Editorial: A Reliance on Animal Tests May Bankrupt Merck
The observation is so common as to be a cliché: Animal tests don’t predict results in humans. We heard it when saccharin caused cancer in rats, due to a characteristic of a rat’s bladder that has no parallel in humans. We hear it every time a new treatment almost magically heals spinal cord injuries in mice or cures cancer in rats, only to fail miserably in human patients. We heard it when the U.S. General Accounting Office reported that 52 percent of new drugs caused serious adverse effects in humans that had not been predicted by pre-market testing. And we are hearing it again in the courtroom, as Merck is raked over the coals for marketing a painkiller that caused heart disease. In animal tests, Vioxx looked safe. But according to the Food and Drug Administration, Vioxx may have contributed to 27,785 heart attacks and sudden cardiac deaths between 1999 and 2003.
But if animal tests are such poor predictors of human risk, why are they used at all? Drug manufacturers know perfectly well that even the most optimistic results in animal tests mean very little regarding human safety. To assess safety, they still rely on the extensive series of human tests currently mandated for every new drug.
Part of the reason for animal testing is that manufacturers are not sure what else to do. Decades-old FDA regulations require animal tests, even when they have no applicability for the drug in question. From the manufacturer’s standpoint, it doesn’t matter if a rat’s heart or liver reacts differently from those of humans. Animal testing is the only path to FDA approval.
Meanwhile, non-animal alternatives are mired in a seemingly endless process of scrutiny by regulatory bodies. Non-animal tests may well be better than animal tests, but if regulators won’t accept them, manufacturers see no point in using them. Case in point: In the Multicenter Evaluation of In-Vitro Cytotoxicity, test-tube tests on human cells were clearly more accurate than rat and mouse tests in predicting the toxicity of a group of chemicals. Sadly, government regulators have yet to give the test system the green light, and it sits on the shelf.
Merck let animal tests cloud its judgment. Even as humans were succumbing to Vioxx-induced heart disease, the company believed in its tests on mice, rats, and monkeys that showed the drug to be safe—even beneficial—for the heart. When human studies showed Vioxx to be more dangerous than another painkiller, naproxen, Merck cited monkey studies showing that naproxen was actually good for the heart; Vioxx only looked dangerous by comparison.
Merck was wrong, and its animal tests may have led it into bankruptcy. Had the company paid attention to human studies showing the drug’s risks, it could have saved itself from judgments that will total well into the billions of dollars. More importantly, it would have saved tens of thousands of lives.
The Vioxx story is a call to action. The Food and Drug Administration and other federal agencies should move away from animal tests?\which, after all, are defined by involving the wrong species, if our aim is to protect human health. They must incorporate testing methods that are both more ethical and more accurate.
The FDA should also have a tighter standard for letting drugs enter the market. Currently, manufacturers must provide evidence that their products are safe and effective. If they also had to show that new drugs were necessary, there would be far fewer injuries and deaths caused by products that were marketed for no reason other than to take market share away from other successful drugs.
Whether driven by compassion, safety concerns, or the economic bottom line, it is time for manufacturers and regulators to move beyond animal tests toward better testing methods.
Neal D. Barnard, M.D.
President of PCRM