Economists like the University of Chicago's Tomas Philipson at the Milken Institute, and MIT's Ernst Berndt at the Sloan School of Management, have reduced the cost-benefit analysis of the PDUFA to a "speed-safety tradeoff of the agency [FDA]" giving a dollar amount to "thousands of life-years lost" which would likely have our Founding Fathers and Framers of the Constitution turning-over in their graves, when viewed against the backdrop of the Fifth Amendment of the U.S. Constitution. The Fifth Amendment has an explicit requirement that the Federal Government not deprive individuals of "life, liberty, or property" without due process of the law and an implicit guarantee that each person receives equal protection of the laws. See Tomas J. Philipson et al., Nat'l Bureau of Econ. Research, Working Paper No. 11724, Assessing the Safety and Efficacy of the FDA: The Case of the Prescription Drug User Fee Acts (Oct. 2005), available at http://www.nber.org/papers/w11724 (Finding user fee regime saves 180,000 to 310,000 life-years at a cost 56,000 life-years).
Attributing cost in life-years lost to numbers of expedited new drugs withdrawn (the distribution of approval and withdrawal times of drugs) is a fatally-flawed argument. We can all agree that "there are relatively few safety withdrawals, pre and post-PDUFA, as compared to the total NMEs [New Molecular Entities] approved." This is precisely the problem with their argument and it is insidious. Many if not most of the unsafe drugs are left in the marketplace. Numbers of safety withdrawals do not correctly reflect drug safety. Their analysis ignores the facts that there are many dangerous drugs presently in the marketplace which should never have been approved in the first place, much less left in the marketplace to continue to wreak harm upon the public. Pfizer's recent fourth settlement ($2.3 billion) over illegal marketing, the withdrawal of Vioxx, and new risks associated with bisphosphonates and long-acting beta agonists (LABAs), are cases in point. Philipson has acknowledged receiving financial support from Pfizer Inc in 2002, 2005, and 2006.
Their analysis has many flaws. Their analysis assumes that adverse events are not under-reported to the AERS (adverse event reporting system). Their analysis does not account for hospitalizations that did not result in a fatality and instead only focused on reported deaths. Their analysis ignores the fact that under each enactment of the PDUFA, clinical researchers are encouraged and emboldened to commit ever more egregious research frauds while FDA officials are encouraged and emboldened to look the other way. Their analysis ignores the profound effect of bias on both medical research and medical practice due to conflicts of interest created by the PDUFA. Their analysis ignores the fact that not all U.S. citizens want or need unfettered access to potentially dangerous drugs whose market approvals were expedited under the PDUFA.
I invite all independent, medically-trained epidemiologists in this country, to comment on the validity of using numbers of drugs withdrawn as a proxy for drug safety under the PDUFA. Clinical epidemiologic arguments as to drug safety, not economic arguments as to corporate and consumer surplusage (profitability), should have been employed to evaluate the utility of the PDUFA to society. Hard endpoints, such as hospitalizations and deaths, not surrogate endpoints, such as the frequently used proxy to assess the FDA's safety record (numbers of drugs recalled), should be the endpoints in the analysis.
Corporate profits should not be given preference to drug safety. The PDUFA is directly responsible for the current drug safety crisis in this country. My personal view is that as a direct result of the PDUFA, there is a "new holocaust". The total number of "endangered and dead" is staggering and growing by the day. Let us not forget that most analysts have put worldwide deaths related to Vioxx to be somewhere in the range of 150,000 to 200,000. Society has no real need for half of today's marketed drugs, e.g., uppers, downers, sex 'toys', me-too drugs, and the other half are of very dubious safety. Quite a few are actually dangerous drugs. Society is either oblivious to this reality, or they don't really care.
Whose drug safety is it anyway? Drug safety belongs to the public. The public deserves an independent Drug Safety Board. The only expedited new drug approvals should be reserved for compassionate use by cancer and pre-terminal patients, not expedited approvals for the vast majority of citizens who would like nothing more than to feel secure in knowing that marketed drugs bear a reasonable measure of safety.
Robert Davidson, M.D., Ph.D.* is a practicing Internal Medicine physician for an outpatient clinic in Gladewater, TX.
*Disclosure: I have no current ties to the pharmaceutical industry. I am not an attorney. The views expressed herein are solely opinion and are in no way intended to represent legal or medical advice.