FLAWED TRIALS. Waxler and Beers say the clinical trials that were used to apply for FDA approval of Lasik devices had flaws that call into question whether the procedure should have been approved from the beginning. They say the studies often included too few subjects. FDA’s guidance for Lasik trials says 300–400 subjects should be sufficient to detect adverse events. Given that the adverse-event ceiling was small—1 percent—using only 300 subjects means that if a trial had a 1 percent adverse-event rate, the true rate, given typical margins of error, could be as high as 2.89 percent. In other words, the actual adverse-event rate could be nearly three times FDA’s 1 percent allowable-risk rate. Given the margin for error, a larger sample size would have allowed for more-accurate results.
What’s even more troubling, however, is that the vast majority of studies didn’t even have 300 subjects. Our review of the clinical-trial data upon which the approval of 31 laser devices for Lasik were approved since 1998 found that only six of these included at least 300 subjects.
Another flaw in the trials, Beers and Waxler say, was poor subject retention. By the end of several trials, for a variety of reasons, significant percentages of subjects weren’t included in the evaluations. The trial sponsors said these patients weren’t “eligible” for evaluation, not that they had been “lost to follow-up,” but the end result is the same: They weren’t included in the final evaluations. This makes the findings much less reliable, or completely meaningless in some cases, such as the one in which we found 76 percent of patients weren’t evaluated at the end of the trial. We asked FDA about this, and the agency insists that “patient accountability was adequate” for all of the approved lasers. However, when we pointed out that FDA’s own guidance for these trials says attrition rates shouldn’t exceed 10 percent, FDA told us that the guidance was a nonbinding suggestion.
Donnenfeld says it’s difficult to retain patients in trials, because they often don’t come back for their visits. “You know why they don’t come back for follow-up? Because they are happy,” he says. “The unhappy ones come back to the doctor.”
Waxler heard that reasoning when he was at FDA, but after seeing evidence that facilities hid adverse events, he no longer buys it. “We made the assumption that these are the guys in the white coats and that they are the bigger experts who had their patients’ best interest at heart,” Waxler says. “The lack of skepticism on my part is pretty outrageous when I think about it.”
What’s even more outrageous is that consumers still aren’t able to get a clear picture on something that might affect their irreplaceable eyesight.
Catherine Elton is a freelance journalist who writes frequently about health issues. Among other topics for Consumers Digest, she investigated mammography, pediatric genetic testing and the overprescription of antidepressants.