Death Points to Risks in Research

Arthritis is a disease in which the immune system attacks the joints, causing painful inflammation and degradation. Even when treated with powerful medicines, up to 40 percent of patients have ongoing pain in at least a few joints.

That medical reality is an economic opportunity worth as much as $3 billion a year, Parker has said. The company hopes to tap that market with tgAAC94, a virus engineered to have an extra gene. Injected into a joint, the virus infects cells and continuously produces proteins that sop up inflammatory molecules, according to the company.

Like other gene therapies -- hundreds of which have been tested since 1990 and all of which are still experimental -- the approach has the potential advantage of having the body crank out its own medicine for months or years after treatment, right where it is needed.

That sounded good to Mohr when Trapp, one of 20 U.S. doctors testing tgAAC94, invited her to join the study on Feb. 12.

There would be two injections, months apart, he explained. The first might be real, or it might be a placebo, but the second would definitely be the test product. She signed up immediately, and Trapp drew several tubes of blood to get the study going.

Two fundamental rules of clinical research were violated that day, experts said. First, consent forms are to be taken home and considered, not signed on first sight. Second, when a patient's own doctor is a principal investigator in a study, someone else is supposed to make the proposal.

"Because of the relationship . . . you have to worry that they won't listen carefully enough to the risks," said Hank Greely, director of the Center for Law and the Biosciences at Stanford University. Patients, he said, may think, " 'After all, if my doctor is doing this, it must be good for me.' That can be difficult to overcome with words in a consent form."

Trapp said he thoroughly explained the risks to Mohr.

Jonathan Moreno, an expert in the ethics of medical experiments at the University of Pennsylvania, said the consent form used by Targeted Genetics to outline the drug's potential dangers was thick with technical descriptions and thin on explaining "what's really going to happen."

"Even a smart person would have a very hard time figuring out what they're talking about," said Moreno, who examined the form at the request of The Washington Post.

The form was approved by one of the growing number of for-hire review boards that contract with biotechnology companies to ensure studies meet patient-protection standards. Targeted Genetics noted that the review firm it used is accredited and accepted by the FDA. But the use of private boards, as opposed to those run by universities or government agencies, has raised alarms among some medical ethicists since a for-profit review board risks losing repeat business if it is too tough on its clients.

Mohr's first shot, administered on Feb. 26, had no noticeable effect, and she wondered whether she got the placebo. But she was excited that the next one would be the real thing, Robb Mohr said.