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Essais cliniques et recherche fondamentale | Prisons

Questions raised over AIDS research on inmates

19 March 2000 (St Petersburg Times)

ORLANDO, 19 March 2000 (St Petersburg Times)

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In a prison in the shadow of Disney, inmates are getting the AIDS drugs of tomorrow. But are they informed of the risks, and is the study under oversight?

By SYDNEY P. FREEDBERG

It was once strictly taboo, evocative of the Nazis and Nuremberg: doing medical experiments on prisoners, often without their full knowledge.

Yet today, about 35 miles from Walt Disney World’s Tomorrowland, dozens of inmates are being treated for HIV and AIDS with combinations of medications that could have unknown dangers.

The prisoners — murderers, rapists, burglars and drug dealers — are human lab rats.

Inmate advocates worry that prisoners may be pressured to become research subjects or don’t fully understand the risks.

The top scientist on the project, a University of Miami professor with a world-renowned reputation and financial support from several drug companies, says she is careful and plays it straight with inmates. Her studies, she says, could help find a cure for AIDS.

The prisoners? Most think they’ve been blessed with everything from comfortable shoes to a chance to take anti-HIV drug combinations, not yet available to the public, that may improve and prolong their lives.

"I’m a living, breathing, walking miracle," said Yakab Dennis, a 33-year-old convicted rapist who readily volunteered for the research, then saw his health rebound dramatically. "I thank God for the study."

The potential for abuse is still there, however. It has been only two years since Florida finished changing its rules to allow research on some of its 3,250 HIV-positive inmates.

Within a year, questions had begun. And then last July, a state prison official wrote a letter assuring an oversight board that the research would easily comply with the Nuremberg Code, adopted after 16 Nazi doctors were found guilty of torturing concentration camp prisoners deemed "unworthy of life."

Recognizing the potential for exploitation, the Florida prison system says it agreed to the testing only after putting in place a system of oversight and creating a watchdog group to protect the inmates.

Yet the watchdog group has been disbanded.

Critics say the Department of Corrections has failed to adequately monitor the studies.

The University of Miami, citing federal confidentiality requirements, declines to release records about the research or safety reports it compiles if an inmate gets a bad reaction to a medication.

And the person originally selected to look after inmates’ interests is a state prison official who has championed the research project — a dual role that ethicists find troubling.

What’s more, two pharmaceutical companies involved in AIDS research say they have given that official, Dr. David L. Thomas, honoraria for his work with the companies. Thomas did not respond to questions about those honoraria. But in an interview in December, he stressed that he follows Florida’s financial-disclosure requirements.

The Department of Corrections, which has been under fire in recent months amid reports of inmate abuse and inadequate medical care, defends Thomas and the state’s oversight of the research project.

"I’m sure you will find someone, whether it’s a prisoner rights advocate or a so-called expert on medical ethics, to criticize us, especially on the issue of informed consent," spokesman C.J. Drake said, adding that the research is ethical, proper and voluntary.

Drake hailed the research site, located in an AIDS prison, as a national model. He said the St. Petersburg Times, in asking questions, is "nitpicking issues of secondary importance."

After questions from the Times, however, federal regulators began an inquiry into whether Florida’s prison studies, which are run by the University of Miami and financed by drugmakers and the National Institutes of Health, comply with rules to protect human subjects.

Dr. Norman Altman, the University of Miami’s vice provost for research, says the university is cooperating with the Office for Protection from Research Risks, a tiny arm of the NIH that oversees human subjects at hundreds of institutions.

"It’s our intention to do this right," Altman said, adding that the university would look into complaints about informed-consent procedures. "And if things aren’t being done right, it’s our intention to correct them."

Two or three times a day, several dozen inmates in freshly starched white uniforms line up outside nurse Ernestine Forbes’ cubicle at the South Unit of the Central Florida Reception Center, 10 miles east of Orlando International Airport.

One by one, they swallow a raft of capsules and tablets that Forbes puts into their outstretched hands. One inmate gulps 53 pills a day: 17 in the morning, 19 in the afternoon and 17 in the evening.

[Times photo: Pam Royal] Julius Samuel joined a study because he wanted drug combinations not available at his other prison. He said he feels as if he has come back from the dead.

For years, the Florida prison system did not use inmates as subjects in medical experiments. Many states, including Florida, banned the practice after revelations in the 1970s that researchers working for drug companies exploited inmates in the name of science or profit.

Prison reformers likened some of the studies, which included tests of cancer and hepatitis drugs, to inhumane experiments conducted by German doctors during World War II. Some ethicists contended that even though the research might hold great promise for society, inmates could never give truly informed consent because they live in a closed environment that can never be free of coercion.

Then came the AIDS epidemic. When it struck in the 1980s, the stakes for medical science suddenly rose dramatically. Gravely ill people, including Florida inmates, began demanding access to experimental therapies that might save their lives.

Enter Dr. Margaret Fischl, a pioneering AIDS researcher. She says she received letters from HIV-positive prisoners who clamored to enter drug studies.

As a young doctor at the University of Miami, Fischl was among the first to report that AIDS was not exclusively a gay disease. She also played a key role in the creation of AZT, America’s first anti-AIDS drug.

A hero to some, Fischl was vilified by others who questioned her AZT research. As the epidemic intensified and AZT didn’t live up to early hopes, some AIDS activists accused Fischl of jiggering study results to make AZT’s manufacturer, Glaxo Wellcome plc, look good.

Fischl, now 50, denies fudging scientific data to get positive results, and federal regulators never found evidence of wrongdoing. "There was never any truth whatsoever to any of it," Fischl said. "I remain proud of that work."

Like many AIDS researchers, Fischl receives financial support for her experiments from pharmaceutical companies, including Glaxo. She says grant money would never sway her objectivity about a new drug, and besides, the University of Miami says, the money goes to a restricted university account, not to Fischl.

Even so, critics contend that such financial relationships, especially over time, can exert a seductive pressure on some scientists.

Fischl’s studies made her one of the most powerful members of the AIDS research establishment in Washington. She brings prestige and millions in federal grants to the University of Miami, and Glaxo reaped a fortune off its global AZT sales.

By 1995, however, Glaxo competitors had begun to introduce new classes of AIDS drugs that patients seemed to tolerate better than AZT. The new drugs, given in combinations known as drug cocktails, sent AIDS deaths plummeting.

Even with HIV-positive patients living longer, the second generation of AIDS drugs had a host of problems. Drug companies remained eager to develop medications that were cheaper, less toxic and had less complex dosing schedules. A month’s supply can cost $15,000.

In the race to get new drug cocktails on pharmacy shelves, the NIH and drug firms spend billions on testing. Typically, companies provide the medication used in a study at no charge. NIH or drug company grants, given to research institutions, cover the costs of test subjects’ clinical visits, blood draws, lab tests and X-rays.

But drug experiments need patients, and some drugmakers, working with researchers like Fischl, soon learned where to find a ready supply: prisons.

For the researchers, inmates are ideal test subjects: a constant, controllable group, eating the same food, following the same routine, always taking the medication. Making them even more attractive commodities, some inmates have never taken HIV drugs. Such "drug naive" patients, or "treatment virgins," tend to do better on new drug therapies, experts say.

Only a handful of the nation’s prisons now allow such research, but the benefits are obvious. They get free drugs and health exams for prisoners whose care would otherwise cost the state thousands of dollars per inmate per year. They also gain reputations as penal pacesetters.

And so it happened that a small group of Florida prison officials quietly lifted the research ban on prisoners.

Fischl agreed to donate her services, and without advertising for research proposals, the Department of Corrections let her set up a screening and testing site at the South Unit in December 1997.

The prison system told her that inmates had to receive good treatment and couldn’t take part in initial experiments to determine whether a drug is toxic.

Corrections officials say Fischl enrolled 64 inmates in nine studies. Six are ongoing. Four of the research trials were funded by the NIH, three by Glaxo Wellcome, one by Merck & Co. and one by Pharmacia & Upjohn Inc.

Under the study rules, the Corrections Department says, HIV-positive inmate-volunteers get combinations of more than a dozen powerful drugs from nine drug companies. The aim is to see which drugs work best in which doses for which kinds of patients.

With her research team, Fischl began showing up at the South Unit, sitting with inmates and sometimes, she says, going over consent forms line by line, again and again. On some of the forms, inmates are told, "We cannot assure you of any benefits."

Many prisoners liked it when a famous doctor showed up in the Florida prison system, where they often complain about bad doctors and bad care. Some inmates saw Fischl as a sort of goddess and took what she said as gospel.

One of them is 44-year-old Julius Samuel, a burglar with HIV. Before becoming a research subject, Samuel was losing weight and spiraling downward. He says he joined a study because he wanted access to new drug combinations that weren’t available at his other prison.

"They have more drugs at the South Unit than where I was at," Samuel said, adding that he feels as if he has come back from the dead. "I don’t have a trace of the virus."

Prisoners do not earn money for joining research trials, which can last up to three years. But, like Samuel, several inmates told the Times they were partly attracted by other inducements, including the prospect of quality drugs and good care that they couldn’t get at other Florida prisons. One inmate’s mother says her son enrolled in a South Unit study after she complained to politicians about his mistreatment at a North Florida prison.

And some inmates mention the nice amenities at the South Unit, such as air conditioning and comfortable sneakers.

"All you got to do is say, "Look, my feet hurt,’ and you get brand new, soft shoes," said Raymond McGee, a 31-year-old former inmate who jumped at the chance to lend his body to medical science. "Compared to other prisons, the way they take care of you at the South Unit is like a newborn child."

In interviews, many prisoners played down the drugs’ side effects, which can include muscle pain, nausea, vomiting, fatigue, sleep disorders, ingrown toenails, tingling legs and numb feet. That’s why they get the sneakers.

At the South Unit, where all but a handful of the 124 inmates are HIV-positive, prisoners say they don’t feel like outcasts. The nurses are kind. The doctors know what they’re doing. And the guards are under strict orders not to block access to medical care.

Dave Whiters, a convicted cocaine dealer with a cross tattoo on one arm and "Demon Dave" on the other, was a "treatment virgin" before joining a three-year study last year. "If you want yourself taken care of, you go to the South Unit," he said.

But when pressed about the study, Whiters, 36, doesn’t seem particularly well-informed.

He’s not sure what questions researchers hope to answer. And, unlike HIV patients in the community, Whiters isn’t in a position to get a second opinion about his treatment options.

He shows a reporter a medication sheet indicating he gets an anti-HIV drug combination that includes at least one placebo, or dummy medication. Asked if he knows what a placebo is, Whiters replied: "No, ma’am."

Former inmate McGee, now living in an Orlando halfway house, claimed to understand key safety information when he signed up for a potent drug combo that includes Glaxo Wellcome’s controversial abacavir (Ziagen). But McGee also says he never asked, nor was he told, about details of what the consent form calls a "potentially life-threatening" hypersensitivity reaction that abacavir sometimes causes.

Nationwide, scientists have investigated eight deaths associated with abacavir, though there was no way to prove if the drug was the cause, according to the Associated Press.

After abacavir came on the market in December 1998, the FDA mandated that every patient receive a detailed notice explaining the hypersensitivity reaction, plus a wallet-sized card to carry that describes symptoms. These can include fever, fatigue and skin rash.

McGee says he’s not concerned. "I never had a reaction to it," he said. "If I didn’t think it was working, I’d stop taking it."

Questions about the research at the South Unit are not isolated. As more vulnerable patients, including children, prisoners and people without medical insurance, enroll in research studies, reports of lax oversight and dubious ethics in medical experiments have sparked investigations by Congress.

The Food and Drug Administration and the federal Office for Protection from Research Risks have cited research institutions for problems ranging from faulty informed-consent procedures to fraudulent practices in recruiting test subjects. Just last month, the NIH revealed that researchers under-reported adverse events in gene therapy studies.

In Florida, Dr. Fischl says the drug combinations she gives inmates have successfully reduced the virus without negative impacts. In fact, she says, she thinks she sees fewer adverse reactions among prisoners than non-prisoners in clinical trials.

Fischl and Department of Corrections officials say emphatically that inmates are under no pressure to volunteer.

"There is no coercion," said Dr. Thomas, the prison system’s director of health services. "There are no promises of better treatment or easier life" at the South Unit.

Thomas, a lawyer, ophthalmologist and former Republican whip in the Florida House of Representatives, has become Fischl’s chief advocate. After joining the Department of Corrections in 1994, he became known as a compassionate conservative who cut costs creatively. He earns $132,251 a year.

But Thomas, 54, says he did not promote the research to save the state money. Rather, he wanted to "bring inmates opportunities for the best care possible," and he says if there are savings, they are "minuscule."

In a letter to the University of Miami last July, Thomas wrote to Fischl’s colleagues that prisoners felt no pressure, not even subtle pressure, to enroll. "We always attempt to exceed the guidelines of the Nuremberg Code," he said.

Thomas’ role as a disinterested observer is debatable, however. In April 1999, a Brown University newsletter listed him as a consultant and speaker for Agouron Pharmaceuticals and Bristol-Myers Squibb. Spokesmen for the firms, which make anti-HIV drugs used in the prison research, say they gave Thomas honoraria for his advice on AIDS in prisons.

After the two drug companies told the Times about the honoraria, Thomas did not return telephone calls or e-mails seeking comment about the honoraria. In an interview in December, he said he owns no drug-company stock and always follows the state’s financial disclosure laws. He told corrections spokesman Drake that he is not a drug-company consultant and that "his primary source of income" comes from the Corrections Department.

"Dr. Thomas is required to report any such things that might be covered by the law in his annual financial disclosure form, if he did in fact receive any," said John Burke, the prison system’s health care administrator.

"Dr. Thomas has a medical degree, a law degree and is a former member of the Legislature," added department spokesman Drake. "If anyone knows what a conflict of interest is, he does. He is not involved in any conflict of interest."

It was Thomas and his predecessor who created a watchdog committee, with no association to Dr. Fischl or the University of Miami, to make sure the research complied with federal patient-protection rules.

But soon after the committee began meeting in 1998, it ran into problems. It had trouble finding members who could attend regularly, so Thomas suggested that his wife, Chris, join the group.

That raised some eyebrows, but the committee went along and voted to include her, according to Karol Lucken, a University of Central Florida criminal-justice professor who was chairwoman of the committee.

"I knew if we’d ask somebody like my wife, we’d have a quorum," Thomas said.

The committee, also composed of ministers, an AIDS activist and a former inmate, among others, had one setback after another. Lucken says its members lacked the expertise to weigh the scientific merits of the studies. They also had trouble getting answers to questions that went to the heart of informed consent:

How were inmates recruited and screened? Who was on which drugs and why? Was there enough staff at the South Unit, and were they trained to notice possible adverse reactions?

"We went around and around on some of these things," Lucken said, "but the procedures seemed nebulous."

When the group examined informed-consent forms signed by the inmates, some members felt they might as well have been written in Greek.

One form is titled: "A phase II, randomized trial of AMPRENAVIR as part of dual protease inhibitor regimens (placebo controlled) in combination with ABACAVIR, EFAVIRENZ and ADEFOVIR DIPIVOXIL versus AMPRENAVIR alone in HIV infected subjects with prior exposure to approved protease inhibitors and loss of virologic suppression as reflected by a plasma HIV-1 RNA concentration > 1000 copies/ml."

At the request of the Times, Education Programs Associates, a California company that writes easy-to-read documents, examined a consent form for a nationwide study that enrolled both prisoners and non-prisoners; in Florida, only non-prisoners took part.

"The format was very difficult to read," the company wrote in a three-page report, concluding the form is written at a 15th-grade level, well above the average inmate’s education. "Important information was buried in densely written paragraphs. . . . Clinical jargon was rarely explained. The typical reader, even if well-educated, would have no way of comprehending the content of the consent form."

Problems understanding consent forms are common in and outside prisons, and Dr. Jay Sosenko, a member of the University of Miami’s institutional review board, says the forms are "made as understandable as possible."

Miami’s review board, he adds, rigorously reviews and tracks Dr. Fischl’s research.

But in March 1998, Lucken wrote a letter to the Department of Corrections, saying that without more information, the watchdog committee couldn’t give its assurance that inmate rights were protected.

Other potential problems turned up when members of the committee interviewed the inmates.

While some committee members thought the prisoners looked healthy and clearly understood what was going on, other members suspected some inmates had been pressured into the trials. They were told if they didn’t sign up that day, the study might be closed to them, according to minutes of a committee meeting.

No one responsible for enrolling inmates in studies said that, corrections officials replied.

They promised to look into an allegation that an inmate was taken off his medication for a week and given other drugs without being told why. (Changing regimens or skipping anti-HIV drugs even for a few days can allow the virus to re-emerge.)

And correction officials said inmates enrolled in studies would continue to receive HIV drugs after they were released from prison. Despite their good intentions, however, they inadvertently lost track of two former inmates enrolled in studies: One was transferred out of state, and the Immigration and Naturalization Service deported another.

AIDS activist Peter Uitdenbosch, a member of the watchdog committee, discovered other problems. He said that one prisoner, a "treatment virgin," had been placed on a potent, mega-drug cocktail and didn’t know he had other, less risky treatment options. And several prisoners weren’t fully informed about the dangerous reaction that Glaxo’s abacavir sometimes causes, according to Uitdenbosch, who is HIV positive and takes abacavir himself.

He says that when he informed one inmate, he "went into a panic" and complained to the administration.

Thomas accused Uitdenbosch of dispensing "invalid medical information" and threatened to "close down" the research if the committee felt it didn’t comply with the Nuremberg Code.

Nobody wanted that. "It’s the process that’s bad, not the studies," Uitdenbosch said.

Last fall, the process took another hit when the Department of Corrections suddenly disbanded the watchdog committee. Thomas said he intended to name a new oversight panel, but for months, none was appointed.

Finally, a few weeks ago, the Corrections Department released the names of 10 new committee members. Seven are Corrections Department employees.

The selections promptly drew more criticism. "That panel should contain no state officials at all," Lucken said. "Evidently, the Department of Corrections thinks it is immune from oversight."

Federal rules require that the University of Miami appoint an inmate or inmate advocate to represent the prisoners’ interests. When the university picked Thomas, critics charged that the selection was fraught with potential conflicts of interest.

"It smacked of cronyism," said Uitdenbosch, noting that Thomas is not only the man in charge of inmate medical care but is also a University of Miami alumnus. "Who represents the prisoners?" Uitdenbosch asked.

Ruth Macklin, a bioethicist at Albert Einstein College of Medicine in New York City, says any prison official serving as an inmate advocate creates a conflict of interest. "Even in the most humane and enlightened prison, it’s utterly preposterous to claim that any individual who is either from a corrections facility or the state is an advocate," she said. "They are adversaries."

Dr. Altman says the university picked Thomas because of his extensive knowledge of prison health care.

"I thought I was an appropriate person," Thomas said. "I’ve got a background in ethics."

— Times researchers Kitty Bennett and Caryn Baird contributed to this report.

Source: http://www.sptimes.com/News/031900/State/Questions_raised_over.shtml