ALLIANCE FOR HUMAN RESEARCH PROTECTION (AHRP)
Promoting Openness, Full Disclosure, and Accountability
The latest chapter in the controversy over infants and children in foster care who were subjected to risks and discomfort in Phase I and II tests of experimental AIDS drugs and vaccines, is not only about the conduct of research. The case serves as a lightening rod illustrating a moral clash between underprivileged children of color who are continually made to bear the burden of dubious medical experiments that often serve no more than a means for self-enrichment for those who conduct clinical trials. They are the corporate-academic biomedical industrial establishment - an especially privileged class in our society. Not only are they supported by taxpayers, but their ethical and legal transgressions are shielded by a battery of lawyers and public relations firms. And they can corral the New York Times to help them divert the focus from deviant research practices. The Times has obliged by selective reporting of the facts, trivializing the moral and legal transgressions, and by casting doubt about the criticsı motives and credibility. See: "Belated Charge Ignites Furor Over AIDS Drug Trial" by Janny Scott and Leslie Kaufman. http://www.ahrp.org/ethical/NYTimes0705/IncarnationArticle.php
At issue is whether the human rights, welfare and legal entitlement of vulnerable children without parents were sacrificed to facilitate AIDS drug research. Federal regulations protect foster care children (i.e., wards of the state) from research risks by restricting their inclusion in research that does not offer "the prospect of direct benefit.² If research involves "a minor increase over minimal risk,² federal regulations mandate the appointment of " an advocate for each child who is a ward.² The advocate must 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 childıs participation in the research and who is not associated in any way [ ] with the research, the investigator(s), or the guardian organization .² [45 CFR 46.409(b)]
January 2004: the story was first reported on the internet by Liam Scheff, an investigative reporter who gained access to Incarnation Children's Center (ICC), a facility originally housing "boarder babies" (born to crack cocaine addicted mothers) and HIV infected children. ICC is under contract with the New York City Administration of Children's Services (ACS) and the Catholic Archdiocese of New York as caretakers for foster children. Scheff uncovered evidence that foster children at ICC were subjected to experimental AIDS drug trials; that children whose guardians refused to give the children drugs that made them sick were removed from their families; and that children who could not tolerate swallowing the drugs were forced to have plastic tubes surgically inserted in their stomachs to ensure compliance. . Scheff interviewed staff members - including Dr. Katherine Painter, the medical director of ICC. See: "The House that AIDS Built² at: http://www.altheal.org/toxicity/house.htm
The disturbing allegations (graphically illustrated) prompted the Alliance for Human Research Protection (AHRP) to investigate:
First a search of Incarnation Centerıs website revealed that:
"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: http://www.volunteernyc.org/org/1208191.html
In the early 1990ıs, ICC began to conduct experimental drug trials on foster children. Indeed, 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 "presumed² infected infants and children. This gave rise to concern that children who might never have developed AIDS were unjustifiably exposed to the horrific adverse effects of highly toxic drugs for purposes other than therapeutic.
AHRP searched the website of the National Institutes of Health (NIH), ( www.clinicaltrials.gov ) and discovered that ICC was the site of 36 trials testing the safety of highly toxic AIDS drugs, vaccines, and drug /vaccine combinations. The trials were mostly phase I and II, which means they posed the highest level of risk for the children without a foreseeable benefit for them. To paraphrase bioethicist, Dr. Art Caplan: if a phase I trial proved beneficial to a human subject, it would be reported as "a miracle!"
February 29, 2004: The New York Post reported that ACS acknowledge only 50 children were used in 13 experiments "with high doses of AIDS medications² at ICC. See: "Aids Tots Used as Guinea Pigsı² http://www.ahrp.org/infomail/04/02/29.php
March 8, 2004: A Freedom of Information request for the adverse event reports from the ICC trials was rejected by NIH, citing "trade secrets² and "privacy² exemptions. AHRP then filed a complaint with the FDA and the Office of Human Research Protections, charging that foster children had been denied federal protections from research risks. See: http://www.ahrp.org/ahrpspeaks/HIVkids0304.php
March 10, 2004: AHRP filed a complaint with the FDA and the federal Office of Human Research Protections (OHRP). The complaint led these two agencies to investigate. See: http://www.ahrp.org/ahrpspeaks/HIVkids0304.php
November 30, 2004: BBC broadcast "Guinea Pig Kids² in the UK causing shock waves among Europeans and galvanizing African-American community activists who launched a campaign to inform the community by holding weekly demonstrations in front of ICC .Several groups led by December 12th Movement, demanded public hearings.
April 2005: After a year of angry denials, when confronted with evidence uncovered by the Associated Press, the Cityıs Administration of Childrenıs Services acknowledged in April 2005, that 465 foster children had been in the trials.
May 4, 2005 : The AP investigation by John Solomon, uncovered evidence that elevated the issue to national prominence: at least 48 AIDS experiments had been conducted on foster children in seven states - Illinois, Louisiana, Maryland, New York, North Carolina, Colorado and Texas. Most were conducted in violation of a federal requirement that foster children must be provided an advocate. And the AP report confirmed that severe adverse effects and deaths had occurred. In one study testing combinations of adult antiretroviral drugs in foster children, AP 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.² In another trial, AP reported that researchers reported a "disturbing" higher death rate among children who took the drug [dapsone]: "overall mortality while receiving the study drug was significantly higher in the daily dapsone group. This finding remains unexplained."
See: "Researchers Tested AIDS Drugs on Children² by John Solomon. http://www.ahrp.org/infomail/05/05/04.php
May 9, 2005: Dr. Jonathan Fishbein, Director of the Office for Policy in Clinical Research Operations of the NIH Division of AIDS - the institute that funded the trials - wrote to the Office of the Inspector General (DHHS), noting that the NIAID Clinical Terms of [grant] Award requires that: "All clinical research supported by NIAID must comply² with applicable federal regulations pertaining to research subject protection (Title 45, Part 46). He emphasized that the regulatory requirement for an independent advocate in research involving greater than minimal risk for children in foster care is unequivocal. "There is no provision in either law or regulation that allows researchers or their oversight boards to waive the rights of children in clinical trials to have advocates."
"The failure of numerous DAIDS/NIAID-sponsored researchers and their institutions to assure that foster children enrolled in their research were appointed individual advocates even where a foster parent exists constitutes a violation of the terms of their grant awards. By any definition, this is a severe violation because it directly impacts the health and safety of foster children, among the most vulnerable populations in our society.²
Dr. Fishbein stressed the need for an audit of the financial and protocol records of every institutions involved, as well as the medical and study records of each foster child enrolled in any AIDS clinical trial "to determine whether any of these children were subjected to unnecessary risk or injury owing to the toxicity of the drugs administered to them, and whether the researchers complied with their obligations to report all adverse events.²
"It is wholly inappropriate for DAIDS/NIAID to consider making awards to any of these applicants who have violated basic human research protections until a full, open and independent investigation has concluded and full restitution is made to both the government and the victims of these unlawful experiments. "
Roberta Harris, Deputy Secretary, Wisconsin Dept. of Health / Family Services, testified that Wisconsin did not approve medical research on foster children:
"because we believe it is our responsibility to provide as much of a safe, nurturing environment for the children in foster care as possible. The types of research that have unfortunately occurred in our nation in the past would also make it difficult for us to earn the trust and confidence of the families we are seeking to help.² Furthermore, "our position on the involvement of foster children in research, especially medical research, is based in large part on a variety of ethical codes related to medicine, social work, and mental health. A major document forming the basis of our position is embodied in the World Medical Association Declaration of Helsinki, originally adopted in 1964 which places great emphasis on the voluntary nature of participation in research.² http://waysandmeans.house.gov/hearings.asp?formmode=view&id=2678
See also AHRP Statement and recommendations for the Record.: http://waysandmeans.house.gov/hearings.asp?formmode=view&id=3042
See: AbleChild Statement and recommendation for the Record: http://waysandmeans.house.gov/hearings.asp?formmode=view&id=3041
May 23, 2005: OHRP preliminary findings fault Columbia University Medical Center for the failure of its IRB to obtain documentation ("information²) to justify the approval of the selection and enrollment of foster care children; for its failure to document parental permission; and for its failure to document equitable selection of subjects. Moreover, four issues of concern are redacted from the letter posted on the OHRP website. See: http://www.hhs.gov/ohrp/detrm_letrs/YR05/may05c.pdf (28 KB pdf file)
July 17, 2005: For over a year, the New York Times had not seen fit to report mounting evidence validating the content of AHRPıs complaint and corroborating that foster children had been deprived of the protection of an advocate to which they were entitled under federal regulations. Exactly one month after AP reported the preliminary findings from the OHRP investigation, the Times published a front page article that appears to have been published not to report the essential elements of the controversy, but rather to offset the damaging public relations impact for a premier New York academic research center.
Journalists are supposed to be guided by a dose of healthy skepticism. But Scott and Kaufman failed to ask probing questions to elicit the truth. If, as is claimed, the trials were in the childrenıs best interest:
(1) why were the children not provided with an independent advocate?
(2) what issues of concern are being concealed from the public by OHRP?
Nowhere does the Times seek accountability from the institutions and government officials who denied vulnerable children federal protections to which they were entitled. Indeed, the reporters trivialized the violations and glossed over documented evidence that some children had suffered harm, and failed to obtain adverse event reports. The Timesı selective reporting omitted even mentioning the Associated Press findings - such as children suffering severe drug-induced adverse effects and unexplained, high mortality rates. Instead, 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.² http://www.ahrp.org/ethical/NYTimes0705/IncarnationArticle.php
Apparently taking their cue from these involved physicians and officials whose defense strategy is to disparage the critics without providing justification for their actions, the reporters attempted to divert 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 drugs and vaccines.
In view of the following facts, the experiments on foster children are indefensible:
First, NO HIV vaccine has ever been found to be safe for use in humans.
The experimental HIV vaccines that were tested on foster children at ICC (and elsewhere) exposed the children to highest unjustifiable risk of harm.
Second, most of the drugs that were approved for adults and tested in the children carry Black Box warnings because of their potential lethal side effects:
Dapsone,** Didanosine, Lamivudine, Nevirapine,** Ritonavir, Stavudine, Zidovudine. See http://www2.kumc.edu/druginfo/drugsafety/BlACK%20BOX.htm and http://www.formularyproductions.com/kumc/ .
Nevirapine / Viramune new warnings have been added to the label in 2005. See: http://www.hivdent.org/drugs1/drugNNLC0105.htm :
"Patients should be informed of: the possibility of severe liver disease or skin reactions associated with Viramune that may result in death.²
"Severe, life-threatening and in some cases fatal hepatoxicity [liver damage], including hepatic necrosis [liver death] and hepatic failure, has been reported in patients treated with Viramune.²
"Severe, life-threatening skin reactions, including fatal caseshave included cases of Stevens-Johnson syndrome, toxic epidermal necrolysis [skin death]² "Viramune is not a cure for HIV-1 infection.²
Nevirapine is a controversial drug whose clinical trials in Africa have been the subject of investigation. See: Associated Press reports: http://www.ahrp.org/infomail/05/07/04a.php ; and http://www.ahrp.org/infomail/04/12/13a.php
Concerns have been raised about the harmful risk / benefit ratio for infants exposed to AZT, such as anemia. David Crowe, President of Alberta (Canada) Reappraising AIDS Society in Calgary, sent the Times a letter citing published reports of serious consequences for infants exposed to AZT: See: http://www.ahrp.org/ethical/NYTimes0705/UnpublishedLetters.php
Dapsone, another drug tested on ICC foster children carries a manufacturerıs warning: "Deaths associated with the administration of Dapsone have been reported from agranulocytosis, aplastic anemia and other blood dyscrasias.²
Indeed, the Associated Press reported that researchers had reported a "disturbing" higher death rate² among children who took dapsone: "overall mortality while receiving the study drug was significantly higher in the daily dapsone group. This finding remains unexplained."
Third, those who argue that research was the childrenıs only available access to "life-saving² drugs are not telling the truth: under state law physicians and the state had a duty to provide "life-saving² treatment to wards of the state, if need be, to provide treatment "off-label.² Thus, it cannot be argued that foster children were enrolled as test subjects to gain access to "life-saving² treatments.
Fourth, physicians who have a stake in the enterprise deliberately blur the distinction between treatment and research. Experimental drugs most often pose greater risks than tried and tested treatments. 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 subject. Furthermore, not all test subjects get the "most promising² 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 essentialthe person should be so situated as to be able to exercise free power of choicewithout any element of forceor coercion²
Seventh, contrary to the assertions made by the physicians and institutions involved, the experimental phase I and II AIDS vaccines, drugs, and drug combinations tested on foster children, 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.
An unfavorable risk/benefit means the trials were not in the childrenıs 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, a logical explanation emerges for the failure of the physicians and institutions to provide foster children with an independent advocate - an inherent conflict of interest. These physicians and institutions received federal and pharmaceutical grants contingent upon the enrollment of subjects. Their self-interest lay in securing subjects for trials in which the risks were greater than any potential benefit for the children. Their interest clashed with the childrenıs interest. An independent, knowledgeable advocate would have thwarted their goal because the advocate would be duty-bound to say, NO, to experiments that were not in the childıs best interest.
July 27, 2005: INSIDE INCARNATION by Liam Scheff was published by New York Press Volume 18, Issue 30. It is the latest follow-up report.
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.²
"One of the things Mimi and the other childcare workers noticed was the constantly shifting medicine regime. "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.
"If you asked the nurses about it, you were told it was normal, and not to ask questions. If you asked the doctors why some kids got AZT and some didn't, you didn't get an answer." "But we knew drug trials were going on," said Mimi. .
"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.²
"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."
"The children who were pumped all the time wouldn't have any appetite left, so they wouldn't eat. And then with the drugs on top of that, with the diarrhea, they wouldn't do well." "But that was the rule," said Mimi. "Keeping to the regimen. Adherence. Give the drugs on time, on schedule, no matter what," Mimi repeated. "Or you're fired." "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." "So, 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."
The drug Mimi remembers giving most often at ICC is the nucleoside analog AZT. In addition to the drug's long list of severe and even life-threatening toxicities, AZT also been linked to lymphoma and other cancers. "The regime has changed," said Mimi, "and so has the place. It's AIDS drugs plus - plus psych meds, anti-psychotics, antidepressants. We came to work here with kids we were told were dying - crack babies - to try to care for them. Today it's a psych ward." In 1999, Mimi left ICC for nearly two years to have a baby. When she came back, ICC was under new management. The nuns who used to administer ICC had been replaced by a nursing-home bureaucracy, headed by Executive Director Carolyn Castro. .
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. When we changed his diapers, it would come out like the drug mixture - rough and sandy like the ground-up pills." 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.
Mimi has a paper from ICC, that she saved from Seon's treatment. "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." See full article: http://www.nypress.com/18/30/news&columns/liamscheff.cfm
The moral and humanitarian issues raised by these experiments require reporting that is wise and sensitive to a people whose often devalued existence has historically led to their use as guinea pigs in risky medical experiments going back at least to the infamous Tuskegee syphilis experiment and continuing to this day to EPA sanctioned lead-poisoning and pesticide experiments on children of color.
**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.² See unpublished letters to the Times Public Editor addressing the breach of journalism ethics: http://www.ahrp.org/ethical/NYTimes0705/UnpublishedLetters.php
Contact: Vera Hassner Sharav