Title: Development of a core outcome set for trials of physical rehabilitation after critical illness
Funder: Department of Health and Social Care

Abstract: Background Muscle wasting and weakness are characteristic in patients following critical illness and are significant drivers underlying physical impairment in survivors. Previous data have reported a 20% reduction in muscle bulk observed in intensive care unit (ICU) patients within the first ten days of admission and this effect is more pronounced in those with multi-organ failure. Observational follow-up of survivors of critical illness has demonstrated deficits in exercise capacity, physical function and health-related quality of life related to physical activity persisting up to five years post index ICU admission.In recent years, the profile, importance and research activity surrounding physical rehabilitation delivered to patients post critical illness has increased. Trials of interventions have been undertaken at each stage of the patient recovery pathway - within the ICU, following transfer to the ward and post hospital discharge. However there is currently no consensus on outcome selection, definition, measurement and reporting for evaluation of interventions limiting synthesis and meta-analyses of data from existing trials.Consensus on a core outcome set (COS) i.e. an agreed, standardised minimum collection of outcomes, has many potential advantages - to facilitate comparison across multiple datasets, reduce selective outcome reporting bias and promote consistency across trials, enhance evidence synthesis through maximum inclusion of studies into meta-analyses, and determine the outcomes of value for key stakeholders including those who may have previously been under-represented e.g. patients.Aims 1. To characterise selection and definition of outcomes used in existing trials of physical rehabilitation after critical illness 2. To obtain consensus on a COS for future trials of physical rehabilitation following critical illness 3. To explore feasibility of the COS in the clinical settingMain research question Which outcomes are ranked by stakeholders as essential for inclusion in a core outcome set for trials of physical rehabilitation after critical illness? Plan of investigation Phase 1 A systematic review of outcome reporting from existing trial evidence of physical rehabilitation after critical illness, including interventions delivered at any stage of the recovery pathway. Metrics of outcomes will be reported and synthesised including definition and detail of primary and secondary outcomes, measurement variables, analysis metrics, method of aggregation, time-point of measurement and classification of the outcome according to the World Health Organisation International Classification of Impairment, Disability and Health model.Phase 2 A two-stage Delphi process to establish stakeholder consensus on core outcomes considered priority for future rehabilitation trials and outcome measurement instrument selection. The findings of the systematic review from Phase 1 will form the basis of this consensus. Stakeholders will include international interdisciplinary expert clinicians, researchers, relevant patient/relatives bodies, and those from policy-making organisations and funding streams.Phase 3 Feasibility of data acquisition using the COS will be investigated in a selection of different UK ICUs who are proposed recruitment sites for a forthcoming national randomised controlled trial of a multi-modal rehabilitation programme following critical illness.Potential benefits to patients and the NHS Development of a COS for trials of physical rehabilitation after critical illness will ensure that outcomes adopted in future trials are meaningful to patients and their recovery. Improving methodological rigour of interventional trials will increase ability to translate scientific findings into clinical practice, thereby enhancing patient benefit through delivery of the most evidence-based services, and with the potential for more streamlined care pathways and cost-savings for the NHS.Randomised controlled trials of complex interventions such as these can be resource-intensive. Appropriate outcome selection will assist with trial planning, conduct and evaluation such that future research is both cost-effective and efficient to the NHS, whilst maximising positive impact and minimising participation-burden for patients.

Lay abstract: Development of a core outcome set for trials of physical rehabilitation after critical illness Aim of the research In this research we aim to develop a main, or 'core', set of outcomes to measure the effectiveness of physical rehabilitation delivered to patients after critical illness. Background Adults requiring Intensive Care Unit (ICU) admission with critical illness often develop muscle wasting and weakness. This can happen soon after admission and is worst in patients with the greatest severity of illness. The muscle wasting and weakness occurs due to the illness itself, and because patients need to be kept unconscious and still in bed whilst they receive treatment.As patients recover, this muscle weakness can cause difficulty in exercising and carrying out normal day-to-day activities. Patients may also become low in mood as a result of the illness, and the effect of their reduced strength. These effects have been noticed in patients throughout the different stages of recovery. This includes whilst patients are still in the ICU, following transfer to the ward, and for many years after discharge from hospital. Physical rehabilitation involves exercise-based activities to help patients regain their muscle strength. Different types of exercise can be used depending on the individual patient and their stage of recovery. A number of previous studies investigating physical rehabilitation have found it helpful to patients. The results of these studies (outcomes) showed that muscle strength, ability to exercise and performance of physical activity were all improved.In order to show these results, the researchers in these studies took different measurements (outcome measures) on patients. One problem with these studies is the number of different outcomes and outcome measures used, when they were measured in patients and for how long. This variability means that it is difficult to compare all the studies together to get an overall idea of how effective physical rehabilitation treatments are for patients after critical illness. If all studies agreed to measure the same outcomes, using the same outcome measures, this would make it easier to combine results. In turn this would give us stronger conclusions about the effectiveness of particular physical rehabilitation treatments. This is the meaning of a 'core outcome set' (COS). Main processes involved In order to develop a COS for physical rehabilitation after critical illness, we will need agreement (or 'consensus') on the most important outcomes and how to measure them. It is important this agreement involves everyone associated with the research. These members are called stakeholders. Stakeholders will include the researchers who carry out the studies, but also the clinicians who look after the patients taking part, and the patients and their relatives themselves. We will also include representatives from organisations that provide the funding to carry out these research studies, and those that write guidelines about delivery of physical rehabilitation after critical illness. In order to gain stakeholder consensus we will carry out surveys asking stakeholders to rate the importance of different outcomes starting from a list of possible options. With each survey we will give feedback on how outcomes were scored. At the end we will remove the outcomes considered least important, and identify the most important outcomes that all stakeholders agree should be included in a COS. Typically this will involve three surveys. Patient and public involvement Patients, and their relatives/carers, are an important stakeholder group in this consensus process. We have asked patients in previous meetings about physical rehabilitation and the different measurements that are taken as part of these treatments. We will invite our patient stakeholders to assist us in gaining wider patient involvement in this project e.g. through membership of patient bodies such as ICU Steps. In addition, we will ask for assistance from patient members in writing lay summaries of the research findings and distributing these to promote patient awareness.How will the research findings be used and distributed? We intend for the COS to be used in future research trials of physical rehabilitation after critical illness. We will therefore distribute the COS widely to researchers and others involved in carrying out these studies, including publishing the findings in scientific journals and presenting at scientific conferences. In addition to the patient-related activities mentioned above, we will also use various clinical and research service networks to widely distribute the results. Finally we will ask funding bodies to consider including the COS in applications for financial support for future trials, and guideline-developers to include the COS as part recommendations on the management of post critical illness patients and their physical recovery.

Research activity codes: 6.7 PHYSICAL;8.4 RESEARCH DESIGN AND METHODOLOGIES (HEALTH SERVICES)
Health categories: GENERIC HEALTH RELEVANCE