Symptom measurement in pediatric chronic idiopathic constipation (CIC) and irritable bowel syndrome with constipation (IBS-C) trials requires appropriately developed clinical outcome assessments (COAs).
Literature was reviewed to identify symptom COAs meeting regulatory standards. Searches were conducted in Pubmed/Medline, EMBASE, and PsychINFO. Title/abstracts were reviewed to identify qualitative studies and those using COAs to measure pediatric CIC/IBS symptoms. Pediatric functional gastrointestinal experts provided input on relevant symptom-concepts to measure.
Review of 1,105 abstracts identified 1 relevant qualitative article and 113 articles including COAs. Symptoms most frequently measured in CIC studies were frequency of bowel movements, fecal incontinence/encopresis, abdominal pain, stool consistency, and painful defecation. Symptoms most frequently measured in IBS were abdominal pain, abdominal distention/bloating, stool consistency, frequency of bowel movements, and gas. Evidence of development/validity of COAs was limited. Expert feedback was broadly consistent with the literature.
Findings demonstrate consistency in the literature on key CIC/IBS symptoms to measure in pediatric trials, but existing COAs do not meet regulatory standards.
This is a preview of subscription content, access via your institution.
Buy single article
Instant access to the full article PDF.
Tax calculation will be finalised during checkout.
Van den Berg MM, Benninga MA, Di Lorenzo C. Epidemiology of childhood constipation: a systematic review. Am J Gastroenterol. 2006;101(10):2401–9.
Hyman PE, Milla PJ, Benninga MA, Davidson GP, Fleisher DF, Taminiau J. Childhood functional gastrointestinal disorders: neonate/toddler. Gastroenterology. 2006;130(5):1519–26.
Hyams JS, Burke G, Davis PM, Rzepski B, Andrulonis PA. Abdominal pain and irritable bowel syndrome in adolescents: a community-based study. J Pediatr. 1996;129(2):220–6.
van den Berg MM, van Rossum CH, de Lorijn F, Reitsma JB, Di Lorenzo C, Benninga MA. Functional constipation in infants: a follow-up study. J Pediatr. 2005;147(5):700–4.
Loening-Baucke V, Miele E, Staiano A. Fiber (glucomannan) is beneficial in the treatment of childhood constipation. Pediatrics. 2004;113(3 Pt 1):e259–64.
Liem O, Mousa H, Benninga M, Di L. Tegaserod use in children: a single-center experience. J Pediatr Gastroenterol Nutr. 2008;46(1):54–8.
Rasquin A, Di Lorenzo C, Forbes D, et al. Childhood functional gastrointestinal disorders: child/adolescent. Gastroenterology. 2006;130(5):1527–37.
Khoshoo V, Armstead C, Landry L. Effect of a laxative with and without tegaserod in adolescents with constipation predominant irritable bowel syndrome. Aliment Pharmacol Ther. 2006;23(1):191–6.
Hyams JS, Treem WR, Justinich CJ, Davis P, Shoup M, Burke G. Characterization of symptoms in children with recurrent abdominal pain: resemblance to irritable bowel syndrome. J Pediatr Gastroenterol Nutr. 1995;20(2):209–14.
FDA. Clinical Outcome Assessment (COA): glossary of terms, 2013. http://www.fda.gov/Drugs/DevelopmentApprovalProcess/DrugDevelopmentToolsQualificationProgram/ucm370262.htm#pro.
FDA Guidance for Industry: Patient-reported outcome measures: use in medical product development to support labeling claims. 2009.
Leidy NK, Vernon M. Perspectives on patient-reported outcomes: content validity and qualitative research in a changing clinical trial environment. PharmacoEconomics. 2008;26(5):363–70.
Reeve BB, Wyrwich KW, Wu AW, et al. ISOQOL recommends minimum standards for patient-reported outcome measures used in patient-centered outcomes and comparative effectiveness research. Qual Life Res. 2013;22(8):1889–905.
Walker L, Sorrells S. Brief report: assessment of children’s gastrointestinal symptoms for clinical trials. J Pediatr Psychol. 2002;27(3):303–7.
Matza LS, Patrick DL, Riley AW, et al. Pediatric patient-reported outcome instruments for research to support medical product labeling: report of the ISPOR PRO good research practices for the assessment of children and adolescents task force. Value Health. 2013;16(4):461–79.
EMEA. Reflection paper on the regulatory guidance for the use of health-related quality of life (HRQL) measures in the evaluation of medical products. 2005; http://www.emea.europa.eu. Accessed 27 Sept 2011.
Blum N, Taubman B, Nemeth N. During toilet training, constipation occurs before stool toileting refusal. Pediatrics. 2004;113(6):e520.
Chao H, Vandenplas Y. Therapeutic effect of Novalac-IT in infants with constipation. Nutrition (Burbank Los Angeles County Calif). 2007;23(6):469–73.
Bahar R, Collins B, Steinmetz B, Ament M. Double-blind placebo-controlled trial of amitriptyline for the treatment of irritable bowel syndrome in adolescents. J Pediatr. 2008;152(5):685–9.
Claar R, Walker L, Smith C. Functional disability in adolescents and young adults with symptoms of irritable bowel syndrome: the role of academic, social, and athletic competence. J Pediatr Psychol. 1999;24(3):271–80.
Kuttner L, Chambers C, Hardial J, Israel D, Jacobson K, Evans K. A randomized trial of yoga for adolescents with irritable bowel syndrome. Pain Res Manag. 2006;11(4):217–23.
Chitkara D, Bredenoord A, Cremonini F, et al. The role of pelvic floor dysfunction and slow colonic transit in adolescents with refractory constipation. Am J Gastroenterol. 2004;99(8):1579–84.
Thomson S, Dancey CP. Symptoms of irritable bowel in school children: prevalence and psychosocial effects. J Pediatr Health Care. 1996;10(6):280–5.
Endo Y, Shoji T, Fukudo S, et al. The features of adolescent irritable bowel syndrome in Japan. J Gastroenterol Hepatol. 2011;26(Suppl 3):106–9.
Endo Y, Shoji T, Tamura D, Sato Y, Machida T, Fukudo S. Abdominal symptoms are changeable in adolescent irritable bowel syndrome: two-year follow up study. Psychother Psychosom. 2013;82:27–8.
Rajindrajith S, Devanarayana NM. Subtypes and symptomatology of irritable bowel syndrome in children and adolescents: a school-based survey using Rome III criteria. J Neurogastroenterol Motil. 2012;18(3):298–304.
Kalani A, Griem A, Crebassa L, et al. A simple intervention program markedly decreases resource utilization for adolescents with irritable bowel syndrome (IBS). Am J Gastroenterol. 2012;107:S700–1.
Scarpellini E, Giorgio V, Gabrielli M, et al. Rifaximin treatment for small intestinal bacterial overgrowth in children with irritable bowel syndrome: a preliminary study. Eur Rev Med Pharmacol Sci. 2013;17(10):1314–20.
Varni J, Lane M, Burwinkle T, et al. Health-related quality of life in pediatric patients with irritable bowel syndrome: a comparative analysis. J Dev Behav Pediatr. 2006;27(6):451–8.
Di Nardo G, Barbara G, Cucchiara S, et al. Neuroimmune interactions at different intestinal sites are related to abdominal pain symptoms in children with IBS. Neurogastroenterol Motil. 2014;26(2):196–204.
Giannetti E, Turco R, Miele E, et al. Prospective observational study on the prevalence of subtypes of irritable bowel syndrome in children at diagnosis and changes of these subtypes at follow-up. Dig Liver Dis. 2012;44:S128–9.
Isoldi S, Di Nardo G, Barbara G, et al. Neuroimmune interactions at different intestinal sites are related to abdominal pain symptoms in children with IBS. Dig Liver Dis. 2013;45:e270.
Chumpitazi BP, Weidler EM, Shulman RJ. Adolescent irritable bowel syndrome (IBS) represents a unique subset of childhood IBS. Gastroenterology. 2012;142(5):S-382. doi:10.1016/S0016-5085(12)61447-4.
Di Nardo G, Barbara G, Oliva S, et al. Efficacy and tolerability of alpha-galactosidase on gas related symptoms in pediatric irritable bowel syndrome. A randomized, double-blind, placebo controlled trial. Dig Liver Dis. 2011;43:S412.
Guandalini S, Magazzu G, Chiaro A, et al. VSL#3 improves symptoms in children with irritable bowel syndrome: a multicenter, randomized, placebo-controlled, double-blind, crossover study. J Pediatr Gastroenterol Nutr. 2010;51(1):24–30.
Bonamico M, Culasso F, Colombo C, et al. Irritable bowel syndrome in children: an Italian multicentre study. Ital J Gastroenterol. 1995;27(1):13–20.
Devitt P, Thornley E, Hinks M. An evaluation of an inter-disciplinary constipation clinic for childhood constipation. J Res Nurs. 2007;12(5):539–47.
Caplan A, Walker L, Rasquin A. Development and preliminary validation of the questionnaire on pediatric gastrointestinal symptoms to assess functional gastrointestinal disorders in children and adolescents. J Pediatr Gastroenterol Nutr. 2005;41:296–304.
Dimenas E, Glise H, Hallerback B, Hernqvist H, Svedlund J, Wiklund I. Quality of life in patients with upper gastrointestinal symptoms. An improved evaluation of treatment regimens? Scand J Gastroenterol. 1993;28(8):681–7.
Svedlund J, Sjodin I, Dotevall G. GSRS—a clinical rating scale for gastrointestinal symptoms in patients with irritable bowel syndrome and peptic ulcer disease. Dig Dis Sci. 1988;33(2):129–34.
Clayden GS, Keshtgar AS, Carcarni-Rathwell I, Abhyankar A. The management of chronic constipation and related faecal incontinence in childhood. Arch Dis Child Ed Pract. 2005;90:58–67.
Lakshminarayanan B, Kufeji D, Clayden G. A new ultrasound scoring system for assessing the severity of constipation in children. Pediatr Surg Int. 2008;24(12):1379–84.
Talley NJ, Fett SL, Zinsmeister AR. Self-reported abuse and gastrointestinal disease in outpatients: association with irritable bowel-type symptoms. Am J Gastroenterol. 1995;90(3):366–71.
Talley NJ, Phillips SF, Wiltgen CM, Zinsmeister AR, Melton LJ III. Assessment of functional gastrointestinal disease: the bowel disease questionnaire. Mayo Clin Proc. 1990;65(11):1456–79.
Walker LS, Smith CA, Garber J, Van Slyke DA. Development and validation of the pain response inventory for children. Psychol Assess. 1997;9(4):392.
Voskuijl WP, van der Zaag-Loonen HJ, Ketel IJG, Grootenhuis MA, Derkx BHF, Benninga MA. Health related quality of life in disorders of defecation: the Defecation Disorder List. Arch Dis Child. 2004;89(12):1124–7.
Fichtner F, Sailer M, Höcht B. Development of a new scoring for the evaluation of incontinence and constipation in children. Coloproctology. 2003;25(1):10–5.
Clawson E. Fears in children with chronic constipation: reliability and validity of the Defecation Anxiety Scale. Diss Abstr Int Sect B Sci Eng. 1997;57(9-B):5910.
Cox DJ, Sutphen J, Ling W, Quillian W, Borowitz S. Additive benefits of laxative, toilet training, and biofeedback therapies in the treatment of pediatric encopresis. J Pediatr Psychol. 1996;21(5):659–70.
Cox D, Ritterband L, Quillian W, et al. Assessment of behavioral mechanisms maintaining encopresis: Virginia Encopresis-Constipation Apperception Test. J Pediatr Psychol. 2003;28(6):375–82.
Patrick DL, Drossman DA, Frederick IO, DiCesare J, Puder KL. Quality of life in persons with irritable bowel syndrome: development and validation of a new measure. Dig Dis Sci. 1998;43(2):400–11.
Drossman DA, Patrick DL, Whitehead WE, et al. Further validation of the IBS-QOL: a disease-specific quality-of-life questionnaire. Am J Gastroenterol. 2000;95(4):999–1007.
Eiser C. Psychological effects of chronic disease. J Child Psychol Psychiatry. 1990;31:85–98.
Shinozaki M, Kanazawa M, Sagami Y, et al. Validation of the Japanese version of the Rome II modular questionnaire and irritable bowel syndrome severity index. J Gastroenterol. 2006;41(5):491–4.
Ball T, Weydert J. Methodological challenges to treatment trials for recurrent abdominal pain in children. Arch Pediatr Adolesc Med. 2003;157(11):1121–7.
Derogatis LR. SCL-90: an outpatient psychiatric rating scale. Preliminary report. Psychopharmacol Bull. 1974;9:13–28.
Saps M, Sztainberg M, Di L. A prospective community-based study of gastroenterological symptoms in school-age children. J Pediatr Gastroenterol Nutr. 2006;43(4):477–82.
Hicks CL, von Baeyer CL, Spafford PA, van Korlaar I, Goodenough B. The Faces Pain Scale-Revised: toward a common metric in pediatric pain measurement. Pain. 2001;93(2):173–83.
Vogels T, Verrips GHW, Koopman HM, Theunissen NCM, Fekkes M, Kamphuis RP. TACQOL manual. Parent and child form. 2000.
Faleiros F, Machado N. Assessment of health-related quality of life in children with functional defecation disorders. J Pediatr. 2006;82(6):421–5.
Varni JW, Seid M, Kurtin PS. PedsQL 4.0: reliability and validity of the Pediatric Quality of Life Inventory version 4.0 generic core scales in healthy and patient populations. Med Care. 2001;39(8):800–12.
Varni JW, Seid M, Rode CA. The PedsQL: measurement model for the pediatric quality of life inventory. Med Care. 1999;37(2):126–39.
Roblin N. Assessment of the effectiveness of paediatric psychoeducational programs on family functioning. Diss Abstr Int Sect A Humanit Soc Sci. 2000;60(8-A):2820.
Achenbach TM. Child behavior checklist/4-18. 1991.
Aksnes G, Diseth T, Helseth A, et al. Appendicostomy for antegrade enema: effects on somatic and psychosocial functioning in children with myelomeningocele. Pediatrics. 2002;109(3):484–9.
Seligman LD, Ollendick TH, Langley AK, Baldacci HB. The utility of measures of child and adolescent anxiety: a meta-analytic review of the revised children’s manifest anxiety scale, the state-trait anxiety inventory for children, and the child behavior checklist. J Clin Child Adolesc Psychol. 2004;33(3):557–65.
Goodman R. The Strengths and Difficulties Questionnaire: a research note. J Child Psychol Psychiatry. 1997;38(5):581–6.
March JS, Sullivan K. Test-retest reliability of the Multidimensional Anxiety Scale for Children. J Anxiety Disord. 1999;13(4):349–58.
Walker LS, Greene JW. The functional disability inventory: measuring a neglected dimension of child health status. J Pediatr Psychol. 1991;16(1):39–58.
Muller-Lissner S, Koch G, Talley NJ, et al. Subject’s Global Assessment of Relief: an appropriate method to assess the impact of treatment on irritable bowel syndrome-related symptoms in clinical trials. J Clin Epidemiol. 2003;56(4):310–6.
Sakano Y. Verification of validity of General Self-Efficacy Scale (GSES). Waseda J Hum Sci. 1989;2:91–8.
Ware JE Jr, Sherbourne CD. The MOS 36-item short-form health survey (SF-36). I. Conceptual framework and item selection. Med Care. 1992;30(6):473–83.
Ravens-Sieberer U, Bullinger M. Assessing health-related quality of life in chronically ill children with the German KINDL: first psychometric and content analytical results. Qual Life Res. 1998;7(5):399–407.
Ravens-Sieberer U, Gosch A, Rajmil L, et al. KIDSCREEN-52 quality-of-life measure for children and adolescents. Expert Rev Pharmacoecon Outcomes Res. 2005;5(3):353–64.
Bausserman M, Michail S. The use of Lactobacillus GG in irritable bowel syndrome in children: a double-blind randomized control trial. J Pediatr. 2005;147(2):197–201.
Castilloux J, Noble A, Faure C. Is visceral hypersensitivity correlated with symptom severity in children with functional gastrointestinal disorders? J Pediatr Gastroenterol Nutr. 2008;46(3):272–8.
Caplan A, Walker L, Rasquin A. Validation of the pediatric Rome II criteria for functional gastrointestinal disorders using the questionnaire on pediatric gastrointestinal symptoms. J Pediatr Gastroenterol Nutr. 2005;41(3):305–16.
Ravens-Sieberer U, Herdman M, Devine J, et al. The European KIDSCREEN approach to measure quality of life and well-being in children: development, current application, and future advances. Qual Life Res. 2014;23(3):791–803.
Bieri D, Reeve RA, Champion GD, Addicoat L, Ziegler JB. The Faces Pain Scale for the self-assessment of the severity of pain experienced by children: development, initial validation, and preliminary investigation for ratio scale properties. Pain. 1990;41(2):139–50.
Arbuckle R, Abetz-Webb L. “Not just little adults”: qualitative methods to support the development of pediatric patient-reported outcomes. Patient. 2013;6(3):143–59.
The authors thank the following expert physicians who participated and shared their views in the Expert Advisory Meeting reported in this article: Warren P. Bishop, Carlo Di Lorenzo, Jeffrey S. Hyams, Paul Hyman, Anthony Lembo, Adrian Miranda, and Miguel Saps.
Disclosure of financial arrangements
This research was funded by Forest Research Institute and Ironwood Pharmaceuticals.
Conflict of interest
Robert Arbuckle, Linda Abetz-Webb, and Elizabeth Gargon are employees of Adelphi Values (or were employees at the time the research was conducted), a health outcomes agency contracted by Forest Research Institute and Ironwood Pharmaceuticals to perform the research. Robyn Carson and Steven Shiff are employees of Forest Research Institute. Barbara Lewis, Caroline Kurtz, and Jeffrey Johnston are employees of Ironwood Pharmaceuticals (or were employees at the time the research was conducted). Jeffrey Hyams and Carlo Di Lorenzo were independent consultants contracted by Forest Research Institute and Ironwood Pharmaceuticals for their participation in the research.
Robert Arbuckle, Linda Abetz-Webb, and Elizabeth Gargon contributed to the study design, performed the literature review, and prepared the first draft of the manuscript. Robyn Carson, Jeffrey Hyams, Carlo Di Lorenzo, Barbara Lewis, Caroline Kurtz, Steven Shiff, and Jeffrey Johnston contributed to the design of the study, provided strategic input into the literature review, and reviewed and approved the manuscript. Rob Arbuckle acts as the overall guarantor for this manuscript.
About this article
Cite this article
Arbuckle, R.A., Carson, R.T., Abetz-Webb, L. et al. Measuring the Symptoms of Pediatric Constipation and Irritable Bowel Syndrome with Constipation: Expert Commentary and Literature Review. Patient 7, 343–364 (2014). https://doi.org/10.1007/s40271-014-0070-3
- Irritable Bowel Syndrome
- Patient Report Outcome
- Bowel Movement
- Irritable Bowel Syndrome Patient
- Stool Consistency