Charles M. Beasley, Jr and Roy Tamura: What We Know and Do Not Know by Conventional Statistical Standards About Whether a Drug Does or Does Not Cause a Specific Side Effect (Adverse Effect)

Charles Beasley’s reply to Barry Blackwell’s comment

        We thank Barry for taking the time to carefully read our work and provide his responsive comments posted on July 25, 2019.  We want to elaborate on and clarify several points in Barry’s response.  Barry states: “The FDA derives 50% of its budget from industry payments for approval of a new drug application (NDA), a requirement imposed by the Republican Regan Administration (1980-1988).”  These “industry payments” are termed user fees, and it is quite important to understand that they are use taxes.  The user fees are paid by industry for review of potential commercial products requiring regulatory review and approval before the potential products can be commercially marketed.  The payment of these user fees is required independent of the results of the review and whether the FDA does or does not approve the potential product for commercial marketing.  Therefore, the payment of these user fees perhaps creates less “conflict of interest” than is suggested by Barry’s comments.

        The approved operating budget for the fiscal year 2019 was $5.725B, as provided in Table 1 (pp. 5-6)  of the Congressional Research Service document The Food and Drug Administration (FDA) Budget: Fact Sheet.  Of this total, $2.575B was paid for through user fees.  This budget was spread across 14 program areas.  Most of these program areas had some bearing on human drugs (divided between pharmaceuticals and biologics [a protein or other substance derived from a biological source, including rDNA and monoclonal antibody products]).  Extracting the program areas of foods, animal drugs and feeds, tobacco products, and export – color certification program areas from the budget figures above because these are the 4 of 14 program areas not related to or minimally related to (i.e., color certification) diagnosis or treatment of human disease,  the following budget figures result:  total budget - $3.747B; paid by user fees - $1.836B (49%).  The 10 program areas include various administrative and infrastructure costs.  If the program areas are restricted to only human drugs, biologics and devices, and radiological health, then total budget is $2.859M; with $1.570M (55%) paid for by user fees.  Of course, if these user fees were not being paid, then the entirety of FDA funding would come from general federal revenues (primarily income taxes).  Is it more appropriate for companies potentially deriving benefit from the decision of the FDA to pay for reviews when the payments for reviews are not contingent on the outcome of the reviews or more appropriate for the American taxpayer (individual and corporation not involved in human health care / not regulated by FDA)?

        Barry states:  “This creates a massive conflict of interest, encouraging the FDA to turn a blind eye to imposing costly sample sizes and elaborate statistical techniques that might and has discouraged industry innovation in the contemporary me-too era.”

        To suggest that FDA is biased in favor of industry with respect to establishing policy and standards for adequate drug development and decisions regarding individual product approvals or rejections based on FDA funding being derived in part from user fees is only speculation. This speculation ignores the relevance of the facts that not all funding is derived from user fees and more importantly that these user fees are paid regardless of whether a regulatory decision is to the economic benefit of a company or deals a severe economic blow to the company.

        Our speculation, based on interactions with one Reviewing Officer, four Review Division Directors, and several more senior FDA staff is that, for the most part, they are excellent scientists attempting to serve the American public.  About safety assessments, they are appropriately conservative.  They are not influenced by any favoritism for industry.  Perhaps on occasion, they can be influenced by congresspersons and senators (and presidents) without a good understanding of science and with significant interests in their political agendas.

        The requirements for the development programs for new pharmaceutical agents used to treat non-life-threatening diseases and used on a longer-term basis promulgated by FDA are in line with those established by committees of regulatory authorities as we have previously discussed,  These other regulatory authorities are funded by alternative methods to those that fund FDA.  Are all these regulatory agencies conspiring to benefit the human health industry?  Alternatively, are these regulatory agencies designing development requirements that reasonably protect human safety while still allowing new pharmaceutical agents to be developed with a practical time frame that often extends well past five years from first human dose? 

        The requirements for the development program for an individual potential new drug are sometimes modified by regulatory agencies from the general guidance that further extends the development timeline as a result of both pre-clinical and clinical observations during development.  Such development program requirements adjustment is as it should be in the service of protecting public health from the consequences of medical disorders and also the real minor harm as well as significant harm that can be done by the treatments for those disorders.

Reference:

Congressional Research Service. The Food and Drug Administration (FDA) Budget: Fact Sheet. 2019. www.everycrsreport.com/files/20190508_R44576_2584438761cef9cafc63c1bdf44ecca14f9b9335.pdf

December 5, 2019