Genomics R&D requires updated understanding
Ethical, other issues come into play
Genome research and accumulated knowledge is changing the way we understand disease and treatment, which, in turn, is changing clinical trials, an expert says.
"For many years we conducted clinical trials with new drugs, and we'd see some responders and partial responders and some with no response, and nobody understood why," says Joan Rankin Shapiro, PhD, MD, an associate dean for research and a research professor in basic medical sciences at the University of Arizona College of Medicine in Phoenix, AZ.
The answer is that not all tumors are the same – even when they're located in the same place.
"We would think of somebody with a diagnosis like breast cancer or lung cancer as having the same kind of tumor," Shapiro says.
"Now, what we have come to appreciate is that whatever transformation is that begins the process, these tumors can evolve down different pathways," she says.
With this knowledge and new technologies, researchers have the ability to look at the complete genome of an individual, searching for abnormalities that exist in that patient's tumor, she explains.
This genetic information can inform both clinical trial studies and treatment. Studies will show which types of tumors respond to certain medications and doses.
"We're now gravitating toward more personal medicine," Shapiro says. "Most clinical trials are taking that more into consideration because of our ability to analyze genomics."
Investigators can analyze the genome for specific changes in patients' tumors. These changes tell them how to more accurately direct a drug to that individual and how to develop a subset of patients based on the abnormalities they have within their tumor, she adds.
"It is the kind of thing that allows us to look more in depth into a clinical trial involving a drug," Shapiro says.
Having the knowledge and ability to conduct this research is not enough. There are ethical and practical logistics that are daunting.
For example, HIPAA privacy rules govern how tissue can be used once it's extracted from a patient.
"Who is going to receive this information?" Shapiro says.
Tissue used in research might be moved from one site or company to another or used in multiple studies.
"When running a clinical trial, and they request tissue from patients, investigators need to know the laws and regulations, including that patients need to know what will be done with their tissue," she says.
The National Public Radio (NPR) and other media outlets have publicized the case of the woman whose tissue was used in studies and laboratories for years without her knowledge, Shapiro notes.
"No patient should donate any tissue without knowing what it's for and what is being used and what is going to happen to it," she says.
HIPAA rules make it more complicated.
"HIPAA says you can store tissue in a bank or take the tissue as long as you tell the patient what it's being used for," Shapiro says. "But if you store it in the bank and then take it out five years from now then how do you let the patient know what it's being used for?"
One way might be to ask patients up front about their tissue being used for research. They might ask these questions:
- Are you willing to donate tissue for Study X at this time?
- At some time in the future would you be willing to donate this tissue for future experiments related to this diagnosis?
- Would you like to be contacted each time there's a potential use for your tissue?
"You could ask the patient right up front what they would like done with the tissue," Shapiro says.
Investigators need to keep in mind that HIPAA does not permit them to consent a patient for the future, she adds.
If they check the box that says, 'Do you wish to be informed if in the future your tissue is to be accessed?' then that means someone needs to call them if the tissue is to be used in a study.
"Even if they leave the box blank most hospitals and universities have compliance policies that will require someone to make that call to the person," Shapiro says.
"The big clause is that maybe they give their tissue to a tissue bank, but five years from now they decide they don't like what the tissue bank is doing with these tissues and they want to withdraw their tissue from the bank," she adds. "Investigators have to put that in the informed consent form – that patients have the right to withdraw their tissue at any time, and investigators have to return it unless patients say it has to just be destroyed."
Most people will agree to donating their tissue to research, but they need to understand they will not benefit personally, but that someone in the future might benefit from its use in research, she notes.
"There's always the hope they will benefit someday, so we have to make people understand they won't benefit from this," Shapiro says.
"And maybe their particular tumor has a receptor that is important to developing a particular drug," she adds. "The patient may never benefit from that drug being marketed 10 years down the road."
So it's very important to be clear in informed consent about how the patient probably will not receive any physical or financial benefit from the use of their tissue in research.
In the past, researchers were less attentive to communicating this message, but now it's important from a regulatory standpoint, as well as from an ethical perspective, that they clearly inform patients about how the process works, what their personal protections are, and how they will or will not benefit from the research.
Investigators also have to be aware of the requirements when a breach of privacy occurs with biospecimens.
"If for any reason their tissue is identified, and there's a breach of confidentiality that exceeds 50 people, then we have to report it to every person involved in the breach," Shapiro says. "If the breach impacts more than 500 people then we have to report it to the federal government and the media."
This requirement puts pressure on researchers and sponsors to protect information very carefully to ensure there is no breach of confidentiality.
The simplest strategy is to de-identify biospecimen samples.
"There's a lot of understanding between the industry and science to make sure we can get as much information as we can get, but still not have the possibility of samples being identified," Shapiro says.
Another issue involves how biospecimens are stored.
Researchers previously have used local freezers, but this increases the risk of a breach of confidentiality, she notes.
"They are now developing biodepositories, " Shapiro says.
The National Cancer Institute (NCI) and the Food and Drug Administration (FDA) have guidelines for repositories. These detail how they are to be stored, how biospecimens are shipped, and how their integrity can be retained, she explains.
Clinical trial sites and investigators should become accustomed to living in a time when many rules apply to how they handle human biospecimens, Shapiro says.
"We live in a litigious society, and in order to protect not only the patient but the investigator and institution, we need to make sure we don't violate these rules," she adds. "You don't want your institution to end up in headlines, saying that 'XX is selling body parts.'"
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