Читать книгу Cobert's Manual Of Drug Safety And Pharmacovigilance (Third Edition) - William Gregory - Страница 100

Q: Is there too close a relationship between the FDA and the pharmaceutical industry?

A: The answer depends on whom you ask. The FDA would (most probably) say that they are not compromised by maintaining correct and formal communications with the industry. Indeed, close communication promotes an understanding of regulatory expectations as well as practical challenges. The industry supplies FDA with much of the post-marketing safety data and nearly all of the pre-marketing safety data. There must be communication between the industry and the Agency to clarify ambiguous points, get further information on critical cases, and so forth. The FDA also encourages (and legislation even requires in some cases) meetings with the industry during the development of regulation and guidance. The FDA also regularly tracks drug development and meets with sponsors to discuss progress and next steps with investigational drugs (in the IND phases) and in post-marketing situations where safety issues arise. It is a professional-to-professional exchange of information to ensure the safety of the American public.

The industry would say that its influence on the FDA is slight. Companies go out of their way to be sure the FDA gets what it needs (and wants) and companies often submit more than regulations require to be sure that the FDA gets what it wants and that the companies are not accused of hiding or under submitting data. The industry often (privately) believes that the FDA is rather tough and tends to not give the industry a fair shake or a level playing field. Some feel the FDA treats big pharma differently from small pharma or start-up companies, cutting the latter a little more slack and giving them more “hand-holding”.

There has been speculation that the substantial PDUFA fees provided by industry for scientific assessment of new data by FDA “guarantee” new product approval, i.e., payment for a positive opinion. For example, in 2017 the fee for review of an application with clinical data was $2,038,100. Of course, integrity and objectivity of FDA reviewers is not adversely influenced by payments to the Agency (not to individuals) for operational expenses that improve efficiency of the drug review process.

Others claim that there is too much interchange of personnel between the FDA and industry, wherein some people start their careers or spend some time at the FDA and then move on to work for pharma companies, or vice versa, carrying with them their contacts and inner knowledge (which often becomes outmoded quickly) of the other. Some feel that this may influence a person’s actions in the company or FDA since his or her next job may be for the “other side”.

The consumer groups and activists believe that the FDA is indeed in bed with the industry and point to the various “fiascos” in safety that have occurred, such as Vioxx, Fen-Phen, suicide in pediatric patients on antidepressants, and contaminated heparin, among others (see other chapters). The FDA and the industry would (probably) counter by saying, quite the contrary that these episodes have shown that the drug safety system in place is indeed functioning and functioning well; the real challenge is to identify these problems earlier and manage the emerging risks.

These criticisms have been made for many other federal agencies, including regulators of banks, insurance companies, Wall Street, the airline industry, and car manufacturers. This is a fascinating and controversial area that is and will remain a work in progress for the foreseeable future.

Q: Should the FDA be broken up into an approving body and a safety body, similar to some other federal regulatory agencies?

A: This proposal has been advanced in the last several years. The argument is that the people who approve a drug have a vested (and emotional) interest in seeing their drug stay on the market and may not act vigorously on safety matters as this might be a tacit admission that their original approval decision was incorrect or too hasty. Organizationally, these functions are already split, but within CDER. It is claimed that separate reviewers should oversee safety, as they have no interest in defending an approval decision and they would be able to better interpret real world evidence, i.e., understand impact of bias and confounders, in data from the post-marketing phase. Thus, the medical skill set involved in post-marketing safety review is arguably different from that required in pre-approval safety review, which focuses on controlled clinical trial data. In all instances, however, safety assessment must always be considered in the context of benefit. Separating the functions would discount the knowledge the reviewing group has obtained over months and years of review of a product, moving post-marketing follow-up to people unfamiliar with the drug. This also would increase the bureaucracy and be more costly. In addition, complete separation would introduce additional challenges in the pre-approval phase when non-routine safety interventions, e.g., REMS, are under discussion. Clearly, each side has valid points. What will evolve will most likely be a political decision. There has also been talk of separating the food part of FDA into a separate agency. This too is under evaluation.