Title: Refining and Optimising a behavioural intervention to Support Endocrine Therapy Adherence: The ROSETA programme
Funder: Department of Health and Social Care

Abstract: BACKGROUND Women with breast cancer who do not adhere to adjuvant endocrine therapy (AET) have an increased risk of mortality, recurrence, and reduced quality-adjusted life-years. AET is offered to approximately 70% of women with invasive breast cancer (~38500 UK women per year). Low adherence and persistence is an unsolved and widespread problem. AIMS AND OBJECTIVES To prepare and optimise a low cost complex behavioural intervention to support medication adherence among women taking AET using the Multiphase Optimisation Strategy. My overall goal is focussed on reducing overall mortality and risk of breast cancer recurrence. Objectives: Preparation phase To develop / adapt four intervention components that target determinants of adherence to AET; To pilot an optimisation trial testing these four components in a fractional factorial design with a nested qualitative study;Optimisation phase To optimise the intervention package using a factorial trial design to evaluate which components improve adherence for a maximum pre-specified cost; To undertake a causal pathway analysis to test the conceptual model; To undertake a mixed-methods longitudinal process evaluation to monitor treatment fidelity.Impact and dissemination phase To disseminate and create impact through push, pull, and linkage and exchange activities; To prepare a protocol and funding application for a definitive RCT.METHODS Preparation phase: I will design and evaluate four intervention components that support medication adherence. Components have been selected to target the mechanisms of action within a conceptual model developed using intervention mapping and with patient input: SMS text reminders (target: memory), Written information (target: medication beliefs), A group-based Acceptance and Commitment Therapy (ACT) programme (target: psychological flexibility) Self-management website (target: living with side-effects).The components will be finalised in a series of mixed-methods studies. A pilot trial (n=80) using a 24-1 fractional factorial design with a nested qualitative study will: 1) examine the feasibility of undertaking such a trial within the NHS and 2) ascertain the availability of outcome data. Optimisation phase: I will optimise the intervention components using a 24 factorial trial design (n=404) with an internal pilot. The planned primary outcome is adherence, assessed by NHS dispensing data. Components will be retained within the intervention package if they demonstrate an effect of d0.28 with the primary outcome, and the overall package can be delivered for a cost likely to meet NICE cost-effectiveness thresholds ( TIMELINE FOR DELIVERY I will complete the Fellowship over 75 months (0.8FTE) to provide opportunities for development outside the Fellowship, and to accommodate trial follow-up. Preparation phase. Months 1-36 Intervention component development (months 1-6) Pilot 24-1 trial with nested qualitative study (months 1-36)Optimisation phase. Months 25-75 24 factorial trial (25-75) Longitudinal mixed-methods process evaluation (months 46-75)Impact and dissemination. Months 19-75 Push activities (e.g. Publications) (months 19-75) Pull activities (e.g. Parliamentary Fellowship) (months 19-24) Linkage and exchange (e.g. Strengthening stakeholder networks) (months 22-75)

Lay abstract: AIMS:I will prepare and optimise a low cost intervention to support women with breast cancer to take their medication as prescribed (medication adherence). Specifically, I will: Develop four interventions to target barriers to medication adherence Use a new type of trial design to establish the feasibility of evaluating these interventions in the NHS Test the four interventions in a larger trial to establish which are most effective at supporting medication adherence Examine how and why the interventions might be working Monitor whether the interventions were delivered as intended Disseminate my findings to maximise patient and NHS impactBACKGROUNDWomen with breast cancer who do not take a prescribed oral medication daily for at least 5 years have an increased risk of their cancer returning, dying prematurely and experiencing lower quality of life. In preparatory work women with breast cancer helped me to identify a range of factors that can reduce willingness to use these medications, including side-effects, forgetting, emotional disturbance, and beliefs about medication being unnecessary and potentially harmful. Existing programmes have failed to support women to take these medications. My new approach holds promise for designing more effective interventions and saving patient lives.DESIGN AND METHODSI will design and evaluate four different interventions to support women's medication adherence: Text message reminders to help with forgetting; Written information to address medication beliefs; A group intervention to support emotional disturbance and side-effect management; A website containing patient stories and advice on how to manage side-effects.The interventions will be finalised in a series of small studies involving patients, healthcare professionals, and research scientists. I will test these interventions with 80 women to examine the feasibility of doing a larger clinical trial in the NHS. If appropriate, I will proceed to the larger trial which I anticipate will involve 404 patients. I will use a new type of trial design to see whether the interventions improve medication adherence individually, and if they work particularly well or poorly when patients are given particular combinations of them. I will calculate the cost of each combination so I can see if the interventions are sustainable for the NHS. I will also use advanced statistics to examine how and why the interventions are working (if at all). With patient consent, anonymised trial data will be made available to researchers and commissioners to accelerate scientific progress and increase the chances of patient benefit. PATIENT AND PUBLIC INVOLVEMENTTo inform this proposal, I have held a stakeholder workshop involving 24 patient representatives. This involved a series of tasks to identify the barriers to medication adherence, and preferences for intervention content, timing, duration and intensity. I have particularly strong relationships with three patient representatives affected by breast cancer, and I will continue to collaborate with them in this fellowship. This will include participating in trial management groups, discussions regarding study design, and dissemination activities. If opportunities for additional involvement arise, I will identify patients using existing links with the Yorkshire Cancer Patient Forum and the Hunts Community Cancer Network. DISSEMINATIONMy dissemination and impact plan will involve a series of activities classified as push (one way dissemination), pull (creating an appetite for the research) and linkage and exchange (building and maintaining relationships). Key examples beyond traditional academic outputs include: Disseminating findings to patient groups through presentations and lay summaries Applying for a Parliamentary Fellowship to write governmental guidance on medication adherence Providing updates to the all-party parliamentary group on breast cancer Hosting a dissemination event for patients, clinicians and commissioning stakeholders

Research activity codes: 7.1 INDIVIDUAL CARE NEEDS
Health categories: CANCER AND NEOPLASMS