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For peer review only
A multi-centre randomised feasibility STUdy evaluating the impact of a prognostic model for management of BLunt
chest wall trauma patients: STUMBL Trial
Journal: BMJ Open
Manuscript ID bmjopen-2017-015972
Article Type: Protocol
Date Submitted by the Author: 13-Jan-2017
Complete List of Authors: Battle, Ceri; Academic Emergency Medicine Research Unit, Emergency Dept, Morriston Hospital Abbott, Zoe; Swansea University, Swansea University Medical School
Hutchings, Hayley; Swansea University, Swansea University Medical School O'Neill, Claire; Swansea University, Swansea University Medical School Groves, Sam; Swansea University, College of Human and Health Sciences Watkins, Alan; Swansea University, Swansea University Medical School Lecky, Fiona; University of Sheffield/ Salford Royal Hospitals NHS Trust, Emergency Medicine; Trauma Audit and Research Network, Institute of Population Health Jones, Sally; Royal Gwent Hospital, Emergency Department Gagg, James; Taunton & Somerset NHS Foundation Trust, Emergency Department Body, Richard; Central Manchester University Hospitals NHS Foundation Trust, Emergency Dept
Evans, Phillip; Academic Emergency Medicine Research Unit, Emergency Department, Morriston Hospital
<b>Primary Subject Heading</b>:
Emergency medicine
Secondary Subject Heading: Research methods
Keywords: Blunt chest wall trauma, Prognostic model, Feasibility trial, Stepped-wedge randomised trial
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A multi-centre randomised feasibility STUdy evaluating the impact of a prognostic
model for management of BLunt chest wall trauma patients: STUMBL Trial
Corresponding author: Dr Ceri Battle: Welsh Institute of Biomedical and Emergency
Medicine Research, Emergency Dept, Morriston Hospital, Swansea, UK., SA6 6NL.
[email protected] Tel: 00 44 1792 703124
Ms Zoe Abbott: Swansea University Medical School, Swansea University, Swansea, UK.
Professor HA Hutchings: Swansea University Medical School, Swansea University,
Swansea, UK.
Dr CBC O’Neill: Swansea University Medical School, Swansea University, Swansea, UK.
Dr S Groves: College of Human and Health Sciences, Swansea University, Swansea, UK.
Associate Professor A Watkins: Swansea University Medical School, Swansea University,
Swansea, UK.
Professor F Lecky: School of Health and Related Research, Sheffield University. Salford
Royal NHS Foundation Trust, Salford, UK
Dr Sally Jones. Emergency Department, Royal Gwent Hospital, Newport, UK
Dr James Gagg. Emergency Department, Musgrove Park Hospital, Taunton, UK
Dr Richard Body. Emergency Department, Manchester Royal Infirmary, Manchester, UK.
Professor PA Evans: Welsh Institute of Biomedical and Emergency Medicine Research,
Emergency Dept, Morriston Hospital, Swansea, UK.
Word count: 3728
Key words: Blunt chest wall trauma; prognostic model; feasibility trial; stepped-wedge
randomised trial.
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ABSTRACT
Introduction: A new prognostic model has been developed and externally validated, the aim
of which is to assist in the management of the blunt chest wall trauma patient in the
Emergency Department (ED). A definitive randomised controlled trial (impact trial), is
required to assess the clinical and cost effectiveness of the new model, before it can be
accepted in clinical practice. The purpose of this trial is to assess the feasibility and
acceptability of such a definitive trial and inform its design.
Methods / analysis: This feasibility trial is designed to test the methods of a multi-centre,
cluster-randomised (stepped wedge) trial, with a substantial qualitative component. Four
EDs in England and Wales will collect data for all blunt chest wall trauma patients over a five
month period; in the initial period acting as the controls (normal care) and the second period,
acting as the interventions (in which the new model will be used). Baseline measurements
including completion of the SF-12v2 will be obtained on initial assessment in the ED. Patient
outcome data will then be collected for any subsequent hospitalisations. Data collection will
conclude with a six week follow-up completion of two surveys (SF-12v2 and Client Services
Receipt Inventory). Analysis of outcomes will focus on feasibility, acceptability and trial
processes and will include recruitment and retention rates, attendance at clinician training
rates and use of model in the ED. Qualitative feedback will be obtained through clinician
interviews and a research nurse focus group. An evaluation of the feasibility of health
economics outcomes data will be completed.
Ethics / dissemination: Wales Research Ethics Committee 6 granted approval for the trial
in September 2016. Patient recruitment will commence in February 2017. Planned
dissemination is through publication in a peer-reviewed Emergency Medicine Journal,
presentation at appropriate conferences and to stakeholders at Professional Meetings.
ISRCTN Trial registration number: ISRCTN95571506
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Strengths and limitations of trial:
1) This established research team has published a substantial amount of background work
supports this trial protocol
2) The trial has full funding, research ethics and HRA approval in place, with the required
number of sites already recruited and randomised for commencement of patient recruitment
3) As this is a feasibility trial, no conclusions can be reported regarding the impact of the
prognostic model.
INTRODUCTION
Blunt chest wall trauma accounts for over 15% of all trauma admissions to Emergency
Departments (ED) worldwide, with reported mortality ranging between 4 and 60%.[1-3]
Despite the reported poor outcomes, no current national guidelines exist to assist in the
management of this patient group unless the patient has severe, immediate life-threatening
injuries.[4] The difficulties in the management of the blunt chest wall trauma patient in the
ED, are becoming increasingly well recognised in the literature.[4,5]
The blunt chest wall trauma patient commonly presents to the ED with no respiratory
difficulties, but can develop complications up to approximately 72 hours after initial
presentation.[1-4] Clinical symptoms are not considered by most clinicians to be an accurate
predictor of outcome following non-life-threatening blunt chest wall trauma.[1-5] Decisions
regarding the appropriate level of care required by the patient following discharge from the
ED are therefore difficult, which is further compounded by the lack of current national
guidelines. An improvement in the ability to identify the high risk blunt chest wall trauma
patient on initial assessment in the ED would potentially lead to a reduction in these poor
outcomes.[8,9]
A new prognostic model to assist in the management of blunt chest wall trauma patients in
the ED, has been developed and externally validated in a large multi-centre study.[1,5-7]
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Guidelines recommend however that prognostic models should not be used in clinical
practice until an impact study has been completed, in which the clinical application of the
model has been tested.[10-11]. Prior to undertaking a large definitive randomised controlled
trial of the clinical and cost effectiveness of the prognostic model, a smaller scale trial is
required to address the issues of feasibility and acceptability.
Trial aims
The aim of this trial (protocol version 5, 6th January 2017) is to establish the feasibility and
acceptability of the final definitive impact trial, which will ultimately determine whether the
prognostic model can be used safely and effectively in clinical practice in the UK. The trial
objectives are to: (1) Evaluate the infrastructure necessary to perform a future definitive trial,
including the Trial Management Group, Trial Steering/Data Management Committee; (2) test
the feasibility of the proposed stepped-wedge, cluster-randomised design; (3) evaluate and
qualitatively explore the compliance of the clinicians in using the prognostic model (and
reasons for non-compliance); (4) assess the appropriateness of the training manual and
consistency of training provided by each principal investigator (PI); (5) quantify the number
of patients required for a full definitive trial through the estimation of the magnitude of effect
and necessary parameters, including the margin of error acceptable to achieve the proposed
outcomes; (6) assess the processes of patient recruitment, consent and reasons for non-
participation; (7) assess the quantity and potential patterns of missing data; (8) test the
feasibility of collecting the proposed outcome measures for a full trial, including optimal time
points, using the electronic case report form on the REDCap data collection system; (9)
decide whether a fully powered, multi-centre randomised trial is indicated by formal
assessment of feasibility trial findings against pre-set progression criteria.
METHODS AND ANALYSIS
Trial design and randomisation
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This feasibility trial is designed to test the methods of a multi-centre, cluster randomised
(stepped wedge) trial,[12] with a substantial qualitative component. Figure 1 outlines the trial
procedure. There will be four hospitals participating in the trial, which will be run using a
stepped wedge design. In accordance with Medical Research Council (MRC) guidance [13],
the unit randomisation will be the EDs, rather than patients, since the intervention will be
used by ED clinicians, with the aim of studying effects on patient outcomes. All participating
EDs will begin as control sites, at the same time, testing conventional management without
the model, for a period of one month (control arm). Every month, following the initial month's
data collection period as controls, one hospital will be randomly assigned to become an
intervention arm (in which all clinicians in the ED will be using the risk model) sequentially,
until all hospitals are acting as interventions.
The randomisation process applies to the hospitals (known as clusters) participating in the
trial, rather than at a patient level. The order in which hospitals EDs convert to intervention
status is based on a purely random process (involving only computer-generated random
numbers, but no information on the individual hospitals or EDs), and can be regarded as
equivalent to the drawing of names at random. As there are four hospitals participating in the
trial, all patient recruitment will be completed over a five month period. This trial design will
test the feasibility of the classic stepped wedge design, to be used in the future definitive
trial.
During the control period, the doctors in each ED will receive training on the model from the
principal investigator (PI) in each ED. Each PI will be instructed at the start of the trial, on
how to train the clinicians and a training manual will be designed and provided.
Figure 1: Schematic representation of the trial’s timelines
Population
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Patients will be included in the trial if they present to the ED with isolated blunt chest wall
trauma, are aged 18 and over and are capable of giving consent to participation. Potential
patients will be excluded if they are under the age of 18, lack capacity to give informed
consent, present with any immediately life-threatening injuries or any concurrent injury that
will determine the patient’s management (rather than the chest trauma). Patients will be
withdrawn from the trial if they lose capacity (including death) to complete the surveys and if
they request to be withdrawn. This data will be recorded as part of the assessment of the
trial’s success criteria, in order to inform the design of the future definitive trial. A list of all
patients who decline to participate will also be completed in order that the trial team can
assess the recruitment rates at the end of the study.
Setting and recruitment
This multi-centre feasibility trial will be run in the EDs of the Royal Gwent Hospital in
Newport, Musgrove Park Hospital in Taunton, Salford Royal Hospital and Manchester Royal
Infirmary (all large teaching hospitals located in the UK). The clinicians or research nurses in
the ED will screen, recruit and consent eligible patients to the trial.
Sample size
A five month recruitment period has been proposed. In 2015, over 1200 blunt chest wall
trauma patients presented to the ED of the hospital of the trial research team, with over 100
of these admitted. If the four participating hospitals recruit for five months each, between 30-
80 patients per site should be recruited, allowing for loss to follow up, low response rates
with follow-up surveys and difficulties with recruiting at weekends if research nurses only
work Monday to Friday. This sample size is the minimum number of participants considered
necessary to test the processes of data collection, based on existing recommendations with
respect to the number of patients required to yield meaningful estimates of parameters of
interest.[14]
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The analysis will lead to an estimation of the sample size for the definitive trial needed to
yield 80% power when using a significance level of 5%, by establishing non-inferiority
between use of the prognostic tool and standard care, as revealed by the feasibility study.
The analysis will include descriptive data (means and standard deviations) on all outcomes
collected, including levels of missing data, leading to the calculation of clinically important
differences. The conventional sample size calculations for the future definitive trial will be
developed using this analysis and the consensus among the Trial Management Group and
Trial Steering Committee of the minimal clinically important difference in these measures. If
the recruitment and retention plan is shown to be optimistic in this feasibility trial, then this is
an important finding which will inform the sample size calculation for the future main
definitive trial.
Interventions
The intervention being investigated in this study is the use of the prognostic model to guide
the clinicians' clinical decision making. The model will be used by the clinician during the
initial patient assessment and will provide a suggestion of the appropriate management in
terms of whether the patient can be safely discharged home, or whether they need
admission to either a ward or critical care. There will be no other differences in patient care.
All patients will be required to complete one survey (SF-12v2),[15] on initial presentation to
the ED and two more surveys at six weeks post-injury (SF-12v2 and a Client Services
Receipt Inventory). A sample of the clinicians using the model will be asked to attend a short
interview in which they will be asked to discuss the model in relation to clinical practice. The
research nurses will be required to attend a focus group in which there will be a discussion
about the trial’s methodology including specifically issues around data collection.
Figure 2: Summary of the patients’ journey through trial:
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Strategies to improve adherence to interventions
Full training (including a training manual) on the use of the model and the trial design will be
provided for each hospital’s principal investigator, who will then be responsible for training
the doctors working in their ED. Feedback from a sample of the clinicians regarding the
model will be provided through a short interview, at a convenient time and location. All
documentation will be available in the Welsh language where applicable, working in
conjunction with the Language Awareness Infrastructure Support Service. Patients will be
offered the chance to be entered into a prize draw if they return their surveys at six weeks
post-injury.
Outcome measures
Primary outcome measure:
Patient recruitment rate will be recorded as the number of eligible patients who consent to
trial participation at the end of the five month data collection period, at each site.
Secondary outcome measures:
1) 'Clinician recruitment rate' will be recorded as the number of eligible clinicians working
within the participating ED who agree to take part in the study by the end of the five month
data collection period, at each site.
2) 'Response rate of follow up data' (quality of life surveys) will be recorded as the number of
patients returning postal surveys at the end of the five month data collection period, at each
site.
3) 'Clinicians Training Attendance rate' will be recorded as the number of clinicians who
receive formal training in the use of the model, prior to the second data collection period
(intervention arm), at each site
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4) 'Compliance with use of model rate' will be recorded as the number of times the clinician
used the risk model for an eligible patient, at the end of the second data collection period
(intervention arm)
5) 'Overall mean quality of life' as reported using the SF-12v2 survey for patients, at the end
of the control and intervention data collection periods (compared to baseline taken on initial
assessment in the ED), at each participating site.
6) ‘Resource usage by patients as a result of the intervention’ as reported on the Client
Services Receipt Inventory at six week follow-up.
Data collection
Data collection to be completed by the on-site research nurse and will include: (1) SF-12v2
survey and prognostic model (if used) completed in the ED; (2) mechanism of injury, a
measure of pre-admission frailty, admission status, hospital and ICU length of stay,
occurrence of complications (mortality or pulmonary morbidity) and re-admission to hospital
will be obtained from medical records prospectively, during the patient's hospitalisation; (3)
at six weeks post injury, the second quality of life questionnaire (SF-12) and Client Service
Receipt Inventory will be sent out to the patient for completion.
Data collection to be completed by the qualitative researcher will include: (1) attendance at
the PI-led training sessions at 2 sites in order to assess consistency of training provided
between sites and the appropriateness of the training manual; (2) clinicians will be asked to
complete an online feedback survey after the training session to collect their views about the
training, for example; travel and time costs incurred, completeness, appropriateness and if
they have any suggestions about possible improvements; (3) a total of 8 doctors (two from
each site) who are using the model will be interviewed at the end of the study period to
understand how the tool was used, ease and time of use, as well as problems with its use. If
it arises, the study team will need to also understand a situation in which the model could
have been used, but was not used, and why that might have occurred. Doctors at
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participating sites who have not used the model (if any) will be invited to participate in
interviews to explore their reasons; (4) a focus group will be facilitated by the qualitative
researcher in which the research nurses responsible for data collection will discuss the trial
process in depth.
An evaluation of the feasibility of health economics outcomes data will be completed as part
of the trial. As this is a feasibility trial, the focus will be on establishing the most appropriate
framework for a future health economic analysis in the full definitive trial. The feasibility of
collecting data on outcome and resource use will be assessed. A provisional assessment of
the cost categories associated with the intervention (for example staff time associated with
training and use of the model) will be completed, through discussion with the qualitative
researcher completing the telephone interviews. To capture resource usage by patients as a
result of the intervention, from an NHS/PSS (Personal Social Service) perspective, an
adapted resource usage questionnaire will be used. The use of the SF-12v2 will be
considered as a measure to derive utilities using the SF-6D. Data will be assessed to
examine the completeness of data captured, such as response rate and potential missing
items.
Data management
REDCap (Research Electronic Data Capture) will be used for data capture and for
completion of the electronic case report forms, hosted at Swansea University.[17] REDCap
is a secure, web-based application designed to support data capture for research studies,
providing 1) an intuitive interface for validated data entry; 2) audit trails for tracking data
manipulation and export procedures; 3) automated export procedures for seamless data
downloads to common statistical packages; and 4) procedures for importing data from
external sources. The use of the REDCap system will be discussed in the focus group with
the research nurses who will be completing the electronic case report forms. Feedback will
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be used to adapt the system to improve the setup, prior to the commencement of the full
definitive trial.
Statistical methods
Quantitative data analysis: Criteria of study success: In order to evaluate the success of the
feasibility trial, with the view to continue to a full definitive impact trial, the Data Monitoring
Committee will assess the final results using the ACCEPT model, developed by
Charlesworth et al, 2013)[17]. The predetermined success criteria are highlighted in Table 1.
Table 1: Trial feasibility criteria
Sample size and participants:
1) 95% or more of clinicians working within the participating ED agree to take part in the study
2) 80% or more of eligible patients consent to data collection and follow up.
3) Follow up data for primary outcomes can be collected for 80% or more of patients
Interventions:
1) All clinicians involved in the trial receive formal training in the use of the model
2) 90% compliance with use of the model during intervention period
Outcomes:
1) Mean quality of life reported in intervention arm is not less than 80% of that reported in control arm
2) Outcome measures reported in the intervention period are equal to, or better than, those reported
during the conventional management period
Qualitative data analysis: Focus groups and interviews will be audio recorded and sent to a
professional transcription service for verbatim transcription. The qualitative researcher will
oversee this process and upon receipt of transcripts will check them for accuracy against the
original recording and undertake anonymisation in accordance with best practice standards.
The cleaned and anonymised transcripts will be uploaded into NVIVO 10 - a qualitative data
analysis program.[18] The qualitative researcher will code the transcripts thematically using
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a code book which developed initially from the background literature and feedback on the
training as well as issues which will emerge through the process of constant comparison
which underpins qualitative data analysis. A sub sample of coded transcripts will be checked
by a second qualitative researcher (by reciprocal arrangement within the wider team at the
trials unit), using the coder comparison query tool.
Trial monitoring and management
An independent, joint trial steering / data monitoring committee will be formed that has no
link to the sponsor and has no competing interests. The role of the committee will be to
monitor adverse and serious adverse events, stopping criteria and trial endpoint success
criteria analysis. Stopping criteria will include; 1) a 5% increase in each of the hospitals, in
the number of patients with an unplanned representation to the ED due to development of
complications, leading to ITU admission and unexpected death (following direct discharge
from the ED on initial presentation), in the intervention period compared to the control period;
2) a 5% increase in each of the hospitals, in the number of patients identified as having a
delayed admission to ITU leading to unexpected death, in the intervention period compared
to the control period. The committee will also be responsible for the overall supervision of the
trial to ensure the trial is completed according to rigorous standards.
There will be no direct change to patient care, however once the model has been introduced
to each ED, the clinicians will be required to use the prognostic model to guide their
management decisions for the patient. The model will only be used as a guide however, so
the clinicians will be instructed to still use their normal clinical decision-making and if
necessary, this can over-ride the prognostic model. Although there are a number of
expected adverse events for patients who have sustained blunt chest wall trauma, the PI
may take appropriate urgent safety measures in order to protect research participants
against any immediate hazard to their health or safety, without prior authorisation from a
regulatory body. Any serious adverse event and urgent safety measures will be reported to
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the CI immediately with details of the measure and a plan for further action. The CI or
Sponsor will notify the main REC and Trial Steering Committee. Serious adverse events will
include; 1) death or ICU admission in patients who have been discharged home as
suggested by the risk score and 2) any trial patient complaint.
ETHICS AND DISSMINATION
Ethical issues
This trial has received ethics approval by the Wales Research Ethics Committee 6 (Ref:
16/WA/0290). Any arising important protocol modifications (such as changes to eligibility
criteria, outcomes, analyses) will be communicated to the relevant parties (investigators,
REC/IRBs, trial participants, trial registries, journals, regulators) in a timely manner.
Compliance with this will be monitored by the trial sponsor (ABMU Health Board R&D
Department). Informed consent will be obtained by the clinicians or research nurses who will
all have received ‘protocol and informed consent specific training’ in alignment with the
principles of GCP and who have signed the trial delegation log. Consent will be sought,
following a full introduction to the study and once the patient has had time to discuss the
Patient Information Sheet with a family member / carer (as appropriate). A study withdrawal
letter will also be attached to the Patient Information Sheet in case the patient wishes to
withdraw consent in the first week following recruitment.
The Trial’s Chief Investigator (CI) will take responsibility to ensure that patient anonymity is
protected and maintained. Information with regards to study patients will be kept confidential
and managed in accordance with the Data Protection Act, NHS Caldicott Guardian, The
Research Governance Framework for Health and Social Care and Research Ethics
Committee Approval. All patients will be allocated a study number once informed consent is
obtained. Personal data will only be identifiable by this study number during data collection.
All patient identifiable data will be removed and data anonymised once data collection using
the survey is complete. The CI will act as the custodian of the data and the records will be
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kept securely for a further 5 years in the Health Board archive facility. The Caldicott
Guidelines will be adhered to throughout the study.
Dissemination policy
Dissemination of the outputs from this trial is proposed through publication in an appropriate
Emergency Medicine journal and by presentation at relevant international conferences. The
aim of this feasibility trial is not to report definitive results regarding clinical and cost
effectiveness however, any important outputs produced in the trial related to the prognostic
model will be published in appropriate Emergency Medicine Journals, as follow-on articles
from our previous published work in this area. We will disseminate our findings to
stakeholders via professional meetings. The Trauma and Audit Research Network (TARN)
newsletter will be used to disseminate the results to the Trauma leads in each ED
participating in TARN in the UK.
Contributors: All authors of the paper have contributed to the design of the trial. CB wrote
this protocol and all other authors edited and made revisions for intellectual content. PE, HH
FL, JG and SJ have been involved in the background development and validation work
leading up to this trial. For the protocol development; PE, FL, RB, SJ and JG provided the
Emergency Medicine expertise, SG provided the health economic expertise, AW provided
the statistical expertise, HH provided patient reported outcomes expertise, HH and ZA
provided overall methodological expertise and CO’N developed and wrote the qualitative
aspects of the protocol. All authors have read and approved the final manuscript for
publication.
Funding: This trial is supported by a Research for Patient and Public Benefit (RfPPB) Grant
by Health and Care Research Wales. Project reference: 1193
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Disclaimer: The funding sources have no role in the design of this trial. The views
expressed are those of the author(s) and not necessarily those of the NHS, Health and Care
Research Wales, the NIHR or the Department of Health.
Competing interests: None declared
Ethics approval: Wales Research Ethics Committee 6 (16/WA/0290)
Provenance and peer review: Not commissioned; externally peer reviewed
Data sharing statement: All trial investigators will maintain full autonomy and involvement
in the design, conduct and reporting of the trial, with all having full access to the data
REFERENCES
1) Battle CE, James K, Hutchings H, et al. Risk factors for the development of complications
in blunt chest wall trauma: a retrospective study. Injury 2013;44:1171-6.
2) Brasel KJ, Guse CE, Layde P, et al. Rib fractures: Relationship with pneumonia and
mortality. Crit Care Med 2006;34:1642-6.
3) Bergeron E, Lavoie A, Clas D, et al. Elderly trauma patients with rib fractures are at
greater risk of death and pneumonia. J Trauma 2003;54:478-85.
4) Unsworth A, Curtis K, Asha SE. Treatment for blunt chest trauma and their impact on
patient outcomes and health service delivery. Resuscitation and Emergency Medicine
2015;23:17.
5) Battle CE, Hutchings H, Evans PA. Risk factors that predict mortality in patients with blunt
chest wall trauma: A systematic review and meta-analysis. Injury 2012;43:8-17.
6) Battle CE, Hutchings H, Lovett S, et al. Predicting outcomes after blunt chest wall trauma:
development and external validation of a new prognostic model. Crit Care 2014;18:R98.
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7) Battle CE, Hutchings H, Evans PA. Expert opinion of the risk factors for morbidity and
mortality in blunt chest wall trauma: Results of a national postal questionnaire survey in the
United Kingdom. Injury 2013;44:56-9.
8) Ahmad MA, Sante ED, Giannoudis PV. Assessment of severity of chest trauma: is there
an ideal scoring system? Injury 2010;41:981–3.
9) Blecher GE, Mitra B, Cameron PA, et al. Failed emergency department disposition to the
ward of patients with thoracic injury. Injury 2008;39:586–91.
10) Moons KGM, Altman DG, Vergouwe Y, et al. Prognosis and prognostic research:
application and impact of prognostic models in clinical practice. BMJ 2009, 338:1487–90.
11) Moons KGM, Royston P, Vergouwe Y, et al. Research methods and reporting. Prognosis
and prognostic research: what, why and how? BMJ 2009, 338:1317–20.
12) Brown CA, Lilford RJ. The stepped wedge trial design: a systematic review. BMC
Medical Research Methodology 2006;6:54.
13) 9) Medical Research Council. Developing and evaluating complex interventions: new
guidance. Available at: www.mrc.ac.uk/complexinterventionsguidance.
14) Lancaster GA, Dodd SR, Williamson PR. Design and analysis of pilot studies:
recommendations for good practice. J Eval Clin Pract 2004;10:307-12.
15) Ware JE, Kosinski M, Keller SD. A 12-Item Short-Form Health Survey: Construction of
scales and preliminary tests of reliability and validity. Med Care 1996;34:220–33.
16) Harris PA, Taylor R, Thielke R, et al. Research electronic data capture (REDCap) – A
metadata-driven methodology and workflow process for providing translational research
informatics support. J Biomed Inform 2009;42:377-81.
17) Charlesworth G, Burnell K, Hoe J et al. Acceptance checklist for clinical effectiveness
pilot trials: a systematic approach. BMC Medical Research Methodology 2013;13:78
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18) QSR International: NVIVO. http://www.qsrinternational.com/what-is-nvivo
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180x120mm (300 x 300 DPI)
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SPIRIT 2013 Checklist: Recommended items to address in a clinical trial protocol and related documents*
Section/item Item No
Description Addressed on page number
Administrative information
Title 1 Descriptive title identifying the study design, population, interventions, and, if applicable, trial acronym _______1______
Trial registration 2a Trial identifier and registry name. If not yet registered, name of intended registry _______2_____
2b All items from the World Health Organization Trial Registration Data Set _____________
Protocol version 3 Date and version identifier _______3______
Funding 4 Sources and types of financial, material, and other support _______14_____
Roles and
responsibilities
5a Names, affiliations, and roles of protocol contributors _______14_____
5b Name and contact information for the trial sponsor ______13______
5c Role of study sponsor and funders, if any, in study design; collection, management, analysis, and
interpretation of data; writing of the report; and the decision to submit the report for publication, including
whether they will have ultimate authority over any of these activities
________13_____
5d Composition, roles, and responsibilities of the coordinating centre, steering committee, endpoint
adjudication committee, data management team, and other individuals or groups overseeing the trial, if
applicable (see Item 21a for data monitoring committee)
______12, 13___
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Introduction
Background and
rationale
6a Description of research question and justification for undertaking the trial, including summary of relevant
studies (published and unpublished) examining benefits and harms for each intervention
____3_________
6b Explanation for choice of comparators _____3________
Objectives 7 Specific objectives or hypotheses ______4_______
Trial design 8 Description of trial design including type of trial (eg, parallel group, crossover, factorial, single group),
allocation ratio, and framework (eg, superiority, equivalence, noninferiority, exploratory)
_____4-6_____
Methods: Participants, interventions, and outcomes
Study setting 9 Description of study settings (eg, community clinic, academic hospital) and list of countries where data will
be collected. Reference to where list of study sites can be obtained
____6_________
Eligibility criteria 10 Inclusion and exclusion criteria for participants. If applicable, eligibility criteria for study centres and
individuals who will perform the interventions (eg, surgeons, psychotherapists)
______7_______
Interventions 11a Interventions for each group with sufficient detail to allow replication, including how and when they will be
administered
_____7________
11b Criteria for discontinuing or modifying allocated interventions for a given trial participant (eg, drug dose
change in response to harms, participant request, or improving/worsening disease)
______7_______
11c Strategies to improve adherence to intervention protocols, and any procedures for monitoring adherence
(eg, drug tablet return, laboratory tests)
_______7______
11d Relevant concomitant care and interventions that are permitted or prohibited during the trial ________7_____
Outcomes 12 Primary, secondary, and other outcomes, including the specific measurement variable (eg, systolic blood
pressure), analysis metric (eg, change from baseline, final value, time to event), method of aggregation (eg,
median, proportion), and time point for each outcome. Explanation of the clinical relevance of chosen
efficacy and harm outcomes is strongly recommended
_______8,9____
Participant timeline 13 Time schedule of enrolment, interventions (including any run-ins and washouts), assessments, and visits for
participants. A schematic diagram is highly recommended (see Figure)
______7_______
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Sample size 14 Estimated number of participants needed to achieve study objectives and how it was determined, including
clinical and statistical assumptions supporting any sample size calculations
______6_______
Recruitment 15 Strategies for achieving adequate participant enrolment to reach target sample size _______8______
Methods: Assignment of interventions (for controlled trials)
Allocation:
Sequence
generation
16a Method of generating the allocation sequence (eg, computer-generated random numbers), and list of any
factors for stratification. To reduce predictability of a random sequence, details of any planned restriction
(eg, blocking) should be provided in a separate document that is unavailable to those who enrol participants
or assign interventions
_____________
Allocation
concealment
mechanism
16b Mechanism of implementing the allocation sequence (eg, central telephone; sequentially numbered,
opaque, sealed envelopes), describing any steps to conceal the sequence until interventions are assigned
_____________
Implementation 16c Who will generate the allocation sequence, who will enrol participants, and who will assign participants to
interventions
_____________
Blinding (masking) 17a Who will be blinded after assignment to interventions (eg, trial participants, care providers, outcome
assessors, data analysts), and how
_____________
17b If blinded, circumstances under which unblinding is permissible, and procedure for revealing a participant’s
allocated intervention during the trial
_____________
Methods: Data collection, management, and analysis
Data collection
methods
18a Plans for assessment and collection of outcome, baseline, and other trial data, including any related
processes to promote data quality (eg, duplicate measurements, training of assessors) and a description of
study instruments (eg, questionnaires, laboratory tests) along with their reliability and validity, if known.
Reference to where data collection forms can be found, if not in the protocol
______9_______
18b Plans to promote participant retention and complete follow-up, including list of any outcome data to be
collected for participants who discontinue or deviate from intervention protocols
_______9,10___
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Data management 19 Plans for data entry, coding, security, and storage, including any related processes to promote data quality
(eg, double data entry; range checks for data values). Reference to where details of data management
procedures can be found, if not in the protocol
_____10________
Statistical methods 20a Statistical methods for analysing primary and secondary outcomes. Reference to where other details of the
statistical analysis plan can be found, if not in the protocol
_______10______
20b Methods for any additional analyses (eg, subgroup and adjusted analyses) _______10-12___
20c Definition of analysis population relating to protocol non-adherence (eg, as randomised analysis), and any
statistical methods to handle missing data (eg, multiple imputation)
____11_________
Methods: Monitoring
Data monitoring 21a Composition of data monitoring committee (DMC); summary of its role and reporting structure; statement of
whether it is independent from the sponsor and competing interests; and reference to where further details
about its charter can be found, if not in the protocol. Alternatively, an explanation of why a DMC is not
needed
______12_______
21b Description of any interim analyses and stopping guidelines, including who will have access to these interim
results and make the final decision to terminate the trial
________12,13__
Harms 22 Plans for collecting, assessing, reporting, and managing solicited and spontaneously reported adverse
events and other unintended effects of trial interventions or trial conduct
______13_______
Auditing 23 Frequency and procedures for auditing trial conduct, if any, and whether the process will be independent
from investigators and the sponsor
________13_____
Ethics and dissemination
Research ethics
approval
24 Plans for seeking research ethics committee/institutional review board (REC/IRB) approval _________13____
Protocol
amendments
25 Plans for communicating important protocol modifications (eg, changes to eligibility criteria, outcomes,
analyses) to relevant parties (eg, investigators, REC/IRBs, trial participants, trial registries, journals,
regulators)
_________13____
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Consent or assent 26a Who will obtain informed consent or assent from potential trial participants or authorised surrogates, and
how (see Item 32)
_______13______
26b Additional consent provisions for collection and use of participant data and biological specimens in ancillary
studies, if applicable
_____________
Confidentiality 27 How personal information about potential and enrolled participants will be collected, shared, and maintained
in order to protect confidentiality before, during, and after the trial
______13_______
Declaration of
interests
28 Financial and other competing interests for principal investigators for the overall trial and each study site ________15_____
Access to data 29 Statement of who will have access to the final trial dataset, and disclosure of contractual agreements that
limit such access for investigators
________15_____
Ancillary and post-
trial care
30 Provisions, if any, for ancillary and post-trial care, and for compensation to those who suffer harm from trial
participation
_____________
Dissemination policy 31a Plans for investigators and sponsor to communicate trial results to participants, healthcare professionals,
the public, and other relevant groups (eg, via publication, reporting in results databases, or other data
sharing arrangements), including any publication restrictions
_______14______
31b Authorship eligibility guidelines and any intended use of professional writers _____________
31c Plans, if any, for granting public access to the full protocol, participant-level dataset, and statistical code _____________
Appendices
Informed consent
materials
32 Model consent form and other related documentation given to participants and authorised surrogates _____________
Biological
specimens
33 Plans for collection, laboratory evaluation, and storage of biological specimens for genetic or molecular
analysis in the current trial and for future use in ancillary studies, if applicable
_____________
*It is strongly recommended that this checklist be read in conjunction with the SPIRIT 2013 Explanation & Elaboration for important clarification on the items.
Amendments to the protocol should be tracked and dated. The SPIRIT checklist is copyrighted by the SPIRIT Group under the Creative Commons
“Attribution-NonCommercial-NoDerivs 3.0 Unported” license.
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Protocol for a multi-centre randomised feasibility STUdy evaluating the impact of a prognostic model for
management of BLunt chest wall trauma patients: STUMBL Trial
Journal: BMJ Open
Manuscript ID bmjopen-2017-015972.R1
Article Type: Protocol
Date Submitted by the Author: 12-May-2017
Complete List of Authors: Battle, Ceri; Academic Emergency Medicine Research Unit, Emergency Dept, Morriston Hospital Abbott, Zoe; Swansea University, Swansea University Medical School Hutchings, Hayley; Swansea University, Swansea University Medical School O'Neill, Claire; Swansea University, Swansea University Medical School Groves, Sam; Swansea University, College of Human and Health Sciences Watkins, Alan; Swansea University, Swansea University Medical School Lecky, Fiona; University of Sheffield/ Salford Royal Hospitals NHS Trust, Emergency Medicine; Trauma Audit and Research Network, Institute of Population Health
Jones, Sally; Royal Gwent Hospital, Emergency Department Gagg, James; Taunton & Somerset NHS Foundation Trust, Emergency Department Body, Richard; Central Manchester University Hospitals NHS Foundation Trust, Emergency Dept Evans, Phillip; Academic Emergency Medicine Research Unit, Emergency Department, Morriston Hospital
<b>Primary Subject Heading</b>:
Emergency medicine
Secondary Subject Heading: Research methods
Keywords: Blunt chest wall trauma, Prognostic model, Feasibility trial, Stepped-wedge randomised trial
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Protocol for a multi-centre randomised feasibility STUdy evaluating the impact of a
prognostic model for management of BLunt chest wall trauma patients: STUMBL Trial
Corresponding author: Dr Ceri Battle: Welsh Institute of Biomedical and Emergency
Medicine Research, Emergency Dept, Morriston Hospital, Swansea, UK., SA6 6NL.
[email protected] Tel: 00 44 1792 703124
Ms Zoe Abbott: Swansea University Medical School, Swansea University, Swansea, UK.
Professor HA Hutchings: Swansea University Medical School, Swansea University,
Swansea, UK.
Dr CBC O’Neill: Swansea University Medical School, Swansea University, Swansea, UK.
Dr S Groves: College of Human and Health Sciences, Swansea University, Swansea, UK.
Associate Professor A Watkins: Swansea University Medical School, Swansea University,
Swansea, UK.
Professor F Lecky: School of Health and Related Research, Sheffield University. Salford
Royal NHS Foundation Trust, Salford, UK
Dr Sally Jones. Emergency Department, Royal Gwent Hospital, Newport, UK
Dr James Gagg. Emergency Department, Musgrove Park Hospital, Taunton, UK
Dr Richard Body. Emergency Department, Manchester Royal Infirmary, Manchester, UK.
Professor PA Evans: Welsh Institute of Biomedical and Emergency Medicine Research,
Emergency Dept, Morriston Hospital, Swansea, UK.
Word count: 3728
Key words: Blunt chest wall trauma; prognostic model; feasibility trial; stepped-wedge
randomised trial.
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ABSTRACT
Introduction: A new prognostic model has been developed and externally validated, the aim
of which is to assist in the management of the blunt chest wall trauma patient in the
Emergency Department (ED). A definitive randomised controlled trial (impact trial), is
required to assess the clinical and cost effectiveness of the new model, before it can be
accepted in clinical practice. The purpose of this trial is to assess the feasibility and
acceptability of such a definitive trial and inform its design.
Methods / analysis: This feasibility trial is designed to test the methods of a multi-centre,
cluster-randomised (stepped wedge) trial, with a substantial qualitative component. Four
EDs in England and Wales will collect data for all blunt chest wall trauma patients over a five
month period; in the initial period acting as the controls (normal care) and the second period,
acting as the interventions (in which the new model will be used). Baseline measurements
including completion of the SF-12v2 will be obtained on initial assessment in the ED. Patient
outcome data will then be collected for any subsequent hospitalisations. Data collection will
conclude with a six week follow-up completion of two surveys (SF-12v2 and Client Services
Receipt Inventory). Analysis of outcomes will focus on feasibility, acceptability and trial
processes and will include recruitment and retention rates, attendance at clinician training
rates and use of model in the ED. Qualitative feedback will be obtained through clinician
interviews and a research nurse focus group. An evaluation of the feasibility of health
economics outcomes data will be completed.
Ethics / dissemination: Wales Research Ethics Committee 6 granted approval for the trial
in September 2016. Patient recruitment will commence in February 2017. Planned
dissemination is through publication in a peer-reviewed Emergency Medicine Journal,
presentation at appropriate conferences and to stakeholders at Professional Meetings.
ISRCTN Trial registration number: ISRCTN95571506
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Strengths and limitations of trial:
1) The main strength of the trial design is that it will test all of the methodological
components of the future definitive trial; including the trial infrastructure, randomisation
process, data management system, both qualitative and quantitative analysis, follow-up
procedures and a health economic analysis.
2) The health economic analysis will ensure accurate future funding applications for the full
definitive trial.
3) The qualitative analysis will inform the researchers’ understanding of the use of the risk
score by clinicians in daily clinical practice.
4) The cluster randomised trial design that needed to be tested in this feasibility trial is
limited by the small number of clusters (EDs participating). In the future definitive trial, more
clusters will be possible, due to the greater number of participating sites.
INTRODUCTION
Blunt chest wall trauma accounts for over 15% of all trauma admissions to Emergency
Departments (ED) worldwide, with reported mortality ranging between 4 and 60%.[1-3] The
difficulties in the management of the blunt chest wall trauma patient in the ED, are becoming
increasingly well recognised in the literature.[4,5] The blunt chest wall trauma patient
commonly presents to the ED with no respiratory difficulties, but can develop complications
up to approximately 72 hours after initial presentation.[1-4] Clinical symptoms are not
considered by most clinicians to be an accurate predictor of outcome following non-life-
threatening blunt chest wall trauma.[1-7] Decisions regarding the appropriate level of care
required by the patient following discharge from the ED are therefore difficult, which is further
compounded by the lack of current national guidelines. An improvement in the ability to
identify the high risk blunt chest wall trauma patient on initial assessment in the ED would
potentially lead to a reduction in these poor outcomes.[8,9]
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A new prognostic model to assist in the management of blunt chest wall trauma patients in
the ED, has been developed and externally validated in a large multi-centre study.[1,5-7]
The model comprises five risk factors; age, number of rib fractures, pre-existing chronic lung
disease, use of pre-injury anti-coagulants and oxygen saturation on initial assessment in the
ED. The patient is scored on each risk factor and the total score is used to guide the clinician
in the ED as to whether the patient should be admitted to the ward, critical care unit or can
be safely discharged home. (See supplementary file) Guidelines recommend however that
prognostic models should not be used in clinical practice until an impact study has been
completed, in which the clinical application of the model has been tested.[10-11]. Prior to
undertaking a large definitive randomised controlled trial of the clinical and cost effectiveness
of the prognostic model, a smaller scale trial is required to address the issues of feasibility
and acceptability.
Trial aims
The aim of this trial (protocol version 5, 6th January 2017) is to establish the feasibility and
acceptability of the final definitive impact trial, which will ultimately determine whether the
prognostic model can be used safely and effectively in clinical practice in the UK. The trial
objectives are to: (1) Evaluate the infrastructure necessary to perform a future definitive trial,
including the Trial Management Group, Trial Steering/Data Management Committee; (2) test
the feasibility of the proposed stepped-wedge, cluster-randomised design; (3) evaluate and
qualitatively explore the compliance of the clinicians in using the prognostic model (and
reasons for non-compliance); (4) assess the appropriateness of the training manual and
consistency of training provided by each principal investigator (PI); (5) quantify the number
of patients required for a full definitive trial through the estimation of the magnitude of effect
and necessary parameters, including the margin of error acceptable to achieve the proposed
outcomes; (6) assess the processes of patient recruitment, consent and reasons for non-
participation; (7) assess the quantity and potential patterns of missing data; (8) test the
feasibility of collecting the proposed outcome measures for a full trial, including optimal time
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points, using the electronic case report form on the REDCap data collection system; (9)
decide whether a fully powered, multi-centre randomised trial is indicated by formal
assessment of feasibility trial findings against pre-set progression criteria.
METHODS AND ANALYSIS
Trial design and randomisation
This feasibility trial is designed to test the methods of a multi-centre, prospective, cluster
randomised (stepped wedge) trial,[12] with a substantial qualitative component. Figure 1
outlines the trial procedure. There will be four hospitals participating in the trial, which will be
run using a stepped wedge design. In accordance with Medical Research Council (MRC)
guidance [13], the unit randomisation will be the EDs, rather than patients, since the
intervention will be used by ED clinicians, with the aim of studying effects on patient
outcomes. All participating EDs will begin as control sites, at the same time, testing
conventional management without the model, for a period of one month (control arm). Every
month, following the initial month's data collection period as controls, one hospital will be
randomly assigned to become an intervention arm (in which all clinicians in the ED will be
using the risk model) sequentially, until all hospitals are acting as interventions.
The randomisation process applies to the hospitals (known as clusters) participating in the
trial, rather than at a patient level. The order in which hospitals EDs convert to intervention
status is based on a purely random process (involving only computer-generated random
numbers, but no information on the individual hospitals or EDs), and can be regarded as
equivalent to the drawing of names at random. As there are four hospitals participating in the
trial, all patient recruitment will be completed over a five month period. This trial design will
test the feasibility of the classic stepped wedge design, to be used in the future definitive
trial.
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During the control period, the doctors in each ED will receive training on the model from the
principal investigator (PI) in each ED. Each PI will be instructed at the start of the trial, on
how to train the clinicians and a training manual will be designed and provided.
Figure 1: Schematic representation of the trial’s timelines
Population
Patients will be included in the trial if they present to the ED with isolated blunt chest wall
trauma, are aged 18 and over and are capable of giving consent to participation. Potential
patients will be excluded if they are under the age of 18, lack capacity to give informed
consent, present with any immediately life-threatening injuries or any concurrent injury that
will determine the patient’s management (rather than the chest trauma). Patients will be
withdrawn from the trial if they lose capacity (including death) to complete the surveys and if
they request to be withdrawn. This data will be recorded as part of the assessment of the
trial’s success criteria, in order to inform the design of the future definitive trial. A list of all
patients who decline to participate will also be completed in order that the trial team can
assess the recruitment rates at the end of the study.
Setting and recruitment
This multi-centre feasibility trial will be run in the EDs of the Royal Gwent Hospital in
Newport, Musgrove Park Hospital in Taunton, Salford Royal Hospital and Manchester Royal
Infirmary (all large teaching hospitals located in the UK). The clinicians or research nurses in
the ED will screen, recruit and consent eligible patients to the trial.
Sample size
A five month recruitment period has been proposed. In 2015, over 1200 blunt chest wall
trauma patients presented to the ED of the hospital of the trial research team, with over 100
of these admitted. If the four participating hospitals recruit for five months each, between 30-
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80 patients per site should be recruited, allowing for loss to follow up, low response rates
with follow-up surveys and difficulties with recruiting at weekends if research nurses only
work Monday to Friday. This sample size is the minimum number of participants considered
necessary to test the processes of data collection, based on existing recommendations with
respect to the number of patients required to yield meaningful estimates of parameters of
interest.[14]
The analysis will lead to an estimation of the sample size for the definitive trial needed to
yield 80% power when using a significance level of 5%, by establishing non-inferiority
between use of the prognostic tool and standard care, as revealed by the feasibility study.
The analysis will include descriptive data (means and standard deviations) on all outcomes
collected, including levels of missing data, leading to the calculation of clinically important
differences. The conventional sample size calculations for the future definitive trial will be
developed using this analysis and the consensus among the Trial Management Group and
Trial Steering Committee of the minimal clinically important difference in these measures. If
the recruitment and retention plan is shown to be optimistic in this feasibility trial, then this is
an important finding which will inform the sample size calculation for the future main
definitive trial.
Interventions
The intervention being investigated in this study is the use of the prognostic model to guide
the clinicians' clinical decision making. The model will be used by the clinician during the
initial patient assessment and will provide a suggestion of the appropriate management in
terms of whether the patient can be safely discharged home, or whether they need
admission to either a ward or critical care. There will be no other differences in patient care.
All patients will be required to complete one survey (SF-12v2),[15] on initial presentation to
the ED and two more surveys at six weeks post-injury (SF-12v2 and a Client Services
Receipt Inventory). A sample of the clinicians using the model will be asked to attend a short
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interview in which they will be asked to discuss the model in relation to clinical practice. The
research nurses will be required to attend a focus group in which there will be a discussion
about the trial’s methodology including specifically issues around data collection.
Figure 2: Summary of the patients’ journey through trial:
Strategies to improve adherence to interventions
Full training (including a training manual) on the use of the model and the trial design will be
provided for each hospital’s principal investigator, who will then be responsible for training
the doctors working in their ED. Feedback from a sample of the clinicians regarding the
model will be provided through a short interview, at a convenient time and location. All
documentation will be available in the Welsh language where applicable, working in
conjunction with the Language Awareness Infrastructure Support Service. Patients will be
offered the chance to be entered into a prize draw if they return their surveys at six weeks
post-injury.
Outcome measures
Primary outcome measure:
Patient recruitment rate will be recorded as the number of eligible patients who consent to
trial participation at the end of the five month data collection period, at each site.
Secondary outcome measures:
1) 'Clinician recruitment rate' will be recorded as the number of eligible clinicians working
within the participating ED who agree to take part in the study by the end of the five month
data collection period, at each site.
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2) 'Response rate of follow up data' (quality of life surveys) will be recorded as the number of
patients returning postal surveys at the end of the five month data collection period, at each
site.
3) 'Clinicians Training Attendance rate' will be recorded as the number of clinicians who
receive formal training in the use of the model, prior to the second data collection period
(intervention arm), at each site
4) 'Compliance with use of model rate' will be recorded as the number of times the clinician
used the risk model for an eligible patient, at the end of the second data collection period
(intervention arm)
5) 'Overall mean quality of life' as reported using the SF-12v2 survey for patients, at the end
of the control and intervention data collection periods (compared to baseline taken on initial
assessment in the ED), at each participating site.
6) ‘Resource usage by patients as a result of the intervention’ as reported on the Client
Services Receipt Inventory at six week follow-up.
Data collection
Data collection to be completed by the on-site research nurse and will include: (1) SF-12v2
survey and prognostic model (if used) completed in the ED; (2) mechanism of injury, a
measure of pre-admission frailty, admission status, hospital and ICU length of stay,
occurrence of complications (mortality or pulmonary morbidity) and re-admission to hospital
will be obtained from medical records prospectively, during the patient's hospitalisation; (3)
at six weeks post injury, the second quality of life questionnaire (SF-12) and Client Service
Receipt Inventory will be sent out to the patient for completion.
Data collection to be completed by the qualitative researcher will include: (1) attendance at
the PI-led training sessions at 2 sites in order to assess consistency of training provided
between sites and the appropriateness of the training manual; (2) clinicians will be asked to
complete an online feedback survey after the training session to collect their views about the
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training, for example; travel and time costs incurred, completeness, appropriateness and if
they have any suggestions about possible improvements; (3) a total of 8 doctors (two from
each site) who are using the model will be interviewed at the end of the study period to
understand how the tool was used, ease and time of use, as well as problems with its use. If
it arises, the study team will need to also understand a situation in which the model could
have been used, but was not used, and why that might have occurred. Doctors at
participating sites who have not used the model (if any) will be invited to participate in
interviews to explore their reasons; (4) a focus group will be facilitated by the qualitative
researcher in which the research nurses responsible for data collection will discuss the trial
process in depth.
An evaluation of the feasibility of health economics outcomes data will be completed as part
of the trial. As this is a feasibility trial, the focus will be on establishing the most appropriate
framework for a future health economic analysis in the full definitive trial. The feasibility of
collecting data on outcome and resource use will be assessed. A provisional assessment of
the cost categories associated with the intervention (for example staff time associated with
training and use of the model) will be completed, through discussion with the qualitative
researcher completing the telephone interviews. To capture resource usage by patients as a
result of the intervention, from an NHS/PSS (Personal Social Service) perspective, an
adapted resource usage questionnaire will be used. The use of the SF-12v2 will be
considered as a measure to derive utilities using the SF-6D. Data will be assessed to
examine the completeness of data captured, such as response rate and potential missing
items.
Data management
REDCap (Research Electronic Data Capture) will be used for data capture and for
completion of the electronic case report forms, hosted at Swansea University.[16] REDCap
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is a secure, web-based application designed to support data capture for research studies,
providing 1) an intuitive interface for validated data entry; 2) audit trails for tracking data
manipulation and export procedures; 3) automated export procedures for seamless data
downloads to common statistical packages; and 4) procedures for importing data from
external sources. The use of the REDCap system will be discussed in the focus group with
the research nurses who will be completing the electronic case report forms. Feedback will
be used to adapt the system to improve the setup, prior to the commencement of the full
definitive trial.
Statistical methods
Quantitative data analysis: Criteria of study success: In order to evaluate the success of the
feasibility trial, with the view to continue to a full definitive impact trial, the Data Monitoring
Committee will assess the final results using the ACCEPT model, developed by
Charlesworth et al, 2013)[17]. The predetermined success criteria are highlighted in Table 1.
Table 1: Trial feasibility criteria
Sample size and participants:
1) 95% or more of clinicians working within the participating ED agree to take part in the study
2) 80% or more of eligible patients consent to data collection and follow up.
3) Follow up data for primary outcomes can be collected for 80% or more of patients
Interventions:
1) All clinicians involved in the trial receive formal training in the use of the model
2) 90% compliance with use of the model during intervention period
Outcomes:
1) Mean quality of life reported in intervention arm is not less than 80% of that reported in control arm
2) Outcome measures reported in the intervention period are equal to, or better than, those reported
during the conventional management period
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Qualitative data analysis: Focus groups and interviews will be audio recorded and sent to a
professional transcription service for verbatim transcription. The qualitative researcher will
oversee this process and upon receipt of transcripts will check them for accuracy against the
original recording and undertake anonymisation in accordance with best practice standards.
The cleaned and anonymised transcripts will be uploaded into NVIVO 10 - a qualitative data
analysis program.[18] The qualitative researcher will code the transcripts thematically using
a code book which developed initially from the background literature and feedback on the
training as well as issues which will emerge through the process of constant comparison
which underpins qualitative data analysis. A sub sample of coded transcripts will be checked
by a second qualitative researcher (by reciprocal arrangement within the wider team at the
trials unit), using the coder comparison query tool.
Trial monitoring and management
An independent, joint trial steering / data monitoring committee will be formed that has no
link to the sponsor and has no competing interests. The role of the committee will be to
monitor adverse and serious adverse events, stopping criteria and trial endpoint success
criteria analysis. Stopping criteria will include; 1) a 5% increase in each of the hospitals, in
the number of patients with an unplanned representation to the ED due to development of
complications, leading to ITU admission and unexpected death (following direct discharge
from the ED on initial presentation), in the intervention period compared to the control period;
2) a 5% increase in each of the hospitals, in the number of patients identified as having a
delayed admission to ITU leading to unexpected death, in the intervention period compared
to the control period. The committee will also be responsible for the overall supervision of the
trial to ensure the trial is completed according to rigorous standards.
There will be no direct change to patient care, however once the model has been introduced
to each ED, the clinicians will be required to use the prognostic model to guide their
management decisions for the patient. The model will only be used as a guide to
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management however, if the clinician believes the suggestion of the risk score places the
patient at risk, they can over-ride the prognostic model. This would be documented and
reviewed by the trial team. Although there are a number of expected adverse events for
patients who have sustained blunt chest wall trauma, the PI may take appropriate urgent
safety measures in order to protect research participants against any immediate hazard to
their health or safety, without prior authorisation from a regulatory body. Any serious adverse
event and urgent safety measures will be reported to the CI immediately with details of the
measure and a plan for further action. The CI or Sponsor will notify the main REC and Trial
Steering Committee. Serious adverse events will include; 1) death or ICU admission in
patients who have been discharged home as suggested by the risk score and 2) any trial
patient complaint.
ETHICS AND DISSMINATION
Ethical issues
This trial has received ethics approval by the Wales Research Ethics Committee 6 (Ref:
16/WA/0290). Any arising important protocol modifications (such as changes to eligibility
criteria, outcomes, analyses) will be communicated to the relevant parties (investigators,
REC/IRBs, trial participants, trial registries, journals, regulators) in a timely manner.
Compliance with this will be monitored by the trial sponsor (ABMU Health Board R&D
Department). Informed consent will be obtained by the clinicians or research nurses who will
all have received ‘protocol and informed consent specific training’ in alignment with the
principles of GCP and who have signed the trial delegation log. Consent will be sought,
following a full introduction to the study and once the patient has had time to discuss the
Patient Information Sheet with a family member / carer (as appropriate). A study withdrawal
letter will also be attached to the Patient Information Sheet in case the patient wishes to
withdraw consent in the first week following recruitment.
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The Trial’s Chief Investigator (CI) will take responsibility to ensure that patient anonymity is
protected and maintained. Information with regards to study patients will be kept confidential
and managed in accordance with the Data Protection Act, NHS Caldicott Guardian, The
Research Governance Framework for Health and Social Care and Research Ethics
Committee Approval. All patients will be allocated a study number once informed consent is
obtained. Personal data will only be identifiable by this study number during data collection.
All patient identifiable data will be removed and data anonymised once data collection using
the survey is complete. The CI will act as the custodian of the data and the records will be
kept securely for a further 5 years in the Health Board archive facility. The Caldicott
Guidelines will be adhered to throughout the study.
Dissemination policy
Dissemination of the outputs from this trial is proposed through publication in an appropriate
Emergency Medicine journal and by presentation at relevant international conferences. The
aim of this feasibility trial is not to report definitive results regarding clinical and cost
effectiveness however, any important outputs produced in the trial related to the prognostic
model will be published in appropriate Medical Journals, as follow-on articles from our
previous published work in this area. We will disseminate our findings to stakeholders via
professional meetings. The Trauma and Audit Research Network (TARN) newsletter will be
used to disseminate the results to the Trauma leads in each ED participating in TARN in the
UK.
Contributors: All authors of the paper have contributed to the design of the trial. CB wrote
this protocol and all other authors edited and made revisions for intellectual content. PE, HH
FL, JG and SJ have been involved in the background development and validation work
leading up to this trial. For the protocol development; PE, FL, RB, SJ and JG provided the
Emergency Medicine expertise, SG provided the health economic expertise, AW provided
the statistical expertise, HH provided patient reported outcomes expertise, HH and ZA
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provided overall methodological expertise and CO’N developed and wrote the qualitative
aspects of the protocol. All authors have read and approved the final manuscript for
publication.
Funding: This trial is supported by a Research for Patient and Public Benefit (RfPPB) Grant
by Health and Care Research Wales. Project reference: 1193
Disclaimer: The funding sources have no role in the design of this trial. The views
expressed are those of the author(s) and not necessarily those of the NHS, Health and Care
Research Wales, the NIHR or the Department of Health.
Competing interests: None declared
Ethics approval: Wales Research Ethics Committee 6 (16/WA/0290)
Provenance and peer review: Not commissioned; externally peer reviewed
Data sharing statement: All trial investigators will maintain full autonomy and involvement
in the design, conduct and reporting of the trial, with all having full access to the data
REFERENCES
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2) Brasel KJ, Guse CE, Layde P, et al. Rib fractures: Relationship with pneumonia and
mortality. Crit Care Med 2006;34:1642-6.
3) Bergeron E, Lavoie A, Clas D, et al. Elderly trauma patients with rib fractures are at
greater risk of death and pneumonia. J Trauma 2003;54:478-85.
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4) Unsworth A, Curtis K, Asha SE. Treatment for blunt chest trauma and their impact on
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and prognostic research: what, why and how? BMJ 2009, 338:1317–20.
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13) 9) Medical Research Council. Developing and evaluating complex interventions: new
guidance. Available at: www.mrc.ac.uk/complexinterventionsguidance.
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recommendations for good practice. J Eval Clin Pract 2004;10:307-12.
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15) Ware JE, Kosinski M, Keller SD. A 12-Item Short-Form Health Survey: Construction of
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180x120mm (300 x 300 DPI)
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SPIRIT 2013 Checklist: Recommended items to address in a clinical trial protocol and related documents*
Section/item Item No
Description Addressed on page number
Administrative information
Title 1 Descriptive title identifying the study design, population, interventions, and, if applicable, trial acronym _______1______
Trial registration 2a Trial identifier and registry name. If not yet registered, name of intended registry _______2_____
2b All items from the World Health Organization Trial Registration Data Set _____________
Protocol version 3 Date and version identifier _______3______
Funding 4 Sources and types of financial, material, and other support _______14_____
Roles and
responsibilities
5a Names, affiliations, and roles of protocol contributors _______14_____
5b Name and contact information for the trial sponsor ______13______
5c Role of study sponsor and funders, if any, in study design; collection, management, analysis, and
interpretation of data; writing of the report; and the decision to submit the report for publication, including
whether they will have ultimate authority over any of these activities
________13_____
5d Composition, roles, and responsibilities of the coordinating centre, steering committee, endpoint
adjudication committee, data management team, and other individuals or groups overseeing the trial, if
applicable (see Item 21a for data monitoring committee)
______12, 13___
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Introduction
Background and
rationale
6a Description of research question and justification for undertaking the trial, including summary of relevant
studies (published and unpublished) examining benefits and harms for each intervention
____3_________
6b Explanation for choice of comparators _____3________
Objectives 7 Specific objectives or hypotheses ______4_______
Trial design 8 Description of trial design including type of trial (eg, parallel group, crossover, factorial, single group),
allocation ratio, and framework (eg, superiority, equivalence, noninferiority, exploratory)
_____4-6_____
Methods: Participants, interventions, and outcomes
Study setting 9 Description of study settings (eg, community clinic, academic hospital) and list of countries where data will
be collected. Reference to where list of study sites can be obtained
____6_________
Eligibility criteria 10 Inclusion and exclusion criteria for participants. If applicable, eligibility criteria for study centres and
individuals who will perform the interventions (eg, surgeons, psychotherapists)
______7_______
Interventions 11a Interventions for each group with sufficient detail to allow replication, including how and when they will be
administered
_____7________
11b Criteria for discontinuing or modifying allocated interventions for a given trial participant (eg, drug dose
change in response to harms, participant request, or improving/worsening disease)
______7_______
11c Strategies to improve adherence to intervention protocols, and any procedures for monitoring adherence
(eg, drug tablet return, laboratory tests)
_______7______
11d Relevant concomitant care and interventions that are permitted or prohibited during the trial ________7_____
Outcomes 12 Primary, secondary, and other outcomes, including the specific measurement variable (eg, systolic blood
pressure), analysis metric (eg, change from baseline, final value, time to event), method of aggregation (eg,
median, proportion), and time point for each outcome. Explanation of the clinical relevance of chosen
efficacy and harm outcomes is strongly recommended
_______8,9____
Participant timeline 13 Time schedule of enrolment, interventions (including any run-ins and washouts), assessments, and visits for
participants. A schematic diagram is highly recommended (see Figure)
______7_______
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Sample size 14 Estimated number of participants needed to achieve study objectives and how it was determined, including
clinical and statistical assumptions supporting any sample size calculations
______6_______
Recruitment 15 Strategies for achieving adequate participant enrolment to reach target sample size _______8______
Methods: Assignment of interventions (for controlled trials)
Allocation:
Sequence
generation
16a Method of generating the allocation sequence (eg, computer-generated random numbers), and list of any
factors for stratification. To reduce predictability of a random sequence, details of any planned restriction
(eg, blocking) should be provided in a separate document that is unavailable to those who enrol participants
or assign interventions
_____________
Allocation
concealment
mechanism
16b Mechanism of implementing the allocation sequence (eg, central telephone; sequentially numbered,
opaque, sealed envelopes), describing any steps to conceal the sequence until interventions are assigned
_____________
Implementation 16c Who will generate the allocation sequence, who will enrol participants, and who will assign participants to
interventions
_____________
Blinding (masking) 17a Who will be blinded after assignment to interventions (eg, trial participants, care providers, outcome
assessors, data analysts), and how
_____________
17b If blinded, circumstances under which unblinding is permissible, and procedure for revealing a participant’s
allocated intervention during the trial
_____________
Methods: Data collection, management, and analysis
Data collection
methods
18a Plans for assessment and collection of outcome, baseline, and other trial data, including any related
processes to promote data quality (eg, duplicate measurements, training of assessors) and a description of
study instruments (eg, questionnaires, laboratory tests) along with their reliability and validity, if known.
Reference to where data collection forms can be found, if not in the protocol
______9_______
18b Plans to promote participant retention and complete follow-up, including list of any outcome data to be
collected for participants who discontinue or deviate from intervention protocols
_______9,10___
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Data management 19 Plans for data entry, coding, security, and storage, including any related processes to promote data quality
(eg, double data entry; range checks for data values). Reference to where details of data management
procedures can be found, if not in the protocol
_____10________
Statistical methods 20a Statistical methods for analysing primary and secondary outcomes. Reference to where other details of the
statistical analysis plan can be found, if not in the protocol
_______10______
20b Methods for any additional analyses (eg, subgroup and adjusted analyses) _______10-12___
20c Definition of analysis population relating to protocol non-adherence (eg, as randomised analysis), and any
statistical methods to handle missing data (eg, multiple imputation)
____11_________
Methods: Monitoring
Data monitoring 21a Composition of data monitoring committee (DMC); summary of its role and reporting structure; statement of
whether it is independent from the sponsor and competing interests; and reference to where further details
about its charter can be found, if not in the protocol. Alternatively, an explanation of why a DMC is not
needed
______12_______
21b Description of any interim analyses and stopping guidelines, including who will have access to these interim
results and make the final decision to terminate the trial
________12,13__
Harms 22 Plans for collecting, assessing, reporting, and managing solicited and spontaneously reported adverse
events and other unintended effects of trial interventions or trial conduct
______13_______
Auditing 23 Frequency and procedures for auditing trial conduct, if any, and whether the process will be independent
from investigators and the sponsor
________13_____
Ethics and dissemination
Research ethics
approval
24 Plans for seeking research ethics committee/institutional review board (REC/IRB) approval _________13____
Protocol
amendments
25 Plans for communicating important protocol modifications (eg, changes to eligibility criteria, outcomes,
analyses) to relevant parties (eg, investigators, REC/IRBs, trial participants, trial registries, journals,
regulators)
_________13____
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Consent or assent 26a Who will obtain informed consent or assent from potential trial participants or authorised surrogates, and
how (see Item 32)
_______13______
26b Additional consent provisions for collection and use of participant data and biological specimens in ancillary
studies, if applicable
_____________
Confidentiality 27 How personal information about potential and enrolled participants will be collected, shared, and maintained
in order to protect confidentiality before, during, and after the trial
______13_______
Declaration of
interests
28 Financial and other competing interests for principal investigators for the overall trial and each study site ________15_____
Access to data 29 Statement of who will have access to the final trial dataset, and disclosure of contractual agreements that
limit such access for investigators
________15_____
Ancillary and post-
trial care
30 Provisions, if any, for ancillary and post-trial care, and for compensation to those who suffer harm from trial
participation
_____________
Dissemination policy 31a Plans for investigators and sponsor to communicate trial results to participants, healthcare professionals,
the public, and other relevant groups (eg, via publication, reporting in results databases, or other data
sharing arrangements), including any publication restrictions
_______14______
31b Authorship eligibility guidelines and any intended use of professional writers _____________
31c Plans, if any, for granting public access to the full protocol, participant-level dataset, and statistical code _____________
Appendices
Informed consent
materials
32 Model consent form and other related documentation given to participants and authorised surrogates _____________
Biological
specimens
33 Plans for collection, laboratory evaluation, and storage of biological specimens for genetic or molecular
analysis in the current trial and for future use in ancillary studies, if applicable
_____________
*It is strongly recommended that this checklist be read in conjunction with the SPIRIT 2013 Explanation & Elaboration for important clarification on the items.
Amendments to the protocol should be tracked and dated. The SPIRIT checklist is copyrighted by the SPIRIT Group under the Creative Commons
“Attribution-NonCommercial-NoDerivs 3.0 Unported” license.
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210x297mm (300 x 300 DPI)
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jopen.bmj.com
/B
MJ O
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