Trials involving adults who lack capacity to provide consent rely on proxy or surrogate decision-makers, usually a family member, to make decisions about participation. Interventions to enhance proxy decisions about trial participation are now being developed. However, a lack of standardised outcome measures limits evaluation of these interventions. The aim of this study was to establish an agreed standardised core outcome set (COS) for use when evaluating interventions to improve proxy decisions about trial participation.
We used established methods to develop the COS including a consensus study with key stakeholder groups comprising those who will use the COS in research (researchers and healthcare professionals) and patients or their representatives. Following a scoping review to identify candidate items, we used a modified two-round Delphi survey to achieve consensus on core outcomes, with equivocal items taken to a consensus meeting for discussion. The COS was finalised following an online consensus meeting in October 2020.
A total of 28 UK stakeholders (5 researchers, 10 trialists, 3 patient/family representatives, 7 recruiters and 3 advisors/approvers) participated in the online Delphi survey to rank candidate items from the scoping review (n = 36) and additional items proposed by participants (n = 1). Items were broadly grouped into three categories: how family members make decisions, their experiences of making decisions, and the personal aspects that influence the decision. Following the Delphi survey, 27 items were included and ten items exhibited no consensus which required discussion at the consensus meeting. Sixteen participants attended the meeting, including additional patient/family representatives invited to increase representation from this key group (n = 2). We reached consensus for the inclusion of 28 outcome items, including one selected at the consensus meeting.
The study identified outcomes that should be measured as a minimum in all evaluations of interventions to enhance proxy decisions about trials. These relate to the process of decision-making, proxies’ experience of decision-making, and factors that influence decision-making such as understanding. Further work with people with impairing conditions and their families is needed to explore their views about the COS and to identify appropriate outcome measures and timing of measurement.
V. Shepherd, F. Wood, M. Robling, E. Randell & K. Hood
- COS methods research
- Consensus meeting
- Delphi process
- Literature review
- Systematic review
The core outcome set (COS) will be developed in accordance with the COMET guidance  and adapted to take account of the nature the phenomenon and novelty of the intervention being investigated. The project will be conducted in three stages:
1. Concept synthesis
The first step is to conceptualise for the first time what constitutes a ‘good’ or high-quality proxy decision about research. Concept synthesis is a mechanism for generating a new concept of theory through drawing together data from sources such as literature and qualitative and quantitative research to provide new insights into a phenomenon . A literature review will be undertaken to explore the conceptual aspects of decision quality relating to proxy decision-making for research and to identify candidate outcome domains. The literature review will explore what are considered to be the constituents of proxy decision-making (i.e the process) and decision quality (i.e the decision itself) and identify domains which capture these aspects. The concepts will inform the search strategy for the scoping review and provide context within which the outcomes can then be identified and considered for inclusion in the COS.
2. Scoping review
Secondly, as no previous interventions have been developed or evaluated for proxy decisions about research, a scoping review  will be conducted to identify candidate outcomes and outcome measures used in trials of other relevant decision support interventions. A search strategy will be developed to identify studies reporting outcomes and outcome measures used for evaluating interventions to improve consent in trials, and studies evaluating decision support interventions to improve proxy decision-making for care/medical treatment. Database searches will include MEDLINE, Cochrane Central, and PsycINFO. Outcomes will be identified and collated for consensus in the third part of the project. Identified outcome measures will be assessed for quality and mapped against the outcome domains identified. Any areas of absence (i.e where there were no outcome measures found for domains identified as relevant in the scoping review or literature review) will be highlighted.
3. Stakeholder consultation
Thirdly, consensus on the most relevant and important outcomes will then be sought with relevant stakeholder groups through a Delphi survey and consensus event. A group of approx. 20 stakeholders (e.g. research nurses, researchers, patients and families/carers, and ethicists with an interest in informed consent/trials) will be invited to participate. In Round 1 the outcome list will be developed into an online questionnaire with items to be rated using a Likert scale, including a free text box for participants to provide include any additional outcomes that have not been included in the list. All outcomes (including any new outcomes identified in Round 1) will be carried forward to the next round. In Round 2, participants will be asked to rescore all outcomes and consider whether they should be included in a core outcome set, with a text box provided for an explanatory comment. In both rounds descriptive statistics will be used to summarise the number of participants who scored each item and the distribution of scores, alongside the number of respondents who scored the items across both rounds, with consensus defined a priori.
The final phase of the consultation will be a face-to-face meeting with key stakeholder participants from the Delphi survey to reach consensus on the items to be included in the core COS. Data from the Delphi survey will be presented for discussion, and agreement reached on the final list of outcomes that will constitute the COS. Following the consensus meeting the final stage of the study is to determine which instruments should be used to measure the identified outcomes. The list of candidate measures identified during the scoping review will be reviewed against the outcome domains identified for inclusion during the Delphi consensus process. Any outcomes for which no appropriate instruments have been identified will be the target for future outcome measure development.
 Williamson PR, Altman DG, Bagley H, Barnes KL, Blazeby JM, Brookes ST, et al. The COMET Handbook: version 1.0. Trials. 2017;18:280
 Walker, LO, Avant, KC. Strategies for Theory Construction in Nursing. 6th Edition. Harlow: Pearson Education Ltd; 2019
 Peters MDJ, Godfrey CM, Khalil H, McInerney P, Parker D, Soares CB. Guidance for conducting systematic scoping reviews. International Journal of Evidence-Based Healthcare. 2015;13:141