Congressional approval of a massive bipartisan bill that will infuse money for the National Institutes of Health, opioid addiction treatment, and cancer research is being hailed by advocates for antibiotic research.
The 21st Century Cures Act, which was passed today by the US Senate, is a 996-page collection of several bills that, among other things, contains several provisions that will change the way the Food and Drug Administration (FDA) evaluates new drugs and medical devices. Among those provisions is a section that establishes a new FDA "limited population approval pathway" for antimicrobials that treat serious or life-threatening infections for which there are unmet medical needs.
After being approved overwhelmingly by the House of Representatives last week, the bill passed the Senate by a vote of 94-5 and is now on its way to President Obama, who is expected to sign it.
Bill allows for smaller clinical trials
Advocates say the limited population approval pathway will help spur development of new antibiotics for serious, multidrug infections by allowing for smaller clinical trials than would be ordinarily required by the FDA, while including safeguards to ensure the new drugs are used safely. Typically, the number of patients affected by multidrug-resistant infections is small, which makes it difficult to identify and enroll enough participants to conduct the large-scale clinical trials necessary for the approval of new drugs.
"It will allow studies to occur that would not have previously been able to occur, and it will allow them to occur more rapidly, because they'll be smaller studies," Amanda Jezek, vice president for public policy and government relations at the Infectious Diseases Society of America (IDSA), told CIDRAP News. "That will help speed drugs to market."
IDSA and other infectious disease groups, including the Society for Healthcare Epidemiology of America, have supported the legislation.
Under the new changes, drug manufacturers will be required to include disclaimers on drug labels stating that the newly approved antibiotics are specifically for a limited population of patients with serious drug-resistant infections. They'll also have to submit promotional materials to the FDA for approval. These requirements are intended to prevent the new antibiotics from being misused, which Jezek says will aid stewardship efforts.
"It will be much more difficult to overuse these antibiotics in the way that traditional antibiotics are overused," Jezek says.
Another provision in the Cures Act will enable faster updating of antimicrobial susceptibility interpretive criteria, commonly referred to as breakpoints. These breakpoints are used for the development of the antimicrobial susceptibility tests that help doctors figure out the best antibiotic treatment for their patients.
Currently, the process of updating breakpoints is lengthy and very labor-intensive. Jezek says the provision will allow the FDA to review and use susceptibility work that has been conducted by other standard-setting organizations (such as the Clinical and Laboratory Standards Institute), which will help the agency update breakpoints more rapidly.
"This will aid in choosing the right drugs for patients and will help reduce inappropriate use that can lead to resistance," Allan Coukell, senior director of health programs at the Pew Charitable Trusts, said in a statement today. Pew's antibiotic resistance project supports policies to spur the creation of new antibiotics and establish stewardship programs.
Critics warn against lowering FDA bar
The legislation is not without its critics, however. In particular, some have argued that the limited population approval pathway and certain other provisions of the bill—such as allowing drug makers to submit "real-world evidence" in support of new indications for existing drugs—will compromise the FDA's drug and medical device approval process and undermine the agency's ability to ensure that new medical products are truly safe and effective.
"Permanently weakening the U.S. Food and Drug Administration in exchange for tenuous promises of increased NIH funding is a bad deal for patients," Michael Carome, MD, director of the Health Research Group for watchdog organization Public Citizen, said in a press release.
Sen. Elizabeth Warren, D-Mass., and other Senate Democrats also voiced strong opposition to the deal, arguing that the funding it provides for the National Institutes of Health and the opioid crisis isn't enough and relies on approval from future Congresses.
"This final deal has only a tiny fig leaf of funding for NIH and for the opioid crisis," Warren said in a floor speech. "And most of that fig leaf isn't even real."
Jezek said that she couldn't comment on elements of the bill that weren't related to antibiotics, but she disputed the notion that the limited population pathway for new antibiotics was in any way undermining the FDA.
"We view this as giving the FDA more tools," Jezek said. "The tools that it needs to consider and hopefully approve the kinds of antibiotics that we need in this era of multidrug-resistant organisms."
Jezek added that while some might argue that smaller clinical trials will produce more limited data and make these limited population antibiotics inherently riskier, IDSA feels the bigger risk is preventing the approval of antibiotics that are desperately needed.
"That's the risk that is unacceptable," Jezek said.
Text of the 21st Century Cures Act
Dec 7 Pew Charitable Trusts press release
Nov 30 Public Citizen press release
Nov 28 text of Elizabeth Warren floor speech