Evidence-based medicine and clinical trials in renal transplantation
- Rita R Alloway, PharmD, BCPS
Rita R Alloway, PharmD, BCPS
- Research Professor of Medicine
- Director, Transplant Clinical Research
- Director, Transplant Specialty Residency and Fellowship
- University of Cincinnati
- Nicole A Pilch, PharmD, MSCR, BCPS
Nicole A Pilch, PharmD, MSCR, BCPS
- Clinical Specialist
- Medical University of South Carolina
Since the introduction of cyclosporine [1,2], there has been a dramatic increase in the number of successful renal transplants and use of non-cyclosporine immunosuppressive agents [3-20]. As the donor and recipient selection criteria for transplantation expand, in combination with the continued introduction of new immunosuppressive agents, the ability to identify the optimal immunosuppressive regimen for a given individual has grown increasingly complex [3-21]. In addition, with improved graft and patient survival secondary to improved immunosuppression, trial outcome measures have also evolved, making individual trial results difficult to compare. To combat this difficulty, a critical, systematic, and scientific method for evaluating ongoing results from clinical trials is needed.
Evidence-based medicine is the explicit and judicious use of current and best evidence to guide clinical decisions [21,22]. Evidence-based medicine must be considered in the context of clinical expertise and with the understanding that its use is based on published literature, which is subject to reporting bias [21,23,24]. Several guidelines for the publication and design of clinical trials in solid organ transplant recipients have been developed [25-27].
This topic provides an overview of the principles of evidence-based medicine in the evaluation of immunosuppressive regimens in renal transplantation. More general issues related to evidence-based medicine and decision analysis are discussed separately. (See "Evidence-based medicine" and "Decision analysis".)
Randomized, double-blind, controlled clinical trials are the most appropriate design to prove the effectiveness of a new treatment. However, this design may not always be feasible or ethical in renal transplantation [23,28,29].
Previously, the gold standard used to assess the efficacy of a new immunosuppressant agent alone or in combination was graft survival and the incidence of acute rejection, with the latter being a predictor for long-term graft survival. However, improvements in short- and long-term allograft survival and the significant decrease in acute rejection rates have led researchers to alternative study designs and endpoints .
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