{"id":129,"date":"2011-06-03T05:41:32","date_gmt":"2011-06-03T05:41:32","guid":{"rendered":"http:\/\/barbarabrenner.net\/?p=129"},"modified":"2011-09-15T19:11:48","modified_gmt":"2011-09-15T19:11:48","slug":"people%e2%80%99s-lives-as-the-endpoints-of-medical-research-%e2%80%93-now-there%e2%80%99s-an-nifty-idea","status":"publish","type":"post","link":"https:\/\/barbarabrenner.net\/?p=129","title":{"rendered":"People\u2019s Lives as the Endpoints of Medical Research \u2013 Now There\u2019s An Nifty Idea"},"content":{"rendered":"

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A little history, from a breast cancer perspective<\/span><\/p>\n

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 \u201cthe primary endpoint.\u201d That\u2019s the effect of the drug under study on what the scientists are trying to study.<\/p>\n

And, during that time, the primary endpoint of many studies shifted from \u201coverall \"\"<\/a>survival\u201d (OS) \u2013 did the people in the study live longer?\u2014to \u201cprogression free survival\u201d (PFS) \u2013 did it take longer for the cancer to grow in people in the study receiving the study drug, as compared to the control group?<\/p>\n

Why did this shift take place?<\/p>\n

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\u2019t 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.<\/p>\n

With most types of cancer, you have study a lot of people for a long time to figure out if the treatment you\u2019re 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.<\/p>\n

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 \u201csurrogate\u201d \u2013 a stand in \u2013 for OS, and studying it is just as good as studying OS.<\/p>\n

The Rub<\/span><\/p>\n

Unfortunately, it turns out that delaying progression of cancer doesn\u2019t predict very well whether a person with the cancer will survive longer.<\/p>\n

In the case of Avastin, a drug made by Genentech and approved for several cancers, the \"\"<\/a>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<\/a>. Just put \u201cAvastin\u201d into the search engine on the site.)<\/p>\n

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.<\/p>\n

The Lesson<\/span><\/p>\n

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\u2019re sick, not ones that may control some biological element related to our disease but not really make us better. And we sure don\u2019t 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 \u201csurrogate\u201d and not enough on the people \u2013 us \u2013 the drugs are supposed to be helping.<\/p>\n

Surrogate Endpoints: They\u2019re Not Just for Cancer<\/span><\/p>\n

There was a story you might have missed in the news in the last week \u2013 what with all the items about tornadoes and debt limits and other scary things — about using drugs to raise \u201cgood cholesterol\u201d in the hopes that, like lowering bad cholesterol, doing so would extend the lives of people with heart disease.<\/p>\n

In this case, the surrogate endpoint was a measurable increase in \u201cgood cholesterol,\u201d on the theory that if that goes up, your heart is healthier.<\/p>\n

\"\"<\/a>The drug used to raise good cholesterol is niacin. It\u2019s apparently pretty hard to tolerate \u2013 patients report flushing and headaches. And the drug did indeed raise good cholesterol, but it didn\u2019t do a thing to improve the heart health of the people taking it. The surrogate endpoint was a failure.<\/p>\n

When it comes to ALS, the disease with which I\u2019m 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\u2019 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\u2019s a good thing.<\/p>\n

Can We Focus More on People?<\/span><\/p>\n

Maybe it\u2019s 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\u2019re not surrogate endpoints; we\u2019re human beings.<\/p>\n

\u00a9 Barbara A. Brenner 2011<\/p>\n