A core outcomes set for clinical trials of interventions for young adults with type 1 diabetes: an international, multi-perspective Delphi consensus study

Type 1 diabetes (T1DM) requires intensive self-monitoring of blood glucose and self-management, including administering insulin, regulating diet and exercise, to maintain optimal glycaemic control [1]. Young adults, aged 15–30 years, are one group of individuals consistently identified as being at higher risk of disengagement from diabetes self-management and adherence to diabetes medication [2]. Young adults have been identified as being at higher risk than other groups of suboptimal glycaemic control [3] and higher incidence of ketoacidosis (DKA) [4]. Young adulthood is often a time of transition during which diabetes self-management can be particularly difficult, with common lifestyle challenges including moving away from the family home for the first time, beginning employment or university, and transitioning from paediatric to adult healthcare services [5, 6].

Effective interventions to improve self-management and outcomes for young adults with T1DM are needed. Systematic reviews of interventions have suggested that there have been relatively few trials and the quality of this research is often low [5, 7]. Furthermore, evidence synthesis within systematic reviews is hampered by the use of diverse outcomes and measures across intervention studies [7].

Within clinical trials research, there is growing awareness that insufficient attention has been paid to what outcome measures are selected [8]. Frequently, trials do not include outcomes which are considered most important to young adults and professionals making decisions about healthcare, limiting the relevance and applicability of research. In addition, synthesizing evidence from trials to determine the most effective interventions is frequently hampered by heterogeneity in outcome measurement [9].

To address this problem, trialists advocate the identification of core outcome sets (COS), defined as agreed standardised collections of outcomes which should be measured and reported in all trials, for specific clinical areas [10]. Such COS are considered to be a minimum set of outcomes, which should be measured and reported in all trials. The involvement of key stakeholders, including patients, the public and healthcare professionals, in the identification of COS can ensure that outcomes are relevant to all stakeholder groups [9]. Previous COS studies with patients or the public have identified outcomes that were not previously identified by other stakeholders [11]. The COMET (Core Outcome Measures in Effectiveness Trials) Initiative (see: http://​comet-initiative.​org/​) brings together people interested in the development and application of agreed standardised sets of outcomes, which has led to a growing number of published COS studies [12‐18]. No COS has yet been produced for clinical trials of interventions for young adults with T1DM.

The aim of this study was to identify a COS for intervention trials aiming to improve clinical, behavioural or psychosocial outcomes for young adults with T1DM. A recent review of such interventions reported a wide range of different outcomes being used across trials and recommended the development of a COS for future research [7]. We have conducted and reported our COS study in accordance with recently published guidelines [8].

We conducted an international, multi-perspective Delphi consensus study, which involved three phases: (1) generation of a list of all possible relevant outcomes; (2) an electronic Delphi survey, which contained two rounds; and (3) a consensus meeting to agree a final COS. A Delphi study involves several sequential rounds of data collection and analysis in order to collate the opinions of participants into a group consensus on a particular topic. After each round, responses are analysed and redistributed to participants for further comment in successive rounds [12]. Ethical approval was granted from the University Research Ethics Committee on 29 January 2016 (ref: CA1427).

Figure 1 shows a flowchart of the study methodology and summarises outcomes at each phase. Details of Delphi survey participants (stakeholder group and gender) at rounds 1 (n = 132) and 2 (n = 81), as well as consensus meeting participants (n = 12), can be seen in Table 2. Of the 12 people who participated in the consensus meeting, eight were women and four were men. The group included three young adults with T1DM, four diabetes health professionals, four diabetes researchers and one diabetes policy maker. Participants were from Ireland (n = 8), Canada (n = 1), Australia (n = 1), Singapore (n = 1) and Denmark (n = 1).

Outcome ratings at rounds 1 and 2 are summarised in Additional file 2: Tables S1–S7. Based on the categorisation of Survey 2 data, the 87 outcomes were categorized as follows: 23 category A outcomes; 63 category B outcomes; and 0 category C outcomes (see Table 3).

Based on the discussion and re-rating of category B outcomes during the consensus meeting, five category B outcomes were re-categorised as ‘new category A outcomes’. Three of these were deemed new category A outcomes as they had reached the consensus criteria on re-rating. These were: ‘Number of missed clinic appointments’ (nine participants rated as 8+); ‘Number of events of severe hypoglycaemia’ (11 participants rated as 8+); and ‘Perceived level of control over diabetes’ (eight participants rated as 8+). Two further items were included as meeting participants argued strongly for their inclusion. These were: ‘Body mass index (BMI)’; and ‘Perceived levels of barriers to treatment’. The group agreed to allow these two additional variables to be included in the ‘new category A outcomes’ list. The re-rating data for these variables can be seen in Table 4.

The final phase of the consensus meeting, which was the decision-making discussion and voting phase, lasted for approximately 1 h. During this phase, 23 ‘original category A outcomes’ and five ‘new category A outcomes’ were discussed and voted upon. Additional file 2: Table S8 shows levels of support for each of the ‘supplementary important outcomes’, i.e. the category A outcomes that were not voted for inclusion in the COS. The final list was agreed through discussion: the names of some outcomes were changed slightly to clarify the meaning, some outcomes were collapsed together and assumed under one outcome title and other outcomes were added. Outcomes whose name was changed to clarify meaning included: ‘Measure of diabetes related burden’, which became ‘Measure of diabetes related burden and stress’; ‘Glycated haemoglobin (HbA_1c) measured by a researcher’ became ‘Objectively measured HbA_1c’; ‘Number of missed clinic appointments’ became ‘Level of clinic engagement’; and ‘Number of hospitalisations and readmissions for diabetic ketoacidosis (DKA)’ was renamed as ‘Number of instances of diabetic ketoacidosis (DKA)’. Two outcomes—‘Number of events of severe hypoglycaemia’ and ‘Severity of events of hypoglycaemia’—were discussed and participants agreed that these could be subsumed under the one outcome heading ‘Number of events of severe hypoglycaemia’. The outcome ‘Quality of life’ was discussed and participants agreed that ‘Diabetes-related quality of life’ was more suitable as a core outcome, so this outcome was included as an additional outcome and voted upon.

When the final COS was presented and reviewed, there was a strongly expressed view that the COS was lacking some aspect of self-management behaviour. Participants agreed to add this outcome (‘Self-management behaviour’) and it was voted to be included in the final COS.

Table 5 shows levels of support for each outcome in the final COS, containing eight outcomes: measures of diabetes-related burden or stress; diabetes-related quality of life; number of severe hypoglycaemic events; self-management behaviour; number of instances of diabetic ketoacdidosis (DKA); objectively-measured glycated haemoglobin (HbA_1C); level of clinic engagement; and perceived level of control over diabetes.

This is the first attempt to produce a COS for intervention trials aiming to improve clinical, behavioural or psychosocial outcomes for young adults (aged 15–30 years) with T1DM. We sought the views of an international sample of young adults with T1DM, diabetes health professionals, diabetes researchers and people who inform policy on diabetes in a Delphi consensus process and agreed a final COS containing eight outcomes: measures of diabetes-related burden or stress; diabetes-related quality of life; number of severe hypoglycaemic events; self-management behaviour; number of instances of diabetic ketoacdidosis (DKA); objectively-measured glycated haemoglobin (HbA_1C); level of clinic engagement and perceived level of control over diabetes. We suggest that future research evaluating interventions in T1DM should assess and report these outcomes. As with all COS, these outcomes are proposed to be included as a minimum, but additional outcomes may be included as appropriate to different interventions and settings.

Our COS covers a broad range of aspects of diabetes, including stress, quality of life, medical or biological markers, self-management behaviour, level of engagement with health services and diabetes management. The fact that stress and quality of life were ranked during the consensus process as more important than measures of metabolic control (such as glycated haemoglobin), supports previous research which has emphasised the need to broaden the types of measures which are traditionally used [19, 20]. Selecting outcomes based on the consensus methods we have used provides a more evidence-based approach to outcome selection than methods generally used, such as simply measuring what has been measured in previous research [21]. Future research is now needed to identify the most appropriate outcome measures for each of these outcomes. Recent guidance has been published offering guidance on this process [22].

These strengths notwithstanding, the present study is not without its limitations. Although Delphi processes have been recommended as an ideal approach to identify which outcomes to measure in clinical trials [21], they have also been criticised regarding the ambiguities which exist around the issue of defining consensus and expertise [23]. While the study aimed to have a reasonably balanced number of participants from all stakeholder groups, this did not prove possible. Policy makers and young adults with T1DM were difficult to recruit and were under-represented in the study. Furthermore, it is possible that the young adult participants were not representative of all young adults, as they are likely to be more active in acquiring information about T1DM and therefore more engaged. Although we attempted to achieve an international sample in our study, the sample came largely from English-speaking countries, predominantly Ireland. We must use caution in claiming the international generalisability of these findings, especially as non-English-speaking and developing countries are under-represented; future research would be useful to test the international relevance of the outcomes identified as core within our study. Another limitation of the study is that by utilising mailing lists and social media to recruit participants it was impossible to calculate the recruitment rate for the study. The reasonably high level of attrition between rounds 1 and 2 of the study also limits the validity of the study. The final consensus meeting was only open to a small number of participants, again limiting generalisability of the findings. In addition, social and peer pressures may have influenced voting behaviour of consensus group participants, as voting was public involving raising hands to indicate support for outcomes.

In conclusion, albeit with limitations, this study was an important attempt to identify a COS for intervention research for young adults with T1DM. It provides guidance about what outcomes are important to young adults with T1DM and other key stakeholders. We sought the views of a sample of young adults with T1DM, diabetes health professionals, diabetes researchers and policy makers in diabetes services. This COS will be useful for future intervention trials in this area, encouraging a more coordinated approach to intervention research in the future than currently exists and facilitating more meaningful synthesis of research findings. It is worth noting that any COS identified is a dynamic, rather than fixed, entity, which will evolve as research is conducted. Future research is needed to replicate the findings from this COS study, in particular testing its international generalisability, and to determine and provide guidance on the best outcome measures to select to measure these variables.