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Real-world & natural history data consistent with placebo data in DMD clinical trials
by Mel J. Yeates  |  Email the author


CAMBRIDGE, Mass.—The Collaborative Trajectory Analysis Project (cTAP), a global research coalition for Duchenne muscular dystrophy (DMD), has reported results from the largest ever multi-national, multi-collaboration study in DMD. The study was published in Neurology.
The results indicate that both real world data (RWD) and natural history data (NHD) are highly comparable to data from patients treated with placebo in multiple recent clinical trials. Results also demonstrate that use of RWD or NHD could supplement — or possibly even replace — use of a placebo arm in future DMD clinical research. This could potentially help to streamline development efforts for new treatments.
“This study found a striking level of consistency in the six-minute walk distance assessment in DMD patients from six clinical trial placebo arms and patients from five different real world and natural history studies,” said Craig McDonald, professor and chair of the Department of Physical Medicine and Rehabilitation at the University of California, Davis, and a co-author of the study. “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.”
In the study researchers analyzed disease progression in 383 patients with DMD who had been randomized to placebo arms in six clinical trials. This was compared with data observed in a real world setting for 430 patients from five clinical registries in the U.S. and Europe. Patient outcomes were assessed based on similar inclusion/exclusion criteria, and adjusted for known prognostic factors.
This is the first study to demonstrate the comparability of disease progression in NHD/RWD and placebo arms of clinical trials in DMD.
To date, the potential for bias in clinical trials versus clinical practice has limited the use of NHD/RWD to supplement or replace placebo controls. This study demonstrates that the potential for bias is low, and as such provides a foundation for drug developers to consider application of NHD/RWD in future trials.
“In particular, a fundamental motivation for this research was the concern that external controls might not be suitable for DMD because performance-based outcomes such as 6MWD [6-minute walk distance] could be biased by differences between clinical trial and RWD/NHD settings. We analyzed >1,000 patient-years of follow-up, encompassing data from all available clinical trial placebo arms and from 5 multinational, multi-institutional RWD/NHD sources. We found that changes in 6MWD over 48 weeks were strikingly consistent between these settings when subjected to equivalent inclusion/exclusion criteria and after adjustment for multiple known prognostic factors,” the article notes. “The 6MWD outcomes were also consistent among the different RWD/NHD sources analyzed. From these findings, we conclude that external controls can be suitable for drug evaluations in DMD.”
“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,” added 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.”
Code: E09082001



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