Revive Regulatory Creativity To Clear Disease Heterogeneity Hurdles, Woodcock Says
Oct 12 2026
• By Bridget Silverman
• 6 min read
Former FDA acting commissioner Janet Woodcock said in an interview that spinal cord injury is not rare, but is varied enough from patient to patient to need rare-disease-style regulatory flexibility, including individualized endpoints that can be tested in randomized trials.
Very heterogeneous diseases like spinal cord injury pose a challenge to conventional drug development.
Key Takeaways
• Former FDA acting commissioner Janet Woodcock argued that the heterogeneous presentation of spinal cord injury makes constructing endpoints a challenge, as the range of functions that are affected can obscure signs of benefit.
• Woodcock is advocating for within-patient controls like an individualized responder index, pre-specified and quantifiable, and said randomization remains possible because SCI is not rare.
• Woodcock urged sponsors to engage the FDA early and for patient groups to lead on endpoints, saying clear policy pathways would attract the sustained investment the field needs.
• Spinal cord injury is not rare, but the condition is heterogeneous enough to need rare-disease-style regulatory adaptability, Janet Woodcock, former US Food and Drug Administration acting commissioner, told the Pink Sheet in an interview.
“Every single person with a spinal cord injury, unless they have a complete transection of the cord, they have a different set of issues, unlike hypertension, say, or acne,” Woodcock said. Autonomic system dysfunction can involve blood pressure, heart rate, bladder and bowel control and temperature regulation. Postural stability and fine motor function can also be affected, with impacts on a “huge range of activities of daily living.”
“The problem is if you focus on one endpoint in a disorder like this,” such as walking time or time to stand, “then you may miss a whole range of improvements that people are seeing,” she said. And with a composite endpoint, poor results on some components can “drag down” the composite score, obscuring benefits on other components.
“You risk missing the signal,” Woodcock said. “That is a regulatory challenge with heterogeneous diseases.”
Woodcock is working with BreakThru SCI, a spinal cord injury advocacy organization that is coordinating a national education and engagement campaign to “ensure the accelerated and patient-informed regulatory review of restorative SCI treatments,” the group said. She spoke at a Sept. 17 congressional briefing that also featured the perspectives of SCI patients who participated in clinical trials.
Shortly after the briefing, the first patient-focused drug development (PFDD) meeting for SCI was held on Sept. 29.
“Despite decades of research, more than 300,000 people in the United States are living with SCI, yet there are currently no FDA-approved drugs capable of restoring function post-injury,” BreakThru SCI said. The organization aims to “elevate experience” to “define what meaningful recovery looks like in everyday life for those living with spinal cord injuries.”
“My reaction to hearing your stories is a terrible sense of urgency,” Woodcock said during the briefing. People with very heterogeneous conditions are in “the same spot right now” as the rare disease community.
“We have a heterogeneous disease,” she said. “We need to have a patient-centric type of investigation, where we identify, for that patient, what are the issues, and then we try to resolve those issues.”
“We can design those kind of trials,” Woodcock said. “They’re simply not the traditional way that’s been done for hypertension or heart disease.”
“We are in a new world, but we have to enable that pathway,” Woodcock told the briefing. “We need clear policies articulated in feasible pathways to get to the market, and then I can guarantee you that will attract the investment and sustained investment that is needed.”
Individualized, Quantifiable And Rigorous
In SCI development, “everyone focuses on walking again, but actually, walking is one of the least of our problems,” Woodcock told the Pink Sheet, pointing to the availability of motorized wheelchairs. Patients have “all these other problems, and they’re different for each person to some extent.”
Janet Woodcock (FDA)
At the congressional briefing, Geoffrey Manley, chief of neurosurgery at Zuckerberg San Francisco General Hospital, used a baseball analogy, saying every therapy is asked to hit a home run. But patients cannot wait for a home run to bring in a cure, he continued, when improvement in hand function that allows patients to feed themselves could be a single.
“If you can rigorously demonstrate and build on small successes, you can move toward home plate,” Manley said. In SCI, constructing a different kind of endpoint is possible, “but it takes some creativity and it takes some work,” Woodcock said during the interview.
Woodcock is advocating for “within-patient controls,” based on “a responder assessment using variable criteria for individualized criteria for response.” Within-patient controls, also known as “patient as their own control” designs, “are very novel, and what sponsors need to do is go in early. They need to have their ducks in a row,” she said.
The approach is not unprecedented, Woodcock said. RECIST criteria in cancer basically assess “did the tumor shrink compared to baseline? How many responses did you get?”
In SCI, an individualized responder index could be constructed.
“You could create an individual listing responder index that’s different for each patient and related to their disease, and you can count numerous things in there,” she said. An analysis could “count the successes on each side.”
“You have to be rigorous,” Woodcock said. Sponsors should avoid the “Hail Mary” attempts sometimes seen in rare disease settings, which she described as: “it’s a terrible disease, so let’s just give them some treatment and then see what happens.”
“You need to pre-specify everything,” Woodcock said. “You need to follow that patient, see what their symptoms are. Can you quantify them, and then can you say what significant improvement would be in each of those symptoms?” Woodcock added that data that is “measurable and quantifiable” is needed.
Because spinal cord injury is not a rare disease, “you can randomize,” she emphasized. “You can still cancel out bias, placebo effect.”
“The problem is, I think, that the RCT standard way of doing has been so successful that people have lost their sense of creativity,” Woodcock said, “including regulators.”
Generating Endpoints
Woodcock helped establish the FDA Center for Drug Evaluation and Research’s qualification process for new endpoints. While the qualification process has become “excessively arduous,” she emphasized that it is thorough and supported by guidance documents.
“You need to understand the performance characteristics” of all elements of endpoints and scales, Woodcock said. In a trial measuring individual symptoms, “you’ve got to have quantifiable metrics for each one of those symptoms.”
“Global indices are useful for seasoned clinicians, but that can’t be everything,” she added. “We‘ve got to go to the source and see how the people are functioning and feeling.”
“The problem with a single endpoint for everyone is that combined endpoints are problematic,” she said. “If your treatment fails to improve a certain component of that, you drive the whole thing down.” A trial can produce “nothing in the end,” even if some “people improved a lot, but these other people didn’t improve at all.”
Woodcock urged researchers to think through how to structure composite endpoints. “How do you validate them and make sure that they’re going to perform OK?”
While the patient-focused drug development meeting provided a “wide net” to collect a range of input from the SCI community, Woodcock said developing a new endpoint is “a broader and much more scientifically intensive process.”
“It really can’t be a huge group effort,” she said.
“Any group trying to develop a new set of endpoints can go back to the community in different ways and get input,” Woodcock added. “But the next step is actually to develop some kind of instrument that captures the heterogeneity, and that has to be linked … with a trial design.”
“The agency is responsive and takes patient input very seriously,” Woodcock said.
Time For Patient Groups To Lead
“What really helps is reasoned analysis [and] independent analysis by the patient advocacy groups,” Woodcock said. The FDA wants to hear about the disease, the extent of its heterogeneity, and “the problems with current trials.”
Some advocates go to the FDA saying “our disease is bad and we don’t have any treatments, and we’re suffering,” she said. “The agency people know this. They’re doctors.”
Since the PFDD initiative, “we’ve seen much more patient engagement in trial design” around feasibility of participation, including issues like decreasing dropouts and increasing recruitment, Woodcock said.
“We have patient groups developing scales, and they know that existing outcome measures are inappropriate for their disease,” but the outcome measures are “often recommended by the agency because they’re familiar with them,” she added. Patient groups can “push back on that.”
In fact, patient groups “have more standing when they do that than any company because there’s no commercial interest,” Woodcock said. “I think patient groups have a great deal of standing, but it requires some sophistication,” she said.