What proportion of people have a follow-up biopsy in randomized trials of treatments for non-alcoholic steatohepatitis?: A systematic review and meta-analysis.

BACKGROUND AND AIM: Trials of treatments for non-alcoholic steatohepatitis require endpoint assessment with liver biopsies. Previous large-scale trials have calculated their sample size expecting high retention but on average did not achieve this. We aimed to quantify the proportion of participants with a valid follow-up biopsy. METHODS: We conducted a systematic review of MEDLINE and Embase until May 2020 and included randomized clinical trials of any intervention in non-alcoholic steatohepatitis with at least 1-year follow-up. We were guided by Cochrane methods to run a meta-analysis with generalized linear mixed models with random effects. RESULTS: Forty-one trials (n = 6,695) were included. The proportion of participants with a valid follow-up biopsy was 82% (95%CI: 78%-86%, I2 = 92%). There was no evidence of a difference by location, trial length, or by allocated treatment group. Reasons for missing follow-up biopsies were, in ranked order, related to participants (95 per 1,000 participants (95%CI: 69-129, I2 = 92%), medical factors, protocol, trial conduct, and other/unclear. Biopsy-related serious adverse events occurred in 16 per 1,000 participants (95% CI: 8-33, I2 = 54%). No biopsy-related deaths were reported. CONCLUSIONS: The proportion of participants with a valid follow-up biopsy in therapeutic trials in non-alcoholic steatohepatitis is on average 82%, with around 1 in 10 participants declining a follow-up biopsy. These findings can inform adequately-powered trials.

Diet, physical activity, and health-related outcomes of endometrial cancer survivors in a behavioral lifestyle program: the Diet and Exercise in Uterine Cancer Survivors (DEUS) parallel randomized controlled pilot trial.

OBJECTIVES: To explore the effectiveness of a theory-based behavioral lifestyle intervention on health behaviors and quality of life in endometrial cancer survivors.' METHODS: This was a secondary analysis of a randomized controlled pilot trial conducted in two UK hospitals enrolling disease-free stage I-IVA endometrial cancer survivors. Participants were allocated to an 8-week group-based healthy eating and physical activity intervention or usual care using 1:1 minimization. Participants were followed up at 8 and 24 weeks, with the 8-week assessment being blinded. Diet, physical activity, and quality of life were measured with the Alternative Healthy Eating Index 2010, Stanford 7-Day Physical Activity Recall, and the EORTC Quality of life Questionnaire Core 30, respectively. We analyzed all eligible participants using the intention-to-treat approach in complete cases, adjusting for baseline values, body mass index, and age. RESULTS: We enrolled 60 of the 296 potentially eligible endometrial cancer survivors (May - December 2015). Fifty-four eligible participants were randomized to the intervention (n=29) or usual care (n=31), and 49 had complete follow-up data (n=24 in the intervention and n= 25 in usual care). Intervention adherence was 77%. At 8 weeks, participants in the intervention improved their diet compared to usual care (difference in Alternative Healthy Eating Index 2010 score 7.5 (95% CI: 0.1 to 14.9), P=0.046) but not their physical activity (0.1 metabolic equivalent-h/day 95% CI: (-1.6 to 1.8), P=0.879), or global quality of life score (5.0 (95% CI: -3.4 to 13.3), P=0.236). Global quality of life improved in intervention participants at 24 weeks (difference 8.9 (95% CI: 0.9 to 16.8), P=0.029). No intervention-related adverse events were reported. CONCLUSIONS: The potential effectiveness of the intervention appeared promising. A future fully-powered study is needed to confirm these findings. TRIAL REGISTRATION NUMBER: NCT02433080.

Recruitment, adherence, and retention of endometrial cancer survivors in a behavioural lifestyle programme: the Diet and Exercise in Uterine Cancer Survivors (DEUS) parallel randomised pilot trial.

OBJECTIVE: Healthy eating and physical activity may help endometrial cancer survivors (ECS) improve their quality of life. However, most ECS do not meet the relevant guidelines. This pilot trial aimed to test the study feasibility procedures for a definitive trial of a behavioural lifestyle programme. DESIGN AND SETTING: This 24-week parallel two-arm randomised pilot trial took place in two hospitals in London, UK (April 2015-June 2016). PARTICIPANTS: Sixty disease-free ECS within 3 years of diagnosis. INTERVENTIONS: Participants were randomised using minimisation to receive the intervention or care as usual. The 'Shape-Up following cancer treatment' programme used self-monitoring, goal-setting, self-incentives, problem-solving and group social support for 12 hours over 8 weeks to help survivors improve their eating and physical activity. OUTCOME MEASURES: The main outcome measures were recruitment, adherence, and retention rates. Further outcomes included barriers to participation and feedback on programme satisfaction. RESULTS: Of the 296 potentially eligible ECS, 20% (n=60) were randomly allocated to the active intervention (n=29) or control group (n=31). Three participants in each arm were deemed ineligible after randomisation and excluded from analysis. Twenty participants (77%; 95% CI 61% to 93%) adhered to the intervention and provided generally favourable feedback. At 24 weeks, 25/26 (96%; 95% CI 89% to 100%) intervention and 24/28 (86%; 95% CI 73% to 99%) control participants completed their assessment. No intervention-related adverse events were reported. Among eligible survivors who declined study participation (n=83), inconvenience (78%; 95% CI 69% to 87%) was the most common barrier. CONCLUSIONS: The trial was feasible to deliver based on the a priori feasibility criteria. Enhancing recruitment and adherence in a definitive trial will require designs that promote convenience and consider ECS-reported barriers. TRIAL REGISTRATION NUMBER: NCT02433080; Pre-results. TRIAL FUNDING: University College London, St. Bartholomew's Hospital Nurses League, and NIHR University College London Hospitals Biomedical Research Centre.