Development of recommendations on standard core outcome set for clinical trials of physical rehabilitation in adults across the continuum of solid organ transplantation

Survival rates have been improving in patients that undergo solid organ transplantation (SOT). 1 Therefore, there is a need for interventions that enhance patient’s quality of life and long-term health outcomes. 2 Physical rehabilitation, which includes structured exercise programs and physical activity may benefit recipients of solid organ transplant improving their maximal aerobic capacity (VO2 peak), physical function, body composition and quality of life. 3 However, scientific evidence in this area is still limited. 3 Currently, clinical trials of physical rehabilitation in SOT have small sample sizes and use different and varied outcome measures, 3, 7 which creates difficulties comparing and combining findings, limiting the interpretation of outcomes among studies.4, 5, 6 In a recent review on outcomes in physical rehabilitation and solid organ transplant, the authors identified 126 different outcome measures that have been used. 7 Standardization of outcomes using a core outcome set (COS) across all studies investigating solid organ transplant and physical rehabilitation is key to improve research methodology and to diminish research bias. 4, 5, 8, 9 Consequently, the COS will strengthen randomized clinical trials, improve the ability to combine and compare results across studies and make it possible to draw more powerful conclusions from multiple studies. Hence, the purpose of this study is to develop consensus-based recommendations on standard COS for clinical trials of physical rehabilitation conducted for candidates waiting for organ transplant (pre-transplant) and organ transplant recipients (post-transplant). The study will use a systematic Delphi procedure followed by a face-to-face meeting to reach consensus amongst the key stakeholders (patients, researchers and clinicians). The study will include an international panel of experts. Ultimately, the results of this study will guide the development of future clinical trials increasing the potential to understand the benefits of physical rehabilitation programs in SOT candidates and recipients.

REFERENCES
1.Lodhi, S. A., Lamb, K. E., & Meier-Kriesche, H. U. (2011). Solid organ allograft survival improvement in the United States: the long-term does not mirror the dramatic short-term success. American Journal of Transplantation: Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons, 11(6), 1226–35.
2.Mathur, S., Janaudis-Ferreira, T., Wickerson, L., Singer, L. G., Patcai, J., Rozenberg, D., Sonnenday, C. (2014). Meeting report: Consensus recommendations for a research agenda in exercise in solid organ transplantation. In American Journal of Transplantation.
3.Didsbury, M., McGee, R. G., Tong, A., Craig, J. C., Chapman, J. R., Chadban, S., & Wong, G. (2013). Exercise Training in Solid Organ Transplant Recipients. Transplantation Journal, 95(5), 679–687.
4.Clarke, M. (2007). Standardizing outcomes for clinical trials and systematic reviews. Trials, 8(1), 1.
5.Blackwood, B., Marshall, J. C., & Rose, L. (2015). Progress on core outcome sets for critical care research. Current Opinion in Critical Care, 21(5), 439–444.
6.Williamson, P. R., Altman, D. G., Blazeby, J. M., Clarke, M., Devane, D., Gargon, E., & Tugwell, P. (2012). Developing core outcome sets for clinical trials: issues to consider. Trials, 13(1), 132.
7.Janaudis-ferreira, T., Mathur, S., Konidis, S., & Tansey, C. M. (n.d.). Outcomes used in randomized controlled trials of exercise interventions in solid organ transplant recipients: What does the International Classification of Functioning, Disability and Health teach us? (World Journal of Transplantation – in press, Oct 2016. )
8.Prinsen, C. A. C., Vohra, S., Rose, M. R., Boers, M., Tugwell, P., Clarke, M., … Terwee, C. B. (2016). How to select outcome measurement instruments for outcomes included in a “Core Outcome Set” – a practical guideline. Trials, 17(1), 449.
9.Prinsen, C. A. C., Vohra, S., Rose, M. R., King-Jones, S., Ishaque, S., Bhaloo, Z., … Terwee, C. B. (2014). Core Outcome Measures in Effectiveness Trials (COMET) initiative: protocol for an international Delphi study to achieve consensus on how to select outcome measurement instruments for outcomes included in a “core outcome set”. Trials, 15(1), 247.

Contributors

Principal Investigators:
Sunita Mathur 1,3 PT, PhD
Tania Janaudis-Ferreira 2,3 PhD,

Affiliations:
1 School of Rehabilitation Therapy, Queen’s University
2 School of Physical and Occupational Therapy, McGill University
3 Canadian Donation and Transplantation Research program, University of Alberta

Further Study Information

Current Stage: Ongoing
Date: November 2022 - July 2023
Funding source(s): Canadian Institutes of Health Research (CIHR) - Planning and Dissemination Grant


Health Area

Disease Category: Rehabilitation

Disease Name: Solid Organ Transplant, Transplant surgery

Target Population

Age Range: 18 - 120

Sex: Either

Nature of Intervention: Exercise

Stakeholders Involved

- Clinical experts
- Patient/ support group representatives
- Researchers

Study Type

- COS for clinical trials or clinical research

Method(s)

- Consensus meeting
- Delphi process
- Systematic review

This study will use an e-survey Delphi method followed by a face-to-face meeting of international experts to reach consensus on the most important and relevant areas or outcomes that should be included and measured in all future clinical trials in physical rehabilitation and solid organ transplant (SOT).(1) We plan to include stakeholders (researchers, healthcare providers and patients) from several countries. The questionnaire will be developed based on a systematic review of randomized controlled trials examining physical rehabilitation in SOT (2). We will use the International Classification of Functioning, Disability and Health (ICF) framework to select and to classify the outcome domains and to develop the questionnaires.(3) Panellists will be asked rate the importance of each outcome domain using a 9-point Likert scale (1-3: not important; 4-6: important but not critical; 7-9: very important – critical), with an option of “don’t know”. 4 They will also have the opportunity to provide other outcome domains of interest that are not included in the initial list. We plan to conduct two rounds of the Delphi survey. In the second round, panellists will be provided with aggregate scores from each stakeholder group to take into account when re-rating the outcome domains. We will not drop any outcomes based on a pre-set threshold between Rounds 1 and 2, in order to allow for panellists to reconsider their ratings in light of the aggregate scores from Round 1. The results of the Delphi survey will be used as a starting point for discussions at the face-to-face meeting. The meeting will be held in Canada, and include a smaller panel of 12-18 invited experts, representing researchers, healthcare providers and patients from several countries. We will use a nominal group technique to reach consensus on the outcome domains. Once consensus is reached, the results will be used to develop recommendations on standard COS for clinical trials of physical rehabilitation in SOT candidates (pre-transplant) and SOT recipients (post-transplant).

REFERENCES
1.Williamson PR, Altman DG, Bagley H et al. The COMET Handbook: version 1.0. Trials, 2017; 18(S3), 280.
2.Janaudis-ferreira, T., Mathur, S., Konidis, S., & Tansey, C. M.. Outcomes used in randomized controlled trials of exercise interventions in solid organ transplant recipients: What does the International Classification of Functioning, Disability and Health teach us? (World Journal of Transplantation 2016 Dec 24;6(4):774-789.)
3.International Classification of Functioning, Disability and Health (ICF) manual (2013). World Health Organization website.