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Biobank uses opt-out approach to gathering blood samples
Bank not technically human subjects research
When Vanderbilt University Medical Center set about creating its BioVU biobank, it went in a different direction than most institutions.
Instead of using an opt-in approach that recruited patients to submit blood samples, the institution instead decided to collect discarded blood samples from routine clinical testing.1
Samples are linked to a deidentified version of the hospital's electronic medical record, so they can be used to look at how genetic differences affect health without involving individually identifiable health information.
Under the federal regulations, this does not constitute human subjects research, so the Office for Human Research Protections (OHRP) did not require prospective informed consent from patients for the use of their samples, says Daniel R. Masys, MD, chairman of the department of biomedical informatics at Vanderbilt University Medical Center (VUMC) in Nashville, TN.
But Masys says the Vanderbilt IRB determined early on that the institution should go further in giving people information about the program and the ability to opt out if they chose. Vanderbilt has conducted education about BioVU using brochures and advertising. A notification on all of its treatment consent forms tells patients about the collection and allows them to check a box to refuse to have their samples stored.
"Both the educational campaign and the opt-out were directly the result of the IRB believing and asserting that the current protections provided by 45 CFR 46 are not in sync with community expectations about genetic research," Masys says.
"We have two, separate thoughtful opinions in writing from OHRP that told us 'You can do this opt-out thing but it's not required by federal regulations,'" he says. "But IRB just didn't think it was right to run it as an invisible, behind-the-scenes program."
The IRB reviews any changes to BioVU and reviews the entire program annually.
After three years of operation, the biobank contains more than 80,000 samples, and Masys expects it to hold a quarter of a million samples by 2014. After years of discussion and surveys of parents, the bank also began collecting pediatric specimens.
The opt-out rate currently stands at about 5%, he says.
"Interestingly, that was predicted by our opinion surveys done ahead of time, which told us that about one out of five people have some concerns about doing this kind of approach, but only one out of 20 have sufficiently held opinions that they actually want to be opted out," he says.
Opt-out contained in consent-to-treat form
When a patient is treated at VUMC, he or she is presented with a Consent to Treatment/Agreement to Pay form that contains a section briefly describing the sample collection:
"I understand and agree that any specimens or tissues normally removed from my body by VUMC in the course of any diagnostic procedures, surgery or medical treatment that would otherwise be disposed of may be retained, used for educational purposes or research, including research on the genetic material (DNA) or other information contained in those tissues or specimens."
The form also notes that any research done will not identify the patient personally and that patients will not benefit financially from any resulting invention or drug.
The patient may check a box that states: "Do not use my leftover blood for the DNA databank."
Masys says patients receive this consent form annually and can withdraw consent at any time for future use of their data.
Once samples are in the system, they are linked to a deidentified version of Vanderbilt's electronic medical record called the synthetic device (SD). Because this system does not allow for recontact of patients, the usefulness of the samples depends upon the usefulness of the medical records system, Masys says.
"We have a very rich EMR and I think that's the cornerstone," he says. "And the IRB as well had to have confidence in our ability to deidentify data in the EMR."
The deidentification process removes or changes all of the required HIPAA identifiers – for example, dates of clinical events are changed, while still preserving the time that passes between events. Masys says the SD is treated as a limited data set, and has strict rules regarding its use.
Users must be Vanderbilt employees, research faculty or staff, and must get IRB approval for any use of individual records – through a streamlined process that can be turned around in about a day.
Anyone with a university login may use a version of the SD that shows information about groups of records.
"For example, if you were a cardiologist and you wanted to know how many people were on Plavix and had had a myocardial infarction, you can get numbers back from that," he says. "But if you want to actually get access to clinical data, you have to go through the IRB review."
He says that if a search turns up only a few records, the system won't allow those individual records to be shown.
"So you couldn't, for example, triangulate and find a single individual because you know they have this rare combination of diseases."
Despite the deidentification process, Masys says there's a possibility that information in the written portions of the records may inadvertently identify a patient. Users are directed to tell the institution about any instances they find so that they can be removed.
He says that users of the SD know that if they misuse data they're at risk for sanctions up to and including losing their jobs.
"We are very sensitive to those issues in the protections around use of the data and we never assume that we have eliminated the risk of reidentification entirely. As much as our lawyers would like us to give that guarantee, we just cannot give that guarantee."
A special community advisory board, drawn from local organizations and patient advocacy groups, was created to guide the institution in its development of the biobank.
"They meet two or three times a year, face to face, only to discuss this project," Masys says. "It is actually a remarkably outspoken, independent, effective board. It's headed by a lawyer who works in the State of Tennessee Office of Disability and is very conversant with issues not only of public perception but of possible scenarios of misuse."
Masys says the advisory board sometimes is at odds with Vanderbilt's own bioethics committee, which can take a more cautious approach.
"The bioethics committee is very concerned about scenarios that might be very rare – they just want to make sure that there's no possibility that something might happen," he says. "And the community advisory board can be a lot more commonsense about that. As the community board has learned more about the project, they sort of want us to go faster – they want us to make more progress with more diseases."
He says the board has given practical advice about educating the public, helping rewrite the education brochures in both English and Spanish and asking that certain questions be addressed such as whether companies have access to the data or in one case, whether DNA in the samples could be used for cloning.
"We would have thought that was a little bit scientifically farfetched, but they said you should address that," Masys says. "They serve as an ongoing reality check for 'Are we missing anything big?' and 'Are we headed in the right direction?'"
Despite the educational efforts and other public outreach, Masys says Vanderbilt does get occasional phone calls from people who learn about the biobank and have concerns. If those people still are unsatisfied after talking to patient services representatives, they talk to Masys.
"So I get the people at the tail end of the curve who are absolutely outraged and believe there should be laws against this sort of thing and believe that this couldn't possibly be legal," he says. "They never realized that federal research regulations have allowed use of existing tissue and data for 40 years now."
Masys says that aside from the sheer number of samples being collected for BioVU, its success can be measured in the types of samples being gleaned – from minorities and other underserved populations who often do not contribute to opt-in biobanks.
"For those of our faculty who are interested in diseases that are preferentially found in minority populations, it's actually become an unexpectedly rich resource to do science they couldn't otherwise do," he says. "At least we're generating hypotheses and gathering preliminary data. And that was a very nice endorsement of building an all-comers biobank in this deidentified space."
Masys believes that close involvement by the IRB throughout the process has been crucial to the success of this approach.
"I think it's a good thing, especially when you're trying to develop a novel research resource, where it is a moving target," Masys says. "The power of genomic technologies is raising ethical issues every week, if not every day. So having the IRB as a participant in the design and operation is not just one of those things you do because of structural necessity, but to actually enhance the project."