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Abstract
Background Primary treatment of an anorectal malformation (ARM) is surgical restoration of the anatomy. These children can experience many problems later in life; therefore, a long-term follow-up by an experienced team is needed. The aim of the ARM and OUtcome Review (ARMOUR-study) is to identify the lifetime outcomes that are important from a medical and patients’ perspective and develop a core outcome set (COS) that can be implemented in a care pathway to support individual ARM management decisions.
Methods First, a systematic review will identify clinical and patient-reported outcomes described in studies conducted in patients with an ARM. Second, qualitative interviews with patients of different age categories and their caregivers will be held to ensure that the COS will include outcomes that are relevant from the patient’s perspective. Finally, the outcomes will be taken forward to a Delphi consensus exercise. Using multiple web-based Delphi rounds, key stakeholders (medical experts, clinical researchers and patients) will prioritise outcomes. During a face-to-face consensus meeting, the final COS will be determined. These outcomes can be evaluated in a life-long care pathway for patients with ARM.
Discussion The development of a COS for ARMs aims to reduce heterogeneity in outcome reporting between (clinical) studies, enhancing the availability of comparable data, which will facilitate evidence-based patient care. Assessment of the outcomes in the COS during individual care pathways for ARM can support shared decisions regarding management. The ARMOUR-project has ethical approval and is registered with the Core Outcome Measures in Effectiveness Trials (COMET) initiative.
Level of evidence Treatment study level II.
- Gastroenterology
- Growth
- Qualitative research
- Adolescent Health
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What is already known on this topic?
Patients with an anorectal malformation (ARM) can experience many difficulties after their primary treatment. Although many of these difficulties are reported in the literature, a structured focus on them in clinical research and throughout the patient’s care pathway is lacking.
What this study hopes to add?
This study was initiated to identify the core outcomes and issues experienced by patients with ARM after primary treatment using qualitative interviews. Together with multiple stakeholders (patients, medical professionals and health researchers) a core outcome set (COS) will be developed that can be used in clinical research and practice.
How this study might affect research, practice or policy?
The development of a COS for ARM will reduce heterogeneity in outcome reporting between (clinical) studies and so facilitate evidence synthesis and evidence-based patient care. Assessment of the outcomes in the COS during individual care pathways for ARM can support shared decisions regarding management.
Introduction
An anorectal malformation (ARM) is a congenital abnormality in which the anus and rectum have not been developed properly.1 2 It occurs in 1:2500 to 1:5000 live births.3–6 An ARM cooccurs in 40%–70% with other congenital malformations,7–11 whereas approximately 40% of new borns present with isolated forms of ARM.4 8 11 12
Standard treatment of patients with an ARM consists of operative restoration of the anatomy in which a neo-anus is formed. In short, depending on the anatomy of the ARM, several operative techniques can be performed such as the laparoscopically assisted anorectal pull-through, the anterior sagittal anorectoplasty and the posterior sagittal anorectoplasty.13–17 Despite the operative restoration, patients with an ARM generally experience a variety of inconveniences and problems during their lifetime. Faecal and urinary incontinence and obstipation occur frequently on the long term.7 13 18 These discomforts highly impact physical, emotional, social and sexual functioning in teenage, adolescent and adult life.13 19–21 Clinicians have increasingly acknowledged that these challenges are as important as the defective development of an anus. Subsequently, it has become clear that this requires life-long follow-up and guidance by an experienced team of (para)medical professionals. However, proper evidence-based and patient-driven care pathways for the treatment and follow-up of an ARM are currently lacking. Care pathways should be based on sound medical aspects, clinical evidence and, moreover, on the needs and wants of patients. The aspect of follow-up and transition has only gained attention since very recently. There are countries who attain general pathways, but this is mostly not evidence based. It varies per hospital and country if steps are taken to try and change these pathways. Good research is thereby needed to be able to construct this core outcome set (COS). A COS represents an agreed minimum standardised set of outcomes that should be assessed and reported in all interventional studies for a specific condition.22 A COS can reduce heterogeneity in outcome reporting and minimise outcome reporting bias.22
The ARM and OUtcome Review (ARMOUR)-project was initiated to identify the core outcomes and issues that are considered relevant from a medical perspective and essential for patients. The aim of this study is to develop a COS for ARM to ensure that clinical studies evaluate these same outcomes, so as to enhance evidence synthesis and subsequently evidence-based practice. This paper describes the protocol for the development of a COS that can be used in interventional studies for ARM that evaluate treatment effectiveness. These outcomes, such as impact on relationships, autonomy and also sexuality at different stages in life, could then also be regularly assessed and discussed throughout the patients care pathway.
Materials and methods
This study has been registered in the Core Outcome Measures in Effectiveness Trials (COMET) database on 26 September 2019 (http://comet-initiative.org/studies/details/1413).
A study management group will oversee the ARMOUR-project and consist of a clinical researcher, two paediatric surgeons, a COS and qualitative methodology expert and a patient representative. The study management group will meet regularly and is responsible for the design and quality of the study. A multistep approach will be followed as recommended by the guidelines for COS development published by the COMET initiative.23 In the first step, potential outcomes will be identified by a systematic review of the literature patient interviews. These outcomes will then be prioritised by patients, patient representatives and healthcare professionals in multiple web-based Delphi rounds. The final step is a face-to-face consensus meeting to decide on the definitive COS. Members of the study management group will invite patients, patient representatives, healthcare professionals, members of the Society of Anal Atresia and methodologists to participate in the Delphi rounds and consensus meeting.
Stage 1. Identification of candidate outcomes
A systematic review of the literature will be performed to identify potential clinician-reported and patient-reported outcomes, including outcome definitions, outcome measurement instruments and timing of outcome assessment. It is expected that clinical studies have predominantly focused on clinical outcomes of ARM treatment as determined by healthcare professionals. To ensure that the outcomes used in the COS are also relevant for patients, patient interviews will be conducted to identify any additional outcomes that are relevant to patients but are not captured with the systematic review of the literature.
Systematic Review
A systematic review of the literature will be conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Statement24 . The systematic review aims to answer the following question: Which patient-reported and clinician-reported outcomes are mentioned in published literature in the treatment of patients with an ARM?
Search strategy
A broad search will be conducted to ensure maximum enclosure of relevant literature. The major healthcare databases PubMed and EMBASE are used for the identification of records. Also, The Cochrane Library will be explored to identify existing systematic reviews in the field of ARM. The search will be limited to studies published during the last 10 years.
Study selection
All studies concerning ARM interventions and experiences will be included, regardless of the study type. This includes prospective and retrospective interventional studies, case descriptions, meta-analyses and reviews concerning ARM. Studies concerning rectal stenosis due to cancer or other non-congenital disease will be excluded as well as studies describing solely other congenital malformations or reporting the genetic origin or the aetiology of ARMs. Furthermore, studies concerning diagnostic techniques and studies conducted to assess the association between ARMs and other anomalies will also be excluded. Full-text review will be performed for potentially relevant articles based on the initial screening of title and abstract. The article selection process will be performed by two members of the study team using these mentioned selection criteria. Any disagreement on study eligibility will be resolved through discussion with recourse to a third reviewer were necessary.
Data extraction
Data will be extracted independently by two review authors using a predefined data extraction form. The following data will be extracted from each individual study: author details, year and journal of the publication, study type, type of intervention performed, age and number of participants in the study population and all primary and secondary outcomes assessed, including their definition, the measurement time points and measurement instruments used. The extracted data will be discussed among the reviewing authors to assess consensus and to ensure that all relevant data have been identified. Disagreement will be resolved through consultation with a third reviewer.
Qualitative patient interviews
Qualitative methods are essential to better understand the life impact of having an ARM. Individual patient interviews will be conducted to (1) obtain a more in-depth understanding of challenges in patients’ lives born with an ARM and the impact on daily activities and (2) to identify the range of outcomes valued by patients and their caregivers, during the patient’s lifetime. Patients of the paediatric surgery department who underwent primary treatment and members of the patient association for ARM in the Netherlands will be recruited and asked to participate in the interviews.
Several groups of patients with ARM will be approached. Four groups are defined for the interviews: parents from children aged 0–5 years and their caregivers/parents, patients aged 6–11 years and their caregivers/parents, patients aged 12–17 and their caregivers/parents and adult patients. All parents of children younger than 17 years and patients aged above 12 years will be asked for written consent. To be able to discuss difficult subjects as sexuality, a separate interview with the patient will take place, after receiving consent of the patient and their parents/caregivers. Only patients with adequate written and spoken comprehension of the Dutch language will be included. We want to create a variety in age, gender and ethnicity, so there will be no exclusion based on these characteristics.
A minimum of five individuals per age category will be invited for the interviews. If saturation, that is, the point at which no new information is heard or outcomes are being uncovered, has not been reached after five interviews, the team may decide to invite more individuals per age category, with a maximum of 10 individuals in total per group. We expect that between 5 and 10 patients in each age category will be sufficient to represent a wide range of patients and thus identification of all relevant issues, outcomes and experiences. This sampling approach is common in qualitative research.25 26
Interview format and analysis
A semistructured interview guide will be used when performing the qualitative interviews. Semistructured interviews ensure that certain topics of interest (eg, treatment complications or sexual dysfunction) are discussed and also allow for participants and interviewer to go into details when needed. Topics that will be included in the interview guide are experienced symptoms or impairments, impact on daily life/activities (such as school or work), caring for a child with ARM (for parents) and important treatment outcomes. It is expected that each interview will take approximately 30–45 min. The interviews will be conducted in a personal setting with one patient and his/her parents or partner(s). Interviews will be audio-recorded, transcribed verbatim and analysed for content independently by a member of the study team. The data will be analysed using a thematic approach.27 This involves a member of the team precoding issues and outcomes, followed by categorisation and looking for overarching themes/patterns (by indicating relationships between categories).28 Quotes will be selected to best describe the findings.
Categorisation of candidate outcomes
Clinician-reported and patient-reported outcomes resulting from the systematic review of the literature and patient interviews will be categorised under broader outcome domains using the taxonomy proposed by the COMET Initiative.29 They will be listed alphabetically to minimise potential bias.22 30 This taxonomy will consist of the following domains: mortality, physiological (or pathophysiological), infection, pain, quality of life, mental health, psychosocial, function (or functional status), compliance with/withdrawal from treatment, satisfaction, resource use, adverse events and knowledge.22 The grouping of outcomes and suitability of the domain names will be assessed by two of the authors.
Stage 2. The Delphi consensus rounds
The list of potential outcomes identified in stage 1 will be entered into a two (if needed three) round Delphi study to achieve consensus from stakeholders on the importance of each outcome. The outcomes will be formatted into questions. To ensure appropriate phrasing and understanding for all stakeholders, healthcare professionals and patient representatives (included in the Study management group (SMG)) will be involved in the designing of the Delphi exercise and the questions will be pilot tested in both groups.31 At the end of the questionnaire, an additional open question will be placed to ask participants to list any additional outcomes they do not feel have been considered.32
The Delphi method, consisting of sequential questionnaires presented electronically which can be answered anonymously, will be used to facilitate consensus about which of the obtained outcomes should be included in the COS.33 The Delphi technique is advantageous in that it is anonymous, whereas all other methods used for the development of a COS involve face-to-face communication. The Delphi method is used because subjective statements on collective basis are made and we wanted to prevent the influence of one person in a group discussion on the results.22 Participants of the Delphi are clinicians, researchers, patients and patient representatives from several European countries (eg, Netherlands, Belgium and Germany).
Each Delphi round will remain open for a period of 4 weeks. A reminder email will be sent to participants who have not completed the Delphi round after 14 days. Participants who have not completed or returned the questionnaire after the 4-week deadline will be sent one final email to ask whether they have encountered any problems answering the questions, or if they decided not to participate in the study. Depending on the number of additional responses we receive, the round will be closed after 4 weeks, or prolonged with 2 weeks. Finally, attrition bias will be considered, which occurs when the participants who do not respond in subsequent rounds have different views from their stakeholder group peers who continue to participate. This will lead to an overestimation of the degree of consensus. To identify whether or not attrition has occurred, scores from the rounds (ie, round 1 and round 2, and if applicable round 2 and round 3) will be compared between stakeholder group participants completing both rounds and participants completing one round only. To minimise the risk of attrition bias, we will only invite people who respond to a pre-Delphi invitation to participate in the first round. In the invitation, people will be informed about the importance of completing all rounds. Participants will be given a unique identifier to allow tracking of attrition at each round.
Stakeholder panels
The group size will be dependent on the number of patients and experts willing to participate, and since ARM has an incidence of 1 to 5000 in the Netherlands as a whole, the number of patients will likely be small.22 It is aimed to include 15 patients, 5 patient representatives and around 30 healthcare professionals and researchers. There is no consensus on group size in a Delphi consensus round.22 In the Delphi study, we want to include patients, patient representatives, medical experts and researchers mostly from several European countries (eg, The Netherlands, Belgium, Germany).
Patients and patient representatives
Patients with an ARM who underwent their primary treatment and/or their caregivers will be eligible for inclusion in the Delphi rounds. The parents of children aged 11 or younger will participate and children aged 12 or above will be able to participate together with their parents. Patients aged ≥18 years old are able to participate independently. Patients and caregivers will be approached for participation by means of an electronic invitation; stakeholders participating the Delphi rounds automatically give informed consent by filling in the online questionnaire. The email will provide all the needed information about the study, participant information which accentuates the importance of autonomy, voluntary participation and the right to withdrawn from the study at any moment.34
Patient representatives of the Society of Anal Atresia will be asked to participate by means of an electronic invitation. The same procedure carried out in the patients’ panel will be followed in the patient representatives’ panel.
Healthcare professionals
Healthcare professionals will be identified through direct colleagues and personal network of the SMG and attendance of meetings/conferences in the field of ARM. Furthermore, each professional will be asked to bring in contact details from acquaintances or colleagues they believe to be suitable for inclusion in the Delphi study. An invitation will be sent to them per email. If possible, an advertisement for participation will be available on the national website of the Dutch national organisation for paediatric surgery, European reference network for urogenital diseases (eUrogen) and the Belgian association of paediatric surgery. As the primary care for ARM is mostly in specialised hospitals with an overall equal amount of practice, there is little risk of overestimation and there will be no maximum number per country nor per hospital. During the first round, the healthcare professionals will be asked about their specialty, years of experience in ARM care and country of origin.
Delphi rounds
Scoring system
Stakeholders will be asked to rate the candidate outcomes on a 9-point (1 to 9) Likert scale with respect to how important they think the outcomes are concerning the treatment and living with ARM.35 36 The scale that will be used, recommended by the Grading of Recommendations Assessment, Development and Evaluation Working Group,35 labels ‘1–3’as an outcome of limited importance (not important), ‘4–6’ as important but not of critical importance and ‘7–9’ as critical (really important).33 37–39
Participants are able to provide a reason for their scores on individual outcomes and this will be summarised as part of the feedback. At the end of each round, the results for all outcomes will be aggregated across participants and descriptive statistics presented. Patients and patient representatives from one stakeholder group, healthcare professionals form the other group.
Since the number of participants of the Delphi phase of the study is not particularly high, it is advised that the results of stakeholder group members should be pooled, especially when the opinions of members are unlikely to differ. Scores will be presented separately per stakeholder group
Round 1
At the start of the first round of this Delphi consensus study, participants will be asked via open-ended questions which outcomes they feel are most important concerning the treatment of ARM. Then, participants will be asked to rank the candidate outcomes from the systematic review and the patient interviews according to importance. Last, there will be room for participants to propose additional candidate outcomes they think are missing and there will be an opportunity to provide feedback on the first round. All the outcomes from the first round will be carried forward to the second round, with their first-round scores displayed. Newly introduced outcomes will be added in the second round. The given feedback will be analysed using the COMET Initiative Delphi Manager.23 The degree of consensus will be assessed by calculating the change in respondents’ scores between rounds.22 Participants who completed the first round will be eligible to participate in the second round.
Round 2
In the second round of the Delphi phase, the results from the first round will be summarised in graphs and presented as anonymous feedback. Participants will be shown their responses of the previous round and the responses from other stakeholders within their stakeholder panel. At the end of the second round, the outcomes that are scored ‘7–9’ by the majority of the voting participants (>70%) will be retained. If less than 70% of all voters rated the outcome ‘7–9’ and the patient group rating was <7, the outcome will be removed from the list. If <70% of all voters rated the outcome ‘7–9’, but the patient group gave the candidate outcome an average rating of >7, the outcome will be considered as important to patients and will, therefore, be included in the third round. Participants who completed the second round will be eligible for entry in the third round of the Delphi study.
Round 3
The results from the second round will be summarised and feedback on previous answers will be presented to the participants. They will be shown their own previous responses and the responses from all stakeholder panels. This way, convergence will be facilitated to obtain a consensus opinion across different stakeholder panels about the outcomes. Participants who completed all rounds will be eligible to participate in the face-to-face consensus meeting.
Stage 3. The consensus meeting
A face-to-face meeting for stakeholder representatives will be conducted to reach definitive consensus for the remaining outcomes. Any disagreement in outcome importance will be discussed. The candidate outcomes will be categorised as ‘consensus in’, ‘consensus out’ or ‘no consensus’. During the consensus meeting, we will use a 1–3 scale, ‘3’ is most important and ‘1’ is least important. An outcome will be categorised as ‘consensus out’ if >70% of the respondents gave the outcome a score of ‘1’ and if the patient group rating will be <1. Outcomes rated >70% as ‘3’ will be ranked as ‘consensus in’. Outcomes rated as ‘2’ by <70% of respondents but with an average of >2 are considered ‘consensus in’. The rest of the outcomes will be considered as not achieving consensus in either way. An electronic and anonymous voting system will be used, and scores will be presented on a screen. There will be no restriction on the number of outcomes eligible for the COS.
Discussion
The aim of the ARMOUR-study is to develop a COS that can be used in future clinical studies evaluating the effectiveness of care pathways and in the daily clinical management of ARM. The ARM-COS defined in this study ensures relevant outcomes from the medical and patient perspective and may help identifying which instruments to measure these outcomes are currently lacking. This knowledge may guide efforts in developing those instruments. The aim is to enhance interpretability, comparability and usefulness of the findings of interventional studies. In time, this may provide better insight in which treatments or care strategies are best for these patients. The extensive participation of patients and their caregivers in all stages of this study will guarantee their valuable input in the COS. While the patient interviews will only be conducted with Dutch patients, in the Delphi study, we aim to include patients and patient representatives not only from the Netherlands but also from Belgium and Germany. Furthermore, participants of the Delphi study include (medical) stakeholders from a variety of countries, so that the COS represents the values of an international community which will promote international uptake of the COS.
This study will give answer to the question on ‘what’ outcomes to evaluate during the lifetime of a patient with ARM, but not to the question on ‘how’ to measure these outcomes. Future research will include the evaluation of outcome measurement instruments available.23
Ethics statements
Patient consent for publication
References
Footnotes
Contributors CBMR and SAMC were the majot contributors in writing the manuscript. SAMC has written the introduction and the methods. CBMR has written the abstract and corrected the methods section. CBMR, SAMC and LH have written the discussion. LH emerged these parts together to form the manuscript and make it suitable for submission. RGJV, MLK, MH and WGvG have substantively revised the manuscript. RGJV, LH and MLK also contributed in the design of the manuscript. LH adjusted the paper according to the comments of the reviewers and submitted the manuscript for revision. All authors read and approved the final manuscript.
Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
Competing interests None.
Patient and public involvement Patients and/or the public were involved in the design, or conduct, or reporting, or dissemination plans of this research. Refer to the Methods section for further details.
Provenance and peer review Not commissioned; externally peer reviewed.