Updated Thoughts on PatientsLikeMe

I have a previous post about PatientsLikeMe, but I importantly did not test creating an account until relatively recently.  I have been continually improving my habits in terms of taking more time to critically assess results and question prior assumptions (in addition to realizing that I may have not had the best title for that previous blog post, in retrospect), so I thought there would be value in providing an updated perspective on this free website.

I have genomics / medical data publicly available to download on my Personal Genome Project page (for hu832966) and I have what I would consider a partial electronic medical record on my PatientsLikeMe page (which I think is an excellent resource for sharing and learning about patient experiences, with the requirement that everybody who participates be completely open; however, you have to sign in with a free account to view my profile).

For those that currently don't have PatientsLikeMe accounts, I thought I should describe a few of my experiences (from the perspective of a patient):

I have taken Citalopram at doses of 20 mg and 40 mg (and 0 mg, during intervals to test the continued benefit of the medication, when my overall stress levels were lowered and/or I learned better cognitive strategies to manage stress).  While it makes quick analysis more difficult, I think being able to see the details of people's experience can be important.  For example, I thought it was interesting that my body's reaction to the medication seemed to change over time (each time I went back on the medication, I think the side effects were more subtle, even though I think the severity of my initial symptoms also gradually improved over time).  If this is in fact true, that would indicate some resistance / reaction that could not be completely captured from studying germline variants (if you are focusing on using DNA genotyping/sequencing for medication guidance), such as somatic variants, epigenetic modifications, etc.

I also like that PatientsLikeMe provides scores for both effectiveness and side-effects (and I admittedly created a PatientsLikeMe account because some plots in the "Health Communities" in 23andMe reminded me of what I had seen for PatientsLikeMe, even without previously creating a PatientsLikeMe account).

On the positive side, I have seen multiple neurologists, and I had previously not really found any of the previous migraine medication that I took to be helpful.  However, my most recent neurologist prescribed me indomethacin, and I found that to be very helpful.  I wrote a positive evaluation for that migraine treatment, and I was surprised to see that this was a relatively rare treatment for migraines.  So, if people found commonly prescribed treatments to not be helpful, I think this might be helpful in brainstorming alternatives.

I also reported 3 negative evaluations for drugs where I experienced moderate-to-severe side effects.  I noticed that severe side effects were self-reported for these drugs among 9-14% of members in the Community Reports (9% was comparable to other drugs that I checked, but the drug for which I had the most severe side effects in 2018 had a the highest severe percentage of 14% and qualitatively most frequent reports that seemed similar to by own experience).  That said, the most commonly prescribed migraine medication (which I never tried) had a reported severe side effect rate of ~20% (so, it seems to me that a self-reported "severe" side effect rate of 5-10% is normal, but 15% or 20%  with hundreds or thousands of patients may be kind of high).  That said, I want to be very careful about being too negative about something that is not my area of expertise (even though the idea of something being helpful for some people and harmful for others seems relevant for genomics research).

Going back to the topic of my anti-depressant (for anxiety or depression, depending upon the time-frame of my treatment that you are talking about), the current maximum recommended dosage of Citalopram is 40 mg (with 60 mg now being considered unsafe), and that would match my own expectation (although for slightly different reasons - I had to drink coffee instead of tea due to extra drowsiness at 40 mg, and I am currently on 20 mg instead of 40 mg).  I can also see a 2016 indication from the FDA that 20 mg is the maximum recommended dose for individuals greater than 60 years of age (so, the maximum recommended dose is currently lower for older individuals).  You can also see more information about this drug in the 1998 drug approval package from the FDA.  To be clear, I am very grateful for the availability of Citalopram and that has made a huge difference in my life, but I think this is something that may be worth discussing more (and I would probably also benefit from understanding better).

There has even been Washington Post article describing a partnership between PatientsLikeMe and the FDA to help with drug reporting (I saw this in a recent e-mail from them, but the article is actually from 2015 - still, it is good to know other people probably have at least somewhat similar thoughts).  While they didn't mention PatientsLikeMe, I think this was also related to the topic of a more recent announcement regarding patients reporting "real-world evidence."  You can also report adverse events to the FDA through MedWatch.

Update Log:

3/9/2019: original blog post
3/26/2019: changed link in 1st paragraph (and added another link in that sentence).
6/28/2019: add MedWatch link

Benefits to a 3-tier system for DTC genetic testing

The popular genetic testing company 23andMe has two rankings for genetic associations present in the scientific literature: Established Research Reports and Preliminary Research Reports.  The relatively recent GAO report on genetic testing claimed that 23andMe provided "reports that showed conflicting predictions for the same DNA and profile, but did not explain how to interpret these different results" (and the response from 23andMe can be viewed here).  However, I think this system provides a useful basis to improve education about genomics research and genetic testing.  In fact, I think it would be even better to provide 3-tier system to describe genetic associations.

In particular, I think genetic associations can be classified as "Based upon Preliminary Evidence," "Based Upon Reproducible Evidence," or "Therapeutically Useful."  In this case, I would consider "Reproducible" associations to be equivalent to 23andMe's "Established Research Reports."  I would consider "Therapeutically Useful" associations to be those that have been proven useful in terms of significantly reducing patient mortality or morbidity.

The "Therapeutically Useful" classification is important because there could be many reasons why individuals with a particular mutation may have a increased risk of dying from cancer that is statistically significant, but information about that particular mutation may not be important for informative for making medical decisions.  For example, models for genetic predisposition may be complicated for certain diseases, and it may be necessary to incorporate currently unknown information about other mutations in order to provide an accurate estimate of risk to develop a given disease.   Also, there are cases where environmental factors may be more important than genetic factors.  And the list goes on.

In practice, I think the FDA could play a role in helping define the third category of genetic tests, and I can think of at least two ways to implement this.  First, genetic testing companies could post some sort of "FDA-approved" icon for tests that have shown to produce positive results when applied in a clinical setting.  Second, the FDA could post a listing of genetic tests that have been proven useful through clinical trails and provide a list of appropriate treatments that correspond to a given test result.

There are benefits to having access to genetic information that doesn't necessarily meet the criteria for a "Therapeutically Useful" test.  For example, there may be no "FDA-approved" diagnostic for a particular problem and an experimental prediction may be the best possible resource.  Furthermore, the FDA has indicated that it does not see a need to regulate the release of "raw genetic information," and it is acceptable to communicate information about genetic associations though other means.  For example, the FDA would never censor an article in the New York Time about a new discovery or preliminary result.  Genetic tests that are"Based upon Preliminary Evidence" or "Based Upon Reproducible Evidence" are basically indicating that "Hey, you have this mutation that has been described in the scientific literature."  If it is too confusing to provide separate predictions for each tier of genetic associations, then genetic testing companies should at least be able to provide a list of publications describing a mutation of interest (and possibly provide a brief summary of the findings).

Information from DTC genetic testing can also fundamentally increase understanding about human genetics and contribute to scientific research, as indicated by 23andMe's publication in PLoS Genetics.  In fact, 23andMe could actually help establish "Therapeutically Useful" tests if customers could upload clinical information that is directly incorporated into their models.  Likewise, companies like PatientsLikeMe could help test the therapeutic value of genetic tests if patients could upload their genetic information

In general, I think individuals should take a much time as they reasonably can to research a topic prior to making a life-altering decision.  Even if a diagnostic is 98% accurate, what if you happen to be in the minority that gets a false-positive?  Even well-established tests can have false positives.  Important information can be gained from independent tests, consulting with a physician or genetic counselor (or getting second opinions from multiple professionals), or even talking to friends who might have went though similar situations.

Although I understand that a "3-tier" system for genetic testing may be confusing for people at first,  I think this system could be a useful tool to educate the public about genetic testing and encourage individuals to take a more active role in making medical decisions.  In fact,  a recent post by John Timmer concluded with the suggestion that heavy regulation of the DTC testing industry will probably not be necessary if a sufficiently large proportion of the general public took the initiative to better educate themselves.

Do patients report symptoms better than physicians?

There is a very interesting article in the New York Times today that discusses how doctors need to pay more attention to patient complaints.  For example, the author opens the article discussing how she stopped taking Bextra after she started to develop a large red blister on her tongue.  Her physician said the symptom was most likely a coincidence, but the drug was taken off the market shortly thereafter because it caused dangerous side effects (including mouth blisters).  Although it is impossible to say what caused the mouth blister in this case, the author does a good job of demonstrating that the doctor should have taken her complaint more seriously.

I found this article to be especially exciting because it emphasizes that patients can directly provide powerful information for evaluating medical treatments and diagnostics.  This reminds me of the success of medical databases based upon information provided directly from patients, such as PatientsLikeMe.  Interestingly, the article also describes a side effect database from the FDA called MedWatch, which allows doctors and patients to report negative systems experienced with various treatments.  I was very excited to see that even the FDA appreciated the value of information reported directly from patients.  I think a system similar to MedWatch can significantly improve the process of conducting clinical trails.

Of course, I should emphasize that the article is not trying to say that medical information should only be based upon information from patients.  Physicians definitely need to play a role in assessing medical treatments.  However, I think databases of patient feedback can be a powerful tool that can help reshape health care and drug development.