Assessing multidimensional fidelity in a pilot optimization trial: A process evaluation of four intervention components supporting medication adherence in women with breast cancer.

Adherence to adjuvant endocrine therapy in women with breast cancer is low. We conducted a 24-1 fractional factorial pilot optimization trial to test four intervention components supporting medication adherence [text messages, information leaflet, acceptance and commitment therapy (ACT), self-management website], in the preparation phase of the multiphase optimization strategy. Guided by the National Institute of Health Behavior Change Consortium fidelity framework, we investigated fidelity of design, training, delivery, receipt, and enactment of four intervention components.

Factors associated with physical activity in individuals with metastatic cancer: a UK cross-sectional survey.

Purpose: Physical activity is safe and feasible for individuals with metastatic cancer and may support symptom management. We investigated the extent to which individuals with metastatic cancer are meeting the World Health Organisation (WHO) moderate-vigorous physical activity (MVPA) guideline, factors associated with meeting the guideline, and perceptions about physical activity and receiving physical activity advice.

Methods: Data were from UK adults with metastatic breast, prostate, or colorectal cancer who completed the Healthy Lifestyle After Cancer survey (N = 588).

Acceptability of Four Intervention Components Supporting Medication Adherence in Women with Breast Cancer: a Process Evaluation of a Fractional Factorial Pilot Optimization Trial.

Adjuvant endocrine therapy (AET) reduces mortality in early-stage breast cancer, but adherence is low. We developed a multicomponent intervention to support AET adherence comprising: text messages, information leaflet, acceptance and commitment therapy (ACT), and side-effect website. Guided by the multiphase optimization strategy, the intervention components were tested in the ROSETA pilot optimization trial.

Reducing self-harm in adolescents: the RISA-IPD individual patient data meta-analysis and systematic review.

Background: Self-harm is common in adolescents and a major public health concern. Evidence for effective interventions is lacking. An individual patient data meta-analysis has the potential to provide more reliable estimates of the effects of therapeutic interventions for self-harm than conventional meta-analyses, to explore which treatments are best suited to certain groups.

Researchers' experiences of the design and conduct challenges associated with parallel-group cluster-randomised trials and views on a novel open-cohort design.

Background: Two accepted designs exist for parallel-group cluster-randomised trials (CRTs). Closed-cohort designs follow the same individuals over time with a single recruitment period before randomisation, but face challenges in settings with high attrition. (Repeated) cross-sectional designs recruit at one or more timepoints before and/or after randomisation, collecting data from different individuals present in the cluster at these timepoints, but are unsuitable for assessment of individual change over time.

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 detection and management of attempted fraud during an online randomised trial.

Background: Online studies offer an efficient method of recruiting participants and collecting data. Whilst delivering an online randomised trial, we detected unusual recruitment activity. We describe our approach to detecting and managing suspected fraud and share lessons for researchers.

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.

Surgical trial design for incorporating the effects of learning: what is the current methodological guidance, and is it sufficient?

Background: Surgical interventions are complex. Key elements of this complexity are the surgeon and their learning curve. They pose methodological challenges in the design, analysis and interpretation of surgical RCTs.

Decline in health-related quality of life and foot and ankle patient reported outcomes measures in patients with haemophilia and ankle haemarthropathy.

Background: Haemophilia is an X-linked recessive genetic disorder characterised by bleeding within soft tissue and joints. The ankle is disproportionally affected by haemarthropathy when compared to the elbows and knees; reported as the most affected joints in patients with haemophilia. Despite advances in treatment, patients still report ongoing pain and disability, however, the impact has not been evaluated, nor has the effect on health-related quality of life (HRQoL) or foot and ankle patient-reported outcome measures (PROMs).

The impact of ankle haemarthropathy in patients with moderate haemophilia.

Introduction: Moderate haemophilia has traditionally been associated with less complications than severe haemophilia. Changes in treatment recommendations have highlighted the burden of moderate haemophilia with a subset of patients with a severe bleeding phenotype. The ankle joint is disproportionally affected by ankle haemarthropathy however the impact has not been evaluated in moderate haemophilia, nor the effect on health related quality of life (HRQoL) or foot and ankle outcomes.

A randomised fractional factorial screening experiment to predict effective features of audit and feedback.

Background: Audit and feedback aims to improve patient care by comparing healthcare performance against explicit standards. It is used to monitor and improve patient care, including through National Clinical Audit (NCA) programmes in the UK. Variability in effectiveness of audit and feedback is attributed to intervention design; separate randomised trials to address multiple questions about how to optimise effectiveness would be inefficient.

A systematic review and narrative synthesis of footwear and orthotic devices used in the management of ankle haemarthrosis and haemarthropathy in haemophilia.

Introduction: Haemarthrosis is a clinical feature of haemophilia leading to haemarthropathy. The ankle joint is most commonly affected, resulting in significant pain, disability and a reduction in health-related quality of life. Footwear and orthotic devices are effective in other diseases that affect the foot and ankle, such as rheumatoid arthritis, but little is known about their effect in haemophilia.

Effectiveness of Enhanced Performance Feedback on Appropriate Use of Blood Transfusions: A Comparison of 2 Cluster Randomized Trials.

Importance: Auditing and feedback are frequently used to improve patient care. However, it remains unclear how to optimize feedback effectiveness for the appropriate use of treatments such as blood transfusion, a common but costly procedure that is more often overused than underused.

Objective: To evaluate 2 theoretically informed feedback interventions to improve the appropriate use of blood transfusions.

Twelve-month prevalence of haemarthrosis and joint disease using the Haemophilia Joint Health score: evaluation of the UK National Haemophilia Database and Haemtrack patient reported data: an observational study.

Objectives: To report the 12-month prevalence of joint bleeds from the National Haemophilia Database (NHD) and Haemtrack, a patient-reported online treatment diary and concurrent joint disease status using the haemophilia joint health score (HJHS) at individual joint level, in children and adults with severe haemophilia A and B (HA/HB) without a current inhibitor.

Design: A 2018 retrospective database study of NHD from which 2238 cases were identified, 463 patients had fully itemised HJHS of whom 273 were compliant in recording treatment using Haemtrack.

Setting: England, Wales and Scotland, UK.

A hypothesis test of feasibility for external pilot trials assessing recruitment, follow-up, and adherence rates.

The power of a large clinical trial can be adversely affected by low recruitment, follow-up, and adherence rates. External pilot trials estimate these rates and use them, via prespecified decision rules, to determine if the definitive trial is feasible and should go ahead. There is little methodological research underpinning how these decision rules, or the sample size of the pilot, should be chosen.

Bayesian design and analysis of external pilot trials for complex interventions.

External pilot trials of complex interventions are used to help determine if and how a confirmatory trial should be undertaken, providing estimates of parameters such as recruitment, retention, and adherence rates. The decision to progress to the confirmatory trial is typically made by comparing these estimates to pre-specified thresholds known as progression criteria, although the statistical properties of such decision rules are rarely assessed. Such assessment is complicated by several methodological challenges, including the simultaneous evaluation of multiple endpoints, complex multi-level models, small sample sizes, and uncertainty in nuisance parameters.

Efficient and flexible simulation-based sample size determination for clinical trials with multiple design parameters.

Simulation offers a simple and flexible way to estimate the power of a clinical trial when analytic formulae are not available. The computational burden of using simulation has, however, restricted its application to only the simplest of sample size determination problems, often minimising a single parameter (the overall sample size) subject to power being above a target level. We describe a general framework for solving simulation-based sample size determination problems with several design parameters over which to optimise and several conflicting criteria to be minimised.

Effectiveness of Dementia Care Mapping™ to reduce agitation in care home residents with dementia: an open-cohort cluster randomised controlled trial.

Objectives: Agitation is common and problematic in care home residents with dementia. This study investigated the (cost)effectiveness of Dementia Care Mapping™ (DCM) for reducing agitation in this population.

Method: Pragmatic, cluster randomised controlled trial with cost-effectiveness analysis in 50 care homes, follow-up at 6 and 16 months and stratified randomisation to intervention ( = 31) and control ( = 19).