Published On February 17, 2016
IN JULY 2015, the United States House of Representatives approved the 21st Century Cures Act with broad bipartisan support. The legislation, which aims to “save more lives and keep this country the leader in medical innovation,” provides $8.75 billion in funding for the National Institutes of Health and accelerates approval processes for drugs and medical devices. But as the bill heads to the Senate for approval, critics argue that pharmaceutical and biotechnology interest groups will benefit at the expense of patient safety.
Yes. The act will allow the FDA to approve effective drugs and devices faster while maintaining high safety standards, says Peter Pitts, a former FDA associate commissioner and president of the Center for Medicine in the Public Interest.
Where you stand depends on where you sit. If you’re a patient with a life-threatening disease, the FDA is often viewed as a roadblock to innovation. If you’ve suffered a serious side effect of an FDA-approved medicine or device, you may view the process as too swift and cavalier. Both positions fail to take into account a basic truth—there is no such thing as a drug or medical device that is 100% safe.
FDA review is based on a benefit/risk balance. What’s new is that the patient’s voice is now being considered in that calculation. And it’s about time. The FDA has also recognized the urgency of a more comprehensive, strategic program for tracking performance once a product is on the market. A focused, more risk-based approach provides important balance to sophisticated cutting-edge scientific techniques, particularly as we move toward a more aggressive effort to validate biomarkers, that now make it possible to truncate the traditional clinical trial process. Shorter review cycles on the front end are being matched with more rigorous, real-time post-market surveillance.
The draft legislation will allow the FDA to approve a groundbreaking drug if it proves effective after a phase II trial. That will deliver treatments to patients much sooner and eliminate the need for some phase III trials, which take years and account for 90% of the total development costs for drugs that eventually gain FDA approval. The 21st Century Cures Act will also spur new drug development by helping innovators to “fail faster” through earlier and more regular meetings in the review process. Identifying even 5% of eventual failures in phase I instead of phase III will save at least $15 million per drug—allowing drug companies to redirect billions toward promising new treatments.
Victory will result in the FDA bringing new products to market both more quickly and with more information about their safety. Initiatives such as 21st Century Cures will transform the FDA from a perceived roadblock to an innovation enabler.
No, because the act will lower the bar for approval of certain therapeutics, says Ameet Sarpatwari, assistant director of the Program on Regulation, Therapeutics and Law, in the Division of Pharmacoepidemiology and Pharmacoeconomics at Brigham and Women’s Hospital.
Two sets of provisions are particularly alarming. The first concerns medical devices. The act would prompt the FDA to treat case histories and peer-reviewed studies as valid scientific evidence and would also loosen regulations controlling the safety and effectiveness of alterations to the devices that take place after their initial approval. The creation of a novel pathway would also enable FDA approval of high-risk medical devices on the basis of “clinically significant” surrogate measures, such as their effect on a biomarker, and would also require the agency to complete its review within six months.
Each of these changes could open the door to patient harm. Making approval decisions based on scant data increases the risk of adverse events once a device is widely used, and many surrogate measures have proved to be poor predictors of actual clinical outcomes. Case histories and peer review, meanwhile, are plagued by quality concerns. Additionally, even small changes to medical devices can prove deadly, as several high-profile recent cases can attest. It is better if such changes are reviewed by the FDA, rather than by the company itself or a third party paid by the company.
The second set of provisions involves antimicrobials. To combat the growing threat of multidrug resistance, the act would also authorize the FDA to approve certain antibiotics and antifungals on the basis of preliminary, uncontrolled clinical trials as long as those medications carry a disclaimer that explains their “indicated use in specific populations of patients.” However, evidence suggests that disclaimers on drug labels are inconsistently read, let alone heeded.
These measures collectively represent a fundamentally flawed attempt to promote medical innovation. They would lower the bar for therapeutic approval in several respects, threatening to take us back in time to the patent medicines era in which unsafe and ineffective products flooded the market. The Senate would be wise to start anew in determining what, if any, changes to the regulatory apparatus are necessary as prescription drug and device development expands in the 21st century.