Development of a core outcome set for clinical trials in childhood constipation: a study using a Delphi technique

Abstract

ObjectivePatients, their parents and healthcare professionals (HCPs) have a different perception regarding the symptoms of functional constipation (FC). Consequently, a lack of agreement exists on definitions and outcomes used in therapeutic trials of FC. Therefore, our aim was to develop a core outcome set (COS) for FC for children aged 0–1 year and 1–18 years.Design and settingProspective study design: primary, secondary and tertiary care settings.MethodsThis COS was developed using a Delphi technique. First, HCPs, parents of children with FC and patients aged ≥12–18 years were asked to list up to five outcomes they considered relevant in the treatment of FC. Outcomes mentioned by >10% of participants were included in a shortlist. In the next phase, outcomes on this shortlist were rated and prioritised by HCPs, parents and patients. Outcomes with the highest scores were included in a draft COS. In a face-to-face expert meeting, the final COS was determined.ResultsThe first phase was completed by 109 HCPs, 165 parents and 50 children. Fifty HCPs, 80 parents and 50 children completed the subsequent phase. The response rate was between 63% and 100% in both steps. The final COS for all ages consisted of: defecation frequency, stool consistency, painful defecation, quality of life, side effects of treatment, faecal incontinence, abdominal pain and school attendance.ConclusionThe use of this COS for FC will decrease study heterogeneity and improve comparability of studies. Therefore, researchers are recommended to use this COS in future therapeutic trials on childhood FC.

Recommendations for pharmacological clinical trials in children with functional constipation: The Rome foundation pediatric subcommittee on clinical trials

“…Children who receive laxatives may have an increased number of bowel movements, but may still have hard stools, painful defecation, abdominal pain, and episodes of fecal incontinence. Thus, considering an increase in bowel movements alone to be representative of a successful treatment, is too simplistic as it does not include some of the most bothersome symptoms for the child and family . In contrast to clinical trials in adults with FC, the use of number of spontaneous bowel movements as primary efficacy endpoint has resulted in negative clinical trials in children.…”

“…Thus, considering an increase in bowel movements alone to be representative of a successful treatment, is too simplistic as it does not include some of the most bothersome symptoms for the child and family. 26 In contrast to clinical trials in adults with FC, the use of number of spontaneous bowel movements as primary efficacy endpoint has resulted in negative clinical trials in children. A pediatric clinical trial on a novel serotonergic agent that used a combination of ≥3 bowel movements weekly and ≤1 episode of fecal incontinence per 2 weeks as primary efficacy endpoints did not show a beneficial effect compared with placebo while the trial was positive when conducted in adult subjects.…”

“…Secondary endpoints of interest include: separate items of the Rome IV criteria, abdominal pain, quality of life, side-effects, and school absence. Recently, Kuizenga-Wessel et al have published acore outcome set to be used in trials on childhood FC 26. This core outcome set was developed using a Delphi questionnaire; healthcare providers, parents and children with FC were asked to list outcomes they considered relevant.…”

Proposals to Approximate the Pediatric Rome Constipation Criteria to Everyday Practice

“…Various studies indicate that one item, instead of two, should suffice for an early diagnosis: -in a cohort study from birth up to 4 years, scybalous stools, hard stools and/or difficult evacuation were by far the most frequent constipation signs, whereas <3 stools/week occurred in only 2.5% and 5.5% at 24 and 48 months respectively, and only 0.7% of 4 years old children off diapers presented 'feces in clothing' (35) ; -by the Boston criteria (36) , which consider only one item for diagnosis, 22.2% of 303 infants in three community Health Centers presented FC, whereas this would have been diagnosed in only 2.6% of them by the Rome III criteria (37) ; -Malowitz et al (32) used Rome III as the inclusion criteria, but in the discussion they stated 'there is a need for programs for primary care clinicians to educate them on recognizing and treating functional constipation according to published guidelines', to say, delay or difficulty in defecation for ≥2 weeks sufficient to cause significant distress in the patient (38) ; -only 12.8% of children seen as outpatients in a secondary-level hospital, with fecal impaction at the rectal exam, presented one additional Rome III criterion (33) ; -in a recent core outcome set for clinical trials in childhood FC, defecation frequency was less often mentioned as the most important treatment outcome by parents and patients than by healthcare professionals, and 'impression of fecal retention' and 'stools that obstruct the toilet' were almost not mentioned (39) .…”

Heterogeneous outcome reporting in adult slow‐transit constipation studies: Systematic review towards a core outcome set

“…Databases of the International Consortium for Health Outcomes Measurement and Core Outcome Measures in Effectiveness Trials provide only one constipation‐related COS for clinical trials in childhood constipation (0–18 years) . This COS, however, does not specifically focus on STC as a subtype of functional constipation and focuses on outcome assessment in children and adolescents.…”