If you like this blog, send it to 3 (or more) of your friends and encourage them to sign up. Let’s keep the conversation going!
A little history, from a breast cancer perspective
During my time at Breast Cancer Action, I became something of an expert on reading clinical trial data. I learned that the success of clinical trials is based on what the scientists call “the primary endpoint.” That’s the effect of the drug under study on what the scientists are trying to study.
And, during that time, the primary endpoint of many studies shifted from “overall survival” (OS) – did the people in the study live longer?—to “progression free survival” (PFS) – did it take longer for the cancer to grow in people in the study receiving the study drug, as compared to the control group?
Why did this shift take place?
It seems logical that if it takes longer for cancer to grow, the people with the cancer will live longer. And both people with cancer and drug companies are impatient for results, though for different reasons. People with cancer want drugs today that don’t have so many side effects and that help them live longer. Drug companies want to get their drugs approved quickly so they can capture a share of the big markets, and cancer is a very big market.
With most types of cancer, you have study a lot of people for a long time to figure out if the treatment you’re giving helps them live longer. The thinking behind the shift in primary endpoints of studies, motivated by impatience, was this: We can determine whether a drug affects PFS more quickly than whether it extends OS.
And, if PFS indicates that a drug will work to extend the lives of cancer patients, then we can get to the market faster. Viewed this way, PFS is a “surrogate” – a stand in – for OS, and studying it is just as good as studying OS.
Unfortunately, it turns out that delaying progression of cancer doesn’t predict very well whether a person with the cancer will survive longer.
In the case of Avastin, a drug made by Genentech and approved for several cancers, the attempt to keep approval for its use in breast cancer has, at least so far, been foiled by the fact that in no study has Avastin been shown to improve overall survival of breast cancer patients, though it does delay progression. (The history of this drug in breast cancer can be found at www.bcaction.org. Just put “Avastin” into the search engine on the site.)
The FDA is still considering whether to withdraw Avastin from the breast cancer market. The stakes are very high for Genentech, but they are higher for people like you and me.
The reason the stakes of the Avastin issue are high for folks like us is that we need drugs that actually help us when we’re sick, not ones that may control some biological element related to our disease but not really make us better. And we sure don’t need any more drugs that make us feel awful (that is, degrade our quality of life) while not helping us at all. We are the ones who take these drugs, and need to them to work in a way that actually helps us. The use of surrogate endpoints puts too much emphasis on the “surrogate” and not enough on the people – us – the drugs are supposed to be helping.
Surrogate Endpoints: They’re Not Just for Cancer
There was a story you might have missed in the news in the last week – what with all the items about tornadoes and debt limits and other scary things — about using drugs to raise “good cholesterol” in the hopes that, like lowering bad cholesterol, doing so would extend the lives of people with heart disease.
In this case, the surrogate endpoint was a measurable increase in “good cholesterol,” on the theory that if that goes up, your heart is healthier.
The drug used to raise good cholesterol is niacin. It’s apparently pretty hard to tolerate – patients report flushing and headaches. And the drug did indeed raise good cholesterol, but it didn’t do a thing to improve the heart health of the people taking it. The surrogate endpoint was a failure.
When it comes to ALS, the disease with which I’m now dealing, the causes and biological drivers are not understood so there are, as yet, no real surrogates to try to control with drugs. ALS drugs that get tested will have to improve peoples’ symptoms, actually delay their decline in function (this is meaningful delayed progression, which improves quality of life), or help them live longer. I think that’s a good thing.
Can We Focus More on People?
Maybe it’s time to take a step back from the rush to approve drugs as fast as possible, and make sure they work for people who are suffering, no matter what the condition being addressed. After all, we’re not surrogate endpoints; we’re human beings.
© Barbara A. Brenner 2011