Clinical research studies aim to improve the effectiveness of interventions, and Core Outcome Sets (COS) provide a standardized approach for evaluating the outcomes of clinical trials. Despite the potential benefits of COS, uptake among clinical researchers is still low due to several factors, including a lack of awareness of COS, patient burden, and outcome measurement variations. Implementation science is needed to better understand the barriers and facilitators of COS use and develop solutions to improve uptake. To increase awareness, an integrated knowledge translation approach, extending dissemination activities beyond academic publications, and engaging key knowledge users in the COS development process can help. Additionally, industry-sponsored trials have a higher likelihood of implementing COS than those not funded by industry, making it necessary to understand why industry-funded trials have higher uptake. Finally, COSMIN (COnsensus-based Standards for the selection of health status Measurement INstruments) can help improve core outcome set development, but more work is needed to better integrate research and clinical outcomes.
The Importance of Core Outcome Sets in Clinical Trials
Randomized controlled trials (RCTs) are crucial in developing evidence on the efficacy and effectiveness of interventions. However, a single trial can only provide a snapshot of evidence. Clinical practice or policy is usually informed by a portfolio of evidence gathered over multiple trials that can provide a summative account of how effective an intervention proves to be under various conditions and in different contexts.
One challenge in developing such summative evidence is the variation in selected outcomes used to demonstrate the effectiveness of interventions. This variation makes it challenging to compare interventions across trials, thus precluding evidence-informed decisions. Moreover, even when the same outcomes are selected, the ways in which they are measured may differ, complicating comparisons across trials.
To address this challenge, there has been an increase in the development of core outcome sets (COS) that are agreed upon minimum sets of outcomes that should be measured and reported in all trials of a specific condition. By consistently collecting and reporting outcomes, the development of cumulative knowledge regarding the effectiveness of interventions in a given area is supported, which can lead to improved care.
The collection and reporting of outcomes also addresses selective non-reporting of outcomes that may not achieve statistical significance in a trial, thereby helping to address reporting bias in the literature. Developing a COS should involve the full range of knowledge users implicated by trials in the area of interest to ensure saliency and promote uptake.
While approaches to developing COS vary, they commonly include empirical work to examine the range and types of outcomes assessed in the area of interest and a consensus process through which the most important outcomes are identified. As of March 2023, the COMET initiative database includes information on core outcome sets for 481 diseases.
The Uptake of Core Outcome Sets in Clinical Research
The uptake of core outcome sets (COS) within clinical trials varies despite the goals of COS developers. A systematic review by Hughes et al. examining studies evaluating the uptake of outcomes recommended by a range of COS found that uptake varied substantially. Among the 337 COS included, studies covered only 17 (5%). Within these studies, the reported uptake rates of full COS ranged from 0% of RCTs in gout to 82% of RCTs in rheumatoid arthritis. In a separate study of trials published in five major medical journals, none of the 95 identified trials reported a full COS, and only two trials (2%) reported on some outcomes included in a COS.
Even when identified core outcomes are included in trials, the way in which they are measured varies. For example, in a study of vitiligo trials, the core outcome of repigmentation was reported in 95% of trials from 2016 to 2021 following publication of the COS. However, repigmentation was measured using 49 different outcome measures in 174 eligible trials.
Potential Barriers to the Uptake of COS
A number of potential drivers of low uptake of COS have been proposed. A lack of awareness of the existence of a COS and a perception of increased patient burden in using a COS have been noted as barriers to uptake. Additionally, the COS development process may not have involved the relevant knowledge users, and there may be outcome preferences and a lack of standardization regarding the measurement of outcomes. Other identified reasons for a lack of use include logistical or practical challenges (such as cost) or discrepancies with relevant regulatory and professional bodies.
There may also be a disconnect between those who potentially benefit from the use of COS in trials and those who bear the burden of implementing them. The availability of multiple COS for a trial potentially increases researcher and participant perceived burden if all items should be measured. A survey of clinical trialists undertaken by Bellucci et al. found that only 10 participants (16%) thought that COS can enhance the patients’ and public’s voices in research while just over one third (37%) thought it could improve the quality of the public’s voice in research.
Conclusion
While core outcome sets have the potential to enhance the quality and consistency of outcomes reported in clinical trials, the uptake of COS varies substantially. Identified potential barriers to uptake include a lack of awareness, increased patient burden, discrepancies in outcome measurement, logistical and practical challenges, and a disconnect between those who benefit from the use of COS and those who implement them. Addressing these barriers may improve the uptake and consistency of COS in clinical research.
Addressing Tensions and Increasing Uptake of Core Outcome Sets
The increasing recognition and advocacy for patient engagement in clinical trials have led to potential tensions with the use of core outcome sets (COS). Engaged patients may disagree with a COS outcome or express concerns over patient burden for data collection of the full COS, which may negate the benefits of COS. Similarly, an increasing number of trials seek to use routinely collected data to increase the efficiency of randomized controlled trials (RCTs) and minimize patient burden for outcome ascertainment. However, if the outcomes included within a COS are not routinely collected, this may require additional outcomes to be collected from patients.
Increasing Uptake of COS
A noted factor associated with the uptake of COS has been awareness of the COS among trialists. Taking an integrated knowledge translation approach, in which key knowledge users are engaged in the development of the COS and kept aware of progress, may improve awareness. Extending dissemination activities beyond academic publication may also increase awareness. A positive perception of the COS and belief that it was developed in an appropriate manner have been identified as potential facilitators of COS uptake.
Williamson et al. suggest potential roles for patient organizations, research funders, regulators, and journal editors in creating awareness and supporting the use of a COS. However, there is a need to develop implementation research regarding COS instead of the ongoing proliferation of new COS. Such an implementation science agenda should include better understanding of who the target end-users are and their needs, extending research to better understand the barriers and facilitators to use and how these may be affected by contextual factors, and developing solutions that address the identified barriers and leverage noted facilitators.
Understanding Industry-Funded Trials
Industry-sponsored RCTs have a higher likelihood of implementing a COS than RCTs not funded by industry. Understanding why industry-funded trials have higher uptake is key to extending the reach of COS.
Conclusion
The increasing recognition of patient engagement and advocacy for routine data collection have led to potential tensions with the use of COS. Increasing awareness of COS among trialists and developing implementation research can help address the challenges associated with COS uptake. Understanding the factors associated with the higher uptake of COS in industry-funded trials can extend the reach of COS beyond industry-sponsored RCTs.
Challenges and Solutions for the Uptake of Core Outcome Sets in Clinical Trials
Clinical trials are crucial in the development of new medical interventions, but the current inconsistency in outcome measurement impedes the accumulation of high-quality evidence. Core Outcome Sets (COS) are a potential solution, but despite the efforts of COS developers, their uptake by clinical researchers remains limited. A recent systematic review found that among 337 COS included in the study, only 17 (5%) were covered by the trials, and the reported uptake rates of full COS ranged from 0% to 82% depending on the condition. Moreover, even when identified core outcomes are included, the way in which they are measured varies, making comparisons across trials difficult.
Barriers to the uptake of COS by trialists include a lack of awareness of the existence of a COS, a perception of increased patient burden in using a COS, and their own outcome preferences. Moreover, logistical or practical challenges, discrepancies with relevant regulatory and professional bodies, and a disconnect between those who potentially benefit from the use of COS and those who bear the burden of implementing them pose further challenges.
To increase the uptake of COS, the authors of the review suggest an integrated knowledge translation approach in which key knowledge users are engaged in the development of the COS and kept aware of progress. Extending dissemination activities beyond academic publication and raising awareness of a COS can improve its uptake, potentially augmenting through a belief that the COS was developed in an appropriate manner. Patient organizations, research funders, regulators, and journal editors can all play roles in creating awareness and supporting the use of COS.
While these potential solutions indicate a way forward, implementation science research is also necessary to better understand the barriers and facilitators to the use of COS. An implementation science agenda could better understand the needs of end-users, the contextual factors affecting COS uptake, and develop interventions and solutions to address the identified barriers and leverage the noted facilitators.
Patient Engagement and Use of Routinely Collected Data
Other potential tensions exist in the use of COS. For instance, patient engagement is increasingly recognized and advocated for with respect to clinical trials. Engaged patients may disagree with a COS outcome or express concern over patient burden for data collection of the full COS, raising the question of which should take precedence: the patients’ preferences or the COS?
Another challenge may be the use of routinely collected data to increase the efficiency of Randomized Controlled Trials (RCTs) and minimize patient burden for outcome ascertainment. If the outcomes included within a COS are not routinely collected, then the benefits of using routinely collected data may be negated if additional outcomes must be collected from patients. The development of the COSMIN checklist may help, but there remains a need to better integrate research and clinical outcomes.
Conclusion
The use of COS offers potential benefits for improving the cumulative evidence base regarding the effectiveness of interventions. However, challenges to the uptake of COS remain, requiring an implementation science approach to better understand the barriers and facilitators to their use, and to develop interventions and solutions to improve uptake. While the challenges are considerable, there is hope that with better awareness and engagement, more widespread use of COS can be achieved, bringing us closer to high-quality evidence-based medicine.
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