The Counterfactual Conundrum

I’m at a juncture in my migraine treatment journey that would not have happened without the thousands of patients who volunteered to take part in breakthrough research into the first ever preventive medication developed specifically for migraine. I am sharing this story as part of the Clara Health #PatientsHavePower Writing Contest, because I want to raise awareness about the importance of clinical trials in medical innovation.

“I think you should look into this clinical trial.” Those were the words my doctor was telling me. We had just gotten done tweaking my medications for the dozenth time in a year and I didn’t have much hope that my chronic, daily migraine symptoms were going to respond any better to these adjustments than they had to all the others. A clinical trial? Had we really come to that point? I had seen the placards on the MBTA over the years, the ones advertising for research subjects at hospitals around Boston. Those were for desperate grad students…but as I thought about it, I was a desperate grad student.

I wasn’t desperate for cash, but relief. Relief from the barrage of migraine symptoms that had plagued me nearly non-stop for a year at that point. The summer before, my life had been turned upside down. Family life, graduate school, and my professional life all got upended at once. My then-undiagnosed anxiety triggered sleepless nights which triggered daily headaches which were, more and more frequently, turning into full-blown migraine attacks. Although I managed to finish my Ph.D., one year later I was facing a leave of absence from work and wondering how much longer I’d be able to hang on to my job. I was quickly exhausting available treatments.

My doctor knew the coordinator for the local trial of the new class of migraine preventive in debrain_abstractvelopment: the CGRP (calcitonin gene-related peptide) antagonists that were the talk of the migraine community. I had been following their progress, but knew we were a while off from getting FDA approval. My one chance to access them would be through a clinical trial.

Being a researcher myself, I understood how research studies typically worked. They strive for something called internal validity. When I was studying for my comprehensive exams and had to explain internal validity in lay terms, I would often describe it as when a study has been designed in a way that ensures that you can say, with as much confidence as possible, that X causes Y. This means that you’ve ruled out other explanations for Y. Knowing all the steps researchers took to rule out those other explanations, I had two big questions about the CGRP trials. First, I wanted to know whether this study was set up so that some participants would receive the CGRP treatment and others the inactive placebo. If so, I wanted to know my odds of being assigned to the group receiving the treatment. Second, I wondered whether I would need to stop or change any of my current treatments.

The doctor who was running the trial was patient and reviewed all the study conditions. First, he explained that it was a double-blind, placebo-controlled study which meant there was one group of participants who would receive the CGRP treatment drug and shot_armanother who would receive an inactive placebo. Participants would be randomly assigned to these groups and neither the participants nor the trial leaders would know which group was which. This type of design is the gold standard in clinical trials. In this case, it ensured that the participants receiving the treatment and placebo were as similar as possible except that one received the CGRP treatment. That way, any difference that was measured at the end of the study – e.g., average number of migraine days in each group – could be attributed to the treatment and not something else. In other words, it ticks that “internal validity” box. However, while the design was strong, it meant some people would not get the treatment. The good news was, my chance of being assigned to the treatment group was two out of three. I was pretty happy with those odds.

The bad news was that I would need to stop several of my current medications as there was a limit to the number of preventive medications study participants could be on. One of my more effective treatments was a particular deal breaker. I was crushed. My symptoms were already poorly controlled. To stop some of my medications hoping both that I would receive the treatment drug and that it would be effective was a big leap of faith. I understood that they couldn’t take the chance of my other medications clouding the picture. They needed to be able to clearly say that if I got better it was due to the CGRP treatment and not one of my other medications.

In the end, I didn’t join the study. I felt I was too sick to take the chance. At a point when I was trying hard to continue working, stopping my medications for a less than 100% shot at the treatment wasn’t an option. Looking back, the researcher in me understands the many eligibility requirements of clinical trials. They ensure internal validity; making it possible to detect the effectiveness of the treatment medication and rule out other possible explanations for differences between the treatment and placebo groups. However, when you are a chronically ill patient desperate to join a study, the qualifications can be daunting. In the future, I hope researchers find more ways to bring the neediest, most complicated participants into their trials while maintaining validity.

For now, I have enormous gratitude for the thousands of patients who had the incredible bravery and strength to help bring a breakthrough new drug to market for those of us with migraine. Patients truly do have power, because this is the first is in its class. Three more should follow suit over the next 12 months, bringing years of research to fruition. The end result is what appears, at this point, to be one of the safest and most effective preventive migraine medications available. Time will be the true test, but this has the potential to improve millions of lives. Although I didn’t participate, I have followed these drugs at every stage and thank everyone who played a role in their development.