In mid-January, Representatives Fred Upton (R/MI) and Diana DeGette (D/CO) previewed their goals for the 21st Century Cures initiative.
The bipartisan duo wanted to “modernize clinical trials to streamline the approval of drugs and devices,” in part by reducing paperwork and promoting adaptive trials, help FDA “better integrate the patient perspective into the regulatory process,” including using public-private partnerships to strengthen science around biomarkers and patient-reported outcomes, promote “better access to and sharing of information such as genomic and other clinical data to foster more collaboration among researchers,” and to invest in programs for young scientists.
Upton—the chair of the U.S. House’s Energy & Commerce Committee—and DeGette also planned to “incentivize new drugs and devices for unmet medical needs” by “streamlining the premarket process while establishing mechanisms to better capture real-world evidence post-market.” They also said they will examine incentives, including “exclusivity or simplifying the reimbursement process,” to stimulate the development of new drugs and devices for unmet medical needs.
Two weeks later the committee released a discussion draft and a Discussion Document without support from Democrats. According to DeGette, “While I don’t endorse the draft document, I know that with continued engagement, we can reach a bipartisan consensus to help advance biomedical research and cures.”
Representative Frank Pallone, Jr. (D/NJ), the ranking Democrat on the Energy & Commerce Committee was more pointed in his criticism. Pallone is “disappointed that the discussion document released today by Chairman Upton does not reflect true bipartisan collaboration.” Pallone added that the “nearly 400 page draft could create more problems for our healthcare system than it solves.” While he did not cite any specific concerns, (did he even read the report?) he did note that the draft “does not include any real dollars to fund additional basic research at the National Institutes of Health.” Was Senator Warren whispering in his ear?
Some provisions in the discussion draft are likely to be sticking points for Democrats, including proposals to exert more centralized control over NIH funding decisions by setting fixed, renewable four-year terms for institute directors, and making directors personally responsible for ensuring that the goals of every grant award are consistent with “a national priority and have public support.”
Proposed FDA Changes
FDA is likely to oppose scores of provisions in the discussion draft that would impose new mandates but do not provide additional funding. For example, the draft would require FDA and HHS to produce about 35 draft or final guidance documents, most of them on tight deadlines. The committee left placeholders in the draft for several topics that are potential political flash points, such as communication about off-label uses of approved products and regulation of diagnostics.
The draft includes a provision allowing FDA to approve a drug with breakthrough designation on the basis of a single Phase II study, contingent on postmarket clinical trials and/or data from observational studies and registries. FDA could withdraw breakthrough approvals if sponsors failed to provide the required data, if evidence emerged showing the drug was not safe or effective, or if the sponsor disseminated false or misleading promotional material. The committee included provisions creating tight deadlines for FDA to assess applications for qualification of biomarkers and other surrogate endpoints.
The draft also attempts to extend and formalize FDA’s efforts to incorporate patient experiences and preferences into regulatory decisions, including using patient data in structured benefit-risk assessments. In other words, it’s time to move from a patient-centered drug development initiative to a patient-driven drug development program.
The draft also incorporates legislation on compassionate access introduced by Michael McCaul (R-TX), as well as the Modernizing Our Drug & Diagnostics Evaluation and Regulatory Network (MODDERN) Cures. The discussion draft has several provisions intended to make CMS decision-making more transparent and consistent, including a process for device and drug sponsors to appeal coverage decisions.
Accelerating Innovation Through Failure
Title IV of the draft legislation calls for “Accelerating the Discovery, Development, and Delivery Cycle and Continuing 21st Century Innovation at NIH, FDA, CDC, and CMS.” Bravo. Upton and his team at E&C understand that innovation is an eco-system. And that’s precisely what 21st Century Cures is all about, creating a sustainable innovation eco-system with government players as an integral part.
One way FDA can help is to assist innovators to fail faster. Killing clinical programs earlier in the development process can save billions that can then be more fruitfully reinvested. When Thomas Edison was asked why he was so successful, he responded, “Because I fail so much faster than everyone else.” Consider the implications if FDA could help companies to fail faster. The following figures are illuminating:
- A 10% improvement in predicting failure before clinical trials could save $100 million in development costs.
- Shifting 5% of clinical failures from Phase III to Phase I reduces out-of-pocket costs by $15 to $20 million.
- Shifting failures from Phase II to Phase I would reduce out-of-pocket costs by $12 to $21 million.
One way to achieve this is for the FDA to finalize and formalize a risk/benefit grid, so that the factors behind regulatory decisions can be better understood—and future ones become more predictable. The EMA does this very successfully. Not having such a regulatory tool gives the FDA the Power of Ambiguity. But predictability is power in pursuit of the public health. Ambiguity also weighs heavily on the soul of those making investment decisions in riskier R&D propositions.
Since FDA, NIH, CDC and CMS all fall under the purview of the Department of Health & Human Services, perhaps the 21st Century Cures legislation should be more directive relative to the co-ordination of government efforts.
How about a 21st Century Cures Czar?