'Malignant' Takes a Critical Look at Cancer Policy

Editor's note: The author of this commentary was previously invited by Johns Hopkins University Press to review the concept and initial full-length draft of Malignant. As a family physician, he is familiar with the evidence on cancer screening and also serves on the Centers for Disease Control and Prevention's Advisory Committee on Breast Cancer in Young Women.

From Richard Nixon's "War on Cancer" to Joe Biden's "Cancer Moonshot," for at least the past half-century, politicians have believed that pouring money into basic research will lead to life-extending cancer treatments. Although there has been great progress, an analysis of clinical trials submitted for the US Food and Drug Administration (FDA) anticancer drug approvals from 2014 through 2017 found that two thirds of trials had at least one important limitation among four domains — lack of randomization, lack of overall survival benefit, inappropriate use of crossover, and use of suboptimal controls.

This theme — that cancer drugs frequently overpromise and underdeliver — has been central to the prolific career of University of California-San Francisco hematologist-oncologist and Medscape contributor Vinay K. Prasad, MD, MPH. In his latest book, Malignant: How Bad Policy and Bad Evidence Harm People with Cancer, he pulls together much of his scholarship over the past decade.

In Malignant, Prasad aims to inform patients as well as advocates, policy makers, journalists, and clinicians about the ways that cancer drug development policies, perverse incentives, conflicts of interest, and exaggerated research findings can cause more harm than good. He describes features of cancer studies that "game" the FDA approval process and takes the agency to task for not utilizing the full extent of its regulatory authority to encourage pharmaceutical companies to develop drugs with greater effectiveness and value. These are not wholly original critiques, but I have not seen them previously marshaled in this way or assembled into a single text.

For example, Prasad finds that the average research and development cost to bring a cancer drug to market is substantially lower than the widely cited $2.7 billion estimate from an industry-funded study. He also criticizes the overreliance on surrogate outcomes such as progression-free survival in randomized trials of cancer drugs, pointing out that improvements in progression-free survival frequently do not correlate with improvements in the patient-oriented outcome of overall survival. Furthermore, in a comparison of cancer drug costs with trial outcomes, "there was nearly no correlation between how well [a] drug worked and how much it cost."

Malignant also highlights a number of other forces that distort cancer medicine, from "hype, spin, and unbridled enthusiasm" to financial conflicts of interest to the limited empirical support for precision oncology (also known as personalized cancer care or genomic medicine). The use of unwarranted superlatives (eg, "gamechanger," "miracle," "breakthrough," "cure") in news stories about new drugs affects not only journalists but also cancer researchers, physicians, and patients. Financial conflicts are highly prevalent in predictable persons (eg, "key opinion leaders," guideline writers, conference speakers) and also in less obvious yet equally influential places (Twitter, patient advocacy groups, federal drug advisory committees).

After showing that conflicts are clearly associated with poor prescribing practices — doctors who receive payments from pharmaceutical companies offer more of the company's drugs even if they are more costly or less likely to be beneficial than alternatives — Prasad proposes a sweeping solution to this problem: "Doctors should not be able to receive personal payments from for-profit companies that sell healthcare products." However, he makes a point of stating that conflicts of interest aren't a problem created by "bad people" but rather a problem of powerful incentives that "foster and encourage financial conflict among doctors, who then come to see the silver lining in marginal drugs and may even ignore the harms, costs, and toxicities."

Prasad's deep dive into clinical trial design, oncology practice, and major cancer trials is the least accessible section of the book for non-oncologists and generalists. Prasad's mastery of the material is evident, but I found myself glossing over many of the technical details.

He recommends that nonconflicted academic experts design trials of new cancer drugs to find "meaningful benefits" (ie, minimum clinically important improvement in overall survival when compared with a control arm that receives the best available therapy). He also suggests that the FDA, the Centers for Medicare & Medicaid Services, and the National Institutes of Health raise the bar for cancer drug approvals, tighten payment policies, and provide more funding for cancer biology research and nonconflicted trials.

Additionally, he gives oncology trainees tips for keeping up with the medical literature and participating in discussions on new cancer therapies, and he provides commonsense advice to patients who are referred to oncologists.

Whether the book is worth your time to read depends on how invested you are in understanding the minutiae of cancer healthcare policy. On the one hand, it is hard to imagine even a highly motivated patient, caregiver, reporter, or other nonhealthcare professional having the persistence to slog through all of the unpronounceable names of cancer drugs, surrogate outcomes, fine points of clinical trial design, and byzantine regulatory approval processes. However, on the other hand, Malignant will have great appeal to current and future oncologists, cancer researchers, and acolytes of evidence-based medicine. It could easily serve as a primary text for a graduate level course on pharmaceutical policy.

Malignant: How Bad Policy and Bad Evidence Harm People with Cancer

By Vinayak K. Prasad, MD, MPH
Johns Hopkins University Press 289 pages, $32.95, hardcover

Kenneth W. Lin, MD, MPH, teaches family medicine, preventive medicine, and health policy at Georgetown University School of Medicine. He is deputy editor of the journal American Family Physician.

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