From misdiagnosis to helping thousands
On any given day, Lauren Stiles wakes up to find emails from patients in Saudi Arabia, doctors in New Zealand, or monks in India, all asking for advice. The organization that Stiles founded in 2012, Dysautonomia International, receives more than 100 messages a day from people seeking information about disorders of the autonomic nervous system (the part of the nervous system responsible for functions that are not consciously directed, such as heartbeat and digestion). Their hunt for advice, for help of any kind, is familiar to Stiles, who spent two years searching for her own diagnosis.
In 2010, Stiles was a busy 31-year-old attorney in New York. She often went surfing or snowboarding on the weekends with her husband. Then she suffered a concussion while snowboarding, and overnight she developed symptoms like fainting, low blood pressure, rapid heartbeat, and GI dysfunction that lead to an unintentional 60-pound weight loss. After nine months of misdiagnosis and countless tests, doctors diagnosed her with carcinoid (a slow-growing neuroendocrine cancer). But through her own research on PubMed, an online medical database, Stiles learned that one of the medications she was taking could cause a false positive for carcinoid biomarkers (a test used to detect cancer). She persuaded the doctors to retest her after a 48-hour break from the medication. In the retest, they found that she didn’t have carcinoid, but they were at a loss about what she did have. Stiles decided to do some more research. She found that her symptoms matched those of a disorder called Postural Orthostatic Tachycardia Syndrome (POTS). POTS is a neurological condition affecting around 1 to 3 million people in the U.S., many of them undiagnosed. Stiles put together a stack of around 50 publications on POTS for the neurologist who was treating her, and he came back from reading the papers with an announcement: “You have POTS.”
After this ordeal, Stiles wanted to help others going through similar circumstances. “When I saw the online support groups for POTS patients,” she said, “there were literally tens of thousands of other people that had gone through the same lengthy misdiagnosis that I did, or worse. I wanted to do something about it.” That was the catalyst for Stiles to start a nonprofit patient advocacy organization, Dysautonomia International, which began with the help of other concerned families and physicians. The organization raises funds for research, offers support groups, and has created a POTS registry with over 3,300 patients enrolled. Dysautonomia International also hosts conferences for doctors, researchers, and patients.
“Public availability of clinical trial data is important, especially the clinical trial data
used by the FDA to determine safety
and efficacy of drugs.”
One of the things Stiles is particularly passionate about is transparency in clinical trials and the standards used to approve drug treatments for patients. A case that she is concerned with now deals with the drug midodrine hydrochloride. Approved in 1996 by the FDA, the drug is taken by patients with low blood pressure, including those affected with dysautonomia-related disorders. At the time the drug was approved, the FDA granted “accelerated approval” to the pharmaceutical company Shire for the drug, with the condition that the company conduct further trials on clinical benefits post-approval. Then in 2010, the FDA issued a notice stating that it was considering withdrawing approval for this drug, writing that “to date, neither the original manufacturer nor any generic manufacturer has demonstrated the drug’s clinical benefit, for example, by showing that use of the drug improved a patient’s ability to perform life activities.”
Since then, Shire agreed to conduct two further trials to verify midodrine’s clinical effect. And in 2012, the FDA put the proposal to withdraw approval on hold. On September 11 of 2014, the FDA sent a letter to Shire, extending the deadline to submit trial results to the FDA from September 12, 2014 to March 31, 2015. That notice was the last public update on midodrine from the FDA.
Stiles says that the suspense surrounding the drug’s future has caused the patient community – many of whom depend on this drug – to feel a great deal of anxiety. “Are we going to be able to get this drug next month? Is the FDA just going to pull it? We have no idea.” She has written about the case extensively on the Dysautonomia International site and argues that it shows the need for timeliness and transparency in the process of creating and approving new drug treatments. “Public availability of clinical trial data is important, especially the clinical trial data used by the FDA to determine safety and efficacy of drugs sold in the U.S.”
Lauren Stiles is the founder and president of Dysautonomia International. She has lectured on autonomic disorders at the National Institutes of Health, Duke University, Harvard University, and Stony Brook University, and has conducted research on autonomic disorders with Vanderbilt University, University of Texas Southwestern, and private practice neurologists. Lauren will participate in a panel discussion on the promises, pitfalls, and reform efforts surrounding clinical trials on September 29 at NYU. The event is free and open to the public.
This medication needs to be approved.
I have NMH/POTS (as Peter Rowe at Hopkins calls it) – it’s apparently hereditary. I’ve had it since I was 14. I learned to sit down in lines when I started feeling “funny” – later I learned to just keep track of my heart rate, and if it suddenly jumped to 120, to GET DOWN before my body made me (by passing out). I embarrassed my sister by sitting on the ground in lines at Disneyland; I embarrassed my kids by sitting on the ground in lines at Disneyworld. Finally, at the age of 45, I learned what I had.
But I learned it because I had just been diagnosed with Myalgic Encephalomyelitis (M.E.), a neuro-immune disorder that involves (in my case) persistent infections with neurotropic viruses such as HHV-6A and CMV (both active in my spinal fluid). I also learned a couple of years later that I had Ehlers-Danlos Syndrome (EDS), a hereditary condition involving connective tissue stretching. These conditions are all correlated to some extent.
When a series of cluster outbreaks of M.E. occurred in the US in the 1980s, CDC & NIH at first called it chronic Epstein-Barr Virus because there was a relationship with EBV at the beginning of the disease for many patients. But in 1988, NIH & CDC held a meeting where they rejected the option of calling it M.E. and connecting it with a 50-year history, and gave it the new name “Chronic Fatigue Syndrome” instead, ensuring it would be ignored for the next 3 decades. At this point, one million adult Americans have it, but 850,000 of those have no idea what is wrong with them – like Lauren and her long search for a diagnosis of dysautonomia.
In my own case, getting M.E. made my NMH/POTS problems go off the charts.
I’m fascinated that Lauren ended up with POTS after a concussion, because most of us end up with it via faulty genes. If your doctor knows where the damage was in your brain, perhaps that could be helpful for those of us who … just HAVE it.
I am also appalled that Midodrine is being held for ransom (so to speak) by FDA. This is a serious condition, and there aren’t very many medications out there for it. (I get a liter of IV saline twice a week and that seems to help).
Probably not by coincidence (because of the interrelationship between NMH/POTS and ME/CFS), the only drug in the FDA pipeline for this disease is Ampligen, a mismatched protein that in my case (I have been on it most of the time since 1999) reversed the immune defects and helped the viruses return to dormancy. Ampligen also lives in the half-world of approved and not approved. We patients wanted a double-blind with a biomarker back in 1999 – but the company didn’t want to pay for the biomarker. We patients did not have a say in this – and FDA doesn’t really care how many patients depend on the drug, or the medical science involved, or whether it might help with other conditions. All they care about is proving or disproving whether the company does or does not deserve to profit by the discovery.
That’s pretty ironic given that FDA let’s companies charge whatever they want once they get past the barrier of Phase III (which is where I am). They go from pushing companies under, or to drop needed drugs entirely, by repeatedly asking for more double-blind studies to prove absolutely that the drug made the difference – to giving the companies the moon and the right to charge whatever they feel like.
Or they take a drug away from people whose world will be crushed without it. I know a lot of people on Midodrine and I did not know that they might lose it. And I live in terror of losing Ampligen (because when I have had to go off it, within a year I have returned to being bedridden in pain and confusion).
For one article, this touched on a number of very important issues. Thank you – and thank you to Lauren for creating Dysautonomia International.
This drug helps so many people.
My son has his life managed and back on track only because of this medication….without it he is on his back in bed. It took over 6 years and missing most of his high school education before dropping out. I then found a Dr who started investigations suspecting POTS. We are in Australia and have to pay full price for this medication but it is the only one that helped after trailing many others.
Thank you, Stephanie, for your careful research on this well-written article. I hope the drug gets approved very soon.
For those suffering and getting help from this medicine–you should continue making it!!