Clinical Trials for Immunosuppression in Transplantation: The Case for Reform and Change in Direction.

Currently trials of immunosuppression in transplantation are in decline because their objectives remain focused on improving acute rejection rates and graft survival in the first 12 months. With 1 year renal graft survival rates of greater than 90% the best that can be hoped for is noninferiority trial outcomes compared with current standard of care. Current trial design is not leading to novel therapies improving long-term outcomes and safety, and hence important unmet clinical needs in transplantation remain unanswered. Issues that need to be addressed include but are not limited to: prevention of subclinical rejection in the first year, better 5- and 10-year graft outcomes, more effective treatment for high immunological risk and sensitized (including donor-specific antibody) patients, immunosuppressive combinations that are better tolerated by patients with fewer side effects and less morbidity and mortality. In September 2015, the Transplantation Society convened a group of transplant clinical trial experts to address these problems. The aims were to substantially realign the priorities of clinical trials for renal transplant immunosuppression with the current unmet needs and to propose new designs for clinical trials for transplant immunosuppression. Moving forward, the transplant community needs to provide trial data that will identify superior treatment options for patient subgroups and allow new agents to be evaluated for efficacy and safety and achieve timely regulatory approval. Trial designs for new transplant immunosuppression must be intelligently restructured to ensure that short- and long-term clinical outcomes continue to improve.