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Establishing Meaningful Clinical Outcome Measures for Gastrointestinal Symptoms in Cystic Fibrosis

Establishing Meaningful Clinical Outcome Measures for Gastrointestinal Symptoms in Cystic Fibrosis 1024 683 Lauren Dembeck

Understanding the minimal clinically important differences of PROMs is crucial in interpreting results in clinical trials.

Patient-reported outcome measures (PROMs) are a set of standardized questions that directly assess the patient’s perspective of their symptoms and quality of life to better understand their experience with a disease or treatment. PROMs support patient-centered care and are increasingly being used in interventional research studies as clinical trial end points. To accurately interpret changes in PROMs, researchers must establish what is a minimal clinically important difference (MCID), or how much of a change in the PROM score is associated with a meaningful change in clinical symptoms.

“Clinically applicable patient-reported outcome measures for gastrointestinal symptoms have been validated for some gastrointestinal disorders but not for cystic fibrosis,” explains A. Jay Freeman, MD, MSc, medical director of Pancreatic Care for the Pancreas and Liver Care Center at Nationwide Children’s Hospital. “In the GALAXY study, we partnered with a community of patients with cystic fibrosis and their caregivers to identify the patient-reported outcome measures that most accurately reflected their experience with gastrointestinal symptoms in cystic fibrosis.”

From that study (ClinicalTrials.gov ID: NCT03801993), Dr. Freeman and colleagues reported the combination of PAC-SYM (Patient Assessment of Constipation Symptoms), PAGI-SYM (Patient Assessment of Upper Gastrointestinal Symptoms), PAC-QOL (Patient

Assessment of Constipation-Quality of Life), and the Bristol Stool scale with four additional symptom-specific questions were the PROMs that comprehensively captured the gastrointestinal experience of persons with cystic fibrosis.

In a new study published in the Journal of Cystic Fibrosis, the research team followed up on the GALAXY study to establish disease-specific MCIDs for the identified PROMs in patients with cystic fibrosis.

The study used data from 402 persons with cystic fibrosis who participated in the GALAXY study. For these patients, baseline values were available for all questionnaires. The patients’ mean age was 20.9 years (range, 2.1- 61.1 year). Patients aged 18 and older (118 females and 115 males) comprised 58 percent of the cohort, while those under the age of 18 (75 females and 94 males) made up the remaining 42 percent.

The researchers determined the MCIDs using two distribution-based approaches for the PAC-SYM, PAGI-SYM, and PAC-QOL and their subscales. The two distribution-based approaches determine the MCIDs quantitatively utilizing the standard deviation (SD) or standard error of the mean (SEM).

“By looking at the distribution of the dates, we looked at the deviation from the center of the curve — asking how far away from the center of the curve is each answer from patient to patient and within the same patient over time, to determine how large of change within the PROM would be statistically significant,” explains Dr. Freeman, who is also a professor of Pediatrics at The Ohio State University College of Medicine.

The team found that the two approaches produced comparable results in trends in MCIDs across the subscales and total scores. They reported that, in general, the MCID estimates of the subscales for all three measurements were higher than their total score MCIDs. The one-half SD- and SEM-based MCID estimates for total scores of each questionnaire were 0.26 and 0.14 for PAC-SYM, 0.32 and 0.15 for PAGI-SYM, and 0.27 and 0.18 for PAC-QOL, respectively.

“We plan to implement and evaluate these MCIDs in a clinical trial evaluating a drug to treat bloating in patients with cystic fibrosis soon. We will then be able to use the changes observed in the clinical trial as the basis for an anchor-based method, which is a stronger approach, for future clinical trials,” says Dr. Freeman.

 

Reference

Lee M, Sathe M, Moshiree B, Vu PT, Heltshe SL, Schwarzenberg SJ, Freedman SD, Freeman AJ. Estimating minimal clinically important difference (MCID) for gastrointestinal symptoms in cystic fibrosis. J Cyst Fibros. 2024 Sep;23(5):991-999.

About the author

Lauren Dembeck, PhD, is a freelance science and medical writer based in New York City. She completed her BS in biology and BA in foreign languages at West Virginia University. Dr. Dembeck studied the genetic basis of natural variation in complex traits for her doctorate in genetics at North Carolina State University. She then conducted postdoctoral research on the formation and regulation of neuronal circuits at the Okinawa Institute of Science and Technology in Japan.

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