House Republicans are promoting a broad new bill supported by drugmakers and medical-device manufacturers that they say would make promising medications and devices available to the public faster and significantly reduce the costs associated with product development.
But critics, including the recently departed commissioner of the Food and Drug Administration, say the 21st Century Cures Act could heighten the risk of patients being exposed to inadequately tested and potentially harmful products while increasing healthcare spending on high-cost drugs and products of marginal value. In addition, it would let manufacturers apply for longer market exclusivity, thus giving them more protection from generic competition and potentially boosting healthcare costs.
Before stepping down as FDA commissioner last month, Dr. Margaret Hamburg called the legislative effort to speed up the drug development process “a terrible mistake” that could harm patients and drugmakers.
In an interview with Modern Healthcare Wednesday, Hamburg challenged the idea that mandating shorter review times will make promising products available to patients more quickly. "Shortening review times is not going to create the scientific understanding and the research and development that needs to be done to translate exciting opportunities in science into new products," she said. “That is the wrong mechanism to achieve that goal.”
Hamburg said she was enthusiastic about Congress' efforts to establish a strong national strategy for the advancement of biomedical product innovation. But she warned that any legislation should focus on what she called “real barriers to progress” and should not try to fix “perceived problems” that are not actually getting in the way.
The Pharmaceutical Research and Manufacturers of America and the Advanced Medical Technology Association strongly support the bill. JC Scott, senior executive vice president of government affairs for AdvaMed, called it a major opportunity to address inefficiencies involved in the FDA review process. Some of the proposals in the bill, he said, would make review of medical devices more efficient and less cumbersome, reducing the cost to bring a product to market.
A 2010 industry study estimated it cost companies an average of $24 million in FDA-related activities to bring a low- to moderate-risk medical device from concept to market, while it took around $75 million to take higher-risk devices through the agency's regulatory process.
“We often talk about improving the regulatory review process, but it's not always about making it faster,” Scott said. “It's also about making it more efficient and predictable for companies to go through that process.”
Debate over the bill comes as elected officials around the country are facing growing pressure from desperate patients and their families to make new medical products more quickly available on a compassionate-use basis. Nearly a dozen states have passed so-called “right to try” laws that allow terminally ill patients to seek an experimental drug without going through the FDA's compassionate-use process.
The rationale for the laws—which are being pushed by the conservative advocacy group the Goldwater Institute—is that the FDA's program is too slow to make potentially lifesaving drugs accessible. Critics say such laws have no practical impact that would help patients get quicker access to unapproved therapies since manufacturers are not required to make their products available. Companies may fear that making products for compassionate use could undermine their clinical testing process and jeopardize FDA approval.
In January, House Energy and Commerce Committee Chairman Fred Upton (R-Mich.) released a 393-page draft of the proposed legislation (PDF). The bill initially had bipartisan support, but House Democrats have turned against it citing concerns that it would weaken regulation of medical product development and potentially put the public at risk.
“I am disappointed that the discussion document released … by Chairman Upton does not reflect true bipartisan collaboration,” said Rep. Frank Pallone Jr. of New Jersey, the ranking Democrat on the committee, in a written statement. He said the bill in its current form “could create more problems for our healthcare system than it solves.”
Vijay Das, a healthcare advocate at the consumer advocacy organization Public Citizen, in Washington D.C., said many Democratic lawmakers see the bill in its current form as too “deregulatory,” catering to the interests of the drug and device industries.
A key provision of the bill would change the FDA's current “breakthrough therapy designation,” a program that began as part of the 2012 FDA Safety and Innovation Act. That law allows the agency to identify drugs whose early clinical evidence shows they may be a significant improvement over current treatments for a serious or life-threatening disease or condition in order to help speed up their review.
Under the 21st Century Cures Act, the FDA could grant market approval to a drug with breakthrough designation based on its early-stage testing for safety and effectiveness. After starting to market the drug, the drug's manufacturer would be required to conduct clinical trials to demonstrate safety and effectiveness. Medical-device makers also would be able to apply for breakthrough designation for products that treat conditions where no alternative exist, or that significantly improve on currently approved therapies.
The bill also would require the FDA to create a new regulatory pathway for antibacterial medications that would allow for faster approval of such drugs by limiting their initial use to specific populations with severe conditions where current therapies have been ineffective. Other provisions of the bill would put new requirements on the FDA to shorten the length of time it traditionally takes to approve a new drug or medical device.
Though experts say these provisions would help accelerate the review of new drugs, critics express concern that such measures would limit clinical testing of new therapies before they entered the market. That increases safety risks to the public.
“The more you speed the process up at the beginning stages—Phase 1 and 2—the more I think you have to toughen up at Phase 4 when things are out in the world and you're trying to see what's going on,” said Arthur Caplan, a bioethicist at NYU Langone Medical Center. But, he said, “I don't think the FDA is talking about really making Phase 4 tougher.”
Under the FDA's clinical trial process, products in Phase 4 testing already have been granted market approval but remain under FDA review for potential safety risks.
Hamburg said placing additional requirements on the FDA in terms of its oversight responsibilities will increase the demands on an already overstretched FDA staff, hampering the review process. “Let's really focus on what's going to make a real meaningful, measurable difference in terms of what needs to be done and focus on those activities,” she said.
Among the more popular measures of the bill is a requirement for the FDA to incorporate patient-reported outcome data within its review process to assess a drug's benefits and its tolerable risks. The bill also calls for additional funding for the National Institutes of Health, although it does not specify any level of funding. In addition, it would expedite the review process for vaccines.
Gregory Daniel, managing director for evidence development and innovation at the Brookings Institution's Center for Health Policy, said he supports some parts of the bill but that it needs more detail, particularly on funding levels to make these reforms possible. “All of this together seems to be going in the right direction toward ensuring that patients have the opportunity to receive really important therapies that address unmet need as quickly as possible,” he said.
Caplan said the bill offers some ways to speed up the regulatory process that “made sense.” One is the broader use of surrogate endpoints, which the agency already uses to predict the likely clinical outcome of a treatment earlier in its review process without spending the years or decades it could take to observe the actual patient outcomes.
Though useful, Caplan warned surrogate endpoints cannot fully predict the long-term risks of a drug. “There's just no way that you can use substitute endpoints and not create more risk for people down the road,” he said. “It's just not as reliable. You get speed, and that's good. But you up the risk.”
Other parts of the 21st Century Cures bill are more controversial. One is a provision intended to improve the FDA's “compassionate use” program that allows access to experimental medications to terminally ill patients on a case-by-case basis. Under the bill, drug companies seeking faster approval of an experimental therapy would be required to make their policies concerning access to those therapies for compassionate use public. That would include an explanation of their application process and notification to patients if their request has been denied and why. The provision appears to be a response to the growing number of “right to try” laws.
Caplan noted, however, that the 21st Century Cures Act would not require a manufacturer to make an experimental therapy available for compassionate use. Rather, the company simply has to establish a compassionate-use policy. “It looks like it's tough in terms of saying you need a policy, but the policy could be that a company simply doesn't do it,” he said.
The legislation also would offer incentives for drugmakers to develop innovative therapies by extending by several years the length of time their products would have market exclusivity. Manufacturers would be able to apply for up to 15 years of patent protection for a product if it was intended to treat “one or more unmet need.” Currently new biologic drugs can receive the maximum of 12 years of market exclusivity, with five years for new chemical drugs and seven years for orphan drugs.
Allowing longer market exclusivity for such a broadly defined category of products raises the possibility that most new drugs would qualify. That could drive up drug spending. Caplan said granting longer market exclusivity would make it “tougher to maintain cost containment.”
It could make consumers and payers wait longer before getting access to cheaper generic alternatives. Some experts say the extended market exclusivity period proposed under the bill could make it even more difficult for patients to afford high-cost drugs such as Gilead Sciences' hepatitis C drug, Sovaldi.
But Daniel of the Brookings Institution said market exclusivity in areas of unmet need might offer needed investment incentives. And the bill's other proposed reforms would “facilitate smaller, faster, smarter clinical trials that get these potentially curative, higher-cost medications on the market quicker, and that will force a lot of new ways of thinking about value.” He said the healthcare system should be looking not at the sticker price of a drug but “at what value can that particular therapy bring to treating a patient.”
Former FDA Commissioner Hamburg said financial incentives play an important role in drug development but the issue needs more analysis to determine what types of incentives are the most effective and do the most public good.
"What we really need is to make sure that all of the components of the ecosystem are aligned so that we can build the science, have a streamlined efficient research and development plan, and move the opportunities in science as quickly as possible into products that will make a difference for patients and consumers while adhering to strong established standards for safety and efficacy,” she said.