Susan L. Smith, MN, PhD


March 31, 2003

The Hierarchy of Evidence

The case of calcineurin inhibitors has been an instructive lesson for the clinical transplant community. Despite initial excellent short-term graft and patient survival rates in patients treated with 1 or the other of the 2 calcineurin inhibitors, these agents are toxic (particularly to the kidney) when given long-term and have a negative impact on long-term outcomes, including survival. Consequently, different regimens consisting of newer agents, regimens of withdrawal of calcineurin inhibitors, and regimens of lower doses of calcineurin inhibitors are being evaluated, frequently necessitating a return to measurement of short-term outcomes. As long as new agents continue to be introduced into the market (the next wave is anticipated to occur in 2005-2006), and until there is a suitable replacement for calcineurin inhibitors, this will be the case. Thus, transplantation clinicians and researchers will be challenged to simultaneously measure, manage, and improve outcomes in patients at 3 points on the posttransplant spectrum: short, medium, and long term ( Table 3 ).


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