What factors influence the uptake of bowel, breast and cervical cancer screening? An overview of international research.

BACKGROUND: For cancer screening programmes to be effective in early detection it is important that those invited can access screening services and understand the benefits of participation. A better understanding of the factors that matter to potential participants of cancer screening programmes can assist in developing strategies to increase current uptake. METHODS: We conducted an overview of systematic reviews to answer the question: What factors influence the uptake of cancer screening services (breast, bowel and cervical) in high-income countries? A thematic approach supported by tabular summaries and qualitative heat maps was used to categorize factors, described as 'barriers' or 'facilitators'. RESULTS: A total of 41 systematic reviews met the criteria for inclusion. The barrier with the greatest number of 'hot spots' across all three screening programmes was a fear of the unknown regarding a possible diagnosis of cancer or abnormal screening results, followed closely by a general lack of knowledge surrounding cancer screening programmes. The greatest collective facilitator to uptake was recommendation by a healthcare provider to attend screening. CONCLUSION: Across all factors 'trust' and 'building trusted relationships' can be seen as integral to the success of cancer screening programmes and must be reflective of collaborative efforts to mitigate barriers and enhance facilitators to uptake. There is future scope to consider interventions that (i) increase demand for screening services, (ii) reduce barriers to uptake of services and/or (iii) are relevant to the healthcare system and those providing services.

Tailoring CONSORT-SPI to improve the reporting of smoking cessation intervention trials: An expert consensus study.

BACKGROUND AND AIMS: Inadequate reporting of smoking cessation intervention trials is common and leads to significant challenges for researchers. The aim of this study was to tailor CONSORT (Consolidated Standards of Reporting Trials)-SPI (Social and Psychological Interventions) guidelines to improve reporting of trials of behavioural interventions to promote smoking cessation. METHOD: Informed by missing data from the IC-SMOKE (Intervention and Comparison group support provided in SMOKing cEssation) systematic review project, this study used a multi-stage Delphi process to examine which items could be added or modified to improve the reporting of smoking cessation trials. The first stage involved an on-line survey of 17 international experts in smoking cessation and trial methodology voting on the importance of items for inclusion in the updated guidelines. This was followed by a face-to-face expert consensus meeting attended by 15 of these experts, where the final inclusion and exclusion of new items and modifications were agreed upon. A nine-point Likert scale was used to establish consensus, with suggested modifications requiring agreement of 75% or more. Disagreements in the first stage were presented again at the second stage for discussion and a second round of voting. Only items which reached the threshold for agreement were included. RESULTS: The experts agreed on the inclusion of 10 new items and the specification of 12 existing items. This included modifications that could apply to trials more widely (e.g. the rationale for the comparator), but also modifications that were very specific to smoking cessation trials (e.g. the reporting of smoking cessation outcomes). CONCLUSIONS: A Delphi study has developed a modified CONSORT-SPI guideline (CONSORT-SPI-SMOKE) to improve the reporting of trials of behavioural interventions to promote smoking cessation.

Patient and Public Involvement (PPI) in outcome selection in breast cancer and nephrology trials.

We recently reported that according to patients and healthcare professionals in breast cancer and nephrology trials, teams conducting the trials got their choice of primary outcome wrong (72% of the time) more often than they got it right (28% of the time). A Patient and Public Involvement (PPI) representative, co-author of this letter, asked (on Twitter) whether PPI contributors had been involved in the design of the original trials and by extension the outcome selection. The purpose of this study was to answer this question.

Response to a novel, weight self-awareness plan used in a multi-component lifestyle intervention programme to reduce breast cancer risk factors in older women-Secondary analysis from the ActWELL trial.

BACKGROUND: The ActWELL randomised controlled trial assessed the effectiveness of a weight management programme delivered by volunteer lifestyle coaches (LCs) in women attending breast clinics. The intervention focused on caloric intake and physical activity, utilising behavioural change techniques including a weight awareness plan (WAP). The current work is a secondary analysis of the ActWELL data and aims to examine the response to the weight self-awareness plan (used as part of the intervention programme). METHODS: The LCs invited participants (n = 279) to undertake an implementation intention discussion to formulate a self-weighing (SW) plan. Bodyweight scales were offered, and recording books provided. The physical activity component of the intervention focused on a walking plan assessed by accelerometers. The LCs contacted participants by telephone monthly and provided personalised feedback. Mann-Whitney tests and chi-squared analysis were used to examine the effect of SW on weight change. A qualitative evaluation utilising semi-structured interviews was also undertaken. RESULTS: Most participants (96.4%) agreed to set a weekly SW goal and 76 (27%) requested scales. At 12 months, 226 (81%) returned for follow up. The median (interquartile range) weight change for those who self- reported at least one weight (n = 211) was -2.3 kg (-5.0 to 0.0) compared to -1.2 kg (-5.0 to 0.03) in those who did not (n = 14). Participants who reported weights on more than eight occasions (39%) were significantly more likely (p = 0.012) to achieve 5% weight loss compared to those who weighed less often. Low numbers of accelerometers were returned that did not allow for significance testing. Qualitative data (n = 24) indicated that many participants found the WAP helpful and motivating. CONCLUSIONS: Greater adherence to the WAP initiated by volunteer coaches is associated with achieving 5% weight loss.

The Achieving Self-directed Integrated Cancer Aftercare Intervention for Detection of Recurrent and Second Primary Melanoma in Survivors of Melanoma: Pilot Randomized Controlled Trial.

BACKGROUND: Melanoma is common with increasing incidence. Guidelines recommend monthly total skin self-examinations (TSSEs) by survivors to detect recurrent and new primary melanomas. TSSE is underperformed despite evidence of benefit. OBJECTIVE: This study compares the effect on psychological well-being and TSSE practice of a self-directed digital intervention with treatment as usual in patients treated for a first stage 0 to IIC primary cutaneous melanoma within the preceding 60 months. METHODS: This randomized clinical trial was conducted at 2 UK National Health Service hospitals (Aberdeen Royal Infirmary, Grampian, and Addenbrooke's, Cambridge). Adults (≥18 years) diagnosed with a first 0 to IIC primary cutaneous melanoma were randomized to receive Achieving Self-directed Integrated Cancer Aftercare (ASICA), a tablet-based intervention prompting and supporting TSSE in survivors of melanoma, or to usual care. The hypothesis was that ASICA would increase TSSE practice in users affected by melanoma and compared with controls without affecting psychological well-being. The main primary outcomes were melanoma worry (Melanoma Worry Scale), anxiety and depression (Hospital Anxiety and Depression Scale), and quality of life (EQ-5D-5L) as well as secondary outcomes collected using postal questionnaires 3, 6, and 12 months following randomization. RESULTS: A total of 240 recruits were randomized (1:1) into the ASICA (n=121, 50.4%) or control (n=119, 49.6%) groups. There were no significant differences between groups for melanoma worry at 12 months (mean difference: 0.12, 95% CI -0.6 to 0.84; P=.74), 3 months (0.23, 95% CI -0.31 to 0.78; P=.40), or 6 months (-0.1, 95% CI -0.7 to 0.51; P=.76). The ASICA group had lower anxiety scores at 12 months (-0.54, 95% CI -1.31 to 0.230; P=.17), 3 months (-0.13, 95% CI -0.79 to 0.54; P=.71), and significantly at 6 months (-1.00, 95% CI -1.74 to -0.26; P=.009). Depression scores were similar, being lower at 12 months (-0.44, 95% CI -1.11 to 0.23; P=.20) and 3 months (-0.24, 95% CI -0.84 to 0.35; P=.42) but only significantly lower at 6 months (-0.77, 95% CI -1.41 to -0.12; P=.02). The ASICA group had significantly higher quality of life scores at 12 months (0.044, 95% CI 0.003-0.085; P=.04) and 6 months (0.070, 95% CI 0.032-0.107; P<.001) and nonsignificantly at 3 months (0.024, 95% CI -0.006 to 0.054; P=.11). ASICA users reported significantly more regular (>5) TSSEs during the study year and significantly higher levels of self-efficacy in conducting TSSE. They also reported significantly higher levels of planning and intention to perform TSSE in the future. CONCLUSIONS: Using ASICA for 12 months does not increase melanoma worry, can reduce anxiety and depression, and may improve quality of life. ASICA has the potential to improve the well-being and vigilance of survivors of melanoma and enable the benefits of regular TSSE. TRIAL REGISTRATION: ClinicalTrials.gov NCT03328247; https://clinicaltrials.gov/ct2/show/NCT03328247. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.1186/s13063-019-3453-x.

Getting it wrong most of the time? Comparing trialists' choice of primary outcome with what patients and health professionals want.

BACKGROUND: Randomised trials support improved decision-making through the data they collect. One important piece of data is the primary outcome - so called because it is what the investigators decide is the most important. Secondary outcomes provide additional information to support decision-making. We were interested in knowing how important patients and healthcare professionals consider the outcomes (especially the primary outcome) measured in a selection of published trials. METHODS: The work had three stages: (1) We identified a body of late-stage trials in two clinical areas, breast cancer management and nephrology. (2) We identified the primary and secondary outcomes for these trials. (3) We randomly ordered these outcomes and presented them to patients and healthcare professionals (with experience of the clinical area), and we asked them to rank the importance of the outcomes. They were not told which outcomes trial authors considered primary and secondary. RESULTS: In our sample of 44 trials with 46 primary outcomes, 29 patients, one patient representative and 12 healthcare professionals together ranked the primary outcome as the most important outcome 13/46 times or 28%. Breast cancer patients and healthcare professionals considered the primary outcome to be the most important outcome for 8/21 primary outcomes chosen by trialists. For nephrology, the equivalent figure was 5/25. The primary outcome appeared in a respondent's top 5 ranked outcomes 151/178 (85%) times for breast cancer and 225/259 (87%) times for nephrology even if the primary was not considered the most important outcome. CONCLUSIONS: The primary outcome in a trial is the most important piece of data collected. It is used to determine how many participants are required, and it is the main piece of information used to judge whether the intervention is effective or not. In our study, patients and healthcare professionals agreed with the choice of the primary outcome made by trial teams doing late-stage trials in breast cancer management and nephrology 28% of the time.

Increasing uptake to a lung cancer screening programme: building with communities through co-design.

BACKGROUND: Lung cancer is the most common cause of cancer death in the UK. Low-dose computed tomography (LDCT) screening has been shown to identify lung cancer at an earlier stage. A risk stratified approach to LDCT referral is recommended. Those at higher risk of developing lung cancer (aged 55 + , smoker, deprived area) are least likely to participate in such a programme and, therefore, it is necessary to understand the barriers they face and to develop pathways for implementation in order to increase uptake. METHODS: A 2-phased co-design process was employed to identify ways to further increase opportunity for uptake of a lung cancer screening programme, using a risk indicator for LDCT referral, amongst people who could benefit most. Participants were members of the public at high risk from developing lung cancer and professionals who may provide or signpost to a future lung cancer screening programme. Phase 1: interviews and focus groups, considering barriers, facilitators and pathways for provision. Phase 2: interactive offline booklet and online surveys with professionals. Qualitative data was analysed thematically, while descriptive statistics were conducted for quantitative data. RESULTS: In total, ten barriers and eight facilitators to uptake of a lung cancer screening programme using a biomarker blood test for LDCT referral were identified. An additional four barriers and four facilitators to provision of such a programme were identified. These covered wider themes of acceptability, awareness, reminders and endorsement, convenience and accessibility. Various pathway options were evidenced, with choice being a key facilitator for uptake. There was a preference (19/23) for the provision of home test kits but 7 of the 19 would like an option for assistance, e.g. nurse, pharmacist or friend. TV was the preferred means of communicating about the programme and fear was the most dominant barrier perceived by members of the public. CONCLUSION: Co-design has provided a fuller understanding of the barriers, facilitators and pathways for the provision of a future lung cancer screening programme, with a focus on the potential of biomarker blood tests for the identification of at-risk individuals. It has also identified possible solutions and future developments to enhance uptake, e.g. Embedding the service in communities, Effective communication, Overcoming barriers with options. Continuing the process to develop these solutions in a collaborative way helps to encourage the personalised approach to delivery that is likely to improve uptake amongst groups that could benefit most.

Predictors of recruitment and retention in randomized controlled trials of behavioural smoking cessation interventions: a systematic review and meta-regression analysis.

AIM: To investigate predictors of participant eligibility, recruitment and retention in behavioural randomized controlled trials (RCTs) for smoking cessation. METHOD: Systematic review and pre-specified meta-regression analysis of behavioural RCTs for smoking cessation including adult (≥ 18-year-old) smokers. The pre-specified predictors were identified through a literature review and experts' consultation and included participant, trial and intervention characteristics and recruitment and retention strategies. Outcome measures included eligibility rates (proportion of people eligible for the trials), recruitment rates, retention rates and differential retention rates. RESULTS: A total of 172 RCTs with 89 639 participants. Eligibility [median 57.6%; interquartile range (IQR) = 34.7-83.7], recruitment (median 66.4%; IQR = 42.7-85.2) and retention rates (median 80.5%; IQR = 68.5-89.5) varied considerably across studies. For eligibility rates, the recruitment strategy appeared not to be associated with eligibility rates. For recruitment rates, use of indirect recruitment strategies (e.g. public announcements) [odds ratio (OR) = 0.30, 95% confidence interval (CI) = 0.11-0.82] and self-help interventions (OR = 0.14, 95% CI = 0.03-0.67) were associated with lower recruitment rates. For retention rates, higher retention was seen if the sample had ongoing physical health condition/s (OR = 1.66, 95% CI = 1.04-2.63), whereas lower retention was seen amongst primarily female samples (OR = 0.83, 95% CI = 0.71-0.98) and those motivated to quit smoking (OR = 0.74, 95% CI = 0.55-0.99) when indirect recruitment methods were used (OR = 0.60, 95% CI = 0.38-0.97) and at longer follow-up assessments (OR = 0.83, 95% CI = 0.79-0.87). For differential retention, higher retention in the intervention group occurred when the intervention but not comparator group received financial incentives for smoking cessation (OR = 1.35, 95% CI = 1.02-1.77). CONCLUSIONS: In randomized controlled trials of behavioural smoking cessation interventions, recruitment and retention rates appear to be higher for smoking cessation interventions that include a person-to-person rather than at-a-distance contact; male participants, smokers with chronic conditions, smokers not initially motivated to quit and shorter follow-up assessments seems to be associated with improved retention; financial incentive interventions improve retention in groups receiving them relative to comparison groups.

ScotCap - A large observational cohort study.

AIM: The aim of this work was to evaluate the performance of colon capsule endoscopy (CCE) in a lower gastrointestinal diagnostic care pathway. METHOD: This large multicentre prospective clinical evaluation recruited symptomatic patients (patients requiring investigation of symptoms suggestive of colorectal pathology) and surveillance patients (patients due to undergo surveillance colonoscopy). Patients aged 18 years or over were invited to participate and undergo CCE by a secondary-care clinician if they met the referral criteria for a colonoscopy. The primary outcome was the test completion rate (visualization of the whole colon and rectum). We also measured the need for further tests after CCE. RESULTS: A total of 733 patients were invited to take part in this evaluation, with 509 patients undergoing CCE. Of these, 316 were symptomatic patients and 193 were surveillance patients. Two hundred and twenty-eight of the 316 symptomatic patients (72%) and 137 of the 193 surveillance patients (71%) had a complete test. It was found that 118/316 (37%) of symptomatic patients required no further test following CCE, while 103/316 (33%) and 81/316 (26%) required a colonoscopy and flexible sigmoidoscopy, respectively. Fifty-three of the 193 surveillance patients (28%) required no further test following CCE, while 104/193 (54%) and 30/193 (16%) required a colonoscopy and flexible sigmoidoscopy, respectively. No patient in this evaluation was diagnosed with colorectal cancer. Two patients experienced serious adverse events - one capsule retention with obstruction and one hospital admission with dehydration due to the bowel preparation. CONCLUSION: CCE is a safe, well-tolerated diagnostic test which can reduce the proportion of patients requiring colonoscopy, but the test completion rate needs to be improved to match that of lower gastrointestinal endoscopy.

Bah humbug! Association between sending Christmas cards to trial participants and trial retention: randomised study within a trial conducted simultaneously across eight host trials.

OBJECTIVES: To determine the effectiveness of sending Christmas cards to participants in randomised controlled trials to increase retention rate at follow-ups, and to explore the feasibility of doing a study within a trial (SWAT) across multiple host trials simultaneously. DESIGN: Randomised SWAT conducted simultaneously across eight host trials. SETTING: Eight randomised controlled trials researching various areas including surgery and smoking cessation. PARTICIPANTS: 3223 trial participants who were still due at least one follow-up from their host randomised controlled trial. INTERVENTION: Participants were randomised (1:1, separately by each host trial) to either received a Christmas card in mid-December 2019 or to not receive a card. MAIN OUTCOME MEASURE: Proportion of participants completing their next follow-up (retention rate) within their host randomised controlled trial. RESULTS: 1469 participants (age 16-94 years; 70% (n=1033) female; 96% (813/847) white ethnicity) across the eight host randomised controlled trials were involved in the analysis (cut short owing to covid-19). No evidence was found of a difference in retention rate between the two arms for any of the host trials when analysed separately or when the results were combined (85.3% (639/749) for cards versus 85.4% (615/720) for no card; odds ratio 0.96, 95% confidence interval 0.71 to 1.29; P=0.77). No difference was observed when comparing just participants who were due a follow-up in the 30 days after receiving the card (odds ratio 0.96, 0.42 to 2.21). No evidence of a difference in time to complete the questionnaire was found (hazard ratio 1.01, 95% confidence interval 0.91 to 1.13; P=0.80). These results were robust to post hoc sensitivity analyses. The cost of this intervention was £0.76 (€0.91; $1.02) per participant, and it will have a carbon footprint of approximately 140 g CO2 equivalent per card. One benefit of this approach was the need to only submit one ethics application. CONCLUSIONS: Sending Christmas cards to participants in randomised controlled trials does not increase retention. Undertaking a SWAT within multiple randomised controlled trials at the same time is, however, possible. This approach should be used more often to build an evidence base to support selection of recruitment and retention strategies. Although no evidence of a boost to retention was found, embedding a SWAT in multiple host trials simultaneously has been shown to be possible. STUDY REGISTRATION: SWAT repository https://www.qub.ac.uk/sites/TheNorthernIrelandNetworkforTrialsMethodologyResearch/FileStore/Filetoupload,846275,en.pdf#search=SWAT%2082.

A novel approach to increasing community capacity for weight management a volunteer-delivered programme (ActWELL) initiated within breast screening clinics: a randomised controlled trial.

BACKGROUND: It is estimated that around 30% of breast cancers in post-menopausal women are related to lifestyle. The breast cancer-pooling project demonstrated that sustained weight loss of 2 to 4.5 kg is associated with an 18% lower risk of breast cancer, highlighting the importance of small changes in body weight. Our study aimed to assess the effectiveness a volunteer-delivered, community based, weight management programme (ActWELL) for women with a BMI > 25 kg/m2 attending NHS Scotland Breast Screening clinics. METHODS: A multicentre, 1:1 parallel group, randomised controlled trial was undertaken in 560 women aged 50 to 70 years with BMI > 25 kg/m2. On completion of baseline measures, all participants received a breast cancer prevention leaflet. Intervention group participants received the ActWELL intervention which focussed on personalised diet advice and pedometer walking plans. The programme was delivered in leisure centres by (the charity) Breast Cancer Now volunteer coaches. Primary outcomes were changes between groups at 12 months in body weight (kg) and physical activity (accelerometer measured step count). RESULTS: Two hundred seventy-nine women were allocated to the intervention group and 281 to the comparison group. Twelve-month data were available from 240 (81%) intervention and 227 (85%) comparison group participants. Coaches delivered 523 coaching sessions and 1915 support calls to 279 intervention participants. Mean weight change was - 2.5 kg (95% CI - 3.1 to - 1.9) in the intervention group and - 1.2 kg (- 1.8 to 0.6) in the comparison group. The adjusted mean difference was - 1.3 kg (95% CI - 2.2 to - 0.4, P = 0.003). The odds ratio for losing 5% weight was 2.20 (95% CI 1.4 to 3.4, p = 0.0005) in favour of the intervention. The adjusted mean difference in step counts between groups was 483 steps/day (95% CI - 635 to 1602) (NS). CONCLUSIONS: A community weight management intervention initiated at breast screening clinics and delivered by volunteer coaches doubled the likelihood of clinically significant weight loss at 12 months (compared with usual care) offering significant potential to decrease breast cancer risk. TRIAL REGISTRATION: Database of registration: ISCRTN. Registration number: 11057518 . Date trial registered:21.07.2017. Date of enrolment of first participant: 01.09.2017.

Cancer prevention through weight control-where are we in 2020?

Growing data from epidemiological studies highlight the association between excess body fat and cancer incidence, but good indicative evidence demonstrates that intentional weight loss, as well as increasing physical activity, offers much promise as a cost-effective approach for reducing the cancer burden. However, clear gaps remain in our understanding of how changes in body fat or levels of physical activity are mechanistically linked to cancer, and the magnitude of their impact on cancer risk. It is important to investigate the causal link between programmes that successfully achieve short-term modest weight loss followed by weight-loss maintenance and cancer incidence. The longer-term impact of weight loss and duration of overweight and obesity on risk reduction also need to be fully considered in trial design. These gaps in knowledge need to be urgently addressed to expedite the development and implementation of future cancer-control strategies. Comprehensive approaches to trial design, Mendelian randomisation studies and data-linkage opportunities offer real possibilities to tackle current research gaps. In this paper, we set out the case for why non-pharmacological weight-management trials are urgently needed to support cancer-risk reduction and help control the growing global burden of cancer.

Earlier diagnosis of lung cancer in a randomised trial of an autoantibody blood test followed by imaging.

The EarlyCDT-Lung test is a high-specificity blood-based autoantibody biomarker that could contribute to predicting lung cancer risk. We report on the results of a phase IV biomarker evaluation of whether using the EarlyCDT-Lung test and any subsequent computed tomography (CT) scanning to identify those at high risk of lung cancer reduces the incidence of patients with stage III/IV/unspecified lung cancer at diagnosis compared with the standard clinical practice at the time the study began.The Early Diagnosis of Lung Cancer Scotland (ECLS) trial was a randomised controlled trial of 12 208 participants at risk of developing lung cancer in Scotland in the UK. The intervention arm received the EarlyCDT-Lung test and, if test-positive, low-dose CT scanning 6-monthly for up to 2 years. EarlyCDT-Lung test-negative and control arm participants received standard clinical care. Outcomes were assessed at 2 years post-randomisation using validated data on cancer occurrence, cancer staging, mortality and comorbidities.At 2 years, 127 lung cancers were detected in the study population (1.0%). In the intervention arm, 33 out of 56 (58.9%) lung cancers were diagnosed at stage III/IV compared with 52 out of 71 (73.2%) in the control arm. The hazard ratio for stage III/IV presentation was 0.64 (95% CI 0.41-0.99). There were nonsignificant differences in lung cancer and all-cause mortality after 2 years.ECLS compared EarlyCDT-Lung plus CT screening to standard clinical care (symptomatic presentation) and was not designed to assess the incremental contribution of the EarlyCDT-Lung test. The observation of a stage shift towards earlier-stage lung cancer diagnosis merits further investigations to evaluate whether the EarlyCDT-Lung test adds anything to the emerging standard of low-dose CT.

Optimisation of the ActWELL lifestyle intervention programme for women attending routine NHS breast screening clinics.

BACKGROUND: Around 30% of post-menopausal breast cancer is related to excess body fat, alcohol intake and low levels of physical activity. Current estimates suggest that there is a 12% increased risk in post-menopausal breast cancer for every 5 kg/m2 increase in body mass index (BMI). Despite this evidence there are few lifestyle programmes directed towards breast cancer risk reduction. This paper describes the process of optimising of the ActWELL programme which aims to support weight management in women invited to attend routine National Health Service (NHS) breast screening clinics. METHODS: A feasibility study of a prototype programme aiming to change lifestyle behaviours was successfully undertaken. The programme used educational approaches and behaviour change techniques delivered by lifestyle coaches using individual face to face meetings and telephone sessions. To optimise the intervention for a definitive randomised controlled trial of weight management, data from the feasibility trial, focus group discussions conducted with the target population, feedback from the trial public advisory group and comments from peer reviewers were obtained. Concepts from implementation research provided further guidance to assist in the refinement of the intervention, which was then discussed and agreed by all investigators and the Trial Steering Group. RESULTS: The results from the feasibility trial were considered appropriate for moving on to a full trial with 70% of participants finding the programme acceptable. The primary outcomes (weight loss and physical activity) provided an important focus for design input from the target group. The contributions highlighted the need to review programme duration, coach contact time, content and use of behaviour change techniques and communications generally (e.g. science and evidence, non-judgemental approaches and avoiding guilt). In addition, the need for emphasis on support rather than education became apparent. The recommendations from peer reviewers focussed on the magnitude of effort required to achieve the intended weight loss and weight loss maintenance. Implementation science supported the use of the capability/opportunity/motivation (COM-B)model in overall design. CONCLUSIONS: The optimisation process has facilitated the development and evaluation of a programme that enables the delivery of a promising intervention to achieve weight management in post-menopausal women. TRIAL REGISTRATION: ISRCTN: ISRCTN11057518. Registered on 21 July 2017. Retrospectively registered.

Five-year cost-effectiveness analysis of the European Fans in Training (EuroFIT) physical activity intervention for men versus no intervention.

OBJECTIVES: Increasing physical activity reduces the risk of chronic illness including Type 2 diabetes, cardiovascular disease and certain types of cancer. Lifestyle interventions can increase physical activity but few successfully engage men. This study aims to investigate the 5 year cost-effectiveness of EuroFIT, a program to improve physical activity tailored specifically for male football (soccer) fans compared to a no intervention comparison group. METHODS: We developed a Markov cohort model in which the impact of improving physical activity on five chronic health conditions (colorectal cancer, Type 2 diabetes, coronary heart disease, stroke and depression) and mortality was modelled. We estimated costs from a societal perspective and expressed benefits as quality adjusted life years (QALYs). We obtained data from a 4-country (England, Netherlands, Portugal and Norway) pragmatic randomised controlled trial evaluating EuroFIT, epidemiological and cohort studies, and meta-analyses. We performed deterministic and probabilistic sensitivity analyses to assess the impact of uncertainty in the model's parameter values on the cost-effectiveness results. We used Monte Carlo simulations to estimate uncertainty and presented this using cost-effectiveness acceptability curves (CEACs). We tested the robustness of the base case analysis using five scenario analyses. RESULTS: Average costs over 5 years per person receiving EuroFIT were €14,663 and per person receiving no intervention €14,598. Mean QALYs over 5 years were 4.05 per person for EuroFIT and 4.04 for no intervention. Thus, the average incremental cost per person receiving EuroFIT was €65 compared to no intervention, while the average QALY gain was 0.01. This resulted in an ICER of €5206 per QALY gained. CEACs show that the probability of EuroFIT being cost-effective compared to no intervention is 0.53, 0.56 and 0.58 at thresholds of €10,000, €22,000 and €34,000 per QALY gained, respectively. When using a time horizon of 10 years, the results suggest that EuroFIT is more effective and less expensive compared to (i.e. dominant over) no intervention with a probability of cost-effectiveness of 0.63 at a threshold of €22,000 per QALY gained. CONCLUSIONS: We conclude the EuroFIT intervention is not cost-effective compared to no intervention over a period of 5 years from a societal perspective, but is more effective and less expensive (i.e. dominant) after 10 years. We thus suggest that EuroFIT can potentially improve public health in a cost-effective manner in the long term.

Patient and public involvement (PPI) in UK surgical trials: a survey and focus groups with stakeholders to identify practices, views, and experiences.

BACKGROUND AND AIMS: Historically, patient and public involvement (PPI) in the design and conduct of surgical trials has been absent or minimal, but it is now routinely recommended and even required by some research funders. We aimed to identify and describe current PPI practice in surgical trials in the United Kingdom, and to explore the views and experiences of surgical trial staff and patient or public contributors in relation to these practices. This was part of a larger study to inform development of a robust PPI intervention aimed at improving recruitment and retention in surgical trials. METHODS: Our study had two stages: 1) an online survey to identify current PPI practice in active UK-led, adult surgical trials; and 2) focus groups and interviews with key stakeholders (surgical trial investigators, administrators, and patient or public contributors) to explore their views and experiences of PPI. RESULTS: Of 129 eligible surgical trial teams identified, 71 (55%) took part in the survey. In addition, 54 stakeholders subsequently took part in focus groups or interviews. Sixty-five (92%) survey respondents reported some kind of PPI, most commonly at the design and dissemination stages and in oversight or advisory roles. The single most common PPI activity was developing participant information sheets (72%). Participants reported mixed practice and views on a variety of issues including the involvement of patients versus lay members of the public, recruitment methods, use of role descriptions and payment for the time of PPI contributors. They suggested some solutions, including the use of written role descriptions and databases of potential PPI contributors to aid recruitment. CONCLUSIONS: UK surgical trials involve patients and members of the public in a variety of different ways, most commonly at the beginning and end of the trial lifecycle and in oversight or advisory roles. These are not without challenges and there remain uncertainties about who best to involve, why, and how. Future research should aim to address these issues.

Randomised controlled trial to assess the impact of a lifestyle intervention (ActWELL) in women invited to NHS breast screening.

INTRODUCTION: In Scotland, the incidence of breast cancer is predicted to rise significantly in the next few decades and while there are measures to support reductions in morbidity and mortality, the breast cancer community is currently exploring preventative opportunities including supporting weight management programmes in postmenopausal women. This study aims to assess the effectiveness and cost-effectiveness of a theory-based, community delivered, minimal contact, weight management (diet, physical activity and behaviour change techniques) programme (ActWELL) in women with a body mass index (BMI) >25 kg/m2 attending routine breast cancer screening appointments. METHODS AND ANALYSIS: The study will be a four-centre, 1:1 parallel group randomised controlled trial of a 12-month weight management intervention initiated in breast cancer screening centres, delivered by trained Breast Cancer Now lifestyle coaches in community settings. The intervention programme involves two intervention meetings with coaches plus (up to) nine telephone contacts over 12 months. The programme will focus on personalised diet (including alcoholic and sugary drinks) and physical activity habits. Behaviour change techniques include self-monitoring, goal setting, implementation intentions, action and coping plans. The study has a sample size of 414 women with a BMI >25 kg/m2 attending routine National Health Service breast cancer screening appointments. Measures will be taken at baseline, 12 weeks and at 12-month follow-up, complemented by qualitative interviews exploring perceived acceptability and impact on habitual behaviours. The two co-primary outcomes are mean change in measured body weight and change in physical activity between groups to 12 months. Secondary outcomes are changes in eating habits, alcohol intake, sedentary time, quality of life, waist circumference, lipid, haemoglobin A1c and insulin profiles, blood pressure and cost-effectiveness of the intervention. ETHICS AND DISSEMINATION: The protocol has been approved by East of Scotland Research Ethics Committee (17/ES/0073). All participants provide written informed consent. Dissemination will be through peer-reviewed publication and conference presentations. TRIAL REGISTRATION NUMBER: ISRCTN11057518; Pre-results.

The effect of optimised patient information materials on recruitment in a lung cancer screening trial: an embedded randomised recruitment trial.

BACKGROUND: Written participant information materials are important for ensuring that potential trial participants receive necessary information so that they can provide informed consent. However, such materials are frequently long and complex, which may negatively impact patient understanding and willingness to participate. Improving readability, ease of comprehension and presentation may assist with improved participant recruitment. The Systematic Techniques for Assisting Recruitment to Trials (MRC START) study aimed to develop and evaluate interventions to improve trial recruitment. This study aimed to assess the effectiveness of an optimised participant information brochure and cover letter developed by MRC START regarding response and participant recruitment rates. METHODS: We conducted a study within a trial (SWAT) embedded in the EarlyCDT Lung Cancer Scotland (ECLS) trial that aimed to assess the effectiveness of a new test in reducing the incidence of patients with late-stage lung cancer at diagnosis compared with standard care. Potential participants approached for ECLS were randomised to receive the original participant information brochure and accompanying letter (control group) or optimised versions of these materials which had undergone user testing and a process of re-writing, re-organisation and professional graphic design (intervention group). The primary outcome was the number of patients recruited to ECLS. The secondary outcome was the proportion of patients expressing an interest in participating in ECLS. RESULTS: In total, 2262 patients were randomised, 1136 of whom were sent the intervention materials and 1126 of whom were sent the control materials. The proportion of patients enrolled and randomised into ECLS was 180 of 1136 (15.8%) in the intervention group and 176 of 1126 (15.6%) in the control group (OR = 1.016, 95% CI, 0.660 to 1.564). The proportion of patients who positively responded to the invitation was 224 of 1136 (19.7%) in the intervention group and 205 of 1126 (18.2%) in the control group (OR = 1.103, 95% CI, 0.778 to 1.565). CONCLUSIONS: Optimised patient information materials made little difference to the proportion of patients positively responding to a trial invitation or to the proportion subsequently randomised to the host trial. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01925625 . Registered on 15 August 2015. Study Within A Trial, SWAT-23. Registered on 12 April 2016.

Detection in blood of autoantibodies to tumour antigens as a case-finding method in lung cancer using the EarlyCDT®-Lung Test (ECLS): study protocol for a randomized controlled trial.

BACKGROUND: Lung cancer is the most common cause of cancer related death worldwide. The majority of cases are detected at a late stage when prognosis is poor. The EarlyCDT®-Lung Test detects autoantibodies to abnormal cell surface proteins in the earliest stages of the disease which may allow tumour detection at an earlier stage thus altering prognosis. The primary research question is: Does using the EarlyCDT®-Lung Test to identify those at high risk of lung cancer, followed by X-ray and computed tomography (CT) scanning, reduce the incidence of patients with late-stage lung cancer (III & IV) or unclassified presentation (U) at diagnosis, compared to standard practice? METHODS: A randomised controlled trial of 12 000 participants in areas of Scotland targeting general practices serving patients in the most deprived quintile of the Scottish Index of Multiple Deprivation. Adults aged 50-75 who are at high risk of lung cancer and healthy enough to undergo potentially curative therapy (Performance Status 0-2) are eligible to participate. The intervention is the EarlyCDT®-Lung Test, followed by X-ray and CT in those with a positive result. The comparator is standard clinical practice in the UK. The primary outcome is the difference, after 24 months, between the rates of patients with stage III, IV or unclassified lung cancer at diagnosis. The secondary outcomes include: all-cause mortality; disease specific mortality; a range of morbidity outcomes; cost-effectiveness and measures examining the psychological and behavioural consequences of screening. Participants with a positive test result but for whom the CT scan does not lead to a lung cancer diagnosis will be offered 6 monthly thoracic CTs for 24 months. An initial chest X-ray will be used to determine the speed and the need for contrast in the first screening CT. Participants who are found to have lung cancer will be followed-up to assess both time to diagnosis and stage of disease at diagnosis. DISCUSSION: The study will determine the clinical and cost effectiveness of EarlyCDT®-Lung Test for early lung cancer detection and assess its suitability for a large-scale, accredited screening service. The study will also assess the potential psychological and behavioural harms arising from false positive or false negative results, as well as the potential benefits to patients of true negative EarlyCDT lung test results. A cost-effectiveness model of lung cancer screening based on the results of the EarlyCDT Lung Test study will be developed. TRIAL REGISTRATION: NCT01925625 . August 19, 2013.

The feasibility and acceptability of trial procedures for a pragmatic randomised controlled trial of a structured physical activity intervention for people diagnosed with colorectal cancer: findings from a pilot trial of cardiac rehabilitation versus usual care (no rehabilitation) with an embedded qualitative study.

BACKGROUND: Pilot and feasibility work is conducted to evaluate the operational feasibility and acceptability of the intervention itself and the feasibility and acceptability of a trials' protocol design. The Cardiac Rehabilitation In Bowel cancer (CRIB) study was a pilot randomised controlled trial (RCT) of cardiac rehabilitation versus usual care (no rehabilitation) for post-surgical colorectal cancer patients. A key aim of the pilot trial was to test the feasibility and acceptability of the protocol design. METHODS: A pilot RCT with embedded qualitative work was conducted in three sites. Participants were randomly allocated to cardiac rehabilitation or usual care groups. Outcomes used to assess the feasibility and acceptability of key trial parameters were screening, eligibility, consent, randomisation, adverse events, retention, completion, missing data, and intervention adherence rates. Colorectal patients' and clinicians' perceptions and experiences of the main trial procedures were explored by interview. RESULTS: Quantitative study. Three sites were involved. Screening, eligibility, consent, and retention rates were 79 % (156/198), 67 % (133/198), 31 % (41/133), and 93 % (38/41), respectively. Questionnaire completion rates were 97.5 % (40/41), 75 % (31/41), and 61 % (25/41) at baseline, follow-up 1, and follow-up 2, respectively. Sixty-nine percent (40) of accelerometer datasets were collected from participants; 31 % (20) were removed for not meeting wear-time validation. Qualitative study: Thirty-eight patients and eight clinicians participated. Key themes were benefits for people with colorectal cancer attending cardiac rehabilitation, barriers for people with colorectal cancer attending cardiac rehabilitation, generic versus disease-specific rehabilitation, key concerns about including people with cancer in cardiac rehabilitation, and barriers to involvement in a study about cardiac rehabilitation. CONCLUSIONS: The study highlights where threats to internal and external validity are likely to arise in any future studies of similar structured physical activity interventions for colorectal cancer patients using similar methods being conducted in similar contexts. This study shows that there is likely to be potential recruitment bias and potential imprecision due to sub-optimal completion of outcome measures, missing data, and sub-optimal intervention adherence. Hence, strategies to manage these risks should be developed to stack the odds in favour of conducting successful future trials. TRIAL REGISTRATION: ISRCTN63510637.