Just over a decade ago, in a fit of hubris that shook the global economy, financial managers came to believe they could take groups of questionable sub-prime mortgages and transmute them into reliable AAA-rated assets. Investment banks gathered high-risk mortgages, mixed and matched them into collateralized debt obligations, and convinced rating agencies to certify the consolidated crap as shiny new gold. Only later did we realize these products were actually financial weapons of mass destruction.
Yet the basic lessons from this disaster have not been learned by some doctors and researchers, who in a process eerily similar to that of investment managers, have in some cases made medical weapons of mass destruction.
In health care, the problem is a technique called “meta-analysis.” It works like this: Suppose a variety of medical studies come to conflicting conclusions on a clinical question, such as are whether hormone replacement therapy prevents heart disease in older women. Doctors are confused. The evidence is unclear. But patients want answers.
Enter meta-analysis. Just as sub-prime mortgages often are lumped together without clear regard for credit-worthiness, various clinical studies are lumped together in meta-analysis without regard for their worthiness. The clinical trials may have included people on different doses of medications or with slightly different forms of a disease, and you take a few dozen patients from a study in Japan, merge them with a few hundred similar from Denmark or Texas, and voila! You now have a presumably statistically larger sample size to answer your clinical question.
But the quality of randomized clinical trials varies widely. Some are fastidiously conceived and executed; others are helter-skelter. In the 1990s, for example, meta-analysis convinced many people that hormone replacement in post-menopausal women could cut heart attacks by one-third to one-half. In 1995, for example, the New England Journal of Medicine cited a meta-analysis that combined 31 mediocre studies to “strongly suggest” hormone replacement stopped heart attacks. But in 2002, a large, randomized trial of over 16,000 women was finally done and it showed heart attacks strongly increased with hormone replacement.
When the underlying data are very strong, meta-analysis can be powerful. For example, when New York Times blogger Nate Silver predicts elections by combining different polls to increase the sample size. He performs a kind of meta-analysis. The secret to his success, as explained by Slate’s Dan Engber, is that the polls are well done in the first place, so the fundamental data is very sound. The same can’t be said of most clinical trials.
Unfortunately, even widely-read medical journals like American Family Physician promote meta-analysis as the best possible source (rated “Level A”) of evidence to guide doctors. The problem is that someone can simply take a bunch of “Level B” evidence, like “lower quality randomized controlled trials,” batch them together using meta-analysis, and suddenly upgrade to an AFP-approved “Level A.”
This has occurred repeatedly, and the results haven’t been pretty. In 1997, a group of Canadian researchers tried to put the brakes on meta-analysis in a startling paper. They pulled 19 meta-analyses from top-tier medical journals, on topics ranging from the effect of drugs on heart attacks to chemotherapy for breast cancer. (Keep in mind that such studies would be considered the highest form on medical evidence.) The researchers then located large, high quality randomized clinical trials on the same issues, performed years later, to see how the meta-analysis performed.
The researchers found the meta-analyses would have lead doctors to adopt useless treatments one-third of the time, and to reject helpful therapies another one-third of the time. After this debacle, why would anyone take the findings of meta-analyses very seriously?
Unfortunately, people do. In only the past month, various meta-analyses have been published in all manner of medical journals, arguing the magnesium can cut colon cancer rates, new drugs stop clots in heart rhythm problems, cholesterol drugs reduce cancer, and my recent favorite, that a gene called Pol-9 turns people into Republicans.
After the vindication of Nate Silver’s meta-analyses of poll data, sales of his book soared by over 850 percent. One can only hope that the number of meta-analyses published in the medical literature won’t enjoy a similar boost. They might work in political campaigns, but they don’t necessarily work in the medical field.