Three days before Christmas in 1995, Linda Horton, a medical researcher in Nashville, Tenn., was diagnosed with a large, fast-growing tumor in her breast. She quickly began her treatment course: chemotherapy to shrink the tumor, followed by a mastectomy—her doctors then told her the cancer was stage II—and additional chemotherapy afterward.

Horton didn’t qualify for any clinical trials for her cancer, but had her oncologist found one, she probably wouldn’t have thought long about signing the informed consent form. Patients consent to a medical treatment or procedure, in theory, only after they’ve been given enough information to make a sound decision. But in the midst of a cancer diagnosis and treatment, feeling fully informed can be challenging—and many patients just want to move forward. “Would I have signed something if he asked me to?” Horton asks. “Yup.”

But nearly two decades later, Horton, now 63, is the manager of a cancer research lab at the Vanderbilt-Ingram Cancer Center in Nashville, and she thinks patients should slow down and learn all they can before putting their name on the dotted line.

Horton, who writes sections of clinical trial informed consent forms related to studies at the lab she manages, hasn’t forgotten what it’s like to face complex medical information under stressful and uncertain circumstances. Recently, to address similar concerns, researchers and institutions such as the National Cancer Institute (NCI) have been working to simplify clinical trial informed consent forms. Yet consent can come into play not only before ordinary treatment or a clinical trial, but also prior to genetic testing or tissue donation. And as informed consent is adapted to new technologies, becoming “informed” has—for some procedures—become increasingly complicated, even as understanding what you are consenting to may be more important than ever.

“Informed consent is definitely a moving target,” says Bronson Riley, a genetic counselor at the Southeast Nebraska Cancer Center in Lincoln, who has helped develop informed consent guidelines for genetic counselors working with cancer patients. “Especially now.”

Consenting to Treatments and Trials

You give consent for medical treatment all the time: when you see a specialist, fill a prescription or have blood drawn for tests. Those events typically carry a low risk, and simply going through the actions of doing them equates to giving consent. Cancer treatments carrying higher risks require written consent.

During the informed consent process prior to treatment, patients and health care providers discuss a plan. A variety of information should be part of this discussion. For instance, you should learn about the benefits and risks of available treatment options, as well as the pros and cons of not receiving treatment.

The process may seem straightforward enough. But, notes Horton, many patients are making these decisions at a time when they “are terrified,” and when the deluge of information about complex therapies can be especially hard to digest. According to Horton, patients should take enough time to be comfortable with their decision. Ask questions of the health care team if any details are unclear, she advises, and discuss your plans with your loved ones. Asking your health care team if you can record your conversations with a voice recorder is recommended by many organizations, including the American Cancer Society.

If you are considering participating in a clinical trial, becoming adequately informed may feel harder because the possible benefits and risks of participation may not be fully known, and because you may continue to receive additional new information throughout the trial. The informed consent process should give you an understanding of the trial, including what is already known about the treatment or procedure from previous research.

Horton points out that clinical trial consent forms are much more patient-friendly than in years past. “I think there’s a lot more effort being put into making the patient comfortable” with the information before joining a clinical trial, she says. In the last 15 years, the NCI and many cancer centers and research institutions have been working to simplify the forms and add reader-friendly language. Recent revisions by the NCI, for instance, cut its typical consent form length from about 16 pages to seven pages.

What You Need to Know About Your Clinical Trial

Learn about the process.

A clinical trial may offer you access to an otherwise unavailable cancer treatment and quality medical care. You can also help advance cancer science. But before deciding whether to join, you’ll want to become informed about the trial and any potential risks. According to the American Cancer Society, the informed consent process should tell you:

  • What the clinical trial is set up to find out
  • What is expected of you and how long you will take part
  • What is known and not known about the new drug or procedure
  • Any benefits you may be expected to receive
  • Any known possible risks to you
  • Other possible treatment options
  • Whom you should contact with questions or problems related to the study
  • That you can leave the study with no penalty and opt for standard medical care at any time
  • How your personal information will be protected

Source: American Cancer Society

Your Genes, Your Information

Though patients involved in the process of informed consent for clinical trials may find the forms less overwhelming than before, those facing informed consent for genetic testing may encounter new complexities. According to the National Institutes of Health, genetic tests are now available for mutations associated with more than 2,000 diseases, including some of the 5 to 10 percent of cancers that are believed to have a hereditary component.

There is inconsistency regarding what information is discussed during the informed consent process—typically led by a doctor or genetic counselor—prior to genetic testing for a mutation that increases cancer risk. Several groups do offer guidelines, however. Riley co-authored updated guidelines for cancer risk counseling that include suggestions for the consent process and were published in 2012 by the National Society of Genetic Counselors (NSGC). Among the recommendations for counselors: Talk to patients about their personal medical history as well as their family medical history going back three to four generations, discuss who can view the results of the genetic test, and address the test’s possible outcomes.

As part of the informed consent process, the counselor should also go through a cost-benefit analysis with the patient, Riley says. To do this, Riley helps patients understand their likelihood of having a mutation based on their personal situation. And then, he works with them as they decide: Is it worth it to pay, in some cases, thousands of dollars for this test?

Patients should also learn about their choices, according to the NSGC guidelines. For example, they may be told that they can choose to wait for the results of a genetic test before making a decision about treatment, or that they could begin treatment before their results are available, says Riley. Individuals who have not been diagnosed with cancer may be informed that options such as active surveillance and risk-reduction surgeries are available if testing reveals a mutation that can greatly increase their cancer risk.

Other organizations have also issued similar guidelines or statements regarding genetic testing. The American Society of Breast Surgeons, for instance, recommends that the informed consent process for patients being tested for BRCA mutations include a discussion of the role of family history, the increased cancer risk associated with BRCA mutations, and the implications of receiving a positive, negative or inconclusive test result.

Prior to genetic testing, you should also be informed about the implications of sharing test results with family members, and learn how results might affect insurance coverage. Federal law prohibits health insurance companies from discriminating on the basis of genetic test results, but “life, long-term care, and disability insurance can use the results of those tests” to change or deny coverage, says Riley.

Many of these issues are not unique to cancer, and the rise of quick, inexpensive full-genome sequencing has raised even more questions: Is it appropriate for labs to test for additional mutations without a patient’s explicit consent? Earlier this year, the American College of Medical Genetics and Genomics (ACMG) released controversial guidelines. These included a recommendation that labs offering genetic sequencing for particular conditions also analyze the patient’s DNA for telltale mutations in—for the time being—56 genes strongly linked to disease. The ACMG recommends that labs report these “incidental findings” to the patient’s doctor. (Currently, some labs do report such findings, and some don’t.)

The patient should be informed that the additional testing is taking place, the ACMG suggests, but also know that consent for one particular genetic test extends to the other genes. According to these guidelines, a patient cannot opt out of selected tests, and separate consent is not required to obtain the other information or report it to a physician.

The ACMG guidelines address mutations associated with disorders for which preventive measures or treatments are available to patients, says bioethicist Amy McGuire, the director of the Center for Medical Ethics and Health Policy at Baylor College of Medicine in Houston, and a co-author of the guidelines. “I don’t think we have good data on whether or not individuals want this [additional genetic] information,” she says, “but there is a presumption that if a laboratory has information about a patient that meets these criteria, then it has an obligation to disclose it to the ordering physician.”

On the other hand, critics argue that the recommendation does not recognize a key right of patients. “Patients have an established right to refuse unwanted medical tests and the information they might disclose,” wrote Susan Wolf, a professor at the University of Minnesota Law School in Minneapolis, and her colleagues, in the May 31 Science, “even if that information would offer potential medical benefit.”

18 Questions to Ask About Genetic Testing

Find out will happen to your genetic information.

If you’re considering genetic testing, you should be fully informed about the test prior to consenting to it. To ensure that you get all of the information you need, print out this list of 18 questions provided by Bronson Riley, a genetic counselor at the Southeast Nebraska Cancer Center in Lincoln, and take it with you to your appointment with your genetic counselor or doctor:

  1. What is my current risk for cancer?
  2. Are there testing criteria for this test and do I meet them?
  3. What is the likelihood that I have a mutation?
  4. If I have a mutation, what is my cancer risk?
  5. How much would the testing cost me out of pocket?
  6. What kind of sample is required?
  7. Am I the appropriate person in my family to be tested?
  8. What are the limitations of this testing?
  9. What is the turnaround time for results?
  10. What kind of results can I receive from this testing (positive, negative, uncertain)?
  11. What is my likelihood of getting inconclusive results with this testing?
  12. How will my results be used?
  13. Are there published management recommendations for mutation carriers? (What can I do to reduce my risk for cancer?)
  14. Does a negative result mean I am no longer at risk for cancer? What about my family members?
  15. What does the laboratory do with my sample after it completes the testing?
  16. Are there emotional risks and/or benefits to being tested?
  17. Are there social risks and/or benefits?
  18. What are the alternatives to genetic testing?

Understanding Tissue Donation Consent

Over the last half century or more, the study of tumor and healthy tissue specimens has helped scientists develop a deeper understanding of how cancer forms and progresses. The data scientists extract from these donations push cancer research forward and help in the development of new treatments.

If you are considering donation, the informed consent process should give you a description of the risks and benefits of donating tissue samples for research, says biologist Nicole Lockhart, who has helped develop informed consent documents for the NCI and now works at the National Human Genome Research Institute in Rockville, Md. You can also ask where your donated tissue is headed: to a hospital or university tissue bank (or “biobank”), a national biobank, or a specific research study or clinical trial.

Lockhart also suggests inquiring about what, if anything, you can expect to learn from the study of your tissue. Many research institutions are starting to provide aggregated results to participants, but some patients may be disappointed to discover that they usually won’t receive information specific to their tissue, such as whether a treatment showed any benefit when tested on their sample. If it’s important to you, learn a biobank’s or clinical trial’s policy on providing information gleaned from your tissue before consenting to donation, advises Carol Weil, a program director for Ethical and Regulatory Affairs in the NCI’s Cancer Diagnosis Program in Rockville. And if you participate in one of the few studies that offer data specific to your own tumor, she adds, you may wish to consider genetic counseling.

Before signing the consent form, you also may wish to find out who will see information related to your tissue sample. Weil recommends that potential donors ask some key questions: Who will have access to my tissue? Will it be in a public or private database? Will it be used in just one study, and will I be contacted if researchers wish to use it later for another project? Will my identity be linked to my donated sample? How will the institution protect my personal data?

That last question may be the thorniest one. Many tissue banks “anonymize” the donations they receive, which means that personal data about each donor is disassociated from the person’s specimen.

But as geneticist Chris Mason at Weill Cornell Medical College in New York City explains, the promise of anonymity may, in fact, be an impossible one to keep, because many genome databases are available publicly online, as is a wealth of personal data from social media sites and other sources. In the Jan. 18 issue of Science, for instance, an international team of researchers reported its analysis of genomes from “anonymous” donors listed in a publicly available database. The data were supposed to have been disassociated from the identity of the donors, but with the help of a computer algorithm, online genealogical databases and other sources, the researchers successfully identified a number of the donors—in five cases, fully identifying individuals and their families—and published their technique to uncover the identities.

Lockhart says no harm came to those patients—their names were left out of the published report—but the ability to identify them was “not something we would have anticipated as a risk.” She says one challenge of the informed consent process is to describe these risks, while also making it clear that there are many benefits to sharing data.

Take Your Time

Ultimately, informed consent is about receiving the facts you need—either at the level of your genes, tissues or body—to make a decision with which you feel comfortable whether or not you decide to give consent. That is why Linda Horton thinks patients should slow down: to get more information, ask for help and understand what’s about to happen.

Even in the face of dramatic changes in technology, Horton says she believes clinicians’ and researchers’ efforts to present clear and correct information to patients has boosted cancer patients’ knowledge about the often complicated realms of treatment and clinical trials. She believes cancer patients are “more comfortable now” when they sign a consent form. “Before, you signed because you were supposed to,” she says. “Now, you sign because you see the purpose.” 

Stephen Ornes is a contributing writer and a reporter-researcher for Cancer Today. He lives in Nashville, Tenn.