Here’s an example of comparative effectiveness that could save the public lots of money — and it was funded by the company whose drug lost.
SATURN, sponsored by AstraZeneca, pitted the company’s Crestor (rosuvastatin) against the soon to be generic Lipitor (atorvastatin). The study seemed like a mismatch. Crestor is better at reducing the bad cholesterol than Lipitor. Some observers may have wondered if the study was even worth doing.
As in sports, research often produces surprises. The results were a dead heat, which makes it pretty tough to make a case for the more expensive drug. Here are some lessons — and cautions — for the future.
We need these head-to-head comparisons. Drugs within a class may have important differences. Among the statins we have seen differences in safety profiles that led Baycol to be recalled. We have also seen some differences in benefit, with the more potent statins like atorvastatin reducing risk more than less potent statins. Such comparisons are too rarely performed, leaving patients and their doctors uncertain about choosing between alternatives.
We should remember that the study did not focus on patient outcomes. The investigators studied the effect of the two drugs on the progression of blockages in the arteries of the heart. This is not an outcome that a patient experiences, but it is believe to be a marker of patient risk. As a result, the study failed to show a difference between the drugs with a study of a marker of risk. We still do not know how these two drugs compare in safety and effectiveness. Nevertheless, these results make it harder to argue that Crestor is worth the cost.
This study is another reminder that the effect of a drug on cholesterol levels may not predict what happens to patients. We saw that most vividly with torceptrapib, the Pfizer drug that raised the good cholesterol, lowered the bad cholesterol and increased the risk of death. Recently we have seen additional examples of favorable changes in laboratory tests without the expected reduction in risk for tight glucose control for diabetes, fibrate therapy for diabetics, and niacin therapy for patients with heart disease. In this case, Crestor did improve the laboratory tests better than Lipitor – that favorable change in cholesterol levels did not translate into a more favorable change in the blockages in the heart arteries.
This is a study sponsored by the company that sells Crestor. The results are likely to make companies less likely to support head-to-head comparisons. The findings are a blow to the Crestor franchise. Notably the company was not required to conduct the study. I commend them for doing the work and asking the key question, but I wonder if the inability to show benefit of their drug will serve as a cautionary tale to others. I hope not, but recognize that we cannot depend on industry to fund studies that may run counter to their business interest. Had this study not been conducted, AstraZeneca could have continued to tout the superior laboratory effects of Crestor, without have evidence that the extra reduction in bad cholesterol may not matter.
We need to find other ways to fund these studies. A negative finding here produces a substantial return-on-investment for society. Perhaps there should be some public-private partnerships in the funding of these studies. And rather than suggesting it was folly for AstraZeneca to support this study, they should receive public praise and encouragement for taking a risk and putting the key question about the marginal benefit of their product on the table.
This study, however imperfect because of its focus on a surrogate endpoint, demonstrates why we need to generate more information about how drugs compare. Our assumptions about relative risks and benefits must be tested if we are to be informed in important health care decisions. We are continually being humbled when we do conduct the studies, because commonly they reveal results that are unexpected and consequential.