The 21st Century Cures Act Needs a Cure Itself

If only the 21^st Century Cures Act lived up to its name.  Since passed by the House of Representatives on July 10, the proposed Act has drawn criticism from drug policy experts writing in the New England Journal of Medicine, the Annals of Internal Medicine and most recently, the New York Times editorial page. The Times takes issue with a host of provisions, including this:

[The Act] would expedite the use of new antibiotics by providing financial incentives to hospitals to use them — benefiting manufacturers but also driving up costs and encouraging overuse, potentially breeding resistant superbugs.

I couldn’t agree more, for three reasons.  First, the impetus to grease the skids for antibiotic development and approval, also promoted by the Act, is predicated on the myth of an “empty pipeline” for antibiotics. News flash:  it isn’t empty.  As of December 2014, at least 37 new antibiotics were in advanced stages of development, at least 22 of them potentially effective against Gram-negative bacteria. Of the seven new antibiotics approved by the FDA in 2014, most target difficult-to-treat conditions. It is true that fewer antibiotics are entering the market than in the 1950s and 1960s—the golden age of antibiotics—but the same is true of many other drug classes. That alone is not evidence of a crisis.

Second, conservation of antibiotic effectiveness could go a long way toward dampening the frenzy for more antibiotics. The hundreds of antibiotics already on the market provide effective treatment for all but the most resistant infections. While we are seeing increasing rates of resistance in many instances, we’re also seeing resistance rates declining where antibiotic stewardship has taken hold most strongly—in the Nordic countries, for instance.  If we applied even a fraction of the new antibiotic R&D investment to stewardship and conservation, we could slow the loss of effectiveness dramatically. As the Times points out, the law does nothing to encourage conservation. In fact, it’s got the incentives going in the wrong direction.

Third, the Act proposes weakening the evidentiary standard for approval of new antibiotics, which has the potential for grievous harm to patients.  Regulations that define the terms of the Food, Drug and Cosmetics Act make clear that “valid scientific evidence” is needed to support the efficacy and safety of new drugs. What would be allowed under the 21^st Century Cures Act hearkens back to the early 20^th century, when laws and regulations were developed to avert the drug-related catastrophes that occurred in the absence of good evidence before drugs were marketed. Scott Podolsky and John Powers, writing in the Annals of Internal Medicine, give five relatively new antibiotics as examples of why the proposed evidentiary loosening is likely to be dangerous to patients.  In all five cases, antibiotics with nothing but positive evidence in the preclinical phases turned out to be deadly to some patients.  In the end, they were all approved only for a very limited list of conditions when no alternatives were available—much more limited than the developers had intended.

As Jerry Avorn and Aaron Kesselheim conclude in The New England Journal of Medicine:

Patients and physicians would not benefit from legislation that instead of catapulting us into the future, could actually bring back some of the problems we thought we had left behind in the 20th century.

I’m not against innovation and do not deny the continued need for some new safe and effective antibiotics. What I want to see is a balance between incentives for conservation and new antibiotic development. And better reading of the evidence guiding public policy than the flawed “empty pipeline” argument.  CDDEP will be setting out a more complete picture in its State of the World’s Antibiotics report, coming out in September 2015.