A lot can happen in 18 months.
In July 2015, the House of Representatives passed the 21st Century Cures Act, which contained public science funding and numerous provisions aimed at adjusting how the Food and Drug Administration (FDA) evaluates new medical products and new indications for existing prescription drugs and devices. Early in 2016, a Senate committee approved several individual bills that addressed some of the issues targeted by the initial House bill, but did not consider the full package of changes.
Finally, on November 25, late Friday over a holiday weekend, Congressional leaders released an amended version of the 21st Century Cures Act. After some final tweaks, the legislation was expected to pass in the House on Wednesday, November 30th. It would then move on to the Senate for consideration. At 996 pages, the revised bill (without the final tweaks) is 90 pages longer than the Affordable Care Act (ACA) and over 600 pages longer than the original bill. More than 1,400 lobbyists have worked to shape the proposed legislation behind the scenes.
Whereas the original bill was lauded for providing National Institutes of Health (NIH) funding for the discovery of new medical advances, the current bill provides significantly less certainty in its support for prevention, research, and regulatory science. In 2017 and 2018, $500 million would be placed in a fund to help states combat the opioid epidemic. Over a 10-year period, $2.8 billion and $430 million would be placed in funds to support NIH research and FDA innovation, respectively. However, this funding would not be guaranteed; Congress would have to vote each year to actually make the money available as part of the appropriations process.
Additionally, most of the proposed NIH funding would come at the expense of cuts to the Prevention and Public Health Fund, which might otherwise vanish if the new Congress repeals the ACA next year.
Easier Pathways, Greater Risk
The current bill also retains some controversial provisions affecting how regulators evaluate certain types of medical products. Despite the insertion of clauses that purport to keep the FDA’s approval standards intact, these provisions could be interpreted to afford the Health and Human Services (HHS) Secretary considerable discretion in applying those standards. The Act, for example, would require the creation of a program to use “real-world evidence” in support of new indications for existing drugs. Defined as information on drug outcomes that are derived from sources other than clinical trials, real-world data are less likely to have been uniformly collected and therefore risk being less reliable. Attempted analysis of real world information is potentially further plagued by systematic differences between populations of interest that may not be captured and, thus, cannot be adequately controlled, which can distort the true benefits and risks of a drug.
Another concerning provision involves a new “limited population” approval pathway for antibiotics treating patients with unmet needs based on a sliding benefit-risk scale, factoring the severity, rarity, or prevalence of the infection to be treated and the availability of alternative therapies. Manufacturers would be required to affix disclaimers flagging this pathway in the drug’s labeling and to submit promotional materials to the FDA for inspection. But research has shown that consumers rarely read, let alone heed, health disclaimers, and the FDA has been increasingly hampered in its ability to regulate pharmaceutical promotion for unapproved or off-label uses.
Numerous sections in the current bill relate specifically to medical device regulation. For example, one section would formalize and expand an ongoing pilot program that entitles “breakthrough” high-risk medical devices to priority review, in which approvals could be made despite greater risk-benefit uncertainty. Yet, as defined in the current legislation, a device could be classified as a breakthrough even if its possible advantages are not “clinically meaningful.” Therefore, many new, high-risk devices would qualify for this pathway, and faster reviews of high-risk medical devices are associated with increased reports of safety problems after approval.
Such provisions will inevitably lead to widespread use of new and costly treatments before they are shown to work or before their risks to patients are adequately known. In many cases, government payers like Medicaid and Medicare would have no choice but to cover these treatments, while private insurers would be forced to play a more pronounced gate-keeping role.
Is It Worth It?
Of course, there are some positive provisions in this 996-page piece of legislation. The bill retains sections from the original legislation that would strengthen the FDA’s ability to hire, train, and retain experienced staff scientists needed to evaluate greater and increasingly complex data. It also adds a requirement for manufacturers to publicly disclose how, if at all, they may make experimental therapies accessible to patients with serious or life-threatening conditions who do not qualify for clinical trials. Such transparency could help physicians and patients learn about the all-too-rare cases in which manufacturers offer such expanded access programs.
Still, we believe the bill’s potential benefits and modestly enhanced funding for scientific advancement are far outweighed by the increased risk of patient harm, and added pressure on the FDA to rush new products to market without adequate evidence. The current 21st Century Cures Act would not drive innovation. Instead, it represents a poor deal for patients.