Reviewed by Till Bruckner
“Malignant: How Bad Policy and Bad Evidence Harm People with Cancer” by Vinayak K Prasad. Johns Hopkins University Press: May 2020 RRP £21.49
“Ultimately, the purpose of cancer medicine is to use as few drugs as possible for as little time [as possible] to minimize side effects while simultaneously maximizing survival and quality of life,” writes Vinay Prasad in Malignant, a book that forcefully argues that people with cancer are being let down by the way oncology is performed today.
At the outset of the book, Prasad lays out evidence that most new cancer drugs provide little or no benefit to patients. To speed up the market entry of new treatments, regulators routinely approve drugs based on clinical trials demonstrating improvements only in progression-free survival and other surrogate endpoints. However, one study found that only 14% of cancer drugs originally approved on surrogate endpoints were later proven to prolong patients’ lives. Pharma companies charge sky high prices for new cancer drugs, but their true value often hovers around zero as they expose patients to harm without providing any meaningful benefits.
The next section deals with hype, spin and financial conflicts of interest in oncology. Prasad rolls out all the usual suspects, from breathless press headlines about supposed ‘breakthroughs’ to conflicted key opinion leaders singing the praises of pharma companies and their wares. While I’m generally unenthusiastic about efforts to conduct more research into these dynamics – adding more evidence to the existing pile seems unlikely to solve any problems – Prasad uses the occasion to raise the very uncomfortable question of whether medical opinion leaders’ widespread silence on the topic of drug prices may be due to industry influence.
“The metric of a successful regulatory system is not how many drugs are approved but how many drugs with meaningful benefits are approved”
The book then circles back to the design and interpretation of studies of cancer treatments. Prasad takes the reader on a fascinating journey through observational data, trial designs and trial outcomes, tracing how the evidence base for various cancer treatments has shifted over time. Inevitably, this discussion can get extremely technical (unidirectional crossovers, anyone?) and the editor has allowed too many acronyms to slip through the net, but perseverance is ultimately rewarded. For example, the trial that documented a “statistically significant 10-11 day improvement in median survival,” that is used to illustrate Prasad’s counterintuitive argument that too large trials can be just as problematic as underpowered studies.
The final section sets recommendations for improving cancer medicine. “The metric of a successful regulatory system is not how many drugs are approved but how many drugs with meaningful benefits are approved,” Prasad writes. He calls on the U.S. Food and Drug Administration to “just say no” more often when confronted with underwhelming trial designs or outcome data. The FDA “already has the regulatory authority to define the size of benefit that warrants approval,” so the agency could significantly raise the evidence bar without new legislation, he notes. Longer term, Prasad proposes a system in which pivotal clinical trials are designed and run by federal agencies rather than by pharma companies, and in which drug prices are tied to actual clinical value added.
The key strength of this book is Prasad’s deep expertise on the subject matter combined with strong opinions that nevertheless steer clear of extreme positions. For example, he concedes that in some cases, temporary ‘accelerated approval’ based on unvalidated surrogate endpoints may be appropriate – if, but only if, regulators mandate postapproval studies and subsequently withdraw any drugs that fail to deliver on their initial promise. In addition, Malignant’s readability is boosted by a smooth writing style that marks a significant improvement over Prasad’s first book, Ending Medical Reversal.
While much of the book narrates Prasad’s own research, even those who follow his academic publications will find enough new material to keep them going to the end. In sum, Malignant is a must-read for anyone interested in evidence-based medicine, oncology or clinical trials.
Till Bruckner
TranspariMED
Published under a CC-BY license