Collecting extra tissue samples should be a no-go without consent
Collecting extra tissue samples should be a no-go without consent
Add-on gene studies pose special concerns for IRBs
In recent years, it has become a common practice for sponsors of clinical trials to collect extra blood and tissue samples from subjects for genetic analysis and possible later use in future research projects. However, trial coordinators should be aware that these types of arrangements — known as add-on studies or tag-on studies — are drawing increasing scrutiny from institutional review boards.
"When industry sponsors propose to add on a genetics study to a traditional clinical trial, this may be viewed as suspicious and potentially create a substantial risk [to subjects] due to the lack of specificity inherent in the protocol," says Barbara Handelin, the CEO of Kenna Technologies Inc., a drug discovery company in West Chester, PA.
In 2000, Handelin, a trained geneticist, helped conduct a research study funded by the U.S. Department of Energy that evaluated the challenges IRBs faced when reviewing genetic studies. In her studies, add-on genetic research was of particular concern for many IRB members.
Two main characteristics of such studies can be troubling for IRBs, she says. One, the potential for unknown future use of the clinical specimens and the afterthought nature of how the consent to participate in the add-on protocol may be presented to potential subjects.
"It is a different approach to conducting research," she notes. "It is a cataloging process more than being hypothesis driven."
With traditional research protocols, investigators have a hypothesis in mind and seek evidence to either support the hypothesis or disprove it.
Now that the human genome has been mapped, however, researchers often simply want to collect and examine the DNA of large populations of people in the hopes that some genetic mutation may be observed and subsequently linked either to a particular disease or condition or a resistance to it.
Lack of specificity troubling
Add-on studies have quickly become very common, particularly in clinical drug trials, says Daryl Pullman, MD, associate professor of medical ethics at Memorial University of Newfoundland in St. Johns.
"Just within the last five years or so, almost every clinical trial has a genetic add-on," says Pullman, who sits on the university’s research ethics board (REB), the Canadian counterpart to U.S. IRBs. "If there is a clinical trial, they often want to ask if they can take another blood sample, telling the subject, Your DNA may be valuable for research purposes and we’d like for you to give us another sample.’"
The problem, he says, is that investigators themselves don’t know what kinds of studies might be performed on the samples in the future, what information might be sought, and how the information will be used. Therefore, they can’t truly inform the subjects about the possible risks and benefits to participation.
Certainly, in many cases, participants in genetic studies can expect to see no individual benefit.
"For example, there is a family that has a high prevalence of a kind of neuropathy that gives them chronic insensitivity to pain," he says. "So there is real interest, from a genetics perspective, in finding out what is the genetic problem that makes these people insensitive to pain. But the interest isn’t in treating the condition so they can become pain sensitive. The interest is in finding out what the genetic link is. There can be all kinds of implications — e.g., developing new analgesics, etc. — so, none of the benefits of the specific research would ever go back to this family. They are just interesting research subjects."
Investigators must be up front in their consent documents and explain the unknown nature of the future research and specify how the subjects’ DNA will be maintained, whether it will be identifiable and how participants may withdraw their consent at a later time, if they so decide, Pullman says.
At Memorial, the REB has prohibited add-on protocols that simply want to collect DNA for any type of future cataloging, he says. Investigators must stipulate that the samples collected will be used for studying a condition related to the subject of current study.
"For example, if the subjects are participating in the trial of a psoriasis drug, the future studies would have to be related in some way to the study of psoriasis — they couldn’t just collect the samples for any purpose," he notes.
Consent is not one-time event
If the samples taken are going to remain linked in any way to the subject’s identifying information, then the subject must also be given information about how his or her privacy will be maintained, where the information will be stored, and provide a way for the subjects to withhold or withdraw their consent, Pullman adds.
"We are very concerned about blanket consent to allow the researchers to do anything they want with the samples," he continues. "If it is de-identified, that is one thing — but oftentimes they want to maintain some kind of linkage with the patient record because that is what is important about the information. In addition, when you obtain consent to use samples for research purpose afterwards, you can’t just use it for any research approved by an IRB; you can only use it for research that is related to rheumatoid arthritis or whatever. And you have to give the subject the option of saying, No, at the end of the study I want my sample destroyed,’ and provide a way for them to ask, if they change their minds later, that their identifiable sample be removed and destroyed."
If the samples will be de-identified early on, potential participants should also be informed of that and informed at what point they will no longer be able to withdraw consent, because the sample will be de-linked and investigators won’t be able to determine which sample belonged to which person.
Separate document required
Memorial’s REB also requires investigators proposing add-on studies to put information about that study in a separate informed consent document, rather than buried within the current study consent form, Pullman says.
"Informed consent documents tend to be overly burdensome in terms of the level of detail and the kinds of information presented; it is difficult sometimes to comprehend what is being proposed. If somebody has cancer or arthritis, we already have enough problems getting them to understand that this is not clinical care that we are proposing, this is research," he explains.
"We don’t think that in the midst of all of that there should be two lines that say, Oh yeah, we’d like to take some additional samples for future use and you’re signing away all rights in the event that we find something that might be of clinical or economic use.’ We have actually required that those kinds of statements be taken out of the informed consent document for the trial. We now require a separate consent form for genetic add-on studies."
The issue of telling subjects they will not be entitled to share in the financial rewards should the study of their DNA yield valuable information is a tricky one, Pullman adds.
Memorial’s REB does not allow informed consent documents to make statements that seem to prohibit subjects from seeking to share in the benefits of the research, but many institutions do, he notes.
"More commonly, consent documents have to at least admit they are looking for something that may have commercial marketability and that might make a profit. They are required to at least be up front and say that might happen, but then they might say, We are not going to pay anything to you in the event that should happen, and that way people know ahead of time."
Pullman and colleagues at the university and in Newfoundland’s provincial government are exploring ways to get sponsors of genetic research to work out separate benefit-sharing arrangements with communities before permitting add-on studies to take place in a certain locale.
In that way, subjects would be able to gather some benefit for participation whether or not their genetic information led to some breakthrough treatment. Such proposals are controversial, however, and legal determinations of who owns human DNA have not been clearly worked out anywhere, he notes.
"But without that process in place, we at least require any statements about the add-on studies to be taken out of the information about the current clinical trial that is taking place and be placed in a separate document," he says. "So the participant considers whether they want to participate in the clinical trial, and then, separately, consider whether they are willing to have their samples saved for later use."
In recent years, it has become a common practice for sponsors of clinical trials to collect extra blood and tissue samples from subjects for genetic analysis and possible later use in future research projects.Subscribe Now for Access
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