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CRITical Thinking is a blog written by staff, directors, and friends of the Collaboration for Research Integrity and Transparency (CRIT), a joint program of Yale Law School, Yale School of Public Health, and Yale School of Medicine. CRIT's mission is to promote health by improving the integrity and transparency of biomedical and clinical research.

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What Does a Pro-Patient, Pro-Public Health Regulatory Agency Look Like?

September 13, 2017

In June 2017, Yale CRIT hosted an international conference titled “Ensuring Safety, Efficacy, and Access to Medical Products in the Age of Global Deregulation.” The following blogpost is the sixth installment of a blog series with commentaries from the conference participants. The views and opinions expressed in this blogpost are those of the author and do not necessarily reflect the position of Yale CRIT. For more blogposts related to this series, see here or click the tag “YaleCRIT17” below.

A pro-patient, pro-public health agenda for the regulation of medical products should, among other things: (a) ensure that these products are safe and effective for their intended uses; (b) maximize transparency regarding regulatory actions and the data used to support those actions; (c) spur the development of new treatments that truly meet the health needs of patients throughout the world; (d) minimize both industry bias in the development of medical products and industry influence on prescribing practices; and (e) ensure that medical products are affordable for all patients who need them and for society.

Implementing such an agenda would require a wide range of reforms, some of which I will highlight, focusing on pharmaceutical products. These ideas have been proposed and developed by groups of scholars and experts in the US/Canadian Pharmaceutical Policy Reform Working Group, which was co-chaired by Adam Gaffney, M.D., at Cambridge Hospital/Harvard Medical School and Joel Lexchin, M.D., at York University. A manuscript discussing these wide-ranging reforms of the system for developing pharmaceuticals has been submitted for publication.

The Working Group identified six principles that should guide reform of the pharmaceutical system:

  1. Medical needs, not financial means, should determine access to beneficial drugs.
  2. Drugs must be affordable to society.
  3. Drug development should be geared towards real innovation that maximizes population health.
  4. The human right to health must take precedence over intellectual property—i.e. patent—rights.
  5. The safety and effectiveness of drugs must be independently and rigorously evaluated.
  6. Complete, objective information on drugs must be available to prescribers and patients.

With these guiding principles in mind, here are several recommendations for designing a pro-patient, pro-public health agenda for pharmaceutical products:

  • The U.S. Food and Drug Administration (FDA) and other regulatory agencies should establish higher evidentiary standards for approving new drugs. As a general rule, trials should compare new agents to efficacious comparators (when they exist) to discourage investment in unneeded “me-too” drugs. Trials, with few exceptions, should be required to have hard clinical endpoints, rather than surrogate outcomes, such as laboratory biomarkers.
  • All clinical trial data, including anonymized patient-level data, should be made publicly available (whether or not a drug gains approval) to facilitate accountability and further research.
  • The National Institutes of Health and the Canadian Institutes of Health Research should create new Institutes for Prescription Drug Development with two divisions. The first—the Drug Innovation Division—would focus on the development of non-patentable agents to the point of readiness for clinical trial testing. The second, the Clinical Trials Division, would select for human testing promising molecules developed by nonprofit laboratories, academic investigators, and pharmaceutical companies. The latter division would fund and oversee trials, which would, in most cases, be designed and conducted by extramural, non-commercial investigators. Publicly-funded trials would offer important benefits: trial data would enter the public domain; commercial conflicts of interest would be minimized; research could be redirected away from “me-too” drugs towards real innovations; and the development of unprofitable but essential treatments would be facilitated.
  • When drugs are approved based on surrogate markers, mandatory post-marketing studies must be completed promptly; drugs should be withdrawn promptly from the market if studies fail to show meaningful benefit or are not completed in a timely manner.
  • Safety-monitoring offices within the FDA and other drug-regulatory agencies should be separated from divisions responsible for approving drugs and empowered to independently order safety advisories and remove unsafe drugs from the market.
  • There should be more intensive review of promotional materials and improved monitoring, with stiffer sanctions for misleading or off-label promotion.
  • There should be universal coverage for all needed drugs. The U.S. and Canada should establish national formularies listing all medically-necessary medications. Where multiple equivalent agents are available, the formulary should include only the safest, most effective and least expensive agent. There should be comprehensive coverage for all formulary medications without cost-sharing—i.e. no copayments or deductibles.

Under a pro-patient, pro-public health regulatory agenda, there would be much greater transparency by the FDA, as discussed in detail in the recently published Blueprint for Transparency at the U.S. Food and Drug Administration, which was authored by the FDA Transparency Working Group—composed of researchers from the Johns Hopkins Bloomberg School of Public Health, Brigham and Women’s Hospital/Harvard Medical School, Yale Medical School, and Yale Law School—and which has been accepted for publication in the Journal of Law, Medicine, & Ethics.

The FDA currently keeps too much information from public view under the guise of “confidential commercial information.” I will highlight just one of the Blueprint’s many important recommendations:

  • The FDA should make public its clinical and statistical reviews of products not approved or for which the marketing applications are abandoned or withdrawn.

The FDA’s long-standing policy is that it does not release its analyses of data submitted for such applications or disclose agency complete response letters notifying drug manufacturers of the non-approval decisions and the reasons for such actions, nor does the agency even notify the public that such rejections or withdrawals have occurred. This lack of transparency is particularly troubling in cases where the FDA has found a currently marketed drug to be ineffective or unsafe for a newly proposed indication. Disclosure of the FDA’s findings in such cases would promote public health by encouraging healthcare providers to avoid prescribing drugs for unapproved (off-label) uses that the agency has deemed to be potentially dangerous or ineffective. This is especially important given the endemic practice within the pharmaceutical industry of illegally marketing drugs for off-label uses.

Michael Carome, M.D. is the director of Public Citizen’s Health Research Group.