Educating Patients about Genetic Test Results: An Interview with Carol Weil about the COMET Study
, by Carol Weil, J.D.
The COMET (COMmunication and Education in Tumor profiling) study, launched in September 2016, is examining whether educating patients with cancer about genetic testing will increase their knowledge and reduce their stress levels after receiving the results of their tumor profiling tests. COMET is an ancillary study to NCI-MATCH, a treatment trial that seeks to match patients whose tumors have specific genetic mutations to drugs that target those mutations.
In this interview, Carol Juliet Weil, program director for ethical and regulatory affairs in NCI’s Cancer Diagnosis Program, describes the COMET study and discusses how the findings could help to empower patients with cancer.
What do you hope to learn from COMET?
There are important unanswered questions about when and how to best communicate to patients the benefits and limitations of genomic profiling of their tumors. The primary research objective of COMET is to test whether 200 patients randomized to participate in a self-guided, online genetic education program before receiving their tumor profiling results are more knowledgeable about the nature and potential impact of genetic information, and have less distress when they get their results, than 200 patients who receive the information in the standard manner in clinic.
The standard care participants can, if they so desire, receive the online education program 3 months after they receive their genetic screening results.
If proven successful in this trial, the education intervention could become a model for future precision medicine oncology trials.
A second study of 100 patients will assess the feasibility and impact of providing remote genetic counseling by telephone to NCI-MATCH participants who receive tumor profile testing results that indicate the possibility of inherited, or germline, mutations.
The NCI-MATCH trial does not include sequencing of patients’ normal tissue, such as blood or saliva, but rather just tumor testing. In other words, NCI-MATCH genomic testing cannot tell with certainty if a tumor mutation may also be in the germline and therefore capable of being passed down within families. If patients learn from their tumor profiling results that they have a potential inherited mutation, confirmatory germline testing would be needed to verify the indicated finding. In this setting, it is appropriate for patients to have genetic counseling in order to decide whether to have further testing to verify the suspected germline indication, and if such testing is sought, to help the patient interpret and understand the results.
Typically, genetic counseling is conducted in person. But in remote areas, or places where a full-time genetic counselor is not available, remote counseling via telephone or videoconference makes these services available to many more people.
About three-quarters of NCI-MATCH participants will not have a match to a targeted therapy. How do you think COMET participants will react if they're among those who don't have a match?
Receiving word that there is no targeted therapy arm available in NCI-MATCH will undoubtedly be difficult and unwelcome news for patients. It is our hope that the genetic education COMET provides will offer some measure of autonomy and comfort to patients who do not receive a therapy match.
Participating in COMET can at least provide patients with a better understanding of their own genes and genetic history. It will also supply information about the nature and meaning of genetic testing in biomarker-driven research generally, including the limits of tumor profiling and potential options for confirmatory germline testing to diagnose inherited disease within families.
Studies have shown that cancer patients often feel more empowered when they get information about their illness, even if it does not offer a clinical course of action.
Why are you drawing COMET participants from NCI-MATCH?
NCI-MATCH is an ideal clinical trial for studying patients’ knowledge of genetics and views about receiving genetic information because so much incidental genomic data not directly relevant to patients’ cancer care will be produced in the study.
Another advantage is that the NCI-MATCH patient population draws from both NCI-Designated Cancer Centers in major metropolitan areas and from community-based providers in rural and less-populated areas through the NCI Community Oncology Research Program. We need to enroll as ethnically and genomically diverse a population of research participants as possible to determine how to best serve all patients.
Although all NCI-MATCH patients, not just COMET participants, can receive their laboratory results, it will be helpful for us to study the reactions of COMET participants to the receipt of their genomic profile results because studies have shown that patients have varying attitudes and preferences about receiving genetic findings, particularly information that may have bearing for family members. So the research we are doing in COMET is really important for us to gain a better understanding of the range of patient views toward learning more about their genetic information.
What about patients who receive uncertain results or results that could affect their family members?
Again, this is an area where a range of responses are possible among patients. Dr. Barbara Biesecker and other researchers at the National Human Genome Research Institute have studied patients’ comfort levels with uncertainty. In studies on the return of results regarding hereditary breast and ovarian cancer, researchers have found that doctors and oncologists are typically less comfortable conveying genetic results than the patients receiving such findings.
Many patients are not put off by genetic information that is evolving or of unclear significance, particularly if the information might be useful to family members in the future. Doctors, on the other hand, often feel uneasy communicating such information.
COMET, and other studies like it, will help us figure out when and why patients are most comfortable and least stressed about uncertain genomic findings. And these studies should also help physicians present genetic findings to their patients more easily and effectively.
Counseling people regarding their genetic testing results does not necessarily lead to positive behavior change, unfortunately; understanding cancer risk and changing behavior are two different things. But the ability to access data about genes and health tends to be a meaningful and constructive experience for many people.
How will COMET benefit people in NCI-MATCH who are not matched with a treatment?
Patients who don't receive a therapy match can use their genetic information for future treatment decisions, or their family members may be able to use it if they are ever faced with a genetic disease. Perhaps the germline information will benefit a child. Returning information to people and empowering them to share it with loved ones provides some glimmer of hope to people facing diseases with uncertain or potentially poor outcomes.
In addition, speaking to a genetic counselor might be very meaningful for NCI-MATCH participants, even if they are not learning anything that can help them personally. People tend to feel connected to their genetic information in a very personal way, and they often appreciate the opportunity to receive data about their unique genes. The popularity of direct-to-consumer genetic testing is a testament to that.
How quickly could the COMET study results change how doctors interact with their patients regarding genetic test results?
First, let me note that it is unlikely that the results from COMET will be published in time to benefit patients who are screened for NCI-MATCH. It will take some time before the findings from COMET influence patient care.
It is understandable that many physicians who care for cancer patients need guidance on how to communicate the results of genetic testing. The use of clinical genomics in cancer treatment and research is still relatively new. One mission of studies like COMET is to raise the comfort level of primary care physicians and oncologists with genomic medicine and, in particular, with the layers of uncertainty inherent in the use of gene sequencing technologies in cancer care.
Educating doctors will be a learning process, and encouraging them to change their practices and habits may not be easy. Most primary care physicians and oncologists do not have a background in genetics, and particularly in the field of inherited mutations, so it may take a while to get them comfortable with the idea of disclosing potential germline findings to patients, or referring patients who want in-depth counseling about suspected germline mutations.
The American Society of Clinical Oncology issued a policy statement update in 2015 on genetic and genomic testing for cancer susceptibility to “ensure that those providing care to patients with cancer receive the necessary education to use this new technology in the most effective, beneficial manner.” With the help of professional societies, I think we can have a well-trained cadre of physicians to help patients navigate their genetic testing results and to provide them with other resources they may need to fully assimilate very complex clinical or research findings.
COMET is an ELSI (Ethical, Legal, and Social Implications of medical research) study. How can studies of this type broaden the impact and effectiveness of treatment trials?
A number of research studies have shown that patients want to receive actionable research results, and that they are more concerned about obtaining potentially actionable information than they are about having their data de-identified to protect their privacy.
But it is incumbent upon us, as cancer trialists, to write clinical trial protocols and consent forms that are transparent about the return of incidental and secondary findings. We must describe the scope of information that might be produced in the study, including information affecting heredity and family members, and provide an opt-out for those who do not wish to receive such information. We must also strive to ensure the protection of patient data to the greatest extent possible, while acknowledging that it is impossible to guarantee privacy.
ELSI studies were designed to aid this transparency in trial protocols; their focus is typically on several specific areas, including the consent process, patient engagement, data sharing models, and the return of incidental findings and secondary research results, which has become an especially important issue with the advent of personalized medicine.