Since 2012, the nonprofit organization TransCelerate Biopharma has worked to develop a template protocol designed to cut costs and shorten timelines for industry-sponsored trials. Separately, the FDA and NIH have also spearheaded an effort to provide a template for all government-funded trials. Several years ago, the two groups began working together, and have now announced that their respective templates have been aligned to further streamline product development in the clinical research industry as a whole.
“The NIH-FDA and TransCelerate templates were developed independently, but released around the same time,” said Peter Marks, M.D., Ph.D., director of the FDA’s Center for Biologics Evaluation and Research. “Both groups realized that there was further benefit if the organization of the two templates were harmonized.”
“Even though the sponsors are different and even though the experiments are different, we all rely on the same FDA reviewers and there is overlap between the academic centers,” said Rob DiCicco, Pharm.D., vice president of Clinical Innovation and Digital Platforms at GlaxoSmithKline. For that reason, the templates share the same basic organizational structure and a standard terminology, said DiCicco, who led the Common Protocol Template Project for TransCelerate.
Interest in standard protocol was fueled by a 2010 analysis by the Tufts Center for the Study of Drug Development, which found major inefficiencies in the protocol development process. That study was followed by a 2016 Tufts analysis, published in the journal Therapeutic Innovation & Regulatory Science, which found that at least 57% of protocols studied had at least one amendment, 45% of which could have been avoided.
To alleviate this problem, TransCelerate and the NIH-FDA Joint Leadership Council developed templates designed to simplify and automate the protocol development process, ultimately bringing new treatments to the market faster. So far, more than 2,800 stakeholders hailing from life science companies, academia, technology provider companies and government agencies have downloaded TransCelerate’s protocol template, said a TransCelerate spokesperson.
One of the most tangible benefits of a standardized, digitized protocol template is the potential to cut down on the number of amendments that are added mid-stream, which cause delays and add additional costs for the sponsor.
The 2016 Tufts study revealed that of the protocols with at least one substantial change, 23% were completely avoidable, and some were due to human error. The study demonstrated that there “is an opportunity to identify low-hanging fruit” by standardizing protocol templates and eliminating the risk of human error, said DiCicco. “There are also some indirect benefits of not reinventing the wheel every time,” he said.
“In the absence of a standardized format,” said the FDA’s Marks, “protocols contained within IND or IDE submissions were sometimes found to be incomplete, lacking specific detail or missing entire required sections that would require revision before a clinical trial could begin, or at times, a clinical hold. This was particularly the case sometimes with protocols from academic investigators and startup pharmaceutical or biotechnology companies.”
“With funding increasingly difficult to get from governments, a lot of investigators are looking for mixed funds,” said Dr. Marina Malikova, executive director, Surgical Translational Research Operations and Compliance, Boston University. “Therefore, the harmonized templates are trying to standardize the process to decrease redundancy so investigators don’t have to repeat certain experiments during the drug development lifecycle.”
The Tufts study also found that 62% of the substantial changes to a trial are made during study enrollment, sometimes to modify the enrollment criteria if a trial is not recruiting as expected. To help take the guesswork out of enrollment criteria, TransCelerate has also developed what it calls CPT Library Files, which contain suggested text relevant to several disease-specific study areas, explained DiCicco.
The main difference between the two documents is that the FDA-NIH template is designed for a single-center site, and the TransCelerate template includes additional considerations for multicenter, global sites, explained DiCicco.
“The TransCelerate template is very process-oriented, whereas the NIH template appears to be more instructional because it is oriented to individual investigators applying for those grants,” said Malikova. Harmonization is important because “no matter how you go about conducting your research, you have to comply with federal regulations,” Malikova said.
“Interestingly, both templates emphasize lifestyle changes, which goes above what is required in current regulations,” Malikova said.
“It’s in the early days,” added DiCicco, but eventually the common protocol template will be paired with electronic health records of millions of patients, which will help sponsors to “dial-in enrollment protocol up-front” instead of amending it later. In addition, TransCelerate has plans to build additional automation using machines. “Theoretically, you could write information one time and in one place and then push that change to other areas,” said DiCicco. “We are piloting that now.”
Moving forward, TransCelerate will continue to share feedback from the industry with the FDA and NIH. Meanwhile, the FDA and NIH have announced future plans to add additional instructional texts for other types of studies beyond merely phase II and phase III trials.
“As we move into the realm of governance and upgrading, we will continue that dialog” with the FDA, said DiCicco.
This article was reprinted from Volume 21, Issue 19, of CWWeekly, a leading clinical research industry newsletter providing expanded analysis on breaking news, study leads, trial results and more. Subscribe »