Thursday, March 15, 2012

Oncologists Answer the Question: What is an Added Month of Life Worth?

We recently surveyed U.S. oncologists in order to gain their perspectives on the emerging changes and challenges in the cancer landscape. The survey results spotlight an increasing tension between oncologists’ overwhelming optimism about the state of advancing science and their deep pessimism about the affordability of care.

One particular line of survey questioning addressed oncologists’ views of the value of incremental survival in the context of advanced cancer. We asked a series of questions designed to assess whether oncologists believe a new therapy that improves survival would be “worth it” under a variety of different contextual scenarios. Holding as a constant the assumption that the baseline price of the next best alternative care would total $15,000, we systematically varied: (1) expected survival time with the next best alternative care (either two months or nine months); (2) incremental survival with the new therapy (from one month to 12 months); and (3) the total cost of the new therapy (from $40,000 to $120,000 -- in other words, an increase in $25,000 to $105,000 over the cost of the next best alternative).

There are two key findings from those questions. First, in order for a majority of oncologists to declare the new therapy “worth it” even at the lowest of the prices we tested, the therapy must deliver a median of three additional months of life. Second, for the majority to judge those three additional months of survival an acceptable value, the cost of each additional month must be no more than roughly $9,000 to $10,000, regardless of whether baseline survival is two months or nine months.

The price-value yardstick that oncologists are using seems to have been appreciated by Roche when it set Zelboraf’s (vemurafenib) price at $9,400 per month. In clinical trials, Zelboraf extended overall survival from about six to 10 months to about 16 months in the approximately 50 percent of metastatic melanoma patients whose tumors are positive for the BRAF V600E gene mutation. Zelboraf was introduced with a companion diagnostic to identify tumors with the relevant mutation. The cost for a patient who takes Zelboraf for six months is $56,400.

After 13 years with no new drug approvals for melanoma, 2011 saw the introduction not just of Zelboraf but also of Bristol-Myers Squibb’s Yervoy (ipilimumab), a targeted immunotherapy that has improved overall survival from 6.4 to 10.1 months in late-stage melanoma. The approved treatment course for Yervoy is one infusion every three weeks for a total of four infusions; the total cost is $120,000.

On its face, Yervoy’s price-value -- four months of incremental survival at a cost of $30,000 per month -- seems to falls short of what oncologists require in order to say that the incremental survival is worth the added cost. But the calculus in this case is not simply a matter of averages. A subset of patients -- about 11 percent -- had striking and potentially longer-lasting responses to Yervoy, although it is not yet possible to identify these patients in advance. A drug that benefits fewer patients for a potentially longer period of time might be able to command a higher price than a drug that works modestly well for many people.

We as a society are in the process of arriving at a framework for thinking about the value of life extension at a time when the model for cancer therapy is slowly shifting away from the mass market to the niche. The economics of these drugs are feasible only if society bears higher costs for a smaller subset of patients because manufacturers have to be able to reap the rewards of developing drugs that are, in some sense, personalized. And this economic perspective seems entirely consonant with our intuitive value system that recognizes that adding a year of life (rather than just a few months) is adding quality, not just quantity. In effect, the scale is not linear.

This is the new challenge of 21st century cancer care. It will be interesting to see how professional and public perceptions of price-value evolve as newer drugs bend the framework. With our survey on oncologists, we have looked at provider perspectives. In the future, we’ll discuss the perspectives of patients and payers on what will be one of most important commercial and ethical questions of the next two decades in medicine.

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