I don’t know about you but I felt last week the Duchenne community was hit with our own hurricane, similar to the 5th deadliest hurricane in US history, 2005 Katrina. I’m not from New Orleans, but have a good friend, Diane, whose home was washed way when the levee system failed and neighboring parishes flooded. The 175 mile winds took everything - house, furniture, photos, memories, life as she knew it. While nearly 2,000 people lost their lives, her family managed to survive. She was in Cincinnati at the time, desperately seeking information and connections to those she loved. I could not imagine how she felt during that time, but saw it on her face: pain, desperation, sadness.
I cannot relate to Katrina, but on Saturday I felt like I was seeing the aftermath of our own ‘hurricane.’ The wind died down and the reality hit. As a community, we were left in the aftermath, trying to makes sense of the news, trying to find some meaning, some hope.
I have been following the discussions, the criticism, the sadness . These trial results are not what we expected or wanted. We all wanted a win for Duchenne. We depended on it as if it would feel like a neon sign that this one win would lead to more, would mean the stars were lining up just right. And sometimes when we hear bad news, everything else in the world looks bleak.
I must have asked Tom how he was feeling a million times, thinking the universe must be against us. Finally he told me I was simply not allowed to ask. I went to the nursing home to see my mother and this sweet 94-year-old German Catholic woman who taught me that "life is not a rehearsal and while you may not be able to control the boulders thrown in your path, you will find a way to walk around, over or compensate for them”; this lovely woman looked at me with tears in her eyes and said that ‘they’ were giving her pills to hurt her and there was no way to reason with her. She was afraid and I could not convince her that I knew what pills she was taking, that I was in contact with the doctors, that I would keep her safe. Senile dementia. I left feeling defeated, helpless. And my daughter Michelle moved into her new flat in London (Primrose Hill, Princess Lane), the boiler failed, and she had no heat or hot water. At that moment, I wanted to fly to London and bring her home to my safe house. (If you were to meet some of my relatives, you would understand that they typically do not allow children to move far from home). I called my other daughter Jenny to make sure she was safe. I had no reason to doubt it, but it felt like the universe had changed on its axis.
The discussions on the website reflect anger and sadness. We are all grieving. Discussions related to trial design – was it the right design? Was the 6 Minute Walk Test (6MWT) the best or worst choice as an outcome measure? How do you measure benefit in a population where clinical variability (function, progression, cognition) are highly variable? Should the stratification of the trial have been more precise as in eliminating boys who could not walk a certain distance (<350m) in the 6MWT? Too many sites/wrong sites? How much dystrophin expressed? What are the individual responses? Why can’t you change course in the middle of a trial? Do something different? Why suspend all trials? What about compassion? And what next?
I find the criticism and the desire to point the finger at someone or something incredibly sad and a bit overwhelming. I understand it as I have been angry since Duchenne entered my home, my vocabulary, my every thought. But it is DUCHENNE I hate, not the people. I thought about my own life and the decisions I have made and how with additional information, I might have made different decisions. I have made good decisions, bad decisions, ‘meh’ decisions (those are not so important decisions), and have had the opportunity to revise and re-do and some of the time, rethinking and redoing has improved the original decision by leaps and bounds. Pity that we don’t have a crystal ball.
On Saturday I received a call from a mom who had been contacted by another mom, whose son was not in the trial. The description of the call was sad – pointing the finger, criticizing people, recommending litigation. I was at first angry and then sadness fell on me like a wet blanket.
After that unsettling call, I drove to the Dorothy Lane Market in Dayton. I bought 3 way too expensive cookies (Laura’s large sugar cookies @ $3.00 per). If I was in New York, I would have gone to the Magnolia Bakery for cupcakes, but I was in Middletown, so the choices were limited. I ate all 3! I think it took less than 5 minutes to consume all of them, what may be upwards of a total of 3000 calories. While they were going down, I loved it. I thought it was perhaps the best investment ever. Then I went to my favorite shop in Hyde Park and tried on pants for summer. I could not button them at the waist and the way they looked in the mirror did not fit with the image I had in my head. So I left. In retrospect, I should not have eaten the cookies, should not have stopped running after freezing my bottom off in Florida in January, and should not have York Peppermint Patties sitting on my desk. Bad decisions and if I could get a do-over, I might make other choices.
Divorce/partners –another example. You marry your partner because it looks like a good decision at the time. Over time you learn more, life throws in a few boulders, and you find you need to make a different decision. And you do and the second time around it is sometimes better. Different factors, new knowledge, experience, wisdom. Your primary endpoint changed? Secondary endpoints different?
All this is trivial in light of a clinical trial that may mean the difference between maintaining/improving function or not and extending the length of life. But in some strange way, there are similarities. Decisions are made based on knowledge at the time. Trials are developed with advice and expertise from a range of individuals to include parents/patients – experts ( specific disease process, drug development, regulatory, business model, etc) and with all of that in mind, trials are conducted and data analyzed. The data informs and based on recommendations (in this case) the trial is suspended. Keep in mind, SUSPENDED is not ENDED. SUSPENDED to regroup, rethink, analyze, and clear the path forward.
I hear the phrase "compassionate use", but the case (based on current data primary /secondary outcomes) is not there.
So, we have to wait. Wait for sub-analysis. Wait for the plan. And once the path is developed, we will do whatever it takes to move toward success. Like you, I have heard the anecdotal stories –both positive and negative. I remain a believer –that Duchenne will have treatments and in the near future, that suppression of premature stops is a promising strategy. That exon skipping, utrophin upregulation, myostatin inhibition,
increasing nNOS – are all potentially promising.
But I am not ready to throw arrows at anyone or anything...except Duchenne.
P.S. Diane sorted through the rubble and found a picture of her dad in perfect condition.