Thursday, January 10, 2008

A Skeptical Look at a Dire Warning: Is Medicare "Willing to Let Seniors Suffer and Die Sooner from Cancer?"

Yesterday's Providence Journal included an op-ed by Robert Goldberg, entitled "Fewer Drugs, Fewer Seniors," featuring this dire warning:

Now, to save money, America’s Medicare program is willing to let seniors suffer and die sooner from cancer....

How in the world could Medicare do that?

As a first step, the Center for Medicare and Medicaid Services (CMS), which runs Medicare, decided to restrict reimbursements for erythropoiesis stimulating agents (ESAs) — drugs that prevent the fatigue from chemotherapy-induced anemia.

In this case, CMS came up with a new standard for paying for new drugs called the Precautionary Principle. This principle, developed by environmental extremists in Europe nearly 20 years ago, states that anything unknown is unsafe and should not be used. CMS asserts that it does not know enough about the safe use of ESAs beyond achieving a specific hemoglobin level. So it won’t pay for anything above that point. No exceptions. If seniors feel fatigued or confused they can pass the hat like Chantelle Hill.

And why in the world would they do that?

The CMS decision has nothing to do with safety and everything to do with cost.

But before hitting the panic button, consider how the author of the op-ed, Robert Goldberg, identified as "Vice President of the Center for Medicine in the Public Interest," tried to support his contention.

First, he ignored the most relevant evidence while criticizing less relevant studies.

CMS says that ESAs cause cancer and heart problems beyond hitting a hemoglobin target of 10 g/dL. But that claim is based largely on two studies that examined the experimental use of extremely high dosages of ESAs in patients without cancer.

Goldberg ignored six studies that used different doses of different erythropoetin products (or ESAs, to use his terminology) to achieve different target hemoglobin levels in patients with various kinds of cancer. Four were published, and all six were summarized last June in the New England Journal of Medicine [Khuri FR. Weighing the hazards of erythropoiesis stimulation in patients with cancer. N Engl J Med 2007; 356:2445-2448. Link here.] Five of the studies showed shorter average survival in patients given erythropoetins. One showed increased progression of disease and a statistically insignificant trend towards decreased survival. This set of studies raise the concern that erythropoetins, rather than preventing early death, may hasten early death.

Next, Goldberg turned to the US Food and Drug Administration (FDA) for support.

The Food and Drug Administration, its European counterpart the European Medicines Agency, and physician groups such as the American Society of Clinical Oncologists recognized the value of these studies in guiding clinical decisions but not restricting them.

It is very rare for the FDA to restrict use of a drug already on the market. Actually, the FDA has emphatically warned about the possibility that erythropoetins may hasten death, rather than increase survival. The FDA considered the six studies summarized in the Khuri article above, and issued the following official "black box" warning for these drugs (for example, see label for Epogen below).

WARNINGS: Erythropoiesis-Stimulating Agents

Use the lowest dose of EPOGEN® that will gradually increase the hemoglobin concentration to the lowest level sufficient to avoid the need for red blood cell transfusion (see DOSAGE AND ADMINISTRATION).

EPOGEN® and other erythropoiesis-stimulating agents (ESAs) increased the risk for death and for serious cardiovascular events when administered to target a hemoglobin of greater than 12 g/dL (see WARNINGS: Increased Mortality, Serious Cardiovascular and Thromboembolic Events).

Cancer Patients: Use of ESAs
• shortened the time to tumor progression in patients with advanced head and neck cancer receiving radiation therapy when administered to target a hemoglobin of greater than 12 g/dL;
• shortened overall survival and increased deaths attributed to disease progression at 4 months in patients with metastatic breast cancer receiving chemotherapy when administered to target a hemoglobin of greater than 12 g/dL;
• increased the risk of death when administered to target a hemoglobin of 12 g/dL in patients with active malignant disease receiving neither chemotherapy nor radiation therapy. ESAs are not indicated for this population.

Finally, Goldberg asserted,

Seniors who are stronger and don’t have to spend time shuttling to the hospital are better equipped to endure newer and more powerful combinations of cancer drugs in the elderly. Indeed, a recent study conducted by Columbia University’s Frank Lichtenberg found that an aggressive chemotherapy regimen for seniors extends life expectancy by 8 to 12 months.

Lichtenberg's study seems so irrelevant that I wonder if it was raised as a deliberate distraction. Goldberg's original warning was about restrictions on payments for erythropoetins, not about chemotherapy. That Lichtenberg's study is not yet published, and that Lichtenberg is an economist at the Columbia Business School, just add to the irrelevance.

So to summarize, Robert Goldberg's dire warning that Medicare is out to make sure, as implied by the title of his article, there are "Fewer Drugs, Fewer Seniors," seemed to be based on a mixture of half-truths and irrelevancies. So why did he make this warning?

I don't know, but what the Pro Jo article did not reveal is some relevant background information about the ties of Goldberg's organization to pharmaceutical companies. We have noted before that Goldberg works for the Center for Medicine in the Public Interest, whose president is Senior Vice President for Global Health Affairs at the big public relations firm Manning, Selvage and Lee. Manning, Selvege and Lee has many big pharmaceutical accounts, as listed on the site. This suggests at least an indirect conflict of interest, favoring the interests of the pharmaceutical industry, that should have been revealed in this op-ed article. Furthermore, in a post on CMPI's blog, Goldberg acknowledged "CMPI accepts grant from drug companies -- and we do so proudly because they actually invent things that help people."

We have previously posted about other stealth health policy advocacy coming from CMPI (here and here.)

If CMPI really accepts money from pharmaceutical and biotechnology companies "proudly," its officers should not be afraid to make this and any other financial ties they may have to these companies clear when they write op-eds in major newspapers. That might at least alert readers who are not trained in evidence-based medicine to be a bit skeptical about the apparently scientific, but actually mostly irrelevant references with which they adorn their writing, and to wonder how much relevant evidence they did not bother to include.

That health care in the US is now in a crisis is now a cliche. Finding our way out of this crisis requires logical discussion based on evidence, not half-truths and irrelevancies promulgated by people with hidden financial ties.


Robert said...

1. The op-ed is based on a much more comprehensive review of all the literature including a considerable amount of research about the impact of blood transfusions on mortality on cancer patients that was not included or reviewed by CMS. In that report I simply call for CMS and companies to work together to find the right dose for the right patient at the right time. Patient-centered medicine is what we are all about.

2. I am assuming therefore that you side with CMS as opposed to ASCO, ASH, EMEA and other professional societies that support using practice guidelines that include the 12g/dl.

3. Is the government objective and right in all cases?

2. Drug and biotech companies do excellent and important work and appreciate the support they provide me and others to conduct policy research. They are not perfect but they are not evil nor are the hundreds of thousands of researchers who in their employ.

3. I hope you apply the transparency standard with equal measure to those with whom you agree including those who would consult for government agencies who have support from foundations with specific policy agendas.

Thank you for considering these remarks. Best wishes for the New Year.

Bob Goldberg
Center for Medicine in the Public Interest

Roy M. Poses MD said...

Thanks for your prompt comments. Here are some responses.

1. But what about the six studies summarized in the NEJM article cited above? All showed that cancer patients who received ESAs did worse than those who didn't.

You may have called simply for better definition of the optimal dose of ESAs in certain situations in your report, but that's not how you ended your op-ed. That ended, "Fewer drugs. Fewer seniors.
Maybe that should be Medicare’s slogan for the future." That's was a bit more inflammatory.

2. I am not an oncologist, but I would suggest that the six studies cited by Khuri suggest the use of the lowest possible dose necessary to prevent excess transfusion.

3. Government agencies and employees are right sometimes and wrong sometimes. Health Care Renewal certainly has not spared both from criticism. In particular, we have posted numerous times about the unfairness of CMS set physician reimbursement policies. We have also criticized the NIH, FDA, CDC, etc.

2a. I appreciate the good work done by pharma/ biotech and device companies. I appreciate their many useful products. I do not think they are anything approaching evil. But I am afraid that some of them have been badly led of late, and that their bad leadership has caused bad consequences.

Finally, I am afraid that if one or one's organization takes money from a given source, there is a natural human tendency to be less critical of that source, and of its interests than would otherwise be the case.

3a. I agree that government agencies and private foundations also may have their own agendas. I do believe that such support should be disclosed, just as support from commercial health care organizations should be disclosed.

Do you plan to disclose CMPI's funding sources in future op-eds and similar writings for general audiences?

I suspect that most commercial health care corporations have more focused agendas, having to do with making money and selling their products and services, than do government agencies and foundations.