Erythropoietin has made the headlines once again.
You may recall a blog I wrote several months ago about this drug, and the controversy that erupted after clinical trial results came to light indicating that the drug—intended to boost red blood cell counts and avoid blood transfusions--may in fact be more harmful than previously thought.
In the meantime, there has been a lot of action surrounding what are now called “erythropoiesis stimulating agents” or ESAs, which are used primarily in patients with cancer and kidney failure patients on dialysis.
The latest event in this ongoing saga came last week, when the Centers for Medicare and Medicaid Services (CMS) issued a final rule intended to control the use of ESAs in the Medicare population.
To understand what has happened, one has to start in the early 1990’s when the drug was first approved to raise the red blood cell counts of patients with cancer, and reduce the need for transfusions.
This was indeed a breakthrough in cancer treatment. Doctors were very concerned about the potential adverse effects of transfusions (they still are), especially in light of HIV infection, and the possibility that the blood supply was not as safe as it could be.
The use of ESAs increased over time, to the present day when they occupy the distinction of being the single most expensive class of drugs used in the treatment of patients with cancer on the Medicare program.
Although the drugs were initially approved for use as supportive therapy in patients undergoing active cancer treatment, they eventually were used “off label” for cancer patients who had chronic anemia related to the cancer itself, including patients not receiving active therapy.
Apparently some patients had their red blood counts—as measured by what we doctors call hemoglobin and hematocrit—raised to normal levels. Colleagues tell me that patients indicated their quality of life was improved when the drug was used this way.
The problem was that there were not many studies that conclusively demonstrated that using the drug for this purpose actually resulted in clinical benefit as opposed to what we call a placebo effect, where the patient thinks the drug is helping but there is no proof that is the case.
Many of us are familiar with the ads appearing on television promoting these drugs and suggesting that they indeed had this type of beneficial effect on patients. Colleagues also have told me about buses covered with “shrink wrapped” advertising being strategically placed outside major cancer centers for patients and their families to see.
Earlier this year, reports surfaced suggesting that in some studies patients who were treated with ESAs and who were not on active therapy had poorer survival than patients who had not received the drugs.
The FDA stepped in, in cooperation with the manufacturers, and placed a “black box” warning on the drug, advising physicians to be very cautious in the use of ESAs because of their potential risk.
CMS announced that they were going to review the use of these drugs in the Medicare program, and proposed a nationwide coverage decision severely restricting the use of ESAs in the Medicare program, when used for the treatment of patients with cancer.
National organizations, including the National Comprehensive Cancer Network, the American Society of Clinical Oncology, and the American Society of Hematology also began taking a careful look at their guideline recommendations for the use of ESAs.
Along the way, a report in the New York Times suggested that the drug companies had paid physicians significant annual “bonuses” for using the drugs. According to the article, these payments amounted to hundreds of millions of dollars.
The Food and Drug Administration convened an expert panel in May, and the panel backed the FDA decision to place the black box warning (the highest level of warning available to the FDA) on ESAs. The panel also supported the need for further research to determine the true benefits and risks of the medication.
Now, CMS has issued their final coverage decision, which is very specific in when and how the drug can be used in Medicare patients with cancer.
For example, CMS ruled that ESAs are not medically necessary to treat the anemia of cancer, which is when a cancer patient has anemia from the disease itself but is not on active chemotherapy.
The drug can also not be used in patients who are being treated for several forms of leukemia, and for patients receiving radiation therapy.
CMS also provided very specific levels for blood counts before the treatment can be started, whether it can be continued, and when it must be stopped.
I know that CMS has been concerned about the use and potential overuse of ESAs in cancer treatment and dialysis for many years.
Up until this time, they haven’t been successful in reining in the use of what has turned out to be a very expensive treatment for the Medicare program (and for private insurers, as well). The events of the past several months have now given them the legal authority to do what they have been trying to do for some time.
But there is another side to this story that is even more intriguing to me.
I have talked with a number of my colleagues who are familiar with Medicare rules and regulations, and none are aware of a ruling that has been so proscriptive regarding a particular treatment.
Yes, Medicare has determined in certain circumstances what procedures and drugs they will cover and what they will not cover.
(What many people may not be aware of is that many of these coverage decisions are made by the regional Medicare carriers, and are called “local medical review policies.” National coverage decisions—that is, nationwide, uniform programmatic decisions to cover or not cover a particular device or drug—are the minority of determinations. Thus, decisions on whether or not to cover a particular device, procedure or drug can differ widely in different parts of the country based on how a particular Medicare carrier views the evidence or the success of a particular drug, procedure or device.)
But I am not aware of any similar circumstance where their regulations have been so specific when it comes to a drug used in the active treatment of patients.
Over the years, many doctors have raised concerns about what they call “cookbook medicine.” What that means is that the doctors are concerned that guidelines established by respected national organizations—such as the American Cancer Society—will be turned in some way by the insurers and/or the government into requirements as to how patients should be treated.
Medicine is still an art, they say, and not an exact science. Thus, there must be leeway for doctors to make decisions as to what is in the best interest of their patients.
A good example is the off label use of medications in cancer treatment. Many oncologists use drugs for the treatment of cancers in a manner not approved by the FDA. They rely on research reports which suggest the drugs may be effective. Insurers and CMS, until now, have granted cancer specialists fairly wide latitude in making those determinations.
That, in a nutshell, is why the use of ESAs grew based on oncologists’ assessments of their patients’ needs rather than firm evidence of effectiveness.
Now, the government has stepped in and said, essentially, “No more.” They have laid down strict rules as to how the drugs can be used.
Nevermind that enforcing these rules is going to be difficult. I can only imagine the chart audits that would be required to prove that a doctor violated the CMS protocol in a particular patient on chemotherapy.
There inevitably will be patients who demand their doctors give them ESAs because they make them feel better. I assume that the doctors will be able to give the drugs—but the patients, not Medicare, will probably have to pay directly to have their request fulfilled (despite the potential risks of the medicine) for what Medicare calls an “uncovered service”.
As you can see, this is a complicated issue and one that is not likely to go away or be resolved soon.
What is equally interesting is whether this approach of detailing which drugs can be used, when, how, at what dose and in which circumstances is just the beginning of a trend for the Medicare program.
I suspect we will be hearing more from my colleagues and their professional organizations over the next several months, as this saga continues to unfold.