When Ellen M. Roche, 24, volunteered for the asthma experiment, she didn't expect to benefit from it--except for the $365 she'd be paid. Unlike clinical trials, in which most patients hope that an experimental therapy will help them, this study was designed just to answer a basic question: how does the way a normal lung reacts to irritants shed light on how an asthmatic lung responds? To find out, scientists led by Dr. Alkis Togias of Johns Hopkins University had Roche and other healthy volunteers inhale a drug called hexamethonium. Almost immediately Roche began to cough and feel short of breath. Within weeks her lungs failed and her kidneys shut down. On June 2 Roche died--a death made more tragic by the possibility that it was preventable. Last week the federal Office for Human Research Protections (OHRP) ruled that Hopkins's system for protecting human subjects is so flawed that virtually all its U.S.-supported research had to stop.
The worst part is that Hopkins, one of the nation's premier medical institutions, is not alone. Two years ago the inspector general of the Department of Health and Human Services warned that the system safeguarding human subjects is in danger of a meltdown. The boards that review proposed studies are overburdened, understaffed and shot through with conflicts of interest. Oversight is so porous that no one knows how many people volunteer to be human guinea pigs (21 million a year is an educated guess), how many are hurt or how many die. "Thousands of deaths are never reported, and adverse events in the tens of thousands are not reported," says Adil Shamoo, a member of the National Human Research Protections Advisory Committee and professor at the University of Maryland. Greg Koski, head of OHRP, has called the clinical-trials system "dysfunctional."
The OHRP findings on Hopkins are nothing short of devastating. After a three-day inspection last week, OHRP concluded that the Hopkins scientists failed to get information on the link between hexamethonium and lung toxicity, even though data were available via "routine" Internet searches and in textbooks. The drug is not approved for use in humans; the hexa-methonium Togias used was labeled [F]OR LABORATORY USE ONLY. The review board, OHRP charges, never asked for data on the safety of inhaled hexamethonium in people. The consent form that Roche signed states nowhere that hexamethonium is not approved by the FDA (the form describes it as a "medication") and didn't warn about possible lung toxicity.
Hopkins itself concluded that the review board did not do all it could to protect the volunteers, and suspended all 10 of Togias's studies. Still, the university--whose $301 million in federal grants for 2,000 human studies made it the largest recipient of government research money last year--is seething. "Hopkins has had over 100 years of doing clinical trials," says Dr. Edward Miller, CEO of Johns Hopkins Medicine. "We have had one death in all of those years. We would have done anything in the world to prevent that death, but [suspending the studies] seems out of proportion." Hopkins calls the shutdown of its experiments "unwarranted, unnecessary, paralyzing and precipitous." OHRP is letting trials continue "where it is in the best interests" of subjects. The rest of the studies can resume once Hopkins submits a plan to restructure its system for protecting research subjects. How quickly that happens, says a government spokesman, depends on Hopkins.