Replication Studies and The Miami Project
Replication Studies and The Miami Project: A Firsthand Report From the Trenches by Dr. Vance Lemmon
Over the past ten years or so a consensus has emerged that, before a new therapy is tested in humans with spinal cord injuries, the original animal studies should be retested to ensure the method is robust and reliable. While there are many reasons for this, the famous “Facilities of Research Excellence-Spinal Cord Injury” (FORE-SCI) program launched in 2003 by the National Institute of Neurological Disorders and Stroke (NINDS), and performed at the University of California, Irvine, the Ohio State University and the University of Miami, clearly demonstrated that many promising studies could not be replicated.
This is not unique to SCI in replication studies. Similar lack of reproducibility in other fields has led the National Institutes of Health (NIH) and international organizations to make specific recommendations about strategies to improve the rigor of biomedical research. Chief among these are improved reporting of methods, ensuring that investigators are blinded to treatments, and that there are enough samples that the results are statistically meaningful.
The SCI research community, including Miami Project faculty (Bixby, Bunge, Guest, Lee, Lemmon, Oudega, Park), has been at the forefront of these efforts – establishing reporting standards and data repositories and implementing best practices.
Because The Miami Project has been so successful at conducting a variety of U.S. FDA approved clinical trials, SCI researchers from around the world often reach out to us for advice about pre-clinical experiments and clinical trial design. One such inquiry led The Miami Project team to China multiple times over the past two years to collaborate and consult on a potential clinical trial.
In early February of 2017, I flew to Beijing for a kick-off meeting, along with Anil Lalwani, a biomedical engineer who had worked at the MP and been heavily involved in the Investigational New Drug (IND) and Investigational Device Exemption (IDE) submissions to the FDA for the Schwann cell clinical trial and medical device studies for pain. At this meeting we saw the rat data as well as unpublished data from studies in monkeys, showing that the biomaterial/growth factor combination had dramatic effects on walking. I and other scientists at the conference, mindful of the poor replication track record of previous “breakthroughs”, strongly recommended that an independent replication study be done prior to moving forward with clinical development of this novel combination approach. Professor Li and his colleagues agreed, in principle, to do this. We then went to Shanghai to visit Tongji Hospital, where they were considering doing the clinical trail. This giant hospital (over 4000 beds) had a large unit set up for conducting early stage clinical research and clinical trials that complied with the Chinese FDA regulations. It also had a very busy spine surgery department that received sufficient numbers of SCI patients to conduct a meaningful phase one safety trial in a relatively short amount of time, especially compared to U.S. hospitals.
After returning to the U.S., we were asked to help organize the replication study. Since we had urged him to do this, it was difficult to say no. We had some significant obstacles to overcome before we could begin the replication study since there were at least five non-trivial problems that needed to be resolved before we could begin replicating the study.
“Spinal cord injuries occur everywhere in the world. It was fascinating to work with Chinese biomaterial experts and molecular biologists to validate their preclinical work with a new biomaterial, and also share The Miami Project’s vast experience in clinical trials. We think these kinds of international collaborations are a win-win for patients and scientists alike,” said Dr. Lemmon.
To read the full story, view page 10 from out latest research review.