Pathway Genomics: the Final Tipping Point for FDA Regulation of DTC Genetic Tests?

On Monday, the New York Times reported that Pathway Genomics, a company selling direct-to-consumer (DTC) genetic and ancestry tests partnered with Walgreens, who was poised to begin stocking its shelves across the nation with kits. Two days later, the FDA sent a letter to Pathway Genomics asking the company to either show it has regulatory approval or explain why the test does not fall under the purview of FDA’s regulations. As a result of this controversy, Walgreens announced it will postpone selling the kit until the company resolves the issue with the FDA.


Pathway Genomics, like other DTC genetic tests, offers DNA testing to provide consumers information relating to genetic markers for risk of developing health conditions, carrier status, drug responses, and adverse medication reactions. Its website promises “with Personal DNA Testing, you can take preventative steps to improve your future, and even extend your life.” Despite these assertions, Pathway Genomics maintains its test should not fall under FDA regulation because it is “not intended for use in diagnosis, treatment or for the mitigation or cure of a disease.” This fine (or nonexistent) line of what constitutes a medical test rather than an informational service was the same argument used by Navigenics and 23andme back in 2008 when they responded to cease and desist letters sent by the California Department of Public Health.



Up until this point, the FDA has declined to regulate tests and active ingredients that a company creates itself in its own laboratory (home brew tests.) [See our previous posting on the topic here and our Direct-to-Consumer Law & Policy Update here.] Accordingly, the FDA has not regulated home brews’ claims of clinical validity, analytic validity, or clinical utility. That is, consumers had no assurance whether the test correctly correlated with the presence, absence, or increased risk of a certain disease; whether the test’s positive or negative test result correlated with the gene sequence; or whether the company provided useful information to translate these results to the consumer.


The Genomics Law Report posits that the sudden change in FDA’s response reflects the fact that Pathway Genomics will be the first company to sell its kit in a store location rather than through the internet, which increases its visibility and availability to consumers.


It also magnifies the potential that consumers may misunderstand or be misled by test results. Even if the test itself provides accurate information, the nature of DTC genetic tests presents inherent shortcomings. First, there is no requirement for a physician to determine whether the test is medically indicated prior to ordering. Second, there is no mandatory genetic counseling to explain the significance and limitations of the results.


Like several other companies, Pathway Genomics charges additional fees for a consumer to purchase telephone sessions with a genetic counselor. Unlike other companies, Pathway Genomics states it will provide a free genetic counseling session if the company deems it “medically necessary.” This gracious offer misses the point that genetic counselors should always be part of the genetic testing equation. It also leaves us to wonder, how does Pathway Genomics decide what constitutes a medically necessary reason?


It seems Pathway Genomics’ business decision to partner with the drugstore giant may have finally caught the FDA’s attention. FDA’s investigation into Pathway Genomics’ test into may turn out to be the long awaited tipping point for FDA to revise its stance and begin to regulate DTC genetic tests.

-Katherine Drabiak-Syed

Long Term Outcomes of Presymptomatic Testing in Huntington Disease

Huntington disease (HD) is a late onset autosomal dominant neuropsychiatric disorder. Symptoms include a movement disorder, mood disturbances and dementia. The average age of onset is approximately 40 years of age and if one of your parents is affected with the disease, you have a 50% chance of having inherited the genetic mutation that causes HD. Men and woman are equally affected.

In 1993, the genetic mutation that causes Huntington Disease was discovered. This discovery meant that direct genetic testing for the presence or absence of the HD mutation could be offered. Testing is usually offered within a multidisciplinary framework including geneticists, neurologists, psychologists, nurses and social workers and within a testing protocol that involves a neurological examination, pretest counseling, results in person and available follow-up. Estimates indicate that in Europe, less than 20% of individuals at risk for HD takes the test. Estimates for the United States suggest that the uptake of testing is even lower. The lack of a cure for HD, or a treatment that can delay the onset or slow the progression of the disease, is likely a major factor in the low uptake of testing.

Recently, in some HD circles, there have been calls to increase the number of individuals getting tested in order to have a cohort of gene positive individuals ready to participate in future clinical trials. This desire to increase the number of individuals tested is, in my opinion, wrong headed for many reasons, but a recent paper on the long term effects of testing also suggests that caution is in order.

In February of 2009, the European Journal of Human Genetics published a paper examining the long term impact of presymptomatic testing for Huntington disease. The authors interviewed 119 (57 gene carriers and 63 non-carriers) asymptomatic individuals after an average delay of 3.7 years after they received their genetic test result. The main outcomes of interest in the paper were social and psychological adjustment after testing (1).

The results were as follows: The overall scores for social adjustment were similar in carriers and non-carriers and were in the normal range for both groups. Carriers were not more anxious than non-carriers, but current depression was significantly more frequent in the carriers. Prior to testing, there were no differences in the number of carriers and non-carriers who had experienced a depressive episode. After testing, however, the percentage of carriers experiencing depression rose from 42% to 49% while the percentage of non-carriers experiencing depression fell from 45% to 31%. Perhaps even more important is the fact that carriers had significantly higher scores than non-carriers when evaluated with the Beck Hopelessness Scale, considered to be a measure of suicidality. Of note is the fact that while there was one suicide attempt and one hospitalization for major depression after testing in the carrier group, three non-carriers also attempted suicide, one was hospitalized for depression and one hospitalized for a psychotic episode. Despite this evident distress, only 31% of the carriers and 15% of the non-carriers were under psychiatric care and only 36% of the carriers and 15% of the non-carriers were under treatment with antidepressant or anti-anxiety medications. Further investigation indicated that the best predictor for the occurrence of depression after taking the test was the presence of a previous depressive episode. In other words, individuals who have experienced depression prior to testing are more likely to experience depression after testing. Finally, when asked to rate the current impact of the test results on their lives, carriers gave a more negative rating than non-carriers and reported that they had less ability to cope with the test results than non-carriers. Again, it is important to note that more than 25% of the non-carriers reported difficulty coping with the test result.

It is possible to compare these results with a previous study looking at long term outcomes 7-10 years after testing (2). This study of 142 tested individuals and their partners found that carriers and their partners were more distressed immediately after the test. Their outlook appeared to improve somewhat in the 2-3 year post test period but became more negative as the age of onset approached. This study also found that carriers who were lost to follow-up reported more pretest distress than did those carriers who participated in the follow-up study. This finding, which reflects both my own experience and the anecdotal experience of other test center directors, is important because it suggests that most studies examining the impact of testing may tend to underestimate the amount of distress that is being experienced by those who have been tested.

So what do these results tell us? In the 2009 study, almost half of the carriers where experiencing depression after testing. However, almost a third of non-carriers were also experiencing depression. At least two studies have suggested that it might take up to five years for non-carriers to experience a positive change in their quality of life after receiving a favorable test result (3,4). One explanation that has been given is that it takes this long to resolve the emotional state of mourning for the loss of being at risk and the end of doubt about one’s genetic status. Others have hypothesized that that non-carriers may be experiencing 1) survivor guilt for not having the HD gene when others in the family might 2) regret for life decisions made in the past as a function of being at risk, 3) inability to leave behind the at risk mind set, 4) inability to truly believe the test results, and 5) negative reactions on the part of family members (1).

Whatever the explanation, these results indicate that individuals at risk, carriers and non-carriers alike, may be a vulnerable population and that it is particularly important to assess and treat depression before testing and to provide psychological support and psychiatric care after testing. These results also suggest that the decision to be tested should not be made lightly and that the impact of testing may last a long time after results are given.
References:

1. Gargiulo M, Lejeune S, Tanguy ML et al, (2009). Long-term outcome of presymptomatic testing in Huntington disease. European Journal of Human Genetics, 17:165-171.

2. Timman R, Roos R, Maat-Kievet A, and Tibben A. (2004) Adverse effects of predictive testing for Huntington Disease underestimated: Long term effects 7-10 years after the test. Health Psychology 23:189-197.

3. Decruyenaere M, Evers-Kiebooms G, Cloostermans T et al. (2003) Psychological distress in the 5-year period after predictive testing for Huntington disease. European Journal of Human Genetics 11:30-38.

4. Almqvist EW, Brinkman RR, Wiggins S, Hayden MR (2003) Psychological consequences and predictors of adverse events in the first 5 years after predictive testing for Huntington disease. Clinical Genetics 64: 300-309.

Kimberly A. Quaid, PhD