A pilot randomised controlled trial of acceptance and commitment therapy for medication decision-making and quality of life in women with breast cancer: The ACTION trial.

OBJECTIVE: Non-adherence to adjuvant endocrine therapy (AET) in women with breast cancer is common and associated with medication side-effects and distress. We co-designed an Acceptance and Commitment Therapy intervention (ACTION) to enhance medication decision-making and quality of life (QoL). We undertook a pilot trial of ACTION to inform the feasibility of a phase III trial, and to examine intervention acceptability. METHODS: This was a multi-site, exploratory, two-arm, individually randomised external pilot trial. Women with early breast cancer prescribed AET were randomised (1:1) to receive usual care (UC) or UC + ACTION. The ACTION intervention comprised a remotely delivered one-to-one ACT session followed by three group sessions delivered by clinical psychologists, alongside a website containing ideas for the self-management of side effects. RESULTS: Of the 480 women screened for eligibility, 260 (54.2%) were approached and 79 (30.4%) randomised. 71 (89.9%) women provided data at 3-month and 70 (88.6%) at 6-month 40 women were randomised to receive UC + ACTION and 32 (80.0%) completed the intervention. Most (75.0%) accessed the website at least once. ACTION was acceptable to participants (Borkovec & Nau Scale: mean = 7.8 [SD = 2.7] out of 10). Signals of effectiveness in favour of the UC + ACTION arm were observed for medication adherence (Adherence Starts with Knowledge questionnaire-12), QoL (work and social adjustment scale), health-related QoL (functional assessment of cancer therapy[FACT] general and FACT-ES-19/23), distress (generalised anxiety disorder -7, patient health questionnaire-9) and psychological flexibility (valuing questionnaire). CONCLUSIONS: The ACTION intervention was acceptable to patients. There were promising signals for effectiveness on primary and secondary outcomes. A phase III randomised controlled trial is feasible. TRIAL REGISTRATION: ISRCTN12027752.

Optimization of an Information Leaflet to Influence Medication Beliefs in Women With Breast Cancer: A Randomized Factorial Experiment.

BACKGROUND: Adherence to adjuvant endocrine therapy (AET) is low in women with breast cancer. Negative beliefs about the necessity of AET and high concerns are barriers to adherence. PURPOSE: To use the multiphase optimization strategy to optimize the content of an information leaflet intervention, to change AET beliefs. METHODS: We conducted an online screening experiment using a 25 factorial design to optimize the leaflet. The leaflet had five components, each with two levels: (i) diagrams about AET mechanisms (on/off); (ii) infographics displaying AET benefits (enhanced/basic); (iii) AET side effects (enhanced/basic); (iv) answers to AET concerns (on/off); (v) breast cancer survivor (patient) input: quotes and photographs (on/off). Healthy adult women (n = 1,604), recruited via a market research company, were randomized to 1 of 32 experimental conditions, which determined the levels of components received. Participants completed the Beliefs about Medicines Questionnaire before and after viewing the leaflet. RESULTS: There was a significant main effect of patient input on beliefs about medication (ß = 0.063, p < .001). There was one significant synergistic two-way interaction between diagrams and benefits (ß = 0.047, p = .006), and one antagonistic two-way interaction between diagrams and side effects (ß = -0.029, p = .093). There was a synergistic three-way interaction between diagrams, concerns, and patient input (ß = 0.029, p = .085), and an antagonistic four-way interaction between diagrams, benefits, side effects, and concerns (ß = -0.038, p = .024). In a stepped approach, we screened in four components and screened out the side effects component. CONCLUSIONS: The optimized leaflet did not contain enhanced AET side effect information. Factorial experiments are efficient and effective for refining the content of information leaflet interventions.

Adjuvant endocrine therapy (AET) is a medication given to women to stop breast cancer from returning. Many women do not take AET every day or stop taking it before they should. Some women do not take AET because they do not believe it will help them, or they have concerns about the side effects. We ran an online study aiming to create the best information leaflet to help women understand how AET is helpful and to reduce their concerns. The leaflet had five sections; diagrams explaining how AET works, visual pictures of the benefits of AET, information about the side effects, answers to common concerns, and quotes from other women with breast cancer. 1,604 healthy women filled in a questionnaire before and after looking at an information leaflet about AET. Women received different combinations of the five sections of the information leaflet. We found quotes from other women with breast cancer led to more positive beliefs about AET. Some sections of the leaflet worked better in combination, while other sections were worse in combination. Our results led us to remove the detailed side effect information from the leaflet, as in combination with the other sections this negatively affected women's beliefs about AET.

Codevelopment of a Text Messaging Intervention to Support Adherence to Adjuvant Endocrine Therapy in Women With Breast Cancer: Mixed Methods Approach.

BACKGROUND: Adjuvant endocrine therapy (AET) reduces breast cancer recurrence and mortality in women with early-stage breast cancer. Unintentional nonadherence to AET is common (eg, forgetting to take medication). Forming habits surrounding medication taking could reduce reliance on memory and improve AET adherence. SMS text messaging interventions may offer a low-cost approach for promoting medication-taking habits. To optimize the likely effectiveness of such SMS text messages, the content should be developed using a transparent approach to ensure fidelity to relevant psychological theory and with user input to increase acceptability. OBJECTIVE: This study aimed to develop a pool of brief SMS text messages promoting habit formation to support AET adherence, which are acceptable to women with breast cancer and show fidelity to theory-based behavior change techniques (BCTs). METHODS: According to published literature, we selected 6 BCTs derived from the habit formation model: action planning, habit formation, restructuring the physical environment, adding objects to the environment, prompts/cues, and self-monitoring of behavior. In study 1, behavior change experts (n=10) created messages, each based on 1 of the 6 BCTs, in a web-based workshop and rated the fidelity of the messages to the intended BCT. In study 2, women with experience of taking AET discussed the acceptability of the messages in a focus group (n=5), and the messages were refined following this. In study 3, women with breast cancer rated the acceptability of each message in a web-based survey (n=60). In study 4, additional behavior change experts rated the fidelity of the remaining messages to the intended BCT in a web-based survey (n=12). Finally, a consultant pharmacist reviewed a selection of messages to ensure that they did not contradict general medical advice. RESULTS: In study 1, 189 messages were created targeting the 6 BCTs. In total, 92 messages were removed because they were repetitious, unsuitable, or >160 characters, and 3 were removed because of low fidelity (scoring <5.5/10 on a fidelity rating scale). Following study 2, we removed 13 messages considered unacceptable to our target population. In study 3, all remaining messages scored above the midpoint on an acceptability scale (1-5); therefore, no messages were removed (mean 3.9/5, SD 0.9). Following study 4, we removed 13 messages owing to low fidelity (scoring <5.5/10 on a fidelity rating scale). All the remaining messages showed fidelity to the intended BCTs (mean 7.9/10, SD 1.3). Following the pharmacist review, 2 messages were removed, and 3 were amended. CONCLUSIONS: We developed a pool of 66 brief SMS text messages targeting habit formation BCTs to support AET adherence. These showed acceptability to women with breast cancer and fidelity to the intended BCTs. The delivery of the messages will be further evaluated to assess their effect on medication adherence.

Supporting adjuvant endocrine therapy adherence in women with breast cancer: the development of a complex behavioural intervention using Intervention Mapping guided by the Multiphase Optimisation Strategy.

BACKGROUND: Adjuvant endocrine therapy (AET) reduces the risk of breast cancer recurrence and mortality. However, up to three-quarters of women with breast cancer do not take AET as prescribed. Existing interventions to support adherence to AET have largely been unsuccessful, and have not focused on the most salient barriers to adherence. This paper describes the process of developing four theory-based intervention components to support adherence to AET. Our aim is to provide an exemplar of intervention development using Intervention Mapping (IM) with guidance from the Multiphase Optimisation Strategy (MOST). METHODS: Iterative development followed the six-stage IM framework with stakeholder involvement. Stage 1 involved a literature review of barriers to adherence and existing interventions, which informed the intervention objectives outlined in Stage 2. Stage 3 identified relevant theoretical considerations and practical strategies for supporting adherence. Stage 4 used information from Stages 1-3 to develop the intervention components. Stages 1-4 informed a conceptual model for the intervention package. Stages 5 and 6 detailed implementation considerations and evaluation plans for the intervention package, respectively. RESULTS: The final intervention package comprised four individual intervention components: Short Message Service to encourage habitual behaviours surrounding medication taking; an information leaflet to target unhelpful beliefs about AET; remotely delivered Acceptance and Commitment Therapy-based guided self-help to reduce psychological distress; and a website to support self-management of AET side-effects. Considerations for implementation within the NHS, including cost, timing and mode of delivery were outlined, with explanation as to how using MOST can aid this. We detail our plans for the final stage of IM which involve feasibility testing. This involved planning an external exploratory pilot trial using a 24-1 fractional factorial design, and a process evaluation to assess acceptability and fidelity of intervention components. CONCLUSIONS: We have described a systematic and logical approach for developing a theoretically informed intervention package to support medication adherence in women with breast cancer using AET. Further research to optimise the intervention package, guided by MOST, has the potential to lead to more effective, efficient and scalable interventions.

Barriers and facilitators to using aspirin for preventive therapy: a qualitative study exploring the views and experiences of people with Lynch syndrome and healthcare providers.

BACKGROUND: The National Institute for Health and Care Excellence (NG151) recommends considering daily aspirin for people with Lynch syndrome to reduce colorectal cancer risk. However, deciding whether to initiate aspirin could be a complex decision for patients and their healthcare providers, as both the potential benefits and harms need to be considered. METHODS: We conducted semi-structured interviews to explore the barriers and facilitators to using aspirin for preventive therapy. We recruited 15 people with Lynch syndrome, and 23 healthcare providers across multiple professions in primary, and specialist care (e.g. clinical genetics) in the United Kingdom. Interview schedules were informed by the Theoretical Domains Framework. RESULTS: There were three themes: 1) Considering potential harms and benefits; 2) Healthcare pathway; 3) Patients' level of interest in aspirin. All healthcare providers, across primary and specialist care, viewed general practitioners (GPs) as being responsible for prescribing and overseeing the use of aspirin. However, GPs were unfamiliar with aspirin for preventive therapy, and concerned about prescribing at higher doses (300-600 mg). To support decision-making, GPs wanted clarification from specialist clinicians on the evidence and dose to prescribe. Not all participants with Lynch syndrome received information on aspirin from their healthcare provider, and several were unsure who to discuss aspirin with. GPs were more inclined to prescribe aspirin for patients with expressed preferences for the medication, however several patients were uncertain and wanted further guidance. CONCLUSIONS: Coordinated and multilevel strategies are needed, addressing the needs of both GPs and people with Lynch syndrome, to ensure consistent implementation of national guidance on aspirin for preventive therapy.

Decision-making in the multiphase optimization strategy: Applying decision analysis for intervention value efficiency to optimize an information leaflet to promote key antecedents of medication adherence.

Advances in the multiphase optimization strategy (MOST) have suggested a new approach, decision analysis for intervention value efficiency (DAIVE), for selecting an optimized intervention based on the results of a factorial optimization trial. The new approach opens possibilities to select optimized interventions based on multiple valued outcomes. We applied DAIVE to identify an optimized information leaflet intended to support eventual adherence to adjuvant endocrine therapy for women with breast cancer. We used empirical performance data for five candidate leaflet components on three hypothesized antecedents of adherence: beliefs about the medication, objective knowledge about AET, and satisfaction with medication information. Using data from a 25 factorial trial (n = 1603), we applied the following steps: (i) We used Bayesian factorial analysis of variance to estimate main and interaction effects for the five factors on the three outcomes. (ii) We used posterior distributions for main and interaction effects to estimate expected outcomes for each leaflet version (32 total). (iii) We scaled and combined outcomes using a linear value function with predetermined weights indicating the relative importance of outcomes. (iv) We identified the leaflet that maximized the value function as the optimized leaflet, and we systematically varied outcome weights to explore robustness. The optimized leaflet included two candidate components, side-effects, and patient input, set to their higher levels. Selection was generally robust to weight variations consistent with the initial preferences for three outcomes. DAIVE enables selection of optimized interventions with the best-expected performance on multiple outcomes.

Intervention optimization involves using data from an optimization trial to select the combination of intervention components that are expected to successfully balance effectiveness (i.e. improving an outcome in the desired direction) with efficiency (i.e. producing a good outcome without wasting resources). Recently, a new method for selecting optimized interventions has been proposed that has a number of advantages, including the ability to use empirical information about more than one outcome variable of interest. Here, we applied this new method to identify an optimized information leaflet designed to support eventual medication adherence in women with breast cancer, using empirical information about three outcome variables that are thought to be important for later medication adherence: beliefs about the medication, objective knowledge about the medication, and satisfaction with the leaflet information. When we let beliefs about the medication be most important; knowledge about the medication to be half as important as beliefs; and satisfaction with information to be half as important as knowledge, the optimized leaflet included enhanced information about side-effects and photos and quotes from women with breast cancer. This decision remained generally the same when we systematically varied the weights used to give outcomes their relative importance.

Awareness of symptoms, anticipated barriers and delays to help-seeking among women at higher risk of breast cancer: A UK multicentre study.

Women with a family history of breast cancer have an increased lifetime risk of the disease. Delay in symptom presentation can lead to poorer outcomes. Low awareness of breast cancer symptoms and help-seeking barriers have been associated with delay in presentation in the general population. Symptom awareness and help-seeking barriers among women at increased risk of breast cancer are unknown. We conducted analysis of survey data which included women with moderate and high risk of breast cancer from 20 secondary and tertiary care clinics in England (n = 408). Women completed a validated survey assessing breast cancer symptom awareness, barriers to help-seeking and anticipated delay in help-seeking. Women recognised an average of 9.1/11 breast cancer symptoms (SD = 2.1). Nipple rash was the least recognised symptom (51.0%). Women educated to at least degree level had higher awareness than those with lower education (ß = 0.14, 95% CI 0.13, 0.99, p = 0.011). Women at lower socioeconomic status (SES) had lower awareness than those at higher SES (ß = -0.13, 95% CI -1.09, -0.07, p = 0.027). Women reported several anticipated help-seeking barriers (mean = 4.0/11, SD = 2.8). Waiting to see if a symptom will pass was the most commonly reported barrier to help-seeking (71.5%). Most women (376/408; 92.2%) reported that they would seek medical help within 2 weeks of discovering a breast cancer symptom. Interventions to increase awareness of non-lump breast cancer symptoms and reduce help-seeking barriers are needed, with considerations of appropriate reading levels and modalities for women with lower education and SES.

Acceptability of aspirin for cancer preventive therapy: a survey and qualitative study exploring the views of the UK general population.

OBJECTIVES: Aspirin could be offered for colorectal cancer prevention for the UK general population. To ensure the views of the general population are considered in future guidance, we explored public perceptions of aspirin for preventive therapy. DESIGN: We conducted an online survey to investigate aspirin use, and awareness of aspirin for cancer prevention among the UK general population. We conducted semistructured interviews with a subsample of survey respondents to explore participants' acceptability towards aspirin for cancer preventive therapy. We analysed the interview data using reflexive thematic analysis and mapped the themes onto the Theoretical Domains Framework, and the Necessity and Concerns Framework. SETTING: Online survey and remote interviews. PARTICIPANTS: We recruited 400 UK respondents aged 50-70 years through a market research company to the survey. We purposefully sampled, recruited and interviewed 20 survey respondents. RESULTS: In the survey, 19.0% (76/400) of respondents were aware that aspirin can be used to prevent cancer. Among those who had previously taken aspirin, 1.9% (4/216) had taken it for cancer prevention. The interviews generated three themes: (1) perceived necessity of aspirin; (2) concerns about side effects; and (3) preferred information sources. Participants with a personal or family history of cancer were more likely to perceive aspirin as necessary for cancer prevention. Concerns about taking aspirin at higher doses and its side effects, such as gastrointestinal bleeding, were common. Many described wanting guidance and advice on aspirin to be communicated from sources perceived as trustworthy, such as healthcare professionals. CONCLUSIONS: Among the general population, those with a personal or family history of cancer may be more receptive towards taking aspirin for preventive therapy. Future policies and campaigns recommending aspirin may be of particular interest to these groups. Multiple considerations about the benefits and risks of aspirin highlight the need to support informed decisions on the medication.

Acceptability, fidelity and trial experience of four intervention components to support medication adherence in women with breast cancer: A process evaluation protocol for a pilot fractional factorial trial.

Background: The Refining and Optimising a behavioural intervention to Support Endocrine Therapy Adherence (ROSETA) programme has developed four intervention components aiming to improve medication adherence in women with early-stage breast cancer. These are (a) text messages, (b) information leaflet, (c) Acceptance and Commitment Therapy-based guided self-help (ACT), (d) side-effect management website. Guided by the Multiphase Optimisation Strategy, our pilot trial will use a fractional factorial design to evaluate the feasibility of undertaking a larger optimisation trial. The pilot will include a process evaluation to maximise learning regarding the fidelity and acceptability of the intervention components before proceeding with a larger trial. The trial process evaluation has three aims: to assess the (1) fidelity and (2) acceptability of the intervention components; and (3) to understand participant's trial experience, and barriers and facilitators to recruitment and retention. Methods: The process evaluation will use multiple methods. Fidelity of the intervention components will be assessed using self-reported questionnaire data, trial data on intervention component adherence, and observations of the ACT sessions. Acceptability of the intervention components and trial experience will be explored using an acceptability questionnaire and interviews with patients and trial therapists. Trial experience will be assessed using a questionnaire and interviews with participants, while barriers and facilitators to recruitment and retention will be assessed using a questionnaire completed by research nurses and participant interviews. The pilot trial opened for recruitment on 20th May 2022 and was open at the time of submission. Conclusions: This process evaluation will provide information regarding whether the intervention components can be delivered with fidelity within a national healthcare setting and are acceptable to participants. We will also better understand participant experience in a pilot trial with a fractional factorial design, and any barriers and facilitators to recruitment and retention. Registration: ISRCTN registry ( ISRCTN10487576, 16/12/2021).

BACKGROUND: The majority of women with early-stage breast cancer are recommended adjuvant endocrine therapy (AET) to reduce the chances of their cancer coming back. Many women given this medication don't take it every day or stop taking it earlier than they should. We have developed four different interventions to help women take AET. These are; text messages reminding women to take AET; an information leaflet explaining how AET works and its benefits and side-effects; a therapy programme to reduce distress, consisting of five support sessions and four module booklets; and a website with strategies to manage AET side-effects. We are now testing whether these interventions can be delivered within the NHS in different combinations, in a small trial. STUDY METHODS: We have three aims: 1. To find out if the interventions can be given and are received in the way they were supposed to (fidelity).2. To find out if the support received as part of the trial was acceptable to women with breast cancer (acceptability).3. To find out what women's experience was of taking part in the trial overall (trial experience). To do this we will: 1. Interview participants to ask them how acceptable they found the interventions, what they understood, whether they used the interventions, and how they found participating in the trial.2. Interview therapists who delivered the therapy programme to see if they delivered it as they were supposed to, and how they found delivering the intervention.3. Ask participants to complete questionnaires about how acceptable the interventions were, and whether they read and used them.4. Ask the staff involved in finding participants for the trial about challenges and improvements. We will use what we find to make improvements in a future trial where we will test whether the interventions help women to take AET.

Refining and optimising a behavioural intervention to support endocrine therapy adherence (ROSETA) in UK women with breast cancer: protocol for a pilot fractional factorial trial.

INTRODUCTION: Women with breast cancer who do not adhere to adjuvant endocrine therapy (AET) have increased risks of mortality and recurrence. There are multiple barriers to AET adherence, including medication side-effects, beliefs about medication, memory and psychological distress. We developed four intervention components, each targeting a different barrier. This pilot trial is part of the preparation phase of the Multiphase Optimisation Strategy, and aims to establish key trial parameters, establish intervention component adherence, establish availability and feasibility of outcome and process data, estimate variability in planned outcome measures and estimate cost of developing and delivering each intervention component. METHODS AND ANALYSIS: The four intervention components are as follows: short message service text reminders (target: memory); a written information leaflet (target: medication beliefs); a guided self-help Acceptance and Commitment Therapy programme (target: psychological flexibility to reduce distress) and a self-management website (target: side-effect management). To evaluate the feasibility of recruitment, acceptability of the intervention components and the availability of outcome data, we will conduct a multisite, exploratory pilot trial using a 24-1 fractional factorial design, with a nested process evaluation. We will randomise 80 women with early-stage breast cancer who have been prescribed AET to one of eight experimental conditions. This will determine the combination of intervention components they receive, ranging from zero to four, with all conditions receiving usual care. Key outcomes of interest include medication adherence and quality of life. Progression to the optimisation phase will be based on predefined criteria for consent rates, patient adherence to intervention components and availability of medication adherence data. ETHICS AND DISSEMINATION: The study was reviewed by the Wales Research Authority Research Ethics Committee 3 (21/WA/0322). Written informed consent will be obtained from all patients before randomisation. The results of this trial will be disseminated in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: ISRTCN10487576.

Strategies to self-manage side-effects of adjuvant endocrine therapy among breast cancer survivors: an umbrella review of empirical evidence and clinical guidelines.

PURPOSE: Side-effects of adjuvant endocrine therapy (AET) are common in breast cancer survivors, and can affect adherence to treatment. We synthesised the evidence for strategies to self-manage these side-effects. METHODS: We searched for systematic reviews and clinical guidelines on self-management strategies for AET side-effects (arthralgia, fatigue, hot flashes, gastrointestinal discomfort, nausea, vulvovaginal symptoms, and sleep disturbance). We searched oncology organisation's websites and eight databases (Inception-November 2020). Screening, data extraction and quality assessment were completed independently in duplicate. PROSPERO: 2019CRD4201914001. RESULTS: We identified 33 systematic reviews and 18 clinical guidelines. 21% of reviews were high quality, and the average quality score for guidelines was 44%. Evidence for most strategies was absent or weak. There was consensus from a low-quality review and multiple guidelines to recommend moisturisers, gels and lubricants for vulvovaginal symptoms. Evidence was weak for physical activity for self-managing most symptoms, although two high-quality reviews indicated yoga and aerobic exercise could reduce fatigue. Primary research was often biased by weak and underpowered study designs. Eleven reviews did not report information on adverse events. CONCLUSIONS: Most self-management strategies for breast cancer survivors experiencing side-effects from AET lack evidence. Primary research is needed using high-quality well-powered designs focusing on implementable strategies. IMPLICATIONS FOR CANCER SURVIVORS: Patients and clinicians should be aware that although the risk of harm is low for these self-management strategies, the likelihood of benefit is often unclear. Women should consider moisturisers, gels or lubricants for self-managing vulvovaginal symptoms, and yoga or aerobic exercise for alleviating fatigue.