The following is a guest post by Rodney Hayward, Director of the Robert Wood Johnson Foundation Clinical Scholars, and the National Clinician Scholars at IHPI. He’s a Professor of Medicine and Public Health at the University of Michigan. Follow him on Twitter at @ProfHayward.
Multiple small clinical trials suggested that PCSK9is (a new class of cholesterol-lowering medications) might be the next super drug-class. These early trials suggested that PCSK9is dramatically decreased cardiovascular disease (CVD) events (strokes and heart attacks) in those who had very high CVD risk and could not take statins (the current standard for treating cholesterol).
But most people with very high CVD risk tolerate statins just fine, greatly limiting the market for PCSK9is. A potential solution was to prove that the drugs worked better even for those on statins already. Unfortunately for the main PCSK9i manufacturer (Amgen), the first large randomized trial examining PCKS9-abs benefits in those on statins was highly disappointing. In the much larger market of high CVD risk people on statins, the relative reduction in non-fatal CVD events was much less than expected (25%) with no effect on mortality.
Although no one wants to have a heart attack or stroke, the lack of a mortality benefit – and the ~$14,500/yr price tag – led most to conclude that the expense was not worth the gain. Some pundits called for a price cut, but last week Amgen came up with a better idea – a full Money-Back Guarantee!
What A Deal!
In response to their falling stock price, Amgen announced last week that they would refund the cost of the drug in full if an individual taking it regularly has a major CVD event. This was portrayed by some media sources as an advance for pay-for-performance, and it certainly makes great intuitive sense. Yes, it may be a small consolation if the PCSK9i didn’t prevent your stroke, but “you get your money back if the medication doesn’t work for you.”
The problem is that the italicized sales pitch above is completely untrue.
What A Scam!
Modern psychology has demonstrated that we humans are terrible intuitive statisticians and that it’s quite easy to fool us with statistical illusions. So let’s briefly go through the math to understand why Amgen’s sales pitch is untrue.
A Best-case Scenario: A sizable group (though a small proportion of all adults) continues to be at very high CVD risk (~5% 5-year risk) after taking a statin, a daily aspirin, and blood pressure medications as indicated (cost ≈ $30-$150/yr). If you give a PCSK9i to 1000 such individuals, current evidence suggests that you would prevent, on average, 12 to 13 non-fatal CVD events over a five year period (0.05 [5-year risk] * 0.25 [PCKS9i’s relative risk reduction] = 0.0125 = 12.5 in 1000) at a cost of ~$72.5 million. We know that more than 30% of these events will be quite minor, but let’s ignore that so as to not be accused of nitpicking. Over 5 years, Amgen would need to return ~$1.4 million to ~37.5 of the 1000 people (2.5yrs [average years to CVD event in the 5-year period] * $14,500/yr * 37.5 [number of people who had a CVD event) ≈ $1.4 million).
But if only 12 to 13 people in 1000 benefited and only 37 to 38 people received refunds, who are the remaining 950 people who did not benefit? They are the 95% of people who were not destined to have a heart attack or stroke regardless.
So the claim, “If the PCSK9i doesn’t work for you, you get your money back!” is a complete scam. Over 98% (950 of ~962.5) of those who did not have a stroke or heart attack over 5-years received no benefit from the PCSK9i because they were not destined to have a CVD event regardless of treatment.
Ironically, the less likely a person is to benefit from the PCSK9i (ie, the lower their CVD risk), the less likely Amgen will need to refund their money.
So let’s restate Amgen’s Money-Back guarantee more accurately.
- Individual Perspective: If you are a very high CVD risk person on a statin and you take a PCSK9i for five years, you have about a 1.25% chance of avoiding a non-fatal heart attack or stroke at a cost of ~$70,000, about a 3.75% chance of having a stroke or heart attack and getting your money back, and about a 95% chance of paying ~$70,000 and receiving no benefit.
- Payer’s Perspective: For every 1000 high CVD risk beneficiaries on statins, paying for a PCSK9i for 5 years will prevent 12-13 non-fatal heart attacks or strokes, on average, and Amgen has generously offered to reduce the price to you by ~ 3.75%, from ~$72.5 million to ~$70 million.