FDA Drug and Development Approval Process: Compromising Safety for Speed
Airi Furui
The Food and Drug Administration (FDA) drug development and approval process is a pivotal stage in the pharmaceutical life cycle and is necessary for the subsequent marketing and consumption of medication in the United States. This process ensures the quality, efficacy, and most importantly, safety of newly developed drugs to protect consumers. However, according to researchers at the Yale School of Medicine, nearly a third of drugs approved by the FDA from 2001 through 2010 had major safety issues years after the medications were available, with 71 out of the 222 approved drugs being withdrawn and given a ‘black box’ warning of their side effects.1 Although the FDA is the ultimate authority for drug approval, various actors including biotech companies, pharmaceutical companies, and politicians can be involved in the drug development process, adding layers of complexity to this issue. This landscape underscores how the financial, political, and public pressures that the FDA faces may influence the pharmaceutical approval process, potentially exposing patients across the country to unsafe drugs.2
The financial power that pharmaceutical and biotech companies exercise over the FDA is evident by the fact that 75% of the drug division of the FDA is financed by these companies, supporting 6,500 jobs within the agency.3 As the FDA works closely with companies that want to launch pharmaceutical products into the market, it is often difficult for the two entities to maintain an impartial and balanced relationship. This issue was reflected in the release and withdrawal of Vioxx, a painkiller drug that was later found to increase the risks of cardiovascular diseases. After its release in 1999, Vioxx – sold by Merck – reached more than 80 million users and caused 38,000 deaths before it was discontinued by Merck in 2004. However, as early as December of 1999, Merck found out that patients who took Vioxx had twice as high a risk of serious heart problems and death compared to people who took naproxen, a similar painkiller drug. In a paper submitted to the New England Journal of Medicine in 2000 by Merck, only 17 of the 20 heart attacks experienced by patients were included and data on other kinds of cardiovascular events were left out. Merck reported these additional cardiovascular incidents to FDA, which made the data available on their website, but did not lead to the immediate withdrawal of Vioxx. This specific case illustrates how pharmaceutical companies may not have the best interests of customers as they may prioritize sales and profit over consumer safety. Vioxx may have reached a smaller population if the FDA had utilized the information provided by Merck to protect the consumers.
In addition to the financial and political conflicts that the FDA faces with private companies, the FDA also experiences pressure from the public that can make it challenging for the agency to safeguard the public from potentially harmful drugs. In fulfilling this responsibility, the FDA is sometimes perceived as a gatekeeper that inhibits patients from accessing potentially lifesaving therapeutics. For the FDA to not be perceived as a gatekeeper, it has increasingly viewed a fast and efficient pharmaceutical approval process as crucial. This is evident by the fact that from 1976-1998, an increase in Washington Post stories about the disease that a given drug targets was associated with a quicker review of said drug by the FDA.4 The study reveals how the FDA values public opinion and may prioritize the review and approval process of drugs that are under media attention. The speedy approval process has its benefits, in that patients receive drugs more quickly, but also comes with the cost of more thorough evaluations of the quality and safety of the drugs.
The FDA established the Accelerated Approval Process in 1992 to provide a pathway for new drugs to reach patients with serious illnesses quickly.5 This program grants approvals to drugs that suggest a health benefit yet have unconfirmed side effects and requires companies to submit follow-up results to confirm their effects. If the confirmatory trials do not demonstrate that the drug has potential, the drug can be removed from the market. Even with the submission of follow-up results, the prioritization of speed by the Accelerated Approval Process comprises the thorough evaluation of the drug. As these drugs may be withdrawn after follow-up investigations, frequent, forthright communication between the companies and the FDA is crucial. Nevertheless, out of the 200 cancer treatments that have been approved through accelerated approval, 26 have been withdrawn and 68 are still waiting for follow-up investigation.5 This reflects how the accelerated approval process may release a drug to the market without clear insights into the clinical benefits of the drug. The issue becomes more concerning when we consider the fact that there are patients with serious illnesses who are being treated with drugs that may be ineffective or outright dangerous.
The FDA drug development and approval process that intends to protect the safety and well-being of consumers face many challenges ranging from financial and political constraints to public pressures. These challenges necessitate a critical examination of the major safety issues arising from the current FDA development and approval framework to avoid future incidents that may threaten the public. Furthermore, the FDA is recognized as having the shortest median drug approval time of 244 days compared to other regulatory agencies in the world.6 On the other hand, other agencies have different processes, for instance, the EU gathers scientific resources from multiple member countries while Japan has a unique safety triangle system with relief programs provided for individuals affected by harmful pharmaceutical products. The FDA could adopt strategies such as creating a shared database of drugs and clinical trials with other countries or organizations. These could promote higher accuracy and consistency in data and improve transparency between the various parties involved in the drug approval process. In addition, if various actors could overlook each other’s actions, it may prevent internal conflicts of interest and the FDA having ‘cozy’ relationships with specific biotech and pharma companies. The challenges will be to find partners to build a collaborative database in addition to ensuring there are no inappropriate relationships between actors. Moreover, the requirements of the accelerated approval program could be made stricter such as requiring larger amounts of data and trials as well as requiring more data on the potential side effects the drug may have. However, this could also jeopardize the purpose of the accelerated approval program as acquiring data will lead to a longer time for the drugs to be released. Although these additional measures may lead to a longer time for the drug to be released into the market, the FDA may benefit from adopting these new regulations that can make the development and approval process more safe, efficient, and effective.
References
[1] Kashef, Z. (2017, May 10). New Safety concerns identified for 1 in 3 FDA-approved drugs. YaleNews. https://news.yale.edu/2017/05/09/new-safety-concerns-identified-1-3-fda-approved-drugs
[2] Prakash, S., & Valentine, V. (2007, November 10). Timeline: The rise and fall of Vioxx. NPR. https://www.npr.org/2007/11/10/5470430/timeline-the-rise-and-fall-of-vioxx
[3] Krumholz, H. M., Ross, J. S., Presler, A. H., & Egilman, D. S. (2007, January 20). What have we learnt from vioxx?. BMJ (Clinical research ed.). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1779871/
[4] Olson, M. (2011, April). Politics or perception: What motivates the FDA? - health affairs. Health Affairs . http://content.healthaffairs.org/content/30/4/795.full
[5] Madhusoodanan, J. (2023, August 9). How a controversial US drug policy could be harming cancer patients worldwide. Nature News. https://www.nature.com/articles/d41586-023-02492-x
[6] New drug approvals in six major authorities 2011-2020. Centre for Innovation in Regulatory Science (. (2021). https://cirsci.org/wp-content/uploads/dlm_uploads/2021/06/CIRS-RD-Briefing-81-6-agencies-v5.pdf
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