The House on Friday is voting on a bill that seems unassailable on its face – the 21st Century Cures legislation promises to modernize medicine and speed the development of lifesaving treatments. Its supporters include Republicans, Democrats, medical organizations, and families with desperately ill children whose future birthdays depend on drugs that haven’t yet been invented.
But a vocal chorus of physicians and pharmaceutical industry watchdogs warn that the bill is full of stealth provisions that could actually put sick people in harm’s way, by speeding the development of treatments that are neither safe nor effective.
It’s not exactly easy to oppose a widely-supported bipartisan bill that is often referred to as just “Cures.” But opponents say the proposed law is full of flaws, starting with its name and its key premise: that bottlenecks in the regulatory process are a big reason we haven’t cured cancer, Alzheimer’s, and a panoply of rare diseases.
To drug companies and patient advocates, expedited access to drugs and devices might seem like a huge boon. But critics are worried that the law will relax America’s standards for evaluating new drugs and devices, which are approved based on careful review of evidence -- including rigorously designed clinical trials. The bill offers up a slew of new ways to evaluate drugs: for example, allowing antibiotics to be approved based on what would today be considered preliminary evidence -- animal and test tube studies and very small trials in people. New medical devices could be approved based on "case histories" -- potentially of just a handful of patients.
“The irony is calling this 21st Century Cures, when they’re talking about standards that were left behind in the 20th century, because they were found to not be good,” said Diana Zuckerman, president of the National Center for Health Research, a nonprofit, non-partisan think tank that does not accept money from drug or medical device companies.
Supporters, on the other hand, say the legislation upholds a gold standard of patient safety, was drafted in close consultation with the FDA, and will relieve burdensome bureaucratic requirements that slow innovation.
“The parts having to do with drugs and devices are intended to help modernize the drug development process. For example, there’s been a societal shift from the doctors telling you what you have… to the patient as a navigator,” said Janet Woodcock, the director of the Center for Drug Evaluation and Research at the FDA. “We need to reflect that shift and keep up with that in drug development.”
However, she noted that it is a common misconception that the approval process itself is slow. She said the time and expense of creating new drugs is in the development process, which takes years and has a high failure rate. Only two in every 10 drugs that are tested in people make it to the market.
“The underlying problem is actually a science problem about being able to develop drugs that are successful,” Woodcock said.
One part of the bill has near-universal support: increased funding for the National Institutes of Health, the main engine of basic biomedical research funding in the U.S. The bill calls for an additional $8.75 billion to be given to the NIH over 5 years and $550 million to the U.S. Food and Drug Administration.
A study published earlier this year in Health Affairs traced the origins of transformative drugs approved between 1984 and 2009 found that federal funding of basic research played an essential role in many of them; meanwhile, the fewest number of drugs originated completely within companies. Federal funding of basic research is seen as the surest path to new cures, although it takes years longer than anyone would like.
Other parts of the 352-page bill include changes to the regulatory process for new therapies and have been divisive.
“What we’re trying to do is trying to find ways to expedite the review and approval of drugs, particularly for diseases we haven't had treatments for," said Rep. Diana DeGette (D-Colo.), who is co-sponsoring the bill with Energy and Commerce Committee chairman Fred Upton (R-Mich.). "We don't want some layer of bureaucracy standing in the way of drug or device approval for diseases for which we haven’t had treatments, but at the same time we want to make sure we ensure the highest levels of safety and efficacy."
Margaret Anderson, director of FasterCures, a think-tank that helped to shape parts of the legislation said it was exciting to have Congress take on the problem.
Anderson noted that such bipartisan support for the bill is rare on Capitol Hill these days, and that the Republican and Democratic representatives behind the bill spent countless hours soliciting input from the medical industry, academics, patient groups and others with a stake in the legislation.
“This was not fly by night,” she said. “It was a very thoughtful, deliberative exercise.”
But critics question whether the bill as constructed can achieve its goal and question whether it might, instead, put vulnerable patients at risk.
“If there’s a shortfall in drug development, it is mostly because the companies have lost their verve in their ability to discover new drugs. You can’t legislate that away,” said Jerry Avorn, a professor of medicine at Harvard Medical School who published a critique of the bill in the New England Journal of Medicine. “Lowering FDA standards for approving drugs and antibiotics without evidence of clinical benefit -- I don’t think that’s going to help, but it could also harm patients. What we don’t need is more drugs approved based on lab tests instead of patient benefit.”
Here are a few of the provisions that have sparked debate:
-The bill would allow antibiotics to be approved based on laboratory and animal tests and small, early clinical trials.
Woodcock said that drug-resistant infections have reached the level of a “societal crisis” and that the bill would help spur the development of treatments for patients who might die of their infections otherwise. She said that the standards of efficacy remain the same, although the tolerance for uncertainty about the risks and benefits of a treatment increases when there are no other options.
But John Powers, an associate clinical professor of medicine at George Washington University School of Medicine and a former FDA scientist, said that such animal research and lab dish experiments often turn out not to predict what will happen in people.
“They are promoting a scientific standard we already know is erroneous,” Powers said. He cited doripenem and tigecycline, two antibiotics that performed well in lab tests, but have more recently been found to carry an increased risk of death compared with other drugs.
-The bill allows companies to seek expedited drug approval based on so-called “surrogate endpoints” -- early indicators that a drug is working, such as whether a tumor has stopped growing in cancer.
The FDA already uses these endpoints at its discretion to evaluate some drugs, especially in cancer and heart disease. But this has sometimes led to quick approval of drugs that don’t work or are harmful.
A study published last month in the journal JAMA Internal Medicine found that efforts to expedite cancer drug approval by using such criteria have resulted in the approval of many cancer drugs that do not extend life, but do have side effects.
“In our rush to find new effective treatments, we should not harm our patients with ineffective toxic ones,” Rita Redberg, editor of the journal, wrote in an accompanying note.
-The bill also threatens disclosure requirements that are intended to limit pharmaceutical companies' influence on physicians. The bill would allow physicians to receive speaking fees and gifts from companies without disclosing them, as long as they were for medical education.
Many patient and medical organizations have signed letters of support for the bill. The American Heart Association, for example, cheered the additional funding for NIH and FDA in its letter. But in an interview, the immediate past president of the organization said that it would pay close attention to the ways in which new kinds of data might be used to approve new therapies as the legislation evolves and as the bill shifts to the Senate.
“We have an established system by which we have approved medical therapies in the past. It is cumbersome and long, and anything we can do to shorten it is desirable,” said Elliott Antman, a cardiologist at Brigham and Women's Hospital. "But we would not wish to see erosion of the rigor by which approval has taken placed in the past in an attempt to accelerate the pace of innovation arriving at the doorstep of the patients."
In the long run, the central concern that drives the bill -- the idea that the onerous approval process stands in the way of new cures -- may be up for debate.
In March, previous FDA commissioner Margaret Hamburg told the Senate that FDA approved more drugs last year than in nearly two decades -- and did so faster than any other developed nation.
“No country is going to have first approval of every drug,” said David Kessler, who served as FDA commissioner under presidents George H.W. Bush and Bill Clinton. “[But] if you get sick anywhere in the world and you want to have access to a drug, the best place to be is the United States. FDA moves as fast as anyone … Almost all important drugs that exist are available in the United States.”
Staff Writer Brady Dennis contributed to this report.
This post has been updated.