FDA chief Robert Califf and Oncology Center of Excellence head Richard Pazdur are worried about clinical trials being moved outside of the United States, and the agency is looking to do something about it, including by simplifying the clinical trial process.
The agency has launched Project Pragmatica, which aims to preserves trial randomization but simplify the overall trial process, Pazdur announced Thursday (Nov. 17) during the Friends of Cancer Research annual meeting. One of the ideas FDA is discussing with the National Cancer Institute is conducting trials with only one endpoint of overall survival and minimal eligibility criteria.
There is an increasing number of oncology development programs based solely or predominantly on clinical data from China, with at least 25 applications from China expected to be submitted or currently under review, Pazdur and Harpreet Singh, director of FDA’s oncology division, wrote earlier this year in the journal Lancet Oncology.
The current trend of marketing applications to the FDA based on foreign data from single-country trials is a departure from decades of multi-regional clinical trials as the consistent approach to drug development, FDA wrote in briefing materials for an advisory committee meeting in February. Multi-regional clinical trials tend to be large, randomized trials, which allow a medical product’s treatment effects to be evaluated among regions, FDA said.
It’s a problematic trend, Pazdur said Thursday. It’s especially a problem if companies and researchers choose to conduct trials outside of the United States because they’re studying a drug that’s inferior to another FDA-approved therapy. People that enroll in clinical trials should be getting the best therapies, Pazdur said.
“There is no asterisk there that says, ‘only available or only approved in your country.’ And I think we are going to have to answer to this if it continues. People are going to potentially lose confidence in a system if they know … they’re getting inferior treatments. We live in a globalized world. There’s no reason why a person in country X can’t go to another country to get that drug. Are those patients adequately being addressed?” Pazdur asked.
Califf agreed, saying globalization is good, but that some factors, like cost, shouldn’t be a reason for moving trials out of the United States.
Not all clinical trials have to be done in the United States, but at least some of them need to be, Pazdur said. FDA wants to see more multi-regional trials that represent the major International Counsel for Harmonisation regions and that include adequate representation of patients from North America, Europe and Asia, the Oncology Center of Excellence chief said.
“By having those countries participate in a multi-regional trial, we’re actually bringing in those countries to the international regulatory community. By doing analysis of different sites and different countries, we’re able to see if there are different results, different toxicities, different efficacy parameters that one would take a look at. So it’s in the really the long-term interest to have multi-regional trials being done throughout the world,” Pazdur said.
Pazdur added that trials have been made “way too complicated,” and he hopes Project Pragmatica can help by preserving randomization while also simplifying the overall trial process. Pazdur said FDA has discussed with NCI the possibility of conducting a trial with only one endpoint of overall survival and minimal eligibility criteria.
“I don’t care about [the participant’s] BMI, I don’t care about their renal function, I don’t care about their platelet count, I don’t care about their hemoglobin. So very minimal eligibility criteria, and basically no safety reporting other than for hospitalizations or toxicities that are not described in the safety endpoint. And I view this as an important trial and something that we really want to collaborate with the NCI on,” Pazdur said.
Pazdur said he’s also like to see NCI work more with companies on clinical trials in which NCI would handle U.S. enrollment for a clinical trial and the companies would enroll people outside of the United States, and then the databases would be combined.
“[This could make] sure that the trial is accruing very rapidly … they could easily be done that way,” Pazdur said.
FDA and its advisers earlier this year discussed issues with single-region clinical trials during a day-long meeting that ended with the agency’s advisers overwhelmingly agreeing that Eli Lilly and Innovent Biologics need to conduct U.S.-focused trials for their lung cancer drug, sintilimab, which was only tested in China and not in a U.S. patient population. FDA officials stressed the data are not adequate for U.S. review and approval and that the clinical trial did not fall in line with U.S. regulations and standard of care. — Beth Wang (firstname.lastname@example.org)