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June 2021

Original Article

Priorities for paediatric critical care research: a modified Delphi study by the Australian and New Zealand Intensive Care Society Paediatric Study Group

Sainath Raman** , Georgia Brown**, Debbie Long , Ben Gelbart , Carmel Delzoppo, Johnny Millar, Simon Erickson, Marino Festa, Luregn J Schlapbach , *Equal first authors

Crit Care Resusc 2021; 23 (2): 194-201

Correspondence:l.schlapbach@uq.edu.au

https://doi.org/10.51893/2021.2.oa6

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  • Author Details

    * Equal first authors.

  • Competing Interests
    None declared
  • Abstract
    OBJECTIVE: Most interventions in paediatric critical care lack high grade evidence. We aimed to identify the key research priorities and key clinical outcome measures pertinent to research in paediatric intensive care patients.
    DESIGN: Modified three-stage Delphi study combining staged online surveys, followed by a face-to-face discussion and final voting.
    SETTING: Paediatric intensive care units in Australia and New Zealand.
    PARTICIPANTS: Medical and nursing staff working in intensive care.
    MAIN OUTCOME MEASUREMENTS: Self-reported priorities for research.
    RESULTS: 193 respondents provided a total of 267 research questions and 234 outcomes. In Stage 3, the top 56 research questions and 50 outcomes were discussed face to face, which allowed the identification of the top 20 research questions with the Hanlon prioritisation score and the top 20 outcomes. Topics centred on the use of intravenous fluids (restrictive v liberal fluids, use of fluid resuscitation bolus, early inotrope use, type of intravenous fluid, and assessment of fluid responsiveness), and patient- and family-centred outcomes (health-related quality of life, liberation) emerged as priorities. While mortality, length of stay, and organ support/organ dysfunction were considered important and the most feasible outcomes, long term quality of life and neurodevelopmental measures were rated highly in terms of their importance.
    CONCLUSIONS: Using a modified Delphi method, this study provides guidance towards prioritisation of research topics in paediatric critical care in Australia and New Zealand, and identifies study outcomes of key relevance to clinicians and experts in the field.
  • References
    1. Centre for Outcome and Resource Evaluation. Australian and New Zealand Paediatric Intensive Care Registry Activity Report 2018. Australian and New Zealand Intensive Care Society, 2018. https://www.anzics.com.au/wp-content/uploads/2020/02/Australian-and-New-Zealand-Paediatric-Intensive-Care-Registry-Activity-Report-2018.pdf (viewed Apr 2021)
    2. Kanthimathinathan HK, Peters MJ. Focus on paediatrics 2018. Intensive Care Med 2018; 44: 2267-70
    3. Schlapbach LJ, Gelbart B, Festa M, et al. Global paediatric critical care research: mind the gaps. Intensive Care Med 2019; 45: 753-4
    4. Schlapbach LJ, Straney L, Gelbart B, et al. Burden of disease and change in practice in critically ill infants with bronchiolitis. Eur Respir J 2017; 49: 1601648
    5. Vella K, Goldfrad C, Rowan K, et al. Use of consensus development to establish national research priorities in critical care. BMJ 2000; 320: 976-80
    6. Tuffaha HW, Aitken J, Chambers S, et al. A framework to prioritise health research proposals for funding: integrating value for money. Appl Health Econ Health Policy 2019; 17: 761-70
    7. Zimmerman JJ, Banks R, Berg RA, et al. Trajectory of mortality and health-related quality of life morbidity following community-acquired pediatric septic shock. Crit Care Med 2020; 48: 329-37
    8. Wielenga JM, Tume LN, Latour JM, van den Hoogen A. European neonatal intensive care nursing research priorities: an e-Delphi study. Arch Dis Child Fetal Neonatal Ed 2015; 100: F66-71
    9. Soeteman M, Potratz J, Nielsen JSA, et al. Research priorities in pediatric onco-critical care: an international Delphi consensus study. Intensive Care Med 2019; 45: 1681-3
    10. Deane HC, Wilson CL, Babl FE, et al. PREDICT prioritisation study: establishing the research priorities of paediatric emergency medicine physicians in Australia and New Zealand. Emerg Med J 2018; 35: 39-45
    11. Harris PA, Taylor R, Thielke R, et al. Research electronic data capture (REDCap) — a metadata-driven methodology and workflow process for providing translational research informatics support. J Biomed Inform 2009; 42: 377-81
    12. Ramelet AS, Gill F, Group APICSI. A Delphi study on national PICU nursing research priorities in Australia and New Zealand. Aust Crit Care 2012; 25: 41-57
    13. Walz A, Canter MO, Betters K. The ICU liberation bundle and strategies for implementation in pediatrics. Curr Pediatr Rep 2020; doi: 10.1007/s40124-020-00216-7 [Epub ahead of print]
    14. Peters MJ, Argent A, Festa M, et al. The intensive care medicine clinical research agenda in paediatrics. Intensive Care Med 2017; 43: 1210-24
    15. Fink EL, Jarvis JM, Maddux AB, et al. Development of a core outcome set for pediatric critical care outcomes research. Contemp Clin Trials 2020; 91: 105968
    16. Pickkers P, Kox M. Towards precision medicine for sepsis patients. Crit Care 2017; 21: 11
    17. Whittaker E, Bamford A, Kenny J, et al. Clinical characteristics of 58 children with a pediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2. JAMA 2020; 324: 259-69
    18. Oczkowski SJW, Au S, des Ordons AR, et al. A modified Delphi process to identify clinical and research priorities in patient and family centred critical care. J Crit Care 2017; 42: 243-7
    19. Yende S, Austin S, Rhodes A, et al. Long-term quality of life among survivors of severe sepsis: analyses of two international trials. Crit Care Med 2016; 44: 1461-7
    20. Maitland K, Kiguli S, Opoka RO, et al. Mortality after fluid bolus in African children with severe infection. N Engl J Med 2011; 364: 2483-95
    21. Alobaidi R, Morgan C, Basu RK, et al. Association between fluid balance and outcomes in critically ill children: A systematic review and meta-analysis. JAMA Pediatrics 2018; 172: 257-68
    22. Gelbart B, Schlapbach L, Ganeshalingham A, et al. Fluid bolus therapy in critically ill children: a survey of practice among paediatric intensive care doctors in Australia and New Zealand. Crit Care Resusc 2018; 20: 131-8
    23. Gelbart B. Fluid Bolus Therapy in pediatric sepsis: current knowledge and future direction. Front Pediatr 2018; 6: 308
    24. Moynihan KM, Alexander PMA, Schlapbach LJ, et al; Australian and New Zealand Intensive Care Society Pediatric Study Group (ANZICS PSG) and the ANZICS Centre for Outcome and Resource Evaluation (ANZICS CORE). Epidemiology of childhood death in Australian and New Zealand intensive care units. Intensive Care Med 2019; 45: 1262-71
    25. Woolfall K, O’Hara C, Deja E, et al. Parents’ prioritised outcomes for trials investigating treatments for paediatric severe infection: a qualitative synthesis. Arch Dis Child 2019; 104: 1077-82
    26. O’Hara CB, Canter RR, Mouncey PR, et al. A qualitative feasibility study to inform a randomised controlled trial of fluid bolus therapy in septic shock. Arch Dis Child 2018; 103: 28-32
    27. Boney O, Nathanson MH, Grocott MPW, et al. Differences between patients’ and clinicians’ research priorities from the Anaesthesia and Peri-operative Care Priority Setting Partnership. Anaesthesia 2017; 72: 1134-8
    28. Crowe S, Fenton M, Hall M, et al. Patients’, clinicians’ and the research communities’ priorities for treatment research: there is an important mismatch. Res Involv Engagem 2015; 1: 2
    29. Burns KEA, Rizvi L, Charteris A, et al. Characterizing citizens’ preferences for engagement in patient care and research in adult and pediatric intensive care units. J Intensive Care Med 2020; 35: 170-8
    30. Schlapbach LJ, Straney L, Alexander J, et al. Mortality related to invasive infections, sepsis, and septic shock in critically ill children in Australia and New Zealand, 2002-13: a multicentre retrospective cohort study. Lancet Infect Dis 2015; 15: 46-54
More than 12 000 children require admission to intensive care in Australia and New Zealand every year for potentially life-threatening conditions. 1 However, there is scarce evidence for most of the interventions and practices, and the number of trials in paediatric critical care internationally remains low. 2, 3 Observational studies demonstrate substantial variability of care even for common interventions and diseases. 4 In order to overcome obstacles to paediatric critical care research, such as heterogeneity and low prevalence of many diseases, collaboration across research networks and prioritisation of topics and outcomes are required. 5, 6, 7

Several research prioritisation studies have been published in related disciplines; for example, in neonatal intensive care nursing, paediatric emergency medicine, or paediatric onco-critical care. 8, 9, 10 However, there is a lack of contemporary research prioritisation studies generated by multidisciplinary clinicians and researchers in paediatric critical care and a corresponding lack of studies identifying and prioritising the key research outcomes.

The Australian and New Zealand Intensive Care Society (ANZICS) Paediatric Study Group (PSG) is a collaborative body of multidisciplinary paediatric intensive care unit (PICU) clinicians that aims to promote, design and conduct multicentre research in critically ill children in Australia and New Zealand.

This study aimed to define the key priorities for research in paediatric critical care pertinent to Australia and New Zealand through a modified Delphi process.
 

Methodology

We conducted a three-stage modified Delphi survey of research priorities and clinical outcome priorities with senior medical and nursing PICU staff working in Australia and New Zealand (Supporting Information, supplemental methods). The study was conducted between 1 September 2019 and 30 April 2020. The surveys for each stage were administered via an online REDCap database, 11 and consent was obtained at the start of the survey. The study was approved by the Human Research and Ethics Committee (Children’s Health Queensland LNR/19/QCHQ/54762).
 

Stage 1: collection of priorities for research and research outcomes

Medical and nursing staff working in PICUs across Australia and New Zealand who met the inclusion criteria were invited to participate in the Stage 1 online survey. 10, 12 Respondents were requested to state the five most important research questions and the five most important outcomes for research, each in free text. Reminders were sent every 2 weeks for 2 months.

All unedited responses were distributed to an expert panel (GB, SR, LJS, DL, SE, MF, JM) for review and refinement (Supporting Information, supplemental tables 1–3). Duplicate questions were excluded. Each reviewer was asked to independently assess each of the proposed research questions with regard to the following criteria:
  • Is the question amenable to multicentre research? As the ANZICS PSG is a multicentre research network, questions of relevance to just a single centre were excluded.
  • Is there sufficient current existing evidence to answer the question? A question was excluded if the expert panel agreed that existing evidence could sufficiently answer the question.
Through this process, the number of items was reduced and suitable questions were formatted using the population, intervention, comparison and outcome (PICO) model. The proposed clinical outcomes were reviewed using a similar approach by the same expert panel.
 

Stage 2: ranking of research priorities and outcomes

The Stage 2 survey consisted of the refined full list of research questions and clinical outcomes generated by Stage 1, with ordering by random sequence. Respondents were requested to score the importance of each research question and clinical outcome on a seven-point Likert scale. The responses for research questions and outcomes were then ranked by their mean score. Only the items that remained in the top 50% for all respondents, nursing respondents or medical respondents progressed to Stage 3.
 

Stage 3: Hanlon prioritisation process

Stage 3 was conducted restricted to the ANZICS PSG committee, including one medical and one nursing representative for each PICU in Australia and New Zealand. The Hanlon prioritisation process measures prevalence, seriousness and feasibility of a research question. During a full-day face-to-face meeting with videoconference option, all of the top 50% of questions and outcomes were discussed individually, organised by random order according to themes (Supporting Information, supplemental tables 2 and 3). The discussion, facilitated by an international expert in paediatric intensive care research (MP), specifically focused on: i) prevalence of the condition; ii) seriousness of the condition; iii) feasibility of the research; and, iv) likelihood to participate in a trial addressing the research question. The participants were then asked to score each PICO question under these four domains; outcomes were scored for seriousness and feasibility only.

Statistical analyses

Respondent characteristics are represented as number (percentage). The Delphi score was calculated as the mean score across all respondents in the Stage 2 survey. The Hanlon score for research questions was the product of mean scores for the three domains (prevalence [P], seriousness [S] and feasibility [F]; Hanlon score = P Χ S Χ F). For outcomes, the Hanlon score was the product of the mean score for importance and feasibility.
 

Results

The overview of the Delphi process and the characteristics of respondents are presented in Figure 1 and Table 1 respectively. A total of 193 PICU staff (33.7%) responded to the Stage 1 survey, including 172 doctors and nurses out of 572 eligible PICU staff in Australia and New Zealand (response rate, 30.1%), of which 134 (77.9%) responded to the Stage 2 survey. Based on the Delphi scores, the list was then reduced to 56 research questions and 50 outcomes to include the top 50% of priorities chosen by the whole group, uniquely by doctors and uniquely by nurses.
 
Twenty-four ANZICS PSG Committee members (92.3%) completed the Stage 3 of the Hanlon prioritisation process.
 

Prioritised research questions

The top research priority was to investigate whether a restrictive fluid strategy improves outcomes in critically ill children (Table 2) (Supporting Information, supplemental table 4 and figure 1). “What matters to the families” was ranked second, followed by health-related quality of life. Key themes were observed in the top 20 research priorities, including fluid therapy (along with fluid resuscitation and early inotropes in sepsis), family experience, care of families and staff (moral distress and burnout in staff), restrictive oxygen therapy, and domains related to the LIBERATION quality improvement initiative. 13
 

Prioritised outcomes

The outcomes receiving the highest priority included mortality, PICU and hospital length of stay, and duration of ventilation (Table 3) (Supporting Information, supplemental table 5). Survival ≥ 12 months with good neurodevelopment and quality of life assessed > 12 months both after PICU discharge were among the highest ranked outcomes on the Delphi score, while they were in the top 20 priority list of outcomes according to the Hanlon score (Supporting Information, supplemental figure 2).
 

Discussion

This ANZICS PSG prioritisation study explored the research priorities in Australia and New Zealand and allowed to prioritise key topics for future research based on their importance and feasibility. Currently, most children requiring PICU admission are exposed to treatments and practices for which there is no or only scarce evidence, many of which have substantial, sometimes life-threatening, side effects. 14 This lack of evidence needs to be considered in light of the vulnerability of patients in terms of severity of disease, brain development, and dependence on parents or caregivers, and contrasts sharply, for example, with the level of evidence available for chemotherapy regimens in paediatric cancer patients. Given limited resources, determining priorities and feasibility for PICU research in defined settings is essential.

Our prioritisation exercise identified opinions of a binational experienced medical and nursing cohort. The top priorities for research themes included fluid therapy, family experience, health-related quality of life following PICU discharge, and family and staff wellbeing. The top-ranked outcomes were mortality, PICU and hospital length of stay, and duration of mechanical ventilation. Interestingly, there was a disparity between the Hanlon and Delphi scores for some of the research questions, likely reflecting conflicting assessment regarding importance versus feasibility, especially for survival versus quality of life at 12 months after discharge. 15

The top priorities for research focused on very common therapies or interventions such as fluids, antibiotics and oxygen. The focus on highly pragmatic trial questions has important implications for future trial designs. 14 Specifically, options to facilitate enrolment of patients into studies at the time of PICU admission, standardised data collection across studies, and extraction of patient, treatment and outcome data from registries and electronic health records need to be maximised. Interestingly, none of the top priorities related to personalised medicine, artificial intelligence, or omics. 16 The Hanlon process does not consider innovation and instead weighs prevalence, seriousness and feasibility, which is expected to result in a more conservative pragmatic prioritisation. Therefore, future research planning should carefully consider targeted support for high innovation approaches. Furthermore, the perceived importance of research is likely strongly influenced by daily practices and current controversies. Of note, we finished the survey shortly before the coronavirus disease 2019 (COVID-19) pandemic affected Australia. 17 Topics related to pandemic and disaster preparedness, personal protective equipment, resource allocation, or telemedicine were not considered to be relevant by our study respondents.

In contrast to previously published prioritisation studies, we deliberately included both medical and nursing staff in all stages of the modified Delphi process. While we observed some differences in ranking of studies in Stage 2, there was broad overlap in the majority of prioritised topics by nurses and doctors. The relevance of patient-centred outcomes was broadly acknowledged by both medical and nursing respondents. The importance of staff wellbeing, patient delirium and pain management, and family-centred care were favoured by nursing respondents. 8, 12, 18

The highest priority research question in our study was whether restrictive versus liberal fluid strategy lead to improved patient outcomes or not. Several further questions ranked in the top 20 priorities dealt with fluid therapy, such as early inotropes in sepsis, type of fluid, fluid boluses, and assessment of fluid responsiveness. 19 Almost a decade after the landmark FEAST (Fluid Expansion as Supportive Therapy) study, 20 and following a large number of observational studies demonstrating increased mortality associated with fluid overload in critically ill children, 21 fluid therapy remains in the spotlight. 10, 22, 23

Another theme that emerged was the focus on outcomes beyond intensive care admission pertaining to quality of life and neurodevelopment. In contrast to the neonatal intensive care unit setting, where long term follow-up has been considered best practice for extremely low and very low birthweight infants for almost two decades, structured follow-up programs in the PICU setting in Australia and New Zealand are largely lacking. As a result, we observed a major gap between the perceived importance of long term outcome measures and the feasibility of performing such follow-up. Correspondingly, traditional ICU outcomes such as mortality, length of stay, or duration of support were ranked top in the Hanlon prioritisation process despite being considered less important than long term outcomes measured in the Delphi process. 24

Our study had a number of limitations. First, several biases are well known to affect survey-based studies, such as respondent selection and survey fatigue. While we attempted to capture the entire senior medical and nursing PICU workforce, the response rate for Stage 1 was only 30%. The response rates for Stages 2 and 3 were substantially higher (77% and 92% respectively). Second, a major limitation of the prioritisation study was that only clinicians were eligible to participate. The relevance of consumer perspectives in PICU research and the need for active engagement of consumer groups at the study design stage is increasingly recognised. 25, 26 There is a need to reconcile research priorities between clinical staff, researchers, patients and families. 27, 28, 29 Finally, the priorities identified through this ANZICS PSG prioritisation study are specific to the epidemiology, resources and workforce of PICU staff in Australia and New Zealand, 30 and may not reflect wider priorities for global paediatric intensive care.
 

Conclusions

The ANZICS PSG prioritisation study enabled the identification of top research topics and outcomes relevant to the design of future research in Australia and New Zealand. Overall, common interventions such as fluid administration ranked highest, indicating a need for pragmatic trials. Future studies need to consider approaches to capturing long term outcomes.

Acknowledgements: We thank Mark Peters, University College London, UK, for sharing his expertise at the Hanlon stage of this exercise. The data team within the Paediatric Critical Care Research Group, Brisbane, Australia helped with the surveys and analyses of the data. We thank all staff from PICUs in Australia and New Zealand and the ANZICS PSG Committee who participated in this study. We acknowledge the local research coordinators and research staff, who assisted with study distribution, promotion and the prioritisation process.
Luregn Schlapbach was supported by a Practitioner Fellowship of the National Health and Medical Research Council of Australia and by the Children’s Hospital Foundation, Brisbane, Australia.
The Australian and New Zealand Intensive Care Society Paediatric Study Group (ANZICS PSG) members are: Anusha Ganeshalingam and Claire Sherring, from the Starship Children’s Hospital, Auckland, New Zealand; Simon Erickson and Samantha Barr, from the Perth Children’s Hospital, Perth, Australia; Sainath Raman, Debbie Long, Luregn Schlapbach (Past Chair), and Kristen Gibbons (Vice Chair), from the Queensland Children’s Hospital and the University of Queensland, Brisbane, Australia; Shane George, from the Gold Coast University Hospital; Puneet Singh and Vicky Smith, from the Sydney Children’s Hospital, Randwick, Australia; Warwick Butt (Chair), Carmel Delzoppo, Johnny Millar (ANZPIC Registry lead) and Ben Gelbart, from the Royal Children’s Hospital, Melbourne, Australia; Felix Oberender, from the Monash Children’s Hospital, Melbourne, Australia; Subodh Ganu and Georgia Letton, from the Women’s and Children’s Hospital, Adelaide, Australia; Marino Festa and Gail Harper, from the Westmead Children’s Hospital, Sydney, Australia, and Breanna Pellegrini (Australian and New Zealand Paediatric Intensive Care [ANZPIC] Registry).
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