Effectiveness and cost-effectiveness of a physical activity loyalty scheme for behaviour change maintenance: a cluster randomised controlled trial

Background
Increasing physical activity in the workplace can provide employee physical and mental health benefits, and employer economic benefits through reduced absenteeism and increased productivity. The workplace is an opportune setting to encourage habitual activity. However, there is limited evidence on effective behaviour change interventions that lead to maintained physical activity. This study aims to address this gap and help build the necessary evidence base for effective, and cost-effective, workplace interventions

Methods/design
This cluster randomised control trial will recruit 776 office-based employees from public sector organisations in Belfast and Lisburn city centres, Northern Ireland. Participants will be randomly allocated by cluster to either the Intervention Group or Control Group (waiting list control). The 6-month intervention consists of rewards (retail vouchers, based on similar principles to high street loyalty cards), feedback and other evidence-based behaviour change techniques. Sensors situated in the vicinity of participating workplaces will promote and monitor minutes of physical activity undertaken by participants. Both groups will complete all outcome measures. The primary outcome is steps per day recorded using a pedometer (Yamax Digiwalker CW-701) for 7 consecutive days at baseline, 6, 12 and 18 months. Secondary outcomes include health, mental wellbeing, quality of life, work absenteeism and presenteeism, and use of healthcare resources. Process measures will assess intervention “dose”, website usage, and intervention fidelity. An economic evaluation will be conducted from the National Health Service, employer and retailer perspective using both a cost-utility and cost-effectiveness framework. The inclusion of a discrete choice experiment will further generate values for a cost-benefit analysis. Participant focus groups will explore who the intervention worked for and why, and interviews with retailers will elucidate their views on the sustainability of a public health focused loyalty card scheme.

Discussion
The study is designed to maximise the potential for roll-out in similar settings, by engaging the public sector and business community in designing and delivering the intervention. We have developed a sustainable business model using a ‘points’ based loyalty platform, whereby local businesses ‘sponsor’ the incentive (retail vouchers) in return for increased footfall to their business.

ARB: Phase II window of opportunity study of short-term preoperative treatment with enzalutamide in ER-positive and triple-negative breast cancer

The androgen receptor (AR) is expressed in 60-80% of breast cancers (BC) across all molecular phenotypes, with a higher incidence in oestrogen receptor positive (ER+) BC compared to ER negative tumours. In ER+ disease, AR-expression has been linked to endocrine resistance which might be reversed with combined treatment targeting ER and AR. In triple negative BCs (TNBC), preclinical and clinical investigations have described a subset of patients that express the AR and are sensitive to androgen blockade, providing a novel therapeutic target. Enzalutamide, a potent 2nd generation anti-androgen, has demonstrated substantial preclinical and clinical anti-tumour activity in AR+ breast cancer. Short-term preoperative window of opportunity studies are a validated strategy for novel treatments to provide proof-of-concept and define the most appropriate patient population by directly assessing treatment effects in tumour tissue before and after treatment. The ARB study aims to assess the anti-tumour effects of enzalutamide in early ER+ breast cancer and TNBC, to identify the optimal target population for further studies and to directly explore the biologic effects of enzalutamide on BC and stromal cells. Methods: ARB is an international, investigator sponsored WOO phase II study in women with newly diagnosed primary ER+ BC or AR+ TNBC of ≥ 1cm. The study has two cohorts. In the ER+ cohort, postmenopausal patients will be randomised 2:1 to receive either enzalutamide (160mg OD) plus exemestane (50mg OD) or exemestane (25mg OD). In the TNBC cohort, AR+ will receive single agent treatment with enzalutamide (160mg OD). Study treatment is planned for 15–29 days, followed by surgery or neo-adjuvant therapy. Tissue and blood samples are collected before treatment and on the last day of study treatment. The primary endpoint is inhibition of tumour-cell proliferation, as measured by change in Ki67 expression, determined centrally by 2 investigators. Secondary endpoints include induction of apoptosis (Caspase3), circulating hormone levels and safety. ARB aims to recruit ≈235 patients from ≈40 sites in the UK, Germany, Spain and USA. The study is open to recruitment.

Challenges in molecular testing in non-small-cell lung cancer patients with advanced disease

Lung cancer diagnostics have progressed greatly in the previous decade. Development of molecular testing to identify an increasing number of potentially clinically actionable genetic variants, using smaller samples obtained via minimally invasive techniques, is a huge challenge. Tumour heterogeneity and cancer evolution in response to therapy means that repeat biopsies or circulating biomarkers are likely to be increasingly useful to adapt treatment as resistance develops. We highlight some of the current challenges faced in clinical practice for molecular testing of EGFR, ALK, and new biomarkers such as PDL1. Implementation of next generation sequencing platforms for molecular diagnostics in non-small-cell lung cancer is increasingly common, allowing testing of multiple genetic variants from a single sample. The use of next generation sequencing to recruit for molecularly stratified clinical trials is discussed in the context of the UK Stratified Medicine Programme and The UK National Lung Matrix Trial.