BMJ Open · Professor F Lecky: School of Health and Related Research, Sheffield University. Salford Royal NHS Foundation Trust, Salford, UK Dr Sally Jones. Emergency Department, Royal

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

For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml

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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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188x195mm (72 x 72 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


BMJ Open on O

ctober 2, 2020 by guest. Protected by copyright.

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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

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.

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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.

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.

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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

18) QSR International: NVIVO. http://www.qsrinternational.com/what-is-nvivo

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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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BMJ Open · Professor F Lecky: School of Health and Related Research, Sheffield University. Salford Royal NHS Foundation Trust, Salford, UK Dr Sally Jones. Emergency Department, Royal