NIH Support for FDA-Approved Medicines

Abstract

A recent budget proposal from the current American administration has compelled discussions about Federal funding for the introduction of new medicines (Reardon et al., 2017Reardon S. Tollefson J. Witze A. Ross E. Nature. 2017; 543: 471-472Crossref PubMed Scopus (11) Google Scholar). While the funding allocated to the National Cancer Institute and the Office of the Director did increase from FY16 to FY17 (though no other institute changed), the President has proposed an 18% cut to funding moving forward (Achenbach and Sun, 2017Achenbach, J., and Sun, L.H. (2017). Trump budget seeks huge cuts to science and medical research, disease prevention. Washington Post, May 23, 2017. https://www.washingtonpost.com/news/to-your-health/wp/2017/05/22/trump-budget-seeks-huge-cuts-to-disease-prevention-and-medical-research-departments/?utm_term=.9ac223009da3.Google Scholar, US Department of Health & Human Services, 2017US Department of Health & Human Services. (2017). HHS FY2017 budget in brief – NIH. https://www.hhs.gov/about/budget/fy2017/budget-in-brief/nih/index.html.Google Scholar). These conversations prompted an analysis of the impact of National Institutes for Health (NIH) funding for innovative Food and Drug Administration (FDA) drug approvals (hereafter referred to as New Molecular Entities or NMEs). To ask if and how NIH support influenced drug development, we aggregated information from publically available documents provided by the FDA and the NIH (via the NIH Reporter tool). Deploying our database of all FDA-approved medicines (Kinch et al., 2014Kinch M.S. Haynesworth A. Kinch S.L. Hoyer D. Drug Discov. Today. 2014; 19: 1033-1039Crossref PubMed Scopus (145) Google Scholar), we assessed the fraction of active ingredients whose research was underwritten by NIH. This included research on the compound itself or on the target prosecuted by each of these medicines. For the latter assessment, a database of mechanistic action was aggregated as reported in a series of studies published from 2014 through 2016 (Kinch et al., 2015Kinch M.S. Hoyer D. Patridge E. Plummer M. Drug Discov. Today. 2015; 20: 784-789Crossref PubMed Scopus (20) Google Scholar). Evidence of NIH support was indicated if funding could be determined in a search of drug target key terms within the NIH Reporter. Our assessment was broadly divided into two categories: one set of analyses focused upon NMEs approved between 2010 and 2016, and a second set of studies focused on the most commonly prescribed medicines in the United States. Specifically, the study asked if there was evidence that the NIH had supported research on these new medicines or their targeting pathways. Our first analysis focused on the 100 most commonly prescribed medicines, excluding vaccines and NMEs approved before 1980. Because some of these medicines contained the same active ingredient, the analysis of the 100 most prescribed drugs identified 76 NMEs. NIH funding was indicated for 71 of these 76 NMEs (93.4%). A second study surveyed all innovative medicines approved from the beginning of 2010 until the end of 2016 (210 different NMEs). Using the same methodologies detailed above, NIH support could be documented for the identification of the drug or its mechanistic basis for 203 of 210 (96.7%) NMEs. Diving deeper, we asked if Federal support was instrumental to the discovery of these medicines. We sought to understand if and how NIH funding had impacted early research. The date of the investigative new drug application (IND) was compared with the dates of funding from the NIH Reporter. According to a 2015 report issued by the Pharmaceutical Research and Manufacturers of America (PhRMA), an average of 10 years is needed to proceed from initial discovery to FDA approval (PhRMA, 2015PhRMA. (2015). 2015 biopharmaceutical research industry profile. http://wwwphrmaorg/profiles-reports.Google Scholar) Therefore, we asked if there was evidence of NIH support for research that had occurred at least 10 years prior to FDA approval. This approach was applied for each of the 100 most prescribed medicines as well as for drugs approved between 2010 and 2016. After excluding funding less than 10 years prior to approval, NIH support could still be documented for 63 of 76 (82.9%) active ingredients of the 100 most prescribed medicines. Likewise, the NIH supported the early research of at least 160 of 210 (76.2%) NMEs approved since 2010. Given the increasing priority applied to the most impactful medicines and to historically under-addressed indications, we focused upon NMEs approved using either a priority or orphan drug evaluation. This constraint revealed NIH support for the early research on all (7 of 7) of the most prescribed medicines approved using a priority review (a designation for new medicines with “significant improvements in the safety or effectiveness of the treatment, diagnosis, or prevention of serious conditions”). Likewise, NIH support was documented for 2 of 2 of the most prescribed drugs originally approved for an orphan disease (a disease affecting fewer than 200,000 American each year). When the same analysis was conducted on drugs approved between 2010 and 2016, NIH support could be documented for 104 of 107 (97.2%) of NMEs approved using a priority mechanism and 95.7% of drugs approved for a rare (orphan) disease. Information conveyed by the NIH Reporter also provided a means to analyze drugs targeting different categories of diseases. Our initial studies focused on the most widely prescribed drugs in the United States. Federal support could be documented for all diseases of the digestive tract or hormonal imbalances (100%), as well as most diseases of the respiratory (86%) and nervous (83%) systems. Likewise, NIH funding supported the research of most NMEs approved for leading causes of death and disease in the United States, including those for cardiovascular (80%) and infectious diseases (80%) as well as cancer (70%). While these data indicate that the NIH plays a key role in ensuring the continuity of new drug approvals, the outcomes likely under-estimate the role of NIH funding for two reasons. First, the full transparency of NIH funding is restricted by the availability of information on the NIH Reporter website, which does not include grants funded prior to 1992. Second, the time needed for an FDA approval has been declining in response to legislative actions such as the 1992 Prescription Drug User Fee Act (PDUFA). Consequently, 10 years may be too restrictive for some NMEs, particularly those targeting orphan indications that tend to occur on a more rapid basis. Beyond the obvious role that new medicines play in improving overall health, these studies do not reflect the economic impact of NIH support. The biopharmaceutical industry is a multi-trillion-dollar enterprise (in terms of market capitalization) whose survival requires a constant replenishment of new products (to offset patent expiries). Despite this dependence, convergent data from multiple sources suggests the private sector is increasingly reticent about supporting early-stage research and development and thus the burden is increasingly encumbered by the NIH. Altogether, these results suggest dire implications for the continuity of drug discovery should support for NIH be curtailed. Given a requirement for continuity in research activities and the long times required for drug discovery, the impact of declining Federal support would not necessarily be felt in the short term. However, the implications of cutbacks could disrupt or prevent future health improvements for many years to come.