NIH Refuses to March In—Again—And National Academies Challenge Human Subjects Regulation

The last few days have seen two significant news items from Washington. First, the National Institutes of Health have refused—yet again—to exercise their “march-in” rights to grant third-party licenses to a patented drug developed with federal funding. The drug in question is enzalutamide, a prostate cancer treatment marketed under the brand name Xtandi by Japanese pharmaceutical company Astellas Pharma. Xtandi was derived from federally supported research at UCLA. Under such circumstances, NIH has the statutory authority to grant a license to a third party if the grantee or its assignee “has not taken, or is not expected to take within a reasonable time effective steps to achieve practical application of the subject invention.” “Practical application” means that that the invention must be “available to the public on reasonable terms.”

In their January 14, 2016 petition to NIH, two non-profits, Knowledge Ecology International and Union for Affordable Cancer Treatment, argued principally that Xtandi, at more than $100,000 per year, is too expensive. In a brief and dismissive response dated June 20, 2016 and signed by Director Francis Collins, NIH said that the petition “provides no information and no information was identified from public sources to suggest that enzalutamide is currently or will be in short supply.” To reduce the conflict to its simplest terms, both letters cited the same statutory provisions, but whereas the petitioners focused on the phrase reasonable terms, NIH emphasized the word available. Both parties are literally right, of course: there seems to be no shortage of enzalutamide, but is $100,000 a year reasonable?

NIH’s refusal to march in is yet another in an unbroken string—the agency has never done so. More than five years ago, I reported on NIH’s rejection of a petition concerning the biologic drug Fabrazyme submitted by patients suffering from Fabry disease, a rare and potentially fatal genetic condition. That seemed an especially compelling situation for marching in: the drug was the only one licensed in the United States, and the lone manufacturer had been shut down because of contamination concerns. In the conclusion of that report, I asked, “Will the NIH ever march in?” The strong presumption remains “no.”

The second significant development is that on June 29, 2016, the National Academies of Sciences, Engineering, and Medicine issued a report on federal research regulation entitled Optimizing the Nation’s Investment in Academic Research: A New Framework for the 21st Century. The report argues that “continuing expansion of federal regulations on research is diminishing the effectiveness of the U.S. research enterprise” and proposes several reforms at both general and specific levels. It recommends “that Congress authorize and the president appoint an independent national commission to examine and update the ethical, legal, and institutional frameworks governing research involving human subjects.”

Cooperation between Congress and the president may be in the when-pigs-fly-and-the-Iranian-moderates-come-to-power category (see the dispiriting impasse over anti-Zika funding), but one specific recommendation in the report may get some immediate attention. In September 2015, the U.S. Department of Health and Human Services issued a Notice of Proposed Rulemaking (NPRM) in an effort to revise and update the Common Rule, which governs the treatment of human subjects in all federally funded research. (Contrast this proposed rulemaking with “governance-by-guidance,” the subject of a recent post.) After an extended period of public notice and comment, the new rule had been widely expected to be issued in September of this year. Among the most controversial of its provisions is the expansion of the definition of regulated “human subjects research” to include research using anonymous or deidentified human biospecimens. The National Academies report criticizes this expansion—with startling bluntness–and urges that the NPRM be withdrawn. The NPRM initiative is entirely within the control of HHS, so this could happen, even though it would mean overcoming massive administrative inertia. But when one of the country’s most prestigious scientific bodies says unambiguously that something is a bad idea, even the federal bureaucracy might pay attention.