Evaluation and performance of a newly developed patient-reported outcome instrument for diarrhea-predominant irritable bowel syndrome in a clinical study population

Leticia Delgado-Herrera, Kathryn Lasch, Bernhardt Zeiher, Anthony J Lembo, Douglas A Drossman, Benjamin Banderas, Kathleen Rosa, Christopher Lademacher, Rob Arbuckle, Leticia Delgado-Herrera, Kathryn Lasch, Bernhardt Zeiher, Anthony J Lembo, Douglas A Drossman, Benjamin Banderas, Kathleen Rosa, Christopher Lademacher, Rob Arbuckle

Abstract

Background: To evaluate the psychometric properties of the newly developed seven-item Irritable Bowel Syndrome - Diarrhea predominant (IBS-D) Daily Symptom Diary and four-item Event Log using phase II clinical trial safety and efficacy data in patients with IBS-D. This instrument measures diarrhea (stool frequency and stool consistency), abdominal pain related to IBS-D (stomach pain, abdominal pain, abdominal cramps), immediate need to have a bowel movement (immediate need and accident occurrence), bloating, pressure, gas, and incomplete evacuation.

Methods: Psychometric properties and responsiveness of the instrument were evaluated in a clinical trial population [ClinicalTrials.gov identifier: NCT01494233].

Results: A total of 434 patients were included in the analyses. Significant differences were found among severity groups (p < 0.01) defined by IBS Patient Global Impression of Severity (PGI-S) and IBS Patient Global Impression of Change (PGI-C). Severity scores for each Diary and Event Log item score and five-item, four-item, and three-item summary scores were calculated. Between-group differences in changes over time were significant for all summary scores in groups stratified by changes in PGI-S (p < 0.05), two of six Diary items, and three of four Event Log items; a one-grade change in PGI-S was considered a meaningful difference with mean change scores on all Diary items -0.13 to -0.86 [standard deviation (SD) 0.79-1.39]. Similarly, for patients who reported being 'slightly improved' (considered a clinically meaningful difference) on the PGI-C, mean change scores on Diary items ranged from -0.45 to -1.55 (SD 0.69-1.39). All estimates of clinically important change for each item and all summary scores were small and should be considered preliminary. These results are aligned with the previous standalone psychometric study regarding reliability and validity tests.

Conclusions: These analyses provide evidence of the psychometric properties of the IBS-D Daily Symptom Diary and Event Log in a clinical trial population.

Keywords: IBS Global Assessment of Improvement; IBS Patient Global Impression of Severity; diarrhea-predominant irritable bowel syndrome; psychometric; responsiveness.

Conflict of interest statement

Conflict of interest statement: L. Delgado-Herrera and C. Lademacher and B. Zeiher are employees of Astellas. K. Lasch is an employee of Pharmerit International. A. Lembo has received consultancy fees from AstraZeneca, Ironwood/Forest, Prometheus, and Salix outside the submitted work. D.A. Drossman has received consultancy fees from Shire and Salix. R. Arbuckle, B. Banderas, and K. Rosa are employees of Adelphi Values (formerly Mapi Values), which was under contract by Astellas for this work; K Rosa has a patent pending.

Figures

Figure 1.
Figure 1.
Clinical trial design. Dosing numbers were targets and do not reflect the number of patients recruited for each treatment arm. BID, twice daily; TID, three times daily. *Day 1 may occur on same day as qualification visit or 3 to 5 days after, if assigned study drug is not onsite.
Figure 2.
Figure 2.
Known groups analysis using IBS PGI-S scores. IBS PGI-S scores indicating more severe symptoms (0–3, least severe; 4–6, moderately severe; 7–10, most severe) were associated with increasing severity on the Diary and Event Log at weeks 1 (a) and 4 (b). IBS PGI-S scores indicating more severe symptoms (0–3, least severe; 7–10, most severe) were associated with increasing severity on the Diary and Event Log at weeks 1 (a) and 4 (b). Between-group differences for each item except for ‘Frequency of gas’ at week 1 were significant. Note that lower scores indicate less severe symptoms. *p < 0.001; †p < 0.01 (ANOVA). ANOVA, analysis of variance; IBS-D, diarrhea-predominant irritable bowel syndrome; IBS PGI-S, IBS Patient Global Impression of Severity.
Figure 3.
Figure 3.
Known groups analysis of five-item, four-item, and three-item summary scores of the Diary using the IBS PGI-S and IBS PGI-C scores at weeks 1 (a) and 4 (b). *p < 0.05 (ANOVA). ANOVA, analysis of variance; IBS-D, diarrhea-predominant irritable bowel syndrome; IBS PGI-C, IBS Patient Global Impression of Change; IBS PGI-S, IBS Patient Global Impression of Severity.
Figure 4.
Figure 4.
Responder analysis. The relative distributions of mean scores for almost every item on the Diary and Event Log, except for ‘Daily percentage of completely emptied bowels’, were consistent with their assignment to responder groups of ‘Improved’, ‘No change’, and ‘Worsened’ using either the IBS PGI-S (a) or IBS PGI-C (b). Note that negative values for changes in scores indicate improvement. *Between-group p < 0.05 (ANOVA); †within-group (change from baseline) p < 0.05 (Student’s t test). ANOVA, analysis of variance; IBS-D, diarrhea-predominant irritable bowel syndrome; IBS PGI-C, IBS Patient Global Impression of Change; IBS PGI-S, IBS Patient Global Impression of Severity.
Figure 5.
Figure 5.
Responder analysis of Diary summary scores. The relative distribution of five-item, four-item, and three-item mean summary scores on the Diary were consistent with their assignment to responder groups of ‘Improved’, ‘No change’, and ‘Worsened’ using either the IBS PGI-S (a) or IBS PGI-C (b). Note that negative values for changes in scores indicate improvement. *Between-group p < 0.05 (ANOVA); †within-group (change from baseline) p < 0.05 (Student’s t test). ANOVA, analysis of variance; IBS-D, diarrhea-predominant irritable bowel syndrome; IBS PGI-C, IBS Patient Global Impression of Change; IBS PGI-S, IBS Patient Global Impression of Severity.

References

    1. Longstreth GF, Thompson WG, Chey WD, et al. Functional bowel disorders. Gastroenterology 2006; 130: 1480–1491.
    1. U.S. Department of Health and Human Services Food and Drug Association. Guidance for industry: patient-reported outcome measures: use in medical product development to support labeling claims. , 2009.
    1. U.S. Department of Health and Human Services Food and Drug Association. Guidance for industry irritable bowel syndrome – clinical evaluation of drugs for treatment. , 2012.
    1. Trentacosti AM, He R, Burke LB, et al. Evolution of clinical trials for irritable bowel syndrome: issues in end points and study design. Am J Gastroenterol 2010; 105: 731–735.
    1. Lasch K, Delgado-Herrera L, Kothari S, et al. The irritable bowel syndrome-diarrhea (IBS-D) daily symptom diary and event log: a newly developed patient-reported outcome (PRO) measure. Gastroenterology 2011; 140: 612.
    1. Marquis P, Lasch KE, Delgado-Herrera L, et al. Qualitative development of a patient-reported outcome symptom measure in diarrhea-predominant irritable bowel syndrome. Clin Transl Gastroenterol 2014; 5: e59.
    1. Rosa K, Delgado-Herrera L, Zeiher B, et al. Psychometric assessment of the IBS-D daily symptom diary and symptom event log. Qual Life Res 2016; 25: 3197–3208.
    1. Lasch K, Delgado-Herrera L, Tesler Waldman L, et al. Development of a new instrument to assess stool form and consistency in irritable bowel syndrome with diarrhea. Gastroenterol Hepatol 2016; 4: 00084.
    1. Lexicon Pharmaceuticals I. Lexicon completes phase 2 study of LX1033 in IBS-D 2014, .
    1. Lewis SJ, Heaton KW. Stool form scale as a useful guide to intestinal transit time. Scand J Gastroenterol 1997; 32: 920–924.
    1. Hays RD, Anderson R, Revicki DA. Quality of life assessment. In: Staquet M, Hays RD, Fayers PM. (eds) Clinical trials methods and practice. New York: Oxford University Press, 1998.
    1. Hays RD, Farivar SS, Liu H. Approaches and recommendations for estimating minimally important differences for health-related quality of life measures. COPD 2005; 2: 63–67.
    1. Turner D, Schunemann HJ, Griffith LE, et al. The minimal detectable change cannot reliably replace the minimal important difference. J Clin Epidemiol 2010; 63: 28–36.
    1. Thompson B. Exploratory and confirmatory factor analysis: understanding concepts and applications. Washington, DC: American Psychological Association, 2004.
    1. Francis CY, Morris J, Whorwell PJ. The irritable bowel severity scoring system: a simple method of monitoring irritable bowel syndrome and its progress. Aliment Pharmacol Ther 1997; 11: 395–402.
    1. Mujagic Z, Leue C, Vork L, et al. The experience sampling method – a new digital tool for momentary symptom assessment in IBS: an exploratory study. Neurogastroenterol Motil 2015; 27: 1295–1302.

Source: PubMed

Sponsorer och medarbetare

Medicinska tillstånd

Läkemedelsinterventioner

3
Prenumerera