WASHINGTON — Patient advocates, industry experts, and FDA‘s top brass offered a variety of thoughts on how patients’ perspectives can inform drug development, review and prescribing habits, at a briefing hosted by the National Health Council on Friday.
FDA Commissioner Scott Gottlieb, MD, said that when he received a diagnosis of state 1 Hodgkin’s lymphoma in 2006, he was told he had a greater than 90% chance of a complete cure.
His own doctor gave him even better odds, yet even a 5% chance of not being alive in 5 years is daunting, he said.
“I pulled every single study and case report I could find. I tortured my doctors,” he said.
“What I was looking for was pristine data — really good outcomes data, large trials. I wasn’t going to do anything experimental,” Gottlieb continued.
His goal: to increase his odds of survival 1 or 2 percentage points. He chose to get chemotherapy but decided against radiation, based on his review of the data.
But, he acknowledged, his own approach to treatment may not be what someone with a more aggressive illness would choose, he noted.
“If you’re told your odds of being alive in 5 years are 15%, 20%, available therapy‘s not that good,” he said.
Those with harder-to-treat illnesses are often more willing to consider treatments with less data behind them, Gottlieb said, even ones that are still in development.
He acknowledged that in serving a patient like himself in 2006, the agency may subvert the interest of another who is willing to take more risks.
“I think we have to think about, as an agency, how do we serve both patients,” he said.
Consistency is Key
One way to shift this culture of the agency and ensure patients perspectives are heard, is to ensure that their voices are included in the review and approval process in a standardized way. Gottlieb stressed the importance of patient-reported outcomes and other “real world” evidence.
“[I]f you want these things to be tangible, meaningful, and enduring, you have to build them into the process, you need guidance documents, you need to build them into the way information is received by the agency, ” Gottlieb said. “There has to be structure, there has to be consistency.”
But when it comes to listening to patients, the culture of the FDA is already changing.
Some supplemental indications now rely on real world evidence, safety questions are being answered by real world data, and some medical devices’ approval has been based entirely on real world evidence.
“Patients who were very obese were willing to assume a little bit more risk than … the agency had perceived,” Gottlieb said.
Those patients were also willing to accept that risk for a lesser magnitude of weight loss than the FDA had thought necessary. Without soliciting the patient perspective, there’s no way the agency would have known that small degree of weight loss mattered to patients.
Suzanne Schrandt, JD, director of patient engagement at the Arthritis Foundation, said that patient surveys showed that even among children, “many folks in this disease population would prefer… a very rare but very serious adverse event to … nausea and vomiting that’s almost assured.”
This didn’t surprise Schrandt, because she’d had to weigh those options herself.
But she was taken aback to learn that clinicians and researchers weren’t aware of their patients’ preferences. It seemed they wanted to protect their patients from a potential serious harm at all costs, she said.
“It really brought home how different it is to live with a disease every day” as opposed to treating it, she said.
Bari Talente, JD, executive vice president of advocacy for the National Multiple Sclerosis Society (NMSS), noted that some clinicians will still prescribe the same first-line disease-modifying treatments they prescribed in the 1990s.
In a survey the group conducted with Johns Hopkins University, caregivers of patients with DMD valued slowing the progression of their child’s disease more than extending their life expectancy.
Indeed, there was a “strong preference for pulmonary benefit and a willingness to trade risks and burden to achieve this benefit.”
But, complicating the picture, the same survey found that patients themselves were less risk-tolerant than caregivers or professionals.
Patients on average saw themselves as willing to accept a 7.3% chance of failure rate, a 3.6% increased risk of kidney damage, and a 7.5% risk of fracture. Caregivers, on the other hand, were willing to tolerate a 21.1% failure rate, as 8.4% increased risk of kidney damage and a 30.6% risk of fracture.
Paternalism versus Patient Choice
Among FDA review panels that urge to protect is strong, Talente said. She recalled one advisory committee’s reluctance to recommend a medication for approval a few years ago because it had serious side effects and adverse events, even though some patients viewed it as “a lifeline,” she said.
“I think our medical system and scientific system still tends to be a little patriarchal sometimes in making what people view as the best decisions for people to protect them, but we have to let people make their own decisions for themselves,” Talente said.
“People are at different points in their life, they’re at different points in their disease state, so they’re going to make different decisions.”
While drug developers may find having multiple perspectives on treatment challenging, it’s important that they keep asking questions and return to the data.
When NMSS surveyed patients on what they wanted in a medication, 90% said they wanted to continue living their daily lives or to continue working.
And while even that response contains nuances, it’s still important that researchers, drug developers, clinicians and advisory panel members ask these question and incorporate patients answers into their work, Talente added.