Need for doubleblind controlled trials and sham surgery

While there has been some resistance to the use of double-blind placebo-controlled trials to assess new surgical therapies, we believe that it is essential to employ this study design in evaluating the safety and efficacy of cell-based therapies for PD (Freeman et al., 1999). Placebo and bias effects can be powerful and seriously distort the results of a trial (McRae et al., 2004). Placebo therapy can also be associated with dopamine release with possible clinical consequences (de la Fuente-Fernandez et al., 2001). There are numerous examples of surgical procedures that were adopted into general practice based on anecdotal observations that were discarded after negative results in more formal clinical trials (Freeman et al., 1999). In PD, we have recently seen that positive results in open label trials of human fetal nigral transplantation, porcine fetal nigral transplantation, and GDNF infusion were not confirmed in double-blind trials. Transplantation therapies in PD are particularly appropriate for evaluation in double-blind trials as the intervention is relatively standardized and the treatment has much in common with drug therapies; issues such as dose, distribution, metabolism/degeneration, delayed response, and immune reactivity must all be considered (Olanow, 2005). Indeed, a recent survey showed that 97% of PD investigators would insist on a doubleblind placebo-controlled trial before accepting that a cell-based or gene therapy procedure was efficacious, despite the need for a sham control (Kim et al., 2005). While a sham procedure is not fully without risk, the alternative is to expose patients to a procedure that might not work, and whose safety and efficacy profile has not been fully defined.

Was this article helpful?

0 0

Post a comment