Order Up: Precision Medicine With All of the Sides - Annals of Internal Medicine: Fresh Look Blog


Wednesday, July 31, 2019

Order Up: Precision Medicine With All of the Sides

By midmeal someone finds out I’m a doctor, and the next thing I know, this guy I barely know is asking me to comment on his “predisposition to X disease.” After my usual disclaimers, (“Well, I am a doctor, but I’m not your doctor”), in the spirit of dinner party etiquette, I inquire, “Why do you ask?”

Inevitably, it was someone’s birthday present, an anniversary gift to parents, or a late-night impulse purchase that resulted in my new acquaintance’s direct-to-consumer (DTC) genetic testing results and my subsequent quandary as the lone physician at the table being asked to interpret them. Welcome to the 21st century, where the more information we have, the less we’re sure what to do with it! At least it’s also the era of mouth-watering farm-to-table cuisine to pair with this journey.

My experiences are well captured in the scenario presented in Annals of Internal Medicine’s inaugural case-based series on the topic: “Cases in Precision Medicine: When Patients Present With Direct-to-Consumer Genetic Test Results” (1).  As the authors note, the core of my predicament is “the clinical utility of providing consumers with health information that can easily be interpreted as medical advice.”

I tell my dinner-mate that precision medicine has given us great things in health care. (I didn’t come for a fight—I came for the seasonal vegetables.) I haven’t yet been out of medical school for 10 years, and there are drugs on the market I’ve never heard of, targeting specific genetic mutations associated with diseases we used to think were nearly impossible to treat. Most of these are attributable to the successes of precision medicine.

Back to the question at hand: What’s the difference between health information and medical advice? I suggest it’s much like the difference between a square and a cube. Information is just one piece of the picture. Advice is multidimensional and considers the available information in a larger context of a person’s health, history, and environment.

This distinction is also the reason I’m fairly confident my job won’t be taken over by robots any time soon. While algorithms can process an entire medical history and genetic sequence, the nuances of test results’ implications are subtle. Before my new friend pours his medical history onto the table like a gleaming balsamic reduction, I go back to the Annals’ piece. The required context has as much to do with the test itself as it does with the patient.

These DTC genetic tests are not comprehensive. They typically screen for a small fraction of potential variants that can predispose to disease. An example report in the article states, “You do not have the 3 genetic variants we tested; 0 variants detected in the BRCA1 and BRAC2 genes.” The authors recommend clinicians interpret those results by saying, “Only 3 out of >1000 variants are tested by 23andMe. Many other genes can increase breast cancer risk. Most breast cancer cases are explained by factors other than these 3 variants.”

That “negative” result may not actually be truly negative. If patients are at high enough risk based on their history or exposures, they may require more thorough testing and counseling. Sometimes the consumers aren’t getting a full square drawn out—only one portion of one side of a bigger story.

It’s still up to clinicians to help patients build the cube of truth from these DTC test results, frequently confirming tests with formal medical-grade genetic analysis, when clinically appropriate. We are then sometimes delivering the tough news that they do carry a predisposition to something like Alzheimer’s, and that we cannot do anything to stop it. In a more comprehensive overview of precision medicine from the same Annals publication date, authors go on to warn that “even after an unambiguous genetic diagnosis, no effective targeted treatments are currently available for most genetic diseases” (2).

The disparity between the general public’s understanding of medical diagnoses and medical information initially led the FDA to demand these DTC companies to cease and desist their operations in 2013, which was reversed only when the company had provided “sufficient evidence that the public was capable of understanding the results.” Capable, perhaps, but not assured to understand them.

The DTC tests are here to stay, and I think that’s OK. Progress comes in all flavors and will continue as long as we have an appetite. Science will make sure we have the entrees, but it’s up to clinicians to make sure we’ve remembered all of the sides.

  1. Artin MG, Stiles D, Kiryluk K, et al. Cases in precision medicine: when patients present with direct-to-consumer genetic test results. Ann Intern Med. 2019. [PMID: 31035287] doi:10.7326/M18-2356
  2. Kiryluk K, Goldstein DB, Rowe JW, et al. Precision medicine in internal medicine. Ann Intern Med. 2019. [PMID: 31035290] doi:10.7326/M18-0425

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