Comments submitted by The Alliance for Human Research Protection
to The National Academy of Sciences
Committee of the Institute of Medicine on Clinical Research Involving Children

AHRP has been closely monitoring pediatric research trends since passage of the FDA Modernization Act of 1997. We believe that medications used in children should be thoroughly tested for safety, effectiveness and appropriate dose. But unlike adults who can exercise their autonomous right to informed consent, children who are enrolled in clinical trials are non-consensual human subjects. They should not, therefore, be made to assume the burden of testing possibly toxic drugs whose safety is unknown.

On July 3 the federal Office of Human Research Protections (OHRP) issued a stinging indictment of the research review and approval process at some of the nation's most prestigious research institutions--including the National Heart Lung and Blood Institute (NHLBI). http://ohrp.osophs.dhhs.gov/detrm_letrs/YR03/jul03a.pdf

The retirement of Dr. Claude Lenfant, director of NHLBI was announced the same day. See: http://www.ahrp.org/infomail/03/07/03.php]

On June 10, 2003, a panel of experts convened by the federal Office of Human Research Protections (OHRP) heard presentations by critics who had filed complaints about $37 million government sponsored, multi-site experiment conducted by major academic institutions participating in the ARDSNetwork, and by the ARDSNet investigators who defend the trial.

The experiment tested two extreme, rarely used methods of mechanical lung ventilation in 861 critically ill, vulnerable patients suffering from acute lung disease (ALD) or acute respiratory distress syndrome (ARDS).

The April 3, 2003 New England Journal of Medicine (NEJM) issue contained an array of articles largely in support of a disputed multi-site, clinical trial sponsored by the National Heart, Lung, and Blood Institute (NHLBI), one of the National Institutes of Health (NIH), involving critically-ill, mentally incapacitated human beings with acute respiratory distress syndrome (ARDS) - who did not give their informed consent.

The accompanying editorial, "Controlling Research Trials," by Dr. J.M. Drazen, who serves on the NHLBI advisory committee that had approved the disputed trial, reveals much about the NIH attitude toward the rest of the world.

Excerpt: Within the last two years numerous independent surveys and investigative news reports have documented systemic breach of research ethics. In October 2002, a Duke University survey of 108 U.S. medical schools revealed that medical institutions fail utterly to meet national and international standards aimed at ensuring the integrity of clinical research and the safety of human subjects. [See, Schulman KA, et al, Provisions in clinical trial agreements, New England Journal of Medicine, v. 347, no 17, Oct 24, 2002, pp 1335-1341.]

Corporate sponsors maintain control over the entire process including, research design, subject selection, data collection analysis, and corporate sponsors selectively skew the findings that are published...

We are writing about the Pediatric Research Equity Act of 2003 (S 650). We are in full agreement that children should have the same safeguards as adults; that medications used in children be thoroughly tested for safety, effectiveness and appropriate dose. However, S 650 does not do this. Instead, it requires that children be used to test all drugs as a condition of licensure by FDA - unless a waiver is obtained from the Secretary of the department of Health and Human Services under section 505B.

Testimony by Vera Hassner Sharav before the Committee on the Use of Third Party Toxicity Research with Human Research Participants; Science, Technology, and Law Program; The National Academies of Science Committee on the Use of Third Party Toxicity Research with Human Research Participants

My name is Vera Sharav and I am the president and founder of The Alliance for Human Research Protection (AHRP) a citizens' watchdog organization monitoring human research to ensure that the moral principles enshrined in the Nuremberg Code and the Declaration of Helsinki are preserved and followed in experiments involving human beings.

Recent public and professional debate about smallpox vaccine and its risks provides the framework for evaluating the ethical justification for conducting clinical trials on children. Dryvax is a particularly impure product made of live vaccinia virus harvested from the pustules of calves infected with (it is believed) cowpox. Although the vaccine, which is scratched on the skin, only causes mild infections in most people, in a small but significant number the infection caused serious adverse reactions similar to the complications of the disease they were designed to prevent: painful, disfiguring skin disorders, blindness, neurological impairments and death.

AHRP Recommendations for the protection of children in clinical research

(1) Federal regulations are predicated on our moral responsibility to protect children - who are not volunteers - from being subjected to medical or behavioral experiments that are not in their best interest. Thus, federal regulations - 45 CFR 46 Sub-part D - restrict the use of children in medical experiments involving greater than minimal risk, if there is no potential medical benefit for them or their condition.

Thank you for your considered response to our July 29 letter to the director of the Office of Human Research Protection.

We are astonished to learn that OHRP found that all 12 major research institutions involved in this multi-site trial had violated Federal protections (45 CFR 46.117):

(a) "in all cases OHRP found that the informed consent documents approved by the institutional review boards (IRBs) for the research failed to describe adequately the reasonably foreseeable risks and discomforts of the research."