Taking medicine is often a gamble. You are betting that the benefits will outweigh the risks. But do you realize a payoff is far from certain?
Drug companies rarely have to prove that their pills actually produce the desired outcome. All they have to show is that the medication moves the needle on some gauge or lab test.
These numbers are called surrogate endpoints. They are things like blood pressure, cholesterol or blood sugar. If you have hypertension, elevated cholesterol levels or diabetes, it is assumed that getting the numbers down is good enough. But the real aim is reducing the risk of kidney disease, strokes and heart attacks. Few drugs are proven to accomplish those goals.
Imagine going to a casino. If you want to play poker or roulette, you buy chips. Those chips are your surrogate money. If you win, you get to cash the chips back in for real money.
Any gambler would be outraged if the casino refused to trade the chips for cash at the end of a successful night. No casino would last long if it didn’t pay up.
Drug companies, though, get away without delivering on the eventual outcome because such studies are expensive and take a long time to complete. It is far easier just to prove that your pills lower cholesterol or blood sugar—and that is all that the FDA requires.
Several recent studies suggest that such surrogates are no longer adequate. A huge diabetes study financed by the federal government was halted prematurely because the results were so disappointing.
The ACCORD trial (Action to Control Cardiovascular Risk in Diabetes) was designed to lower blood sugar aggressively in high-risk diabetes patients. To everyone’s surprise, those who got the most intensive treatment with insulin and oral medications were more likely to die than those on standard therapy.
Researchers were shocked that better blood sugar control did not result in an improved outcome as expected. In fact, just the reverse occurred. It would be like winning the lottery and discovering you had to pay money instead of taking your winnings.
Another study, ALLHAT, shocked the cardiology community when it revealed that an inexpensive diuretic outperformed newer, fancier drugs in preventing heart attacks and heart failure. All the drugs lowered blood pressure, but most doctors expected the more expensive drugs to provide a survival advantage. Some of the most popular pills actually increased the risk for heart failure.
These disappointments are reminiscent of another recent setback. The ENHANCE study was supposed to prove that lowering bad LDL cholesterol aggressively with a combination pill called Vytorin (Zetia plus simvastatin) would reduce clogging of carotid arteries. Vytorin did work better than simvastatin alone to reduce LDL. But to everyone’s surprise, the lower cholesterol numbers did not lead to cleaner arteries.
The study was not large enough to tell scientists whether the drug would reduce the likelihood of heart attacks or strokes. Those studies will take years to complete. In the meantime, the unexpected outcome of the ACCORD trial should make everyone wary of just assuming that lower numbers by themselves mean better health and longer survival.