I’ve known since I was a little girl that cystic fibrosis is a disease that only gets worse. Every day it destroys lung cells and tightens the small airways in my chest, taking me closer to the point when my ravaged lungs stop working. I’ve never questioned if there was some way the disease’s progress could be stopped. Until now.

Exciting research into restoring the function of the cystic fibrosis transmembrane conductance regulator (CFTR) protein holds the possibility of slowing, stopping, and maybe even reversing the damage wrought by CF. I imagine that having a functioning CFTR protein that would expel chloride out of my cells, hydrate the surface of my lungs, and halt the accumulation of the thick, sticky mucus that has enveloped my airways in a suffocating cloak all these years would feel like being rescued from drowning.

Unfortunately, I am still drowning.

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Excited by the possibility of participating in a CFTR trial, I found one at my local adult CF clinic that was recruiting participants. I reached out to the study coordinators, only to be told, “I’m very sorry Ms. Balasa, but you will not be able to participate in this clinical trial.”

I met all of the criteria to be eligible to participate in that trial except one. It’s the same one that has kept me from taking part in other trials testing investigational medications for the symptoms of CF.

That criteria is called forced expiratory volume in one second (FEV1). As the name suggests, it’s the amount of air an individual can forcibly blow out in one second. It is usually given as a percentage of “normal.” The lower your FEV1, the worse your lung function.

Most cystic fibrosis studies, including Phase 1, 2, and 3 trials, require participants to have an FEV1 of at least 40 percent. Mine is 25 percent which, for more than 10 years of my life, has made me ineligible for clinical trials. I’m not alone.

That requirement overlooks the fact that cystic fibrosis affects different people in different ways. Some who need supplemental oxygen, have a hard time completing daily tasks, are unable to work, and are on disability have FEV1s above 40 percent and so would qualify for trials. Others, like me, who work, travel, have good quality of life, and use oxygen only when sleeping or during laborious physical activity, yet have FEV1s of 30 percent, are excluded from taking part in trials. I know many people in the CF community who lead successful, fulfilled lives with lung function below 40 percent.

As someone who works in the science field and who values the efforts of scientists and clinicians doing clinical research, I started to wonder: Where does this requirement come from? Should this single variable be such a deciding factor in determining who can take part in cystic fibrosis clinical trials and who can’t? Are we getting comprehensive results from these trials if an important subset of patients is omitted?

Inclusion and exclusion criteria for participating in cystic fibrosis clinical studies and trials are designed by the Food and Drug Administration, with advice from the Cystic Fibrosis Foundation. These criteria are there to protect the safety of participants.

There are surely safety (and data) concerns to consider when thinking about including participants with FEV1 scores below 40 percent. Individuals with lower lung function have a higher chance of developing respiratory infections and acute worsening of symptoms, called pulmonary exacerbations, during the trial period, either because of advanced disease or adverse effects from the drug. That could result in their withdrawing from the trial and a decrease in data points. Those with more scar tissue and lung damage probably won’t achieve the same level of symptom relief and disease reversal as those with milder CF. And they may not experience a significant change in lung function, which means fewer positive results for the company to present to the FDA when seeking approval for a new drug.

That said, the 40 percent threshold tends to lead to trials that include a disproportionate number of younger participants, as CF causes steadily decreasing lung function over time. Yet as CF treatment has rapidly progressed and patients’ life expectancies have increased, there are more adults with CF in the United States today than children.

I believe that FEV1 alone is an insufficient proxy for identifying candidates for cystic fibrosis trials. It should be just one of many factors that indicate an individual’s overall health with CF. Considering potential participants’ quality of life and overall health is a reasonable adjustment to current inclusion and exclusion practices.

You can’t, of course, simply lower the FEV1 inclusion criteria to 30 percent or 20 percent. Some people with lung function in that range are severely ill, which increases the odds their illness will worsen or they will die during a trial. But including a separate cohort that includes some patients who are relatively “healthy” but whose lung function is lower than the 40 percent cutoff could provide novel data about the treatment.

Their progress could be evaluated by tests that measure the levels of blood oxygen and carbon dioxide, or by physical endurance — like the six-minute walk test — instead of focusing on changes in FEV1. Those are viable indicators of improving or deteriorating lung health. Using such criteria, physicians and study coordinators could be given the discretion to select healthier patients with lower lung function scores.

Another valuable addition to cystic fibrosis trials would be the inclusion of information about patient-reported outcomes, which are currently underused in clinical trials. They provide standardized, valid, and reliable ways of evaluating patients’ perspectives on the benefits and drawbacks of trial medications. Patient-reported outcomes have even been reported to be predictors of survival in people with cystic fibrosis.

Including a broader patient population in cystic fibrosis trials, specifically individuals with lower FEV1 scores, is important for understanding the effects of a new drug on this population. Excluding them means that individuals with lower FEV1 scores and their doctors are flying blind when a new drug is approved. Relaxing inclusion and exclusion criteria would also increase the pool of potential participants. Many clinical studies and trials are small, as few as a half-dozen patients; and increasing the number of participants potentially increases the quality of the results.

A few weeks ago, I met with a team from a pharmaceutical company that wanted to learn what it can do to better serve the cystic fibrosis community. I briefly mentioned the seemingly arbitrary exclusion of people with FEV1 scores under 40 percent from clinical trials, but hadn’t thought it through completely. I hope they are listening now.

I really want to take part in clinical trials that could change the course of treatment for people like me with cystic fibrosis. I’m healthy, committed, and want to help make a difference in the fight against this disease. It’s a shame that a single number blocks me from doing this.

Ella Balasa, diagnosed with cystic fibrosis at age 1, is a columnist for CF News Today and the Cystic Fibrosis Foundation blog; a director for the United States Adult Cystic Fibrosis Association; and a microbiology lab manager at Virginia Commonwealth University. She currently lives a fulfilled life with 25 percent lung function. A version of this article appeared earlier on MedPage Today.

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  • Sorry to hear of your struggles.
    The problem is the way the FDA judges the success of a clinical trial in terms of efficacy and safety. I believe the clinical trial process, which aims to protect patients, is fundamentally flawed.
    The criteria required in clinical trials rarely replicates in the real world setting which severely limits the applicability of information derived from the RCT

  • My daughter was diagnosed within 3 days of birth. She did really well until college. It was very hard for her as a young adult. At age 32 they told her that her time on earth was done. At age 33 she had new lungs and has done very well with them. The rejection meds on the other hand have been very hard on her bringing on the side effects. I pray for better health for you and other cf patients.

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