Background Well designed and properly executed randomised trials are considered the most reliable evidence on the benefits of healthcare interventions. However, there is overwhelming evidence that the quality of reporting is not optimal. The CONSORT (Consolidated Standards of Reporting Trials) statement was designed to improve the quality of reporting and provides a minimum set of items to be included in a report of a randomised trial. CONSORT was first published in 1996, then updated in 2001 and 2010. Here, we present the updated CONSORT 2025 statement, which aims to account for recent methodological advancements and feedback from end users. Methods We conducted a scoping review of the literature and developed a project-specific database of empirical and theoretical evidence related to CONSORT, to generate a list of potential changes to the checklist. The list was enriched with recommendations provided by the lead authors of existing CONSORT extensions (Harms, Outcomes, Non-pharmacological Treatment), other related reporting guidelines (TIDieR) and recommendations from other sources (eg, personal communications). The list of potential changes to the checklist was assessed in a large, international, online, three-round Delphi survey involving 317 participants and discussed at a two-day online expert consensus meeting of 30 invited international experts. Results We have made substantive changes to the CONSORT checklist. We added seven new checklist items, revised three items, deleted one item, and integrated several items from key CONSORT extensions. We also restructured the CONSORT checklist, with a new section on open science. The CONSORT 2025 statement consists of a 30-item checklist of essential items that should be included when reporting the results of a randomised trial and a diagram for documenting the flow of participants through the trial. To facilitate implementation of CONSORT 2025, we have also developed an expanded version of the CONSORT 2025 checklist, with bullet points eliciting critical elements of each item. Conclusion Authors, editors, reviewers, and other potential users should use CONSORT 2025 when writing and evaluating manuscripts of randomised trials to ensure that trial reports are clear and transparent.

Biopsy-confirmed liver fibrosis is a prognostic factor for patients with nonalcoholic fatty liver disease (NAFLD). We performed a systematic review to quantify the prognostic value of fibrosis stage in patients with NAFLD and the subgroup of patients with nonalcoholic steatohepatitis (NASH) and to assess the evidence that change in fibrosis stage is a surrogate endpoint. We searched the MEDLINE, Embase, Cochrane Library, and trial registry databases through August 2018 for prospective or retrospective cohort studies of liver-related clinical events and outcomes in adults with NAFLD or NASH. We collected data on mortality (all cause and liver related) and morbidity (cirrhosis, liver cancer, and all liver-related events) by stage of fibrosis, determined by biopsy, for patients with NAFLD or NASH. Using fibrosis stage 0 as a reference population, we calculated fibrosis stage-specific relative risk (RR) and 95% confidence interval (CI) values for mortality and morbidities. We performed fixed-effect and random-effect model meta-analyses. Metaregression was used to examine associations among study design (prospective vs retrospective cohort), overall risk of bias (medium or high), and mean duration of follow-up (in years). Our meta-analysis included 13 studies, comprising 4428 patients with NAFLD; 2875 of these were reported to have NASH. Compared with no fibrosis (stage 0), unadjusted risk increased with increasing stage of fibrosis (stage 0 vs 4): all-cause mortality RR, 3.42 (95% CI, 2.63-4.46); liver-related mortality RR, 11.13 (95% CI, 4.15-29.84); liver transplant RR, 5.42 (95% CI, 1.05-27.89); and liver-related events RR, 12.78 (95% CI, 6.85-23.85). The magnitude of RR did not differ significantly after adjustment for confounders, including age or sex in the subgroup of NAFLD patients with NASH. Three studies examined the effects of increasing fibrosis on quality of life had inconsistent findings. In a systematic review and meta-analysis, we found biopsy-confirmed fibrosis to be associated with risk of mortality and liver-related morbidity in patients with NAFLD, with and without adjustment for confounding factors and in patients with reported NASH. Further studies are needed to assess the association between fibrosis stage and patient quality of life and establish that change in liver fibrosis stage is a valid endpoint for use in clinical trials.

Coronary heart disease (CHD) is the single most common cause of death globally. However, with falling CHD mortality rates, an increasing number of people live with CHD and may need support to manage their symptoms and prognosis. Exercise-based cardiac rehabilitation (CR) aims to improve the health and outcomes of people with CHD. This is an update of a Cochrane systematic review previously published in 2011. To assess the effectiveness and cost-effectiveness of exercise-based CR (exercise training alone or in combination with psychosocial or educational interventions) compared with usual care on mortality, morbidity and HRQL in patients with CHD. To explore the potential study level predictors of the effectiveness of exercise-based CR in patients with CHD. We updated searches from the previous Cochrane review, by searching Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, Issue 6, 2014) from December 2009 to July 2014. We also searched MEDLINE (Ovid), EMBASE (Ovid), CINAHL (EBSCO) and Science Citation Index Expanded (December 2009 to July 2014). We included randomised controlled trials (RCTs) of exercise-based interventions with at least six months’ follow-up, compared with a no exercise control. The study population comprised men and women of all ages who have had a myocardial infarction (MI), coronary artery bypass graft (CABG) or percutaneous coronary intervention (PCI), or who have angina pectoris, or coronary artery disease. We included RCTs that reported at least one of the following outcomes: mortality, MI, revascularisations, hospitalisations, health-related quality of life (HRQL), or costs. Two review authors independently screened all identified references for inclusion based on the above inclusion and exclusion criteria. One author extracted data from the included trials and assessed their risk of bias; a second review author checked data. We stratified meta-analysis by the duration of follow up of trials, i.e. short-term: 6 to 12 months, medium-term: 13 to 36 months, and long-term: > 3 years. This review included 63 trials which randomised 14,486 people with CHD. This latest update identified 16 new trials (3872 participants). The population included predominantly post-MI and post-revascularisation patients and the mean age of patients within the trials ranged from 47.5 to 71.0 years. Women accounted for fewer than 15% of the patients recruited. Overall trial reporting was poor, although there was evidence of an improvement in quality of reporting in more recent trials. As we found no significant difference in the impact of exercise-based CR on clinical outcomes across follow-up, we focused on reporting findings pooled across all trials at their longest follow-up (median 12 months). Exercise-based CR reduced cardiovascular mortality compared with no exercise control (27 trials; risk ratio (RR) 0.74, 95% CI 0.64 to 0.86). There was no reduction in total mortality with CR (47 trials, RR 0.96, 95% CI 0.88 to 1.04). The overall risk of hospital admissions was reduced with CR (15 trials; RR 0.82, 95% CI 0.70 to 0.96) but there was no significant impact on the risk of MI (36 trials; RR 0.90, 95% CI 0.79 to 1.04), CABG (29 trials; RR 0.96, 95% CI 0.80 to 1.16) or PCI (18 trials; RR 0.85, 95% CI 0.70 to 1.04). There was little evidence of statistical heterogeneity across trials for all event outcomes, and there was evidence of small study bias for MI and hospitalisation, but no other outcome. Predictors of clinical outcomes were examined across the longest follow-up of studies using univariate meta-regression. Results show that benefits in outcomes were independent of participants' CHD case mix (proportion of patients with MI), type of CR (exercise only vs comprehensive rehabilitation) dose of exercise, length of follow-up, trial publication date, setting (centre vs home-based), study location (continent), sample size or risk of bias. Given the heterogeneity in outcome measures and reporting methods, meta-analysis was not undertaken for HRQL. In five out of 20 trials reporting HRQL using validated measures, there was evidence of significant improvement in most or all of the sub-scales with exercise-based CR compared to control at follow-up. Four trial-based economic evaluation studies indicated exercise-based CR to be a potentially cost-effective use of resources in terms of gain in quality-adjusted life years. The quality of the evidence for outcomes reported in the review was rated using the GRADE method. The quality of the evidence varied widely by outcome and ranged from low to moderate. This updated Cochrane review supports the conclusions of the previous version of this review that, compared with no exercise control, exercise-based CR reduces the risk of cardiovascular mortality but not total mortality. We saw a significant reduction in the risk of hospitalisation with CR but not in the risk of MI or revascularisation. We identified further evidence supporting improved HRQL with exercise-based CR. More recent trials were more likely to be well reported and include older and female patients. However, the population studied in this review still consists predominantly of lower risk individuals following MI or revascularisation. Further well conducted RCTs are needed to assess the impact of exercise-based CR in higher risk CHD groups and also those presenting with stable angina. These trials should include validated HRQL outcome measures, explicitly report clinical event outcomes including mortality and hospital admissions, and assess costs and cost-effectiveness.

Importance The protocol of a randomised trial is the foundation for study planning, conduct, reporting, and external review. However, trial protocols vary in their completeness and often do not address key elements of design and conduct. The SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) statement was first published in 2013 as guidance to improve the completeness of trial protocols. Periodic updates incorporating the latest evidence and best practices are needed to ensure that the guidance remains relevant to users. Objective To systematically update the SPIRIT recommendations for minimum items to address in the protocol of a randomised trial. Design We completed a scoping review and developed a project specific database of empirical and theoretical evidence to generate a list of potential changes to the SPIRIT 2013 checklist. The list was enriched with recommendations provided by lead authors of existing SPIRIT/CONSORT (Consolidated Standards of Reporting Trials) extensions (Harms, Outcomes, Non-pharmacological Treatment) and other reporting guidelines (TIDieR). The potential modifications were rated in a three-round Delphi survey followed by a consensus meeting. Findings Overall, 317 individuals participated in the Delphi consensus process and 30 experts attended the consensus meeting. The process led to the addition of two new protocol items, revision to five items, deletion/merger of five items, and integration of key items from other relevant reporting guidelines. Notable changes include a new open science section, additional emphasis on the assessment of harms and description of interventions and comparators, and a new item on how patients and the public will be involved in trial design, conduct, and reporting. The updated SPIRIT 2025 statement consists of an evidence based checklist of 34 minimum items to address in a trial protocol, along with a diagram illustrating the schedule of enrolment, interventions, and assessments for trial participants. To facilitate implementation, we also developed an expanded version of the SPIRIT 2025 checklist and an accompanying explanation and elaboration document. Conclusions and relevance Widespread endorsement and adherence to the updated SPIRIT 2025 statement have the potential to enhance the transparency and completeness of trial protocols for the benefit of investigators, trial participants, patients, funders, research ethics committees, journals, trial registries, policymakers, regulators, and other reviewers.