The Incidence of Hospital Acquired Pneumonia in Patients Who Undergo Temporary Tracheostomy With Oromaxillofacial Resection and Reconstruction for Head and Neck Cancer.
Conditions: Head and Neck Cancer, Tracheostomy Complication, Hospital-acquired Pneumonia, Surgery
Sponsor: Guy's and St Thomas' NHS Foundation Trust

 
 
 
 
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1. Protocol details 
1.1 PROTOCOL TITLE: 
The incidence of hospital acquired pneumonia in patients who undergo temporary 
tracheostomy with oromaxillofacial resection and free flap reconstruction for head and neck 
cancer. 
1.2 Names (titles), roles and contact details of: 
Sponsor 
Kings College London 
Professor Reza Razavi 
Vice President & Vice Principal (Research) 
King’s College London 
Room 5.31, James Clerk Maxwell Building  
57 Waterloo Road 
London SE1 8WA 
Tel: +44 (0)207 8483224 
Email: reza.razavi@kcl.ac.uk 
 
Chief Investigator/clinical supervisor 
Dr Gareth Jones 
Rehabilitation lead - Physiotherapy 
Guy’s Hospital 
Great Maze Pond 
London 
SE1 9RT 
Gareth.jones@gstt.nhs.uk 
02071885111 
 
Principle Investigator/Student 
Rachel Wijayarathna 
Highly specialist physiotherapist – head & neck oncology 
Guy’s Hospital 
Great Maze Pond 
London 
SE1 9RT 
Rachel.wijayarathna@gstt.nhs.uk 
02071885110 
 
Academic supervisor 
Dr Andrea Xyrichis 
Senior lecturer 
Kings college London, 
57 Waterloo Road,  
London,  
SE1 8WA 
Andreas.xyrichis@kcl.ac.uk 

 
 
 
 
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0207 8483649 
 
Clinical Supervisor 
Mr Ricard Simo FRCS(ORL-HNS) PhD 
Consultant Otorhinolaryngologist Head, Neck and Thyroid Surgeon 
Clinical Lead in Head and Neck Surgery 
Surgical Lead in Thyroid Cancer 
Honorary Senior Lecturer KCL 
Department of Otorhinolaryngology Head and Neck Surgery 
3rd Floor Southwark Wing 
Guy’s and St Thomas’ Hospital NHS Foundation Trust 
St Thomas’ Street 
London SE1 9RT 
Ricard.simo@gstt.nhs.uk 
02071887188 
 
Statistician – reviewed data plan, not affiliated in any other capacity 
Mr Bola Coker 
Senior Data Manager, NIHR GSTT/KCL Biomedical Research Centre 
Visiting Senior Data Manager, School of Population Health & Environmental Sciences, KCL 
Guy's & St Thomas' NHS Foundation Trust 
5th Floor Addison House 
London 
SE1 1UL 
020 7848 8687 
bolaji.coker@kcl.ac.uk 
 
1.3 Protocol details 
Version number 1 
Final 
Date 24.09.2021 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
 
 
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2 Signature Page 
 
The Chief Investigator and the R&D (sponsor office) have discussed this protocol. The investigators 
agree to perform the investigations and to abide by this protocol  
The investigator agrees to conduct the trial in compliance with the approved protocol, EU GCP, the UK 
Data Protection Act (1998), the Trust Information Governance Policy (or other local equivalent), the 
Research Governance Framework (2005’ 2nd Edition; as amended), the Sponsor’s SOPs, and other 
regulatory requirements as amended. 
 
Chief investigator 
Gareth Jones 
 
 
 
 
24/09/21 
 
Signature 
Date 
Sponsor Representative 
R&D to Add  
 
 
GSTFT 
Signature 
Date 
 
 
 
 
This Protocol template is intended for use with UK sites only. 

 
 
 
 
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Contents Page 
1. 
Protocol details ............................................................................................................................... 2 
1.1 
PROTOCOL TITLE: .................................................................................................................... 2 
1.2 
Names (titles), roles and contact details of: ........................................................................... 2 
1.3 
Protocol details ....................................................................................................................... 3 
2 
Signature Page ................................................................................................................................ 4 
Contents Page ......................................................................................................................................... 5 
3 
List of Abbreviations and Definitions .............................................................................................. 7 
4 
Summary/Synopsis .......................................................................................................................... 8 
4. Introduction ...................................................................................................................................... 10 
4.1 Head and neck cancer incidence ................................................................................................. 10 
4.2 Head and Neck cancer treatment ............................................................................................... 10 
4.3 Airway security during surgery ................................................................................................... 11 
4.4 Temporary tracheostomy insertion ............................................................................................ 11 
4.5 Endotracheal and Nasopharyngeal intubation ........................................................................... 11 
4.6 Patient experience ...................................................................................................................... 12 
4.7 Summary and the research problem .......................................................................................... 12 
5 
Trial objectives and purpose ......................................................................................................... 13 
6 
Study design & Flowchart ............................................................................................................. 13 
6.1 
Study Design.......................................................................................................................... 13 
6.2 
Primary outcome tool ........................................................................................................... 14 
7 
Subject selection ........................................................................................................................... 14 
7.1 
Subject inclusion criteria ....................................................................................................... 14 
7.2 
Subject exclusion criteria ...................................................................................................... 14 
8 
Study procedures .......................................................................................................................... 15 
8.1 
Subject recruitment .............................................................................................................. 15 

 
 
 
 
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8.2 
Screening Procedures ........................................................................................................... 15 
8.3 
End of Study Definition ......................................................................................................... 15 
9 
Assessment of Safety .................................................................................................................... 15 
9.1 
Ethics Reporting .................................................................................................................... 15 
10 
Data ........................................................................................................................................... 15 
10.1 
Data to be collected .............................................................................................................. 15 
10.2 
Primary outcome tool ........................................................................................................... 16 
10.3 
Data handling and record keeping ........................................................................................ 16 
11 
Statistical considerations .......................................................................................................... 18 
11.1 
Sample size calculation (some pilot/feasibility studies may not require a formal sample size 
calculation) ........................................................................................................................................ 18 
11.2 
Statistical analysis ................................................................................................................. 18 
12 
Ethical considerations ............................................................................................................... 18 
13 
Financing and Insurance ........................................................................................................... 20 
14 
Reporting and dissemination .................................................................................................... 20 
References……………………………………………………………………………………………………………………………………….22 
 

 
 
 
 
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3 List of Abbreviations and Definitions 
AE 
 
 
Adverse Event  
 
 
AR 
 
 
Adverse Reaction 
ASR 
 
 
Annual Safety Report 
CA 
 
 
Competent Authority 
CI 
 
 
Chief Investigator 
CRF 
 
 
Case Report Form 
CRO 
 
 
Contract Research Organisation 
DMC 
 
 
Data Monitoring Committee 
EC 
 
 
European Commission 
GAfREC Governance Arrangements for NHS Research Ethics Committees 
ICF 
 
 
Informed Consent Form 
MA 
 
 
Marketing Authorisation 
MS 
 
 
Member State 
Main REC 
 
Main Research Ethics Committee 
NHS R&D 
 
National Health Service Research & Development   
PI 
 
 
Principle Investigator 
QA 
 
 
Quality Assurance 
QC 
 
 
Quality Control 
Participant 
 
An individual who takes part in a clinical trial 
REC 
 
 
Research Ethics Committee 
SAE 
 
 
Serious Adverse Event 
SDV 
 
 
Source Document Verification 
SOP 
 
 
Standard Operating Procedure  
SSA 
 
 
Site Specific Assessment 
TMG 
 
 
Trial Management Group 
TSC 
 
 
Trial Steering Committee 
 
 

 
 
 
 
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4 Summary/Synopsis 
 
Title  
 
 
The incidence of hospital acquired pneumonia in patients who undergo 
temporary tracheostomy with oromaxillofacial resection and 
reconstruction for head and neck cancer. 
Version 1 – 24.09.2021 
 
Protocol Short Title/Acronym 
 
HAP in temporary tracheostomy 
Protocol Version number and Date 
 
1 24.09.2021 
Study Phase if not mentioned in title 
 
Observational cohort 
IRAS Number 
 
295395 
REC Reference 
 
 
Sponsor Reference 
 
 
Study Duration 
 
7 months 
Sponsor name 
 
GSTT/KCL 
Chief Investigator 
 
Dr Gareth Jones 
Funder 
 
N/A 
Medical condition or disease under 
investigation 
 
Oromaxillofacial surgery in head and neck cancer  
Purpose of research  
 
Retrospective data analysis identifying hospital acquired pneumonia in 
patients who undergo temporary tracheostomy with oromaxillofacial 
surgery and free flap reconstruction 
Primary objective 
 
Undertake an adequately powered, robustly designed observational 
cohort study that describes the rates of hospital acquired pneumonia in 
patients who undergo a tracheostomy and those that undergo 
overnight intubation during oromaxillofacial surgery for HNC. 
Secondary objective (s) 
 
To investigate whether smoking history, respiratory history (COPD, 
asthma) or size of tumour are associated with an increased risk of 
developing hospital acquired pneumonia. 
Number of Subjects/Patients 
 
193 
Study Type 
 
Observational cohort 
Endpoints 
 
January 2023 
Main Inclusion Criteria 
 
Patients who underwent oromaxillofacial resection with free flap 
reconstruction and tracheostomy from 1st January 2018 to 31st 
December 2018. 
Patients who underwent oromaxillofacial resection with free flap 
reconstruction and with overnight intubation from 1st January 2014 to 
31st December 2014 
Statistical Methodology and Analysis 
 
A power calculation has been used to determine the sample size 
required for statistical analysis of data.  Statistical significance for rates 
of HAP will be tested between the two groups. It is anticipated that 

 
 
 
 
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data will not normally distributed and non-parametric testing will be 
used (Mann Whitney U/Chi-square depending on data type. Odds 
ratios using logistic regression will be used to explore the risk factors 
for HAP in this scenario which have previously been indicated to have 
been smoking, respiratory history and tumour size. 
Human Tissue Samples (if applicable) 
 
n/a 
Data collected/storage (if applicable) 
 
n/a 
 
 
 

 
 
 
 
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4. Introduction 
This study aims to explore the rates of hospital acquired pneumonia (HAP) in those that undergo 
temporary tracheostomy with oromaxillofacial surgery (OMFS) and free flap reconstruction for head 
and neck malignancy. The study also aims to identify risk factors that may be associated with 
developing a HAP in this patient cohort. This introduction provides a background to the study, 
outlining surgical management of these cancers, the risks and benefits associated with siting a 
tracheostomy. It outlines the importance of knowing the risks associated with tracheostomy 
placement which in turn could allow the exploration into interventions that may any risks identified.  
4.1 Head and neck cancer incidence  
Head and neck cancer (HNC) involves epithelial malignancies of the upper airway and digestive tract 
(e.g. oral and nasal cavities, paranasal sinuses, pharynx and Larynx). They are heterogeneous group 
of tumours and are the eighth leading cause of cancer in the United Kingdom (UK) (Ferlay et al. 
(2010)with an annual incidence rate of 12,422 new cases (Cancer Research UK 2016-2018). OMF 
cancer comprises of malignant tumours located within the jaw, face, mouth and neck. Owing to 
pattern of HNC spread, lymph node excisions within the neck, termed neck dissection, are often 
performed alongside excision of the primary tumour Bullock et al. (2019). OMF malignancy rates 
have risen by more than 30% since the 1990’s (OCIU head and neck profiles) as a result an increasing 
number of patients are undergoing extensive surgical resections and gruelling oncological treatment 
regimes. OMF malignancy is commonly diagnosed around 70 years of age and 69% of cases are 
diagnosed in men (Cancer research UK 2016-2018). Lifestyle & environmental factors can 
significantly increase the risk of developing OMF cancer, smoking can increase the chance of 
developing OMF cancer by up to 91% and excessive alcohol consumption by up to 81%. 
Socioeconomic deprivation is also attribute to high OMF cancer rates, increasing the risk of 
developing OMF cancer by up to 64% in females and 101% in males (Huber & Dort, 2018). A number 
of co-morbidities affecting major organ systems are directly correlated with smoking, high alcohol 
consumption and social deprivation. This combined with the risks of major OMF surgery (OMFS) can 
result in high treatment complication rates, further adding to the complexity in managing this 
disease (Goepfert et al., 2017).  
4.2 Head and Neck cancer treatment  
HNC treatment can consist of one, or a combination of treatments that includes radiotherapy, 
chemotherapy, immunotherapy and/or surgery. The covariance between the health and fitness of 
the patient, and the site, type, and stage of cancer, determine the nature, duration, and intensity of 
treatment. Between 45-75% of patients undergo oral and maxillofacial surgery as their primary 
treatment (Cancer research UK 2015-17). Surgery includes removal of the tumour & surrounding 
nodes with free flap reconstruction using autogenous bone grafting from a secondary donor site to 
improve aesthetics, speech, and swallow function. Resection of tumours within the oral cavity and 
maxillofacial area significantly impact on the structures involved with breathing, mastication, 
speech, swallowing and cosmetic appearance (Wang, Fu, Liu, Liu, and Cao (2018). The location of 
these tumours means airway security during and after surgery is paramount. Reconstruction of 
these areas with free tissue transfer (bone and soft tissue) and microvascular surgery repairs the 
defect and with rehabilitation, restores function (Patel, Kim, and Ghali (2019). The magnitude of 
insult to these two surgical sites is considerable as is the risk of post-operative complications, further 
compounded by the patients’ chronic medical and lifestyle co-existing conditions (McMahon et al., 
2013).   

 
 
 
 
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4.3 Airway security during surgery   
Airway security in OMFS is a subject of wide controversy and discussion (Goetz, Burian, Weitz, Wolff, 
and Bissinger (2019)), unlike other major head and neck surgery where tracheostomy insertion is 
necessary due to more extensive resections on more than one critical structure responsible for 
breathing, speaking, eating and drinking.  Some units’ preference is to insert a tracheostomy to 
maintain a secure airway during surgery (Marsh, Elliott, Anand, and Brennan (2009)). In contrast, 
others mitigate the risk associated with tracheostomy insertion by opting for overnight intubation 
either via endotracheal (ETT) or nasopharyngeal (NP) intubation (Singh, Sankla, & Smith, 2016Singh, 
Sankla, and Smith (2016)). In the acute post-operative phase intraoral swelling can occlude the 
upper airway necessitating a means of airway security (Coyle, Shrimpton, Perkins, Fasanmade, and 
Godden (2012); (Goetz et al., 2019).  The risk of catastrophic bleed and loss of perfusion resulting in 
flap loss is thought to be around 5% (Bianchi, Copelli, Ferrari, Ferri, and Sesenna (2009)); (Zubair et 
al. (2020)), however timely resolution is paramount, risk of morbidity or mortality increases in the 
instance of catastrophic bleed.  In the event of flap loss, the surgical insult a patient receives for a 
second flap from another site increases the risk of post-operative complications, length of stay and 
functional recovery.  Intraoral swelling can make emergency endotracheal intubation challenging, 
and insertion of emergency tracheostomy may be required (Coyle et al. (2012)). As such, OMFS 
management of intra and post-operative airway security in the UK is variable (Rogers, Russell, and 
Lowe (2017)).  
4.4 Temporary tracheostomy insertion  
Tracheostomy formation is more prevalent than either methods of intubation - a UK national survey 
observed that 69% (39/57) of maxillofacial units would “usually” or “almost always” insert a 
tracheostomy for uncomplicated free flap surgery, whilst 24% preferred ETT intubation to mitigate 
morbidity associated with tracheostomy insertion (Marsh et al. (2009)). This suggests that for HNC 
surgeons the dominant risk is airway security, which is best managed by tracheostomy formation 
despite the secondary risks created. The risks associated with tracheostomy insertion are widely 
acknowledged with reported complication rates between 8-45% (Margaret J Coyle et al. (2013)). 
They include tracheal stenosis, respiratory arrest due to tube blockage or displacement, 
haemorrhage, fistula, failure to decannulate, pneumothorax, injury to surrounding structures and 
hospital acquired pneumonia (HAP) (Coyle et al., 2013; Crosher, Baldie, and Mitchell (1997)). 
Tracheostomy complications can be life threatening and distressing for patients, and are associated 
with an increased length of stay and mortality. Pulmonary complications such as HAP in patients 
who undergo tracheostomy for all types of head and neck surgery are reported to be around 45% 
(Morton 1990). Patients who develop a HAP have a longer critical care and hospital stay. For 
example, Castling, Telfer, and Avery (1994) reported a 4 day admission to ICU and hospital LOS of 25 
days compared to 2 and 14 days in those who did not develop a HAP. Increased care needs involving 
a number of specialist clinicians, equipment such as tracheostomy tubes, suction, methods of 
humidification and antimicrobial medications individually and collectively have financial implications 
for the cost of patient care. Rates of HAP specifically in OMFS is unknown, if such data was available 
and was found to be clinically or statisitically significant in either the tracheostomy group or 
overnight inubation group work investigating methods to reduce the rate of HAP, such as early 
mobility or humidification would be justified.   
4.5 Endotracheal and Nasopharyngeal intubation 
Despite temporary tracheostomy insertion continuing to be the preferred choice for airway security, 
there is some evidence that the current approach might need to adapt; patient experience data has 
shown that given the choice, patients would avoid tracheostomy formation if possible (Nakarada-

 
 
 
 
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Kordic, Patterson, Wrapson, and Reay (2018)). Furthermore there are studies demonstrating that 
patients who undergo these procedures can be safely managed with overnight intubation. M. J. 
Coyle et al. (2013), and Singh et al. (2016) both demonstrated that overnight ETT intubation was 
associated with a lower rate of HAP (10% vs 38% and 6% Vs 12% respectively), and shorter hospital 
length of stay (12.9 Vs 18.0 days and 20.4 Vs 27.2 days P=0.03 respectively). Despite these data 
demonstrating more favourable outcomes when compared with tracheostomy, standardised criteria 
to assess complication outcomes were not used increasing the risk of detection bias. Statistical 
integrity is also questionable due to absent power calculations or small sample sizes. As a result the 
evidence justifying intubation remains equivocal. However, anecdotally, the evidence supports the 
notion that not only will patients avoid the risks and morbidity associated with tracheostomy 
insertion, they will be able to speak cough and clear secretions independently sooner (Coyle 2012) 
which will positively impact their overall post-operative recovery and experience.  
4.6 Patient experience  
There are few papers that have reported on patient experience with a tracheostomy, however it is 
an emerging theme of interest. Sherlock, Wilson, and Exley (2009) explored the hospital experience 
of patients who had a temporary tracheostomy sited for medical or surgical reasons, conducting 8 
semi-structured interviews over a 12-week period. Patients reported finding the physical and 
psychological effects more disturbing than expected; experiencing discomfort, fear, and frustration 
when attempting to talk, eat and drink, and during routine care-activities (e.g. suction to remove 
tracheostomy secretions). A study conducted by  Rogers et al. (2017) using a multi-staged approach 
to record the experience of a patients who underwent tracheostomy during surgery for HNC 
reported similar findings. They conducted 15 semi-structured interviews, and used themes identified 
during these interviews to construct a postal questionnaire. The response rate was a respectable 
69% (86/125) and found 60% of patients would “very much” avoid a tracheostomy if at all possible. 
Patients also reported they had “very much or “quite a bit” of a problem with tracheostomy 
communication, routine care, choking, discomfort, and sleeping. The Rogers et al (2017) study 
included selected comments from patients who underwent tracheostomy and included:  
“Horrendous. I used to be a nurse with children and you don’t realise what it 
is like. I would sooner be dead than go through it again. It is a horrible, 
fearful, horrendous feeling especially when coughing and sucking down the 
tracheostomy. It was difficult to get a comfortable position getting the oxygen, 
alright when removed, over quite quickly. You don’t know what it is like unless 
you have had it done. The feeling of sucking out was awful”.  
These findings support the notion that temporary tracheostomy should not be considered a minor or 
routine procedure and that the risk of life-threatening airway compromise should be balanced 
against the risks associated with tracheostomy as well as poor patient experience. However further 
work fully exploring the experience of patients who undergo temporary tracheostomy is needed and 
any outcomes that may improve experience such as specialist tracheostomy nurses and pre-
operative patient counselling could be investigated.  
4.7 Summary and the research problem 
The association between lifestyle and environmental factors and increased risk of developing HNC 
cancer are widely acknowledged. Smoking, alcohol consumption, socioeconomic status and low 
mental wellbeing are important determinants and highly prevalent factors affecting the onset, 

 
 
 
 
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prognosis and recovery from HNC (McCarter et al. (2018)).  Rates of morbidity and mortality are higher 
in those who present with co-morbidities associated with the above-mentioned risk factors.   
There is some evidence in support of safely managing OMFS patients with overnight intubation, 
however work needs to be done to establish what patients are suited to either method of airway 
protection. Tracheostomy remains the method of choice for airway security during OMFS, despite 
demonstrated and assumed risks associated with insertion, the associated financial burden and 
emerging evidence reporting on poor patient experience. HAP remains a prevalent perceived risk in 
those that undergo tracheostomy and is associated with increased length of critical care, and 
hospital length of stay, morbidity, and mortality. There is a need to accurately identify and quantify 
HAP rates with both methods of airway protection in OMFS. If such data were available clinicians 
and patients could make informed decisions on the best method of airway protection for the surgical 
procedure they are undergoing. If rates were found to be high in either scenario, and any patient risk 
factors were associated with the development of a HAP, further work could explore what pre or pre 
or post-operative interventions could be deployed to help reduce the risk of developing a HAP. 
5 Trial objectives and purpose 
Student MRes project 
 
To select patients according to a pre-defined set of inclusion and exclusion criteria  
 
Collect pre-determined quantitative data relevant to the study question using hospital medical 
records 
 
Describe patient demographic data and explore any relationship between these and the 
development of a HAP 
 
Assess rates of HAP using historical medical data and pre-defined criteria that identifies hospital 
acquired pneumonia 
 
Describe rates of HAP in patients who did not have a tracheostomy inserted for maxillofacial 
surgery with free flap reconstruction 
 
Describe rates of HAP in patients who did have a tracheostomy inserted for maxillofacial surgery 
with free flap reconstruction 
6 Study design & Flowchart 
6.1 Study Design 
In 2017, a new maxillofacial surgeon was appointed to Guy’s & St Thomas’ NHS Foundation Trust 
who’s preference was to insert a temporary tracheostomy for all patients undergoing 
oromaxillofacial surgery with free flap reconstruction. Prior to this there was a wide variation in case 
selection with the majority of patients undergoing overnight intubation. Since subsequent practice 
has now changed and all patients now undergo tracheostomy insertion within OMFS, a prospective 
design is not possible, therefore, a single site retrospective observational design will be adopted, 
allowing data from two cohorts of patients identified to be collected within a feasbile timeframe 
dictated by the module deadlines. Electronic and paper notes of patients from cohorts before and 
after the change in maxillofacial surgical practice (2014 and 2018) will be screened. 

 
 
 
 
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6.2 Primary outcome tool 
HAP is an acute lower respiratory tract infection that is acquired after at least 48 hours of admission 
to hospital and is not incubating at the time of admission (BMJ best practice; Hospital acquired 
pneumonia (non covid-19) 2022). It is more common in patients that have undergone major surgery, 
those admitted to critical care, and those with a prolonged hospital admission (BMJ no 6 best 
practice). Developing a HAP is associated with an increase in morbidity and mortality as patients 
with these risk factors are also likely to have one or a combination of multiple co-morbidities, critical 
illness and frailty. Using a standardised outcome measure to assess the primary outcome reduces 
the risk of bias and increases reliability and reproducibility. The primary outcome in this study was 
hospital-acquired pneumonia as defined by the British Medical Journal (BMJ), best practice 
guidelines on hospital-acquired pneumonia (non-covid-19). The criteria are the following; 
A new and/or persistent shadowing (consolidation) on chest x-ray, which is otherwise unexplained, 
plus at least two of the following confirms the diagnosis: 
 
Fever >38ºC (>100ºF) 
 
Leukocytosis (WBC >10 x 10 9 /L) or leucopenia (WBC <4X10 9/L) 
 
Purulent sputum 
 
Decline in oxygenation 
 
The primary investigator will identify eligible patients from a database collected as part of routine 
clinical care, trust service evaluation and audit. Electronic and paper records from eligible patients 
will be screened and data relevant to the study extracted and recorded. This data will then be 
analysed.  
7 Subject selection 
Participants will be identified by screening consecutive sets of case notes and electronic records for 
the years of 2014 (those before tracheostomy insertion was routine, therefore those who did not 
have a tracheostomy inserted) and 2017 (tracheostomy insertion was routine). Eligibility criteria 
includes all patients who underwent oromaxillofacial surgery with tracheostomy and free flap 
reconstruction. Only those with missing or unavailable data will be excluded. The PI is an employee 
of Guy's and St Thomas' NHS foundation trust (GSTT) and will be undertaking all aspects of data 
collection and recording. As employees of GSTT the CI and PI have undertaken all relevant 
information governance mandatory training permitting access to required data. The study will take 
place at a single site – Guy’s & St Thomas’ NHS Foundation Trust. 
7.1 Subject inclusion criteria 
 
Patients who underwent maxillofacial resection with free flap reconstruction and 
tracheostomy from 1st January 2018 to 31st December 2018. 
 
Patients who underwent maxillofacial resection with free flap reconstruction and with 
endotracheal intubation from 1st January 2014 to 31st December 2014 
 
Patients over the age of 18 
7.2 Subject exclusion criteria  
 

 
 
 
 
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 
Patients who did not undergo maxillofacial resection with free flap reconstruction and 
tracheostomy from 1st January 2018 to 31st December 2018 – not relevant and will not 
answer the study question 
 
Patients who did not undergo maxillofacial resection with free flap reconstruction and with 
endotracheal intubation from 1st January 2014 to 31st December 2014 - not relevant and 
will not answer the study question 
 
Patients under the age of 18  
 
8 Study procedures 
8.1 Subject recruitment 
Subjects will not be recruited or consented. The study is a retrospective observational cohort study, 
reviewing retrospective data collected as part of routine clinical care.  
8.2 Screening Procedures  
The primary investigator will identify eligible patients from a database collected as part of routine 
clinical care, trust service evaluation and audit.  
8.3 End of Study Definition  
Full data collection and analyses. 
9  Assessment of Safety 
The study is an observational cohort study, involving analysis of retrospective patient data collected 
as part of routine clinical care. There are no interventions or contact with patients.  The primary 
investigator is an employee of GSTT, and is directly involved in the delivery of clinical care to this 
patient group in their normal clinical role.  
9.1  Ethics Reporting 
The study is an observational cohort study, involving analysis of retrospective patient data collected 
as part of routine clinical care. There are no interventions or contact with patients. 
10 Data 
10.1 Data to be collected 
The PI will identify eligible patients from a database collected as part of routine clinical care for trust 
service evaluation and audit. Electronic and paper records of eligible patients will be screened and 
data appropriate to the study extracted. Descriptive demographic data including age, gender, cancer 
site, stage, surgery type, neck dissection, flap site, and factors known to increase risk of HAP; 
smoking history, respiratory history, tumour size, hospital length of stay, and mortality will be 
recorded. The primary outcome tool will be retrospectively applied to case notes and electronic 
records of included patients, by a single therapist (the PI) between day 1 and 7 post operatively.  It is 
anticipated data collection will take around 2 months.  

 
 
 
 
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10.2  Primary outcome tool 
HAP is an acute lower respiratory tract infection that is acquired after at least 48 hours of admission 
to hospital and is not incubating at the time of admission (BMJ best practice). It is more common in 
patients that have undergone major surgery, those admitted to critical care, and those with a 
prolonged hospital admission (BMJ no 6 best practice). Developing a HAP is associated with an 
increase in morbidity and mortality as patients with these risk factors are also likely to have one or a 
combination of multiple co-morbidities, critical illness and frailty. Using a standardised outcome 
measure to assess the primary outcome reduces the risk of bias and increases reliability and 
reproducibility. The primary outcome in this study was hospital-acquired pneumonia as defined by 
the British Medical Journal (BMJ), best practice guidelines on hospital-acquired pneumonia (non-
covid-19), the criteria is the following; 
A new and/or persistent shadowing (consolidation) on chest x-ray, which is otherwise unexplained, 
plus at least two of the following confirms the diagnosis: 
 
Fever >38ºC (>100ºF) 
 
Leukocytosis (WBC >10 x 10 9 /L) or leucopenia (WBC <4X10 9/L) 
 
Purulent sputum 
 
Decline in oxygenation 
 
Data collected will be continuous, nominal, ordinal and discrete.  
10.3 Data handling and record keeping 
The PI can confirm that patient demographic data electronic data (e.g. Age, DOB, sex, past medical 
history, head and neck surgical and oncological history) will be transferred from their electronic 
patient record to the secure networked digital data store. Data will be backed up on a secure trust IT 
provided memory stick that will be stored in a locked filing cabinet stored within a room that can 
only be accessed with trust ID. All patient identifiable data and link back spreadsheets will be held at 
GSTT sites and not transferred to KCL during or after the study. 
Any identifiable and personal data will only be accessed by the PI who is an employee of Guy's and St 
Thomas' NHS Foundation Trust and directly involved in the delivery of clinical care to this patient 
group, and is held to account on the NHS Trust's information governance policy. All data will be 
protected and confidentiality maintained following the NHS Code of Confidentiality (2003).  Data will 
only be accessed by the PI and will be stored on a password protected, trust laptop that will be 
stored in a locked cupboard within an office that can only be accessed with trust ID (rehabilitation 
room on Blundell ward at Guy's Hospital). The data will be backed up on a trust provided encrypted 
memory stick. 
Any identifiable and personal data will only be accessed by the investigator who is also an employee 
of Guy's and St Thomas' NHS Foundation Trust and in their clinical role deliver clinical care to this 
patient group,and is held to account on the NHS Trust's information governance policy. All data will 
be protected and confidentiality maintained following the NHS Code of Confidentiality (2003). 

 
 
 
 
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All data files containing data will be anonymised using a code that does not allow direct 
identification of the participant. The key to the code will be stored in a separate file together with 
the personal details of each participants. The key, personal details and log will be stored only on the 
secure storage facility. This data will be stored using a password-protected excel spreadsheet. 
Patient's hospital numbers will not be held in the same database as clinical data. It will be stored in a 
separate database and linked through a unique study number. On initial identification it will be 
stored in a separate password protected database that will be saved on a secure trust laptop, stored 
in a locked cabinet in a room that can only be accessed with trust swipe ID access.  
The data (stored on password protected computers that are stored in a secure office of the PI at 
Guy's Hospital Site) generated by the study will be analysed in commercially available software 
(SPSS) by the PI. 
The data will not include any participant identifiable data. Anonymized participant characteristic and 
study data for this study will be stored securely in Microsoft Excel files – it is a small non-
interventional observational study and while we do not envisage the characteristic data changing, if 
it does then separate files will be created to create an audit trail. 
The data will be analysed on the Guy's Hospital site, on a GSTT laptop, by the PI only. All participant-
identifiable data will have already been removed from the laptop and transferred to an encrypted 
external storage device (an encrypted USB device provided by the GSTT IT department kept in a 
locked filing cabinet in locked, secured offices in an area that can only be entered with a security 
swipe-card at Guy's Hospital. The encrypted external storage device will be backed-up on a secure 
networked digital datastore that is accessible only to the PI on PCs that are password protected at 
login kept in locked, secured offices in an area that can only be entered with a security swipe-card at 
Guys hospital. Any GSTT laptop will not therefore have participant-identifiable data kept on its hard 
drive. 
Excel spreadsheets will be used, data stored within excel spreadsheets will be periodically saved as a 
PDF (to lock the data) and saved in a password protected folder with the Excel database. The PDF 
will be printed off and validated by the PI. A hard copy will be retained securely should the Excel file 
become corrupt as a back-up. 
Data Protection: 
Data will be processed according to trust information governance processes and the PI is compliant 
with all information governance mandatory training and good clinical practice principles 
No data will be obtained that is not required for the current study and its stated end points 
Every effort will be made to ensure data will be recorded accurately and thoroughly checked prior to 
analysis 
Data for the current study will be kept on a secured GSTT trust laptop in a secure, locked office 
accessed only by trust ID for a maximum of 5 years 

 
 
 
 
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All patients identified as eligible for the study will be assigned a code the code will be kept on a 
secure GSTT trust laptop within a secured locked office at GSTT 
No data will be disclosed outside of the EU. The outcomes of the study may presented at national 
and international conference that may include the EU, and/or published in peer review journals that 
include the EU - all data will be deidentified. 
11 Statistical considerations 
Statistician advising on power calculation and analysis procedure. 
Mr Bola Coker 
Senior Data Manager, NIHR GSTT/KCL Biomedical Research Centre 
Visiting Senior Data Manager, School of Population Health & Environmental Sciences, KCL 
Guy's & St Thomas' NHS Foundation Trust 
5th Floor Addison House 
London 
SE1 1UL 
020 7848 8687 
bolaji.coker@kcl.ac.uk 
 
11.1 Sample size calculation (some pilot/feasibility studies may not require a 
formal sample size calculation) 
The sample size required is 193. Using G*Power 3.1.9.2 Universität Düsseldorf: G*Power (hhu.de) 
the study has been powered at 80%, with a type 1 error of 5%, two-tailed, to detect an effect size 
difference, expressed as an odds ratio, of 2.33 using binary logistic regression. It is assumed that 30% 
of patients that did not have a tracheostomy inserted for maxillofacial surgery with free flap 
reconstruction (2014 cohort) develop HAP. It is further assumed that the 2018 cohort (those with 
endotracheal intubation) will make up 41% of the combined cohort. The primary independent 
variable will be binary to represent the two cohorts being studied. 
11.2 Statistical analysis 
A power calculation will be used to determine the sample size required for statistical analysis of 
data. Statistical significance for rates of HAP will be tested between the two groups. It is anticipated 
that data will not normally distributed and non-parametric testing will be used (Mann Whitney 
U/Chi-square depending on data type). Odds ratios using logistic regression will be used to explore 
the risk factors for HAP in this scenario which have previously been indicated to have been smoking, 
respiratory history and tumour size. 
12 Ethical considerations 
The proposed work will be conducted according to the principles set out in the Helsinki Declaration 
(World Medical Association Declaration of Helsinki. Ethical Principles for Medical Research involving 
Human Subjects, as amended by the 56th WMA General Assembly, Fortaleza, Brazil, October 2013. 

 
 
 
 
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Review within the host organisation incorporates directorate-level peer review led by its respective 
clinical research and audit lead, accountable to the Foundation Trust clinical governance directorate 
lead. 
Masters projects are subject to a thorough review through KCL and review bodies. This provides 
assurance that there is valid research question and that the research has been confirmed as suitably 
designed. 
Peer review has been undertaken anonymously and has been sent to GSTT R&D separately to 
maintain anonymity. 
HRA approval is required.  
Patient & Public involvement 
Details of involvement: PPI remote meeting via video conferencing September 2021 
Expert patients who had undergone oromaxillofacial resection with free flap reconstruction and 
temporary tracheostomy were contacted. They were invited to voluntarily take part in a small 
workshop that aimed to gain an insight into how important patient's feel this project will be, if they 
have any thoughts on the design of the project, handling and storage of patient data and the best 
timing and format to disseminate the results. 
Who was involved? 
Patients who had undergone oromaxillofacial resection with free flap reconstruction and temporary 
tracheostomy. 
How were they involved? 
5 patients agreed to participate, 2 requested to attend via video call and 3 had no preference. The 
decision was made to conduct the 1 hour meeting via video call using commercial and accessible 
video conferencing service supported by GSTT IT - MS teams. Prior to that meeting, the CI will 
communicate with members by email and/or telephone. The PI chaired the meeting and another 
physiotherapist working within head and neck surgical oncology recorded the minutes - the PI also 
reviewed the minutes after to ensure all discussion was accurately recorded. 
How and when will you feedback? (Them to you, you to them).  
Patients were asked if they would like to receive updates with regard to study progress, results and 
any publications, and if so in what format and how. All patients requested to receive updates from 
email, and would like to receive a lay version of results and study write up. Therefore the PI will 
feedback to the group members by email providing an update on study progress (outcome ethics, 
data collection, results and write up).  Once complete a copy of a lay abstract of results will be sent 
via email. 

 
 
 
 
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13 Financing and Insurance 
The lead sponsor, King's College London, will take primary responsibility for ensuring that the design 
of the study meets appropriate standards and that arrangements are in place to ensure appropriate 
conduct and reporting. King's College London also provides cover under its No Fault Compensation 
Insurance, which provides for payment of damages or compensation in respect of any claim made by 
a research subject for bodily injury arising out of participation in a clinical trial or healthy volunteer 
study (with certain restrictions). The co-sponsor, Guy's & St Thomas' Foundation NHS Trust, take 
ultimate responsibility for arranging the initiation and management of this research, and will take 
responsibility for ensuring that appropriate standards, conduct and reporting are adhered to regarding 
its facilities and staff involved with the project. 
14 Reporting and dissemination 
Study results are planned to be published in a relevant head and neck peer reviewed journal, and 
presented at a relevant head and neck national/international conference. Raw data will not be 
published. Publications will be discussed with the sponsor.  
Useful reading/websites 
 
Integrated Research Application System (IRAS) 
https://www.myresearchproject.org.uk/  
 
Health Research Authority (HRA) 
www.hra.nhs.uk  
 
HRA Guidance for Patient Information Sheet and Informed Consent  
http://www.hra.nhs.uk/research-community/before-you-apply/participant-information-sheets-and-
informed-consent/  
 
CONSORT statement  
  
 
ICH Harmonised Tripartite Guidelines for Good Clinical Practice (1996) 
http://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Efficacy/E6/E6_R1_Guidel
ine.pdf  
 
Martin Bland et al, Statistical guide for research grant applications 
http://www-users.york.ac.uk/~mb55/guide/guide.htm  
Includes detailed information and definitions of many aspects required for a research protocol.  
 
Declaration of Helsinki  
(http://www.wma.net/en/30publications/10policies/b3/index.html) 
 
 

 
 
 
 
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Appendix 1 – Information with regards to Safety Reporting in Non-CTIMP 
Research 
 
Who 
When 
How 
To Whom 
SAE 
Chief 
Investigator 
-Report to Sponsor 
within 24 hours of 
learning of the event 
 
-Report to the MREC 
within 15 days of 
learning of the event 
 
SAE Report form for Non-
CTIMPs, available from NRES 
website. 
Sponsor and MREC 
Urgent Safety 
Measures  
Chief 
Investigator  
Contact the Sponsor and 
MREC Immediately 
 
Within 3 days  
By phone 
 
 
 
 
Substantial amendment 
form giving notice in writing 
setting out the reasons for 
the urgent safety measures 
and the plan for future 
action. 
Main REC and 
Sponsor  
 
 
 
Main REC with a 
copy also sent to 
the sponsor. The 
MREC will 
acknowledge this 
within 30 days of 
receipt.  
Progress 
Reports  
Chief 
Investigator  
Annually (starting 12 
months after the date of 
favourable opinion) 
Annual Progress Report 
Form (non-CTIMPs) available 
from the NRES website 
Main REC 
Declaration of 
the conclusion 
or early 
termination of 
the study 
Chief 
Investigator  
Within 90 days 
(conclusion) 
 
Within 15 days (early 
termination) 
 
The end of study should 
be defined in the protocol 
End of Study Declaration 
form available from the 
NRES website 
Main REC with a 
copy to be sent to 
the sponsor  
Summary of 
final Report  
Chief 
Investigator 
Within one year of 
conclusion of the 
Research 
No Standard Format 
However, the following 
Information should be 
included:- 
Where the study has met its 
objectives, the main findings 
and arrangements for 
publication or dissemination 
including feedback to 
participants 
Main REC with a 
copy to be sent to 
the sponsor 
 
 
 
 

 
 
 
 
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