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Background: When developed properly, disease-specific patient reported outcome measures have the potential to measure relevant changes in how a patient feels and functions in the context of a therapeutic trial. The Huntington’s Disease Health Index (HD-HI) is a multifaceted disease-specific patient reported outcome measure (PROM) designed specifically to satisfy previously published FDA guidance for developing PROMs for product development and labeling claims. Objective: In preparation for clinical trials, we examine the validity, reliability, clinical relevance, and patient understanding of the Huntington’s Disease Health Index (HD-HI). Methods: We partnered with 389 people with Huntington’s disease (HD) and caregivers to identify the most relevant questions for the HD-HI. We subsequently utilized two rounds of factor analysis, cognitive interviews with fifteen individuals with HD, and test-retest reliability assessments with 25 individuals with HD to refine, evaluate, and optimize the HD-HI. Lastly, we determined the capability of the HD-HI to differentiate between groups of HD participants with high versus low total functional capacity score, prodromal versus manifest HD, and normal ambulation versus mobility impairment. Results: HD participants identified 13 relevant and unique symptomatic domains to be included as subscales in the HD-HI. All HD-HI subscales had a high level of internal consistency and reliability and were found by participants to have acceptable content, relevance, and usability. The total HD-HI score and each subscale score statistically differentiated between groups of HD participants with high versus low disease burden. Conclusion: Initial evaluation of the HD-HI supports its validity and reliability as a PROM for assessing how individuals with HD feel and function.

Objective:To determine the prevalence and relative importance of symptoms experienced by children and adults with Friedreich’s ataxia (FA) and to identify factors associated with a higher burden of disease.Methods:We conducted qualitative interviews with individuals with FA and caregivers of pediatric individuals with FA to identify potential symptoms of importance to those living with FA. We subsequently performed a cross-sectional study to assess which symptoms have the highest prevalence and importance in FA and to determine which factors are associated with a higher burden of disease.Results:Thirty-nine participants provided 2,527 quotes regarding the symptomatic burden of FA. Two-hundred and two individuals (153 with FA and 49 caregivers) participated in a subsequent cross-sectional study. Individuals with FA and caregivers identified impaired coordination, limitations with mobility and walking, inability to do activities, fatigue, and lower extremity weakness as the most prevalent and life altering symptomatic themes in FA. Muscle stiffness and functional staging for ataxia were associated with the prevalence of symptomatic themes in FA. In addition, the length of the smaller GAA expansion and the mean length of both GAA expansions were strongly associated with the onset of symptoms in FA.Conclusions:There are a wide variety of symptoms that affect the lives of individuals with FA. These symptoms, many underrecognized, have different levels of importance and occur at different rates in the FA population. The most common and life altering of these symptoms represent potential targets for future therapeutic interventions.

INTRODUCTION:Patients with Crohn's disease (CD) experience a variety of symptoms that significantly affect their lives. In this study, we (i) ascertain the most prevalent and impactful symptoms in CD and (ii) identify modifying factors that are associated with a higher disease burden in CD.METHODS:We conducted semistructured interviews with adult participants with CD to determine what issues have the greatest impact on their lives. Next, we conducted a large cross-sectional study of individuals with CD to determine the prevalence and relative importance of those symptoms and themes and to identify the demographic features that are associated with a higher disease burden.RESULTS:Sixteen individuals with CD provided 792 direct quotes regarding their symptomatic burden. Four hundred three people with CD participated in our cross-sectional study. The symptomatic themes with the highest prevalence in CD were gastrointestinal issues (93.0%), fatigue (86.4%), dietary restrictions (77.9%), and impaired sleep or daytime sleepiness (75.6%). The symptomatic themes that had the greatest impact on patients' lives (0–4 scale) related to fatigue (1.82), impaired sleep or daytime sleepiness (1.71), gastrointestinal issues (1.66), and dietary restrictions (1.61). Symptomatic theme prevalence was strongly associated with a higher number of soft stools per day, greater number of bowel movements per day, missed work, employment and disability status, and having perianal disease.DISCUSSION:Patients with CD experience numerous symptoms that affect their daily life. These symptoms, some underrecognized, vary based on disease and demographic characteristics and represent potential targets for future therapeutic interventions.

Study Aim: The goal of this research is to develop and validate a novel, disease-specific patient-reported outcome measure (PRO) for use in clinical monitoring and therapeutic trials in Lung Cancer (LC). Methods: LC currently accounts for the greatest number of cancer deaths worldwide, driving an increased need for novel therapeutic development in LC. To bolster clinical trial infrastructure, it is critical to have a comprehensive, sensitive and reliable PRO that accurately tracks LC multifactorial disease burden. This research describes the development and validation of the Lung Cancer-Health Index (LC-HI) as an efficient mechanism for assessing how patients with LC feel and function in response to therapeutic treatment. We conducted semi-structured, qualitative interviews with 15 individuals diagnosed with LC and collected 653 direct participant quotes to determine the most frequent and important symptoms in LC. Based upon participant responses, we designed a survey that inquired about 162 symptoms from 14 symptomatic themes. This survey was implemented in a cross-sectional study with 139 participants with LC. The collected data was used to generate the first version of the LC-HI, which contained symptom questions showing the highest impact to the population and the potential to respond to therapeutic intervention. Symptom questions were grouped into distinct subscales using factor analysis. We beta-tested the LC-HI with 15 patients with LC to evaluate its usability, clarity, and applicability. Based on patient feedback, we modified the instrument and evaluated its test-retest reliability with 22 individuals with LC. Known groups testing was performed with the final instrument. Results: The final version of the LC-HI contains 45 symptom questions grouped into 10 subscales that measure the following areas of LC health: 1) fatigue, 2) physical function, 3) emotional health, 4) sleep and daytime sleepiness, 5) activity participation, 6) breathing function, 7) gastrointestinal function, 8) cognitive function, 9) social performance, and 10) pain. Total LC disease burden is measured using a weighted composite of these subscale scores. During beta interviews, individuals with LC deemed the instrument to be easy to use, clear, relevant, and comprehensive. Statistical and psychometric analyses confirmed that the LC-HI is reliable, valid, sensitive, specific, of high internal consistency, and able to differentiate between groups with known varying levels of disease burden (based on disability status and smoking history). Conclusions: Our research demonstrates the validity of the LC-HI as a marker of the multifaceted disease burden in LC. This disease-specific PRO provides researchers and clinicians with a reliable tool to use in patient monitoring, clinical trials, and to support FDA drug labeling claims. Citation Format: Anika Varma, Spencer Rosero, Jamison Seabury, Jennifer Weinstein, Charlotte Engebrecht, Christine Zizzi, Nuran Dilek, John Heatwole, Megan Baumgart, Deborah Mulford, Ronald Maggiore, Lainie Conrow, Jennifer King, Jacinta Wiens, Chad Heatwole. Development and validation of the Lung Cancer-Health Index (LC-HI), a clinically-relevant, disease-specific patient-reported outcome measure. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4383.