Cross-Sectional Quantitative Evaluation of a Novel Patient-Reported Outcome Measure in Familial Chylomicronemia Syndrome

Abstract

Background

Familial chylomicronemia syndrome (FCS) is a rare metabolic disorder that impacts physical, emotional, social, and cognitive functioning. The FCS-Symptom and Impact Scale (FCS-SIS) patient-reported outcome (PRO) measure assesses common symptoms and impacts of FCS. This study was conducted to evaluate cross-sectional psychometric properties of the FCS-SIS and its scoring method.

Methods

This multisite, cross-sectional, observational study of individuals with FCS was conducted in the United States and Canada. Participants completed a survey composed of 7 PRO measures, including the FCS-SIS, and questions about clinical characteristics and demographics. The structure of the FCS-SIS was evaluated using inter-item and item-scale correlations and internal consistency reliability. Construct, known-groups, and criterion validity were evaluated by examining associations between FCS-SIS item and composite scores and other measures included within the survey.

Results

Most of the 33 participants were female (63.6%) and White (78.1%). On average, participants reported first noticing FCS symptoms at ~16 years, with abdominal pain the most frequently reported initial symptom (n=20). Participants reported 2.5 acute pancreatitis attacks on average over the past year. Average FCS-SIS symptom item scores ranged from 1.8 to 3.9 (on a 0-to-10 scale [none-to-worst-possible]) within the 24-hour recall period, with an average Symptom composite score of 2.7. The average impact item scores on the FCS-SIS ranged from 1.6 to 3.0 (on a 0-to-4 scale), with an average Impact composite score of 2.1. Inter-item correlations between the FCS-SIS Symptom items ranged from 0.32 to 0.78. Corrected item-total correlations were highly satisfactory for Impact items, ranging from 0.62 to 0.85. All a priori validity hypotheses were supported by observed correlations and score differences between known groups.

Conclusion

The results of this study support the structure, reliability, and validity of the FCS-SIS, laying the psychometric groundwork for longitudinal evaluation of its utility in assessing treatment benefit in FCS clinical studies.

Keywords:

• psychometric evaluation
• FCS
• validity
• reliability
• rare disease
• patient reported outcome measure

Data Sharing Statement

Data may be available from Ionis Pharmaceuticals upon reasonable request. Inquires may be sent to Ionis Pharmaceuticals ([email protected]).

Ethics Approval and Consent to Participate

The study materials were reviewed by the Advarra Institutional Review Board (IRB) and subsequently received an exempt determination. Sites requiring a local or academic IRB were responsible for their own IRB submission based on the study materials. Study participants provided consent to participate. Research was conducted in line with the Belmont Report and the Declaration of Helsinki.

Acknowledgments

The authors thank Brian Samsell, PhD, and Sara Musetti Jenkins, PhD, of RTI Health Solutions, for medical writing assistance. We also thank Nikki Williams, BS, and Emily Bratlee-Whitaker, PhD, RN, of RTI Health Solutions, for analytic support. We gratefully acknowledge the patients who participated in this research.

Author Contributions

All authors declare that they have made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; have drafted or written, or substantially revised or critically reviewed the article; have agreed on the journal to which the article will be submitted; have reviewed and agreed on all versions of the article before submission, during revision, the final version accepted for publication, and any significant changes introduced at the proofing stage; and agree to take responsibility and be accountable for the contents of the article.

Disclosure

TMB and SF are full-time employees of RTI Health Solutions, an independent nonprofit research organization, which was retained by Ionis Pharmaceuticals to conduct the research which is the subject of this manuscript. Their compensation is unconnected to the studies on which they work. CK was an employee of RTI Health Solutions at the time the research was conducted. MVL, ASK, and AY are employees of Ionis Pharmaceuticals and hold shares and/or stock options in the company. The authors report no other conflicts of interest in this work.

Additional information

Funding

Ionis Pharmaceuticals provided the financial support for the study. RTI Health Solutions, an independent nonprofit research organization, received funding under a research contract with Ionis Pharmaceuticals to conduct this study and provide publication support in the form of manuscript writing, styling, and submission.