Hearing of the NYS Assembly Committee on Health and Committee on Children and Families

Testimony
by Vera Hassner Sharav, President
Alliance for Human Research Protection (AHRP)
www.ahrp.org

September 8, 2005
New York City

I speak on behalf of the ALLIANCE FOR HUMAN RESEARCH PROTECTION (AHRP), the organization that filed the federal complaint about the enrollment of foster care children as experimental subjects of Phase I and II trials of AIDS drugs, vaccines, and drug/vaccine combinations. See: http://www.ahrp.org/ahrpspeaks/HIVkids0304.php

AHRP wholeheartedly agrees with the committees' moral position: "Children placed in the State's custody should be protected by placing the physical, mental and emotional needs of the children above all else." Indeed, the overriding issue is whether the welfare of vulnerable infants and children in foster care was sacrificed to facilitate AIDS drug research?

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. Arthur Caplan: if a phase I trial proved beneficial to a human subject, it would be reported as "a miracle!" These experiments were NOT conducted to save the children's lives. The facts contradict the claims made by the NYC Administration of Children's Services and the researchers involved. At the time the children were enrolled in these high risk 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 AHRP complaint led to several federal investigations - and these have validated the concerns raised.
(1) The Associated Press report, "Researchers Tested AIDS Drugs on Children" by John Solomon, May 5, 2004: http://www.ahrp.org/infomail/05/05/04.php;
(2) OHRP letter, May 23, 2005: (http://www.hhs.gov/ohrp/detrm_letrs/YR05/may05c.pdf)

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 City Administration for Children's Services (ACS) - were REQUIRED to provide the mandated federal protection of an independent advocate for each child.

This case 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. This case serves as a lightening rod for public debate about the approval of ethically questionable pediatric research by an institutional system that operates in secret and is not held accountable.

As we discovered on the website of the National Institutes of Health (NIH) (www.clinicaltrials.gov) Incarnation Children's Center, which was the site of 36 trials, was the only non-medical facility in the country that received federal research grants from NIH-AIDS division. The grants were for testing experimental AIDS drugs and vaccines - even on infants and children who were only "presumed" to be HIV-infected. In fact, the principle investigators have written that "The incidence of transmission of HIV from an infected mother to her offspring is estimated to be in the range of 5%--40%. [1]

This presumption gave rise to our 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 non-therapeutic purposes. As we have recently discovered, these concerns were justified.

After a year of denial by ACS, 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. The AP 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 AP 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, 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."

A Freedom of Information request by AHRP to the National Institutes of Health, for adverse event reports from the trials was rejected by claiming the information falls under "trade secrets" and "privacy" exemptions.

THE FOLLOWING FACTS SHOW THE EXPERIMENTS ARE INDEFENSIBLE:

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

Fact: Infants and children - 1 month to 18 years old - were subjected to unjustifiable risks of harm and discomfort in Phase I vaccine tests.

For example, published reports between 1998 and 2002 acknowledge that ACTG # 218 a multiple vaccine trial co-sponsored by NIH (NIAID) and the vaccine manufacturers, Genentech, MicroGeneSys, and Chiron/Biocene. Not only did the vaccines show

"no clinical benefit to vaccine recipients" - the trial resulted in the:

"unexpected inverse association between viral diversification and [vaccine-associated immune] response." This, the researchers acknowledge, "raises the possibility that these RGP vaccines may have had a deleterious impact on antiviral effector mechanisms." [1]

There also seems to be a discrepancy between the inclusion criteria and the number of children involved. The ACTG #218 protocol states: "Patients must have: Documented asymptomatic HIV infection" and the "Expected Total Enrollment" was 72.

However, the published reports show that "HIV-Uninfected subjects" were used. According to one report: "125 immunized children proved to be HIV uninfected." [3]

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 3 days or less. A published report describes the extensive biochemical response of uninfected infants to an experimental vaccine that never made it through advanced trials: "Responses to heterologous HIV antigens by treatment group (HIV-uninfected subjects only). The number given is 157. [1]

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 warnings: http://www2.kumc.edu/druginfo/drugsafety/BlACK%20BOX.htm

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, did NOT offer the children a benefit justifying the risks - as is 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. The full extent of harm resulting from the unlawful enrollment of children in these exploratory medical experiments is not yet fully known.

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. See complete article: http://www.nypress.com/18/30/news&columns/liamscheff.cfm

Incarnation Children's Center acknowledges on its website:

"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. 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". J. of infectious Diseases. 2000; 181:890

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)

A detailed chronology of the facts is posted on the AHRP website: http://www.ahrp.org/ethical/incarnation/timeline0805.php.

FDA required Black Box WARNINGS for drugs tested in foster children:

* 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: http://www.hivdent.org/drugs1/drugNNLC0105.htm

Nevirapine is a controversial drug: its clinical trials in Africa have been the subject of investigation. See: AP reports, for example: http://www.ahrp.org/infomail/05/07/04a.php

The Alliance for Human Research Protection (AHRP)
www.ahrp.org

Contact: Vera Hassner Sharav
212-595-8974