Wednesday, July 9, 2014

Fred Thompson: Do You Really Think the DOD Spent $140 Billion to Protect the Lowland Gorilla?

Note: Here is another dispatch from Fred Thompson.  

We were talking about the Ebola Virus outbreak in West Africa, which has been boiling for several months now, when a colleague asked: “There are Ebola vaccines for primates and mice, but not for humans.  Why?” And, answered: “for the same reasons that there has been a West Nile vaccine for horses for a decade, but none for humans— partly regulatory hurdles, but more decisively the actions of that ‘free marketplace’ that our governmental and corporate elites are so fond of.”

I replied, colleague, the Center for Disease Control has a limited budget. It is obligated to allocate its resources in the most cost effective manner possible – which means doing as much good as it can with the funds at its disposal – if other initiatives generate more quality-adjusted life years (QUALYs) per dollar, they have first call on the dollars. Normally, where health issues are concerned, Congress appropriates funds whenever an agency can show that a program will generate net benefits (expected additional QUALYs @ $400K each less program cost – in this case the cost of developing and distributing a vaccine – is greater than 0). Presumably, the CDC has not made such a representation with respect to Ebola. As for West Nile Fever, the finding was negative (taking account only of threats to Americans).

Decision tree for vaccination program analysis

My colleague replied: “The CDC’s evaluation concerns only the desirability of widespread vaccination, and they’re probably right on that point. But this doesn’t address the prior question of the non-existence of the human vaccine. I continue to feel that the government should be in the business of developing and manufacturing vaccines, and perhaps all pharmaceuticals.”  

So far as vaccines are concerned, I agree. But vaccines are a special category of pharmaceuticals. Pharmaceuticals generally look like toll goods (non-exhaustible but excludable). Vaccines look more like pure public goods. Left to the private sector, they would almost certainly be undersupplied. For that reason, most vaccine development is underwritten by public agencies. In some instances, those agencies will not stop with research and development, but will also guarantee sufficient purchases to pay for the testing needed to prove the safety (to humans) and efficacy of new formulations, which the FDA requires before it will grant regulatory approval for a prescribed use. In most cases, however, the US government will underwrite these activities only where it is deemed cost effective to do so. Consequently, your horse can get a jab for West Nile virus, but you cannot. Moreover, you won’t be able to get one legally in the US until the FDA is satisfied through clinical tests that the vaccine is both safe and effective (unless, of course, you are a uniformed member of the US military deploying abroad).

Note that the legal requirements for the approval of new formulations (or the application of existing formulations for new purposes) are not subject to any kind of benefit cost test, but are very close to absolute fiat (although, under special circumstances, the FDA can put a new formulation on a fast track aimed at reducing testing costs; it can also weigh relative health risks, although it does so very cautiously). Moreover, proving the efficacy and safety of a vaccine is fraught with difficulties not encountered by other drugs. First, they are supposed to be prophylactic. One doesn’t have a population of the afflicted to test the formulation upon (using a nice neat double-blind experimental design, with the test population randomly assigned to treatment and control groups). Consequently, testing for efficacy under normal circumstances requires large sample sizes and monitoring over a wide area for a long period, which greatly increases the cost of approval and the return on investment (no matter who makes the investment). Second, with respect to safety, vaccines are inherently hazardous. This is way over the top but it gives a feel for the potential for litigation that vaccines entail; yet another reason business enterprises usually avoid vaccine development.

What’s up for grabs?

Novartis’ and Pfizer’s applications to the FDA for fast-tracking vaccines aimed at preventing meningitis B infections is the kind of exception that proves the rule. Current vaccines approved in the US cover four strains of bacterial meningitis, but not strain B. In this case, the vaccine is already available in Canada and Europe and there is solid evidence that it is safe and good reason to believe that it is also effective. So we have a situation in which there are no or minimal development costs, compelling evidence that the clinical trials will be successful, and even the expectation that FDA will fast track approval. That isn’t the case with respect to the Ebola or West Nile vaccines.

Why doesn’t the US government just pay for vaccine research for diseases prevalent in the 3rd world? It does, but its budget is limited. Moreover, in most instances vaccination programs aimed at diseases for which vaccines now exist are far more cost effective than the development of new vaccines. “A systematic review of the literature on the cost-effectiveness and economic benefits of vaccines in low- and middle-income countries conducted by IVAC was published in the December 17, 2012 issue of Vaccine. The review identified 108 relevant articles from 51 countries spanning 23 vaccines. Among the 44 articles that reported costs per QUALY saved, vaccines cost less than or equal to $100 per QUALY in 23 articles (52%) and less than $1,000 per QUALY in 38 articles (86%).” Ozawa et al. –

Finally, even where it is not cost effective to do so, US government will pay for vaccine research against terror threats – and Ebola has been deemed a bioterror threat. But the government still won’t finance widespread clinical trials because of the enormous costs. Scientists from the Vaccine Research Center (VRC) at the National Institute of Allergy and Infectious Diseases (NIAID) have been conducting limited human trials on Ebola vaccines since 2003 and on fast acting vaccines since 2007. Both vaccines have been tested for safety on dozens of volunteers without significant adverse effects (not nearly enough for FDA approval but probably enough for military purposes) and both produce antibodies with the appropriate markers.

Also, March 5, a Canadian firm, Tekmira Pharmaceuticals, reported that the U.S. Food and Drug Administration had agreed to fast-track testing of TKM-Ebola, an anti-Ebola viral therapeutic, also developed under the sponsorship of the U.S. Department of Defense. 

Are these treatments effective in humans? (Actually, according to one report, in 2009, a researcher in Hamburg, Germany, accidentally pricked herself with an Ebola-infected syringe. She was treated with a vaccine brought in from Canada, which consisted of a weakened vesicular stomatitis virus genetically engineered to contain a portion of an Ebola virus protein that had been proven effective in monkeys. She was subsequently observed to be asymptomatic.) It’s hard to imagine financing the massive clinical trials that would be required to answer the effectiveness/safety questions under normal circumstances.

Epidemics can change this calculus. They raise the possibility of human trials in situations where volunteers, treatment and controls, are directly exposed to the disease, vastly reducing the needed sample size and trial time. Doctors without Borders, which had positive results from a quick and dirty vaccine in the Congo, has been pushing hard for permission to run clinical trials of these vaccines in West Africa, both from NIH and the local governments in question.

So, dear colleague, the US is already pretty much doing what you want, although maybe not exactly. Reasonable people can disagree about how many dollars to spend and for what. But it doesn’t look to me like slavish adherence to “the ‘free marketplace’ that our governmental and corporate elites are so fond of” is of more than tangential importance here. Rather, in the case of pharmaceuticals, our regulatory apparatus is simply much more sensitive to the threats from dangerous drugs than it is to the threats from dangerous diseases and, maybe, that’s not an entirely bad thing. With respect to Ebola and West Nile, we have vaccines. They will probably work on people. In a serious emergency they would almost certainly be used.


fthompso said...

Folks other than Doctors without Borders (MSF) are starting to talk publicly if not loudly about human testing in the context of the Ebola outbreak:

fthompso said...

louverFurther updates on Ebola Vaccines/TKMEbola: