Division of Dockets Management (HFA-305)
Food and Drug Administration
5630 Fishers Lane, Rm. 1061
Rockville, MD 20852
Comments of the National Center for Health Research on
PDUFA VI Commitment Letter
[Docket No. FDA-2016-N-1895]
The National Center for Health Research respects the Food and Drug Administration (FDA) and we’re committed to ensuring that it has the resources it needs to keep our medical products safe. Given the inadequate appropriations provided to the FDA, we strongly support increasing user fees to improve FDA’s resources in order to enable the agency to fulfill its public health mission.
We are disappointed that the focus of the FDA’s commitment letter is on speed. The commitment letter states that “PDUFA’s intent is to provide additional revenues” so the FDA can make medicines available to patients “sooner without compromising review quality or FDA’s high standards for safety, efficacy, and quality.”[1] We believe that user fees should be used to improve the safety and efficacy of approved drugs, not just the speed of approval. PDUFA focuses too much on speeding new drugs to the market and not enough on safety issues. In the 46-page PDUFA VI commitment letter, only two pages are devoted to the FDA drug safety system.
In PDUFA V, we supported earlier and increased meetings between FDA and drug companies during the drug approval process. PDUFA VI calls for even more meetings. The result is that the percentage of drugs that the FDA is approving is higher than ever. But that isn’t necessarily a good result, because numerous recent studies have shown that too many of these drugs are not effective. It seems likely that these meetings result in pressure on FDA staff to approve products based on inadequate scientific evidence, just because the agency has invested so much staff time in the review process.
FDA’s primary mission is “protecting the public health by assuring the safety, efficacy and security” of medical products.[2] User fees should fund an independent review of how the program has affected overall public health. Have user fees changed FDA’s priorities? Is FDA now treating industry as a customer that it needs to please, instead of acting as a regulator to ensure the public health? Independent researchers suggest that user fees are harming, not helping, the FDA’s public health mission.[3], [4] That must change.
Regarding the Sentinel program, we agree it deserves additional funding. However, we urge FDA to make Sentinel databases available to independent researchers so other stakeholders can perform their own assessments of drug safety. One option FDA should consider is to ensure that the Reagan-Udall Foundation’s Innovation in Medical Evidence Development and Surveillance (IMEDS) program has the resources to provide access to these databases to independent researchers at low or no cost. This is essential because FDA is approving more and more drugs through expedited approval pathways, based on surrogate endpoints and other preliminary evidence. In addition, the smaller, shorter-term studies typical of expedited pathways provide completely inadequate evidence of safety, since uncommon and long-term risks are unlikely to be evident.
Although the FDA does not directly influence the price of drugs, they are indirectly contributing to skyrocketing costs of drugs by approving products that have little if any benefit. For example, a recent analysis indicated that the average yearly cost per patient for the 100 top selling orphan drugs was nearly $112,000 compared to $23,000 for non-orphan drugs.[5] One chilling example is when Keveyis was classified as orphan drugs and the price went from $50 a bottle to $13,650 a bottle.5
Another example is Cabometyx, which the FDA approved for thyroid cancer based on preliminary data. Subsequent research indicates it is no better than placebo for thyroid cancer. And yet our Center has learned that it costs $169,000 per year per patient and FDA has not rescinded approval for that indication.
PDUFA VI emphasizes a flexible approach to approving orphan drugs, based on biomarkers and other research designs and endpoints that may show promising results that are ultimately found to be nothing but false hope. These faster, less thorough reviews will cost patients and taxpayers billions of dollars but many will later be found to offer risks that far outweigh the benefits. The FDA needs to find a way to prevent that from happening and when it does happen, FDA needs to have access to user fee funds to rescind approval very quickly.
PDUFA VI should provide funding to monitor off-label uses of drugs. Although physicians may use their own judgment to prescribe drugs off-label, drugs used in this manner have less information about the benefits and harms for the condition for which they are prescribed. A JAMA Internal Medicine article stated that, “researchers found a 54% increase in adverse events when drugs were prescribed for off-label uses. The risk was highest for patients taking more than one drug, which includes most Medicare patients.”[6] With PDUFA funding, FDA could identify the top drugs prescribed off-label and target them for increased postmarket surveillance to better protect the public health. User fees should also be used to fund the development and implementation of informed consent procedures for drugs used off-label. Doctors should be required to tell patients and their families about contraindications and other warnings as part of the informed consent process when drugs are used off-label.
Given growing evidence that off label uses have many risks, PDUFA funds should be used to help monitor direct-to-consumer ads. In 2015, PhRMA spent $5.4 billion on direct-to-consumer (DTC) ads, and in that same year Americans spent a record $457 billion on prescription drugs. There is a need to carefully review all ads to reduce the misuse of prescription drugs. In the past, drug makers have advertised atypical antipsychotic drugs as if they were antidepressant drugs. Despite misleading ads that confuse patients, some of which are still on TV today, the FDA did nothing about it. PDUFA funds should be used to enhance FDA’s Division of Drug Marketing, Advertising, and Communications (DDMAC).
Regarding the August 15, 2016 Public Meeting on Prescription Drug User Fee Act (PDUFA) Reauthorization, we are deeply concerned about the lack of public health and consumer perspectives at the meeting and the lack of those perspectives in the commitment letter itself. Three panels included invited speakers to discuss post-market safety, regulatory decision tools, and administrative enhancements. Not one stakeholder on the panel was a consumer or public health advocate. Instead, the panels included only stakeholders from industry-affiliated patient groups as well as BIO and PhRMA representatives. Perhaps that is why not one of them pointed out that the commitment letter overwhelmingly focuses on speed of drug approval and hardly mentions patient safety.
Conclusions
The FDA has been under-funded for years and, in today’s budgetary climate, user fees are necessary. FDA is struggling to manage expanded demand with inadequate appropriations. While we are happy with the increased resources for Sentinel, and for hiring and retaining employees, we are not convinced that the increased PDUFA fees will be adequate to cover the increased workload, such as resource intensive-performance goals focused on speed, not safety or efficacy. The proposed performance goals call for numerous time-consuming meetings between FDA and industry, several new draft guidance documents, and frequent public workshops or public meetings.
Patients and consumers and the groups that represent them have a right to influence how user fees are spent. We do not pay the fees, but we do pay for the medications. We pay directly when we use our own money to buy the products, pay for insurance and federal health programs, or pay for the health problems that may result when the medicines don’t work well. And, as taxpayers we pay for the appropriations that are still supporting a major proportion of FDA resources. It is inappropriate that patients and consumers who are independent of industry are not included in the PDUFA decision-making process. As a result, our priorities and needs are not adequately met in the PDUFA VI commitment letter.
- Federal Register (July 19, 2016). Food and Drug Administration. Prescription Drug User Fee Act; Public Meeting: Request for Comments. [Docket No. FDA-2016-N-1895]. https://www.federalregister.gov/articles/2016/07/19/2016-16916/prescription-drug-user-fee-act-public-meeting-request-for-comments
- Food and Drug Administration (December 7, 2015). What We Do. http://www.fda.gov/AboutFDA/WhatWeDo/
- Light DW, (July 17, 2013). Risky Drugs: Why The FDA Cannot Be Trusted, Harvard University, Edmond J. Safra Center for Ethics http://ethics.harvard.edu/blog/risky-drugs-why-fda-cannot-be-trusted
- Light DW, Lexchin J, Darrow JJ (June 1, 2013). Institutional Corruption of Pharmaceuticals and the Myth of Safe and Effective Drugs, Journal of Law, Medicine and Ethics, 2013, Vol. 14, No. 3: 590-610
- Johnson CY (August 4, 2016). High prices make once-neglected ‘orphan’ drugs a booming business. The Washington Post. https://www.washingtonpost.com/business/economy/high-prices-make-once-neglected-orphan-drugs-a-booming-business/2016/08/04/539d0968-1e10-11e6-9c81-4be1c14fb8c8_story.html?_hsenc=p2ANqtz- _xsGN3x_dcjctNPxU71jgeOMWP5IBStU9q_NCcddIDRTgCtcTzar0xei8ReXtRlBu0kNDgFlI5BRsf51BB_8uZ2iMUgg&_hsmi=32543650&utm_campaign=KHN%3A%20First%20Edition&utm_content=32543650&utm_medium=email&utm_source=hs_email
- Good CB, Gellad, WF (January 2016). Off-label Drug Use and Adverse Drug Events (Invited Commentary), JAMA Internal Medicine. http://archinte.jamanetwork.com/article.aspx?articleid=2467779