Luke Versten received his B.S. in Biological Sciences from The University of Chicago and is currently pursuing an MPH in Epidemiology of Microbial Disease at Yale University.
Although ‘First, do no harm’ is a phrase traditionally recognized as part of the Hippocratic Oath historically avowed by physicians prior to beginning the practice of medicine, it may also be time to have our congressional representatives swear by the same principle.
The 21st Century Cures Act passed yesterday in the U.S. Senate by an overwhelming 94-5 vote. Although the sweeping bipartisan support for the bill is enough of a reason for alarm, a closer look into the details of the legislation reveals the shocking reality of its content. At first look, the bill’s inspiring name as well as its $4.8 billion provision for the National Institutes of Health over the next ten years gives the impression that this is a pro-research windfall for the scientific community, a group who in the weeks after the election considered future funding to be in jeopardy. In reality this funding is contingent on annual appropriation by Congress, largely from a $3.5 billion budget cut from the Prevention and Public Health Fund. Furthermore, the bill is also a boon for pharmaceutical companies, as industry lobbying has led to provisions that significantly loosen the standards for FDA approval of new antibiotics by allowing approval based on trials involving so-called “limited populations.”
Limited populations are in essence smaller groups of patients on which drugs will be tested, which directly translates into much weaker evidence than what can usually be expected of the larger, well-controlled phase three clinical trials required for drugs that treat serious infections. Because of the lower sample size, statistical power in determining efficacy is severely undermined. This means that potential issues with drug safety or efficacy across different age groups and other demographics may go undetected, and that antibiotics approved under these weaker guidelines could ultimately be used inappropriately in larger patient populations.
Case in point: Section 2123 of the act. This sub-heading of the legislation stipulates that hospitals receive payment for every time their patients are treated with antibiotics approved under new FDA guidelines as opposed to currently existing treatments. Perhaps such an incentive was purposefully included in the bill since pharmaceutical companies could reasonably expect physicians to be reluctant in having to use these less rigorously tested drugs on their patients. More worryingly, the dollar amount the hospital would receive in such a scenario is undisclosed.
These monetary incentives brazenly act as reassurance for the use of newer, less proven antibiotics in hospitals, an environment where antimicrobial resistance is already a dire issue. Legalized payment arrangements to hospitals which incentivize use of under-studied antibiotics as treatments could potentially push physicians and patients deeper in the quagmire of inappropriate use, and potentially contribute to an even greater number of drugs to which superbugs are resistant. Most of the ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacter species) responsible for clinical infections can only be treated with just one class of antibiotics each, if at all. As a result of their highly antibiotic resistant character, these superbugs deserve careful attention when developing safe, efficacious, and sustainable treatment protocols, a process that is currently under threat by the proposed legislation.
In light of the already substantial risk of infection faced as a result of antibiotic resistance (one that will plausibly continue to increase in the future), incoherent policies aiming to speed up drug development are not only impractical, but also scientifically and medically unjustifiable. We must remember that adequate and well-controlled trials do not make the study of new antibiotics infeasible, rather they strengthen evidence and minimize unnecessary risk to patients and ensure maximal therapeutic benefit. From the language of the legislation at hand, it is clear that provisions indulging the pharmaceutical industry are prioritized over ensuring delivery of proven safe and efficacious treatment to patients.
The compromises reached in this legislation are a step backward from the integrity and principles of the scientific method. Shirking proper FDA approval guidelines cannot be used as political bargaining chips in exchange for short term funding compromises. Given that the health of patients are at stake, any legislation aiming to amend FDA guidelines and approval procedures ought to exist as a distinct measure unconnected with NIH funding promises.
The principles that substantiate the authority of the medical and public health fields ought not stoop to the level of the political-industrial complex, and more responsible legislation is merited that would support research into treatments for human diseases. Biomedical research is not something to be fast-tracked for purposes of expediting products to market. The possible innovative therapies that are being championed by supporters of the 21st Century Cures Act are not helpful to patients if they don’t work, or worse, if they cause harm.