Dr. Michael Kirsch, who blogs as the MD Whistleblower, posted what amounts to a terrific primer on surrogate markers measuring things like colon polyps, arterial plaque, cholesterol, and tumor markers:
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.
Please read his entire post, but here’s the punchline about the impact of surrogate markers on journalists’ reporting – and on the public trying to make sense of stories and studies:
Those of us who have been reading journals for some time are skeptical before we celebrate the medical breakthrough of the day or week. What is sound medical dogma today may fade over time and become junk science. This is particularly true of surrogate studies, which are indirect by definition.
Those who earn their living and their reputations from medical research may have a different view on surrogacy than I do. Indeed, surrogate research is an important research tool, that can open important therapeutic avenues and stimulate additional research. We must be mindful, however, how easy it is to exaggerate their conclusions beyond the data. 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.
Some of us understand things better with a dose of humor. James McCormack, PharmD, provides it in this video, “The Surrogate Battle: Is lower always better?“
Other resources on surrogate markers:
- Dr. Victor Montori of the Mayo Clinic and two co-authors wrote, “The Idolatry of the Surrogate” in the BMJ. We captured excerpts of that piece on our blog. They wrote that the use of surrogate outcomes to suggest a benefit from medical interventions – instead of “important patient outcomes such as death, quality of life or functional capacity” – was damaging patient care.
- A piece in BMC Medical Research Methodology is entitled, “A perfect correlate does not a surrogate make.”
- Also in the BMJ, Ray Moynihan wrote, “Surrogates under scrutiny: fallible correlations, fatal consequences.” (Subscription required for full access.)
- On the JAMA Internal Medicine Blog, see “Surrogate outcomes: That’s not why we play the game.”
- See “The Slippery Slope: Is a Surrogate Endpoint Evidence of Efficacy,” by John Fauber of the Milwaukee Journal Sentinel and Elbert Chu of MedPage Today. It’s part of a series.
- For a deeper read, you might be interested in “Evaluation of Biomarkers and Surrogate Endpoints in Chronic Disease,” a report by the Institute of Medicine.
- Dr. Vinay Prasad and co-authors wrote, “The Strength of Association Between Surrogate End Points and Survival in Oncology.”
- For humor, along with education on this topic, see Hilda Bastian’s Statistically Funny blog post about surrogate markers.
- We frequently comment on stories that fail to point out these caveats. A couple of examples were posted here.
- We’ve also written about drug ads and surrogate endpoints.