how many times to capture economic quality of life,iv. Illustrate the influence of timing of assessment on the estimation of the quality-adjusted life year (QALY)To investigate the appropriateness of the current value set, to generate a QALY, for any fluctuating condition, the objective of the valuation study is to:v. Explore whether values for the EQ-5D change when health states are fluctuatingBenefit to patients and the NHS: This research will lead to patients' concerns and experiences, during fluctuating health states, being captured more accurately. Accurate measures of quality of life will ensure an efficient use of health resources and better treatments and pathways of care for patients. The results of the valuation study will determine how much the current value set can be relied upon when influencing policy through the National Institute for Health and Care Excellence (NICE) guidelines.Design and methods The research involves five work packages. The measurement study involves patients who are undergoing chemotherapy (packages 1-4) and the valuation study involves the general public (package 5):1: Systematically review the literature to identify the current evidence on the use of economic quality of life measures in chemotherapy for cancer.2: Conduct thinkaloud interviews with patients undergoing chemotherapy as they complete EQ-5D and SF-12, to understand how patients complete questionnaires with current recall periods, and when they are changed.3: Timing of assessment and recall Part 1: Assess the extent of fluctuations and reporting in current practice, by asking patients to complete SF-12 and EQ-5D daily during one chemotherapy cyclePart 2: Investigate whether timeframe influences the quality of life and QALY results, by amending the recall period, using the thinkaloud and systematic review findings, for EQ-5D-5L and SF-124: Determine the influence on the QALY outcome by exploring alternative assumptions for extrapolation between measurement time points. Assumptions will be generated using evidence from previous work packages and discussions with the advisory group.5: Conduct a feasibility valuation study with the general public to assess whether the cyclical fluctuating nature of health states affects the values placed on them.

Lay abstract: Background: 1 in 2 people in the UK will get cancer. More than 331,000 people are told they have cancer each year. Chemotherapy treatment is used to cure cancer. It can also make other treatments work better, lower the chances of cancer coming back, or help with symptoms if the cancer cannot be cured.Although chemotherapy can be useful for treating cancer or helping with symptoms, it causes major side effects that affect quality of life. Patients have chemotherapy in cycles. One cycle can last 3 to 4 weeks depending on the type of cancer. Each cycle has a treatment and a rest period so the body can get better. The patients' quality of life is changing all the time during the cycle. Roughly 4-8 cycles (up to 8 months) of treatment are needed.To see which treatment gives the best value for money for the NHS, information on quality of life, and cost is considered. Decision-makers decide which quality of life measures to use. These measures may not be useful for conditions that have changing symptoms or treatments that have changeable side effects. If the right measures and methods are not used, quality of life results could be wrong and the best treatments may not be used.Aim: To explore how best to include the impact of changing symptoms in quality of life questionnaires Using chemotherapy treatment for cancer, my plan is to: Understand how patients who have changing symptoms complete the quality of life measures, See how much the wording in the measures affects the results, Decide when to ask about quality of life and how many times to ask during a treatment cycle See how much the time at which the measure is asked affects the results I will also look at whether the standard quality of life values used in the recommended measure, EQ-5D, change when quality of life is changing.Benefit to patients and the NHS: The findings from this research will mean quality of life values are accurately calculated. Patients' concerns and experiences will be fully considered, as we will have a more exact measure of their symptoms for value for money analyses. This will ensure a better use of health resources and better pathways of treatment and care for patients by influencing NHS policy through the National Institute for Health and Care Excellence (NICE) guidelines. We could also use these findings for further research in other conditions with changing symptoms to improve quality of life measurement on a greater scale. Design and methods I will use mixed methods to see how much changes in symptoms affects quality of life and treatment decisions in chemotherapy for cancer. I will work with patients who are having chemotherapy and members of the public. The work will be carried out in five stages;1: I will review the literature to identify the evidence on the use of quality of life measures in chemotherapy for cancer.2: I will interview patients having chemotherapy asking them to thinkaloud' as they answer quality of life questions. This will help me to see how questionnaires are completed where recall periods refer to the past month' or health today' and when the recall period is changed.3: Part 1: I will ask patients to complete a questionnaire daily during one cycle of chemotherapy to see the full effect of treatment on quality of life.Part 2: I will change the wording of the recall periods in the questionnaires and ask patients to complete them. This is to see if we get more accurate responses.4: I will look at the effect of assumptions used to join quality of life values collected at different time points to create the quality of life outcome (quality-adjusted life year). By comparing different assumptions we can see which approach is best for changing symptoms. 5: I will see whether current methods to value quality of life are suitable for conditions with changing symptoms. I will ask the public to value health states when the symptoms are changing, not constant. I will test the effect of changing the type and level of changes. This will tell me the importance of changing symptoms on quality of life.Dissemination: I will publish the findings in academic journals and present the research at conferences. I will be supported by my advisory group and the University of Bristol public engagement team to share findings to patient groups, charities, industry, decision-makers, and at science cafes or research festivals.

Research activity codes: 7.1 INDIVIDUAL CARE NEEDS;8.2 HEALTH AND WELFARE ECONOMICS
Health categories: CANCER AND NEOPLASMS