Beware surrogate markers: colon polyps, arterial plaque, cholesterol, tumor markers

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Michael Kirsch, M.D, who blogs as MD Whistleblower, offers an educational insight about surrogate markers – especially helpful if you don’t know much about these. And, in his estimation, many news stories don’t seem to reflect much knowledge on the topic. Excerpt:

Why do some medical studies, which achieve breaking news status, often fall so short of our expectations? Physicians are cynical about these medical milestones, since they are often short-lived. Today’s cure may become tomorrow’s disease.

A common practice and serious flaw in medical research is to rely upon a surrogate marker when studying a disease. Let me explain. If you endure the following few paragraphs of literary driftwood, you will understand press reporting of medical studies on a deeper level. This could directly affect your medical care and generate some interesting conversations during your next doctor visit.

The impact on medical care from misunderstanding surrogate markers could be profound. Here’s his definition:

A surrogate marker is an event or a laboratory value that researchers hope can serve as a reliable substitute for an actual disease. A common example of this is blood cholesterol levels. These levels are surrogates, or substitutes, for heart disease. If a medical study demonstrates that a medication can lower cholesterol level 10%, then we assume that this will also lower the risk of cardiovascular disease. Why doesn’t this same study determine if an anti-cholesterol drug decreases heart attack rates directly? After all, most folks would rather be spared a heart attack than have a silent decrease in their blood cholesterol levels.

Surrogates often take on a life of their own, far removed from the actual disease they represent. Patients shouldn’t care if their ‘surrogates’ are improving; their objective should be to prevent disease, feel better and live longer. Yet, we physicians have often convinced our patients that surrogate improvement means better health. Monitoring cancer blood tests called tumor markers illustrates this point well.

“Great news Mrs. Bedridden. Your cancer blood test improved 10 points!”

“Thank you doctor, but I still can’t walk.”

As a gastroenterologist, Kirsch also frames colon polyps as a surrogate marker.

Polyps are not diseases. They are surrogates for colon cancer. We hope and believe that when we remove pre-cancerous polyps that we are reducing your risk of colon cancer. Interestingly, there is no double-blind placebo controlled trial (the gold standard of medical research) that establishes that colonoscopy reduces colon cancer. Just because it sounds logical, doesn’t mean that it’s true.

The public needs to understand this issue. Think about this the next time you read a news flash that promises a medical miracle. Chances are that the miracle is a mirage.

Amen. Everytime I’ve written recently about what we don’t know about colonoscopy, someone always rises up defending the test from the perspective of intuition, not science. It’s good to hear this honest assessment from a gastroenterologist.

Read his entire piece at the link above. It’s good for journalists, consumers and physicians.

Since we stumbled onto colonoscopy a bit with the above, I want to draw attention to a commentary, “Colonoscopy vs. Sigmoidoscopy Screening: Getting It Right,” in the Journal of the American Medical Association last week, raising more questions about colonoscopy. Excerpt:

“From a public health and policy perspective, these apparent limitations of colonoscopy can no longer be ignored. The accumulating evidence has not established the long-held belief that colonoscopy carries greater benefits than sigmoidoscopy. How should the medical establishment advise the public given this conflict between widespread belief and current evidence?

And, from earlier in the piece, this excerpt:

A third approved screening mode for colorectal cancer is the fecal occult blood test (FOBT), which has had efficacy proven in randomized trials. …Whether sigmoidoscopy plus FOBT is a superior screeningstrategy vs sigmoidoscopy alone remains a question.

I can’t leave this issue alone. We should discuss more openly, more often, what we know and what we don’t know about all screening tests. This should include the difference between what we know and what we want to believe.

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Paul Scott

August 3, 2010 at 12:39 pm

Blood sugar levels in diabetes is another apparently meaningless surrogate. A meta analysis in the Annals last year by Mayo’s Victor Montori found that drugs like Actos and Avandia, while capable of lowering blood sugar, did not reduce any symptoms of the illness meaningful to patients (heart attacks, vision problems, etc etc.) Those two drugs consumed $3.6 billion last year in the US alone.


August 7, 2010 at 7:40 am

The whole object is of course to sell drugs. The more meaningless surrogates there are, the more the public can be convinced there is something wrong with them, and that they are in imminent danger if they don’t have whatever drug or procedure is recommended to change, rectify or reduce whatever the ‘problem’ measurement is.
There is no focus on health.