Methodological implications for future studies

Users' involvement: Actively involving young people and their perspectives in transition's research can help in the ethical design and conduct of research. Thus, the research and intervention are more relevant, useful and beneficial to the patients. It may also help to define what is of high priority and acceptable to participants; improve the process of informed consent; improve the experience of participating in research; and improve the communication of findings to participants.45 ,46

Recruitment: Conducting studies in the field of paediatric clinical research is challenging due to the small number of patients in the area of transition studies. Participant recruitment is well known to be a limiting factor in the realisation of high-quality randomised controlled trials (RCTs).47 The inclusion of a sufficient number of patients is not always possible, particularly in the field of transition. Thus, a better adapted methodological approach is needed for intervention assessment that includes a basis on reasonable and relevant hypothesis that allow a realistic sample size to conclude. The choice of a quantitative criterion, ideally one proposed by the consensus study,48 reduces the number of participants required.

For example, 264 patients are required if the calculation is made on the assumption of a decrease in the proportion lost to follow-up (binary criterion) from 15% to 5% (with α=5%, 1−β=80%) while 72 patients are required if the calculation is made on the assumption of an increase in the transition satisfaction score (quantitative criterion) from 7/10 to 9/10 (with SD=3).

An alternative solution for investigators could be to broaden the recruitment to achieve the required number. A possible solution to insufficient recruitment—due to the low numbers of young people in transition in each medical specialty—could be to provide interventions targeting groups of young people suffering from various chronic diseases. Our review found that intervention programmes are in fact generally non-specific, which leads us to suggest that a pooling of resources and interventions could be beneficial. Similarly, about one in five studies excluded young people with intellectual disabilities: restrictive inclusion criteria tending to retain the ‘good performers’ should be avoided to ensure the external validity of the study.49 Last but not least, the possibility to carry out multicentre RCTs should be considered.

Control groups: Only a quarter of the studies reviewed were RCTs. The use of historical comparison groups was the most common method. It may introduce bias, and the results must be interpreted with caution.50 There is no guarantee that the historical group is comparable to present patients: service recruitment and medical conditions may have changed over time. Moreover, care may have evolved, particularly in the transition field where healthcare teams are increasingly aware and informed.39 Among RCTs, two-thirds involved were non-active groups. In regard to recommendations published over the two last decades, the control group should benefit from the following usual care for transition: ongoing information throughout the care pathway, inclusion of the family, consideration of developmental aspects, proposal of specific education and resources, coordination with primary care, time of transfer adapted to the individual level.51

Blinding: Only two studies reported the use of blinding strategies. One reported the blinding of analysts and outcome assessors,24 and one planned the blinding of participants in the context of a phone and computer-based intervention.25 Other studies were open-label design. The nature of the interventions often makes it impossible to blind participants or personnel; however, assessors of at least some outcomes may be blinded. In the absence of a blinding strategy for patients, patient-reported outcomes will inevitably be collected with knowledge of the intervention received, but outcomes like clinical or physiological aspects may be measured by an independent outcome assessor to fulfil quality requirements27 and avoid detection bias.52

Measurement validity: Among studies using questionnaires, half of them used validated questionnaires. The remaining studies used non-validated questionnaires, whose content is generally not described. In designing new studies, we would advise research of existing validated tools for assessment, and that the use of existing, pertinent and valid tools should be preferred. Design and use of new measurement tools need to be accompanied by validation studies to ensure valid, precise and reproducible measures.53 Furthermore, to allow interstudies comparison the use of non-disease-specific questionnaires will be relevant. The Transition Readiness Assessment Questionnaire (TRAQ), best-validated transition-readiness tool,42 ,54 which measures the independence in transition-relevant skills and the 36-item Short Form Health Survey (SF-36) which was found to be useful in differentiating the global health benefits produced by a wide range of different treatments41 can be considered to assess the independence and QOL criteria. Unfortunately, there is currently no generic validated questionnaire that measures transfer to adult healthcare satisfaction.43

Standardised assessment: Transition interventions are complex with various components at different levels. Here a median number of four outcomes are used to assess the effects of interventions. Cost is used as an end point in only one study. However, as it is a complex intervention, investigators should systematically include economic measures, in addition to outcomes relevant to patients and to the health system.55 Cost assessment is crucial to gauge effectiveness and feasibility on a large scale.

Among the studies we reviewed, outcomes were multiple and varied thus, comparison between studies was not conducive. The international consensus study identified one indicator that was considered as essential and a very important indicator to assess transition success.48 There should be a shared reflection on standardised methodologies of assessment, including the best timing of data collection. In the studies reviewed, the time of data collection after transfer of patients, varies between 3 and 96 months. This illustrates that standardised assessment criteria alone will not solve the problem of comparison if methods of data collection are not the same. Attendance at an adult care clinic should be a starting point given that it has been identified as consensual,48 but the timing or frequency of data collection and the exact nature of what is being measured (at least one adult consultation, any missed consultation, number of months elapsed since the last visit in specialised care or any structure of care) remains to be determined. Among the historic recommendations on transition assessment, Blum stated that the research should follow patients for sufficient time (3–5 years) to account for the variation in natural history among their conditions. For reasons of feasibility and costs, assessments at 3 years appear to be relevant. Finally the use of administrative databases for transition assessments must be considered since it enables the access of data regularly updated, with no additional costs of collection, in addition to the capture of individuals who may not respond to surveys and the potential linkage with other data sets.56

Effects interpretation: The transition period between childhood and adulthood involves many rapid changes in physical, emotional, mental, psychological, social and cognitive terms. Emerging adults with chronic disease also have to assume increasingly full responsibility for disease management. The transitioning youth's developmental and functional abilities may influence the transition's success.2 These may complicate the evaluation of transition programme. These changes may act as a third factor linked both to intervention and outcome and can skew the cause–effect relation. This is why the use of a randomised controlled group is particularly relevant. Random allocation ensures no systematic differences between intervention groups in factors that may affect outcome. Thus, only the effect of intervention explains the differences observed.57 As complex interventions, transition programmes' effects have to be interpreted in regard to some specific factors as it has been mainly described in the guidance of the Medical Research Council (MRC).44 The observed effects should be interpreted taking into account the theoretical efficacy of the intervention itself as well as contextual factors that may affect implementation, intervention mechanisms and outcomes. In fact, transition interventions are not only complex interventions they take place in a period of developmental changes as well as structural care-related changes that are important contextual factors. Lack of effect may reflect implementation failure rather than genuine ineffectiveness; a thorough process evaluation is needed to identify implementation problems. The MRC recommends the realisation of a pilot study to examine the key uncertainties that have been identified during development that may impact on the effects obtained in the following efficacy study (including questions of acceptability, compliance, delivery of the intervention, recruitment and retention, expected effect sizes).17 When interpreting the results of the transition programme it is necessary to take into account possible implementation failure, variability in individual level that may reflect higher level processes, the choice of the primary outcome that may not make best use of the data, the strict standardisation of the intervention that may be not adapted to each local settings.

Reporting: As noted in the Template for Intervention Description and Replication (TIDieR) checklist,58 description of an intervention involves more than providing a label or an ‘ingredients list’; all the key features can influence efficacy and replicability. For complex interventions, providing details for each component of the intervention is a minimum requirement to enable other researchers to replicate the intervention or to build on research findings. For this purpose, a specific set of criteria has been developed to ensure high-quality reporting of studies for the development and evaluation of complex interventions.28 In contrast it has also been reported that in non-pharmacological interventions59 and complex interventions,38 the completeness of intervention information is often insufficient.

Indeed, if we refer to guidelines27 ,28 ,58 for complete reporting of diverse study designs, the transition studies included in our research have some gaps. All four elements—population, intervention, comparison and outcomes—show specific areas for possible improvement. For instance, in terms of population, age at transfer of the populations studied is rarely reported, although this characteristic is a key element of population description in the context of transition intervention.60 ,61 Concerning the intervention, it is important to clarify, for example, what is the educational background of the transition coordinator and what materials are used during education sessions of the intervention or if it was provided individually or in a group. ‘The usual care must also be described with a high level of detail. For example, authors should explain the content of the therapeutic education programme delivered in usual care, which varies greatly between different teams, and potentially has an impact on the preparation of youth during the transition’. Regarding the comparator, it is important to describe the context in which the transition took place when the comparison involves a historical group or another centre, and particularly the differences in terms of handover and structure. Furthermore, the modalities of transition for control groups receiving ‘usual care’ must be explicitly described. In complex interventions, the standard practice used as a control can be as complex as the intervention, and may change with time.55 Concerning outcomes, it is necessary to specify the timing of data collection, its frequency and the period between data collection and intervention or between data collection and transfer. In addition to the tools or technologies used, the mode of questionnaire administration has to be specified, knowing that variations in the results may result from the collection method.62

Finally, we need to consider that such interventional research should be replicated. Tools have been designed to identify the key domains and factors that facilitate implementation of complex health interventions,63 ,64 and these could be used in approaching the possible dissemination of the evaluated intervention on a large scale, as was done in the transition programme Ready Steady Go.65

Strengths and limitations

To the best of our knowledge, this is the first study focusing on the methodological issues used in transition interventions that examines the uptake of key recommendations in the field of transition. One of the strengths of this study is the extensive research of the literature in multiple databases and the inclusion of studies in progress. For some of the published studies, data were not available; this enabled us to observe reporting quality, but we have not contacted the authors to retrieve missing data.

We did not focus extensively on existing information which exist in guidelines and checklists developed in the field of complex interventions. It is however necessary that investigators wishing to develop or evaluate a transition action go beyond the references we cited in this review and applied appropriate existing recommendations.

We excluded qualitative assessment studies while quantitative studies are only part of the whole works of assessment transition programmes. We did not analyse the methodologies used and specific challenges of qualitative research evaluation. This remains to be done since the qualitative research can add value, for example, by providing more insightful and illuminating ways of understanding phenomena and the ways in which they can best be managed.

We selected solely those studies that had at least one part of their assessment of outcomes after transfer. This allows us to focus on studies that evaluate of the whole transition process. The whole process includes the preparation of transition which happens in paediatrics before transfer—and which is undoubtedly a very important part of the process—as well as transfer and the after transfer periods.6 To have access to the methodologies used in the most recent studies, we extended our search to an online trial registry. We used a single register. Regarding the exhaustiveness of protocols found, the International Committee of Medical Journal Editors (ICMJE) requires and recommends that all medical journal editors require registration of clinical trials in a public trials registry at or before the time of first patient enrolment as a condition of consideration for publication. One limitation is that this search is more specific to the trials than to quasiexperimental designs that could be eligible for this review. Protocols found with the register search are perhaps not representative of the whole comparative studies currently underway in the field of transition, with a possible over-representation of experimental trials.

We did not undertake an assessment of the risk of bias in RCTs, since most of these are in progress and methodological characteristics (details on randomisation or blinding procedures, intention to treat, and analysis plan) were not systematically described in the online registry. We conducted a bias evaluation without the use of a specific tool; however, we discussed the various sources of bias that we identified during the review. A specific risk of bias assessment tool is missing to evaluate the level of bias of non-randomised studies in the field of complex intervention.