Clinicians wanting to develop new devices and treatments for children face formidable barriers: regulators’ need to protect the most vulnerable coupled with a lack of commercial interest. But determined innovators do have options, including creative funding sources, says Thomas Krummel, MD, director of surgical innovation at Stanford Medical School.
"Technology developed specifically for children has been a low priority," Krummel began at a two-part talk at Boston Children’s Hospital this summer (read our coverage of the other part). "The FDA barriers are incredibly high, and ultimately, investors just demand returns that pediatric markets won’t necessarily deliver."
As Krummel detailed, the FDA barriers are there for a reason: a past history of ethical abuses in human subjects research. In 1966, physician Henry Beecher, MD, exposed many examples in The New England Journal of Medicine, such as withholding effective treatment for the sake of research, proceeding with a treatment despite recognized hazards, or failing to disclose risk to patients. Institutional Review Boards (IRBs) arose in the mid-1970s to protect research subjects – protections that are especially strict when that research is done in children.
But there’s also a deep-seated reluctance to break with the status quo. In the 1950s, Arnall Patz was an ophthalmology resident who questioned the standard practice of delivering supplemental oxygen to premature babies. He believed the practice was blinding some of the infants. When he wrote a grant to get the funds to prove it, the application was roundly rejected by the National Institutes of Health. One obituary cites a grant reviewer as writing: "These guys are going to kill a lot of babies by anoxia [inadequate oxygen] to test a wild idea."
"The medical standards of the day are relative, and the experts of the day are frequently clueless in terms of the future."
But Patz did the experiment with money borrowed from his brother and eventually showed that elevated oxygen levels destroy the arteries of the eye, causing retinopathy of prematurity. Practice changed almost overnight, abruptly ending an epidemic in which more than 10,000 children were blinded.
Another example: Thomas Fogarty, a scrub technician in the 1960s who conceived of using a balloon catheter (devised from a urinary catheter and the finger of a latex glove) to remove blood clots from the leg. It’s hard to believe this now, but at the time, surgeons would make a full-leg-length incision anteriotomy – a cut from groin to ankle – to extract the clot, a procedure sometimes leading to death or amputation. Fogarty’s idea was vilified, but it revolutionized noninvasive therapy.
The commercialization barriers to innovation have proved just as formidable, especially in pediatrics. In 1980, innovation took off with the Bayh-Dole Act, which transferred patents from the federal government to the researchers and institutions receiving federal funding.
But as regulation increased, so did time to market, and investment slowed. In pediatrics, inventors often seek an adult application first, since the far larger (and less risky) market is often needed to justify the investment.
"Because of our risk aversion, we have a reverse of Moore’s Law in technology development," Krummel said. "Every 18 months, it costs twice as much."
In the pre-FDA era, for example, Fogarty’s balloon catheter went from invention to first U.S. use in two months, at a cost in time and materials of about $1,800. Today, new devices (even those for adults) commonly take a decade or more to get to market.
But Krummel stressed the importance of going to the right places for support – and that many new options are emerging to support pediatric innovation.
A growing number of venture philanthropy and social entrepreneurship organizations – many of them with a passionate mission – are pursuing a nontraditional funding model that’s not based on economic returns. Kiva, Endeavor and Ashoka are just a few examples.
Groups of pediatric hospitals are forming collaborative initiatives such as the MISTRAL Pediatric Device Consortium in alliance with the nonprofit SRI International and the Institute for Pediatric Innovation. Training programs are emerging to support inventors, such as the Fellowship for Innovation in Pediatric Devices funded by the Lucile Packard Children’s Hospital and the Kauffman Foundation.
The bottom line, according to Krummel, is this: "The medical standards of the day are relative, and the experts of the day are frequently clueless in terms of the future. So when you’ve got a great idea and someone tells you it’s the stupidest thing they ever heard of, just ignore them, do the experiment with your own money and prove to the world that you know what you’re doing."
His parting advice? "Under-promise and over-deliver."
Ed. note: Read about creative alternatives for financing cures for the ultimate orphans – neglected diseases – in this previous Vector post. For more, attend the Innovation Acceleration panel discussion next week at Boston Children’s Hospital’s National Pediatric Innovation Summit + Awards.
Nancy Fliesler, Vector’s editor, has been senior science writer at Children’s Hospital Boston since 2003, spotting innovation trends and covering virtually every clinical and laboratory research department in the hospital. She previously worked for the ABC News medical unit, helped produce science programs for K-8 teachers for the Harvard-Smithsonian Science Media Group, and worked on video productions for the Mental Illness Education Project. Prior to that, she was executive editor of Journal Watch, and also produced and directed the award-winning documentary Lifestyles of the Poor and Unknown. She holds a BA from Oberlin College (Phi Beta Kappa) and an MS in science and medical journalism from Boston University.