1997 Drug Test on Teenage Inmates Probed

Stanford University was allowed to test a powerful psychiatric drug on dozens of teenage inmates in an experiment that the California Youth Authority now believes violated admittedly conflicting state laws.

The university and the CYA jointly conducted 1997 research that the agency’s director acknowledges probably was “not in compliance” with a law prohibiting medical research on prisoners.

During the eight-week study, 61 male inmates ages 14 to 18 were given Depakote--commonly used to battle seizures and mania--to see if it would make them less aggressive.

The experiment at the state correctional center in Stockton is under investigation by the CYA, the state attorney general and the new state inspector general, who was directed earlier this month to look into the “propriety and legality of Stanford’s study using CYA wards,” said Hilary McLean, a spokeswoman for Gov. Gray Davis.

“We’re not going to put up with wards being used as guinea pigs,” McLean said.

None of the youths appear to be harmed by the Depakote experiment, said officials, who had the young men examined. And all agreed to take part. But experts say such research in a prison setting is fraught with problems. The youths were asked by the institution that holds power over their living conditions and release time to take part in testing a potent drug.

The experiment also has highlighted a tangled, contradictory web of state and federal laws governing medical research on prisoners and children.

A state statute clearly says “no biomedical research shall be conducted on any prisoner in this state.” In the only previous attempt to conduct such research on CYA wards--a vitamin and mineral study--a special law was passed to allow it.

But a second state law, passed to allow inmates access to experimental HIV and AIDS medications, says prisoners can be given drugs that are available only through studies if it is in “the best medical interest of the patient.”

State officials believe the Depakote experiment violated the first statute and are investigating whether the second statute applies--and if so, whether the study was in the best interest of each teenager.

Stanford officials said the CYA’s former medical director assured them of the study’s legality, and they believe it met the requirements of the second statute.

Regardless, said Robert Presley, the state’s top corrections official, it won’t happen again.

“In the legal sense, and maybe in the moral sense, we missed the boat on this one,” he said.

Two weeks ago, he issued a plain-spoken directive that the CYA is not to conduct, or allow anyone else to conduct, medical research on the youths it imprisons unless it is first approved by the governor and codified into law.

Initial Enthusiasm

When the research took place, it was hailed as a coup for Stanford psychiatry professor Hans Steiner, who had managed to gain entry to a population usually off-limits to medical research. In a talk to colleagues last fall, he said the drug clearly helped some of the youths control their anger.

Stanford said it followed all the proper research regulations in approving the study. Steiner said his research was an effort to combat the growing problem of juvenile violence.

Current top CYA officials say they weren’t aware of the Depakote experiment, partly funded by drug maker Abbott Laboratories, until this year, after Steiner proposed a follow-up study on the teenagers.

When CYA attorneys looked at the details, red flags flew up, said CYA director Greg Zermeno, who learned about the study weeks after taking office.

CYA officials admit that their system for protecting the teenagers they imprison broke down. They are trying to find out why no concerns were raised at the time by former agency medical director Dr. Dan Cashman, and research director Elaine Duxbury, who not only allowed the study but served as co-investigators. The agency also is looking at what role, if any, two former officials, Richard W. Tillson, then deputy director for institutions and camps, and James C. Barnett, then agency deputy director, played in the approval of the study. Both men are listed as recipients of copies of a letter to Stanford, signed by Cashman, approving the study.

CYA officials say such a study is typically reviewed by the agency’s legal department and often by the director. In the case of the Depakote study, no official authorization for the study was given, state officials said.

Tillson, Barnett and Cashman have left the CYA. Barnett declined to comment. Duxbury, also listed as a co-investigator on the proposed follow-up study, referred questions to the agency’s public affairs office.

J.P. Tremblay, assistant director for communications, declined to comment on Duxbury’s role, citing personnel restrictions, but said “We are looking at all of this. . . . Anything that is in violation of [agency policy] or state law will be dealt with.”

Zermeno said there is “no chance” that Steiner will be allowed to do his follow-up.

“We’re taking precautions to ensure it never happens again,” said Zermeno, who recently issued his own in-house directive requiring his approval of even minor research projects. “We’re not going to take anybody’s word for what’s appropriate anymore--no matter how prestigious the organizations are.”

Presley, who said he first heard about the study after The Times began asking questions, said news of the study surprised him.

As a state senator, Presley sponsored the 1989 law that allowed the CYA vitamin study. The statute expired in 1995. Presley is now the secretary of the Youth and Adult Correctional Agency, and he had issued a directive banning future research.

In the past, he said, “Everyone assumed if you’re going to do [medical research] you have to have statutory authority to do it. No one ever questioned you had to have it.”

Presley said state officials must understand that any medical research on prisoners cannot go forward without a bill like the one he introduced a decade ago.

Researchers covet prison populations for studies, experts say, because they provide a constant, controllable group. The inmates all eat the same food, sleep the same number of hours and are easily accessible.

Prison rights advocates say CYA inmates are a literally captive population who might feel unduly pressured to take part in research.

“These kids are at such a disadvantage,” said Sue Burrell, an attorney with the Youth Law Center in San Francisco. “They have so little access to the world, to even talk to someone about this.”

Burrell questioned whether the teenage inmates, “kids who have problems with judgment and decision-making to begin with,” could really give informed consent to such a study. “The kids in there may be chronologically one age and mentally another age,” she said.

It is precisely because of such ethical concerns that California has stricter rules than the federal government for medical research on prisoners, legal advocates say.

Stanford University officials said they followed a detailed checklist to address regulations regarding research on prisoners and minors. The school’s human research oversight committee approved Steiner’s experiment.

Kathy McClelland, Stanford’s research compliance director, said in a statement, “The study satisfied federal requirements.” McClelland said the committee relied upon a letter from the CYA’s medical director to confirm that the study complied with state law.

But CYA officials, while acknowledging their part, blame Stanford for leading them to believe the university had done a thorough legal review.

Under federal regulations regarding research, Stanford is responsible for ensuring that the research meets both state and federal laws. When state law is more restrictive, it takes precedence over federal statutes.

“We believed Stanford University,” Zermeno said. The CYA no longer will rely on outside organizations in such cases, he said. “We are in the process of setting up our own medical and legal review team to make sure.”

Strong Credentials

Steiner, a respected adolescent psychiatrist, has conducted nonmedical research at the CYA for 15 years. The 53-year-old physician has focused recently on delinquency and how personality traits might be used to predict criminal behavior.

As a next step, he said in an interview, he theorized that psychiatric medications might work in violent teenagers to limit aggressive outbursts. He wanted to see whether teenagers who had committed violent acts could be helped by a drug.

Initially, Stanford’s McClelland said, Steiner proposed using one set of CYA teenagers as a control group and giving them a placebo.

But Stanford’s research oversight committee told Steiner that by law he couldn’t give one teenage inmate treatment and another nothing, McClelland said. Each teenager had to benefit from the study under federal regulations designed to protect young human subjects from harm. So Steiner set two drug doses, one low and one up to 10 times higher, and was allowed to begin his study, McClelland said.

His team screened about 175 teenagers at the O.H. Close Youth Correctional Facility in Stockton who had been convicted of at least one violent crime. In a consent form, the teenagers were told they would be given a drug that could help them control their emotions, especially their anger.

“The Federal Drug Administration has not yet approved this medication for the treatment of angry emotions, and that is why we have to do this study to learn more about the medicine,” the form stated.

The main side effects of the drug, an anti-epileptic, are drowsiness, nausea, indigestion and vomiting but could also include hair loss, anxiety, depression and a decrease in white blood cells.

Inmates who agreed to participate in the study, Steiner said, signed consent forms and were told that if they didn’t participate they would not suffer any repercussions. Attempts were made to secure their parents’ permission, but if their parents didn’t respond in 30 days, the CYA consented for them.

Sixty-one teenagers eventually agreed to participate in the study.

So unusual are drug experiments on juvenile inmates that Steiner was introduced as a trailblazer during a talk he gave at the 1998 meeting of the American Academy of Child and Adolescent Psychiatry in Anaheim. The Times obtained a tape recording of his talk.

“It’s remarkable that anyone has successfully pulled off a trial in a juvenile justice population,” said the talk’s moderator. “But Hans has.”

During the talk, Steiner explained how he preserved the quality of his research despite the restrictions of university officials.

“There’s a legal mandate that you cannot give one kid treatment and the other one not while they’re incarcerated,” Steiner said. “So whatever you offer has to be some form of treatment.”

But Steiner said that he set the low dose at a level he hoped would provide no therapeutic benefit.

“Remember,” Steiner told them, “we had to [give the low dose] in order to get the study through the system at all. We had to offer some treatment and the 125 [milligrams], we figured, was good enough to at least assuage some of the concerns on the part of the CYA, but not enough, hopefully, to get a lot of [therapeutic] responses.”

His calculations were largely on-target, Steiner said in the talk: Most of the teenagers given the low dose of the drug received little or no therapeutic benefit.

For many in the other group, Steiner told colleagues, the drug successfully reduced aggression with few negative impacts. He said one boy told researchers, “The staff used to tell me to count to 10 before I hit someone. Maybe I’d get to 2. Now I can count to 8.”

A Gray Area

In an interview, Steiner confirmed that he had wanted the low dose to be medically useless. But he said he didn’t know for sure it would be a placebo--he had “hoped” it would be. “What I wish for and what I know [were] two different things,” he said. “The researcher wants for there to be no reaction for the [sake of the] research.”

By law, Steiner said, “you have to deliver treatment to both. But from a research point of view, that’s not a good thing--that’s what most reviewers will criticize me for.”

In fact, the entire study has aroused the dismay of state and federal officials.

Presley, the top corrections official, said that while the knowledge about the drug’s ability to help violent youth would be good to have, “this wasn’t the way.”

Dr. Thomas Pugliese, director of human subject protection at the U.S. Department of Health and Human Services research risk office, said his office would have some serious questions if Steiner indeed gave a dose that was known to be a placebo to some of the youths.

“It would be hard to make the arguments that it would have had a reasonable probability of improving their health and well-being,” he said.

Stanford officials say they did not believe at the time of the research, and do not now believe, that the low dose was the equivalent of a placebo.

But prisoner advocates say the incarcerated teenagers appear to have been used as lab rats.

“It’s extremely disturbing,” said Steve Fama of the Prison Law Center in San Francisco.

If the youths had a medical or mental health condition that needed treatment, he said, “then the children should have been treated--not experimented on.”

But Steiner said he needed to conduct his research on children who had performed violent acts.

“People are not very cognizant about the biological underpinnings of this stuff,” he said. “There’s some forms of violence you can’t treat any other way [than with medications], and we’re depriving ourselves of tools.”

Steiner said he chose Depakote for the first test of his theory--although it probably wasn’t the most effective drug available--because of its relative lack of side effects and good safety record. He planned to try other medications when the CYA became more comfortable with the drug research, he said.

“I didn’t want CYA to get upset,” said Steiner, who is still working on other, non-medication research projects at CYA facilities. “[The Depakote experiment] was Dr. Steiner saying to the CYA, ‘I think we need to do something more for these kids.’ ”