It’s in vogue in medicine to market drugs offering slight benefit to desperately ill patients at cost of between $50,000 and $100,000/year.
What’s the real cost of these “advances.”
In a hypothetical (but typical) situation lets say the drug is used in 100 patients and compared with another group of 100 patients receiving placebo (or standard therapy).
As one would hope the group of patients receiving the study drug appears to have some response. In the distant past a response was defined as a decrease in tumor bulk of 50%. In recent years that definition has been broadened, some would say undermined, to mean that there was no evidence of tumor progression during treatment. Since we are in “modern” times lets use the definition of response being no progression.
We do our study and find in the group of patients receiving placebo (or standard therapy) 25% showed no progression. While in the study group receiving the new drug of 100 patients 40% showed no progression.
Drug companies take such data as evidence of the drug’s efficacy and try to get FDA approval. Note there is no evidence at this point of extension of life.
The real cost of this advance is interesting to contemplate. Consider treating 100 patients with a $100,000 drug–that’s 10 million dollars. Consider that just 40% get a “benefit” with the drug and 25% had the same “benefit” with placebo (or standard therapy)–and a marginal “benefit” at that. That means that 6 million dollars was spent on patient who got no “benefit” at all from the drug (the 60 of 100 patients without “benefit”). 2.5 million dollars on the 25 patients who would have shown no progression with placebo (or standard therapy). The incremental “benefit” of the drug over placebo or conventional therapy was therefore a total of 15 patients.
That means in our hypothetical but somewhat typical new drug situation 85 out of 100 patients will be treated with the $100,000/year drug and get nothing from it. 15 patients get a limited improvements. The cost/patient that improved is $100,000 X 100 patients treated/15 patients who get the improvement=$666,666 expended for each patient who improved. It should be noted that this is a cost per year figure for a single drug.
How much is a reasonable amount for the system to spend for an improvement. It’s been thought in the literature that between $50,000 and $150,000 per year of life gained was an affordable sum. It’s never been clear to me where these numbers came from but in the cost efficacy literature they seem to be the most used figures.
In our hypothetical situation our outcome was no progression of disease during the treatment period. But for the sake of our discussion lets say the study continues and the study patients (the 15% with benefit) lived a median of 2,3,4,5, or 6 months longer. For what it’s worth except for the very rare super effective new agent (Gleevec for example) most new biological agent’s improvement of survival is in the 2-6 month range.
If the median improvement is 2 months then the cost of a 12 month survival would be 6 X $666,666 (the cost/patient who benefitted) or about $4,000,000 to buy a total of a year’s survival time for patients who benefit from the treatment.
If the improvement is 6 months then the cost of 12 months survival would be 2 X $666,666 or in the range of 1.33 million dollars.
Neither would be considered cost effective by any of our current measures.
Medicynical Note: You won’t find the drug companies funding cost efficacy studies nor touting their results as cost efficient. Instead our hypothetical study would be touted as showing a 60% improvement in response rates between placebo and study group. (40% response rate with drug/25% with placebo or conventional Rx X 100=160%) It won’t be easy to find out that the difference between a “response” to placebo and the study drug was 15% (40% vs 25%) or that the benefit was just 2-6 months, if that. That the American way of drug marketing.
In case you think the above is exaggerated consider these from real life NEJM 355:2542-2550
The median survival was 12.3 months in the group assigned to chemotherapy plus bevacizumab, as compared with 10.3 months in the chemotherapy-alone group (hazard ratio for death, 0.79; P=0.003). The median progression-free survival in the two groups was 6.2 and 4.5 months, respectively (hazard ratio for disease progression, 0.66; P<0.001), with corresponding response rates of 35% and 15% (P<0.001). Rates of clinically significant bleeding were 4.4% and 0.7%, respectively (P<0.001). There were 15 treatment-related deaths in the chemotherapy-plus-bevacizumab group, including 5 from pulmonary hemorrhage.
Or this from today’s (April 25, 2010) Seattle Times:
Dendreon’s case rests largely on a study of more than 500 men with an advanced form of prostate cancer that spread to other parts of their bodies. Of the men who got Provenge, nearly a third were still alive in three years, compared with less than a quarter of those who got placebos. (medicynical emphasis) The vaccine boosted median survival time by 4 months, from 22 months in the placebo group to 26 months in the Provenge group.
How much difference is there between nearly a third and less than a quarter? I wonder who provided this verbiage? I figure an 8% benefit. Affordable?
Medicynic 