Functional defecation disorders in children: Associated comorbidity and advances in management - Chapter 6: Development of a core outcome set for clinical trials in childhood constipation

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Functional defecation disorders in children

Associated comorbidity and advances in management Kuizenga-Wessel, S. Publication date 2017 Document Version Other version License Other Link to publication

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Kuizenga-Wessel, S. (2017). Functional defecation disorders in children: Associated comorbidity and advances in management.

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Chapt%r

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DEVELOPMENT OF

A CORE OUTCOME SET

FOR CLINICAL TRIALS

IN CHILDHOOD

CONSTIPATION

H. Szajewska, M.M. Tabbers

ABSTRACT

Objective

Patients, their parents and healthcare professionals (HCPs) have a different perception regarding the symptoms of functional constipation (FC). Conse-quently, a lack of agreement exists on definitions and outcomes used in thera-peutic trials of FC. Therefore our aim was to develop a core outcome set (COS) for FC for children 0-1 and 1-18 years.

Methods

This COS was developed using a Delphi technique. As first step, HCPs, parents of children with FC and patients aged ≥12-18 years were asked to list up to 5 outcomes they considered relevant in the treatment of FC. Outcomes mentioned by >10% of participants were included in a shortlist. In the next step, outcomes on this shortlist were rated and prioritized 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.

Results

The first step was completed by 109 HCPs, 165 parents and 50 children. Fifty HCPs, 80 parents and 50 children completed the subsequent step. 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, fecal incontinence, abdominal pain and school attendance.

Conclusion

The use of a 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.

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INTRODUCTION

Functional constipation (FC) is a common problem consisting of infrequent, painful and hard defecation. The pathophysiology of FC is not well under-stood yet. In approximately 95% of children with constipation, no organic or anatomic cause can be identified, and therefore these patients are consid-ered to have FC. The worldwide prevalence of FC in childhood varies widely ranging from 0.7-29.6%.1

Although standard definitions and criteria for FC have been formulated, these are rarely used in research and clinical practice.2 _{In 1999, the first}

diag-nostic criteria for various functional gastrointestinal disorders in children were published: the Rome II criteria. Several studies showed, however, that the Rome II criteria were too restrictive, and were therefore modified into the Rome III criteria in 2006, and recently into the Rome IV criteria.3–6

Differences in outcome measurement across clinical trials and inconsistencies in how outcomes are defined and reported make it difficult to pool results of studies. Moreover, negative results are less likely to be reported, which can cause bias.7 _{These inconsistencies and bias could be tackled by the}

devel-opment of agreed standardized sets of outcomes, known as core outcome sets (COS). COS should be measured and reported as a minimum in all trials for a specific clinical area.8,9 _{Each COS serves as a guide for what should}

be collected and reported, but the measured outcomes do not need to be restricted to the outcomes in the COS. Consequently, researchers can examine other outcomes that might be of interest for their research.10

If a COS leads to improvements in healthcare and increases consensus about the efficacy of an intervention, it needs to contain outcomes that really matter to the stakeholders. In order to avoid overlooking outcomes, it is important to involve healthcare professionals (HCPs), parents and patients with FC in the development of the COS. Especially since literature has shown that parents of children with FC have different concerns regarding the symptoms of their child compared to HCPs11_.

In the last couple of years, COS have been employed in several pediatric fields. Karas et al.12 _{developed a COS for clinical trials in children with acute}

diarrhea and Steutel et al.13 _{developed a COS for infant colic. Both studies}

used the Delphi technique to identify clinically important outcomes for HCPs and parents. Sinha et al. also involved patients ≥12 years in this process.14

This work, was part of a larger consensus group on Outcome Measures Made in Pediatric Enteral Nutrition Clinical Trials (COMMENT), an initiative of the European Society for Pediatric Gastroenterology Hepatology and Nutrition (ESPGHAN). COMMENT agreed that consensus on a core set of

outcomes, including those related to constipation, was needed. Therefore the aim of this study is to develop a COS for clinical trials in children with FC, by involving HCPs, parents and patients.

METHODS

The methods for the development of the COS for childhood FC was based on previous publications.12–14

STEP 1 REPORTING OUTCOME MEASURES IN TRIALS OF FC

We systematically assessed how definitions and outcome measures were defined in therapeutic randomized controlled trials (RCTs) of children with FC. These results were published in 2 manuscripts; one article concerning RCTs in children ≤4 years 2 _{and the other in children aged 1-18 years.}15

STEP 2 COLLECTING IMPORTANT TREATMENT OUTCOMES

HCPs

A survey was conducted among HCPs visiting two international pediatric gastroenterology conferences. Participants were asked to list up to five harmful and/or beneficial treatment outcomes, which they considered important and which guided their clinical decision making in outpatient and inpatient settings, as outcome measures could differ in these clinical settings. Data regarding country of practice and profession were collected.

Parents

We aimed to include 160 parents in four countries (Belgium, Italy, Poland and the Netherlands). Parents were randomly approached by their child’s treating physician to participate in this anonymous survey. Parents were asked to list up to five aspects of treatment that made them feel comfortable or gave them the feeling their child was being treated adequately. As outcomes could differ, they were also asked to list up to five aspects of treatment that made them feel uncomfortable or gave them the feeling their child was being treated inadequately. Survey questions were translated into the native language of the parents and answers were carefully translated back to English by their HCP. Patients ≥12 years

We also assessed which aspects of treatment were relevant to FC patients ≥ 12 years.14 _{As an anonymous pilot study, we aimed to include 50 adolescent}

C O S f or F C 6

patients at the pediatric gastroenterology outpatient clinic of the Emma dren’s Hospital/Academic Medical Hospital, Amsterdam, the Netherlands. Chil-dren were randomly invited by their doctor and the questions from the parental survey were adjusted for this population.

STEP 3A CREATING A SHORTLIST

Reported outcomes were classified in predefined domains based on our find-ings of Step 1 (defecation, associated symptoms, use of medication, treatment success, quality of life (QoL) and hospital)2,15_{. In order to create a shortlist,}

reported outcomes were grouped and outcome measures mentioned by at least 10% of the participants were included. Ten separate shortlists were created: four for HCPs (outpatient and inpatient, for both age groups), four for parents of children with FC (comfortable and uncomfortable, for both age groups) and two for children ≥ 12 years with FC (comfortable and uncomfortable).

STEP 3B RATING THE OUTCOMES ON THE SHORTLIST

Shortlists for HCPs were sent to HCPs that previously agreed to participate in this phase. They were asked to rate the clinical relevance of every outcome on a scale of 0–4 (0= not relevant, 4= very relevant) and to prioritize the outcomes by selecting five outcome measures they thought to be most important in guiding their clinical decision making.

A new group of parents of patients with FC were invited to participate in this phase. The same countries participated in this step. They received the short-list for parental and patient outcomes and were asked to rank the outcome measures on a scale of 0–4 (0= does not make me feel (un)comfortable, 4= makes me feel very (un)comfortable) and to prioritize them by selecting the five outcome measures that made them feel most (un)comfortable. Surveys were returned anonymously. Based on previous literature concerning COS develop-ment, we aimed to include 80 parents and 50 patients.12,14

STEP 3C CREATING THE TOP 5 OUTCOMES

Subsequently, a “Top 5” was created for all groups, by selecting the five outcomes with the highest ranks. This resulted in preliminary outcome sets for HCPs, parents and children, for both age groups.

STEP 3D CREATING THE FINAL COS

After combining the preliminary outcome sets for each age group, a draft COS was presented to an expert panel during the meeting of the Outcome Measures Made in Paediatric Enteral Nutrition Clinical Trials (COMMENT) Working Group

in Athens of the European Society for Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN), Greece (2016) where consensus regarding the final COS was reached.

RESULTS

STEP 1 REPORTING ON OUTCOME MEASURES IN TRIALS OF FC

SRs evaluating the efficacy of interventions in childhood FC showed a lack of agreement about definitions, primary outcome measures, and instruments to measure these outcomes.2,15

STEP 2 COLLECTING IMPORTANT TREATMENT OUTCOMES

HCPs

109 of 143 (76%) HCPs completed the first questionnaire (Figure 1). They orig-inated from 28 countries and included 52 pediatric gastroenterologists, 24 general pediatricians, 17 fellows, 4 residents in pediatrics, 4 pediatric nutrition-ists, 3 researchers, 3 not specified, 1 intern and 1 general doctor (Attachment 1). Outcomes that were reported most frequently are summarized in Table 1. Infants 0-1 years

For the outpatient and inpatient setting respectively, 89 and 74 different outcomes were reported.

Children 1-18 years

For the outpatient and inpatient setting, respectively 76 and 72 different outcomes were reported. See Attachment 2 for an example of the reported outcomes in this step. The other tables with reported outcome measures of Step 2 are available from the authors.

Parents

165 parents (100%) of children with FC (according to the Rome III criteria) completed the first questionnaire (Figure 1). See Table 1 for the outcomes that were reported most frequently.

Infants 0-1 years

In total, 28 treatment outcomes were reported that made parents feel comfort-able and 26 outcomes that made them feel uncomfortcomfort-able .

C O S f or F C 6 Figure 1 titel ST EP 2 outpatient setting inpatient setting rating shortlist outpatient To p 5 outpatient rating shortlist inpatient Top 5 inpatient Preliminary CO S HC P 0-1 years D ra ft CO S 0-1 years comfortab le uncomfortable n/a n/a To p 5 comfortab le To p 5 uncomfortable Preliminary CO S parents 0 -1 ye ars outpatient setting rating shortlist outpatient To p 5 outpatient inpatient setting rating shortlist inpatient To p 5 inpatient Preliminary CO S HC P 1-18 years D ra ft CO S 1-18 years comfortab le uncomfortable rating shortlist comfortab le rating shortlist uncomfortable To p 5 comfortab le To p 5 uncomfortable Pre lim ina ry CO S parents 1 -18 ye ar s comfortab le uncomfortable rating shortlist comfortab le rating shortlist uncomfortable To p 5 comfortab le To p 5 uncomfortable Pre lim ina ry CO S patients ≥ 12 ye ars Fina l CO S 0-18 years HCPs 0-1 years _{143 approached} completed by 109 (76%)

Parents 0-1 years 77 approached

completed by 77 (100%)

HCPs 1-18 years 143 approached

completed by 109 (76%)

Parents 1-18 years 88 approached

completed by 88 (100%) Patients ≥ 12 years 50 approached completed by 50 (100%) shortlist _outpatient shortlist inpatient shortlist comfortab le shortlist uncomfortable shortlist _outpatient shortlist inpatient shortlist comfortab le shortlist uncomfortable shortlist comfortab le shortlist uncomfortable 80 approached compl et ed by 50 (63% ) n/a 80 approached compl et ed by 50 (63% ) 80 approached compl et ed by 80 (100%) 50 approached compl et ed by 50 (100%) ST EP 2 ST EP 2 ST EP 2 ST EP 2 ST EP 2 ST EP 2 ST EP 2 ST EP 2 ST EP 2 ST EP 3A ST EP 3A ST EP 3A ST EP 3A ST EP 3A ST EP 3A ST EP 3B ST EP 3B ST EP 3B ST EP 3B ST EP 3B ST EP 3B ST EP 3A ST EP 3A ST EP 3B ST EP 3B ST EP 3B ST EP 3B ST EP 3B ST EP 3B ST EP 3C ST EP 3C ST EP 3C ST EP 3C ST EP 3C ST EP 3C ST EP 3C ST EP 3C ST EP 3C ST EP 3C

Children 1-18 years

In total, 52 treatment outcomes were reported that made parents feel comfort-able and 45 outcomes that made them feel uncomfortcomfort-able.

Patients ≥ 12 years

Fifty children ≥ 12 years (mean age 14.8 years; response rate 100%) completed the first questionnaire (Figure 1). Patients reported 21 outcomes that made them feel comfortable and 22 that made them feel uncomfortable (Table 1).

STEP 3 CREATING A SHORTLIST AND FINAL CORE OUTCOME SET

HCPS

Fifty of 80 HCPs (63%) completed the second questionnaire regarding the rating and prioritizing of the outcomes on the shortlist. This resulted in four “Top 5” lists: an outpatient and inpatient shortlist for both age groups (Attachment 3). Since outcomes for the outpatient and inpatient setting were rather similar, we were able to combine these “Top 5” lists into one preliminary outcome set per age group (Figure 1).

Parents

In Step 2, only 5 outcome measures were mentioned by >10% of the parents of infants 0-1 years. Since it was our goal to create a “Top 5 ”list, it was not necessary to approach parents of infants 0-1 years for Step 3, as the rating and prioritizing would not affect the “Top 5” list. The two “Top 5” lists for infants 0-1 years old are therefore identical to the outcomes from Step 2 (Figure 1). For this reason, only parents of children 1-18 years old were approached in this step. All 80 parents of children 1-18 years (100%) completed Step 3. Attachment 4 shows the shortlists that were rated and prioritized by the parents. Since outcomes that made parents feel comfortable and uncomfortable were rather similar within the age group, we were able to combine these “Top 5” lists into one preliminary outcome set per age group.

Patients ≥ 12 years

Shortlists that were developed based on outcomes mentioned in Step 2, were rated and prioritized by 50 patients (mean age 13.8 years; response rate 100%) (Attachment 5). Outcomes that made patients feel comfortable and uncomfort-able were rather similar and we were therefore uncomfort-able to combine these “Top 5” lists into one preliminary outcome set (Figure 1).

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Table 1 Outcomes most often reported in Step 2

Infants 0-1

HCP Outpatient setting Inpatient setting - defecation frequency (51%) - abdominal pain (32%) - stool consistency (30%) - defecation frequency (46%) - stool consistency (28%) - abdominal pain (20%)

Parents Comfortable Uncomfortable

- stool consistency (39%) - defecation frequency (38%) - crying (17%) - stool consistency (56%) - straining (38%) - defecation frequency (34%) Children 1-18 years

HCP Outpatient setting Inpatient setting - defecation frequency (55%) - abdominal pain (39%) - stool consistency (30%) - defecation frequency (46%) - abdominal pain (27%) - stool consistency (26%)

Parents Comfortable Uncomfortable

- defecation frequency (41%) - abdominal pain (39%) - stool consistency (25%) - abdominal pain (40%) - fecal incontinence (25%) - defecation frequency (25%)

Patients Comfortable Uncomfortable

- abdominal pain (66%) - defecation frequency (40%) - fecal incontinence (32%) - abdominal pain (58%) - defecation frequency (35%) - fecal incontinence (28%)

STEP 3 CREATING THE FINAL COS

The preliminary COS of HCPs and parents of children 0-1 years old were comparable. We therefore combined the preliminary COS of these groups into the following draft COS: defecation frequency, stool consistency, painful defe-cation, discomfort, crying, abdominal pain, treatment success, straining and QoL of parents.

We repeated this process for children 1-18 years but added the outcomes mentioned by patients aged ≥12 years. The preliminary COS of HCPs, parents and patients appeared to be comparable as well, except for the following outcomes: “abdominal pain” (mentioned by parents and patients), “treatment success” (parents) and “school attendance” (patients). We combined outcomes into the following draft COS: defecation frequency, stool consistency, painful defecation, QoL (child and parents), fecal incontinence, abdominal pain, school attendance and treatment success.

The draft COS for both age groups was presented in a COMET Working Group meeting. Regarding the COS for 0-1 years, there was an unanimous deci-sion to exclude “discomfort”, “abdominal pain” and “crying” in the final COS, since these outcomes are nonspecific and cannot with certainty be attributed to FC or to the effect of treatment. In addition, it was decided to exclude “straining”, since “painful defecation” was already included in the COS. “Treat-ment success” was not included as it is assumed to be a combination of the included outcome measures.

Regarding the COS for 1-18 years, it was unanimously decided to add two outcome measures mentioned by parents and/or patients: “abdominal pain” and “school attendance”. Again, “treatment success” was not included as it is a combination of the included outcome measures.

Since the applicability of a treatment depends on a balance between benefits and side-effects, it is recommended to always assess “side-effects” as part of the COS.16 _{Although “side-effects” were mentioned by <10% of the respondents, we}

added this outcome to the final COS. The COS for infants 0-1 years therefore consists of: defecation frequency, stool consistency, painful defecation, QoL of the parents and side-effects. The COS for children 1-18 years includes: defecation frequency, stool consistency, painful defecation, QoL of patients and parents, fecal incontinence, abdominal pain, school attendance and side-effects.

For practical reasons, we decided to combine these into one final COS for all children aged 0-18 years: defecation frequency, stool consistency, painful defe-cation, QoL of parents and patients, side effects, and if age-appropriate: fecal incontinence, abdominal pain, and school attendance (Table 2).

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Table 2 Final core outcome set for functional constipation

Core outcome set for children (0-18 years) with functional constipation

Defecation frequency Stool consistency Painful defecation

Quality of life of parents and patients Side-effects

Fecal incontinence, if applicable Abdominal pain, if applicable School attendance, if applicable

DISCUSSION

Using a Delphi technique, in which HCPs, parents and patients ≥12 years were involved, we developed a COS for FC in children 0-18 years old. This COS consists of: defecation frequency, stool consistency, painful defecation, QoL and side-effects. The following outcomes should be added if age-appropriate: fecal incontinence, abdominal pain and school attendance.

As literature has shown before12–14_{, it is feasible and useful to involve HCPs,}

fami-lies and patients in identifying which outcomes are important when making shared decisions about management in clinical practice. In our study, all stake-holders (HCPs, parents and patients) agreed on which outcomes were most important. For both age groups, stakeholders agreed that defecation frequency, stool consistency and painful defecation should be included in the COS. Indeed, infrequent defecation and hard stools, two characteristic features of childhood FC, and included in the Rome IV definition for FC6 _{are often measured in}

clin-ical trials in children with FC.2,15 _{Although there was agreement among}

stake-holders that QoL should be measured in clinical trials, previous SRs have demonstrated that this is relatively infrequently assessed in clinical trials in FC.2,15

As these outcomes are considered relevant as mentioned by all involved stake-holders, we recommend that they should be measured in future trials as well. A discrepancy between stakeholders was found regarding the importance of having abdominal pain and school attendance. Parents and patients found the

presence or absence of abdominal pain more important than HCPs. Although abdominal pain is not a characteristic feature of FC, and also not included in the Rome IV, FC criteria, it has been reported that 10-70% of children with FC are suffering from abdominal pain and these complaints can have a large impact on the wellbeing of the child.17 _{Since complaints of abdominal pain can}

also result in reduced participation in social activities and school absenteeism, it is explicable that school attendance is mentioned as well as an important outcome by a majority of patients. Therefore, both outcome measures are included in the COS for childhood FC.

As we have explained more detailed in the results section, not all outcomes mentioned by parents or patients were included in the final COS. The Working Group unanimously decided that these outcomes were nonspecific for FC (crying, discomfort) or already included in the COS (straining, treatment success). Although side-effects were mentioned as relevant by a minority, we felt justified to add this outcome measure to the COS16_.

It should be noted that this COS is the basis for what should be measured and reported in clinical trials. As stated by the COMET18_{, the outcomes measured}

in clinical trials do not need to be restricted to the outcomes in the COS. Researchers can add outcome measures pertinent to their trial, but selective reporting should be avoided by presenting the findings for both core outcomes and all additional outcome measures. Furthermore, in order to compare trial results, there is not only a need for consensus regarding outcomes, we also need homogeneity in used definitions of FC. We therefore recommend that the recently published and internationally accepted Rome IV criteria for FC should be used in future trials.6

COS have the potential to improve the evidence base for healthcare, but the creation of a COS does not automatically lead to its implementation and it would therefore be valuable to assess how widely this COS is being imple-mented.

One of the strengths of this study is the high response rate in both Step 2 and 3. In addition, the participation of physicians around the globe, the involvement of parents from four European countries and inclusion of patients increases the applicability of our COS. Some limitations should be taken into account when interpreting our findings. First, our study focused on children whose FC is managed by hospital pediatricians. In some of the participating countries, however, healthcare is organized in such a manner that pediatricians represent

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primary care as well. Data collection from HCPs occurred at two international pediatric gastroenterology conferences. This may have caused bias since these HCPs often treat patients with severe and long-lasting FC, and they could therefore have chosen different outcome measures compared to primary care physicians.

Another potential limitation is the use of questionnaires that were developed in English and thereafter translated in four different languages. Although this was done carefully, it is possible that this resulted in subtle changes in ques-tions or answers. Although the Delphi technique is well suited as a method for consensus-building, it is a time consuming process. Another disadvantage is a potentially high dropout rate, because this method requires active participa-tion throughout the Delphi process.19 _{However, the current response rate was}

between 63 and 100% in both steps. In addition, some responses in Step 2 were somewhat open to interpretation and therefore it is possible that we may have misinterpreted and incorrectly combined some responses in Step 2.

CONCLUSION

In conclusion, we recommend researchers to use this COS for childhood FC (0 – 18 years), which consists of defecation frequency, stool consistency, painful defe-cation, QoL and side-effects. Fecal incontinence, abdominal pain and school attendance should be measured if age-appropriate. The use of this COS will decrease outcome heterogeneity and improve comparability of study results.

Acknowledgements

we would like to thank all HCPs, parents and patients who completed the questionnaires, and J.J. Korterink, M.H. Vriesman and K. Wojtyniak for their help with the recruitment.

REFERENCES

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3 Baker SS, Liptak GS, Colletti RB, et al. Consti-pation in infants and children: evaluation and treatment. A medical position statement of the North American Society for Pediatric Gastroenterology and Nutrition. J Pediatr Gastroenterol Nutr. 1999;29(5):612–26.

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5 Rasquin A, Di Lorenzo C, Forbes D, et al. Childhood functional gastrointestinal disor-ders: child/adolescent. Gastroenterology. 2006;130(5):1527–37.

6 Hyams JS, Di Lorenzo C, Saps M, et al. Func-tional Disorders: Children and Adolescents. Gastroenterology. 2016.

7 Benstoem C, Moza A, Autschbach R, et al. Evaluating outcomes used in cardiothoracic surgery interventional research: a systematic review of reviews to develop a core outcome set. PLoS One. 2015;10(4):e0122204.

8 Wuytack F, Smith V, Clarke M, et al. Towards core outcome set (COS) devel-opment: a follow-up descriptive survey of outcomes in Cochrane reviews. Syst Rev. 2015;4:73.

9 Gargon E, Williamson PR, Clarke M. Collating the knowledge base for core outcome set development: developing and appraising the search strategy for a systematic review. BMC Med Res Methodol. 2015;15:26.

10 Clarke M, Williamson PR. Core outcome sets and systematic reviews. Syst Rev. 2016;5:11.

11 Farrell M, Holmes G, Coldicutt P, et al. Management of childhood constipa-tion: parents’ experiences. J Adv Nurs. 2003;44(5):479–89.

12 Karas J, Ashkenazi S, Guarino A, et al. Devel-oping a core outcome measurement set for clinical trials in acute diarrhoea. Acta Paediatr. 2016;105(4):e176–80.

13 Steutel NF, Benninga MA, Langendam MW, et al. Reporting outcome measures in trials of infant colic. J Pediatr Gastroenterol Nutr. 2014;59(3):341–6.

14 Sinha IP, Gallagher R, Williamson PR, et al. Development of a core outcome set for clin-ical trials in childhood asthma: a survey of clinicians, parents, and young people. Trials. 2012;13:103.

15 Kuizenga-Wessel S, Heckert SL, Tros W, et al. Reporting on Outcome Measures of Func-tional Constipation in Children-A System-atic Review. J Pediatr Gastroenterol Nutr. 2016;62(6):840–6.

16 Boers M, Kirwan JR, Wells G, et al. Devel-oping Core Outcome Measurement Sets for Clinical Trials: OMERACT Filter 2.0. J Clin Epidemiol. 2014;67(7):745–753.

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C O S f or F C 6

Attachment 1 Background of healthcare respondents

Figure A1a Professional background of healthcare respondents (n=109)

Figure A1b Country of practice of healthcare respondents (n=109)

Italy n=18 Israel n=14 UK n=10 Poland n=9 Nederland n=7 Mexico n=4 Turkey n=4 Belgium n=3 Ecuador n=3 Germany n=3 Greece n=3 USA n=2 Czech Rep n=2 New Zealand n=2 Norway n=2 Brazil n=2 Romania n=2 Thailand n=2 Sweden n=2 Australia n=1 Philippines n=1 Japan n=1 Croatia n=1 Canada n=1 Russia n=1 France n=1 Spain n=1 Jordan n=1 Not reported n=6 General Pediatrician n=24 Pediatric GI n=52 Fellow n=17 Nutritionist n=4 Resident n=4 Research n=3 Not reported n=3 General physician n=1 Interning n=1

Attachment 2 Outcome measures

Table A2 Outcome measures as reported by healthcare professionals

for the outpatient setting in children 1-18 years; Step 2 (n=109)

Domain Outcome Total no. (%)

Constipation Duration of constipation Constipation

Disappearance of constipation

n=3 (3%) n=2(2%) n=2 (2%) Defecation frequency Defecation frequency

Regular soft bowel movements

n=60 (55%) n=1 (1%) Stool consistency Stool consistency

Quality of stools

n=34 (31%) n=3 (3%)

Painful defecation Pain with defecation n=21 (19%)

Fecal incontinence Fecal incontinence n=28 (26%)

Bowel habits- other Blood in stool

Less anxious to defecate Normal bowel movement Less stool withholding Clarity of bowel movement Amount of stool

Sensation of emptying Number of days without stool

Emergency defecation on the way to school

n=9 (8%) n=3 (3%) n=2 (2%) n=2 (2%) n=1 (1%) n=1 (1%) n=1 (1%) n=1 (1%) n=1 (1%) Straining Straining n=3 (3%)

Quality of life Quality of life of child/parents Behavior/energy/mood of child Normal social life

n=18 (17%) n=3 (3%) n=1 (1%) Abdominal pain / discomfort Abdominal pain Discomfort No bowel distention Abdominal bloating n=42 (39%) n=14 (13%) n=1 (1%) n=1 (1%)

Other GI complaints Less gas n=1 (1%)

Fecal impaction Rectal impaction Fecal impaction resolves Efficiency of disimpaction No effect of clean out

n=3 (3%) n=1 (1%) n=1 (1%) n=1 (1%) Satisfaction Satisfaction of child/parent

Patient satisfaction Parental satisfaction

n=4 (4%) n=1 (1%) n=1 (1%) Adequate relief Adequate relief rated by patients and parents n=1 (1%)

Education Parental reassurance

Explanation of normal stool pattern Explanation of long duration of therapy Re-education

Explanation about the disease

n=1 (1%) n=1 (1%) n=1 (1%) n=1 (1%) n=1 (1%)

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Domain Outcome Total no. (%)

Diet Diet

Improve appetite / normalization of food intake Eating problems Less milk More fiber Nutritional status n=3 (3%) n=3 (3%) n=2 (2%) n=1 (1%) n=1 (1%) n=1 (1%)

Medication Use of laxatives

Characteristics of medication (like taste and side-ef-fects)

Re-education of pharmacologic treatment No medication required

Efficacy of medication

Decrease of harmful medication Already used medication

n=8 (8%) n=8 (8%) n=2 (2%) n=2 (2%) n=2 (2%) n=1 (1%) n=1 (1%) Hospital visits Fewer consultations with healthcare professionals

Number of visits to outpatient department

n=3 (3%) n=1 (1%)

Growth Thriving / growth

Weight loss

n=5 (5%) n=1 (1%)

Treatment compliance Treatment compliance n=5 (5%)

Other School attendance

Reduce stress in family Crying

Reduce parental anxiety Manage anal fissure Sleep

Time to improvement of symptoms Parent’s discomfort

Improvement of clinical status Frequency of voiding

Costs of treatment Lack of success

Presence of alarm symptoms Adequate nursing by family Physical examination Colonic transit time

Decrease of diameter of the rectum Control of sphincter n=4 (4%) n=4 (4%) n=4 (4%) n=3 (3%) n=3 (3%) n=2 (2%) n=2 (2%) n=1 (1%) n=1 (1%) n=1(1%) n=1 (1%) n=1 (1%) n=1 (1%) n=1 (1%) n=1 (1%) n=1 (1%) n=1(1%) n=1 (1%)

Three unclear outcomes such as “familiar environment” and “organization” were not displayed Three unclear outcomes such as “familiar environment” and “organization” were not displayed

Attachments Shortlists

Attachment 3a Shortlist outcome measures healthcare professionals

(rated and prioritized) for children 0-1 years old

Rank Outcome measure Percentage Average rating

Outpatient setting

1 Defecation frequency 96% 3.14

2 Painful defecation 94% 2.98

3 Stool consistency 82% 3.20

4 Discomfort 74% 2.28

5 Quality of life parents 64% 1.76

6 Abdominal pain 36% 1.44 7 Crying 36% 0.18 8 Fecal incontinence 18% 0.76 Inpatient setting 1 Defecation frequency 92% 3.18 2 Stool consistency 88% 3.24 3 Painful defecation 84% 2.94 4 Discomfort 72% 2.30

5 Quality of life parents 62% 2.31

6 Time of hospitalization 52% 1.82

7 Abdominal pain 28% 1.50

C O S f or F C 6

Attachment 3b Shortlist outcome measures healthcare professionals

(rated and prioritized) for children 1-18 years old

Rank Outcome measure Percentage Average rating

Outpatient setting

1 Fecal incontinence 94% 3.63

2 Defecation frequency 84% 3.50

3 Painful defecation 78% 3.24

4 Stool consistency 78% 3.16

5 Quality of life (child and parents) 76% 3.31

6 Abdominal pain 66% 2.60 7 Discomfort 24% 1.76 Inpatient setting 1 Fecal incontinence 88% 3.59 2 Defecation frequency 86% 3.48 3 Stool consistency 78% 3.24 4 Painful defecation 74% 3.18

5 Quality of life child/parents 70% 2.98

6 Abdominal pain 52% 2.54

7 Time of hospitalization 40% 2.28

8 Discomfort 12% 1.72

Attachment 4a Shortlist outcome measures parents of children

0-1 years old

Rank Outcome measures

Comfortable 1 Stool consistency 2 Defecation frequency 3 Crying 4 Abdominal pain 5 Treatment success Uncomfortable 1 Stool consistency 2 Straining 3 Defecation frequency 4 Crying 5 Painful defecation

Attachment 4b Shortlist outcome measures parents (rated and prioritized)

of children 1-18 years old

Rank Outcome measure Percentage Average rating

Comfortable

1 Quality of life (child and parents) 83 3.41

2 Abdominal pain 77 3.30 3 Fecal incontinence 76 3.24 4 Painful defecation 66 2.96 5 Stool consistency 65 3.16 6 Treatment success 64 3.08 7 Defecation frequency 47 2.67

8 Complete information given by doctor 36 2.81 Uncomfortable

1 Lack of treatment success 88 2.40

2 Abdominal pain 84 2.95

3 Stool consistency 78 2.57

4 Defecation frequency 68 2.40

5 Fecal incontinence 62 2.28

6 Lack of information given by doctor 44 1.92

Attachment 5 Shortlist outcome measures patients ≥ 12 years old

Rank Outcome measure Percentage Average rating

Comfortable

1 Abdominal pain 86% 3.52

2 School absence 74% 3.14

3 Fecal incontinence 66% 2.86

4 Quality of life (child) 54% 2.94

5 Defecation frequency 52% 2.58 6 Stool consistency 42% 2.46 7 Use of medication 16% 1.92 Uncomfortable 1 Abdominal pain 86% 3.38 2 School absence 70% 3.08 3 Fecal incontinence 68% 3.06

4 Quality of life (child) 50% 2.74

5 Defecation frequency 48% 2.48

6 Stool consistency 40% 2.42