Slicing the Baloney

The shoving over Federal FY 2012 spending ratcheted up a notch this week with  publication of the President’s budget proposal and the many counter proposals being pushed by the several legislative factions and lobbies.  Of interest to the academic biomedical research lobby is the NIH budget which the administration’s plan will increase $1 billion to $32.3 billion (a 3.3% increase), or essentially flat since the increase in biomedical research costs is estimated to be about 3% (Fierce Biotech article), and which the House Republican plan will cut by $1.6 billion (AHS News).  Of course, to groups like the Federation of American Societies for Experimental Biology, the latter will mean lay-offs, research grinding to a halt, death, and destruction (FASEB News).  Moreover, according the FASEB president, his group is not seeking the additional funding “for itself but for the untold number of people whose lives could be saved or improved by medical advances” (Chronicle of Higher Education article).  I wondered what may be the evidence for federal research creating medical advances that save the lives of untold numbers of people if any of them are among the untold billions not lucky enough live in the US.

Coincidently, a recent publication in the New England Journal of Medicine by several notables of the academic technology transfer field, including my colleague, Ashley Stevens of Boston University, sheds light on this question.  In “The Role of Public-Sector Research in the Discovery of Drugs and Vaccines” (Stevens et al. 2011), they try to connect the dots between publicly-funded research in the biomedical sciences and specific products, which, of course, are really what are used to save or improve lives.  They found that “during the past 40 years, 153 new FDA-approved drugs, vaccines, or new indications for existing drugs were discovered through research carried out in PSRIs [public-sector research institutions]” and conclude “Public-sector research has had a more immediate effect on improving public health than was previously realized.”  This sounds impressive, and the study was cited by one news source in the context of the budget battles (Businessweek article), but I think some clarification is due.

First, the authors use the phrase, “discovered through,” rather than  “discovered by,” and don’t clearly say what they mean by the former.   I agree with Karl Popper, the philosopher, that all science is applied (eventually) so that the FASEB president is right (as is supported by the studies cited in Stevens et al.) in that publicly-funded science is good for society by generating knowledge that others can apply to creating (generally) useful products.  And for drug products, the application may take decades, according to Stevens et al. who cite Toole 2008 as finding the lag time between research funding and a product is around 17 years.  Although the authors imply that PSRI research is the proximate cause, or origin, the products they list, a quantification of the time frame is needed.

Second, the authors include a wide range of products in their total of 153 which I think should not have been included or at least counted differently.  I reviewed their list, nicely provided as an appendix, and found:

  • 8 diagnostics which are not drugs or vaccines;
  • 13 drugs which are variations of naturally-occurring substances like vitamins (e.g., calcitrol), hormones (e.g., estradiol, Factor IX, protein C), or bioactive molecules (e.g., nicotine, potassium, gallium) that were known before being used as drugs; and
  • at least 2 discontinued drugs (Calederol and Supprelin).

Moreover, the authors included products that are connected to the PSRI research by patents that claim:

  • a method of finding a drug (“screening”) which is not, in my mind, particularly relevant since the patent does not “enable” a specific drug;
  • methods of making or formulating a drug, also not particularly relevant since there can be many ways to make or formulation a drug; and
  • a method of treating, which may not be relevant since new uses often result from clinicians trying approved drugs for new uses.

I found the number of listed products connected to PSRI research by these kinds of patents and not a composition patent is 53.

Finally, I had a hard time confirming the connections supporting the authors’ discovery claim.  They used the FDA Orange Book as a primary source.  The FDA publishes the Orange Book, which I guess at one time was printed on orange paper but now is made of electrons, to identify therapeutically equivalent drugs to increase competition and lower prices (FDA Orange Book Preface) but it also lists the patents submitted by companies as part of their New Drug Applications (NDA).  These are the patents that confer “exclusivity” to the drug, that is, patents owned or licensed solely to the applicant which claim the product’s formulation/composition or approved use (more below).  I took a look at the specific patents listed in the Orange Book for a few of the listed products, picked the earliest issued (assuming it to be the primary patent), and checked the ownership.  I found only one in five was owned by a PSRI:

Product* Patent No. Owner
Abacavir sulfate 5034394 Burroughs Wellcome
Desloratadine 6100274 Schering
Triptorelin pamoate 5134122 Debiopharm S.A
Cetrorelix 5198533 Zentaris GmbH (DE)
Enfuvirtide 5464933 Duke University

*Generic name

Perhaps I am mis-using the source (the Orange Book), or perhaps my samples were instances in which a PSRI and a company discovered the product through cooperative research or independently as the authors acknowledge occurs (p. 537).

Granted my review of Stevens et al. is quick and superficial (the authors used additional sources that I did not have access to), but I think I have a case that the number of drugs and vaccines “discovered through” research conducted by PSRI may be substantially fewer than the 153 claimed.  I’d ballpark the number at 40 novel products (not new formulations or uses), primarily biologic drugs and vaccines which require less effort to find a bioactive, bio-available, and nontoxic product.   So what do we, the public, get for the billions invested in PSRIs each year?  Lots of publications to be sure (around 85000, NSF Scientific Publishing), lots of jobs for life scientists and research administrators, and lots of useful information that companies have turned to products.  And, since I accept the “discovered though” claim, at least a handful of antivirals and vaccines that are saving lives around the world.  Maybe we need an National Institute of Global Health to speed discovery.

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2 thoughts on “Slicing the Baloney

  1. It is great to see others rigorously looking through these articles. Thanks, Chris.

    First, however inflated these numbers of treatments “discovered through” public investment, I imagine (hope!) that Stevens, et al., used the same criteria to select the total number of treatments discovered. If so, it seems reasonable that *proportionally* PSRI’s are influencing the development of about one fifth of the treatments out there.

    The bigger concern I have, which you bring up indirectly, is that there is a lot of non-transparent research on these topics. This research influences policy debates, but for some reason it is not held to the same standards as, say, a genetics article in Nature. The issue tracing numbers and definitions has leaked into a lot of articles I have read on efficiency/ROI of public indirect and direct investments in research, the American patent system, exclusivity periods, etc.

    • Hi, Eric: thanks for your thoughtful comment and for highlighting the lack of critical thinking on the ROI of public spending on research. Just like all public spending that has a powerful entrenched constituency, the governmental support of biomedicine should be assessed in a consistent way we payers and our reps can understand and accept.

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