This is a very brief summary of the concerns of coalition members.
The purpose of federal regulations is to protect the U.S. public from harm by implementing reasonable safeguards. The purpose of U.S. public health agencies is to support scientifically sound research and protect the integrity of the scientific enterprise. Even our current regulatory oversight has failed to protect hundreds of thousands of patients from unsafe drugs and defective devices, as evidenced by the needless deaths linked to Vioxx and serious injuries from metal on metal hips. Voluntary safeguards are not sufficient, nor is reliance on public/private negotiations to develop research agendas or scientific research safeguards.
The American taxpayer is the customer for U.S. public health agencies, not private industry.
We are very concerned that the 21st Century Cures Discussion Draft focuses almost exclusively on speeding new medical products to market, largely ignoring whether those products are safe or effective, or more beneficial than products already proven safe and effective. It would drastically reduce patient safeguards that the U.S. Congress and the FDA have developed on the basis of decades of experiences such as the thalidomide tragedy of the 1960s, the AIDS crisis of the 1980s, the Vioxx recall of 2004, or the metal-on-metal hip recalls of 2011. Even more worrisome, the legislation would respond to 21st century challenges such as software platforms and social media by taking away the authority that the FDA already has, de-regulating devices that millions of Americans depend on and de-regulating industries direct-to-consumer advertising and promotional activities.
Many provisions in the 21st Century Cures discussion draft also would greatly weaken the regulatory authority of the FDA and the decision-making authority of the NIH, replacing unbiased scientific decision-making with micromanagement from Congress, placing private industry in the driver’s seat, and putting patients’ lives at risk.
Medical Devices
Despite recent high profile device-related health tragedies such as power morcellators, metal-on-metal hip implants, and surgical mesh, the safety or effectiveness of medical devices are hardly mentioned in the 21st Century Cures discussion draft. Patients want safe and effective devices cleared in a timely matter—not the fastest device out of the lab. Safety is not mentioned once in three device sections and is mentioned only twice in the large medical device reforms section.
Patients want to be able to trust that will improve their health or survival. The discussion draft would be less burdensome to device companies but would move that burden to patients and physicians. Neither patients nor their physicians would have confidence that new devices are safe or effective. Approximately 18% of moderate to high-risk devices are recalled under the current standards.[1] Lower standards are likely to result in more harm to patients. The proposed micromanagement of the already under-resourced Center for Devices and Radiological Health (CDRH) staff would create significant morale and resource problems, creating unnecessary burdens and potentially overruling scientific judgment for inappropriate reasons. This could lead to a mass exodus of the agency’s best scientific staff, and would make those remaining less able to meet the review deadlines imposed by FDASIA.
While improved communication between industry and the agency is a laudable goal, the inherent role of a regulatory agency is to be in charge and make decisions without undue pressure from Congress or the companies it regulates. Provisions in this discussion draft tip the balance in ways that would greatly weaken FDA’s authority and autonomy and require enormous additional resources at CDRH – resources that neither Congress nor the device industry has been willing to provide in appropriations or user fees.
Drugs
A key focus of the numerous provisions on drug approvals is to lower FDA approval standards by pushing for shorter and smaller clinical trials.
The provisions on biomarkers and surrogate endpoints dangerously undermine the authority of the FDA, essentially privatizing a crucial regulatory function. Surrogate markers – a laboratory value or event that is anticipated to predict a patient outcome – often do not reliably predict the impact of a drug on actual patients.[2],[3] By expanding the use of surrogate markers without adequate safeguards, it would put millions of patients at risk. By including industry experts in the evaluation of surrogate markers, and offering a new appeals process when an industry request for approval of a surrogate marker is denied, the provisions would waste FDA resources and greatly increase opportunities for bias stemming from financial conflicts of interest and political interference.
Although surrogate markers are intended to predict meaningful health outcomes, such as survival or improved health, many surrogate markers are poor predictors. Despite the well-known problems in accurately selecting effective surrogate endpoints, the draft bill proposes to use surrogate markers much more widely, without adequate safeguards. Drugs should not be approved based on preliminary data unless they are urgently needed, but the draft would pressure the FDA to do just that. The provisions on surrogate endpoints should be deleted in their entirety.
The provisions on breakthrough therapies encourages FDA to approve drugs that have not been tested in Phase 3 clinical trials, if the drugs are intended to treat serious or life-threatening diseases or conditions. This would not be limited to drugs that meet unmet needs. Approving a wide range of drugs on the basis of the more preliminary Phase 2 trials poses many risks to patients. Many drugs that are promising in Phase 2 trials are found to be unsafe or ineffective in Phase 3 trials. Once approved under the proposed new mechanism, however, the companies would be able to advertise and sell the product widely and have no incentive to conduct phase 3 studies in a timely manner. This would eviscerate the powers of the FDA to ensure the drugs we use are safe and effective, powers granted after the thalidomide disasters of the early 1960s. Accelerated approval mechanisms already exist to achieve the goals in this section of the bill, and compassionate use mechanisms make experimental drugs and devices available to patients.
Since the FDA does not control the practice of medicine, and since this legislation would make it easier for drug companies to advertise new drugs for unproven treatments, this provision would put millions of patients in danger. This section needs to be greatly revised or deleted to preserve the balance between speed and safety.
The bill’s provisions to encourage smaller clinical trials to expedite approval directly contradicts the provisions in FDASIA aimed at increasing the number of women, people of color, and adults over 60 in clinical trials. Smaller clinical trials would make it impossible to conduct subgroup analyses to determine if a new medical product is safe or effective for women, men, people of color, and older adults.
Instead the bill would push the requirements of proving that a drug (or device) is safe or effective from the approval application to studies that are required after the product is approved. Unfortunately, research shows that such unproven drugs are likely to be sold to patients for a decade or longer before those post-market studies are completed.[4],[5] Moreover, despite requirements to do so, post-approval studies often fail to include the diverse populations that the company promises to study; companies have no incentive to ensure diversity once their drug/device has already been approved for the general population.
Antibiotic Resistance
The proposed Antibiotic Drug Development legislation purports to solve the problem of antibiotic resistance but would fail to do so. It contains so many loopholes and insufficient safeguards to protect patients or to protect the efficacy of new or existing antibiotics by reducing overuse. The newly introduced HEAL Act (H.R. 931) would be a much more effective strategy to encourage antibiotic drug development targeted to the patients who most need new antibiotics.
Conflicts of Interest
The discussion draft creates many advisory committees, working groups and other structures that do not adequately restrict the participation of members who have significant financial ties to industries that will benefit from relaxed regulations.
Advertising in Social Media
This draft would enable companies to promote their drugs and devices without informing the audience about the product’s risks. This would mislead patients and providers and would be dangerous for many patients.
References
- Zuckerman D.M., Brown P., Nissen S.E. (2011). In Reply, Archives of Internal Medicine, 171, 1045.
- Khana, R. (Aug. 26, 2014). “Surrogate Outcomes: That’s Not Why We Play the Game,” Journal of American Medicine Internal Medicine Blog, 26 Aug. 2014. http://internalmedicineblog.jamainternalmed.com/2014/08/26/surrogate-outcomes-thats-not-why-we-play-the-game/
- Fleming T.R., Demets DL (Oct. 1, 1996). Surrogate end points in clinical trials: Are we being misled? Ann Intern Med 125(7):605-13. http://www.ncbi.nlm.nih.gov/pubmed/8815760
- Carpenter, D. Reputation and power: organizational image and pharmaceutical regulation at the FDA. Princeton University Press, 2014: 609
- Fain, K., Daubresse, M., and Alexander, G. C. The food and drug administration amendments act and postmarketing commitments. JAMA 310, no. 2 (2013): 202-204