GlaxoSmithKline's "Guinea Pig Kids"
"Epivir," AIDS and the NYC Incarnation Children’s Center

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Suggested articles to read before continuing:
The House That AIDS Built
Inside Incarnation
UK Firm Tried HIV Drug on Orphans
Guinea Pig Kids
Guinea Pig Kids (transcript)

What follows below is a reprint of the research and work product generated by Vera Sharav of the Alliance for Human Research Protection (AHRP):

A moral controversy is spiraling as additional evidence is uncovered about the use of infants and children in foster care as experimental subjects of Phase I and II trials of AIDS drugs, vaccines, and drug/vaccine combinations. The case serves as a lightning rod for public debate about the approval of ethically questionable pediatric research by the current institutional review board system. The case also demonstrates that underprivileged children of color are continually made to bear the burden of dubious medical experiments that are not expected to offer a therapeutic benefit to the children.

As the numeric designations imply, Phase I and II are the first two rounds of testing done on an experimental drug, which means they pose the highest level of risk without a foreseeable benefit for the children. The primary objective of Phase I and II tests is not to provide therapy to the patient-subjects. Rather,

  • The objective of a Phase I test is to assess the toxicity of a drug (i.e., how poisonous is the drug).
  • The objective of a Phase II test is to assess whether a drug has any impact whatsoever on the intended disease (i.e., does it do anything vis-à-vis AIDS).
  • To paraphrase bioethicist, Dr. Art Caplan: "If a phase I trial proved beneficial to a human subject, it would be reported as "a miracle!"

    Thus, at the time the children were enrolled in these experiments, there was no scientific basis for anyone to claim that:

    (1) the drugs were safe and not dangerous to the children; or that

    (2) the drugs held the promise of any therapeutic value whatsoever. The full extent of harm resulting from the unlawful enrollment of children in these exploratory medical experiments is not yet fully known.

    September 8, 2005 Hearing

    Two NYS Assembly Committees — Health and Children — will hold a hearing. The overriding issue is whether the welfare of vulnerable infants and children in foster care was sacrificed to facilitate AIDS drug research?

    Location & Time

    250 Broadway, Assembly Hearing Room 1923, 19th Floor, New York, NY 10:30 a.m. Eastern Time

    Children in foster care are “wards of the state.” Federal law protects wards from being exploited as research guinea pigs by restricting their inclusion in research that does not offer a reasonable “prospect of direct benefit” to the child. If research involves even “a minor increase over minimal risk,” federal regulations mandate the appointment of “an advocate for each child who is a ward. The advocate shall be an individual who has the background and experience to act in, and agrees to act in, the best interests of the child for the duration of the child’s participation in the research and who is not associated in any way…with the research, the investigator(s), or the guardian organization.” [45CFR 46.409(b).]

    The nature and level of risk involved in these Phase I and II experimental trials dictated that the agencies responsible for the care of these foster children — such as the New York City Administration for Children’s Services (ACS) — were required to provide the mandated federal protection of an independent advocate for each child. After a year of denial by ACS, an investigation by the Associated Press uncovered evidence revealing that 465 NYC foster children were subjects in these trials and less than one third (142) of those children were provided with an advocate. ACS failed to provide the minimum protections afforded by law.

    ACS now admits that it gave permission for the enrollment of at least 465 children under its care in experimental AIDS drug trials. A recent article in The New York Times attempted to divert the focus from unethical research practices by its selective reporting of the facts, by trivializing the moral and legal transgressions, and by casting doubt about the critics’ motives and credibility. See: Belated Charge Ignites Furor Over AIDS Drug Trial by Janny Scott and Leslie Kaufman.

    ACS officials defend its actions as a good faith attempt to provide sick children with the best available medical care. However, the excuses proffered by ACS and the physician-researchers involved in the tests are hollow and disingenuous. There is absolutely no medical justification for the claim that ACS enrolled foster children in drug experiments — some of who were merely “presumed” to be HIV infected — in order to provide those children with cutting edge medical care.

    According to the website of the NYC Incarnation Children’s Center (ICC), a foster care facility that began to conduct AIDS clinical trials in the early 1990s:

    "Early in the [AIDS] epidemic, HIV disease of childhood was considered to be a downhill course leading to death. But in the late 1980's, before AZT was available, many very ill children admitted to ICC got dramatically better with proper nurturing and high quality medical and nursing care."

    See link.

    A search by the Alliance for Human Research Protection of the National Institutes of Health website revealed that ICC was the site of 36 trials, and ICC was the only non-medical facility in the country that received federal research grants from NIH-AIDS division to test experimental AIDS drugs and vaccines on HIV infected or “presumed” infected infants and children. This presumption gave rise to concern that children who might never have developed AIDS were unjustifiably exposed to lethal risks and the horrific adverse effects of highly toxic drugs for purposes other than therapeutic. As revealed below, these concerns were justified.

    On March 8, 2004, a Freedom of Information request for the adverse event reports from the trials conducted at ICC was rejected by the National Institutes of Health, citing “trade secrets” and “privacy” exemptions. AHRP then filed a complaint (March 10) with the FDA and the Office of Human Research Protections (OHRP), charging that foster children had been deprived of federal protections from research risks to which they were entitled.

    See link.

    AHRP’s complaint has been validated by two investigations:
    (1) Researchers Tested AIDS Drugs on Children by John Solomon, May 5, 2004
    (2) OHRP: letter, May 23, 2005

    The Solomon investigation uncovered evidence that elevated the issue to national prominence: at least 48 AIDS experiments had been conducted on foster children in seven states — mostly in violation of the federal requirement of an advocate. And the Solomon report confirmed that children had suffered severe adverse effects, and some died. In one study testing the drug dapsone, "at least 10 children died from a variety of causes, including four from blood poisoning,” and researchers said they were unable to determine a safe, useful dosage. They said the deaths didn't appear to be "directly attributable" to dapsone but nonetheless were "disturbing." In another study testing combinations of adult antiretroviral drugs, Solomon reported that of the 52 children in the trial, “there were 26 moderate to severe reactions — nearly all in infants. The side effects included rash, fever and a major drop in infection-fighting white blood cells.”

    On July 17, 2005, exactly one month after Solomon reported OHRP’s initial findings — the New York Times published a front page article on some aspects of the controversy. Regrettably, the Times selective reporting misrepresented the facts; the reporters trivialized the violations enumerated in the OHRP letter, and glossed over documented evidence, dismissing concern for these children’s welfare — as if they were not worthy of consideration. In fact, the Times even failed to mention the Associated Press report and its documented findings that some children had suffered harm, some died. Rather than demanding accountability from the institutions and government officials who had denied vulnerable children federal protections to which they were entitled, the Times lent an appearance of legitimacy to unsubstantiated claims of those at the center of the dispute:

    “Physicians and federal health officials involved in the trials have strongly defended their work. They say hundreds, perhaps thousands, of children benefited; many of those were children not in foster care. To have withheld promising drugs from sick children just because they were in foster care would have been inhumane, the doctors say. They say they obtained legal permission for the children's participation, either from the biological parents or child welfare officials, in all but a small number of cases. Numerous doctors interviewed said they knew of no foster child who died as a result of the trials.”

    See link.

    Apparently, Scott and Kaufman took their cue from the physicians and officials involved, whose defense strategy is to divert the discussion away from their actions by disparaging the critics. These reporters similarly attempted to shift attention from the essence of the controversy by casting doubt on the motives and credibility of everyone who criticized the morality of using foster children to test toxic experimental drugs and vaccines. The Times did not “see fit to print” a single letter to the editor about the controversy. [1]

    The following facts show these experiments are indefensible:

    First, NO HIV vaccine has ever been found to be safe or effective for human use.

    Fact: Infants and children — one month to 18 years old — were subjected to unjustifiable risks of harm and discomfort in Phase I vaccine tests. For example, published reports acknowledge that:

    ACTG # 218 a vaccine trial co-sponsored by NIH (NIAID), Genentech, and MicroGeneSys, “showed no clinical benefit to vaccine recipients.” [2]

    The ACTG 218 protocol states: “Patients must have: Documented asymptomatic HIV infection” and the “Expected Total Enrollment” was 72.

    However, one published report states: “125 immunized children [ ] proved to be HIV uninfected.” [3]

    Another published report states: “A total of 126 children were not infected.” [4]

    Another HIV Phase I vaccine trial, ACTG #230, tested two experimental vaccines, one by Genentech, another by Chiron/Biocine. The protocol stated: “Accepts Healthy Volunteers.”

    The subjects, who were randomized to one of three doses of either experimental HIV vaccine or placebo, were newborn infants aged three days or less.

    These reports validate concerns raised by AHRP about the possibility that infants and children who were not even at risk of AIDS were exposed to unjustifiable risks and discomfort in speculative, non-therapeutic drug and vaccine experiments that offered absolutely no potential benefit for them.

    Second, most of the drugs that were approved for adults with AIDS and tested in these children carry Black Box warnings because of potentially lethal side effects:

    *Aldesleukin, **Dapsone, Didanosine, Lamivudine, ***Nevirapine, Ritonavir, Stavudine, Zidovudine. [See below] See warnings.

    Third, those who argue that the trials were the children’s only available access to “life-saving” drugs are not telling the truth.

    Fact: Under state law physicians and the state had a duty to provide “life-saving” treatment to wards of the state, if need be, to provide treatment “off-label.” It cannot, therefore, be argued that foster children were enrolled as test subjects to gain access to “life-saving” treatments.

    Fourth, physicians who have a stake in the enterprise deliberately blur the distinction between treatment and research.

    Fact: The purpose of clinical trials is to gain safety and efficacy information that may prove helpful for subsequent patients. Clinical trials are NOT designed to benefit the individual subjects. Furthermore, not all subjects get the “most promising” drug in a trial, some get placebos.

    Fifth, federal regulations restrict the inclusion of children who are wards of the state in greater than minimal risk research — so that their vulnerability will not be exploited by those who seek human subjects.

    Sixth, those who argue that research presents an acceptable means for disadvantaged populations to obtain essential treatment, are trying to legitimize an immoral quid pro quo that collides with fundamental ethical principles of research which are enshrined in the Nuremberg Code: “The voluntary consent of the human subject is absolutely essential…the person should be so situated as to be able to exercise free power of choice…without any element of force…or coercion.”

    Seventh, contrary to the assertions made by the physicians and institutions involved, the experimental phase I and II AIDS drug and vaccine trials tested on foster children, the experiments did NOT offer the children a benefit justifying the risks — as required under federal regulations.

    Indeed, the evidence reveals that many (if not, most) of the experimental drugs and vaccines tested on foster children presented an UNFAVORABLE risk/benefit ratio.

    That means the trials were not in the children’s best interest: they should, therefore, not have been approved.

    Indeed, the significant unfavorable risk/benefit ratio in these phase I and II trials should have precluded the inclusion of ANY children in the trials.

    Finally, the physicians and institutions who failed to provide children with an advocate had a financial stake in the trials — they received federal and pharmaceutical company grants. Inasmuch as they sought to secure subjects for clinical trials in which the risk/ benefit ratio for the children was UNFAVORABLE, their failure to provide foster children with an independent advocate may have been motivated to protect their self-interest. An independent advocate would be duty-bound to say, NO, to such experiments.

    In January, 2004, “The House that AIDS Built,” by Liam Scheff, ignited the controversy on the Internet. A recent follow up report by Liam Scheff, Inside Incarnation, was published by New York Press Volume 18, Issue 30, July 29, 2005. Excerpt:

    Mimi Pascual gave the children drugs every day and every night, on schedule, as the doctors ordered. She shook the children awake and popped the pills into their mouths, or squirted a syringe full of ground pill and water to the back of their throats. She and the other child-care workers made the rounds: midnight, 3 a.m., 5 a.m. Some kids took the pills by mouth, some through nasal tubes, and some through tubes jutting out of their stomachs. The children didn't like the drugs. They'd wake up vomiting or with bad diarrhea. But Mimi and the workers at Incarnation Children's Center had to follow the regimen, or they'd be fired. "The drugs had side effects, everybody knew that," said Mimi. But the workers were told the drugs were saving the children's lives. After a young girl who had just gone on the drugs had a stroke and then quickly died, and another young boy who was put on thalidomide wasted away on a respirator, Mimi stopped believing that the drugs were just saving lives. She believed they were killing the children too.

    Mimi Pascual worked at Incarnation Children's Center for eight years over a nearly 10-year period, taking care of the abandoned HIV-positive children of drug-addicted mothers in New York City's Washington Heights neighborhood. She started at ICC in 1995, when she was just 17. …. Like Mimi, the vast majority were originally from the Dominican Republic, and had no medical background.

    "In the beginning we were taking care of little abandoned crack babies who had no one, but then it changed. More and more of the kids were there for compliance. They didn't want to take drugs, or their parents didn't want to give them, so they got put in ICC.”

    "Some children got AZT, some didn't. Then it would switch. Then it was a new drug, then it was a drug that we never heard of. "We figured it out," she said. "These were experimental treatments." Marta, another child-care worker, put it more bluntly, "This is the guinea-pig business," she said….

    "The nurses said these children were lucky because they were getting the new drugs, but at the same time, when the kids vomited, or had diarrhea, or a bad rash," Mimi said, "we knew it was the meds. Even the nurses told us it was the meds. You couldn't hide it. It happened too regularly, it was predictable.” "But we had to give them. We were always told that without the meds they would die," said Mimi. "Is that what happened?" I asked. "No," said Mimi. "It wasn't that predictable. Some kids lived and some kids died. But the ones who were drugged the most did worse." She added, "The ones with the tubes always did worse."

    When Mimi started at ICC, the tubes were used infrequently. "But when the kids got older, a lot of them started to refuse the medication," she recalled. "Then they started coming in with the tubes more and more." "Kids who refused too much, or threw up too much, they'd get a tube. First it was through the nose. "But then it was more and more through the stomach. You'd see a certain child refusing over and over, and one day they'd come back from the hospital from surgery, and they had a tube coming right out of their stomach. "If you asked why, the doctors said it was for 'compliance' — the regimen. Got to keep up the regimen," said Mimi. "Those were the rules."….

    "Adherence" was the word of the day in late 2003, when I interviewed Dr. Catherine Painter, ICC's current medical director, about the relentless drug schedule. Painter explained, "What we're asking of our families and patients in terms of adherence is something beyond 100 percent — all of their medicines all the time, whether they have them on-hand or not, whether the medication makes them sick or not, or whether they're sick with a concurrent illness."

    Mimi describes how children suffered — and how some died: “One girl, a six-year-old, Shyanne — she came in for adherence. She was the most delicate little flower — beautiful, polite, full of life. Her family never gave her meds. So Administration for Children's Services brought her into ICC….she came in, and started the meds. And it was three months, maybe three months. And she had a stroke. She couldn't see. She was this normal girl, singing, jumping, playing. Then, poof, stroked out. Blind. We were freaked out. Then, in a few months, she was gone — dead." …

    Mimi described a boy named Seon, who died in spring of 2004. "He had all these soft, fatty lumps. We even called him "lumpy." She said. They sent him to get the lumps on his neck removed in surgery, and they would just grow back. They told us it was cancer, but he was on all those drugs. He had a tube, and they were always pumping him…. Mimi said that after he died, she read about the phenomenon of "buffalo humps," large fatty lumps on the back and neck that result from the newer AIDS drugs called protease inhibitors. Rhonda, the former ICC nurse, and Mimi both remember another boy at ICC who developed a breast while on the drugs. "He had a mastectomy, and then the other one started to grow. They couldn't hide that it was because of the drugs, but with Seon, they told us it was cancer," said Mimi.

    "One day I got a sheet from the nurses about a drug they were going to give Seon — it said any woman who was pregnant or who was of child-bearing age should not touch the drug, even with gloves on." "I couldn't pronounce the name, so I kept the sheet. Thalidomide. That's what they gave him." "They pumped Seon with it; he deteriorated fast," Mimi said. "One day we came in and he was bleeding from every hole in his body — his rectum, his nose, his mouth. He was in such pain. He would scream when he had to go to the bathroom. They put him on a respirator. They induced a coma with drugs so they could put him on a respirator. They told us they did it so he could breathe better." Mimi said, her voice getting a little rough. "I sat with him; he couldn't talk, but he was crying-tearing from his eyes. "He got all dry and scaly; he shriveled up like a snail — and he died."

    Incarnation Children’s Center acknowledges: “before AZT was available, many very ill children admitted to ICC got dramatically better with proper nurturing and high quality medical and nursing care." How then, can anyone justify exposing non-symptomatic, “presumed” HIV infected infants to the horrific side effects and risks of experimental AIDS drugs?

    An investigation must address the following: How many children who were not ill — non-symptomatic — and how many infants, who were not HIV-infected, were used like guinea pigs — to test AIDS drug and vaccines? How many died? How many suffered severe adverse effects?

    References:

    1. At least seven critical letters were sent to the Times about its breach of journalistic ethics. But to date, not a single letter was seen “fit to print.” See letters and detailed chronology of the facts with citations posted on the AHRP website.

    2. Essajee, SM, Borkowsky,W. et al. “Recombinant Glycoprotein Vaccines for Human Immunodeficiency Virus-Infected Children and Their Effects on Viral Quasispecies,” Clinical and Diagnostic Laboratory Immunology, January 2002, p. 79-82, Vol. 9, No. 1

    3. Borkowsky W; Wara D et al "Lymphoproliferative responses (LP) to receive HIV-1 envelope antigens in neonates & infants receiving gp120 vaccines [abstract]" Conference on Retroviruses & Opportunistic Infections, 1998 Feb 1-5;5():129 (abstract no. 268)

    4. Borkowsky W; Wara D, et al. "Lymphoproliferative responses to recombinant HIV-1 envelope antigens in neonates and infants receiving gp120 vaccines. AIDS Clinical Trial Group 230 Collaborators" Journal of Infectious Diseases. 2000; 181:890

    Black Box Warnings:

    *Aldesleukin: manufacturer’s warning: “Aldesleukin is not approved for the treatment of HIV… Aldesleukin is a highly toxic drug. Adverse effects associated with aldesleukin therapy are common, often serious, and sometimes fatal….Aldesleukin is approved for the treatment of metastatic renal cell carcinoma and metastatic melanoma in patients 18 years and older.”

    **Dapsone: manufacturer’s warning: “Deaths associated with the administration of Dapsone have been reported from agranulocytosis, aplastic anemia and other blood dyscrasias.” (Indeed, the Associated Press reported that 10 children died in the Dapsone trials: "overall mortality while receiving the study drug was significantly higher in the daily dapsone group. This finding remains unexplained.")

    ***Nevirapine new 2005 label warnings 2005: “Patients should be informed of: the possibility of severe liver disease or skin reactions associated with Viramune /Nevirapine that may result in death.” See link.

    Nevirapine is a controversial drug: its clinical trials in Africa have been the subject of investigation. See: AP reports, for example.