Invented by Maurizio Fava, director of clinical research and executive vice chair of psychiatry at MGH, and David Schoenfeld of the MGH Biostatistics Center, SPCD is an alternative method for conducting well-controlled clinical trials that substantially decreases the impact on trial outcomes of any placebo effect and can reduce the time and cost of conducting their clinical trials. This methodology, which PPD is branding as Trimentum, has been particularly effective in studying major depressive disorder (MDD), but is applicable to clinical trials in many disease areas where outcomes can be impacted by placebo effects.
The SPCD method incorporates two sequential placebo-controlled stages into the process, the second of which includes a re-randomization of placebo non-responders from the first.
Trials in psychiatric indications are particularly vulnerable to placebo effects due to the subjective nature of the assessments. Due to its basic structure, SPCD reduces the number of patients required for a given trial by 20% to 40%. This not only decreases the cost and time it takes to conduct a trial, but also eliminates some of the factors that make results more difficult to interpret.
Daniel Burch, PPD VP of global product development and therapeutic area head for neuroscience, told us: “This method is particularly successful in neuroscience, a therapeutic area that lends itself to using alternative designs for clinical trial development. Greatest evidence of success of this design is seen in indications that are prone to high placebo effect, particularly in depression studies, but it also has promise in other areas of psychiatry, pain and any chronic disease that has subjective measures and is associated with a placebo response.”
He also noted the model works well for the following trials:
• Pivotal trials with expected high placebo response;
• Proof-of-concept trials;
• Trials conducted under post-marketing commitments;
• Trials in pediatric and adolescent populations;
• Orphan disease trials;
A total of 22 SPCD trials are completed, ongoing or planned. These include Phase II and Phase III trials by corporate sponsors that are licensees of RCT Logic, as well as trials with the National Institutes of Health (NIH) and charitable funding.
“Incorporating the Trimentum model has become more prevalent for all stages of clinical trials,” Burch told us. “Successful negotiations for the use of this model in depression trials to support a marketing application in depression have been reported. We intend to model and probe further utility in adjacent areas in psychiatry, pain, neurology, GI and beyond.”
As a result of this acquisition, PPD owns an exclusive license from MGH and PPD intends to continue RCT Logic’s practice of offering licenses to any qualified trial sponsor.
PPD has conducted more than 270 studies across all phases of development over the past five years in a range of neurology, psychiatry and pain management indications.