The best way for the NIH to reduce drug prices is to address drug spending

As STAT reported recently, the Senate Committee on Health, Education, Labor, and Pensions (HELP) has indicated that it will not consider the nomination of Monica Bertagnolli as director of the National Institutes of Health unless she pledges to take specific steps to reduce drug prices.

However, the HELP Committee may want to focus on reducing drug spending, the product of price and units prescribed, rather than simply pricing.

It does not seem likely that any actions taken by NIH would have significant impact on drug prices. However, NIH does have significant opportunities to conduct practice-changing clinical trials that would decrease drug prescribing, and thus total drug spending. For example, NIH could fund studies of expensive drugs already on the market. This strategy, which my colleagues and I have called interventional pharmacoeconomics, assesses alternative treatment regimens involving lower doses, less frequent dosing, shorter duration of dosing, or less expensive alternatives for marketed drugs.

This is not a new concept, as it was implemented more than 30 years ago for zidovudine (azidothymidine), the first drug approved for HIV. After approval of this drug, there was public outrage regarding its cost. NIH eventually funded a series of trials that demonstrated that the originally approved dose was excessive, and lower doses became the standard, reducing both costs and side effects.

More recently, NIH funded studies comparing two treatments for the common eye disease macular degeneration. One was the FDA-approved agent Lucentis; the comparator was low-dose bevacizumab (approved as Avastin for the treatment of cancer), a 40-fold less expensive option. The two treatments had similar efficacy and side effects. Thus, it demonstrated the potential for reduced drug spending for macular degeneration without any impact on the price of either agent under investigation.

Currently, the greatest drug spending is for the treatment of cancer. There has been a longstanding belief that the optimal dose of these cancer drugs is the maximally tolerated dose, thus leading to expectations of significant toxicity for patients receiving cancer treatment. However, it is now understood that this historical approach is not appropriate for most new drugs, and FDA’s Oncology Center of Excellence has recently released draft guidance that essentially requires all sponsors optimize the recommended dose prior to initiation of any registration trials. This new policy has been designated Project Optimus. (Disclosure: I am on the board of directors of the Optimal Cancer Care Alliance, which promotes post-marketing dose optimization studies.)

However, the FDA’s current authority does not permit them to require post-marketing dose optimization for fully approved drugs, many of which have been approved at excessive doses. For example, a recently completed randomized trial conducted in India demonstrated that 6% of the standard dose of an expensive immunotherapy drug (Opdivo) is effective, thereby markedly expanding the availability of that agent for Indian cancer patients.

There are many other expensive drugs for which clinical trials could demonstrate that a lower dose, frequency, or duration of treatment can maintain efficacy, while reducing toxicities and costs. NIH could fund and/or organize such studies, with potential input from the FDA and academic experts. These studies could be conducted at relatively low cost since they would not involve the administration of any investigational agents.

Furthermore, these interventional pharmacoeconomic studies have a negative net cost overall since the drug cost savings (often 25% or more of total drug spending) more than offset the cost of the clinical trial. Colleagues and I have recently suggested that the Centers for Medicare and Medicaid Services initiate such a program themselves, in collaboration with the FDA and NIH. While such studies would not be expected to lead to labeling changes, the results of such studies would be reflected in national treatment guidelines, such as those published by the National Comprehensive Cancer Network. CMS and other payers could then incorporate the results of these studies in their formulary guidelines.

NIH could also consider the economic impact of all clinical trials that it funds. For example, clinical trials that aim to develop new indications for marketed drugs should be of low priority, unless the eventual prescribing of those drugs would be clearly cost-effective. Similarly, clinical trials of patent-protected industry-owned investigational agents should also be a low priority. The pharmaceutical industry has the motivation and means to conduct these studies and does not need to be subsidized by the NIH.

While there are opportunities to reduce drug prices through promotion of generic drug entry, these are best left to other agencies, such as the Patent and Trademark Office, as well as pending legislation. The Interagency Patent Coordination and Improvement Act of 2023 aims to reduce the issuance of obvious patents that extend exclusivity for marketed drugs by promoting interactions between the Patent Office and FDA. Furthermore, Congress may also wish to consider legislation that would modify drug exclusivity rights.

All of these strategies are worth exploring. But the NIH director-nominee should not be accountable to the Senate for the excessive drug prices of today.

Mark J. Ratain is the Leon O. Jacobson professor of medicine and the director of the Center for Personalized Therapeutics at the University of Chicago, and a director of the Optimal Cancer Care Alliance. His current research focuses on oncology drug dosing and pharmaceutical policy.