Sequential Transplant Research: A Consensus Guideline Endorsed by the International Society for Organ Donation Professionals, the Canadian Donation and Transplant Research Program, and the Canadian Society of Transplantation
Maureen O. Meade, Annabelle Cumyn, Frédérick D’Aragon, Prosanto Chaudhury, Darin Treleaven, Sameer Parpia, Markus Selzner, M. Khaled Shamseddin, John S. Gill, Jeffrey M. Singh, Aviva Goldberg, John Basmaji, Charles Weijer, Nicholas Murphy, Marat Slessarev, Steven Paraskevas, Karen E. A. Burns, Jean-Frédéric Ménard, Olwyn Johnston, Aldo J. Montano-Loza, Heather E. Talbot, Borong Wang, Yang Wang, Afsana Lallani, Sandra C. Holdsworth, Justin S. Gill, Graziano Oldani, Sadia Baig, Rhea Varughese, Diana N. Brodrecht, Deborah J. CookBackground.
Sequential transplant research is the administration of distinct study interventions in sequential phases (donor, organ, recipient) of the same organ transplant. This guideline provides a framework for assessing the suitability of implementing ≥2 transplant studies sequentially.
Methods.
We applied World Health Organization guideline methodology. The guideline panel included transplant researchers, transplant patients and organ donor family members, randomized trial methodologists and biostatisticians, and research ethics scholars. Three principal themes included the impact of sequential research on patient safety, study findings, and strategies for effective implementation. The panel met on 7 occasions during 4 mo.
Results.
Patient safety indicates that sequential studies have potential to harm transplant recipients in 3 situations: when investigational drugs are the same in both studies, they have a classic drug-drug interaction, or they have similar adverse effects. Study findings indicates that sequential research might influence study estimates of relative risk only if 1 intervention modifies (ie, amplifies or suppresses) the effects of another. In contrast, with or without effect modification, sequential research can influence the power of a study to detect expected treatment effects. An appreciable impact on study power will only arise, however, when there is a high rate of sequential enrollment in the study population. Implementation indicates that ideally, to maximize research efficiency, independent bodies will judge the suitability of sequential research, and research organizations will develop an equitable approach to support studies found unsuitable for sequential implementation.
Conclusions.
This guideline represents a starting point to advance the safe implementation of sequential trials in transplantation.