Drugs and the FDA: Safety, Efficacy, and the Public's Trust

This book documents the evolution of a social institution from when and how authority delegated to that institution the power to regulate the marketing of commercial products with regard to their safety and efficacy. It also tells the story of how that institution evolved into an authoritative public/private partnership that took on the mission of bringing commercial products to market with a different regard to their safety and efficacy.The author documents how the process of evaluating a drug for the market proceeds though a collection of evidence and data to an advisory committee’s politically (i.e., democratically) produced recommendation, but the actual approval to market a drug is not democratic - it is the judgement of authority. It becomes clear that this process, although fed with evidence and data, is not based on science. A judgement on the benefit of efficacy given the risk of its injury is not scientific. A judgement on the benefit of progressive free survival is not scientific. If either our experience or science could have solved these issues, there would be no need for authoritative judgement and its inherent biases and foibles.In our history, the individual choices made on benefits were based on other authoritative, informing social institutions (eg, norms, customs, religions, etc). When government became an authority to which people could petition for redress of grievances, a novel method emerged for informing choice. The authority that had previously empowered itself to form the narratives of the res publica (the affairs of the public) now established and delegated that authority to the FDA to inform the choices on products. Now authority to pronounce judgment on the marketability of a product with regard to safety and efficacy resides with the FDA. This book provides some insights into the workings of the FDA, but I do not believe it provided insight into why authority, on one day, approved the marketing of a specific commercial product and, on another day, disapproved it.The closest it comes to that insight was described in how Act-Up and other advocacy groups petitioned for redress of grievances and how authority acquiesced with accelerated approvals, parallel tract protocols, compassionate-use applications, expanded access policies, etc. This is an informative example of how authority submits only to authority. These new processes allowed the FDA to approve marketing of drugs deemed only reasonably safe and having only a promise of effectiveness. Perhaps we are expected to believe this occurred only to benefit those to whom these drugs were marketed rather than to benefit those who market them. There is no doubt that those marketing these produces also have their ways to inform authority. Nevertheless, there is evidence that sick people have benefited by these policies. There is also evidence that people have been enriched by them. Remember this isn’t science. The Prescription Drug User Fee Act and the 21st Century Cures Act are not about science. At best, this legislation addresses the state of technology that allows for the gathering of data that might be deemed ‘with regard to’ the FDA’s domain.The approval to market a drug does follow a process, but it is not the result of a process - the approval is a judgement. The author describes the difficulties the public, the regulated companies and even the authority’s own advisory committees had and struggled with to understand the requirements of authority. Clearly the authority owes no accounting of itself. We can only hope for an honest and transparent ‘explanation’ of why authority acts this way or that. An explanation that we can perhaps incorporate into our own understanding of the circumstances. What is safe, what is effective, and what is acceptable is not understood similarly by all people and even by the regulatory authorities of other countries. What becomes marketable in this country is understood. The approval process may include data, evidence and risk-benefit analysis, but the approval itself is the judgment of authority.At the end of the book the subject of eroding Public Trust in the FDA was introduced: "The coin of the realm for the FDA is the trust the public holds in the agency . . . . But that same trust is eroded when drugs with accelerated approval are yanked in the setting of worrisome toxicities or lack of efficacy—even if the removal is also safeguarding the health of the public. This is particularly true when the initial approval occurred despite a negative vote from an independent panel of experts on a committee such as ODAC."One submits to authority or not, and it is easier to submit when one trusts and believes authority is right. Yet, regardless of its righteousness, a shared, cohesive explanation has always informed the choice of more people than has the truth.

Balanced look at the opportunities and challenges of our current approval system for cancer drugs. The author presents an interesting and informative review of this process based on his experience on the FTA’s oncology, drug advisory committee worth reading for delay in professional public.

Great first account narrative of how does it feel (and not only what ones think rationally about the data) and what goes on inside a high stakes voting FDA advisory committee than can make or break an oncology drug, by taking it out of the market. It is a true story with true characters, based on factual sources and events. The narrative is interesting and has elements of a novel. Very interesting to hear how this AC member dealt with "Dylanesque" patients protesting etc and the tough decisions he and is AC colleagues had to make. I don't rate it 5 stars but only 4 because for additional credibility the author should have avoided mixing politics with medical and regulatory science by repeatedly throughout the book suggesting his political party preferences. For a contrasting example "For Blood and Money" by Vardi which I did rate 5 stars besides not mixing political divide with drug development is also a more thrilling and better told story of what goes in drug development and associated medical/finance/regulatory events. Thus that one feels more genuine, that in that case the author is genuinely wanting to inform readers with no agenda.

One of the best books I read in 2022 and I don’t say that lightly. Sekeres does an excellent job revisiting the drama around avastin initial approval; it was like watching a movie. Kudos. Must read.

The FDA is an agency about which everyone has an opinion. This book lifts the veil of mystery that many of us have. I was very impressed with the material and storylines and appreciate the way that Dr. Sekeres presents things in a way that laymen can understand.

I loved this book. The storytelling is great, with excellent writing as it uses the FDA Avastin hearings as a backdrop for the history of the FDA. The writing is conversational, and Dr. Sekeres uses humor when appropriate. The book is also about people and I found some of the stories touching and thoughtful. Since Dr. Sekeres was involved in the hearings, his personal insights were both invaluable to the storytelling and fascinating. This book is well worth reading. Thank you to Netgalley and MIT Press for the digital review copy.