Every year, more than a million children under age 3 undergo operations in the nation's hospitals using anesthetics that the Food and Drug Administration and many clinical scientists fear may be damaging their developing brains.
The FDA has known about it for years. In 2011, its top scientists published a commentary in the New England Journal of Medicine calling attention to the growing body of animal studies documenting neurological damage to young mammals exposed to commonly used anesthetics.
A few human studies also have signaled a clear warning. One sample of 383 children who underwent hernia repair had twice the diagnoses later in life of developmental or behavioral disorders compared with a control group. Other studies showed that using multiple anesthetics—such as in complex operations for cleft palate or heart repair—increased the risks of long-term damage to young patients and resulted in intelligence deficits.
Given the risks, and the growing number of parents who expose their children to simple operations such as inserting ear tubes to prevent infections, you'd think clinical-trial researchers would have launched definitive studies by now to gauge the risks and tested different drug regimens to come up with the safest course. Unfortunately, it's not on the underfunded National Institutes of Health agenda. Nor has the drug industry taken up the challenge.
Most of the anesthetics are generics whose profit margins are thin. If the FDA demanded that generic manufacturers conduct trials to prove their drugs were safe for children, most companies would probably abandon production rather than absorb the costs.
The FDA has done all that it can with its limited resources and statutory authority. It pulled together a coalition of researchers under the auspices of the International Anesthesia Research Society to raise private funds for research. The group, dubbed SmartTots, has already listed its prospective clinical trial on the federal government's website.
But the group's efforts to raise the $10 million to $30 million needed to conduct properly designed trials have come up empty. “This is the kind of problem that doesn't fit easily into the NIH's existing research paradigm,” said Tom Cooper, executive director of SmartTots.
And their efforts to cajole the mainstream pharmaceutical industry, whose patents on anesthetics ran out long ago, to fund studies also have come to naught. “The question, either spoken or unspoken is, 'What's the business case for us?' ” Cooper told me. “There isn't one.”
The U.S. research establishment in the public and private sectors focuses most of its attention on coming up with miracle cures for major diseases such as cancer. Yet there are dozens of drugs, devices, tests and procedures deployed millions of times annually with inadequate evidence about their immediate or long-term safety profiles.
The potential to save lives, reduce harm and lower long-term healthcare costs by focusing more research dollars on such research questions is enormous.
Yet not much is heard in Washington these days about funding this orphan research agenda, as a commentary last week in JAMA described it. The 21st Century Cures Act, now hurtling through Congress with bipartisan support, will make it easier to bring new drugs and devices to market, no matter how little benefit they bring. It offers nothing for improving the technologies we already have.
One measure that could find its way into the bill is increased funding for the NIH, whose finances have been stagnant for nearly a decade (except for the one-time $10 billion shot included in the 2009 stimulus bill). Last week, former House Speaker Newt Gingrich wrote an op-ed in the New York Times calling for doubling the NIH's budget, which last happened when President Bill Clinton sat in the White House and the GOP Gingrich led controlled Congress.
But that's no panacea unless funds are earmarked for orphan research questions. NIH's research funding process isn't designed to solve clinical problems like the potential harm caused by anesthetic use in children. More than 80% of its budget goes for basic science research in universities, where scientists are looking for new pathways to treat diseases for which there are no cures. That admirable goal fits in nicely with the 21st Century Cures Act. But it won't help the kids.
Should the GOP-controlled Congress temporarily abandon its fixation on budget deficits and beef up the NIH's budget, it should earmark some of those funds for orphan research questions whose resolution could significantly improve the care we're already providing.
