Protocol for the development of a tool (INSPECT-SR) to identify problematic randomised controlled trials in systematic reviews of health interventions.

INTRODUCTION: Randomised controlled trials (RCTs) inform healthcare decisions. It is now apparent that some published RCTs contain false data and some appear to have been entirely fabricated. Systematic reviews are performed to identify and synthesise all RCTs that have been conducted on a given topic. While it is usual to assess methodological features of the RCTs in the process of undertaking a systematic review, it is not usual to consider whether the RCTs contain false data. Studies containing false data therefore go unnoticed and contribute to systematic review conclusions. The INveStigating ProblEmatic Clinical Trials in Systematic Reviews (INSPECT-SR) project will develop a tool to assess the trustworthiness of RCTs in systematic reviews of healthcare-related interventions. METHODS AND ANALYSIS: The INSPECT-SR tool will be developed using expert consensus in combination with empirical evidence, over five stages: (1) a survey of experts to assemble a comprehensive list of checks for detecting problematic RCTs, (2) an evaluation of the feasibility and impact of applying the checks to systematic reviews, (3) a Delphi survey to determine which of the checks are supported by expert consensus, culminating in, (4) a consensus meeting to select checks to be included in a draft tool and to determine its format and (5) prospective testing of the draft tool in the production of new health systematic reviews, to allow refinement based on user feedback. We anticipate that the INSPECT-SR tool will help researchers to identify problematic studies and will help patients by protecting them from the influence of false data on their healthcare. ETHICS AND DISSEMINATION: The University of Manchester ethics decision tool was used, and this returned the result that ethical approval was not required for this project (30 September 2022), which incorporates secondary research and surveys of professionals about subjects relating to their expertise. Informed consent will be obtained from all survey participants. All results will be published as open-access articles. The final tool will be made freely available.

Protocol for the development of Core Outcome Sets for Early intervention trials to Prevent Obesity in CHildren (COS-EPOCH).

INTRODUCTION: Childhood overweight and obesity is prevalent in the first 5 years of life, and can result in significant health and economic consequences over the lifetime. The outcomes currently measured and reported in randomised controlled trials of early childhood obesity prevention interventions to reduce this burden of obesity are heterogeneous, and measured in a variety of ways. This variability limits the comparability of findings between studies, and contributes to research waste. This protocol presents the methodology for the development of two core outcome sets (COS) for obesity prevention interventions in children aged from 1 to 5 years from a singular development process: (1) a COS for interventions targeting physical activity and sedentary behaviour and (2) a COS for interventions targeting child feeding and dietary intake. Core outcomes related to physical activity and sedentary behaviour in children aged ≤1 year will also be identified to complement an existing COS for early feeding interventions, and provide a broader set of core outcomes in this age range. This will result in a suite of COS useful for measuring and reporting outcomes in early childhood obesity prevention studies, including multicomponent interventions. METHODS AND ANALYSIS: Development of the COS will follow international best practice guidelines. A scoping review of trial registries will identify commonly reported outcomes and associated measurement instruments. Key stakeholders involved in obesity prevention, including policy-makers/funders, parents, researchers, health practitioners and community and organisational stakeholders will participate in an e-Delphi study and consensus meeting regarding inclusion of outcomes in the COS. Finally, recommended outcome measure instruments will be identified through literature review and group consensus. ETHICS AND DISSEMINATION: Deakin University Human Research Ethics Committee (HEAG-H 231_2020). The COS will be disseminated through peer-reviewed publications and engagement with key stakeholders.

Data sharing-trialists' plans at registration, attitudes, barriers and facilitators: A cohort study and cross-sectional survey.

Data unavailability impedes research transparency and is a major problem for individual participant data (IPD) meta-analyses as it reduces statistical power, increases risk of bias, and may even preclude completion. The primary objectives of this study were to determine IPD sharing plans reported in recently registered clinical trial registration records, how data sharing commitment relates to clinical trial characteristics, and principal investigators' attitudes, motivations and barriers to data sharing. The secondary objective was to derive recommendations to overcome identified barriers to data sharing. This was a retrospective cohort study of all interventional trials registered on the Australian New Zealand Clinical Trials Registry (ANZCTR) from 1 December 2018 to 30 November 2019, and an online cross-sectional survey of their principal investigators. In the cohort study of all clinical trials registered on the ANZCTR in the study period (n = 1517), commitment to share data was low (22%, 329/1517). In the cross-sectional survey (n = 281, 23% response rate), principal investigators showed strong support for the concept of data sharing (77%, 216/281) but a substantially lower intention to actually share data from their clinical trials (40%, 111/281). Major barriers to data sharing included lacking informed consent to share data, protecting participant confidentiality and preventing misinterpretation of data or misleading secondary analyses. There is a gap between high in-principle support for data sharing, and low in-practice intention from investigators to share data from their own clinical trials. Multiple pathways exist to bridge this gap by addressing the identified barriers to data sharing.

The AEDUCATE Collaboration. Comprehensive antenatal education birth preparation programmes to reduce the rates of caesarean section in nulliparous women. Protocol for an individual participant data prospective meta-analysis.

INTRODUCTION: Rates of medical interventions in normal labour and birth are increasing. This prospective meta-analysis (PMA) proposes to assess whether the addition of a comprehensive multicomponent birth preparation programme reduces caesarean section (CS) in nulliparous women compared with standard hospital care. Additionally, do participant characteristics, intervention components or hospital characteristics modify the effectiveness of the programme? METHODS AND ANALYSIS: Population: women with singleton vertex pregnancies, no planned caesarean section (CS) or epidural.Intervention: in addition to hospital-based standard care, a comprehensive antenatal education programme that includes multiple components for birth preparation, addressing the three objectives: preparing women and their birth partner/support person for childbirth through education on physiological/hormonal birth (knowledge and understanding); building women's confidence through psychological preparation (positive mindset) and support their ability to birth without pain relief using evidence-based tools (tools and techniques). The intervention could occur in a hospital-based or community setting.Comparator: standard care alone in hospital-based maternity units. OUTCOMES: Primary: CS.Secondary: epidural analgesia, mode of birth, perineal trauma, postpartum haemorrhage, newborn resuscitation, psychosocial well-being.Subgroup analysis: parity, model of care, maternal risk status, maternal education, maternal socio-economic status, intervention components. STUDY DESIGN: An individual participant data (IPD) prospective meta-analysis (PMA) of randomised controlled trials, including cluster design. Each trial is conducted independently but share core protocol elements to contribute data to the PMA. Participating trials are deemed eligible for the PMA if their results are not yet known outside their Data Monitoring Committees. ETHICS AND DISSEMINATION: Participants in the individual trials will consent to participation, with respective trials receiving ethical approval by their local Human Research Ethics Committees. Individual datasets remain the property of trialists, and can be published prior to the publication of final PMA results. The overall data for meta-analysis will be held, analysed and published by the collaborative group, led by the Cochrane PMA group. TRIAL REGISTRATION NUMBER: CRD42020103857.

Prospective registration trends, reasons for retrospective registration and mechanisms to increase prospective registration compliance: descriptive analysis and survey.

OBJECTIVES: To analyse prospective versus retrospective trial registration trends on the Australian New Zealand Clinical Trials Registry (ANZCTR) and to evaluate the reasons for non-compliance with prospective registration. DESIGN: Part 1: Descriptive analysis of trial registration trends from 2006 to 2015. Part 2: Online registrant survey. PARTICIPANTS: Part 1: All interventional trials registered on ANZCTR from 2006 to 2015. Part 2: Random sample of those who had retrospectively registered a trial on ANZCTR between 2010 and 2015. MAIN OUTCOME MEASURES: Part 1: Proportion of prospective versus retrospective clinical trial registrations (ie, registration before versus after enrolment of the first participant) on the ANZCTR overall and by various key metrics, such as sponsor, funder, recruitment country and sample size. Part 2: Reasons for non-compliance with prospective registration and perceived usefulness of various proposed mechanisms to improve prospective registration compliance. RESULTS: Part 1: Analysis of the complete dataset of 9450 trials revealed that compliance with prospective registration increased from 48% (216 out of 446 trials) in 2006 to 63% (723/1148) in 2012 and has since plateaued at around 64%. Patterns of compliance were relatively consistent across sponsor and funder types (industry vs non-industry), type of intervention (drug vs non-drug) and size of trial (n<100, 100-500, >500). However, primary sponsors from Australia/New Zealand were almost twice as likely to register prospectively (62%; 4613/7452) compared with sponsors from other countries with a WHO Network Registry (35%; 377/1084) or sponsors from countries without a WHO Registry (29%; 230/781). Part 2: The majority (56%; 84/149) of survey respondents cited lack of awareness as a reason for not registering their study prospectively. Seventy-four per cent (111/149) stated that linking registration to ethics approval would facilitate prospective registration. CONCLUSIONS: Despite some progress, compliance with prospective registration remains suboptimal. Linking registration to ethics approval was the favoured strategy among those sampled for improving compliance.