Summary: Refreshingly honest overview of cancer research, proposes sensible ways to fix what’s gone wrong, and a really great overview of cancer research. Highly recommended!
"Malignant" is a somewhat atypical book in the cancer space, as Prasad admits in his introduction. It reads a lot more like a combo of investigative journalism and outraged policy wonk than my preconception of the 'typical' cancer book, which, according to Amazon, is cancer cookbooks, 'holistic' ways to cure cancer, and a sprinkling of cancer biology.
Malignant’s simplified thesis is that over the last 25 years or so, increasingly lax regulatory standards + pervasive financial conflicts of interest +other factors have led to a proliferation of marginally useful cancer drugs, in addition to some truly useful game-changers, all at impressively high prices.
To be honest, when I first heard about the book, I wasn’t too excited. Cancer has never been my wheelhouse, and I wasn’t too excited about a book that I initially thought would be warmed-over criticism of cancer drug prices or something like that.
But, I gotta say, my instincts were wrong: like in Ending Medical Reversal, the apparent focus of the book—cancer drugs—is really a lens on a ton of other questions.
You might not think that “progression-free survival” should matter to anybody but an oncologist, but the utility or lack thereof of a metric is increasingly important in a metric-focused world. Like Prasad suggests when he quotes Plato, “They see only their own shadows, or the shadows of one another”, there are lots of difficult problems in clinical medicine that should make us think deeply about medical epistemology. Good thing, according to his CV, he was an undergrad philosophy major.
Cancer research, in addition to being philosophically interesting, is also morally compelling: it features the best and worst of modern medicine, the miracle cures like Imatinib and occasionally immunotherapy, and the arguably useless drugs that squeak by with a barely significant increase in surrogate endpoints.
So in addition to recommending “Malignant” to those in healthcare, I recommend it to anybody interested in decision-making under uncertainty, health policy, and the pharmaceutical industry. From a technological stagnation perspective there’s some interesting grist as well. 5/5!
On to the book’s thesis. Prasad makes so many separate points that summarizing in order would be unmanageable, so I tried to categorize them: Lax approval standards + financial conflicts of interests +byzantine cost shifting in American healthcare +irresponsible hype from many sources.
All those put together lead to very expensive, very mediocre drugs, with no real competition, and no market or regulatory forces driving costs down.
In this story, the “original sin” in cancer research is lax approval standards at the FDA. These come in many forms, of which the most important are FDA approvals based on surrogate endpoints that are NOT followed up with hard survival data and RCT’s conducted in ways that don’t mirror clinical practice.
The second main theme is financial conflicts of interest. Its not that the average physician is all that influenced by a free steak dinner once a year or a handful of free branded pens—though those likely influence behavior at the margin—but that the top physicians in a field, the ‘thought leaders’ (sort of an Orwellian term tbh!) receive quite a bit of $ from pharma: “125 guideline writers and found that 84% had taken personal payments from pharma, and the average was just over $10,000 ($10,011), with a huge range ($0 to $106,859)”. Prasad documents a few studies showing similar findings in that vein and has some neat studies looking at physicians’ Twitter activities and how positively they talk about new drugs. In addition, the practice of paying oncologists a fixed % of the drugs they administer, Prasad notes, perversely incentivizes more costly drug administration.
Prasad rightly criticizes the overwhelming hype in cancer research: “Every new drug seems to be a miracle, breakthrough, game changer, or cure, irrespective of how well it works or for how many people”, and wants to save the headlines for drugs that are truly transformative, “good rule of thumb for a game changer is this … kind of drug where, if the doctor had the disease, he or she would breathe a sigh of relief. That’s true for HIV drugs. That’s true for imatinib”.
A high bar, but the constant overuse of hyperbole likely erodes public trust in scientists, and trust is slow to gain and easy to lose. Much of this fault can be placed on journalists and university press release offices, but he also provides examples of regulatory officials (like former FDA head Scott Gottlieb) making much ado over only incremental improvements.
Some of the changes he proposes: studies that use survival as their primary endponts, enroll wider groups of patients, use standard-of-care control arms, and use ASCO guidelines for meaningful improvements.
He calls for a substantial increase in the $ allocated to clinical trials, which would give us better estimates of how much of our healthcare budget is spent on truly useful products, and compared to how much we spend on questionable treatments, would be a bargain.
Overall, I think this book lays out a refreshingly honest overview of cancer research and proposes sensible ways to fix what’s gone wrong. He doesn’t pull any punches with his critiques, but is also generally fair-minded about giving the other side their due.
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Trainees (of all stripes) must read!
In an expert, yet incredibly engaging manner, Dr. Prasad writes about how the current drug regulatory environment facilitates novel compounds coming to the market as cancer therapeutics. Regrettably, as Dr. Prasad illustrates, there often is little evidence that these new drugs make people live longer or better, all while the leadership of the US FDA gleefully boasts about the number of new compounds it approves each year.It’s sobering to read Malignant as a newly minted physician who ostensibly wants to be a hematologist involved in clinical and translational research. How do I proceed, knowing that the path of least resistance would have me become a pawn of the industry (a “Key Opinion Leader”) involved in conducting trials that improve surrogate endpoints, designed to capture a large portion of the market, without much regard for the actual lives of patients who suffer from cancer? This book was a hard stop for me; a moral awakening of sorts. Dovetailing with Ending Medical Reversal, Prasad beckons us to be better - on behalf of not only cancer patients, but society at large. If you are a trainee planning to go into gastroenterology or cardiology, the lessons in this book are pertinent and should hit close to home. Also, it’s worth saying that the fluidity and concision of the text is commendable given how heavy the material is. It’s a delight to read, and I recommend that you buy it! -Kevin Miller, MD, PGY1 internal medicine resident, Boston, MA
Top reviews from other countries
Guillaume Viaules
Very educational on Cancer medecine
Reviewed in France on May 20, 2022
Jan Vyjidak
A must read for anyone involved in medicine or public health
Reviewed in the United Kingdom on December 5, 2020Rishi Dhawan
Must-read book for all Haem-Onc physicians and trainees
Reviewed in India on July 27, 2020