How to talk to patients about genetic testing
■ What is the primary care doctor’s role in direct-to-consumer genetic testing?
The Ethics Group provides discussions on questions of ethics and professionalism in medical practice. Readers are encouraged to submit questions and comments to email@example.com, or to Ethics Group, AMA, 515 N. State St., Chicago, IL 60654. Opinions in Ethics Forum reflect the views of the authors and do not constitute official policy of the AMA. Posted May 7, 2012.
Your patient, Ms. X, says she is planning to order a comprehensive genetic profile on herself from a commercial laboratory (such as 23andMe or MapMyGene). She asks for your opinion, since someone told her to check with her physician before going ahead.
Reply: From the viewpoint of ethical principles, the usual four horses — plus one — should guide your response.
You must respect Ms. X’s autonomy — her right to choose and act as she wishes. Although the cost of $500 to $1,000 is beyond the means of many, justice is not an issue in her paying out of pocket a fair price for a test on her DNA (from a mouth rinse). It is a marketplace transaction, although you could wonder about compensation for clinical interpretations of the results.
The beneficence conferred by the testing could include her gaining knowledge she thinks she wants, revealing a predisposition to colon cancer, for example, or a pharmacogenomic trait that could alter the dose of a medication she may need, or identifying her as a carrier for a mutant gene that, should her partner carry the same gene, could result in an offspring with a serious autosomal recessive condition like cystic fibrosis or Tay-Sachs disease. Completely normal results could bring assurance and comfort.
Nonmaleficence, “first do no harm,” may be what she is checking out with you — the possibility of getting “bad news” in the form of a nonsymptomatic condition or predisposition to a condition that has no treatment.
The additional principle, solidarity, is not often cited in medical ethics, since it challenges the popular dominance of the principle of respect for autonomy, at least in present-day America. Broadly considered as “the common good,” solidarity comes up in genetics because it emphasizes that Ms. X shares genes not only with her close and perhaps distant relatives, or members of her ethnicity or heritage but, in fact, with all human beings.
Three U.S. professional societies of geneticists, including the American College of Medical Genetics and Genomics, have addressed the issue (casually referred to as “recreational genetics”) that Ms. X presents. The gist of their statements is that, while respecting the patients’ and laboratories’ rights and enterprise, there are serious concerns that the chance of maleficence outweighs the prospects of benefit to the patients.
Specifically, they call for involving a professional geneticist before testing to assure a fully informed decision is made, based on exactly what the test can and cannot say about future health and, if testing is elected, expert clinical interpretation after receipt of results.
In 2006 and 2010, the Government Accountability Office reported on obvious, vague and misleading interpretations in sometimes voluminous reports of results (“avoid smoking”) and technical difficulties that reflect poor reliability and consistency among direct-to-consumer laboratories in detecting DNA changes. The Food and Drug Administration claimed that such tests are medical devices requiring its approval, but it has not issued regulations.
The April issue of the Journal of Genetic Counseling has 16 articles on the topic. Suggestions from that issue include emphasis not only on principle-based ethics, but also on the “ethic of care,” namely, the desirability of having an empathic personal relationship with a knowledgeable professional. Actual experience to date is scant but shows the need to clarify the patient’s goals and purposes before testing and illustrates the meager clinical utility of test results, which at best provide a nudge toward a healthier lifestyle. In short, the direct-to-consumer genetic testing laboratories seem to overpromise and under-deliver, in a sense, “geneticizing” health and implying that genes are more deterministic than they really are.
Two trends are emerging. More companies are offering professional genetic counseling service by telephone (generally for a price) and are requiring a physician’s order for the test. These are steps in the right direction but hardly are sufficient. A helpful registry of companies and the genes they assay is available.
Western European countries tend to be very restrictive in allowing the public to initiate genetic testing themselves. The debate will change as sequencing becomes so cheap that total sequencing will be preferred early in the diagnostic odyssey, rather than testing individual genes later on in an attempt to explain a patient’s disorder. In March, the American College of Medical Genetics and Genomics addressed the specific issue of completely sequencing the 1% of a patient’s genome — the exome — that directly codes for proteins.
The statement dwells mostly on diagnostic use by a professional on affected patients. For asymptomatic individuals interested in sequencing for health screening, the statement points out “the virtual certainty of finding variants of uncertain significance.” In short, since every human being is unique, as more individual genomes are totally sequenced thousands of variations are seen, but determining which variations have implications for a person’s health is arduous and imperfect. Hence, achieving the benefit of assuring Ms. X that her DNA is “normal” is now impossible. One certain outcome is your having to say, “They found changes in your DNA that cannot be interpreted.”
You could hardly be faulted if you wish to say, “No comment. It’s not my area. I can refer you to a clinical colleague who is a geneticist.” That person, or you, should engage Ms. X, in a dialogue like the following in a supportive counseling manner, again before the test sample is sent.
First, which test is she considering? Total genomic sequencing is not being offered directly to consumers. Exome sequencing? A panel of “carrier” genes? A panel of genes related to sports performance, to cancer predisposition? For diseases seen to excess in certain ethnic groups, like Ashkenazi Jews? Does she want to identify possible Native American heritage? Is there a hidden agenda concerning possible pregnancy and question of paternity?
Second, what are her motivations and her questions? What benefit is she seeking? A focused three-generation family health history may reveal her concern for an excess of miscarriages, or a single gene trait like fragile X syndrome or hemophilia, or a pattern of breast and ovarian cancer. Is she getting married soon to a man with a strong family history of bipolar disorder or skeletal defects, like achondroplasia or Marfan syndrome?
Third, just as physicians are encouraged to order tests only when the result would change clinical care, what would she do if her results revealed carrier status of little or no consequence because she’s never been pregnant and is postmenopausal?
Fourth, Ms. X should know that, with a plethora of genomewide association research studies, some variants are found to increase the risk of disease by a very small increment, such as an odds ratio of 1.2, a 20% increase, usually of a low absolute risk. Such small increases usually fail to justify any medical or lifestyle changes, but are addressed, poorly, by the direct-to-consumer laboratories.
John J. Mulvihill, MD, Children’s Medical Research Institute/Kimberly V. Talley Chair in Genetics, University of Oklahoma
The Ethics Group provides discussions on questions of ethics and professionalism in medical practice. Readers are encouraged to submit questions and comments to firstname.lastname@example.org, or to Ethics Group, AMA, 515 N. State St., Chicago, IL 60654. Opinions in Ethics Forum reflect the views of the authors and do not constitute official policy of the AMA.