Distinguishing statistical significance from clinical significance

In the past post I was talking about the difference between statistical and clinical significance and how many reported studies have apparently mixed up the two. Now here's a nice case where people seem to be aware of the difference. The article is also interesting in its own right. It deals with AstraZeneca's cholesterol lowering statin drug Crestor being approved by the FDA as a preventive measure for heart attacks and stroke. If this works out Crestor could be a real cash cow for the company since its patent does not expire till 2016 (unlike Lipitor which is going to hit Pfizer hard next year).

The problem seems to be that prescription of the drug would be based on high levels not of cholesterol but of a protein named C-Reactive Protein whose high levels are supposed to constitute an inflammatory marker for high cholesterol. The CRP-inflammation-cholesterol connection is widely believed to hold but there is no consensus in the medical community about the exact causative link (many factors can lead to high CRP levels).

The more important recent issue seems to be a study published in The Lancet which indicates a 9% increased risk of Type 2 diabetes associated with Crestor. As usual the question is whether these risks outweigh the benefits. The Crestor trial was typical of heart disease trials and involved a large population of 18,000 subjects. As the article notes, statistical significance in the reduction of heart attacks in this population does not necessarily translate to clinical significance:

Critics said the claim of cutting heart disease risk in half — repeated in news reports nationwide — may have misled some doctors and consumers because the patients were so healthy that they had little risk to begin with.

The rate of heart attacks, for example, was 0.37 percent, or 68 patients out of 8,901 who took a sugar pill. Among the Crestor patients it was 0.17 percent, or 31 patients. That 55 percent relative difference between the two groups translates to only 0.2 percentage points in absolute terms — or 2 people out of 1,000.

Stated another way, 500 people would need to be treated with Crestor for a year to avoid one usually survivable heart attack. Stroke numbers were similar.

“That’s statistically significant but not clinically significant,” said Dr. Steven W. Seiden, a cardiologist in Rockville Centre, N.Y., who is one of many practicing cardiologists closely following the issue. At $3.50 a pill, the cost of prescribing Crestor to 500 people for a year would be $638,000 to prevent one heart attack.

Is it worth it? AstraZeneca and the F.D.A. have concluded it is.

Others disagree.

“The benefit is vanishingly small,” Dr. Seiden said. “It just turns a lot of healthy people into patients and commits them to a lifetime of medication.”

To some this may seem indeed like a drug of the affluent. Only time will tell.