In the aftermath of the COVID-19 pandemic and other high profiles events concerning the Food and Drug Administration (FDA), such as the controversial approval of Alzheimer's drug aducanumab, there has been some increased interest in the regulatory and investigational procedures and standards involved in bringing a drug to market. Responding to this, Mikkael A. Sekeres, a professor of medicine and chief physician of the division of hematology at Miami's Sylvester Comprehensive Cancer Center, has penned <i>Drugs and the FDA: Safety, Efficacy, and the Public's Trust</i>, a fairly comprehensive yet accessible description of the FDA approval process for investigational drugs that is woven around a 2011 controversy concerning withdrawal of a breast cancer drug made by Genentech, Avastin. Sekeres' book also includes a brief history of the FDA, focusing on some of the horror stories that motivated public demand for increased drug safety (e.g. thalidomide-related birth defects) and, later, more rapid access to likely effective drugs (e.g. advocacy from HIV and cancer patients). The glue that holds together the information that one could mostly glean from the FDA's website or other sources is Sekeres' broader human interest narrative comprised of anecdotes from treating cancer patients and serving on the Oncologic Drugs Advisory Committee (ODAC). <i>Drugs and the FDA</i> also partially serves as a defense of the FDA's current regulatory program, insisting that it has responded to public demands while remaining faithful to its core mission of ensuring safe and effective drugs reach patients.

Although the central story about the withdrawal of Avastin (Bevacizumab) for the treatment of HER2-negative metastatic breast cancer after lackluster follow-up clinical trial results is awkwardly distributed throughout the work, it is still an illustrative anecdote. It allows Sekeres to introduce the FDA's accelerated approval program, which started in the early 1990s in response to HIV/AIDS and was designed (as the name indicates) to speed up the process for getting drugs to market for serious conditions with unmet needs. Drugs that receive accelerated approvals have to finish or perform follow-up studies that confirm the safety and clinical benefit that was demonstrated by earlier trial results (often called surrogate endpoints). The focus on the accelerated approval program is telling and topical. The current commissioner of the FDA was only able to corral support from the senate finance committee for his nomination by promising reform to this program. It is an unfortunate that the program is a hot-button issue for regulators and legislators given that clinical and financial analyses of the accelerated approval have suggested that it has been a huge success, especially for biomarker-guided target therapies in cancer.

The story of Avastin withdrawal also enables Sekeres to detail the general standards that the FDA relies on for guiding their approval decisions. The FDA essentially assesses the totality of clinical trial data, as opposed to relying only on a couple metrics, and then applies expert clinical judgement with an eye toward balancing benefits and risks. In other words, a drug must be safe-enough and provide a meaningful benefit to patient (preferably survival in serious conditions like cancer) in order to gain full approval. This can be a challenging and sometimes moving bar to clear, which can cause much consternation among patients and pharmaceutical companies. The entire process is time and resource intensive, involving many experts and stakeholders, who are asked to evaluate relevant data and provide guidance that the FDA takes into consideration before making final decisions. The insider look from Sekeres humanizes all of those involved and is for the most part understanding of all the competing interests involved with only mild critique of the financial interests at stake.

<i>Drugs and the FDA</i> is a defense of a frequently assailed institution from a partial insider. Sekeres has a decidedly establishment perspective and a generally positive appraisal of the FDA. It would have been interesting to see a more rigorous evaluation of the FDA performance in a work like this. The most interesting facts and figures in the book typically concern longitudinal perspectives on the FDA decision-making and patient outcomes and needs. I think the book, in trying to be a defense of the FDA's delicate balancing act, reveals some obvious bureaucratic deficiencies, such as ambiguity in approval standards and siloed evaluations of drug applications. The book also doesn't discuss in detail (though does briefly mention) how precision medicine in the genomic era is rapidly changing the indication-based paradigm for drug approvals in cancer. These so-called tumor-agnostic or pan-cancer approvals are premised on particular biomarkers that are identified via laboratory assay, including those that leverage next-generation sequencing technologies. The genomic era will likely lead to important and dramatic changes to what we need from the FDA. A slow and unwieldy regulatory environment may risk stifling innovation and growth. I would have appreciates a deeper look at this trend, especially from an oncologist like Sekeres.

<i>Drugs and the FDA</i> is a quick read that makes a complicate bureaucratic body's work legible to lay readers and supplies a human interest angle to keep readers engaged. Those who have any interest in clinical medicine and pharmaceuticals may want to pick this up as an introduction to this space, though much of the critical information can be quickly located via online sources.

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.

This was a well researched and informative read. Definitely opened my eyes! Mikkael Sekeres—a leading oncologist and former chair of the FDA’s cancer drug advisory committee—tells the story of how the FDA became the most trusted regulatory agency in the world. It took a series of tragedies and health crisis, as well as patient advocacy, for the government to take responsibility for ensuring the efficacy and safety of drugs and medical devices.