Proposed legislation “modernizing” the Food and Drug Administration's approach to approving breakthrough drugs and devices would undermine the agency's ability to protect the American public from unproven and possibly unsafe new products.
The so-called 21st Century Cures Act also contains sections that would hamstring healthcare providers and insurers in their efforts to lower the cost of care. Unless the legislation is sharply revised, it should be rejected by Congress or, if need be, vetoed by the president.
To gain bipartisan support, the drafters of the bill included more money for the National Institutes of Health and a new role for patient-reported outcomes. Those are laudable goals—especially the boost for basic science research, which is the foundation of innovation in medicine.
But there was no need to simultaneously degrade the scientific basis of new drug and device approvals; allow Congress to impose its own rules for what constitutes acceptable medical evidence; or weaken the standards for protecting human subjects in clinical trials—all of which is in the bill.
For no apparent reason, the legislation also imposes new disclosure requirements on hospitals and insurance companies when they create preferred drug lists or formularies, which enable substitution of lower-priced, comparable products. It also absolves the industry from having to disclose payments to doctors for attending continuing medical education run by a third party they've funded.
Those two provisions are not about coming up with new cures. They are designed to give drug and device companies more freedom to market the less effective and more expensive cures they already have.
But even if the bill were stripped of those extraneous provisions, providers and insurers have a huge stake in understanding how the regulatory standards included in this legislation would pose a grave threat to the government oversight process.
Since 1962, the FDA has required manufacturers to test their new products in randomized clinical trials comparing the actual clinical outcomes in two comparable groups, only one of which received the drug. Sometimes products that affect surrogate biomarkers such as high cholesterol or high blood pressure—neither of which is a disease—get approved. But they must conduct clinical trials that definitively show that a drug affecting those biomarkers leads to clinically meaningful outcomes, which in those cases means reducing heart attacks and strokes.
In place of that tried-and-true scientific method, Congress would substitute a new standard for drugs to treat life-threatening diseases such as cancer, where hope for new breakthroughs these days lies in targeting the tumors' mutated genes or their protein expressions. Those are biomarkers, and under the legislation, manufacturers could get accelerated approval from the FDA if the tested molecule had an effect on a biomarker that is “reasonably likely to predict clinical benefit.”
Do we really want a “reasonably likely” standard to determine if the healthcare system should pay $10,000 a month per patient for the next new cancer drug?
The bill also requires the FDA to create a pathway where manufacturers could submit “evidence from clinical experience”—observational trials, registries or case reports—to support expanded uses of already-approved drugs.
Devicemakers get a similarly easy path for a new “breakthrough” device designation. Instead of controlled trials, they could submit case histories, registry data or studies published in peer-reviewed journals. If they provide the latter, the FDA would have to submit a written request for the underlying data. If those data weren't available, the agency still would have to consider the study.
Patients volunteering for clinical trials will want to be on guard should the legislation pass. Waivers to the informed-consent requirement have always been allowed when it is not feasible to obtain consent. The bill would add another exception: when “the proposed clinical testing poses no more than minimal risk.”
Even if the risk is minimal, why would the authors of this legislation waive a central tenet of international agreements designed to protect the rights of human subjects in clinical trials?
In her final address last month as FDA commissioner, Dr. Margaret Hamburg wisely noted that “innovation doesn't matter if the product doesn't work ... It is foolish—in fact dangerous—to believe that reducing regulatory standards will make new treatment interventions appear if the science is not there.”
Rep. Fred Upton (R-Mich.) and Rep. Diana DeGette (D-Colo.), the bill's sponsors, should heed her warning. Back to the drawing board on the 21st Century Cures Act.
