Malignant: how policy, not just biology, fails patients

Malignant: How Bad Policy and Bad Evidence Harm People with Cancer was published by Johns Hopkins University Press in 2020. Its author is Vinayak K. Prasad. He is a practicing oncologist and a health-policy researcher. His academic work has focused on the quality of evidence in medicine. Part of it deals with what he and colleagues call medical reversal. That is when a widely adopted practice is later shown not to work. Better evidence is what shows it.

The book is not a memoir. No single patient's story sits at its center. It is a sustained policy argument. It is aimed at how cancer drugs get approved. It is also aimed at how screening tests get recommended. And it looks at financial incentives inside the healthcare and pharmaceutical systems. Prasad argues those incentives can shape decisions in ways that do not always serve patients.

Prasad's central claim is about how new treatments are judged. He argues oncology has adopted shortcuts, more than many fields have. One shortcut is the use of surrogate endpoints, such as tumor shrinkage. Those stand in for the outcomes that matter directly to patients. Those outcomes are living longer, or living better. He argues these shortcuts combine with financial incentives. Those incentives fall on drug companies, hospitals and journals. Together, he says, they have let treatments and tests reach patients too early. The evidence behind them is not as strong as patients likely assume.

The book is explicitly a critique from inside the field. Prasad treats patients as an oncologist. He frames his argument as an attempt to make oncology more accountable. The standard he holds it to is oncology's own standard for evidence. It is not an attack on cancer treatment itself.

The book is organized around a series of case studies and arguments. Each is built around a specific policy mechanism the author argues has gone wrong. Chapters examine FDA's accelerated approval pathway. That pathway lets a drug reach the market based on a surrogate endpoint. A confirmatory trial to establish an effect on survival comes later. The book's concern is that confirmatory trials can be delayed or weak.

The book's screening critique centers on prostate cancer. The worry is that enthusiasm for early detection can outrun proof that it saves lives. This overlaps with the argument in Overdiagnosed.

The book also examines financial and institutional incentives. Prasad argues they distort these decisions. One example is the incentive for drug makers to seek the fastest pathway to approval.

The book argues for reform. In this page's summary of it, the aim is stronger evidence standards. That means survival and quality of life, not surrogate markers alone. This page has not checked the book's specific recommendations against the text.

The book's strongest material is its use of FDA's own accelerated approval framework. That framework is real, and it is named. It creates exactly the surrogate-endpoint dynamic Prasad describes. This is not a claim invented for the book. It is how the pathway is designed to work. Confirmatory trials are a built-in follow-up requirement.

The author is an oncologist and health-policy researcher. His critique deals with how drug approval and trial design work.

The book is also useful for naming an uncomfortable structural reality plainly. A drug company seeks approval. A hospital seeks to offer the newest treatment. A patient hopes for any additional option. None of those incentives lines up neatly with another one. That other incentive is to run a slow, rigorous confirmatory trial.

The book argues one position in a live debate. Other experts disagree with parts of it. Treat it as one view, not a settled consensus.

The book was published in 2020. Things have moved since then. FDA's accelerated approval rules can change. So can the status of any drug the book names. A reader should check a drug's current FDA status instead of relying on the book's 2020 account.

The book reads as advocacy for reform, not a neutral survey. Weigh its claims against the current federal standards described below.

Prasad states his own standard throughout the book. It is a workable general tool for judging a treatment claim. Ask whether the treatment has been shown to improve overall survival. Ask the same about quality of life. That showing has to come from a randomized trial. Or ask whether it moved only a surrogate marker. Tumor response and progression-free survival are two such markers. A claim resting only on a surrogate marker is weaker. A claim with survival data behind it is stronger. Both may be described in the same confident language.

A second standard from the book concerns money. Ask who benefits financially from a given claim being believed. Then ask whether the study behind it was designed and funded independently of that interest. This does not make an industry-funded study wrong. But it is a reasonable prompt to look for independent confirmation.

Readers can apply the same tests to the book's own claims. Prasad criticizes specific drugs and approvals. Check whether the confirmatory trial for one of them has since been completed. Then check what that trial showed. That is exactly the kind of update that can settle a contested claim. It can settle it in either direction.

The book's screening critique focuses heavily on prostate cancer. Current USPSTF guidance reflects a broadly similar concern. That concern is about overdiagnosis and overtreatment. The Task Force reached it through its own evidence review. It did not reach it through the book's argument.

The USPSTF recommendation, dated May 2018, grades PSA-based prostate cancer screening for men aged 55 to 69 as Grade C. The Task Force says the decision to be screened should be an individual one. It estimates screening prevents about 1.3 prostate cancer deaths per 1,000 men over 13 years. It weighs that against harms. These include false-positive results that lead to biopsies, overdiagnosis, and treatment effects. About 1 in 5 men who have a radical prostatectomy develop long-term urinary incontinence. About 2 in 3 have long-term erectile dysfunction. For men 70 and older, USPSTF recommends against PSA-based screening. That is a Grade D. The USPSTF page says an update is in progress, so check it for the latest.

FDA's accelerated approval program page describes the pathway plainly. Approval can be granted based on a surrogate endpoint "reasonably likely to predict clinical benefit," with the sponsor required to conduct confirmatory trials afterward to verify that benefit. If the confirmatory trial does not show clinical benefit, FDA has procedures that could lead to removing the drug from the market. How well and how fast that works in practice is part of what the book debates.

For the fuller current picture on prostate screening, see prostate cancer screening. The book shares a broader overdiagnosis concern with Overdiagnosed. On that, see cancer overdiagnosis.

It is worth being direct about where this book's argument sits today. It is a serious, credentialed critique from within the field. It is not a fringe position. But it is not the only view within oncology either. Oncologists disagree about how far to curtail accelerated approval. They disagree about screening enthusiasm too. Some experts share concerns like his about confirmatory trials. Some of them disagree with him on scope. They question how broadly the concerns apply to the specific drugs or programs he singles out. Readers will meet strong claims in both directions. One is that a specific accelerated-approval drug is essentially unproven. The other is that criticizing accelerated approval denies patients access to promising treatment. Both are claims to check against the trial data for that specific drug. General principle alone will not settle the question. The book is most useful as a framework for asking the right questions of a specific case. It is not a verdict on any treatment a reader might currently be considering.

This book suits a reader who wants a pointed, well-informed critique. Its subject is how cancer drugs get approved and how screening gets recommended. It comes from someone inside the field who is willing to name specific cases. It rewards a reader already at ease with some statistical and policy vocabulary. A reader willing to look terms up as they go will do fine too.

It does not suit a reader looking for a balanced survey of the accelerated approval debate. It presents one strong side of an active disagreement. It also does not suit a reader with a different question. Some want to know whether a treatment they have been offered is well supported. The book cannot resolve that on its own. That question needs a conversation with their own oncology team. It needs current evidence, not the book's 2020 case studies alone.

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• FDA — Accelerated Approval Program
• USPSTF — Prostate Cancer: Screening

This page discusses Malignant for education. It is not medical advice, and nothing here is a judgement of anyone's real medical care.