In the largest multinational analysis of data from clinical trials of potential treatment for Duchenne muscular dystrophy (DMD), results of placebo treatment suggest real-world (RWD) or natural history data (NHD) could be used instead. Substituting RWD or NHD for placebo treatment potentially aid efforts to modernize how new treatments for DMD are tested as well as increase enrollment in clinical trials.
In the study, clinical progression data from 383 participants with DMD who received placebo in 1 of 6 clinical trials were compared to data from 430 individuals in 5 clinical registries. Inclusion and exclusion criteria determined participant outcomes and were used to adjust for known prognostic factors.
"This study found a striking level of consistency in the 6-minute walk distance assessment in DMD patients from 6 clinical trial placebo arms and patients from 5 different real world and natural history studies," said Craig McDonald, a coauthor of the study and professor and chair of the Department of Physical Medicine and Rehabilitation at the University of California Davis. "This rigorous study establishes a strong foundation for using natural history data as a substitute for placebo control in clinical trials and as a comparator to determine the effectiveness of prescribed drug treatments versus standard of care treatment."
Currently, there is limited use of NH/RWD to supplement or replace placebo controls because of the potential for bias in clinical trials vs clinical practice. This study demonstrates that the potential for bias is low, and as such provides a foundation for drug developers to now consider application of NH/RWD in registration trials.
"The results of this landmark research effort have profound implications for clinical research in DMD and potentially many other rare diseases. We applaud cTAP for supporting this research effort and look forward to sharing these insights with all of the stakeholders in DMD research including regulators, industry, clinicians and patient advocates," said Francesco Muntoni, professor and chair of Pediatric Neurology at University College London. "This effort, which addresses a key priority for patient foundations, shows clearly that by working together we can identify better solutions to advance clinical research that can facilitate the development of new treatments for DMD."
Danielle S. Shpiner, MD; Crystal Dixon, MD; Melissa R. Ortega, MD; and Henry Moore, MD
Jason A. Ellis, MD; Benjamin W. Y. Lo, MD; Chirag G. Bhatia, BS; Yona Feit; Steven Mandel, MD; and Dana Shani, MD
Shailee S. Shah, MD, and Andrew McKeon, MD