By Shira Klapper, Senior Writer/Editor

Epoetin alfa and darbepoetin were approved by the U.S. Food and Drug Administration in 1993 and 2002, respectively, after clinical trials showed a significantly reduced need for red blood cell transfusions among patients who received the drugs. In the wake of the FDA approval, oncologists quickly embraced these erythropoiesis-stimulating agents (ESAs). In fact, between 2001 and 2005, use of ESAs increased by 340%; in that same time period, Medicare payouts for the drugs exceeded $1 billion.

But as early as 1998, data began to emerge showing that ESAs increased the chances of thrombosis and decreased rates of survival among patients. In light of this data, in 2007 the FDA released recommendations limiting the use of ESAs to patients who met the criteria on the drugs’ labels. In that same year, the Centers for Medicare and Medicaid Services (CMS) issued a new coverage policy stating that doctors seeking to be reimbursed for ESA claims would have to submit detailed forms showing that patients met the strict FDA criteria pertaining to hemoglobin levels, the number of doses, and other variables.

An opportunity to study the intersection of policy and drug use

This story—of the rise of a drug and subsequent restrictions by the FDA and Medicare—caught the attention of researchers from Columbia University and Presbyterian Hospital and is the focus of a Journal of Oncology Practice (JOP) study, “Erythropoiesis Stimulating Agent Use Following Changes in Medicare Reimbursement Policies,” published online, before print, April 15, 2014. It was in this story of ESAs that the researchers saw an excellent opportunity to study how policy affects the way doctors prescribe drugs. Specifically, they asked: When it comes to doctors changing their behaviors, do FDA guidelines or CMS reimbursements have a bigger impact?

Dawn L. Hershman,  MD, MS

The answer, it turns out, is CMS reimbursement. The study found that ESA use continued to rise even after the FDA issued warnings and restrictions. Only when CMS changed their reimbursement criteria did prescriptions sharply drop off.

“This study shows that—as opposed to an FDA black-box warning of tumor progression, shortened survival, and thrombotic risks—reimbursement has far greater impact in terms of changing physician behavior,” said study first author, Dawn L. Hershman, MD, MS, of Columbia University College of Physicians and Surgeons and Mailman School of Public Health. “If physicians are not going to get reimbursed for the drug they’re giving out, then they pay a lot more attention to making sure that they’re giving it correctly.”

A sharp rise in denied claims

To understand how the FDA warnings and CMS restrictions affected prescription of ESAs, the researchers looked at 121,169 patients from the SEER-Medicare database who were diagnosed between 2000 and 2007 with breast, lung, prostate, ovary, or colon cancer. Looking at the average number of ESA claims per year, the researchers were able to see that between 2000 and 2006, the percentage of patients with at least one claim for an ESA increased from 12.4% to 16.2%, but then fell to 7.9% by 2008. Importantly, 2007 was the year CMS issued their new restrictions. In addition, from 2006 to 2008, the number of doctor’s claims that were denied rose from 6.7% to 17.7%.

“When the new reimbursement criteria were put into place by CMS in 2008, there was a substantial change in use, down to the month,” said Dr. Hershman.

Interestingly, the researchers observed that the annual percentage of patients undergoing transfusion did not change in the same time period, indicating that lower use of ESAs did not result in more patients requiring a transfusion.

Can policy be too effective?

Dr. Hershman noted that the success of the CMS policy does come with a caveat: the strict criteria and paperwork requirements might result in doctors not prescribing ESAs to patients who legitimately need the drugs.

“The concern is that if cumbersome barriers are put in place, one runs the risk of not prescribing the drug to patients who may get a benefit from it,” said Dr. Hershman. “It could be that reductions in ESA use may have resulted in patients experiencing more fatigue, more dose delays in chemotherapy, or that there were other consequences we can’t measure in this type of data set.”

According to Dr. Hershman, the goal, ideally, is to strike the right balance between real medical need and regulations.

“The challenge going forward is to figure out how to prevent overuse but at the same time allow effective therapies to be given to people who really need them in an unencumbered way.”

Dawn L. Hershman, MD, MS, is an Associate Professor of Medicine at Columbia University Medical Center. She has been an ASCO member since 1999.

Source

Click here to read the abstract.

Click here to read the PDF.

Hershman, DL, Neugut, AI, Shim, JJ, et al. Erythropoiesis stimulating agent use following changes in Medicare reimbursement policies. J Oncol Pract. Published online before print, 4.15.14.

The Exclusive Coverage series on ASCO.org highlights selected research from JCO and JOP with additional perspective provided by the lead or corresponding author.

@ 2014 American Society of Clinical Oncology