Informed consent process at center of another suit

Ongoing consent seems to be lacking

In March, members of the Havasupai Indian Tribe of northwestern Arizona filed two federal lawsuits seeking a total of $75 million in damages against Arizona State University (ASU), the Arizona Board of Regents, and three university researchers. The lawsuit claims that blood samples taken from tribe members as part of a diabetes study were destroyed, lost, or used in studies of schizophrenia, inbreeding, and population migration without the donors’ consent.

The tribe alleges that nearly 400 blood samples were collected from more than 180 donors between the years 1990 and 1994 as part of a larger study of the incidence of diabetes among its members. According to the lawsuit, the tribe was told the study consisted of three parts: diabetes education, collecting blood samples from members for research, and genetic testing to identify which genes in the Havasupai caused diabetes.

However, researchers later used their access to Havasupai medical records, in addition to the blood samples, to initiate studies of schizophrenia and inbreeding, and transferred some of the samples to researchers at other institutions, some of whom used the samples in research into theories of population migration, the tribe’s attorney, Robert Rosette, JD, of the Sacramento, CA, law firm Monteau & Peebles, LLC, told Clinical Trials Administrator.

The lawsuit alleges fraud; violation of federal, state, and local research regulations; improper transfer of blood samples; and infliction of emotional distress, he states.

Not the first

The Havasupai suit is the latest in a line of recent legal actions on behalf of participants in research studies who believe investigators misled or exploited them to further their professional aims.

• In 2001, the families of five cancer patients who died while participating in experimental bone marrow transplant research over a 12-year period at the Fred Hutchinson Cancer Research Center in Seattle sued the center, claiming researchers engaged in fraud, violated federal regulations governing the protection of research subjects, and violated medical and research ethics by failing to sufficiently disclose the risks of an experimental treatment designed to minimize the occurrence of graft-versus-host disease. In April, a jury cleared the center and the researchers of misconduct allegations, finding in favor of only one of the plaintiffs.

The jury ruled that the center negligently caused that participant’s death by mishandling bone marrow donated by his brother.

• In 2000, a group of 380 women sued Tampa (FL) General Hospital for performing medical experiments, including multiple amniocenteisis procedures, on them while they were pregnant, allegedly without their consent.

A key allegation of the plaintiffs was that the consent forms used by researchers contained language not appropriate to the education level of the participants. The claim was for violation of the subjects’ right to be treated with dignity and to be free of unwanted treatment. The case was settled out of court.

These cases and others like them are putting increasing pressure on clinical researchers and institutional review boards to improve informed consent processes. But it’s important not to allow accusations and media coverage alone to shape research policy, says E. Haavi Morreim, PhD, professor in the department of human values and ethics in the College of Medicine at the University of Tennessee Health Science Center in Memphis.

Is too much expected?

Morreim has studied several court cases involving allegations of research misconduct and notes that legal arguments may distort both the actions of investigators and the legal and ethical obligations of both researchers and institutional review boards.

"I have noticed some statements made in the legal allegations that would seem to place unrealistic expectations on institutional review boards," she says.

"For instance, I have seen statements that indicate the IRB is supposed to ensure proper reporting’ and make certain’ that the trial conforms to ethical standards. How can an IRB ensure that a PI [principal investigator] does the PI’s job of reporting? The only way that an IRB can ensure reporting is to look not only at what they receive, but also look over the shoulder of each investigator every day to see what they are doing and match what they are doing with what is being reported. That is beyond any reasonable expectation of an IRB’s function," Morreim points out.

Other statements seem to indicate a perceived legal obligation to monitor the day-to-day progress of each ongoing study at their institution — an impossible task.

"I have read statements about the IRB’s failure in appropriately monitoring the informed consent process and the conduct of the experiment," she continues. "I wonder, What are we expecting here?’ I think we need clarification of what IRBs are supposed to do in the way of monitoring."

It’s important that investigators and institutional review boards get clarification of their responsibilities from the federal Office of Human Research Protections or the Department of Health and Human Services in this area, rather than the various allegations, legal decisions, and articles covering the disputes, she contends.

A jury may determine that a plaintiff’s allegations are unfounded, or institutions may decide to settle legal cases for financial reasons.

Neither of these scenarios, however, provides an answer for other investigators hoping for guidance about appropriate research conduct, Morreim notes.

"So many of these suits get settled out of court, then you get these standards’ for what investigators are supposed to do are left lingering out there as though they have validity," she says.

And information published about a case is not always accurate, she has found. "I always caution people to go to the primary sources, whenever possible," Morreim states. "If you want to know about a lawsuit, read what the parties file in court, not what is written about the case later."

Even then, the information may not be as clear.

With regard to the Havasupai case, she says judgments about the quality of informed consent can only be made by someone able to independently look at the informed consent documents and examine the context in which consent was obtained.

"I wouldn’t know unless I saw the consent forms themselves and what statements they made about further uses of the material," she states. "And did investigators allow participants to take forms home and study them, or did they ask potential subjects to sign them right away? What language did they use? Was it understandable?"

Populations at risk?

One important function the lawsuits have had, however, is to shine a spotlight on the special challenges of research involving specific groups of people.

It is important for investigators and clinical trial administrators to realize that it’s vital they not only adhere to the letter of the law, but the spirit of proper informed consent, says Dale Hammerschmidt, MD, an associate professor of medicine at the University of Minnesota School of Medicine and director of Education in Research Ethics and Compliance at the school.

Particularly with respect to the plaintiffs in the Havasupai, concerns about informed consent take on a new light when research subjects are members of a vulnerable population.

Discussions about protection of human subjects, and the federal regulations governing human research protections, have focused on the potential benefits and harms to the individual, and have been more cautions in their consideration of whole populations as units, he says.

However, when investigators conduct research that either reveals information about an entire group of people or holds them up to increased scrutiny or ridicule, informed consent documents that only deal with potential risks to each individual member as a person may be insufficient.

Culturally problematic? 

It can still be argued that use of the samples for research that the Havasupai would find culturally problematic, for example, and which still identified them as a group, constituted an inappropriate breach of their right to informed consent, he adds.

"Was there, in fact, an understanding that the samples would not be used for something else?" he wonders. "Was information sought or generated that could itself be problematic? For example, did they discover health risks or problems for which there would normally be an intervention?"

Even if the individual members could not be identified in the data or in publications, the group might be identified in a way that created breach of confidentiality or other informational risks, Hammerschmidt says.

The Arizona State researchers gained the approval and cooperation of the tribal government by presenting their research project strictly as a proposal to study diabetes among tribal members, Rosette claims. Tribal leaders never would have consented to the research projects ultimately undertaken.

"Tribal governments are very communal in nature, and they have a lot of power in the community," he explains. "Their approval goes a long way in members’ determining what outside projects they will participate in and which ones they won’t."

Individual participants did sign consent forms, some of which contained general statements about possible future uses information from the blood samples, but none of which specified what type of research, he continues. And participants were definitely left with the overriding belief that their samples and information would only be used to study diabetes.

The projects involving studies of schizophrenia and inbreeding were offensive and degrading, but members were particularly upset by a project that used the genetic information to argue that the ancestors of the Havasupai crossed the Bering Strait thousands of years ago. "Those arguments contradict their religious beliefs and are completely disrespectful of their religion and culture," he says.

In addition, investigators now cannot determine whether the blood samples were appropriately anonymized after collection because no appropriate mechanism was followed for tracking them. Some of the samples apparently were lost completely, he claims.

The extended use of the information came to light in different ways. Some members of the tribe read publications that published the research results and recognized it was their tribe the articles were discussing. University personnel at ASU discovered what had happened and asked the university to initiate an internal investigation, Rosette says.

The university shared the results of the investigation with the tribe, which then decided to pursue legal action.

"I want to emphasize that we feel the university has been very helpful during this process," Rosette says. "Arizona State has a long history of working with the tribe; it sponsors a program on Indian law; and has a history of being very open and welcoming to Indian students, and in other interactions with the tribe. We don’t think this unfortunate situation reflects on the environment at the university at all."