Ways to improve genetic trials informed consent

Be sensitive to disclosure risks

While an argument could be made that collecting genetic information from individuals is no different from collecting any other type of health information, the fact remains that the very word "genetic" may raise additional concerns among potential research participants.

For this reason, a few genetic ethics and research experts have offered these suggestions for how clinical trial administrators and researchers may best handle the informed consent process during genetic or pharmacogenetics clinical trials:

• Disclose financial interests. "Researchers need to make full disclosure of financial interests," says Mark A. Rothstein, JD, director of the Bioethics Institute at the University of Louisville (KY) School of Medicine.

The importance of this policy was highlighted in 2000 when families of children suffering from Canavan disease, a rare neurological disorder, sued researchers over control of the Canavan gene, he explains.

Families of children who had Canavan disease had encouraged a geneticist to research the disease. The families provided tissue samples that were essential to the success of the research, which eventually discovered the gene responsible for the disease. The Miami Children’s Hospital, where the research was conducted, then licensed the genetic test and barred the Canavan Foundation from offering free genetic screenings. The families from whom these tissue samples were obtained were never offered informed consent or disclosure about the financial implications of the research, according to news reports of the lawsuit.

The hospital eventually settled the lawsuit and the terms were not made public, Rothstein says.

As a result of this case, disease foundations now are filing their own patents, and they’ve become more savvy in terms of the contracts they sign with researchers, he adds.

But the important take-home message for clinical trial administrators and researchers is that they must disclose all financial interests to potential enrollees, Rothstein says.

• Be clear about potential risks and benefits. Most potential risks only are relevant if the research involves individually identifiable data, he notes.

"Potential risks are only generally relevant if the results find their way into the clinical file of the individual," Rothstein says.

It’s important to make certain that the likely and pertinent risks are thoughtfully discussed with research participants, says Laura Lyman Rodriguez, PhD, special advisor to the director of the National Human Genome Institute in Bethesda, MD.

While less probable risks could be included in the discussion, the focus should be on the more important aspects of the research, she adds.

"There are areas where particular attention might be paid, and one is the potential impact on family members," Rodriguez says.

For example, if the trial provides for participants to receive their own genetics information, then potential risks may include the psychosocial impact of that information on the participants, as well as on their families if they choose to share the information.

"A participant should be told when enrolling whether individual results will be returned; and if there is an option to find out what the individual results are, then they have the option also to not receive them," Rodriguez says. "Some people may not want to learn the information because of how it might effect them personally."

• Have a direct dialogue with the IRB (institutional review board). Investigators need to speak with IRBs directly to explain what they’re doing and to inform IRB members about the nature of the genetic research and the informed consent process, suggests Barbara Handelin, PhD, chief executive officer of Kenna Technologies Inc. in West Chester, PA.

Training and guidance integral

• Encourage institutions to develop guidance. Institutions and IRBs need to have a conceptual framework for genetics research that involves human subjects, Handelin says.

She suggests that some of the issues that need to be considered within such a framework or guidelines are as follows:

  • What are the privacy concerns and measures that your institution cares about?
  • If genetics are part of the protocol, does the institution have some special requirements for researchers? For example, would an institution agree to have any protocol, especially an industry-sponsored one, involve DNA samples from subjects that are associated with personal identifiers, such as names, social security numbers, and clinical history, Handelin says. "Or would the institution be in the camp of saying, You can do it, but you have to make the sample anonymous?’"
  • Does the institution have a gatekeeper or repository keeper who can be the privacy firewall for the institution and for any subjects participating in genetics research?
  • What are the logistical mechanisms for permitting patients to opt out of a genetics study?
  • If participants opt out of a genetics study, how does the institution want to be sure that the sponsor did everything it said it was going to do, such as destroying samples, stripping samples of all identifiers, etc.?

• Add depth to the informed consent process. Generally, the informed consent process is similar to what one would use for any type of human subjects research, Rothstein notes.

"You need to identify the most important matters that would be relevant to a reasonable, potential research subject," he says. "Set out these issues, disclose them, and make sure it’s not a rote process."

Also be sure that all questions are asked and answered and that people have time to think about whether they’d like to participate, Rothstein adds.

However, since genetics research is evolving so rapidly, there are many instances when samples collected for one particular type of genetics research may come in handy for another type down the road. This possibility raises the question of how informed consent may be obtained for unknown future studies.

"Nobody should ever sign off on a protocol that asks for blanket consent up front," Handelin says. "On the other hand, a sponsor or IRB might say, Here’s the specific question that we want to ask right now for this study.’"

Then the clinical trial administrator might want to ask patients whether they could keep the sample for future studies that have not yet been determined, Handelin adds.

It would be up to IRBs to decide whether they want investigators to have permission to ask that last question or whether they want investigators to return with a specific informed consent whenever additional research is required, Handelin says.

"DNA is a constant and because it is such a rich source of information about people and their medical predilections and how that relates to their current or future disease process; it is a resource that most researchers want to hang on to once they collect it," Handelin says.

• Provide subjects only with genetic information that meets medical standards. One issue that becomes pertinent to risks involved in genetic research is how personal genetic information is disclosed, when the protocol is set up so such a disclosure is possible.

For example, when a medical patient is tested for genetic information, that test would meet the standards of the Clinical Laboratory Improvement Act (CLIA), Handelin explains.

However, these same high standards are not always required for anonymous clinical research involving genetics because the objective is to obtain statistical information involving a population, not health care information involving a particular individual.

Handelin, who once ran a genetics diagnostic laboratory, does not believe that investigators should give genetics research participants any of their personal genetics results unless those tests had been conducted under rigorous CLIA conditions.

A research laboratory may not be able to provide the same rigor that a clinical laboratory has to do when it is giving people information with which they will make a medical decision, says Handelin.

"One way to deal with this is if the test information is profoundly important and it can be duplicated in a CLIA-registered lab, then you can provide it back to the participant," she adds. "But if it can’t be duplicated, then, no, don’t do it."

The risks for an individual who receives inaccurate genetics information is far greater than the risks for a group of people, Handelin adds.