Guidelines for American oncologists often recommend expensive and harmful cancer drugs for patients based on “weak evidence”, according to a new study in the British Medical Journal.
The BMJ research looked at drugs recommended for conditions not approved by the US Food and Drug Administration, a practice called “off-label” prescribing.
Off-label prescribing, or using a drug for purposes that may be well known but not approved by a regulatory agency, is common, especially in oncology. But recently approved cancer drugs can cost hundreds of thousands of dollars and have severe side-effects.
“They’re not your grandpa’s old cytoplasmic drugs,” said Vinay Prasad, an oncologist at the Oregon Health and Sciences University, referring to early cancer drugs. “They are $100,000 drugs. They bring $1bn per year to the drugmakers.”
Prasad, the study’s lead author, said: “It would be one thing if we were talking about drugs that were cheap and have no side-effects.” He added that many recently approved cancer drugs “have risk-benefit analyses that are just tilted toward benefit. [But] you can get to a net harm condition.”
Prasad’s study looked at the US National Comprehensive Cancer Network, a body that publishes guidelines developed by oncologists. The NCCN’s recommendations influence treatment decisions and determine which cancer drugs insurers are required to pay for.
Medicare, a US public health insurance program for 55 million elderly and disabled Americans, is required to pay for all conditions NCCN recommends. Many private insurers follow suit. The NCCN’s role is similar to that of the National Institute for Health Care Excellence (Nice) in the United Kingdom.
In oncology, between 50% and 75% of current prescriptions are off-label, according to some estimates. It is illegal for drugmakers to advertise drugs for off-label uses.
Prasad’s study focused on 47 new drugs approved by the FDA between 2011 and 2015. The FDA approved those drug for 69 different indications. However, the NCCN recommended those drugs for 113 indications, 44 more indications than the FDA approved.
Only a minority of those additional recommendations were based on either randomized controlled trials (23%), considered the gold standard, or advanced-level phase three trials (16%). The team also followed up after 20 months on whether the FDA eventually approved medications for those 44 additional indications NCCN recommended. Only 14% were eventually approved by the FDA.
The study concluded that the research “raises concern that the NCCN justifies the coverage of costly, toxic drugs based on weak evidence”.
The report comes after recent research that found 90% of the researchers and physicians who helped develop the NCCN received money from the pharmaceutical industry.
“It’s clear with cancer drugs, one has to be very judicious about using them beyond where they’ve been studied,” said Prasad.
His advice to patients who might be trying new treatments is to ask about existing evidence.
“If you’re a cancer patient, I think it is so easy to get drawn into a discussion where the doctor starts to tell you of how a treatment should work,” said Prasad. “Patients have to force doctors to change the conversation from ‘how might this help me’, to ‘what is the evidence this drug helps patients like me?’”
Robert Carlson, the chief executive of the NCCN, said the guidelines rely on the “strongest scientific evidence available”.
“[The] NCCN’s 1,355 panel members come from 27 leading academic cancer centers in the United States,” he said. “Their expertise allows them to evaluate complex circumstances based on all available data, in order to come to a consensus about what constitutes optimal care.”