Scientists Court New Ethics Distinctions

A 42-year-old woman came to the office of Louisville neuropsychologist Martine RoBards in 1999. Once the "star" of her workplace, a railroad mechanic shop, the woman now suffered insomnia, depression, anxiety, and memory loss. She had trouble organizing her thoughts and reciting her own history. The woman reported eight years of chronic exposure to mixed organic solvents used to clean engine parts. RoBards, who describes herself as a medical Nancy Drew, with help from a neurologist, made a diagnosis of chronic toxic encephalopathy1 caused by exposure to the solvents. She then set off to examine 92 of the woman's coworkers. Little did RoBards realize this small study would propel her on an 18-month odyssey. Eventually RoBards would help prompt a federal investigation into the University of Michigan's institutional review board (IRB), and of a team of UM investigators whose paper on toxic encephalopathy won a prestigious award.2 The paper, financed in part by CSX Transportation, reported on a random and anonymous sample of rail workers who had sued CSX, alleging that the solvent exposure had caused them brain damage--solvent toxic encephalopathy. The UM researchers had obtained a waiver of informed consent from the university's IRB, as required by federal regulations, before using the worker's data. The principal investigator, James Albers, a professor of neurology and co-director of the neurobehavioral toxicology program, had originally examined the rail workers as an expert witness for the railroad company, and he and his colleagues performed a retrospective study on the results, which was then published. Albers also had received a $30,000 Sphere Award from Dow Chemical Corp., a company that had manufactured some of the solvents. Albers and his team concluded that solvent encephalopathy did not exist in the studied workers. He had previously testified that he had never seen a patient with cognitive or behavioral problems in association with solvents in the workplace. Yet, toxic encephalopathy is documented in environmental health textbooks. The Journal of Occupational and Environmental Medicine (JOEM), which published two of Albers's papers, disclosed that the research was partially financed by CSX and Dow.3 Albers (who would not comment for this article) also had testified in an affidavit that he and his colleague, Stanley Berent, director of the UM neuropsychology program, had satisfied requirements for protecting human research subjects. "I have approached this project in a manner consistent with the ethical standards of my profession, including ethical review by the University of Michigan Medical School Institutional Review Board," said Albers in the March 1999 affidavit (www.med.umich.edu/opn/clinicalres/#albers1). But the ethical precautions provided no balm to RoBards and her medical team--who would testify for plaintiffs in lawsuits. The workers would not have agreed to allow Albers to use their data in a published, peer review study that could be used in court to blunt their own and other workers' legal claims, RoBards asserted. "To be precise, according to NIH guidelines, all of these patients fell into the category of 'potentially vulnerable subjects,' in that they were at Dr. Albers' facility against their will and already had been diagnosed with significant cognitive difficulties by other fully qualified professionals in medicine and neuropsychology," RoBards wrote in a Feb. 26, 2001 letter to the UM IRB. "The very purpose of the 'study' and the resultant publications was to harm the 'subjects' themselves in the most direct way possible." New Ethical Frontiers The UM Medical School IRB reviewed Albers' and Berent's research protocols twice over the past eight months, and twice approved the original granting of the waiver of informed consent. Established regulations for protecting human research focus "almost entirely on risks to individuals, and not risks to groups," says Jeffrey Cohen, director of education at Office of Human Research Protection. "If you have a category of people who could potentially be harmed [by the results], but you can't, through the research, link up to an individual, then the regulations are really silent about that." Cohen will not speak specifically about the Albers case, but he says the human subject research regulations--45 CFR part 46--would have no effect if the researchers doing a retrospective study ensured that no individual subject would be identified. Cohen could not say whether patients who knew their personal data was part of research that reduced their ability to obtain damages for injuries would be regulated under the human research subject protections. "That's a good question, that's the one that really requires some serious thought," he says. At this time there are no specific guidelines for this scenario; the local IRB would decide which regulations apply to the work. "If it is something [subjects] would refuse to participate in if they knew about it, then that adversely affects their rights and welfare." David S. Wendler, head of the Unit on Vulnerable Populations for the NIH Center for Bioethics, says that in deciding whether to obtain informed consent, researchers "should care more about whether or not it is just going to cause physical or financial harm. You should look at what they [the subjects] want and what they want to contribute to." Wendler says subjects may not want to contribute to certain kinds of research efforts because of their values or cultural beliefs. "There is nothing in the regulations that says specifically that IRBs have to take that into account, he comments. "To what extent should IRBs be taking into account the broader interests of the subjects? It seems reasonable to me to do that, but it remains an open question." Still, under more rigid rules, science is "going to lose a lot of research that everyone thinks is worthwhile," Wendler says. "I'm not sure I'm convinced on what's right here, and, certainly, the community is not convinced." Paul Brandt-Rauf, editor of the JOEM, says that research of a population involved in litigation could be difficult if regulations required informed consent. "It is a very tricky issue," Brandt-Rauf says. "The downside is that effect might be negative, and we might not get any research. But the primary concern should always be the individuals themselves." Solvents and the Brain The toxic exposure case began roughly 15 years ago when physicians issued the first diagnosis of encephalopathy in the first railroad workers. Because workers' compensation laws do not cover the patients, they had to sue their employer, CSX Transportation, under the Federal Employers Liability Act of 1908, to recover the costs of their medical treatment, job losses, and damages for pain and suffering. The solvents used in the railroad industry were predominantly chlorinated hydrocarbons--carbon tetrachloride, 1,1,1-trichloroethane (TCA), trichloroethylene (TCE), and perchloroethylene (PCE) were the most common. As more patients came forward, prompting concerns by clinicians, the National Institute for Occupational Safety and Health sponsored a workshop to coordinate efforts and to establish research priorities. Albers and Berent, who had already testified on behalf of CSX, attended that November 1996 workshop, which also covered the impact of litigation on the science of solvent-exposure toxicity. "Participants in litigation may, at times, avoid sharing information openly, advocate strongly for their positions, minimize uncertainties in data, avoid speculation and hypothesizing, and focus more on assessing available data than generating new data--all approaches more suitable for advocacy than for scientific dialogue," wrote Howard Frumkin, a professor of occupational and environmental health at the Rollins School of Public Health, Emory University, and a member of a team that reported about the workshop in a 1997 letter to the editor of the JOEM.4 Some workshop participants challenged the existence of chronic neurologic damage due to solvent exposure, saying that studies were inconsistent. In 1997, Albers and Berent proposed a retrospective study of the data they had collected in independent medical exams used for the CSX litigation. The medical school IRB approved the protocol and granted a waiver of informed consent. Kara Gavin, a UMMS spokesperson, estimated that Albers and Berent examined 60 to 70 patients. Larry Lockwood Jr., an attorney for some of the rail workers, says he didn't learn that his clients may have been unwitting participants in a study with conclusions used to refute the claims about solvent toxicity until he deposed Albers on Nov. 17, 1998. "[The workers] are feeling taken advantage of," says Lockwood. "CSX uses the study, they [the patients] never agreed to be a part of, to defeat other valid workers' claims." Lockwood says he attempted to prevent three additional clients from being examined by Albers and Berent, but a court order in early 1999 compelled the workers to complete their independent medical exams at the University of Michigan. Rail Requests Halt to Study RoBards says she was conducting her own survey of the workers in the spring of 1999 when J.M. Kelly, director of risk management at CSX, contacted her. Kelly refused to comment. According to RoBards, he asked who was funding her, and why she was conducting the research. She was surprised at the attention her small practice had attracted, especially because she was not involved in any litigation with CSX. "If he hadn't made that call," says RoBards, "I probably never would have become so involved." The railroad industry has almost completely eliminated the use of chlorinated hydrocarbon solvents. Jim Bruggers, a reporter from The Courier-Journal in Louisville, Ky., who coauthored a series of investigative stories on the rail workers, reported that CSX has paid out more than $35 million in settlements.5 CSX has confirmed that there have been over 600 lawsuits filed involving solvent exposure. Railroad officials have said that financial considerations rather than culpability motivated the settlements. Rather than commenting specifically on the rail workers, CSX issued a statement endorsing Albers and his study: "Dr. James Albers is a noted neurologist whose research has been published widely in peer-reviewed journals during a distinguished career of more than 25 years." Since the publication of the investigative articles by the The Courier-Journal, Lockwood says, he has seen a dramatic increase in the number of new calls concerning solvent encephalopathy. Meanwhile, RoBards has evaluated at least 10 new railroad workers since May. Katherine Uraneck is a physician and writer based in New York City. References 1. M.L. Bleecker, Occupational Neurology and Clinical Neurotoxicology, Baltimore, Williams & Wilkins, 1994. 2. J.W. Albers et al., "Absence of polyneuropathy among workers previously diagnosed with solvent-induced toxic encephalopathy." Journal of Occupational & Environmental Medicine, 41[6]:500-9, 1999. 3. J.W. Albers et al., "Neurologic evaluation of workers previously diagnosed with solvent-induced toxic encephalopathy," Journal of Occupational and Environmental Medicine 42[4]:410-23, 2000. 4. H. Frumkin, A. Ducatman, and K. Kirkland, "Solvent exposure in the railroad industry," Journal of Occupational and Environmental Medicine, 39[10]: 1997. 5. J. Bruggers, S. Shipley, "Hundreds of workers exposed," The Courier-Journal, May 13, 2001.

Scientists Court New Ethics Distinctions

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