By Ed Silverman @Pharmalot
In the complicated world of medicine and money, the federal government relies on a handful of privately run directories to determine which cancer medicines it should pay for, and under which circumstances.
Unfortunately, there are some disturbing problems with these compendia, and they need to be fixed — because they’re costing taxpayers and run the risk of harming patients.
Here’s the story: There are five independent compendia, which are published by companies, a nonprofit, and a professional society. These directories contain a wealth of material, including recommendations for so-called off-label prescribing, which is when a doctor turns to a medicine that wasn’t specifically approved to treat a patient’s condition. This happens regularly — especially in oncology, where experimentation is a fixture of medical practice.
Congress requires Medicare to cover any off-label use of a medicine that’s listed in at least one of the compendia. And some states require private insurers to do the same. As a result, these digests have a key role in determining how drugs are used to treat cancer.
But that can be an expensive proposition.
Cancer drug spending is forecast to increase up to 10.5 percent a year through 2020 and reach $150 billion, according to IMS Institute for Healthcare Informatics, a research firm. And judging by the recent past, off-label prescribing will likely continue to contribute significantly to the bill. Off-label use of 10 common cancer drugs accounted for nearly $5 billion in costs in 2010, according to a study in the Journal of Clinical Oncology.
Regrettably, these circumstances create the potential for influence peddling. How so? Even if the Food and Drug Administration does not approve a medicine for a particular purpose, drug makers know they can make money from off-label prescribing, so long as it has the stamp of approval from at least one compendia. And companies are free to lobby the compendia to have off-label uses added.
Conflicts of interest, meanwhile, may also complicate matters.
Most physicians and researchers who help develop treatment guidelines published by the National Comprehensive Cancer Center — arguably, the most influential of the five compendia — have financial ties to manufacturers. Specifically, 86 percent of 125 experts who served on NCCN panels held at least one financial conflict of interest in 2014, according to a new study in the Journal of the American Medical Association.
“The compendia really act like a shadow system for reimbursement,” said Dr. Ethan Basch, a professor at the University of North Carolina-Chapel Hill department of medicine, who coauthored the JAMA study along with an essay that critiqued reliance on compendia for off-label use. “And the potential for bias is concerning, because for a drug company, listing in a compendia is a big deal.”
Other factors also make reliance on the compendia worrisome.
An analysis published in the Annals of Internal Medicine in 2009 found the quality of evidence cited in compendia for off-label usage was less rigorous than standards for uses approved by the FDA. And sometimes, the evidence was not up to date. That means Medicare or a private insurer may be forced to pay for a drug that is not shown to be safe or effective — thanks to one of the compendia.
Basch and his colleagues attempted a similar exercise in reviewing compendia recommendations for off-label use of Tarceva, which is approved to treat non-small cell lung cancer and pancreatic cancer. They found inconsistencies: Different compendia listed Tarceva for off-label use for different forms of cancer.
The researchers also found weak evidence supporting the off-label listings. That evidence included single case reports, small case studies, and a Phase 1 clinical trial, all of which can be questionable because the evidence may be minimal or not fully developed.
For their part, the organizations that publish the compendia defend their practices.
Gerald McEvoy, editor of the AHFS Clinical Drug compendia, wrote that his organization applies “the highest evidentiary standards” and prefers to rely on studies that have been published in peer-reviewed journals. Small case reports and Phase I studies “generally do not meet an adequate level of evidence,” he added. And he noted the AHFS has disclosure rules designed to weed out conflicts of interest, as does the NCCN.
Still, the system does not inspire confidence. So what can be done?
The JAMA essay suggests that the government should settle on using just one compendium; standards of evidence should be strengthened; conflicts of interest should be minimized; and the recommendations should be publicly accessible, rather than kept behind an expensive paywall.
“Unfortunately, there’s no master plan” for sorting out treatment decisions and insurance coverage, said Dr. Clifford Hudis, the chief executive officer of the American Society of Clinical Oncology.
Some kind of plan is needed, though. Doctors should be free to consider all options, including off-label use of drugs, but at a time when the cost of medicines is increasingly straining budgets, relying on inconsistent tools is counterproductive.