Registry-based randomised clinical trials: a remedy for evidence-based diabetes care?
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SUBMITTER: Eriksson JW
PROVIDER: S-EPMC9334551 | biostudies-literature | 2022 Oct
REPOSITORIES: biostudies-literature
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Registry-based randomised clinical trials: a remedy for evidence-based diabetes care?
Eriksson Jan W JW Eliasson Björn B Bennet Louise L Sundström Johan J
Diabetologia 20220729 10
This narrative review describes a new approach to navigation in a challenging landscape of clinical drug development in diabetes. Successful outcome studies in recent years have led to new indications and guidelines in type 2 diabetes, yet the number of clinical trials in diabetes is now declining. This is due to many environmental factors acting in concert, including the prioritisation of funding for other diseases, high costs of large randomised clinical trials, increase in regulatory requirem ...[more]
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Project description:ObjectivesRandomised controlled trials report group-level treatment effects. However, an individual patient confronting a treatment decision needs to know whether that person's expected treatment benefit will exceed the expected treatment harm. We describe a flexible model for individualising a treatment decision. It individualises group-level results from randomised trials using clinical prediction guides.MethodsWe constructed models that estimate the size of individualised absolute risk reduction (ARR) for the target outcome that is required to offset individualised absolute risk increase (ARI) for the treatment harm. Inputs to the model include estimates for the individualised predicted absolute treatment benefit and harm, and the relative value assigned by the patient to harm/benefit. A decision rule recommends treatment when the predicted benefit exceeds the predicted harm, value-adjusted. We also derived expressions for the maximum treatment harm, or the maximum relative value for harm/benefit, above which treatment would not be recommended.ResultsFor the simpler model, including one kind of benefit and one kind of harm, the individualised ARR required to justify treatment was expressed as required ARRtarget(i)=ARIharm(i)?×?RVharm/target(i). A complex model was also developed, applicable to treatments causing multiple kinds of benefits and/or harms. We demonstrated the applicability of the models to treatments tested in superiority trials (either placebo or active control, either fixed harm or variable harm) and non-inferiority trials.ConclusionsIndividualised treatment recommendations can be derived using a model that applies clinical prediction guides to the results of randomised trials in order to identify which individual patients are likely to derive a clinically important benefit from the treatment. The resulting individualised prediction-based recommendations require validation by comparison with strategies of treat all or treat none.
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Project description: Not available
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Project description:IntroductionSystematic reviews collate trial data to provide evidence to support clinical decision-making. For effective synthesis, there must be consistency in outcome reporting. There is no agreed set of outcomes for reporting the effect of burn care interventions. Issues with outcome reporting have been identified, although not systematically investigated. This study gathers empirical evidence on any variation in outcome reporting and assesses the need for a core outcome set for burn care research.MethodsElectronic searches of four search engines were undertaken from January 2012 to December 2016 for randomised controlled trials (RCTs), using medical subject headings and free text terms including 'burn', 'scald' 'thermal injury' and 'RCT'. Two authors independently screened papers, extracted outcomes verbatim and recorded the timing of outcome measurement. Duplicate outcomes (exact wording ± different spelling), similar outcomes (albumin in blood, serum albumin) and identical outcomes measured at different times were removed. Variation in outcome reporting was determined by assessing the number of unique outcomes reported across all included trials. Outcomes were classified into domains. Bias was reduced using five researchers and a patient working independently and together.Results147 trials were included, of which 127 (86.4%) were RCTs, 13 (8.8%) pilot studies and 7 (4.8%) RCT protocols. 1494 verbatim clinical outcomes were reported; 955 were unique. 76.8% of outcomes were measured within 6 months of injury. Commonly reported outcomes were defined differently. Numbers of unique outcomes per trial varied from one to 37 (median 9; IQR 5,13). No single outcome was reported across all studies demonstrating inconsistency of reporting. Outcomes were classified into 54 domains. Numbers of outcomes per domain ranged from 1 to 166 (median 11; IQR 3,24).ConclusionsThis review has demonstrated heterogeneity in outcome reporting in burn care research which will hinder amalgamation of study data. We recommend the development of a Core Outcome Set.Prospero registration numberCRD42017060908.
| S-EPMC6398699 | biostudies-literature
Project description:BackgroundTraditional randomised controlled trials (RCTs) are the gold standard for evaluating the effectiveness of interventions in clinical research. Traditional RCTs however are complex, expensive and have low external validity. Registry-based randomised controlled trials (RRCTs) are an emerging alternative approach that integrates the internal validity of a traditional RCT with the external validity of a clinical registry by recruiting more real-world patients and leveraging an existing registry platform for data collection. As RRCTs are a novel research design, there is limited understanding of the RRCT landscape in Australia. This qualitative study aims to explore the RRCT landscape in Australia including current capacity and capabilities, and to identify challenges and opportunities for conducting RRCTs.MethodsWe conducted 30 semi-structured interviews with 18 clinician researchers, 6 research program managers and 6 research governance officers. Interviews were audio-recorded and transcribed verbatim. We analysed the data using thematic analysis.ResultsWe identified four overarching themes: (1) understanding of the RRCT methodology concept and knowledge of Australian clinical registries and RRCT landscape; (2) enablers and barriers in the uptake and conduct of RRCTs; (3) ethics and governance requirements impacting the conduct of RRCTs and (4) recommendations for the promotion, support and implementation of RRCTs. Understanding of and ability to define an RRCT varied considerably amongst participants, as did their appreciation of the role the registry should play in supporting these trials. Lack of ongoing funding to support both registries and RRCTs, along with low awareness and minimal education around this methodology, were identified as the predominant barriers to the uptake of RRCTs in Australia. The simplicity of RRCTs, specifically their pragmatic nature and lower costs, was identified as one of their best attributes. There was consensus that inadequate funding, onerous research governance requirements and poor awareness of this methodology were currently prohibitive in enticing clinicians and researchers to conduct RRCTs. Recommendations to improve the uptake of RRCTs included establishing a sustainable funding model for both registries and RRCTs, harmonising governance requirements across jurisdictions and increasing awareness of RRCTs through education initiatives.ConclusionsRRCTs in Australia are an evolving methodology with slow but steady uptake across a number of clinical disciplines. Whilst RRCTs are increasingly identified as a beneficial alternative methodology to evaluate and improve current standards of care, several barriers to effective RRCT implementation were identified. Creating greater awareness of the benefits of RRCTs across a number of stakeholders to help secure ongoing funding and addressing both registry and RRCT governance challenges are two essential steps in enhancing the uptake of RRCTs in Australia and internationally.
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