Cinnamon Wood, a high school science teacher in Willow Springs, North Carolina, was attending a conference in 2006, when she was approached by the National Institute of Environmental Health Sciences (NIEHS) about donating a blood sample for a cross-sectional study of single nucleotide polymorphisms — the most common type of genetic variation among humans. Always happy to further the cause of science, Wood readily agreed.
About two years later, Wood received a letter from the NIEHS noting that she had a unique polymorphism affecting how her body reacted to steroids, which the institute wanted to study further. Wood’s participation continued for a few years. Wood provided follow-up information when asked and even allowed researchers to give her a small dose of steroids to see how her body responded. “It’s been very interesting,” Wood says. “There have been a couple of papers published because of the work they have done on people who have my polymorphism.”
Throughout her participation in the NIEHS study, Wood received numerous informed consent documents to sign, sometimes three or more per clinical visit. “Every single study I was involved with, I had to sign another paper,” she recalls. “They confirmed that I understood what my sample was being used for, that I understood the study could lead to further developments, and I freely gave it for the purposes of scientific research.”
Wood says her experience with informed consent has been very positive. She was given the documents to read in advance, and a nurse walked her through the process point by point, stopping periodically so Wood could ask questions. “I had a bit of a leg up because I teach workshops on biotechnology, so I know what it’s all about,” Wood observes. “Would a layperson have a full understanding? I’m not sure.”
Informed consent refers to the specific policies and protocols that ensure that medical patients and research participants understand what they are agreeing to and the potential consequences of such an agreement. The push for it dates back to just after World War II, when the world confronted the horrific medical atrocities performed on unwilling subjects by German and Japanese doctors. The resulting Nuremberg Code, released in 1946, defined legitimate medical research and specifically addressed the issue of informed consent.
“Historically, the term ‘informed consent’ was first used in a court of law in 1957,” says Erica Spatz, a cardiologist and an assistant professor at the Yale School of Medicine. “However, it was not until the 1980s that all states had laws on the books regarding informed consent.” Among medical researchers, informed consent is now commonly guided by the so-called Belmont Report. Released in 1979 by the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research, it summarizes ethical principles and guidelines regarding the use of human test subjects.
“Today, the primary purpose of informed consent is to empower the patient,” observes Arthur Caplan, the director of the division of medical ethics at NYU Langone Medical Center in New York, and a Genome board member. “But I think it would be accurate to say that once lawyers for institutions doing research got near informed consent, they started to modify it to include protection of the researcher and the institution. That’s a shift you can see happening even today. Consent is now a little less patient oriented, a little more oriented to institutional protection.”
There can be some significant differences between informed consent for a medical procedure, such as genetic testing, and informed consent to participate in medical research, especially genomic research, adds Jennifer McCormick, an assistant professor of biomedical ethics at the Mayo Clinic in Rochester, Minnesota. In both cases, the documents are meant to inform patients and ensure understanding, but informed consent for research now anticipates the future use of data.
“When we start talking about genetics and genomics, especially in the research context, the consent document takes on a new twist,” McCormick explains. “That is because in many studies, investigators are requesting that individuals allow them to keep their sample and data to be used for unspecified future use and/or to allow the data and samples to be shared with other investigators. Both of those aspects bring a new twist to consent, because the typical paradigm for clinical trials is a limited period of time. When you start making requests to keep a sample forever, for future unspecified use, you’re deviating from the typical script.”
Indeed, informed consent for research now typically addresses special considerations for genomic data, such as:
- Data may be stored and used indefinitely.
- Researchers may inform participants of susceptibility to a range of conditions, some of which may be unexpected, given personal or family history.
- Data may show risks that are uncertain or unclear.
- Data may be reinterpreted and change in relevance over time.
“One point that is applicable to both patients seeking genetic testing and individuals considering participation in a genomic research study is whether any choice is offered in what they will learn or not learn,” notes McCormick.“Stated another way, whether they have to learn everything the ‘experts’ determine to be important or whether they can say, ‘I want to learn only about these types of conditions but not those other types.’ Similarly, if someone is having clinical genomic testing done, they should fully understand whether they will get everything they want, or whether there will be limits on what is analyzed and returned, as determined by experts and evidence the experts are comfortable with.”
Don’t be afraid to ask questions
The informed consent process can be confusing to those who have never gone through it. “I don’t think individuals who are approached to participate in studies realize that they can and should ask questions,” says McCormick. “They don’t have to passively listen to the researcher; it’s okay for them to stop the investigator and say, ‘Can we back up? I didn’t catch that. Can you explain it a little more?’ It’s also permissible to take the document home so you can read it more thoroughly, and to decline to participate if you feel the study is not right for you.”
“I’ve had many patients who, after hearing about the specifics of a procedure, say, ‘I’m glad we discussed this because that’s actually not for me,’” adds Spatz, who often discusses informed consent with her patients. “Or, ‘I thought it was going to prolong my life, but if you’re telling me it’s not going to achieve this, I’m not interested.’ The informed consent process really informs their decision-making.”
Clinicians and researchers say it’s also common for patients to express concern that their genetic data may be used against them for employment or insurance. Patients may be unaware that they are protected for the most part by the 2008 Genetic Information Nondiscrimination Act. (For more on GINA, see “The Question,” page 22). They may also be concerned that their personal medical information can be hacked. This is understandable in an age where even classified government computers have been tampered with, though it’s important to note that medical data acquired for most research studies is thoroughly de-identified and is stored on protected servers, where it can be accessed only by approved investigators. (De-identification of data is usually not done for clinical diagnostic testing.) “I’m more concerned about someone having access to my bank account or credit card number than I am about someone getting access to my medical information,” says McCormick, who is enrolled in the Mayo Clinic Biobank.
Read before you sign
The goals of informed consent are education, understanding, and transparency, but a lot can get in the way of that understanding. For example, some patients may be intimidated by the sheer size of the document, which, depending on the type of study, can be several pages in length. “The long form is a detriment to understanding anything,” Caplan states. “Think about signing up for Google or Facebook, or when you get a credit card. No one actually reads that stuff.”
It’s also common for participants to merely scan the document before signing it, trusting the investigators to do the right thing, or to be hindered by a lack of education, low health literacy, or because English is not their primary language. According to Caplan, informed consent documents tend to be produced in English and a few other dominant languages, such as Spanish, but if a patient speaks a less common language, there can be problems. And lastly, many people don’t really pay attention to what the investigator is telling them because they are nervous about what is to come.
There can be some significant differences between informed consent for a medical procedure, such as genetic testing, and informed consent to participate in medical research, especially genomic research.
However, a lack of understanding can have serious consequences, researchers note. For example, a patient may be surprised when something goes wrong, even though he or she was informed of the possibility. “There are adverse events, and people may be shocked to learn that,” says Caplan. “Other potential issues include loss of privacy, loss of confidentiality, or finding out that the research involves something you don’t approve of morally, such as stem cell research or the development of a new contraceptive. People tend not to take seriously the non-physical harms. Though they care about them very much, they don’t ask about them.”
The return of research results, as outlined in an informed consent document, can also lead to potential problems. A genetic study, for instance, may reveal unexpected health issues, such as a higher risk of breast cancer, that the patient was not prepared to receive. “It’s more a psychological harm, but it can cause a lot of anxiety,” says McCormick.
Researchers are aware of the potential problems and are working to improve it. A 2013 study published in BMC Medical Ethics examined ways to improve patients’ understanding when they give informed consent for research studies and concluded that the most effective approaches were enhanced consent forms and extended discussions.
Caplan also urges patients to take the informed consent document home for a thorough read and then ask the clinician or investigator to explain any aspects that you don’t understand. “It may also help to bring a tape recorder so you can review the conversation later,” Caplan advises. “Or bring someone with you who can act as a second set of ears.”