Skip to content

Pink Sheet – FDA’s Califf Calls For Return To Large, Simple Trials Without The ‘Useless Stuff’ That Slows Development

Pink Sheet – FDA’s Califf Calls For Return To Large, Simple Trials Without The ‘Useless Stuff’ That Slows Development

Industry should return to large, simple clinical trial designs that rely on randomization and endpoints that matter most to patients – and remove the excessive data collection that often leads to problems with recruitment, retention and trial cost, Food and Drug Administration Commissioner Robert Califf said.

“Randomization as a tool is an amazingly elegant tool” to answer important clinical questions, Califf said at the Prevision Policy/Friends of Cancer Research Biopharma Congress last month. “It’s astounding. And somehow, along the way, we’ve ruined it by adding on all kinds of useless stuff that doesn’t help. I don’t know why that became the norm. It’s really a problem.”

Califf made those comments after listening to a session on the Oncology Center of Excellence’s “Project Pragmatica,” which encourages streamlined trials in cancer, starting with a Phase 3 extension of the Lung-MAP trial in partnership with Merck & Co., Inc. and Eli Lilly and Company. (Also see “Project Pragmatica: US FDA’s OCE Initiative Aims To Encourage Simple Clinical Trials” – Pink Sheet, 21 Nov, 2022.)

“I felt like my entire career was relived during that discussion,” Califf said. “We need to answer the questions that matter to patients. That’s been a distinguishing feature of the oncology part of FDA.”

Califf reflected on his days of running large cardiovascular outcomes trials that focused on “life or death” questions for patients. “In 1988, we didn’t know how to treat heart attacks, and it was obvious that the thing people care about the most is whether they are dead or alive.”

Quality of life endpoints are “very important,” but in most circumstances, “people want to be alive,” he observed wryly. “You can’t answer the questions that need to be answered without looking at [survival endpoints] and if you collect a thousand of pages of useless stuff, it makes it hard or impossible to get the right answer.”

Large, simple trials worked well in cardiovascular disease, Califf noted: “We were randomizing 40,000 people per trial, internationally, with a three-page case report form. It did just fine; it got FDA indications, and we rolled out a whole series of trials,” he said. “I hope we can rediscover what we knew in the 1980s and get people the answers to the questions that they have.”

Califf praised both Project Pragmatica and the “very powerful” partnership between OCE Director Rick Pazdur and National Cancer Institute Director Monica Bertagnolli.

The dedication to the FDA/NCI partnership, however, “is not just a leadership thing; it’s throughout the ranks,” he added, noting that the panel discussion featured OCE Deputy Director Paul Kluetz and NCI Cancer Therapy Evaluation Program’s Elad Sharon.