In April 1995, Nicole Wan, a healthy 19-year-old student, volunteered for an experiment at the University of Rochester testing the effects of air pollution. She was to be compensated $150 for her participation.
Instead, she died of an overdose of lidocaine, an anesthetic used on a tube that was inserted into her lungs to remove cell samples. The 1996 Department of Health case report that looked into how the experiment was conducted stated: "Research was being carried out with insufficient safeguards to adequately minimize risks and protect individuals."
There are very few legal restraints to protect those who volunteer for medical research. This invites a cowboy mentality, as researchers circumvent moral issues such as patient safety requirements in order to meet market demands. Right now experiments are being conducted on human beings without adequate safeguards, informed consent or clinical justification.
Major systemic flaws undermine the safety of human subjects in medical research, and we believe those flaws will result in greater numbers of human casualties. As the drug-development business becomes more competitive and fast-paced, the priority of clinical research is no longer a patient's safety. Media reports and investigations into researchers' conduct -- resulting in temporary shutdowns at eight major academic institutions -- may be only a prelude to further disclosures of subjects being harmed. The boom in clinical trials and its recruitment techniques puts vulnerable people, including children, at undue risks of harm. For example, an estimated 18,000 children are expected to be enticed into studies with promises of receiving such things as gift certificates to places like Toys 'R Us. And parents are offered payments of up to $1,000 to sign up their kids.
Our concern was first raised in 1993 by the revelation that experiments on schizophrenia patients at the Bronx Veterans Administration were designed to induce -- rather than prevent -- psychotic relapse. The Federal Office of Protection from Research Risks recently ruled that federal regulations -- including informed consent -- had been violated. Then in 1997, research subjects from scores of different experiments testified before the National Bioethic Advisory Commission that harmful procedures such as abrupt medication withdrawal ("washout") and chemical "challenge" painfully exacerbated their conditions. Most recently, last year gene therapy experiments came under fire. Evidence showed that researchers failed to disclose risks to prospective patients, or to report adverse incidents -- including deaths -- to federal oversight agencies as required by federal regulations.
All of these speculative, high-risk experiments were approved by institutional review boards (IRBs), the gatekeepers responsible for making sure there are proper safeguards in place for every experiment involving human subjects. This is the first of several major systemic flaws that undermine the safety of human subjects in clinical trials.
First, there are many built-in conflicts of interest: IRBs are supposed to evaluate research studies to ensure that they do not pose undue risks to subjects. However, many members of such boards are employed by the institution carrying out the research; some are consultants to drug companies whose protocols they review. IRBs are also under pressure from university administrators and colleagues to approve lucrative research, especially when a financial interest is at stake.
Recently, questions have arisen about the integrity of some studies reported in scientific journals. An editorial that appeared in the June 22 Journal of the American Medical Association accused industry-sponsored researchers of writing favorable reports -- even when the data did not support those findings.
Second, there are no uniform federal regulations: One set of regulations covers only research supported by the federal government; the other covers clinical drug trials sponsored by commercial companies seeking marketing approval from the Food and Drug Administration. All other commercial trials operate without any mandatory oversight.
Third, there are no independent monitoring organizations, oversight auditors or agency that is effective in enforcing the federal regulations. The system fails to deter would-be violators of ethical standards, or to hold them accountable. Yet such protections do exist for laboratory animals whose ethical treatment is ensured under the 1966 National Animal Welfare Act.
As a result, experiments that pose significant risks to children and teenagers have been approved by IRBs -- even those that are not medically justified. For example, experiments that exposed healthy 6- to 10-year-old African-American and Hispanic children to fenfluramine (the active component of the obesity drug, fen-phen, which has been recalled by the FDA because it was found to produce heart valve damage). Others are creating illness by speculation where none exists. At Yale University, healthy teenage siblings of schizophrenia patients, some as young as 12 years old, are being put at risk of severe adverse side effects from a powerful anti-psychotic drug, to test whether it will prevent schizophrenia in siblings. This Eli Lilly-sponsored experiment is being expanded to include 1,500 clinically healthy teens in eight countries, according to a recent article in the Wall Street Journal.
The problem is, there is no evidence that drugs can prevent schizophrenia. But there is evidence that anti-psychotic drugs have high risks and serious side effects in a significant number of patients. Moreover, the risk of schizophrenia for siblings is only 2 to 10 percent: There is a 90 percent probability that these children will not develop schizophrenia at all. If we start treating the siblings of schizophrenics, the market for anti-psychotic drugs could expand from $6 billion a year to $25 billion -- by turning healthy children into lifelong patients as a result of the debilitating side effects these drugs produce.
We foresee children being treated with drugs for conditions that they don't even have, yet they will be told that it is necessary because some other family member may have that particular medical disorder. Is this medical progress or the perversion of medical research in the interest of profit? Recognizing the dangers that conflicts of interest pose for the integrity of science, Bernadine Healy, the former director of the National Institutes of Health, recommended that investigators should not profit financially from their clinical research. We wonder whether it is in the public interest for academic institutions to engage in clinical research with human beings for profit -- especially if they expect generous taxpayer support at the same time.
Congress is currently considering legislation to curb experimental abuse. To be effective, such legislation should contain the following provisions:
Finally, to regain the public trust, federal legislation must provide assurance to patients who are considering participating in clinical research that they will receive the best therapeutic treatment available -- just as they can expect in clinical care.