Implementing early rehabilitation and mobilisation for children in UK paediatric intensive care units: the PERMIT feasibility study

Study management

The work package was led by BRS. The study management group was responsible for defining and reviewing scope of search. JYT performed searches, data extraction, risk of bias assessment, evidence synthesis and first draft of chapter. Second screening of articles, data extraction and risk of bias performed by Dr Olivia Craw, JMc and JMen. Methodological expertise provided by DM and BRS.

Search strategy

Searches were conducted in the bibliographic databases [Excerpta Medica Database (Embase) (via OVID), Cumulative Index to Nursing and Allied Health Literature (CINAHL) (via EBSCO), MEDLINE (via OVID), PEDro, Open grey or Cochrane CENTRAL)]. Original search was from inception to 12 October 2019 and an updated search was performed 1 November 2021, using strategies that combined, where relevant, free text and index terms for:

1. children and young people (CYP);

2. admitted to paediatric critical care settings;

3. receiving early (within 7 days) rehabilitation and mobilisation.

The search strategy was developed in MEDLINE (via OVID) (see Appendix 2) and adapted for other databases.

Database of Abstracts of Reviews of Effects, National Health Service (NHS) Economic Evaluation Database and Health Technology Assessment database (all via Centre for Reviews and Dissemination) were searched for relevant systematic reviews to identify primary studies for the review. These were supplemented by relevant websites using hand-searching for mobilization-network.org and search terms for clinicaltrials.gov or Chinese clinical trial registry, checking reference lists of relevant studies, and forward citation-checking of included studies in Web of Science. We screened reference lists to identify relevant primary studies and contacted primary authors to find full texts of incomplete records.

Eligibility criteria

We included all completed studies published in English that met the following criteria:

1. Study participants: critically ill infants, children or young people aged ≤18 years, admitted to PICUs, who received an intervention described as rehabilitation or mobilisation delivered by any health professional within ≤7 days after admission. Rehabilitation or mobilisation interventions could include but were not limited to physiotherapy (PT), occupational therapy, speech and language therapy (SLT) and bundled interventions; these included ABCDEFH bundles (spontaneous awakening and breathing trials; choice of sedation and analgesia, delirium prevention, surveillance and management; early mobilisation and exercise programmes with or without adjuncts; family engagement and empowerment; proper nutrition and humanism) so long as their application was considered within the first 7 days of admission; AND

2. Outcome: at least one outcome was related to participants’ health and well-being, health service utilisation, feasibility, acceptability or intervention implementation.

3. Study design: primary research studies of any designs, with >10 participants to synthesise evidence on intervention effectiveness. Case reports, case series with ≤10 patients, qualitative studies and systematic reviews were excluded if relevant primary studies were not identified in the references. Abstracts or ongoing studies identified from clinical trial registries were used to highlight the presence of future emerging research.

Screening and selection

Records identified were imported into a bibliographic referencing software programme (EndNote X9, Thomson Reuters, San Francisco, CA, USA), and duplicates were removed. One PT researcher (JT) and one clinical academic (BS or JMen) independently screened titles and abstracts for relevance against the eligibility criteria within Rayyan systematic review software. 1 The full texts of relevant articles were obtained and assessed against the selection criteria by two reviewers independently (JT, Dr Olivia Craw). A wider range of publication types (abstracts and full texts) were selected to identify all possible lists of ERM interventions but were not analysed to summarise types of ERM. Reasons for exclusion were noted. Discrepancies were discussed via consensus meeting with a third author (JMc).

Data extraction

Data were extracted using a standardised, piloted data-extraction form in Excel. Information within the following domains was extracted:

• Study – author, year of publication, country, study design using an algorithm for classifying studies. 2

• Patient demographics – age, sex, admission diagnosis, the severity of illness and, comorbidity using established criteria3 or paediatric scoring tools such as Pediatric risk of mortality (PRISM III), the Pediatric logistic organ dysfunction (PELOD), the Pediatric Cerebral Performance Category (PCPC) and the Pediatric Overall Performance Category (POPC). We also considered the following prognostic factors when assessing non-randomised studies: age, sex, weight or body mass index (BMI) in percentile, baseline severity, comorbidities and admission diagnosis on the intervention.

• Intervention details – definition of ERM, type of interventions, the volume of ERM (time-to-initiation, duration, number of sessions), implementation strategies such as safety and progression criteria, involvement of health professionals or availability of organisational support.

• Study comparators and outcome – components of usual care, primary and secondary outcomes (where specified) and assessment time points. When outcome measures were not specified or reported, the outcomes most proximal to the health domain were considered the primary outcome.

Data were extracted (JT) and independently verified by co-authors (Dr Olivia Craw, JMc and JMen). We used all eligible studies, abstracts or full texts that reported any intervention to summarise types of interventions. We only included full-text reports where ERM was initiated within the first 7 days of admission to PICU to synthesise ERM outcomes.

Quality assessment of individual studies

Risk of bias was assessed in randomised controlled trials (RCTs) the using Cochrane Risk of Bias tool version 24 and in non-randomised studies using the Risk Of Bias In Non-randomised Studies – of Interventions (ROBINS-I) tool. 5 One reviewer (JT) assessed the methodological quality of studies and this was independently verified by a second (Dr Olivia Craw, JMc).

We evaluated the reporting quality of studies using the Consensus on Exercise Reporting Template (CERT). 6 Due to the nature of the study interventions included in this review, participants, providers and assessors were aware of the intervention, which can affect compliance, outcome assessment or intervention fidelity. To understand implementation, we grouped studies that provided information on different aspects of delivering ERM, such as core content of ERM, who commonly delivers it, mode, timing, frequency of delivery, and the adaptation process for tailoring ERM.

Data synthesis

A narrative synthesis of all included studies was undertaken. Due to the heterogeneous nature of paediatric populations and interventions, meta-analysis was not appropriate. All outcomes were grouped as short-term (≤6 months post-discharge) or intermediate-term (≥6 months post-discharge) outcomes.

Characteristics of included studies

As shown in Figure 1, 2580 unique records were screened for relevance, and 62 relevant full-text articles were assessed for inclusion. Twenty-six of these were excluded, mainly due to the ineligibility of the study design or outcomes. Eighteen of the 36 studies that met the eligibility criteria were abstracts, and 18 had full-text reports. Most were conducted in North America,7–25 Australia,26 Belgium,27,28 Brazil,29,30 Italy,31 Japan,32–34 the Netherlands,35 Turkey36,37 and the UK. 38–41 One study was conducted across 15 countries in Europe42 (see Appendix 2, Table 32).

FIGURE 1.

PRISMA diagram.

Five studies15,18,21,22,24 were conducted across multiple PICUs, and two studies15,43 used controlled designs. Three studies were prospective cohorts,24,41,42 2 were interrupted-time series,7,27 9 non-comparative studies,8,10,13,22,30,31,34,36,40 11 before–after studies9,11,12,17,23,25,32,33,35,38,44 and 9 non-concurrent cohort studies. 14,16,18,19,21,26,28,37,45

Types of interventions identified

Of the 36 studies that evaluated PICU rehabilitation, we identified two broad categories of early rehabilitation or mobilisation (ERM): non-mobility and mobility interventions. Non-mobility interventions mentioned in included studies were pain and agitation assessment,23 sleep hygiene/delirium screening,17,22,23,35 ERM screening checklist,26 cuddles,18,40 SLT8,12,15,21 and chest PT. 21 The majority were mobility interventions and included mobility goals/orders,22,23,35,40,41 out-of-bed exercises,15,17 in-bed cycling,11,19,20,46 edge-of-bed mobility,40 bed-mobility exercises,15,17,21,32 interactive boxing,7 physical therapy8,10,12–16,18,21,30,32 and OT. 8,10,12–16,18,21,30 When usual care15,20,24 was used as a comparison, it consisted of positioning,

Interventions were commonly administered from 24 to 72 hours after PICU admission. The volume of sessions varied widely, but most sessions were delivered twice daily. In some situations,32 information on initiating ERM delivery was unavailable. Five studies7,11,19,26,43 used single-component interventions. One study13 reported the number of encounters or admissions but provided no information about patient characteristics. Multicomponent interventions (12/16 studies) consisting of PT, OT and SLT were more commonly explored.

Patient and study characteristics

Out of the 36 studies that met our eligibility criteria, 18 full-text records evaluated at least one ERM outcome (as defined by the study authors) within 7 days after admission; the results reported here are for these 18 full-text publications. The study population consisted of day-old children to ≤18 years, with sample sizes of 12–722 participants. In almost all studies (n = 17/18), patients were admitted with a mixture of medical and surgical diagnoses – respiratory, neurological and cardiac conditions.

Outcomes

Among 18 studies that evaluated ERM, the feasibility and safety of ERM alongside process outcomes were the most frequent outcomes considered. See Appendix 2, Table 32.

Adverse events

Fifteen studies7,10–14,17–19,24,25,32,36,42,43 provided information on adverse events (AEs). The most common event was tachycardia/desaturation. 13,14,24,42 Three studies reported haemodynamic changes7,15,42 or tube removals. 7,10,42 Other events mentioned include pain,7 fall,7 behavioural changes,24 excessive secretions24 and discontinuation of therapy. 14,15,43

Evaluation of early rehabilitation and mobilisation interventions

Feasibility/prevalence of early rehabilitation and mobilisation in observational prospective and retrospective studies

Secondary or clinical outcomes in observational prospective and retrospective studies

Predictors of early rehabilitation and mobilisation

Three studies evaluated predictors of ERM using multivariate analysis. 18,24,42 The adjusted odds ratio (aOR) for out-of-bed mobility was negatively associated with the presence of an ETT (aOR, 0.13; 95% CI 0.08 to 0.2), a urinary catheter (aOR, 0.28; 95% CI 0.14 to 0.57), opioid infusion (0.42; 95% CI 0.24 to 0.73) and severe baseline disability (PCPC 4 vs. 1) (aOR, 0.59; 95% CI 0.4 to 0.87). Longer PICU LOS and lower nurse-to-patient ratio (1.82; 95% CI 1.2 to 2.8) increase the odds of out-of-bed mobilisation. For children <3 years old, family presence was associated with out-of-bed mobility (aOR, 4.55; 95% CI 3.1 to 6.6) while being older predicted PT or OT (aOR, 3.1; 95% CI 2.01 to 4.79). 18 In another study,24 the presence of ETT or infusion among children ≤3 years reduced the likelihood of receiving therapist-provided out-of-bed mobility [odds ratio (OR) 3.62; 95% CI 1.49 to 8.82]. However, this improved when the family were present. 24

Ista and colleagues42 showed that older age (2.28, 95% CI 1.23 to 4.22), moderate baseline disability (defined as PCPC: 3 vs. 1) (2.12, 95% CI 1.02 to 4.56), severe baseline disability (PCPC: 4 vs. 1) (2.24, 95% CI 1.14 to 4.40), having a central venous line (CVC) in place (aOR 1.63, 95% CI 1.02 to 2.62) and family presence (aOR 5.13, 95% CI 2.55 to 10.32) increased the odds of receiving a mobility session. However, the presence of a urinary catheter reduced the chance of mobilisation (aOR 0.46, 95% CI 0.22 to 0.92). MV through an ETT (aOR 0.29, 95% CI 0.12 to 0.68), being admitted for a surgical reason (aOR 0.58, 95% CI 0.35 to 0.95) and the presence of a urinary catheter (aOR 0.39, 95% CI 0.19 to 0.81) reduced odds of out-of-bed mobility, but this improved with family presence (aOR 7.83, 95% CI 3.09 to 19.79). 42

Quality assessment

Prospective and retrospective studies

We used the ROBINS-I tool to assess the quality of observational studies (see Appendix 2, Table 33). Overall, most studies were judged to have a serious or critical risk of bias. Three studies (3/18)18,24,42 were judged to have a low risk of bias. Nine10,12,13,15,19–21,25,32 were judged to be at moderate risk of bias, while in four there was serious risk. 11,14,16,31 In some studies bias was judged as critical,8 or information reported was insufficient17 and could not be assessed (Figure 2).

FIGURE 2.

Pictorial presentation of quality assessment using ROBINS-I.

The primary reason for downgrading studies was bias due to blinding or poor consideration of baseline confounding. There was no indication of selection bias during enrolment; studies were judged as adequate except in three retrospective studies. 14,17,31 The lack of a clear definition of ERM hierarchy limited the evaluation of demonstrable effects on objective clinical outcome measures. This made it challenging to determine intervention superiority. Broadly, intervention categories of non-mobility and mobility were consistent across studies, which were judged to be at risk of misclassification bias half of the time (9/18). We assessed the impact of bias due to deviations from the intended response as adequate in most studies. In some studies,7,8,10,11,13,14,16,17,21,32 the technique for handling missing data was unclear or not reported. We did not identify any evidence of selective outcome reporting or errors due to outcome measurements. Most studies demonstrated congruence between previously defined analyses and outcomes reported. However, none of the studies published a protocol. Overall, most studies did not provide definitive evidence of the effects of the intervention. However, consistent evidence across all studies supports the feasibility of ERM as an intervention in PICU, while physical therapy was the most common intervention considered.

Quality of consensus on exercise reporting

We described techniques considered during intervention design and excluded items not relevant to this review. These items included item no. 3 (descriptions of individual or group exercises), item no. 9 (use of home equipment; discharge interventions were not considered) and item no. 12 (setting of exercise delivery; all studies were conducted in PICUs). See Appendix 2, Table 34 for details.

Quality of consensus on exercise reporting reporting

Most studies (12/18)7,10,16–18,20,21,24,25,31,32,42 provided details on the type of ERM intervention to aid replication. Some studies (4/18)18,21,25,32 provided training or engaged multidisciplinary teams (MDTs) to facilitate ERM delivery. Organisational strategies were sometimes applied across MDTs to facilitate PICU culture change. Some studies (12/18) explicitly mentioned using qualified providers such as physiotherapists, nurses or other therapists to supervise sessions and ensure intervention fidelity. 10,11,13–15,17,18,21,24,25,42,43 However, the detail provided was insufficient to explain how differences in experience levels, treatment approaches and therapists’ behaviour in these circumstances influence outcomes.

Intervention components were generally tailored and not standardised. Sometimes, it was unclear what aspects of the interventions were usual practice or complementary during ERM delivery. In most studies, information on how deviations from study protocols were handled (i.e. regression or progression) and how these events may have affected outcomes was unavailable. Personalising the volume of ERM was a common concept across studies used to improve compliance. However, since interventions were tailored to tolerance levels, we did not assess intervention fidelity. Some studies provided a detailed description of how compliance or adherence was measured. Strategies mentioned include rehabilitation sheets11,19,20,32 and electronic records during PICU ward rounds. 17,18 Two studies7,11 used an objective outcome to measure compliance – ACTi-graph accelerometers. This outcome measure can be used as a benchmark for future studies, incorporating routinely collected outcomes to increase transferability. 47 Labour-intensive or ad hoc approaches for determining adherence or compliance, such as caregiver verbal confirmation following direct observation, charts or checklists, may limit the implementation of rehabilitation and future attempts at service evaluation.

Early rehabilitation and mobilisation change techniques

No study provided explicit details about applying complex intervention theories when designing interventions, while details on the implementation processes were inconsistently reported. Therefore, it is unclear to what extent interactions between intervention volume of ERM and health systems produce positive effects. It is not impossible to envisage a situation where contextual factors such as how the intervention works, for example the presence of a local champion or an ERM enthusiast, staff turnover, population demographics, or existing PICU culture, affect outcomes, either positively or negatively. No study provided details on motivation strategies or precise details on how interventions were personalised. Safety guidelines (underpinned by clinical stability), verbal feedback and tolerance levels to determine progression were commonly used across studies. Eight studies10,14,17,18,21,24,25,42 provided information to enable replication. Hence, these studies can be used as a springboard to undertake detailed intervention mapping when designing ERM manuals. Overall, key aspects of intervention delivery were poorly reported, such as co-interventions, strategies for tailoring interventions and motivating patients.

Evidence

We found that children under 3 years of age admitted to PICU tend to be given passive and active in-bed activities. Children 3 years and older were primarily involved in out-of-bed activities when this was considered safe. In addition, one study18 reported higher ERM incidence among male children, but this finding was not consistent across studies. Hence, it is unclear what interventions should be administered to these age groups and whether certain combinations of interventions are superior to those given to their older counterparts.

We found equivocal evidence suggesting that other factors such as time to admission, tube presence, MV, or sedation also influenced developmental or mobility goals. Only four studies13,18,24,42 evaluated baseline severity of illness (measured using validated tools) and comorbidities that affected clinical and functional outcomes in multivariate models. Consequently, the effect of residual confounding or chance on the estimated intervention effect remains unknown. Overall, the evidence about subgroup effectiveness was indicative of clinical pragmatism but otherwise inconclusive.

Comparison with the broader literature

Our findings reflect the evidence in previous systematic reviews of ERM interventions within adult and paediatric PICU. 53–56 The evidence emerged from North American PICU contexts, and its transferability to the UK settings remains uncertain. 38,39,46,57 Besides variation in practice, interactions within complex health systems have additional issues. As an additional complexity, due to the nature of interventions considered in this review, it is difficult to determine if intervention effects are additive, multiplicative (biologically plausible) when combined or neutralise each other and plateau.

Most outcomes of feasibility or acceptability were exploratory findings, and the strength of the evidence for objective clinical or functional outcomes remains unclear. Nevertheless, PT and OT, sometimes with SLT, were frequently implicated in the exposure-mechanism-outcome pathway. Furthermore, barriers reported reflect previous literature and support the need for activity orders.

Study management

The work package was led by BRS. JYT co-ordinated survey responses and developed the on-line tool. The study management group provided input into survey questions and designs. The study was piloted in Birmingham and Nottingham by JYT, Emily Brush and Francesca Ryde. Statistical analysis of the full survey was undertaken by JYT, BRS, JMen, JMan and JMc. Qualitative analysis of the free-text responses was undertaken by JYT.

Demographics

We received responses from PCCS-SG link members in 26/29 (90%) UK PICUs. A total of 191 health-care professionals opened the survey link with 124 (65%) submitting responses, with a median of 4.5 participants (IQR 3–6) per PICU.

Most respondents were nurses (n = 34, 27%), physiotherapists (n = 28, 23%) and doctors (n = 22, 18%) (see Appendix 3, Table 36). Respondents also included occupational therapists (OT) (n = 19, 15%), play therapists (n = 7, 6%), psychologists (n = 7, 6%), dieticians (n = 6, 5%) and SLTs (n = 1, 1%). Almost three-quarters of health professionals had ≥5 years’ experience, with 48 (39%) ≥15 years.

Description of early rehabilitation and mobilisation

We invited participants to describe ERM in their own terms, with 104 (84%) responding. Participant definitions of ERM aligned to four categories, ‘Activity-focused’, ‘Tailored’, ‘Promote recovery’ and ‘Timing of ERM’ (Table 1). Overall ERM was an individualised package of graded interventions, based on an activity-focused programme, to reduce the sequelae of critical illness or injury. However, responses differed for when ERM should be initiated, often emphasising the need for individualisation.

Most respondents considered ERM to be a priority, either crucial 15 (12%), very important 67 (55%) or important 35 (29%) in the care of PICU patients (see Appendix 3, Table 37).

Availability of established early rehabilitation and mobilisation protocols

Respondents were asked to describe the content of established ERM protocols within their PICU. Only 12 (10%) participants from 5/26 PICUs reported having an established ERM protocol. The most common components of ERM protocols were ‘physical therapy not requiring additional equipment’ (9/12, 75%) and ‘OT interventions’ (8/12, 67%). Only 4/12 (33%) referred to play therapy or SLT, and no ERM protocol specified input from psychologists or psychiatrists.

All participants were asked about the content of non-ERM protocols in their PICU. Only 18/124 (15%) participants reported that guidance for physical or OT activities existed in other, non-ERM protocols that were used in the PICU setting (see Appendix 2, Table 35).

Recipients of early rehabilitation and mobilisation

Despite the paucity of ERM protocols, 51 (41%) respondents reported that all PICU patients ‘always’ or ‘very often’ received ERM (Table 2). ERM was reported to be more likely to be delivered to patients when PICU LOS exceeded 28 days. Patients admitted for 28 days or more were more likely (91, 75%) to ‘always’ or ‘very often’ receive ERM in comparison to only 17 (13%) of those reported to stay fewer than 3 days. Participants reported that patients with acquired brain injury (75, 60%) and severe developmental delay (54, 44%) were ‘always’ or ‘very often’ likely to receive ERM.

Perceived benefits of early rehabilitation and mobilisation

Participants ranked the 5 most important potential benefits of ERM out of 13 options (Figure 3). The most important outcomes identified were: (1) reduced PICU LOS, (2) improved psychological outcomes for patients after PICU, (3) reduced days of MV, (4) improved participation in activities of daily living and (5) improved patient satisfaction.

FIGURE 3.

Perceived benefits of ERM. Ranking of participants’ potential top five perceived benefits of delivering ERM within PICUs. Sum of rank score: ranking of top five (1–5) (first-placed rank scored five points to fifth placed scored one point). Ranked scores of 121/124 (98%) participants.

Initiation and delivery of early rehabilitation and mobilisation

The decision for ERM initiation was perceived by respondents to be primarily led by physiotherapists (96, 77%), doctors (92, 74%) and bedside nurses (64, 52%). Parents were felt to initiate ERM by only 24 (19%) of respondents (see Appendix 3, Table 38).

Factors that influenced ERM initiation included patient stability (69, 56%) and LOS, specifically within 3 days of admission (31, 25%). Five (4%) respondents reported they would not consider ERM at all. The influence of perceived clinical stability is demonstrated in respondents’ free-text comments:

We are involved as early as required depending on the child/young person medical stability and their rehabilitation needs.

(OT, 033)

Usually, ERM activity is not considered until patients can physiologically tolerate movement and are cardio-vascularly stable.

(Nurse, 008)

Assessment of patient stability and tolerance of ERM were less well described. Most respondents (98, 79%) provided subjective cues or informal clinical criteria. These included monitoring of vital signs, physiological changes, observation of behavioural changes and documentation of AEs.

Physiotherapists (113, 92%), nurses (103, 84%) and parents or family members (92, 75%) were ‘always’ or ‘very often’ involved in the ongoing delivery of ERM, with less frequent input from other members of the MDTs (see Table 2).

Barriers to early rehabilitation and mobilisation implementation

Figure 4 presents the perceived barriers of ERM. The most significant factors identified as barriers at the institutional levels were insufficient resources/equipment (83, 69%) and inadequate funding (73, 61%). Participants provided examples of resources having to be shared across organisations or having to be specially ordered to deliver ERM to patients.

FIGURE 4.

Perceived barriers of ERM.

All equipment shared with the whole therapy department at present, therefore dependent on availability.

(OT, 010)

Most PICUs had access to standard lifting 22/26 (85%) and specialist static seating equipment 25/26 (96%). However, bedside or in-bed cycling machines were only available in 10 (38%) of PICUs (see Appendix 3, Table 39).

A lack of established protocols (69, 57%), ERM champions (68, 57%), space (68, 56%) and robust patient-screening processes (63, 58%) were also issues identified by respondents.

Limited staffing was the most frequently reported barrier to ERM being delivered (101, 79%). Approximately half of the respondents agreed issues such as training, patient safety, lack of decision-making authority and delays in recognition of patients’ ERM needs were barriers to ERM initiation. However, only 25 (21%) identified that the impact of ERM potentially prolonging the working day was a barrier.

At the patient level, the two most frequently reported barriers to delivering ERM were physiological instability (101, 81%) and sedation (91, 73%).

Institutional, patients and provider barriers to ERM

Table 2 shows the percentage of responses for the categories strongly agree, agree, neutral, disagree and strongly disagree. Responses ranked on the cumulative score of percentage ‘strongly agree and agree’.

Study management

The work package was led by BRS. The study management group provided input into protocol and ethics design. JYT was study co-ordinator and piloted and developed the Research Electronic Data Capture (REDCap) database. Statistical analysis was undertaken by JYT, BRS and James Martin. Data interpretation was by BRS, JYT, JMan and JMen with input from all study management group.

Study design

A multicentre prospective observational study.

Target population/setting

All CYP (0 to <16 years) admitted to PICU and remaining on PICU by 9 a.m. on day 3 after PICU admission were eligible to participate. The exclusion criteria included a local decision by PI or treating clinical team not to include patients (e.g. receiving end-of-life care) and parents or guardians who choose to opt out. The broad study inclusion criteria allowed for the observation of all types of patients admitted for PICU care (e.g. planned and unplanned admissions), and all age ranges.

Site and patient selection

The Paediatric Early Rehabilitation and Mobilisation during InTensive care (PERMIT) study was an observational study conducted in 15 UK PICUs across two 21-day periods: (1) 26 November–16 December 2019 and (2) 14 January–3 February 2020. PICUs were identified from the PERMIT survey (see Chapter 2). The PICUs selected were of varying sizes (n = 6 large: >800 admissions/year, n = 5 medium: 500–800 admissions/year, n = 3 small: <500 admissions/year) and reported ERM activity of differing levels in the survey.

This study was conducted in two separate time periods to maximise efficiency, overcome recruitment hurdles and meet the target. Ten sites recruited and collected data during period 1, with a further five sites in period 2. Patients were observed on study day 1–14 with a further week to complete follow-up (study day 15–21). Individual patient data collection and observations took place for up to 7 days after patients were recruited or until PICU discharge, whichever was sooner.

Recruitment/enrolment

The study protocol, manual of operation, checklists and case report forms (CRFs) provided details on the study procedures. Staff at participating sites received remote training on research conduct before, and ongoing support sessions during, the study period.

Research staff screened patients admitted to PICU for the PERMIT study using a bespoke study screening log. The daily screening process ensured patients becoming eligible (e.g. the day before their third day) were identified. Designated research co-ordinators entered data on ERM activities recorded by clinical staff in clinical notes on the study proformas. Data were transferred to a secure electronic database (REDCap™), with scanned copies uploaded for data validation. Data were pseudo-anonymised at the local site before secure transfer to the PERMIT trials office.

Consent

As the study was observational, Regional Ethics Committee (REC) approved data collection without seeking prior consent from parents/legal representatives. In addition, this avoided unnecessary burden for parents/legal guardians in approaching consent during a very sensitive time. Information about the study was provided to all eligible patients’ families and was displayed within public areas of participating PICUs. This explained the study to parents, family, friends and children who were able to make autonomous decisions. Parents/legal guardians were able to opt the child’s data out of the study at any time and were aware that the future care their child would receive would not be affected.

Study procedure and data collection

Site staff collected demographic data on the third day of admission. Clinical and ERM data were collected from enrolment until discharge at the end of the study period. Data were collected twice, between 09.00 and 10.00 and between 14.00 and 15.00, each day.

Patient-level data

Patient characteristics collected at PICU admission included age (in categories); reason for admission; primary diagnosis; the severity of illness using Pediatric Index of Mortality (PIM3) score, with clinical function being assessed at baseline (pre-PICU state) and admission via the PCPC and POPC, which scores from 1 to 6 (1: normal, 2: mild disability, 3: moderate disability, 4: severe disability, 5: vegetative state or coma and 6: death). 63 PICU LOS was also recorded.

Clinical data

Data collected during PICU stay included healthcare interventions; requirement for MV; sedation and level of consciousness; presence of delirium; critical care interventions; indicators of physiological status; and individual patient PICU resource use. We calculated PELOD score (PELOD-2),64 which is a measure to describe the severity of organ dysfunction/illness in critically ill CYP, daily at 9 a.m.

Observed early rehabilitation and mobilisation active interaction

Clinical staff performing ERM activities were instructed to record the planned and delivered ERM activity duration in medical records. A research nurse or co-ordinator used these data to complete the bespoke active interaction CRF, which was submitted to the PERMIT study office. CRFs were completed hourly between 9 a.m. and 5 p.m. by the local site research nurse. A retrospective review of clinical case records of ERM activities that occurred overnight was carried out, with CRFs completed accordingly. Overnight ERM interventions were defined as the time from the end of the observed active interaction period 17.01 until 08.59 before the start of the next period.

We defined a priori ERM as (1) any ERM activity, (2) any mobility ERM activity and (3) mobility activity out of bed, informed by scoping review and survey (see full breakdown of ERM activities, ERM group and level of ERM detailed in Appendix 3, Table 40). We excluded chest PT, tracheal tube suctioning and routine nursing ‘cares’ (such as mouth and eye cleaning).

Patients were defined as receiving any ERM intervention if any ERM was recorded on study day. Details on interventions such as type of ERM activity (mobility, non-mobility, out-of-bed, passive, active and psychological) and safety events (such as changes in heart rate, oxygen saturation, removal of tubes or falls) were recorded.

Primary outcome

• the delivery of any ERM activity on day 3 post admission (study day 1).

Secondary outcomes

• the delivery of any ERM activity on days 4–10 post admission (study day 1–7);

• the delivery of ERM involving any mobility activity and out-of-bed mobility ERM on days 3–10;

• the number, type and duration (e.g. dose) of ERM delivered on each day;

• predictive factors related to the delivery of ERM on day 3 post admission.

Data analysis

We reviewed data for errors: missing data, duplicated records and outliers. Extreme values were set to missing if they were deemed impossible, based on their validity range. Continuous variables were reported as mean and SD or median and IQR based on data distribution. Categorical variables were described in numbers and/or percentages.

The prevalence and scope of ERM were described as the proportion of patients provided with any ‘active interaction’ of any ERM on day 3 post admission. Proportions of eligible patients receiving ERM interventions were analysed for each day. Rate ratios of patients receiving an ERM intervention during the study period were analysed using a Poisson regression model.

Cumulative prevalence for each day in PICU after day 3 up to day 10 post admission was calculated. Cumulative proportion of patients receiving ERM interventions as per prespecified categories during the study period was described graphically using Kaplan–Meier estimation and event rate plots.

We undertook further analysis to understand potential predictive factors associated with ERM and the incidence of ERM. We performed multivariable logistic regression to evaluate predictive factors of ERM provided on day 3. Factors of interest were established following the PERMIT survey and expert group consensus. These included age; baseline PCPC score; unplanned versus emergency admission; ventilation status; requirement of vasoactive infusion, sedative infusion, or neuromuscular blocking drugs; presence of urinary catheter, CVC or arterial line; family member present or participating in ERM activity; and presence of PICU protocol.

We calculated level of mobility activity using a modified progression score previously described in the EU-PACK (European Prevalence of Acute Rehabilitation for Kids in the PICU) study42 – Level 1: passive ROM, 2: sitting and exercise in bed, 3: sitting edge of bed, 4: held by parent or nurse (cuddle), 5: transfer to chair, 6: mat play, 7: standing, 8: walking in room/PICU, 9: walking out of PICU (see Appendix 3, Table 40). Further post hoc categorisation of ERM activities as enrichment, passive and active activities was also applied.

Adverse events rates were calculated per ERM activity. For zero rate observed AEs, the upper 95% CI are presented using Hanley’s formula. 65

Patient and public involvement and engagement

For an overview of the approach to patient and public involvement and engagement (PPIE) adopted throughout the study, please see Chapter 8. With this element of the study, we explored the potential consent model, especially the acceptability of an ‘opt out’ approach to consent. There was a study recruiting at the time on PICU with an ‘opt out’ approach – the Sedation AND Weaning In Children trial (SANDWICH) trial. 66 At the time, the SANDWICH trial had recruited over 700 patients at Birmingham Children’s Hospital (BCH), with only three families choosing to opt out of their child’s data being collected. It was therefore regarded as a highly successful approach to consenting.

For the SANDWICH trial, parents were given a leaflet outlining that data collection was taking place on data routinely collected as part of ‘normal care’ which goes to the national PICU audit. 67 They were told that the SANDWICH team would have access to some of this information. In addition, the research team would also collect information from the child’s medical notes and charts. All the data were anonymised and there were no interventions (at the individual level), just data collection. Parents were not asked for their informed consent. They received the Participant Information Sheet (PIS). If they did not want to take part, they then spoke to the clinical staff, who informed the research staff, and this was documented as an ‘opt out’.

We spoke to families who had received the information to ask how they had experienced the process of approach for the SANDWICH study. In addition, we approached families who were participating in other research studies known to the PPIE lead (JMen) and whose children had recently been discharged from hospital. We spoke to six parents of four children (aged 0.3–6 years) who had experienced one or more PICU admission(s) and had experience of their child being recruited to research. We also spoke to three young people (aged 17–20) naive to PICU to participate as PPIE participants. Different models of consent were discussed and where there was no intervention then an opt-out model of consent was universally popular (Table 3). We also discussed the PISs and poster to inform parents about the observational study with them and they suggested a number of changes to the language, graphics and layout of them.

Eligibility and enrolment

A total of 169 patients were enrolled into the study from 15 PICUs, with each PICU enrolling a median (IQR) of 10.0 (9.5–15.3) patients.

During the 14-day enrolment period, the median census on each PICUs was 10.5 patients (IQR 7.0–17.0; range 3–26). Overall, there was a median (IQR) of 1 patient (0–2) eligible per PICU per study day of whom 1 patient (0–1) was enrolled into the study per PICU per study day. This identified 203/2447 (8.7%) patients within each PICU eligible, of whom 158/203 (77.8%) were enrolled over the 14-day enrolment period (enrolment data were missing from 1 unit which recruited 11 patients). Ineligible patients had either not reached day 3 or had already reached day 4 or greater on day of screening. Table 4 shows PICU patient census, eligibility and enrolment proportion. During days 8–14, some sites reported not enrolling as they had already reached their target of 10 patients. Enrolment rate in study days 1–7 was 98/108 [90.7% (95% CI 83.6% to 95.4%)].

Demographics

Of the 169 patients, 59.2% were male; median age was 4.5 months (IQR 1.1–37.9). The majority (81%) were <4 years with 62.7% <1 year. Only 48 (28.4%) were ambulatory prior to PICU admission (key demographics at admission are in Table 5).

The most common admission diagnosis was bronchiolitis in 55 (32.5%). Eighty-four (49.7%) were admitted from another hospital, requiring retrieval into PICU. There were 127 (75.1%) emergency admissions, 150 (89.3%) required invasive ventilation at admission, 5 (3%) extracorporeal membrane oxygenation (ECMO) and 60 (35.5%) required cubicle isolation. Prior to admission, 66% had a PCPC score of 1 or 2 and 50% a POPC score 1 or 2, indicating a high proportion with moderate to severe disability pre-PICU. Admission predicted probability of mortality, as measured by PIM3, was median 1.2% (0.5–4.4%) and 68 (40.2%) children were enrolled in a PICU with an existing ERM protocol (as reported in the PERMIT survey – Chapter 2).

Patient clinical status on day 3 of admission (study day 1)

Between PICU admission and study day 1, 12 (7.1%) had surgery, 1 had a cardiac arrest. Most (119; 70%) remained ventilated by an ETT, 40 (23.7%) required vasoactive infusions and 3 remained on ECMO (Table 6).

Sedative medications were used in 108 (63.9%); 102 on opiates, 40 on benzodiazepines and 26 (15.3%) were on neuromuscular blocking drugs. In patients who could be assessed and on sedative drugs, comfort B sedation score was median (IQR) 12 (11–14), and 12 (12–15) if not receiving sedation. No patient was screened for delirium in any PICU. PELOD2 severity of illness median score was 4 (IQR 2–6). Central venous access was used in 103 (60.9%), arterial access in 72 (42.6%), and 103 (60.9%) had a urinary catheter. Pressure ulcers were reported in 6 (3.6%) patients.

Early rehabilitation and mobilisation prevalence

On the first day of PERMIT study (day 3 post-PICU admission) overall 162/169 (95.9%) received at least one ERM activity. A mobility ERM activity was delivered to 147/169 (87.0%) of which an out-of-bed mobility ERM was delivered to 64/169 patients (37.9%).

Figure 5 shows the reduction in number of patients remaining in PICU following enrolment to PERMIT and the prevalence for (1) any ERM, (2) mobility ERM and (3) out-of-bed ERM mobility. Of note, by day 7 post PICU admission, half of patients enrolled into PERMIT had been discharged and by day 9, 113 (67%) had been discharged and 2 (1%) had died.

FIGURE 5.

Prevalence of ERM for each study day in PICU.

The rate of receiving ERM during the PERMIT study period, analysed using a Poisson regression model, did not change across the study period. We did not identify a significant trend with rate ratios of (1) any ERM: 0.98 (95% CI 0.92 to 1.05, p = 0.57), (2) mobility ERM: 0.97 (95% CI 0.93 to 1.01, p = 0.14) and (3) out-of-bed mobility 0.97 (95% CI 0.93 to 1.01; p = 0.14).

Cumulative probability of early rehabilitation and mobilisation

Figure 6a shows that while over 95% of enrolled patients were observed to have received an ERM intervention on day 1 of the study period, mobility ERM and out-of-bed ERM were less frequent (see Figure 6b and c). However, by day 6 of the study, 98% of patients had received a mobility ERM and 80% (see Figure 6b) of patients had received an out-of-bed ERM at some point during their observed period (see Figure 6c).

FIGURE 6.

Cumulative probability of (a) any ERM, (b) mobility ERM and (c) out-of-bed ERM.

Description of early rehabilitation and mobilisation

In total, 3696 ERM episodes capturing 4978 ERM activities occurred during 729 patient days. On the first study day (day 3 post PICU admission), 169 patients received 977 ERM episodes and 1302 ERM activities [median IQR 7 (4–10) ERM activities per patient].

Analysing the whole study period, positioning (which incorporated the mobility element) (1205/4978; 24%) and non-mobility positioning (1177/4978; 23.6%) were the most frequent activities (Figure 7). Active mobility was less frequent: the majority were active movement (e.g. rolling, active ROM) and sitting up in bed or transfer out of bed to chair or mat. No in-bed cycling was reported throughout the observation period.

FIGURE 7.

All ERM activities ranked by active, enrichment and passive categories.

Table 5 compares the baseline characteristics of patients receiving any ERM, mobility ERM or out-of-bed ERM and those who did not on the first study day. Patients receiving mobility ERM tended to be older that those who did not; however, the opposite was seen in out-of-bed mobility, where younger patients (especially <3 months) were more likely to receive mobility out of bed (e.g. cuddles). We identified no difference across ethnicity groups or diagnostic admission group in the proportion of patients receiving each category of ERM. We did identify that patients with moderate (PCPC 3) or severe disability (PCPC 4) received less out-of-bed mobility.

Table 6 compares the clinical status of patients with ERM type on the first study day. Patients receiving or not receiving any ERM or mobility ERM were similar in respect to the majority of measured clinical status factors. The only differences were between patients receiving out-of-bed mobility or not. There were more patients receiving invasive ventilation (high-frequency oscillation and conventional ventilation), use of neuromuscular blocking drugs, sedative drugs and with additional lines or tubes (e.g. central venous catheter, arterial line, urinary catheter and chest tubes) in the group not receiving out-of-bed mobility. This was also reflected in the higher PELOD2 organ dysfunction score for patients not receiving out-of-bed ERM [5 (IQR 3–6)] versus those who did receive [2.5 (IQR 0–5)].

Mobility activities

Using the ranking scale described by Ista et al. 42 on the first day of study 147/169 (87%) had a mobility ERM activity. The ranked activities are shown in Table 7. Most were either passive ROM or cuddles. Only 29 (17%) involved ranked 5–9 activities (transferring out of bed, mat play, standing or walking).

Staffing and parental involvement in early rehabilitation and mobilisation

We examined staffing and parent data across all ERM episodes (which may have involved a combination of activities). As shown in Figure 8, registered nursing staff were involved with the majority of ERM episodes (3127/3696, 85%). Parents/guardians were present for 1614/3696 (44%) and participated in delivering 1372/3696 (37%). Physiotherapists delivered only a small proportion of ERM episodes (361/3696; 10%).

FIGURE 8.

Number of parents, guardians or healthcare professionals involved in ERM episodes.

For individual patients, on the first study day, only 57/162 (35%) of patients received at least one ERM episode delivered by a physiotherapist. Across the duration of the study period this increased to 95/162 (59%) of patients having the input of a physiotherapist for at least one ERM activity. While the majority of ERM episodes were delivered by registered nursing staff or parents, without specialist therapy input there is a risk that ERM activity quality may be low (e.g. not targeted at the patient acuity or developmental age).

Timing and duration of early rehabilitation and mobilisation

ERM episodes were commenced throughout the 24-hour period of PICU with 1855/3730 (49.7%) occurring between 09.00 and 17.00 (Figure 9). The median duration of ERM episode was 15 (IQR 10–30) minutes and 37% of ERM episodes were of short duration (1–14 minutes) (Figure 10).

FIGURE 9.

Histogram of ERM start time.

FIGURE 10.

Duration of ERM episode (data available n = 3410).

As the professional group present at the bedside 24/7, nursing staff delivered 85% of ERM activities and 48% of these activities were commenced outside ‘9 a.m. to 5 p.m. office hours’ and emphasise the need to view ERM as a 24/7 intervention and not just an activity performed during office hours by physiotherapists. Less than 10% of ERM episodes delivered by a physiotherapist were outside 9 a.m. to 5 p.m..

Predictive factors associated with out-of-bed mobility

We created a multivariable logistic regression model to explore predictors of interest for out-of-bed ERM on study day 1 (day 3 of PICU) (Figure 11). Factors associated with a decreased odds of out-of-bed mobility included pre-PICU severe disability (PCPC score 4 vs. 1) [OR 0.09 (95% CI 0.01 to 0.61)], invasive ventilation [OR 0.23 (95% CI 0.06 to 0.83)] and presence of a urinary catheter [OR 0.16 (95% CI 0.16 to 0.42)]. The only statistically significant factor associated with increased odds of out-of-bed mobility was the presence of a parent or guardian and/or their involvement in the ERM activity [OR 13.46 (95% CI 1.05 to 172.7)], although the CI was wide. Of note, a vasoactive infusion was associated with increased out-of-bed mobility [OR 1.85 (95% CI 0.5 to 6.82)] and use of neuromuscular blocking drugs was associated with decreased out-of-bed mobility [OR 0.33 (95% CI 0.08 to 1.4)]; however, both of their CIs crossed 1. We were unable to create models for any ERM or mobility ERM because of the high rate of positive events for both on study day 1.

FIGURE 11.

Forest plot of odds of out-of-bed mobility on study day 1 by key factors.

Adverse events

There were 106 recorded AEs during 78 separate ERM episodes (Table 8). Overall proportion of ERM activities with an AE was 106/3696 (2.87%; 95% CI 2.35 to 3.45), which equates to 1 in 35 (95% CI 1 in 29 to 1 in 43) ERM activities. The most frequent reported event was desaturation in 38 (1.03%; 1 in 97) of ERM activities and discomfort of patient or tiredness in 18 (0.49%; 1 in 205). There was only one ETT tube dislodged, and seven other tubes dislodged, during the entire study period. Overall ERM delivery was safe, with a very low rate of AEs.

Study management

Phase 2 was co-led by co-applicants JMc, RF and TR (the core intervention development team). Two research associates (Dr Laura Cutler and Dr Olivia Craw, Faculty of Medical Sciences, Newcastle University) supported the organisation of the workshops and literature-based work. The study management group provided input into protocol, ethics application design and data interpretation.

Important changes to protocol

The PERMIT protocol planned a Phase 2a, Health Research Association (HRA) approved, workshop with parents and children. In discussion with and approval of National Institute for Healthand Care Research (NIHR) Health Technology Assessment (HTA) funder, this subphase was not started due to the impact of the COVID19 pandemic.

Formal reflection – establishing core issues

Purpose: to formally describe and synthesise the key messages, assumptions and uncertainties that emerged from our prior Phase 1 work to guide our intervention development work.

Methods: we reviewed the results of the survey, observational study and scoping review (see Chapters 1, 2 and 3), and undertook discussions with the wider PERMIT research team. We further refined and conceptualised the core findings of this process by aligning them to elements of the template for intervention description and replication (TIDieR) checklist. 79

Results: as outlined in Table 9, people see the potential value of ERM for the diverse patient populations within PICU and are willing to support its (safe) delivery but are uncertain how best to deliver it. The current evidence base and analysis of existing practice demonstrate that ERM is defined and enacted in multiple ways, ranging from more formal referral processes (directing patients only to specific allied health professionals), to a range of mobilisation and non-mobilisation activities, to being seen as encompassing everyday standards of good practice in PICU care. Core questions remain unresolved in relation to the conceptualisation of ERM, the pragmatics of operationalisation (e.g. how ‘early’ should ERM be delivered), and how best to measure the delivery and potential impact of ERM.

User development – generating guiding principles for the intervention

Purpose: to explore clinical stakeholders’ views and experiences of ERM for different populations, including feasible and acceptable content, delivery, implementation and important outcomes of ERM.

Methods: we took forward the key messages and uncertainties from Phase 1 into interactive workshops with UK NHS healthcare professionals and international ERM experts. The workshops received ethical approval from Newcastle University (NU Reference 14224/2018). We also planned to conduct workshops and interviews with parents and CYP in Spring 2020. These received HRA approval (IRAS 270791) but were unable to proceed as NHS Research and Development were not allowing non-COVID research at the time.

Sampling and recruitment: we recruited a multidisciplinary group of NHS healthcare professionals with diverse experience of ERM in PICU settings. We recruited from those who had participated in the Phase 1 survey and agreed to be approached about further work. They were approached via e-mail and a total of 18 professionals from 5 PICUs were included – 3 consultant doctors, 3 senior nurses, 5 physiotherapists (including 2 clinical specialists), 5 OTs (including 1 clinical specialist), 1 dietician and 1 play specialist. We also recruited a multidisciplinary group of international experts leading research and quality improvement on ERM in paediatric and adult intensive care settings. We recruited individuals who are active in the ERM community, identified from reviewing recent published work and from the team’s clinical and research networks. These people were approached via e-mail and a total of three were included from Europe and the USA – a senior clinical academic doctor, a senior clinical academic nurse and a senior physiotherapist.

Data collection: we undertook three face-to-face workshops with NHS healthcare professionals and one online workshop with international experts. Initial workshop plans were designed to explore the key reflections from Phase 1 and examples of existing ERM protocols. Plans evolved through findings from prior workshops shaping the focus of the next. The workshops were audio recorded and transcribed and facilitators recorded contemporaneous fieldnotes. The workshops lasted for between 90 minutes and 2 hours.

Data analysis: we drew on standard procedures from rigorous qualitative analysis80 including coding, constant comparison, memoing and team debrief sessions. The core intervention development team (JMc, RF, TR) reviewed, discussed, organised and summarised the analytic work. Following ideas from PBA,76 we focused on generating ‘guiding principles’ in relation to:

• Intervention design objectives – what an ERM manual must do to address the needs of target users and enhance engagement.

• Key features of the intervention – how these design objectives may be achieved in practice.

These guiding principles were critically discussed and revised with the wider PERMIT research team.

Results: as outlined in Table 10 ERM can be conceptualised as patients engaging in progressive movement and mobility in the context of individually meaningful and purposeful activities and a supportive environment that promotes familiar and orientating daily routines. Several discrete interventions can be legitimately conceptualised as either closely related to or a core part of ERM and these topics are being investigated in their own right (e.g. sedation, ventilation, delirium, nutrition and mental health). 66,81–84 A specific focus on progressive movement and mobility within PERMIT would add to the current research and further advance the overall goal of improving PICU care. Clinical stakeholders perceive that ERM is relevant for most patients and can be actively considered from the second morning of admission for those anticipated to still be on the unit the following day. However, clinicians especially require safety guidelines for delivering ERM to the most severely ill and complex patients. Factors influencing the implementation of ERM vary according to unit, team, individual clinician and individual patient. Therefore, both ERM activities and ERM implementation support need to balance flexibility (so they can be highly tailored) and specificity (so they can be differentiated from usual care, implemented and evaluated). Clinicians’ views on the potential impact of ERM seem to converge on a small cluster of key clinical, functional, psychological, family-related, QoL and economic outcomes.

Literature-based work – developing a prototype intervention manual

After the workshops, we conducted a range of literature-based work to identify available concepts, tools and resources to develop and shape the form and content of a prototype ERM intervention manual. This work took place alongside formal and informal meetings with clinical members of the wider PERMIT research team (see user development – reported below) and had an iterative relationship.

User development – refining the prototype intervention manual

Purpose: to refine the prototype ERM intervention manual through exploring clinical stakeholders’ views on acceptability and feasibility.

Methods: we took forward key topics and outstanding issues and uncertainties emerging from the ERM intervention manual development process into a series of formal and informal meetings with clinical members of the wider PERMIT research team. These meetings took place alongside the literature-based work (reported above) and had an iterative relationship.

Sampling and recruitment: we worked with existing members of the wider PERMIT research team. They represented a multidisciplinary group of NHS healthcare professionals with diverse experience of ERM in PICU settings. A total of 13 professionals from three PICUs took part in the process – four consultant doctors (three paediatric intensivists and one paediatric neurologist), two senior nurses (one clinical academic and one PICU lead) and seven senior physiotherapists.

Data collection: we undertook nine online group meetings. Meeting focus evolved with findings of literature-based work and insights from prior meetings shaping the focus of the next. The core intervention development team would present materials from the bedside bundle and implementation toolkit and/or facilitate the discussion and the clinical team members would support, refine and challenge elements of the manual. Members of the intervention development team recorded contemporaneous fieldnotes. The meetings lasted for 60 minutes. We also undertook additional formal and informal smaller meetings, with specific people, to further explore or refine difficult issues, as well as to undertake ‘walk-throughs’ of manual processes and explore reactions.

Data analysis: we focused on reviewing fieldnotes, memoing and debrief sessions within the core intervention development team. We reviewed, discussed and summarised the meetings, and worked to adapt the manual in an iterative fashion focusing on maximising potential successful introduction and embedding of the intervention.

Results: Table 11 summarises the content of the PERMIT ERM intervention manual. The key feedback points that were used to refine the prototype manual and improve its overall feasibility and acceptability can be summarised as follows:

• Introduction and orientation – tell the user what is in the manual, where to start and how to work through the different sections.

• Layout and formatting – introduce the bedside bundle first as this is of primary importance to users. Keep the manual brief, simple and accessible by ensuring that each of the clinical materials in the bedside bundle and each of the steps in the implementation toolkit fits onto one side of A4. Minimise the burden of flipping between sections in the manual by clearly separating the bedside bundle and implementation toolkit from the lengthier training and support materials.

• Language and tone – use labels that are already familiar and acceptable, for example a ‘checklist’ for implementing the pause and re-assess criteria evokes more confidence and positive emotion than a ‘risk assessment’. When providing instructions, ensure the tone comes across as flexible and enabling – clear and straightforward instructions may inadvertently come across as too prescriptive or authoritarian.

• Promote and enable ownership – make it explicit how the bedside bundle builds on systems, processes and expertise that are already in place across a unit. Empower users by highlighting where the intervention manual can be tailored to fit in with local practice and actively encourage them to tailor and take ownership of the materials and resources.

• Minimise extra burdens and manage expectations – remove unnecessary detail from the tables and flowchart within the bedside bundle. Make it clear which training and support materials are provided within the manual and clarify any materials that will need to be developed or tailored locally by the unit. Take advantage of all opportunities to build the manual into existing documentation rather than introducing new paperwork to the unit.

• Create a positive buzz and maintain interest – consider providing branded promotional materials such as pens, stickers etc.

In addition, the wider research team identified several key topics that warranted further exploration in our subsequent feasibility study (see Chapter 5): for example, the practicalities around recording ERM intervention data within existing documentation systems and processes, the impact of different clinical perspectives about how to deliver ERM to particular patient populations such as those on ECMO, and the acceptability of our conceptualisation and specification of ERM to diverse stakeholders beyond the PERMIT research team and study participants.

Logic model – refining our understanding

Purpose: to refine a PERMIT ERM logic model.

Methods: we had already developed a preliminary ERM logic model based on current literature and the clinical expertise within the research team. We reviewed and refined our logic model in relation to findings from the manual development process, the correspondence between the outcomes within our guiding principles and the published PICU core outcome set,47 and through discussions within the wider PERMIT research team.

Results: the refined logic model is presented in Figure 13. It provides an overview of the proposed intervention components and implementation processes set out in the refined ERM intervention manual, as well as the proposed outcomes of ERM and the key contextual factors thought to influence its implementation and potential effectiveness.

FIGURE 13.

Logic model of PERMIT.

Study management

The work package was co-led by BRS, JMen and FK. The study management group provided input into protocol, ethics application design and data interpretation. Sati Sahota was trial co-ordinator. JYT designed, adapted and managed REDCAP database. Statistical analysis performed by BRS, RF and James Martin.

Objectives

• Determine enrolment, recruitment and delivery of the PERMIT intervention.

• Monitor the safety of the PERMIT intervention and related AEs.

• Establish whether clinically important outcomes can be measured following delivery of the PERMIT intervention.

Design

A non-randomised unblinded intervention feasibility study with embedded process evaluation.

Intervention

The PERMIT intervention, as described in Chapter 4, was defined as a PICU-wide, healthcare professional-delivered intervention, aiming to promote opportunities for the delivery of ERM. The intervention included strategies to develop an organisational environment that supported the delivery of ERM, as well as ERM activities that could be tailored for each individual patient. Each PICU received the PERMIT intervention manual (see Table 12). The manual defined two key steps: preparing for the PERMIT intervention; and recruiting patients and delivering the ERM intervention. Within these two steps there were six key phases (Figure 14).

FIGURE 14.

Phase 3 feasibility study overview.

Step 1 - PICU preparation: to prepare the PICU for implementing the PERMIT intervention, a group of PERMIT champions (lead multidisciplinary healthcare professionals and managers) was formed (Phase 1 ‘build the team’). The team then led a rapid self-assessment of their PICU’s readiness to implement ERM (Phase 2 ‘take stock’). Relevant stakeholders were then brought together to participate in local discussions about ERM (Phase 3 ‘get buy-in’). The local PERMIT team reviewed, adapted and tailored the PERMIT intervention manual to suit the unique circumstances of their PICU and planned how best to incorporate ERM into local work routines (Phase 4, ‘get ready’).

Step 2 - Patient delivery: once the PICU self-assessed themselves as ready to start to deliver the PERMIT intervention to CYP, the site then progressed into Step 2. At this point, the local PERMIT team started to recruit patients to the trial, receiving ERM as defined by the manual (Phase 5 ‘make it work’). The study team reviewed the implementation process and worked with the local clinical teams to support ongoing education and training, adjust elements of the process as needed and plan for sustaining the programme beyond the end of the study (Phase 6 ‘keep it going’).

Setting

The study is based in PICUs within three NHS organisations: Birmingham Women and Children’s NHS Foundation Trust (Birmingham), King’s College Hospital NHS Foundation Trust (London) and University Hospital Southampton NHS Foundation Trust (Southampton). The PICUs were selected because of their diversity in (1) clinical expertise and the patient populations they serve (e.g. two PICUs were both cardiac and specialist PICUs, one non-cardiac but a large neurocritical care and liver transplantation programme), (2) the types of resources and staff groups they have available (e.g. allied health professionals, play specialists, rehabilitation equipment) and (3) ERM experience to date of implementing ERM within usual care (e.g. two units with minimal experience of implementing ERM and one with nationally recognised expertise in ERM).

Sampling and recruitment

Since this study was focused on feasibility and acceptability, an a priori sample size estimation was not required. Instead, our sample size was sufficient for capturing data across the diverse patient groups receiving ERM and the multidisciplinary healthcare professionals involved in implementing ERM.

Children and young people

We aimed to recruit 30 CYP (10 per unit) to receive ERM. All CYP were screened daily against the following eligibility criteria: aged 0–<16 years at the point of admission, admitted to PICU for any reason and likely to remain in the PICU on day 3 post admission. We excluded individuals where, for any reason, the local clinical team did not feel it was appropriate to include them in the study and we recorded the reasons. The majority of CYP were unable to provide informed consent or participate in an assent process (e.g. because of their very young age, levels of sedation medication). We therefore relied primarily on consent from parents/legal guardians (see below). However, where possible and appropriate, we attempted to take steps to involve CYP in decision-making and inform them about the study to the fullest level of their understanding.

Parents/legal guardians

To gain consent for delivering ERM, we approached parents/legal guardians of eligible CYP on day 1 or 2 of admission. As a minimum, they could choose to consent only to their child receiving ERM and to the accompanying data collection (i.e. clinical data about their child and intervention data about the delivery of ERM). This placed no direct burden of data collection on the parents/legal guardians themselves, offering option of participation, without any additional demands during the PICU admission. If parents declined the study then the child received ‘standard care’ in accordance with the local PICU policy. In addition, parents/legal guardians could choose to consent to completing outcome measures at two different time points – during their child’s stay in intensive care and around the time of discharge or shortly afterwards. They could agree to this when they were first approached on day 1 or 2 of admission or at a later stage during their child’s PICU stay. We also invited parents/legal guardians to take part in qualitative interviews (see Chapter 6: Process evaluation).

Data collection

We collected data about the CYP receiving ERM, the delivery of ERM to patients and the health-related outcomes of relevance to ERM. In this chapter, we report CYP clinical data, PERMIT intervention delivery data and parent/guardian outcome measurement data (Table 14). Chapter 6: Process evaluation contains details about the data collection of debrief conversations with PICU champions, interviews and survey with health professionals and interviews with parents/legal guardians.

Children and young people receiving ERM: currently, all CYP admitted to PICU have clinical data routinely recorded via the Paediatric Intensive Care Audit Network (PICANet). 67 We identified PERMIT study participants on the PICANet web-based system and conducted a data download of a pseudo-anonymised comprehensive data set pertaining to each individual CYP enrolled into the PERMIT study.

The data download included the PICANet minimum data set for each individual participant. This included demographic and socioeconomic data (participant’s date of birth, sex, ethnicity); pre-PICU health status (past medical history including underlying conditions and comorbidities); acute illness data [PIM3 (model of PIM that assesses the risk of mortality among children admitted to a PICU)]; PICU admission and discharge diagnoses; comorbidities; operations and invasive procedures performed; type of admission; PICU and hospital LOS, duration of MV, high-frequency oscillatory ventilation, ECMO, renal replacement therapy and vasopressor/inotropic support; sedative medications and days of exposure.

We also collected additional clinical data. The majority of data were collected daily from time of enrolment into the study until PICU discharge (see Table 14) and included:

• Level of organ dysfunction: PELOD-2 score.

• Level of physical activity: Children’s Chelsea Critical Care Physical Assessment Tool (cCPAx).

• Skin integrity: Braden QD was completed to assess skin integrity and risk of pressure damage/injury.

• Presence of delirium: Cornell Assessment of Pediatric Delirium (CAPD).

• Level of sedation: The COMFORT behaviour scale (COMFORT‐B scale) sedation assessment score.

• POPC and PCPC (these were collected at admission to reflect the child’s pre-admission status and PICU discharge only).

Data were recorded on individual patient CRFs and transferred for analysis into the REDCap database for the PERMIT study.

Paediatric early rehabilitation and mobilisation during intensive care intervention data: the Local PERMIT Research Team conducted daily screening of CYP on PICU, to calculate the number of patients fulfilling inclusion eligibility and number of patients approached, consented/declined for the study.

Once parents/legal guardians (and CYP where appropriate) had consented, the patients received the PERMIT intervention until PICU discharge. The Local PERMIT Research Team used the PERMIT CRF for each individual CYP to collect the following data about the PERMIT intervention at ward rounds, ERM intervention sessions and through discussion with local clinicians:

• patient acuity level;

• prescribed ERM activity level and specific ERM activities;

• delivered ERM activity levels and specific ERM activities (including timing, duration, number and type of staff or family member assisting);

• reasons for deviating from the prescription, where relevant;

• use of pause and reassess criteria;

• safety and AEs;

• any intervention/manual tailoring proposed or undertaken within the site.

Outcome measurement tools: the Local PERMIT Research Team distributed outcome measurement tools (questionnaires) to parents/legal guardians at two time points: during their child’s PICU admission and at the point of PICU discharge or within 30 days after PICU discharge, whichever occurred first. The outcome measurement tools were administered initially as paper questionnaires then by additional methods at parents’/legal guardians’ preference. The information was entered into the PERMIT study REDCap database.

During PICU admission: parents/legal guardians provided a retrospective report based on their child’s pre-admission status (2 weeks before) by completing a QoL and a fatigue measure (1 and 2) and an assessment of the family pre-admission status (3) from the Pediatric Quality of Life Inventory (PedsQL)™ family of questionnaires:

1. PedsQL™ Infant Scales Version 4.0 – Acute (Aged: 1–23 months) OR PedsQL™ Generic Core Scales Version 4.0 – Acute (Aged: 2 years+);

2. PedsQL™ Multi-dimensional Fatigue Scale Version 3.0 – Acute;

3. The PedsQL™ Family Impact Module Version 2.0 (parent report).

At point of PICU discharge or within 30 days post admission to PICU: parents/legal guardians completed questionnaires based on their child’s current health status (1–3) and the family status (4–7):

1. PedsQL™ Infant Scales Version 4.0 – Acute (Aged: 1–23 months) OR PedsQL™ Generic Core Scales Version 4.0 – Acute (aged: 2 years+);

2. PedsQL™ Multi-dimensional Fatigue Scale Version 3.0 – Acute;

3. the PedsQL™ Family Impact Module Version 2.0 (parent assessment);

4. parent Stressor Scale;

5. the EMpowerment of PArents in The Intensive Care – 30 Item Version (EMPATHIC-30);

6. Patient Health Questionnaire-4 (PHQ-4).

Feasibility and acceptability of the questionnaires were captured through monitoring completion rates and feedback from the parent/carer interviews. This is reported in Chapter 6: Process evaluation.

Data analysis

We reviewed data for errors, missing data, duplicated records and outliers. Extreme values were set to missing if they were deemed impossible, based on their validity range. Continuous variables were reported as mean and SD or median and IQR based on data distribution. Categorical variables were described in numbers and/or percentages.

Descriptive statistics were used to summarise the PERMIT intervention data, including: success of implementation, recruitment, proportion of consented patients triaged from the acuity table, proportion of consented patients allocated an ERM intervention from the manual appropriate to their acuity level, proportion of consented patients receiving the prescribed ERM, number of AEs and proportion of patients experiencing AEs. Results are presented in text and tables with a narrative summary of findings. Stata v16 was used for all statistical analyses.

Patient and public involvement and engagement

For an overview of the approach to PPIE adopted throughout the study, please see Chapter 8. PPIE in this phase of the study focused on exploring the appropriate model of consent, refining participant-facing documents and establishing the overall acceptability of the study. We had planned to speak to parents with direct experience of involvement in research studies, but the research suspension imposed in response to directives to prioritise COVID-related research made this challenging. 100 We spoke to parents of four children (aged 1 month to 16 years) who had experienced one or more PICU admission(s) at BCH and Kings College London. One parent had experience of their child being recruited to a number of non-PICU research studies.

The concept of a staged approach to consent to help reduce the burden about deciding on all aspects of the study at once was liked by the parents (Table 15). The challenge of speaking to families so early on in the child’s PICU stay was recognised. One parent described the overwhelming emotions and the importance of reducing the demands being placed upon them:

There’s also the challenge of emotional engagement. When * first came in, there was an overwhelming, primeval pain. This developed into a rollercoaster of positive and negative emotions which over-rided my ability to absorb information ….

(PPIE parent)

Being able to stagger the informed-consent process until a parent was better placed to consider what was being asked of them was endorsed. Other factors that helped were having these messages clearly conveyed in the PIS and ensuring that this process was supported by someone who could provide clarification and answer questions. Parents noted that the material was written at the right level for them; however, concerns reflected the volume of information – ‘It’s like a book!’ – to read and digest. All commented on the value of figures or illustrations to help visualise the sort of interventions that would be involved.

We had also hoped to explore outcome measures and the interview schedules (for consenting parents and declining parents) but this was not possible. All four patients were inpatients on either PICU or had just been discharged to the ward. The parents we worked with were the only parents allowed with their child, so they had a lot of competing demands. It was not felt to be appropriate to provide them with multiple outcome measure questionnaires or interview schedules to review; in fact, this was not allowed in some ward areas due to COVID. The study team therefore drew on our PPIE work from other recent PICU studies that were involved in selecting questionnaires (the OCEANIC study101) and qualitative interviews (BRICC trial102) to shape the decision-making.

The study received Health Research Authority approval (ref 21/SC/0127), and was registered at https://clinicaltrials.gov/ct2/show/NCT04909762.

Site implementation and recruitment to PERMIT study

Overall, three PICUs participated in the PERMIT feasibility study. The PICUs were chosen as a pragmatic sample with variation in average annual admissions, number of overall PICU staff, types of paediatric specialties and stand-alone children’s hospital, co-located adult/paediatric centre.

Sites 1 and 2 started Step 1 of the PERMIT implementation programme in early June 2021. Site 3 was delayed due to contract issues until 2 August 2021 (Figure 15). All three sites (100%) achieved the primary outcome and progressed through phases 1–4 of Step 1 (PICU preparation phase) of the PERMIT manual. Time to complete Step 1 and progress to Step 2; site 1: 12.9 weeks, site 2: 15.0 weeks, site 3: 8.4 weeks. Table 16 reports key feasibility outcomes.

FIGURE 15.

Progress of sites through Phase 3 feasibility study.

All three sites (100%) recruited their target of 10 patients within Step 2. Site 2 over-recruited (n = 11) as one patient was discharged from PICU a few hours after signing consent and was excluded from reporting below. Full recruitment was completed within 53, 23 and 57 days from the start of Step 2. Overall, 31/35 (89%) of eligible patients were successfully recruited. Only four families declined consent to PERMIT.

Sites completed follow-up to discharge or 30 days (whichever was sooner) of all recruited patients by 91, 32 and 57 days respectively of commencing Step 2.

Of the 31 patients who agreed to consent A (participation in data collection and to receive ERM interventions), 21/31 (68%) also consented to consent B (follow-up assessment tool collection and to be approached about an interview). One patient was discharged from PICU very soon after consent so no data were collected. Therefore, 30 patients were included in ERM assessment data.

Outcome assessment tool completion

Assessment tools were completed at baseline, during daily clinical status assessments and at follow-up (discharge or 30 days after PICU admission) (Table 17).

Baseline assessment tools for PCPC and POPC were recorded in 30/30 (100%) of cases. Additional baseline forms were scored for the families consenting to consent B (n = 20). Of these, 19/20 (95%) completed the Family Impact Scale and PedsQL parental core reports, with 7/7 (100%) of those eligible completing the PedsQL Multi-dimensional Fatigue Scale.

The daily patient assessment scores and organ dysfunction scores (PELOD-2 and cCPAX) were collected in nearly all cases (see Table 17). In more than 91% of available PICU study days the CAPD, Braden QD and Comfort B scores were collected. Missing data were related to unavailability of research staff to calculate scores contemporaneously, indicating that these were not routinely collected clinical scores by bedside staff.

Follow-up outcome assessment score completion rate was much lower (12/20; 60% of patients), although these were all fully filled in. The protocol defined follow-up time occurring at point of PICU discharge or within 30 days post admission to PICU with flexibility for research staff to assess feasibility. Time from PICU admission to follow-up assessment completion was a median (IQR) of 31.5 (30–40) days. The length of time from discharge of PICU to follow up was median (IQR) 26 (13–36) days.

Demographics

The median age of the 30 patients recruited was 1.8 years (IQR 0.4–5.4) with around a third (9/30; 30%) <12 months (Table 18). The most common primary admission diagnosis was a respiratory illness (40%) and 8/30 (27%) were admitted following surgery. Prior to admission, 16/30 (53%) had a normal (PCPC 1) cerebral performance score, and 11/30 (37%) a normal (POPC 1) overall performance score with 19/30 (63%) ambulatory. This population was similar to the general population observed in Phase 1c observational study (see Chapter 3).

On day 1 of the study (day 3 PICU stay), the median PELOD 2 score was 4 (IQR 3–6). Nearly all were on assisted ventilatory support; 23/30 (77%) invasive MV and 5/30 (10%) on non-invasive support [bilevel positive airway pressure (BIPAP), continuous positive airway pressure (CPAP) or high flow nasal cannula], 6/30 (20%) were on vasoactive infusions and 2/30 (7%) were on neuromuscular blocking drugs (Table 19).

Prior to the first study day, four patients had screened positive for delirium. On the first study day the median CAPD score was 14.5 (IQR 9–19). The standard cut-off CAPD score indicating delirium is a score of >12. Therefore, a high proportion (16/30; 59%) screened positive for delirium.

Patients’ total LOS on PICU from admission was a median (IQR) of 5 (1–13) days. Following recruitment to PERMIT, the number of study days per study participant was median (IQR) 2 (1–7) days and patients were potentially available to receive ERM on 191 study days. Site 1 had the largest number of ERM study days (n = 108) compared to site 2 (n = 42) and site 3 (n = 41) as a result of a longer LOS for patients at site 1 (Table 20).

Number of early rehabilitation and mobilisation activities prescribed per children and young people following patient acuity screening

Of the 191 available study days, 174 (91%) had a morning ward round observed. During the ward round the patient acuity was recorded on 161/174 (93%) occasions. The median (IQR) acuity level (level 1, most unwell to level 4 least, unwell) for study patients was 3 (3–4); only 23/161 (14%) were level 1 or 2 (i.e. most sick). A corresponding ERM activity level for the patient was documented for 159/174 (91%) and an ERM activity prescribed on 137/174 (79%) occasions. PERMIT local researchers were present at the time of the ward round on over half of occasions (58%), providing a range of levels of support (from 17% ‘lots of support’ to 29% ‘no support’) to the ward round clinical team.

In total, 825 ERM activities were delivered within 328 ERM episodes on 140/191 (73%) of patient study days across the three study sites.

Type of early rehabilitation and mobilisation

On study day 1, 26/30 (87%) patients had an ERM activity prescribed and 22/30 (73%) had an ERM episode delivered. Of the eight patients who did not receive ERM, five had an ERM prescription for an activity. One of the four patients not prescribed ERM received an ERM activity on study day 1. Across the first 7 days of the study (Figure 16), the rate of receiving a mobility ERM was similar to receiving any ERM. The proportion of patients receiving out-of-bed mobility gradually increased across the study period. For illustration, Appendix 28 shows the range of ERM activities prescribed and the corresponding proportion that were delivered on study day 1. All sites prescribed a wide range of ERM with a good conversion rate from prescribed to delivered for passive, enrichment and active mobility ERM activities.

FIGURE 16.

Prevalence of ERM delivered on study day 1 by any, mobility and out-of-bed categories.

Duration of early rehabilitation and mobilisation

Times were recorded at the start and end of ERM episodes. Recording was variable in the database, with some documented episodes as a single ERM activity, others recorded as multiple ERM activities, or continuous delivery of ERM making interpretation difficult.

Appendix 29 shows the distribution of recorded durations of ERM: 36/266 (14%) recorded times were <15 minutes duration and 61/266 (23%) 15–29 minutes. The median duration was 30 (IQR 15–75) minutes, which was longer that the median time observed in the Phase 1c observational study of 15 minutes.

Safety and adverse event rates during an early rehabilitation and mobilisation activity

The ‘pause and assess’ criteria embedded within the ERM manual for safe deliver and re-assessment of patients before and during an ERM activity were used in 21/330 (6%) of ERM episodes across 13/30 (43%) patients (Table 21). The most frequent categories were desaturation limit exceeded (5/21; 24%) and agitation, anxiety and distress (4/21; 19%).

Only 2/328 (0.6%) of ERM activities in two patients were associated with an AE as specified in the study protocol (Table 22). The first was a nasogastric tube dislodged during an ERM episode, but not related to the activity and with mild severity impact on the patient. The second was a blood-pressure change, possibly related to ERM activity, with mild impact on the patient.

Study management

The work package was co-led by BRS, JMen and FK. The study management group provided input into protocol, ethics application design and data interpretation. Sati Sahota was trial co-ordinator. JMen led the process evaluation, with methodological expertise by TR. Qualitative analysis was performed by JMen, TR and Natalie Read.

Sampling and recruitment

We invited two groups of health professionals to take part in feasibility and acceptability work: firstly, ERM champions, those people identified, as part of the PERMIT intervention, as leading the implementation of ERM in the unit and secondly PICU multidisciplinary health professionals involved in any aspect of preparing for or delivering ERM across the unit. Each site aimed to recruit 2–5 ERM champions to take part in weekly debrief conversations (20 debriefs per site; n = 60 total). PICU health professionals were invited to take part in a survey at three time points, aiming for 30 in total per site (n = 90) and consenting staff could also volunteer for a qualitative interview aiming for four or five participants per site (n = 12–15). Parents/legal guardians of CYP recruited to receive the PERMIT intervention were also asked about completing optional outcome measurement tools and an interview. This included those who consented for their child to participate in the PERMIT study (aiming for a sample size of 12–15) and those who declined their child’s participation (aiming for one participant per site, n = 3). The study received Health Research Authority approval (ref 21/SC/0127).

Data collection

Weekly debriefs were conducted with ERM champions from each site, either in person or remotely (telephone/video conference). They were recorded in contemporaneous fieldnotes. Qualitative interviews with PICU health professionals and parents were conducted in person or remotely (telephone/video conference/face to face) and were audio-recorded, intelligently transcribed. 105 and edited to ensure respondents’ anonymity. Finally, PICU health professionals also completed a brief online survey at three time points (beginning, middle and end of study period).

Debrief conversations, interviews and survey with health professionals focused on exploring implementation progress, determinants and key learning; this happened throughout the study period. Interviews with parents focused on exploring acceptability and feasibility of PERMIT intervention and study processes; this happened towards the end of PICU admission or following PICU discharge (up to 30 days post admission to PICU).

Initial topic guides for debrief and health professionals and parent interviews were designed, drawing on prior literature, experience, NPT71,72 and TFA. 73 They evolved during the course of data collection, allowing for tailoring and gradual integration of a variety of follow-up issues and topics. The survey was based on the NoMAD Questionnaire, a 20-item self-report instrument104 (see Appendix 3, Table 41 for NoMAD survey). The survey was distributed by the local PERMIT champion team through internal e-mail lists, and survey participants had the option to consent to be contacted about an interview with a member of the central PERMIT study team. To ensure both the surveys and interviews captured diverse views across the three units, local teams were encouraged to promote the survey widely to promote different professional groups to engage and participate (criterion-based recruitment). 106 Although data saturation is aspired to within qualitative research, that is when no new themes are emerging,107 we recognised this would not be achievable within the time scales of this feasibility study.

Data analysis

Notes from the debriefs were imported into NVivo 12 and deductively coded and analysed using a qualitative content analysis approach of systematic coding and categorising. 58 Two researchers (JM, NR) independently familiarised themselves with the data and conducted open-coding, utilising NVIVO™ software for data management. Codes were then discussed and organised into higher-order subcategories and categories. 59,60 In relevant sections of the paper free-text quotes from respondents are reported to add clarity, staying close to the original meanings and context. 61

The interviews were analysed using a thematic analysis approach. This approach was taken because thematic analysis allows for the identification of common threads that extend across an entire interview or set of interviews. 108 It also values the detailed and nuanced account of data, particularly emphasising the context. 60 Analysis was informed by the work of Braun and Clarke,109 with NVivo™ software used to assist in the organisation and coding of data. The Framework approach was then used to facilitate systematic, rigorous and transparent data management. 110,111

The survey data were analysed descriptively. Three questions explored: (1) how familiar ERM felt, (2) if ERM was a ‘normal’ part of work and (3) if it will become a normal part of work – responses were on a scale of 0–10 (e.g. 0 very new up to 10 completely familiar). The remaining 20 questions required a Likert-scale response (strongly disagree, disagree, neutral, agree, strongly disagree). Responses were allocated a score −2 (strongly disagree) to +2 (strongly agree) for interpretation; median scores for each question are presented.

Study participants

We undertook 48 debrief sessions with ERM champions (Table 23). Despite recruiting well to the champion role at each site, the debrief calls were attended consistently by the same people. Debrief attendees included nurses (n = 2), medical representatives (n = 3), physiotherapists (n = 2), OT (n = 1) and clinical research nurses (n = 3).

We received survey responses from 118 health professionals across the MDT. The largest response group (66/118; 56%) were registered nurses and overall most had been in PICU 3 years or longer (88/118; 75%) (Table 24).

We interviewed 13 health professionals, including medical representatives (n = 4), PICU physiotherapists (n = 3) and one physiotherapist from a different team (provided on-call cover), advanced nurse practitioners (ANP) (n = 2), one OT, one bedside registered nurse and one team leader registered nurse.

In total, 21 parents consented to participate with the optional questionnaires and the interview, with 15 parents interviewed. Of the six who did not participate, two subsequently declined the interview when contacted, one was only in the study for a few hours so did not feel they could offer any insight and the second child had been re-admitted to hospital so parents did not feel able to participate at the time. One child died before discharge from hospital and three parents did not respond when contacted, after a median of three attempts to contact them. One parent was interviewed but then withdrew therefore interviews from 14 parents were included in the analysis. Interviews took place between November and December 2021 and were conducted in a variety of ways, subject to parental preference. Two were conducted face to face at BCH, five took place on Zoom and seven took place over the telephone. The final analysis included mothers (n = 12) and fathers (n = 2). All of the parents had experience of their child having been intubated and mechanically ventilated during their admission to PICU, and 12 were parents of a child admitted as an unplanned admission.

Pre-paediatric early rehabilitation and mobilisation during intensive care context – questions of capacity

The PERMIT study was introduced into three PICU sites. Across all the sites, potential issues around capacity, especially in relation to levels of MDT staffing, as well as priorities, in relation to place of ERM in ongoing care, were present (Table 25). All sites reflected that although ERM was part of care, they ‘didn’t do it actively or in a structured way’ (Site Two: Medic interview). Patients with defined pathways – neurology patients, those classified as ‘long stay’, infants and patients who were elective and had a more predictable recovery – were more likely to receive ERM. Delivery did not often occur ‘early’ and was undertaken inconsistently:

quite limited in terms of what was being done on the unit. There were elements of, I guess, what you could classify as ERM starting to emerge, but I think the timing was definitely at a later point of the child’s stay.

(Site Three: Physio interview)

In addition, it was more likely to occur on weekdays, in office hours, and interventions were likely to be ‘low level’ and often movement-focused. In Site 1, an ERM programme had been launched in 2019, with good leadership and good staff engagement. However, the programme had floundered – with maternity leave, staff turnover and service pressures – and in 2021 there was little awareness of the programme. The champions felt that the feasibility study would be an opportunity to reinvigorate an ERM programme and secure staff buy-in. Neither of the other two sites had a pre-existing ERM programme, although they both reported being very enthusiastic about the idea of commencing one.

Introducing PERMIT – (re)organising the work

Throughout the whole study period all three units experienced huge service demand, running significantly over capacity with reduced staffing. In addition, alongside the impact of COVID-19, there were unanticipated challenges or competing demands. At Site 1 this included the move of the whole PICU to a temporary location. The sites progressed through the first four phases at different paces (see Figure 15). Due to the prior history of an ERM programme, Site 1 progressed through initial phases quickly, with more time spent on Phase 3 – supporting staff engagement and training – and Phase 4 – adapting the manual and planning how to effectively deliver the ERM intervention and the trial at their site. Site 2, in contrast, spent more time on Phases 1 and 2. There was less focus on education and training and the specifics of where and how discussions about ERM took place, and more on the logistical factors associated with running the research study and capturing the data. Site 3 experienced a significant delay (9 weeks) in commencing the study, due to local site approval issues. This delay was not only frustrating for a site enthusiastic to start staff training and education, but also added pressure about the feasibility of recruiting 10 patients within an 11-week period. As a result, the site spent relatively little time in each of the phases, with the site starting to screen and recruit by week 16, only 1 week after Site 2 and only 3 weeks after Site 1.

To embed ERM, all sites realised – often more strongly in retrospect – the fundamental importance of ‘education, education, education! … I think that’s the key thing I think to try and make it work’ (Site One: Physio interview). Staff training and education were central to conveying information to all staff on the PICU, supporting them to understand the key principles of the ERM programme and build experience and confidence in delivering ERM. Ongoing education and teaching within formal contexts (e.g. organised study days), alongside informal, ad hoc moments (e.g. at bedside) and being ‘more opportunistic with teaching when clinical’ (Site Two: Debrief) were needed to support delivery of ERM. A refined, considered, educational strategy was introduced in Site 1:

Clear education plan, trainers are being trained and there is a training log planned to keep track of who has had what training.

(Site One: Debrief)

This strategy focused on identifying what key information staff needed to understand, how many people needed training and a plan for how to train them.

There were challenges to providing the education and training sites that were felt to be required to achieve adequate staff commitment, confidence and skills. A core factor was the short trial period – 20 weeks from start to finish, less for Site 3, due to delays. At Site 2, someone commented that ‘the speed at which we had to put it in place and the speed at which we had to then recruit I don’t think gave us time to grow the roots enough’ (Site Two: ANP interview). At this site an additional challenge emerged, with educational resources having to be directed towards getting staff trained as quickly as possible on a new ventilator. Sites felt that the absence of any pre-prepared education and training materials accompanying the manual had been a challenge throughout the 5-month study period. As a result, Site 1 shared training material (which was then localised and rebranded) as well as access to a core trainer to support training and education at the other sites.

Delivering PERMIT – integrating early rehabilitation and mobilisation

Despite all the challenges associated with education and the speed with which the study was rolled out, PERMIT was seen by health professionals and parents as worthwhile (Table 26). All three sites reported positively about how the ERM programme cultivated multidisciplinary working, helped with clarification of roles and helped with elements about leadership and staff buy-in around ERM. MDT work was recognised as being central to delivering the desired level of ERM. This meant embracing multidisciplinary working to optimise service provision:

There are not enough hours in the day for a therapist to deliver the amount of ERM they’d like to be seeing going on. … It needs to become an MDT-based focus … everybody’s role. Therapists can’t be the only ones delivering this.

(Site Three: Physio interview)

In particular, the role of the bedside nurse was recognised as vital to support delivery. The challenge was about raising the profile of ERM as a priority in nurses’ daily work so ERM was no longer seen as just a desirable component, but an essential aspect of care provision. At moments, people struggled with whether to prioritise supporting colleagues:

Nursing staff report feeling guilty that they’re doing nice things with patients – play, music etc. when the rest of the staff are very busy and struggling with unit demands.

(Site One: Debrief)

However, exposure to ERM over time, especially seeing ERM in action on a unit, could help in the process of it becoming embedded as ‘standard care’.

Exposure was, in part, challenging, however, because there were differences across sites to the extent that PERMIT was rolled out. At Site 1, ERM following the PERMIT manual – that is assessment of acuity, activity planning, risk assessments and family involvement – was regarded as the standard for all patients. At the other sites, only patients recruited to PERMIT received ERM as per the manual. Although there was variety in the use of the bedside bundle, there was recognition of the value to support ERM delivery and a shift in the traditional mind-set of a patient needing to be stable to be eligible to receive ERM. In practice, exposure emerged in a variety of ways, be that through strategies in place to promote staff buy-in and enhance involvement over time:

there’s posters going up, conversation in the coffee room taking place. Physio colleagues are more active in reminding clinicians at the bed space, or at least reminding the nurses to ask doctors doing the ward rounds … lots of general awareness that early rehab and mobilisation is actually important for the patients.

(Site One: Medic interview)

In and through taking part in PERMIT, staff exposure to ERM increased over the study period. Ward rounds also offered a space in which to undertake ERM discussions, at the very least in relation to whether a patient may be eligible for the study, as well identifying activities of rehabilitation for those recruited, if not for others outside PERMIT. Additionally, positive family feedback about involvement with ERM, when shared with staff, increased exposure and understanding of potential impact.

Over time, health professionals understood that ERM was important for the physical and psychological recovery of the CYP, as well as the psychological well-being of parents/carers supporting their involvement in their child’s care. For example, one site noted that:

Parents are engaged and involved, really keen on the ERM process. Parents are filling out the activity booklet and adding lots of detail. Seems to give them a focus and a process to be involved in.

(Site Three: Debrief)

All the sites reported that PERMIT has supported parental involvement. Feedback from parents was reported as ‘overwhelmingly positive and everyone’s saying how important it was within their journey’ (Site Three: Physio interview). All parents commented that there had been benefits to participating. This seemed to span from the emphasis the programme placed on parental involvement to the purpose that the programme provided. However, parental involvement in activity selection varied, with some referring to paperwork to help guide choices, while for others it appeared to be more led by the health-care professionals, whereas other parents reported not seeing a list or feeling actively involved in activity selection. Engagement in process was clearly enabling for parents:

It was quite nice to know, “Oh we can move onto the next stage” or you know, “Oh look there’s a new activity on the list, oh I hadn’t thought about doing that activity with him”. Or realising that sitting in the bed is a milestone almost. You know, it’s a new activity. As a parent you can see that as a milestone of their recovery.

(Site Two: Parent interview)

Overall, most of the activities were undertaken while their child was ‘in bed’. The most commonly reported activities were cuddles, reading, singing, talking, touch or massage and stretches, which matched recorded activities completed by the bedside staff. The impression was that most parents felt the activities were tailored and appropriate for the stage the child was at.

Many parents reported feeling more confident in becoming involved in supporting ERM, that for them ‘I think it was so empowering’ (Site One: Parent interview). Parents reflected on how sick their child had seemed to them initially, but once they were familiar with what ERM involved and how they could be involved it gave them a sense of purpose:

But it also gives us something to do to feel useful because you’re in a situation where it’s one to one care. They know exactly what they’re doing, we’ve got no idea. We can’t help do anything in ICU, but you’re just looking at your child and you can’t do anything. But being able to have a structure as to what we can do to help, all of the activities that we could do … it meant that we could do something to actively help his recovery.

(Site Two: Parent interview)

Parents perceived that being recruited to the study provided guidance to staff about activity assessment and selection and also encouraged them to consider the child holistically. They also felt more confident leaving their child to have a much-needed break because they trusted that staff would also follow the programme. Some saw a direct benefit to their child. Others were less sure or queried whether it was fully relevant to their child because they were an infant, but still saw the study as worthwhile. For many the main positive impact for their child was the contact the programme encouraged with parents. This spanned all aspects of care, particularly cuddles. Parents recognised how central they were to their child and their presence was therefore important to help support their child. However, outside the context of PICU delivery, support and guidance for delivering ERM were lacking. Several families reported that leaving PICU is only the first stage in recovery and more needed to be done to support them with ERM beyond PICU discharge.

Delivering PERMIT – integrating trial processes

Having access to research delivery support was central to supporting recruitment, data collection and data entry. This reduced demand on bedside staff as well as freeing up the site team for education and ERM delivery. Sites 1 and 2 worked with research nurses – with Site 1 having access to a clinical research nurse from Stage 4 – whereas at Site 3 did not. At Site 3 the lead champion took on all the workload associated with implementing the study and evaluating ERM delivery and they noted that:

The research side is very time consuming. The data collection and research collection are the biggest barrier to doing the ERM, the data collection, the consent process, the questionnaires – it’s all so time-consuming.

(Site Three: Debrief)

All three sites commented on the large volume of work associated with conducting the PERMIT study. A research team presence, ideally to cover all days and times of the week, was seen as essential. All parents also provided positive feedback about the role and presence of the research team during recruitment: their professionalism, the sensitivity with the timing of discussions and their ability to respond to questions.

Overall, the families were positive about the study recruitment process. Two parents referred to the challenge of written leaflets for parents with additional needs. As ERM was rendered as the ‘usual’ standard of care within the units – by the PIS and research team – many parents had low expectations about the potential risk of participation:

My main question was about if there was anything extra that was going to be done, anything invasive, and if it wasn’t then I didn’t see any reason why I wouldn’t consent to it.

(Site One: Parent interview)

For the majority the perception of ‘minimal’ to ‘no’ risk meant that they found this a relatively simple decision. The choice of a staged consent model was significantly influenced by other studies within the PICU environment66,102 and the PPIE work conducted within the PERMIT study (see Chapter 8). Of the 30 children recruited to the trial, 21 of the parents/legal guardians consented to participate in the ‘additional’ aspects of the PERMIT study (70% consent rate). Seven families (33%) consented in a staged approach, with 14 (67%) happy to consent to all parts in one go. Some parents felt signing up in stages had been really helpful for them, not overloading them at a difficult time. There was also a sense from some families that because ERM was standard practice on a PICU that an opt-out consent approach where families did not have to actively consent or could be asked at a later stage could be acceptable.

Introducing and embedding the study paperwork was challenging at times. This was only produced as physical documents and Site 2 did not have time or capacity to adapt it to their electronic patient management system, so

[h]aving the documentation all on paper created resistance from staff, they like everything to be done on the computer. This was perceived as a lot more work to have to do.

(Site Two)

Easy access to documents at the bedside helped support and sustain study work. Sites also had some concerns about the outcome measurement tools provided to families, in part tied to the logistics of managing the process – with uncertainty about the time points required and the challenge of getting these completed. They also were uncertain about the volume of questionnaires to be provided to families. However, on the whole the questionnaires were viewed as acceptable by parents. Negative comments reflected that some questions were inappropriate for their child in terms of their ability to do the developmental outcomes (mostly for the parents of neonates), length and the slightly repetitive nature of some questions.

Embedding ERM post-PERMIT and PERMIT trial – (continuing) questions of capacity

As part of Phase 4 work, a debrief was held 2 months after the study had closed to recruitment. Despite huge enthusiasm about the potential for ERM to continue after PERMIT closed, all ERM activity related to the programme had stopped at Sites 2 and 3. However, at Site 1, even in the contexts of increased PICU workloads and COVID creating challenges for staffing, they still felt that ERM had shifted to being seen as part of routine care. They noted how ‘the research has increased frequency and awareness of ERM’ (Site One: Debrief), with most patients now having their acuity assessed daily and staff considering what ERM could be conducted, even if it was not always possible to undertake the planned activities. Bedside nurses appeared to have increased confidence in initiating and conducting ERM, with increased awareness of what each MDT member could contribute to ERM.

Core issues to embedding ERM after PERMIT remained, with Site 3 reflecting that

the challenges have taught us so much! … Need increased presence and visibility of an ICU specific therapy team to fully integrate into ICU. We learned also that therapy doesn’t need to be so structured and planned, we can do it in so many ways.

(Site Three: Debrief)

They felt they would ‘review, revamp and re-launch!’ with more time factored in for the programme to embed, and that the ‘minimum time to make this really embed would be 12 months’ (Site Three: Debrief). All three sites felt that additional resources were required to support (ongoing) staff education and training; that visibility, experience and (positive) feedback around multidisciplinary ERM working was key, as well nursing staff taking ownership being central to embedding.

The NoMAD survey results align with the way that sites, over time, began to realise the complexity of the work of introducing and embedding an ERM programme. Between time point one and two there was an increase in ERM familiarity through initial engagement, with a realisation that ERM was currently part of normal practice and would become part of normal practice (see Appendix 3, Figure 20). However, by the final and third survey the level decreased back to baseline.

A similar temporal pattern was seen in four NPT items: around questions of the legitimacy of ERM being a part of their role (Q15); being open to working with colleagues in new ways to use ERM (Q16); and notably, continuing to support ERM (Q17) and that sufficient resources are available to support ERM (Q23) (see Appendix 3, Figure 21). However, across all time points there was strong (and stable) agreement about seeing the potential value of ERM in their work (Q13) and strong (and stable) disagreement across all time points that ERM disrupts working relationship (Q19).

Study management

The work package was led by BRS. JMen led the PPIE component. Rebecca Wooley and Karla Hemmings (BCTU trial statisticians) performed sample size calculation. RF co-ordinated PICANet data analysis. The study management group participated in consensus conference and reviewed the future trial proposal.

Parent consensus meeting

We invited all parent/family member participants (n = 17) who consented and provided contact e-mail address details in Phase 3 to a virtual meeting (via Zoom) in January 2022. Invitations were sent in December 2021 and a reminder invitation in January 2022. The meeting included a presentation by BS (study design, rationale and key quantitative results), Natalie Read (results from site debriefs) and JMen (key results from healthcare professional and parent interviews).

The video presentation (30 minutes duration) was recorded, uploaded to a private web-based video-housing channel and a summarised leaflet with key study findings (pdf format) was created.

Following the meeting all parents/family members were sent the slides and video link with a short online questionnaire relating to feasibility and acceptability. No sensitive or identifiable information was collected. Implied consent was indicated on completion and submission of the online questionnaire.

The questionnaire asked:

1. whether they found it useful to see the study results;

2. appropriateness of an opt-out consent in future study;

3. which outcome measures should be included in a future study (ranked according to importance);

   1. the amount of ERM a child received (dose);

   2. the type of ERM activities a child received;

   3. the length of time spent on PICU;

   4. the length of time on a ventilator;

   5. the LOS in hospital;

   6. physical measure such as muscle strength;

   7. an outcome reflecting longer recovery (e.g. return to nursery/school);

4. other suggestions of what should be measured (free-text response);

5. whether a future trial of ERM was required.

Healthcare practitioner consensus meeting

We planned to hold an online HCP consensus meeting to discuss a proposed future trial design. However, additional COVID pandemic restrictions and NHS workforce pressures in January 2022 resulted in the cancellation of this meeting, with a plan to reschedule in May 2022 during the national PCCS-SG annual investigators meeting.

Study management group trial design

The study management group met on three occasions to review the findings of the Phase 3 feasibility study and discuss the design and structure of the future trial. Additional methodological expertise was obtained from Birmingham Clinical Trials Unit statisticians and study team at PICANet. Meetings were conducted over Zoom and, following the verbal consent of all attendees, recorded for comprehensive notes to be made to inform trial development.

Parent consensus meeting

An invitation to attend the parent consensus meeting was sent to 17 participants in the Phase 3 feasibility study with the recorded materials. No parents/legal guardians (n = 0/17, 0%) attended the live virtual meeting. However, four parents/legal guardians responded to the online survey. All respondents (n = 4) found it useful to see the key study findings and agreed that an opt-out model of consent was appropriate for a future study.

The outcome measures were rated as follows.

All four respondents rated as very important:

1. the amount of ERM a child received (dose).

In addition, they ranked from highest to lowest the following outcomes:

1. the type of ERM activities a child received (highest ranked);

2. the length of time spent on PICU;

3. the length of time on a ventilator;

4. the LOS in hospital;

5. physical measure such as muscle strength;

6. an outcome reflecting longer recovery, e.g. return to nursery/school (lowest ranked).

Other measures suggested in free-text response included:

For younger children/babies perhaps a measure of stress/anxiety – do erm activities such as reading help with sat [oxygen saturation] stability or overall sats [oxygen saturation] vs. children who do not receive ERM. E.g.: we continued to read night-time stories to try and maintain a degree of normality as well as comfort.

(Parent C)

Two parents replied Yes: further research on ERM was required and two said No: reasons being that they felt the evidence was conclusive:

Probably not, the benefits are obvious and the feedback is conclusive I would say. (Parent D) I guess to get this to be a standard of care you will need more evidence it works. But with the positive feedback from parents I personally think enough research has been done – it provides a positive environment for all.

(Parent C)

Impact for future paediatric early rehabilitation and mobilisation during intensive care trial

Parent satisfaction is extremely high surrounding ERM and contributed to two parents feeling that from their perspective further research was not required. However, there was recognition that for this to become a standard of care for all patients this would require more evidence, with further work focusing on identification of outcome measures relevant to patients and parents/legal guardians.

Importance of research question and professional support for early rehabilitation and mobilisation

There remains a clear need to improve the morbidity and mortality of children requiring care within PICU after PICU critical surgery, illness or injury. We identified evidence from our scoping review that ERM is safe, feasible and, in combination with the adult literature, has the potential to be effective at improving patients’ recovery from critical illness; however, further trials are needed. We identified significant HCP enthusiasm, across the multidisciplinary groups within PICU, regarding the role and potential of ERM intervention. The Phase 1b survey demonstrated wide community buy-in for future studies, the Phase 1c observational study had a high level of interest, investment of time and participation by bedside nursing staff and therapists, and the speed and number of PERMIT champions recruited in Phase 3 was very reassuring. Establishing ERM as a credible PICU intervention through a future definitive study is clearly a high priority with NHS staff.

Intervention

The development of the PERMIT manual and the successful, safe, implementation of the manual within the PERMIT Phase 3 feasibility study has confirmed that a complex, multidisciplinary, PICU-wide ERM intervention can be evaluated. The PERMIT manual includes a six-step implementation guide, learning and training resources, and ongoing site support from ERM experts. It incorporates daily acuity scoring, activity-level guidance and a pause and assess safety structure, which are modified to local resources, environment and staffing structure. Through research staff investment, debriefs and local site involvement, we have established the initial implementation of the manual takes approximately 12 weeks. This time period should be integrated into any implementation training phase in a trial.

Trial design and consent model

As with other trials in PICUs, the most powerful trial would use a stepped-wedged cluster design. Not only would this increase the power of the trial, it would also mean that all PICUs involved would benefit from training in the intervention. This design has worked well in PICU previously; the HTA-funded SANDWICH trial66 of a sedation and ventilator liberation protocol intervention recruited 8843 patients across 18 UK PICUs over 18 months.

Opt-out consent is the preferred model of consent. This was successful in the Phase 1 observational study and strongly recommend in the Phase 3 process evaluation, interviews and PPIE work. This consent model would work within a cluster RCT design and implementation of the PERMIT manual and ERM delivery across the whole PICU.

Population

The PERMIT programme of research has clearly shown that elements of ERM are delivered in some form to nearly all patients in PICU, including the sickest patients on maximal organ support. Therefore, the whole diverse spectrum of PICU patients should have the opportunity to benefit from ERM early in their PICU care pathway and for as long as is required. However, for ERM to impact a measurable patient-related outcome it would be logical that a period of exposure to the ERM intervention is required. Therefore, patients with short stays in PICU (e.g. <48 hours) are unlikely to gain measurable benefit. Our approach of including patients on day 3 of PICU in the Phase 1c observational study and Phase 3 feasibility study allowed identification of this patient group. Trial inclusion criteria should allow selection of these patients for assessment of efficacy of ERM, although the ERM intervention could and ideally should be delivered to every patient within the PICU to ensure maximal embedding of the ERM manual and processes with staff. We therefore recommend that a future trial population includes critically ill/injured patients of all ages (0–<18 years) admitted to PICU. They would be identified and enrolled in the study early in their PICU stay (e.g. within 72 hours after PICU admission). This would allow the interventions in the PERMIT manual to be commenced in patients who could receive an adequate amount of ERM, which may lead to measurable benefit. Patients would be excluded by parents/guardians opting out, or clinicians’ decision that ERM or trial inclusion is inappropriate (e.g. anticipated death in PICU, or planned palliative care and withdrawal of life-sustaining therapies). We recognise that ERM activities may be important and recommended end-of-life interventions in this population (e.g. part of pain relief, enrichment to surroundings patient and family PICU experience); however, these would require different patient-reported outcomes or to be delivered outside of a trial setting.

Comparison

The comparison (control arm) would be standard of care before implementation of the PERMIT manual. We have established that even PICUs with an existing ERM programme can benefit and improve with the PERMIT manual and programme (e.g. Site 1 in the Phase 3 feasibility study). The ability for the PERMIT manual to work alongside and enhance, refine and develop existing programmes would allow increased recruitment of PICU sites to a future study. The research programme and process evaluation are also attractive to PICU sites as additional resources would be available.

Outcomes

Through PPIE and parent/family feedback, the amount and dose of ERM were identified as the most important outcome measure. However, we identified in Phases 1 and 3 that it is very difficult to quantify ERM dose due to (1) a heterogeneous patient population (e.g. 0–<18 years of age, developmental stages, size, ambulatory status), and (2) diverse types of ERM activities delivered. Inclusion of health-related QoL outcome measures is recommended in PICU studies47 and is felt important by healthcare professionals and parents/carers; however, the burden on families to complete these tools was clear in Phase 3. Therefore, a pragmatic measure of improvement in critical illness or injury recovery would be required, with accompanying intervention fidelity assessment (i.e. measurement of increased ERM dose delivery at the site and patient levels). Potentially suitable outcomes include length of MV and LOS in PICU (or days free of ventilation/PICU). The advantages to length of MV as an outcome is that it has a clearly defined beginning and end point (e.g. successful extubation without the need for re-intubation). It is also the primary outcome measure in the ongoing pilot, stepped-wedge trial of ERM in the USA PICU UP! study, which would allow direct comparison. 112 The disadvantage is that this will exclude up to 35% of PICU patients with critical illness not requiring ventilation. LOS, as an outcome measure, would allow all patients admitted to PICU to be included in a trial. However, the disadvantage is that the end point is less precise. Discharge from PICU can be to any of step-down to high-dependency unit, ward location, other hospital PICU, neonatal intensive care, home, palliative care facility. The timing of this discharge can be affected by additional factors external to improvement in critical illness and injury (e.g. bed availability on the ward) and is therefore subject to measurement inaccuracy, which may affect trial findings.

With no definitive primary outcome choice, we present a draft proposal based on LOS and length of ventilation (LOV). We need to explore this area further.

Sample size

Approximately 20,000 patients are admitted to PICU each year, of whom around 65% receive invasive MV at admission. The eligible population, using LOV as an outcome, would come from the patients who are on MV on day 3 and stay in ICU for an additional 4 days (this gives us the population who are both most likely to benefit and can receive at least a minimal amount of ERM). The UK national PICANET data report that approximately 19% of patients admitted fulfil these criteria, so 2470 patients will be eligible per year. 67 Allowing for ~5% attrition, 2350 patients will be available for analysis. This equates to approximately seven eligible participants per 1-month period per cluster.

There is a total of 26 suitable PICUs across the UK. Provisional interest in participation in a full PERMIT study is high, and it is reasonable to assume that 21 PICUs would want to participate, which could also include the three sites in the feasibility study. This trial design requires that all participating PICUs begin the control phase of the trial when the data-collection period begins. Further analysis will be required to accurately estimate required parameters for a stepped-wedge cluster randomised trial including the intracluster coefficient (ICC) and cluster autocorrelation coefficient (CAC). Provisional data from BCU PICU provided a mean length of time on MV as 19.3 days for those in PICU more than 7 days, with a SD of 28.4. A reduction of 1.5 days on MV is considered to be meaningful to patients and parents. The SANDWICH trial66 estimated the ICC to be 0.005. Personal correspondence from the USA PICU Up! trial and SANDWICH trial66 leaders suggests that the CAC may be close to 1.

Our proposed design is in shown in Figure 17. Similar to the SANDWICH trial protocol (adapted under CC BY 4.0 license http://creativecommons.org/licenses/by/4.0/),113 there will be an initial 3-month period of baseline data collection during which the PICU will not be exposed to the intervention. Following this, every 3 months, three sites will be randomly selected to transition to the intervention. This will start a 3-month training period of the intervention. As we cannot assume that the PICUs are exposed or not exposed to the intervention during the training, no patients will be recruited through this 3-month period. Once a PICU crosses over to the intervention, it will remain exposed to the intervention for the remaining duration of the study. There will be a final 12-month period during which all PICUs will be fully exposed after the last PICU has transitioned to the intervention. This 12-month period is to ensure that the ERM programme is fully embedded following implementation, which is a key requirement expressed by clinicians to be part of PERMIT and was not achieved in the feasibility study. Assuming an average of seven patients per 1-month period, and total follow-up period of 36 months, 80% power would be achieved. This would equate to a sample size of 4851 participants.

FIGURE 17.

PERMIT trial design cluster, stepped-wedge.

If LOS is used as primary outcome this increases the eligible population to 3800 (19% of 20,000) (Table 30). Allowing for 5% attrition provides a population size of approximately 3600 patients and approximately 11 participants per 1-month period per cluster. The same data from BCH PICU provide a mean estimate of LOS to be 23.7 with a SD of 31.0. Using the same design matrix as for length of time on MV, and an ICC of 0.02 estimated from the PICANet data, the sample size of 7623 would provide over 80% power to detect a 1.5 reduction in LOS.

There will be an initial 3-month pre-implementation block for 21 clusters (e.g. PICUs), stepping into a 3-month training block (staggered for 3 clusters at a time) with 12 months or more post-implementation period.

A further sample size calculation will be performed using the whole PICANET data set with LOV outcome for UK population. At the time of report submission these data were not available because of a cyber-incident on the Leeds University server.

Additional consideration

Chapter 7 concludes with a list of trial elements which will be important to incorporate into a future trial design (see Tables 27, 28 and 29).

In addition, further evaluation of the sample size and primary outcome will be required to justify the size and scale of a definitive trial. We acknowledge that plausible effect size for the primary outcome will also need to be estimated in an internal or external pilot phase of a future study.

Important considerations are needed on the potential confounders which may occur in a large pragmatic trial. The risk of education contamination bias, for example retaining separation between arms of the trial, is important. The huge investment of staff time, resources and effort that we identified during the Phase 3 feasibility study would be replicated in a definitive trial in each PICU. The risk of this occurring outside of the conduct of the trial and at the correct step in the design we believe is low. However, we acknowledge that PICUs in the UK have implemented ERM programmes in various forms, but we also recognise that those PICUs have struggled with maintaining programmes, without well-theorised implementation programmes like PERMIT (e.g. Birmingham and the MOVE4WARD programme).

Finally, the PERMIT feasibility study was conducted with a limited budget and although we provided research support staff funding for data collection and trial conduct at each site, we did not provide resources for any additional ERM delivery by therapists or nursing staff. In addition, we did not undertake an economic evaluation or involve a health economist in the PERMIT feasibility study as per the original commissioning brief. In a future trial, additional NHS support costs will be needed for adequate staff support of both the implementation and the delivery of ERM within clinical care, as identified in Chapter 6: Process evaluation.

Study management

The PPIE work throughout Phases 1, 2, 3 and 4 was led by JMen and SL (our PPIE co-applicant). The study management group inputted into protocol designs, ethics application scope and drafting of the PPIE report.

Planning patient and public involvement and engagement – developing a plan for patient participation, involvement and engagement in a trial

The study team adopted an approach based on consultation, where people are asked for their views, which are then used to inform decision-making. 116 Although this is regarded as the lowest rung of the patient form of involvement117 this was felt to be appropriate given the nature of the research context and the specific remit of the NIHR funding. The team were keen to contribute to the knowledge base surrounding PPIE within the PICU context118 and highlight the impact of PPIE at each stage. A plan was therefore made, although this had to be adapted significantly due to COVID.

Planning patient and public involvement and engagement – identifying parent contributors

Researchers are advised to approach patients and public through formal patient groups, charities, community groups, national directories such as ‘People in Research’ or Health and Social Care patient advisory panels. 119 Partnership with parents who are in a similar situation to potential study participants is vital to ensure that important aspects of the research question have been considered. 120 However, there is recognition that there can be challenges with identifying appropriate contributors. 121,122 The concept of ‘similar situation’ is challenging in the PICU context as the service provision is for all CYP aged 0–<18 years and there is a broad case mix of underlying diseases and diagnosis. 123 In addition, the PERMIT team faced a challenge in accessing a formal established group. There were no pre-established groups in existence within the Clinical Research Network (CRN), the affiliated Trusts for the research (Birmingham Women’s and Children’s NHS Foundation Trust and Southampton Children’s Hospital), and none within the two sites’ PICUs. There were also no national groups of parents with experience of PICU established,118,124 a situation which continues to the current day. In these circumstances identifying people through personal contact or recommendation is therefore acceptable. 119 Our PPIE co-applicant SL and her daughter both felt that it was important that we made efforts to engage with parents who had experience of a child being admitted to PICU. Families without this experience might not understand the extreme emotions parents experience during the first few days of a PICU admission. This approach is supported by other national PICU studies. 120,125–127

Planning patient and public involvement and engagement – impact of COVID

The plan to recruit to a PERMIT-specific parent advisory group made up of parents who had experience of their child being in a PICU was then compounded by COVID. The PERMIT team were re-deployed to clinical work, contact with families was hindered through the wearing of personal protective equipment (PPE) impairing communication and there were the additional challenges of restricted visiting and parental exclusion if parents were symptomatic. 128

In addition, there was an added challenge to speaking to parents with experience of deciding about research participation in PICU because of research suspension. Despite fewer children with COVID-19 admitted to hospital and even fewer admitted to ICUs, PICUs experienced the same disruption to clinical research as adult ICUs. Seventy-five per cent of PICU/ICUs internationally suspended recruitment to some if not all research during 2020. 100 Suspension of research recruitment reduced the number of studies which were open and recruiting and reduced researchers contact with families. This created additional challenges for the PPIE lead to speak to parents with experience of being recruited to research.

There were therefore challenges to the number of parents we could engage with for PPIE. INVOLVE (2012)129 recommend a minimum of two PPIE participants and there is growing recognition that the available number of participants with the relevant experience may be low. 119 We therefore did not set a specific number of PPIE participants, but aimed to involve parents with as varied experience as possible.

Planning patient and public involvement and engagement – children and young people

Conducting PPIE work with CYP was also challenging. A previous review had identified that few PICU studies had managed to conduct PPIE work with CYP with experience of PICU. 118 Although there are excellent Young People’s Advisory Groups available through the NIHR130 and locally131 their membership at the time included no CYP with experience of a PICU admission. Previous studies have consulted with siblings of CYP who have had experience of PICU132,133 However, COVID meant there were no sibling visitors allowed on site within the hospital (still the situation currently) and the YPAG groups were suspended for a period of time.

The decision was therefore made to conduct ‘standalone’ PPIE – identifying and liaising with parents/carers as required for each of the phases. The team also had extensive wider PPIE and qualitative research experience from related studies which were drawn on. Pre-COVID efforts were made to engage with CYP and siblings where possible but this was not possible from 2020 onwards.

One of the concerns of the study, especially pertinent given the additional challenges of COVID, was to ensure that we facilitated parents/legal guardians to have the opportunity to shape and influence research. In a study which was designed to be relevant to all patients admitted to PICU it was vital that we considered equality, diversity and inclusivity in our PPIE. Study materials were specifically developed with graphics to help those for whom English was not their first language, those with dyslexia and those with lower literacy levels. PPIE was also conducted across more than one site to ensure there was representation of parents from a wide geographical area as well as families who lived locally in Birmingham and London. A variety of methods were used to assist with families’ engagement. Face-to-face introductions helped to explain that this was to inform research design, rather than to participate in research. Short information leaflets were provided about what was required. Parents could provide feedback face to face with the PPIE lead or a member of the local research team or by writing responses and returning them in a stamped addressed envelope. PPIE activity could happen within the hospital or within the home environment (if it coincided with other research activity).

Planning patient and public involvement and engagement – allocating appropriate costs

Historically PPIE participants have not always received any payment for their time and involvement; however, this payment is now recognised as good practice. 134 All PPIE activities were costed in line with NIHR (2018) guidance on reward and recognition for public contributors and participants appropriately rewarded. 135

Planning patient and public involvement and engagement – managing the expectations of public contributors

The PERMIT PPIE co-applicant and the parent representative on the Trial Steering Committee were prepared for their roles with clear guidance on the role and what was required. PPIE participants were provided with information about the consultation work by the staff member approaching them. The expectations of their role were identified and as they were involved with ‘standalone’ PPIE there was no ongoing commitment.

Supporting patient participation, involvement and engagement

For patients new to a PPIE role, support to develop their abilities and confidence to express their views and question researchers may be relevant. In order to support our parent co-applicant and the parent representative recruited to the Study Oversight Group both were offered access to appropriate training via a number of resources. Materials supplied included guidance on involvement in PPIE,136 links to local resources within the West Midlands CRN and on-line training available through NIHR. 137 In addition, SL attended a national one-day UK symposium about PICU outcomes and rehabilitation (2017) with members of the PERMIT team in order to help her understand the wider perspective.

There are many PPIE tasks where training is not necessary, where a different perspective or experience of a healthcare condition is the required expertise. 119,134 In line with this PPIE participants within PERMIT did not receive any formal training.

Recording and evaluating patient participation, involvement and engagement

While there is consensus that PPIE has considerable potential to benefit clinical trials, there has been little formal evaluation of its impact. 115 None of the PICU studies in a UK review provided an objective measurement of the impact of PPIE. 118 The PERMIT team were therefore keen to create a clear picture of when and where PPIE happened, what impact this had on the trial, the nature of PPIE activities and the impact of the activity on the trial design and conduct. 138 This is captured in the report above, with specific examples of what changed as a result of consultation detailed below.

Question 1: who should my trial results apply to?

Parents

All parents of children admitted to PICU and approached for the feasibility study (Phase 3) were also offered the opportunity to be study participants and provide feedback about their child and family experience through questionnaires (21/30) and an additional optional interview (n = 14 participated). There were no exclusion criteria, although we were unable to provide translated versions of the validated questionnaires and we did not have the option to interview participants in any language other than English. In addition, we sought to hear the voice of parents who declined their child’s participation in the study. This perspective is seldom heard and the four families which this applied to were all offered the opportunity. Unfortunately, this was declined by all four families.

Are the groups identified in Question 1 likely to respond to the treatment in different ways?

A number of previous ERM studies have excluded patients <3 years of age,20,15 even though 60% of UK PICU admissions are <36 months. 62 The PERMIT Phase 3 study team was therefore keen to ensure that families of infants were offered the opportunity of participation. This was successfully achieved across the three study sites with 9/30 (30%) participants under 12 months of age. We were also concerned to ensure that the study captured patients at risk of or experiencing multiple organ failure. Twenty-seven per cent (n = 8) of patients were admitted following surgery, including two patients who had undergone cardiac surgery. Other admission reasons included trauma (n = 2), infectious/inflammatory (n = 2) and neurosurgery (n = 1). In addition, 63% of recruited patients had an underlying disability (mild-severe) as indicated by a baseline POPC score. We therefore feel that opportunities to participate in PERMIT were offered equitably and ensured that under-served CYP and families had an opportunity to participate in research.

Will my trial intervention and/or comparator make it harder for any of the groups identified in Question 1 to engage with the intervention and/or comparator?

Evidence has shown that admission to PICU is extremely stressful for parents and many find it difficult to consider research during the initial few days. 141 Our concern was that this would then serve as a barrier to families who were approached about the study for a full informed consent. Our PPIE work indicated that an opt-out consent approach would be appropriate in Phase 1 (observational only), which was confirmed by 100% (n = 169) of parents choosing for their child’s data to be included in the study. In Phase 3 an informed consent approach was required; however, steps were taken to help parents to understand each step of the study and reduce the stress associated with participation. Study participants endorsed this approach and, importantly, helped provide vital insight into the low perception of risk associated with a future trial. A future trial could therefore proceed with an opt-out consent, which helps facilitate research engagement for a wider range of patients and families.

Will the way I have planned and designed my trial make it harder for any of the groups identified in Question 1 to consider taking part?

We worked hard with our PPIE participants to design the trial and the patient-facing information as clearly as possible given the challenging situation eligible families were in. We also provided thorough training within the site initiation visit (SIV) with sites to discuss the importance of a sensitive approach to families and the value of the staged informed consent approach. We view the relatively low decline rate of 4/34 (12%) as testament to the clear participant information sheets and support of the research delivery teams. One aspect where we were mindful of ensuring choice was in the method of completing outcome measures. We did not want to digitally discriminate or disadvantage families so offered outcome measures in a number of different formats, including paper, online and completed with a researcher by phone.

Phase 1a: scoping review

In our scoping review of paediatric ERM literature, we identified that optimal aspects of ERM intervention delivery, timing, content, active ingredients, dose–response relationships, progression and implementation strategies have yet to be established. Multicomponent ‘non-mobility’ and ‘mobility’ ERM interventions were feasible and safe and most involved physical therapy, OT and SLT.

Children under 3 years old were more likely to receive interventions such as cuddles or in-bed mobilisation, whereas non-ventilated children or those aged 3 years and older were more likely to receive mobility interventions involving physical therapy or OT. Importantly, family involvement appeared crucial, and the lack of a well-defined ERM protocol was a significant barrier to ERM implementation. With no clear evidence on the impact of bundles of care or behavioural interventions incorporated within ERM, further research in this area is essential.

Phase 1b: survey of current practice

This national survey of HCPs from UK PICUs identified the importance of ERM as an intervention which participants believe can improve the physical, psychological and cognitive recovery of critically ill or injured infants and children across all ages. Our findings indicated support for ERM, but highlight uncertainty with suitability, variability with the definition of this complex intervention, variation in timing of initiating and which patient groups should receive ERM. Similar to our scoping review, the reported lack of ERM protocols in most (21/26) UK PICUs reinforced a strong requirement for evidence-based standardised protocols with optimal timing, intensity, frequency and duration of ERM. There is a need for flexible protocols to allow for tailoring rather than prescription. Key barriers to ERM delivery were identified (e.g. funding and staffing) and potential clinical (e.g. improved psychological outcomes) and economic (e.g. reduced PICU LOS) benefits to patients and PICUs.

Phase 1c: observational study of early rehabilitation and mobilisation practice

We observed ERM practice in 169 patients across 15 PICUs who reached 9 a.m. on day 3 after PICU admission in our 14-day observation period. Ninety per cent of eligible patients were enrolled using an opt-out consent model. On the first study day (day 3 after PICU admission) 162/169 (96%) of patients received an ERM activity; 87% involved a mobility and 38% an out-of-bed mobility. The rate of ERM activities for patients remained constant across the subsequent 7 days of their PICU admission (or until PICU discharge).

Over the observation period, 3696 ERM episodes delivered 4978 ERM activities across all PICUs. Most were delivered by a registered nurse or parent/family member. Positioning with and without mobility elements accounted for nearly half of all ERM activities. A wide range of ERM activities were reported, but were more likely to be passive or enrichment activities rather than active ERM. ‘Cuddles’ by a family member/nursing staff was the most frequent out-of-bed activity. We identified that family presence significantly increased out-of-bed ERM, although MV, presence of a urinary catheter and pre-existing severe developmental delay were associated with not receiving out-of-bed ERM. Presence of an ERM protocol did not impact the chance of out-of-bed mobility. However, ERM was delivered to nearly all patients, including those of all ages, admission diagnosis and with the highest level of organ dysfunction or organ support.

ERM was delivered safely with a low (<3%) reported rate of AEs per ERM activity. Most AEs did not require any corrective intervention. Of concern was that delirium screening was universally absent in study-participating PICUs and this requires attention. Nursing staff and parents delivered the majority of ERM activities throughout the 24 hours period. Physiotherapists only delivered 10% of ERM although 59% of patients received at least one PT-delivered ERM episode at some point. There was minimal input from other medical, therapy, or support staff reported. Any ERM manual or intervention plan will need to be designed to utilise available staff or require significant increased resources to support them.

Phase 2: paediatric early rehabilitation and mobilisation during intensive care manual development

Our synthesis of the key messages, assumptions and uncertainties that emerged from our prior Phase 1 work showed that ERM is currently defined and enacted in multiple ways. Importantly, people see the potential value for the diverse patient populations within PICU and are willing to support the safe delivery of ERM but are uncertain how best to deliver it. Our three face-to-face workshops with NHS HCPs (n = 18) and one online workshop with international experts (n = 3) helped generate some core guiding principles around the potential shape and content of the intervention. For example, everyone in PICU (doctors, nurses, physiotherapists, and parents) is essential for ERM delivery – everyone should take some ownership. Also, ERM needs to be as inclusive as possible, with a focus on promoting movement and mobility as early as possible and with progressive increases over time. Our review of existing ERM protocols and discussions with healthcare professionals enabled us to develop a prototype ERM manual that was focused both on the safe delivery of ERM for each patient, and on the introduction and embedding of an ERM approach within a PICU. The manual was informed by current evidence, experience, and theory. It offered a flexible, progressive, approach to the delivery of ERM, with resources including essential clinical materials – the ‘bedside bundle’ – that consist of an ERM daily flowchart, patient acuity levels, ERM activity levels, and pause and re-assess criteria. It also included a step-by-step guide to putting ERM into practice – the ‘implementation toolkit’ – that focused on building ERM leadership, generating staff buy-in, making ERM workable, and keeping it going over time.

Phase 3: feasibility trial and implementing evaluation of non-randomised early rehabilitation and mobilisation intervention

All three sites implemented the PERMIT programme as described in the manual. The families were positive about the study recruitment process and all sites successfully recruited the 10-patient target. To achieve ERM delivery, all patients (1) had an acuity level scored (and repeated on 84% of ward rounds) and (2) had an acuity level correctly linked to an ERM activity prescription and then subsequently to a delivered ERM activity. The level of activity was broadly representative of the acuity level.

Other key findings were that a large number of clinically relevant patient outcomes were measured through validated tools and all patients received ERM activities safely using the pause and assess criteria with only two trial reported AEs and no severe AEs. ERM was important for the physical and psychological recovery of the CYP, as well as the psychological well-being of parents/carers supporting their involvement in their child’s care. PERMIT was seen by health professionals and parents as worthwhile, feasible and acceptable. Finally, having access to research delivery support was central to support recruitment, data collection and data entry.

Phase 4: consensus study and trial design

With input from PPIE, parent/family members and multidisciplinary members of the study management group we reviewed and refined the findings from Phases 1, 2 and 3 of PERMIT. We confirmed that a future PERMIT ERM clinical trial was necessary and likely to be feasible with consideration of additional trial design elements. The most suitable trial design for the complex intervention is a clustered stepped-wedge randomised control trial within PICUs across the NHS. The primary outcome requires further consideration. LOV (or days free from ventilation) is a pragmatic compromise on measurable PICU outcome and a likely accurate measure of improvement in critical illness recovery. It would also allow comparison of the PERMIT manual and intervention with the only other similar PICU-wide ERM intervention study, the PICU UP! programme, ongoing in the USA. 112 Further consensus work in developing the primary outcome will be required with the UK PCCS-SG and trialists prior to a definitive study proposal. Any future trial will require health economic evaluation in addition to assessment of patient-related outcomes.

Phase 1a: scoping review

We conducted a comprehensive search using broad inclusion criteria, but the risk of publication bias remains. We also acknowledge the inherent limitations of vote-counting used to determine effective ERM interventions since RCTs included in this review were not adequately powered, and findings may not be clinically relevant.

The majority of studies included in this review had design flaws, and varied in the consistency and reporting of interventions or outcomes evaluated. No between-group mean/SDs or effect with precision intervals were ever reported. These outcomes might have different implications on the strength of the evidence when the cost effectiveness of ERM is considered. Lastly, most studies did not provide information about intervention delivery to understand active drivers of successful implementation. Consequently, inferences drawn are based solely on explanatory findings.

Phase 1b: survey

The strength of this survey was an inclusive representation of 90% of UK PICUs and views from the wider MDT. A limitation was the use of a non-validated questionnaire. None or partial responses may indicate poor engagement in the ERM topic, and as with all self-reported surveys, responses indicate reported rather than necessarily actual clinical practice. Finally, the findings represent the views of UK NHS staff and may not be generalisable to other healthcare settings.

Phase 1c: observational study

We observed over half of all UK PICUs, geographically diverse, with varying population characteristics, PICU size, case mix and staffing structures during the two observation periods. However, the types of PICUs may not be generalisable to other UK or non-UK PICUs. To focus observations on early ERM, but to avoid very short-stay PICU patients (e.g. <48 hours), we started observation at 9 a.m. on the third day after PICU admission. ERM practice and delivery to patients in the first 72 hours of PICU stay may also be important in guaranteeing dose and efficacy of intervention. In addition, we stopped observation after 7 days of study observation (day 10 of PICU) or at discharge. Thirty-two per cent (54/169) of our cohort continued to stay in PICU and longer-term PICU care and use of ERM may also be important. Also, ERM may have a role in step-down high-dependency care or ward areas.

We acknowledge the potential risk of observer bias and Hawthorne effect in our study design. ERM activities were listed on the bedside activities document to allow ease of recording. Presence of the documentation or the known process of observation may have affected the amount of ERM delivered to patients during the observation period (e.g. increased number, duration or variety of ERM activities, stimulated by the bedside information).

ERM activities were recorded in the medical records by bedside clinical staff. Research staff extracted this information for our PERMIT CRFs. AEs were self-reported by the clinical team without independent confirmation and therefore may have under- or overestimated the frequency of events or relatedness to the ERM activity; however, the rates identified closely matched those extracted in the scoping review.

We identified a very high rate of ERM activity on study day 1 using the inclusive definition of any ERM. This limited any ability to perform the planned logistic regression modelling to explore patient-, site- or ERM-related factors. In our out-of-bed logistic regression model, due to the small number of patients per site, we were unable to use site as a random effect. Further exploratory analysis of factors affecting different subtypes of ERM are planned and may highlight wider variation in practice across sites.

Phase 2: manual development

A strength of this study was the multiple sources of evidence we used to develop the ERM intervention manual: evidence from a wide range of existing studies, concepts, tools and resources, as well as the experience of diverse practitioners and topic experts. A further strength was that the manual was informed by a range of theories of implementation. However, given the COVID context during the study, we were unable to conduct workshops and interviews with parents and CYP with PICU experience, so we were not at all successful in using their direct experience to shape the ideas within the manual. The work of learning from parents’ experiences was instead undertaken through the process evaluation work in Phase 3.

Phase 3: part 1 feasibility study

A strength of this study was the phased introduction and embedding of a novel intervention (the PERMIT manual) alongside a set of novel trial processes. A further strength was the engagement of staff within and across sites, including those who championed and led the ERM programme, those who delivered ERM, as well as those other staff at the sites not directly involved in bedside ERM delivery. This enabled us to introduce an ERM programme at pace, enrol planned numbers of patients and parents, demonstrate data collection is feasible and the ERM is delivered safely. We were not successful in obtaining timely local site approvals at one site, which meant that the introduction of the ERM programme was delayed. As a result, this site spent relatively little time in each of the phases. Also, when research staff were not available at sites – notably on ward rounds – we did lose some quality and accuracy in some areas of data collection. A health economic evaluation was removed from the feasibility study after the request of the HTA board. Full health economic evaluation and support in a future study are required.

Phase 3: part 2 process evaluation

A strength of our data is the spread of data across methods, as well as across sites and participants. We obtained a comprehensive account of the difficulties of introduction and embedding across the sites. A further strength was the multidisciplinary respondents from each site – including those who championed and led the introduction, those who delivered ERM, as well as those other staff at the sites not directly involved in bedside ERM delivery. This enabled us to document the range of perspectives on problems and tensions around the evolving context and delivery across the sites. Parental accounts were helpful in clarifying trial processes, as well as providing insight into their perspectives of delivering ERM, and were essential to the highlighting of elements to change in future. We were not successful in recruiting parents who had refused consent to the main study for an interview to explore their reasons for declining.

Phase 4: consensus and trial development

The short duration of the Phase 4 study and continued impact of COVID pandemic on PICU health-care staff and parents and families who participated in PERMIT limited the scope of consultation and feedback. Further work with PPIE groups and the PICU clinical community is required to evaluate the definitive primary outcome. This will include additional sample size calculations with more extensive PICANet data after overcoming the cyber-incident at the University of Leeds.