Proning Pillows for Intensive Care Unit: Comparison of Chest and Pelvis Interface Pressure Distributions Between a Novel Proning Pillow System and Standard Pillows in Healthy Subjects
Phase: NA
Conditions: Pressure Ulcer
Sponsor: Liverpool University Hospitals NHS Foundation Trust

 
Proning Pillow Study Protocol 
version 2.0  Date 11th January 
2022 
 
Page 1 of 25 
 
 
 
 
 
 
 
 
Study Title:  Proning pillows for Intensive Care Unit (ICU): Comparison of chest and pelvis 
interface pressure distributions between a novel proning pillow system and standard pillows in 
healthy subjects 
Internal Reference No: SP0857 
Ethics Ref: N/A 
IRAS ID: 304653 
 
 
Version No: 2.0 
Date:   11th  January 2022 
 
 
 
 
 
 
 
 
 
 

 
Proning Pillow Study Protocol 
version 2.0  Date 11th January 
2022 
 
Page 2 of 25 
 
 
 
 
 
              
               SIGNATURE PAGE 
The undersigned confirm that the following protocol has been agreed and accepted and that 
the Chief Investigator agrees to conduct the study in compliance with the approved protocol 
and will adhere to the principles outlined in the Declaration of Helsinki, the Liverpool 
University Hospitals NHS Foundation Trust SOPs, and other regulatory requirement. 
I agree to ensure that the confidential information contained in this document will not be used 
for any other purpose other than the evaluation or conduct of the investigation without the 
prior written consent of the Sponsor 
I also confirm that I will make the findings of the study publically available through publication 
or other dissemination tools without any unnecessary delay and that an honest accurate and 
transparent account of the study will be given; and that any discrepancies from the study as 
planned in this protocol will be explained. 
 
For and on behalf of Liverpool University Hospitals NHS Foundation Trust 
 
Signature:  
...................................................................................................... 
 
Date: 
....../....../...... 
Name (please print): 
...................................................................................................... 
 
 
Position: 
...................................................................................................... 
 
 
 
 
 
Chief Investigator: 
Signature: 
...................................................................................................... 
 
Date:  
Name: (please print):Dr Tristan Payne 
......................................................................................................
 
 
 
 
 
 
 
 
 

 
Proning Pillow Study Protocol 
version 2.0  Date 11th January 
2022 
 
Page 3 of 25 
 
 
 
 
 
 
 
 
 Key Study Contacts 
Chief Investigator 
Dr Tristan Payne 
Medical Physics and Clinical Engineering 
Royal Liverpool Hospital 
Liverpool University Hospitals NHS Foundation Trust 
Duncan Building, 1st Floor 
Prescot Street 
Liverpool L7 8XP 
tristan.payne@nhs.net, +44(0) 1517064225 
Student 
Kalpani Vitharana 
Medical Physics and Clinical Engineering 
Royal Liverpool Hospital 
Liverpool University Hospitals NHS Foundation Trust 
Duncan Building, 1st Floor 
Prescot Street 
Liverpool L7 8XP 
kalpani.vitharana@nhs.net 
 
Sponsor 
Heather Rogers   
R&I Governance Manager 
Research Governance Committee Chair 
Liverpool University Hospitals NHS Foundation Trust 
Prescot St  
Liverpool  
Tel: 0151 706 3702 
Email: RGT@RLBUHT.nhs.uk  
 
Joint-sponsor(s)/co-sponsor(s)  
N/A 
Funder(s) 
N/A 
 
Key Protocol Contributors - 
Statistics 
Dr. Antonio Eleuteri 
Department of Clinical Engineering 
Liverpool University Hospitals NHS Foundation Trust 
1st floor Duncan Building 
Prescot Street, Liverpool 
L7 8XP 
eleuteri@liverpool.ac.uk 
Committees 
N/A 

 
Proning Pillow Study Protocol 
version 2.0  Date 11th January 
2022 
 
Page 4 of 25 
 
 
 
 
Confidentiality Statement 
This document contains confidential information that must not be disclosed to anyone other 
than the Sponsor, the Investigator Team, host  (s), regulatory authorities, and members of the 
Research Ethics Committee.   
TABLE OF CONTENTS 
1. 
AMENDMENT HISTORY ................................................................................................ 7 
2. 
SYNOPSIS ..................................................................................................................... 8 
3. 
ABBREVIATIONS ........................................................................................................... 9 
4. 
BACKGROUND AND RATIONALE ............................................................................... 10 
5. 
OBJECTIVES ............................................................................................................... 11 
5.1 
Primary Objective .................................................................................................. 11 
5.2 
Secondary Objectives ............................................................................................ 11 
6. 
CROSS-SECTIONAL COMPARATIVE  DESIGN .......................................................... 11 
6.1 
Summary of Study Design ..................................................................................... 11 
6.2 
Primary and Secondary Endpoints/Outcome Measures ......................................... 11 
6.3 
Study Participants .................................................................................................. 11 
6.4 
Study Procedures .................................................................................................. 12 
6.5 
Definition of End of Trial ......................................................................................... 13 
6.6 
Discontinuation/ Withdrawal of Participants from Study Treatment ........................ 14 
6.7 
Source Data ........................................................................................................... 14 
7. 
TREATMENT OFstudy PARTICIPANTS ....................................................................... 14 
7.1 
Description of Study Intervention(s) ....................................................................... 14 
7.2 
Maintenance and storage of device ....................................................................... 16 
7.3  
Concomitant Medication (if applicable)................................................................... 16 
8. 
SAFETY reporting ......................................................................................................... 16 

 
Proning Pillow Study Protocol 
version 2.0  Date 11th January 
2022 
 
Page 5 of 25 
 
 
8.1 Reporting of AE .......................................................................................................... 16 
8.2 Reporting of DDs/SAEs/SADEs/USADEs ................................................................... 16 
8.3: Annual Reports .......................................................................................................... 17 
9. 
STATISTICS ................................................................................................................. 17 
9.1 
Description of Statistical Methods .......................................................................... 17 
9.2 
The Number of Participants ................................................................................... 17 
9.3 
The Level of Statistical Significance and Model Validation ..................................... 17 
9.4 
Procedure for Accounting for Missing, Unused, and Spurious Data. ...................... 17 
9.6 
Procedures for Reporting any Deviation(s) from the Original Statistical Plan ......... 18 
9.7 
Inclusion in Analysis ............................................................................................... 18 
10. 
Direct Access to Source Data/Documents ................................................................. 18 
11. 
Quality Control and Quality Assurance Procedures ................................................... 18 
12. 
Ethics ........................................................................................................................ 18 
12.1 
Declaration of Helsinki ........................................................................................... 18 
12.2 
ICH Guidelines for Good Clinical Practice .............................................................. 18 
12.3 
Approvals ............................................................................................................... 18 
12.4 
Participant Confidentiality ...................................................................................... 19 
13. 
Data Handling and Record Keeping .......................................................................... 19 
14. 
Financing and Insurance ........................................................................................... 20 
15. 
End of study definition ............................................................................................... 20 
16. 
Publication Policy ...................................................................................................... 20 
17. 
Archiving ................................................................................................................... 20 
18. 
REFERENCES .......................................................................................................... 21 
19. 
Appendix ................................................................................................................... 22 
19.1 Definitions ................................................................................................................. 22 
19.2 Description of Statistical Methods ............................................................................. 23 
 

 
Proning Pillow Study Protocol 
version 2.0  Date 11th January 
2022 
 
Page 6 of 25 
 
 
 
 

 
Proning Pillow Study Protocol 
version 2.0  Date 11th January 
2022 
 
Page 7 of 25 
 
 
1. 
AMENDMENT HISTORY 
Amendment 
No. 
Protocol 
Version 
No. 
Date 
issued 
Author(s) of changes 
Details of Changes 
made 
 
 
 
 
 

 
Proning Pillow Study Protocol 
version 2.0  Date 11th January 
2022 
 
Page 8 of 25 
 
 
2. 
SYNOPSIS 
The study will compare the pressure distribution between novel proning pillows and standard 
pillows used in the ICU. NHS staff will be recruited and will be asked to lie on each pillow for 
a short period of time. The pressure distribution will be measured using a pressure mat placed 
between the subject and pillow.  
Study Title 
Proning pillows for Intensive Care Unit (ICU): Comparison of chest and 
pelvis interface pressure distributions between a novel proning pillow 
system and standard pillows in healthy subjects  
Internal ref. no. 
 SP0857 
Type of study 
Interventional 
Trial Design 
Cross-sectional comparative study  
Trial Participants 
NHS staff 
Planned Sample Size 
50 
Follow-up duration 
N/A 
Planned Trial Period 
1 year 
Primary Objective 
To evaluate any differences in chest and pelvis interface pressures 
between novel proning pillows and standard pillows used in ICU. 
Secondary 
Objectives 
N/A 
Primary Endpoint 
Peak interface pressure differences between the two pillows 
Secondary 
Endpoints 
N/A 
Device Name  
Prone Pillow System 
Manufacturer Name  
Putnam Health Co Ltd (Devon, UK) 
Principle intended 
use  
The proning system has been specifically designed and shaped to work 
together to assist with the positioning of proned patients to aid even 
distribution pressure reducing the number of pressure points and 
enable positioning in the neutral position to reduce the need for frequent 
repositioning and therefore need for trained manpower, which in 
significant shortage due to the surge in COVID patients on 'Critical 
Care. 
Length of time use 
the device has been 
in use.  
Device has been in use since January 2021 

 
Proning Pillow Study Protocol 
version 2.0  Date 11th January 
2022 
 
Page 9 of 25 
 
 
3. 
ABBREVIATIONS 
AE 
Adverse event 
ADE  
Adverse Device Effect  
CI 
Chief Investigator 
CRF 
 
Case Report Form 
CRO  
Contract Research Organisation 
CT 
 
Clinical Trials 
CTA 
 
Clinical Trials Authorisation 
                    GCP 
 
  Good Clinical Practice 
GP 
General Practitioner 
ICF 
Informed Consent Form 
ICH 
International Conference of Harmonisation 
LUHFT 
Liverpool University Hospitals NHS Foundation Trust 
MHRA 
Medicines and Healthcare products Regulatory Agency 
NHS 
National Health Service 
NRES 
National Research Ethics Service (previously known as COREC) 
PI 
Principal Investigator 
PIL 
Participant/ Patient Information Leaflet 
R&I 
 R&I Department 
REC 
Research Ethics Committee 
SAE 
Serious Adverse Event  
SADE 
Serious Adverse Device Effect  
SIL 
Subject Information Leaflet (see PIL) 
SOP 
Standard Operating Procedure 
TMF 
Trial Master File 
USADE 
Unanticipated Serious Adverse Device Effect  
 
 
 
 

 
Proning Pillow Study Protocol 
version 2.0  Date 11th January 
2022 
 
Page 10 of 25 
 
 
4. 
BACKGROUND AND RATIONALE 
During the COVID-19 pandemic, intensive care units (ICUs) across the country have been 
inundated with increasing numbers of COVID patients. Hypoxic patients in ICU require 
mechanical ventilation and this can be improved by proning these patients to improve 
oxygenation and prevent ventilator-induced lung injury (Guerin et al, 2013). Standard practice 
is to use standard hospital pillows to support the pelvis and chest of the patient while they are 
proned. These pillows do not provide much support to the patients and often need to be 
adjusted due to the patient ‘sinking’ into them. Prolonged pronation also leads to pressure 
sores in these anatomical locations which burden the Trust financially and also cause distress 
to patients.  
A new proning pillow system was developed by Dr Sashika Selladurai and manufactured for 
the ICU in Aintree hospital which is made from polyurethane memory foam designed to relieve 
pressure on the patients and prevent pressure sores that often occur during prolonged proning. 
The pillow system is also designed to withstand the load of heavier patients and reduce the 
risk of ‘sinking’ into the pillows when proned for long periods of time.  
The aim of the study is to compare the performance of the new proning pillow system with 
standard pillows, particularly in relation to the risk of pressure sores, by evaluating differences 
in chest and pelvis interface pressures between the two pillow types. This will be done by 
having healthy NHS staff lie on the pillows in the prone position for a short period of time while 
recording the pressure distribution on the pillows using pressure mats placed between them 
and the pillows. This will help understand the relative risk of pressure sores developing when 
the new pillow system is used. It is hypothesised that the new pillow system does not increase 
the risk of pressure sores developing.  
The new proning pillow system is a Class 1 CE marked medical device. The proning pillow 
system consists of a chest pillow and a pelvis pillow made from memory foam designed to 
reduce contact pressures and peak interface pressures in patients and allow patients to be 
placed in neutral position for ventilation. 
This research is to be submitted in fulfilment of an academic qualification, a Masters of Science 
in Clinical Sciences (Clinical Engineering). The student will be doing this project under 
supervision. The student will recruit participants, take informed consent and take 
measurements. 
 

 
Proning Pillow Study Protocol 
version 2.0  Date 11th January 
2022 
 
Page 11 of 25 
 
 
5. 
OBJECTIVES 
5.1 
Primary Objective 
To evaluate any differences in chest and pelvis interface pressures between novel proning 
pillows and standard pillows used in ICU. 
5.2 
Secondary Objectives 
None 
 
6. 
CROSS-SECTIONAL COMPARATIVE  DESIGN 
6.1 
Summary of Study Design 
Each participant will use both the Proning Pillow System and standard pillows. Each participant 
will only visit once with no further follow-up periods.  
6.2 
Primary and Secondary Endpoints/Outcome Measures 
The primary outcome measure is the peak interface pressure, as measured by the pressure 
mat, for both types of pillows.  
6.3 
Study Participants  
6.3.1 Overall Description of Study Participants 
Healthy participants working for the NHS.  
6.3.2 Inclusion Criteria 
• 
Work for Liverpool University Hospital NHS Foundation Trust 
• 
Participant is willing and able to give informed consent for participation in the study. 
• 
Agree to have weight, height, chest and waist measurements taken 
• 
Agree to the study protocol 
• 
Aged 18 years or above.  
6.3.3 Exclusion Criteria 
The participant may not enter the study if ANY of the following apply: 
• 
Presentation of skin lesions 
• 
Absence of any limb 
• 
Female participant who is pregnant 

 
Proning Pillow Study Protocol 
version 2.0  Date 11th January 
2022 
 
Page 12 of 25 
 
 
• 
Have a lower back problem  
• 
Pain or injury in shoulders or arms 
• 
History of conditions that would make it difficult to lie prone, such as pressure injury or 
surgery within six months leading up to the study 
• 
Any conditions that significantly affect movement and sensation such as diabetes or 
mobility limitations 
6.4 
Study Procedures 
6.4.1 Screening and Eligibility Assessment 
 
Staff from the Clinical Engineering Department at the Royal Liverpool University Hospital as 
well as staff from other departments such as the ICU in Aintree Hospital will be sent an email 
regarding the study and asked to participate. Staff must be over 18 years of age, and must 
agree to have their height, weight, chest and waist measured. The email will consist of a 
description of what the study is about. Interested participants will then be asked if they have 
any conditions mentioned in the exclusion criteria (Section 0). If they do, they will be excluded.  
 
6.4.2 Informed Consent 
The participant must personally sign and date the latest approved version of the informed 
consent form before any study specific procedures are performed. 
Written and verbal versions of the participant information and Informed consent will be 
presented to the participants detailing no less than: the exact nature of the study; the 
implications and constraints of the protocol; the known side effects and any risks involved in 
taking part.  It will be clearly stated that the participant is free to withdraw from the study at any 
time for any reason without prejudice to future care, and with no obligation to give the reason 
for withdrawal. 
 
The participant will be allowed as much time as wished to consider the information, and the 
opportunity to question the Investigator, their GP or other independent parties to decide whether 
they will participate in the study.  Written Informed Consent will then be obtained by means of 
participant dated signature and dated signature of the person who presented and obtained the 
informed consent. The person who obtained the consent must be suitably qualified and 
experienced, and have been authorised to do so by the Chief/Principal Investigator. A copy of 
the signed Informed Consent will be given to the participants if requested.  The original signed 

 
Proning Pillow Study Protocol 
version 2.0  Date 11th January 
2022 
 
Page 13 of 25 
 
 
form will be retained at the study site.  
6.4.3 Baseline Assessments 
Height, weight, gender.  
6.4.4 Randomisation and Codebreaking 
All participants will lie on both sets of pillows.  The only randomisation will be the order of 
pillows that participants will be asked to lie on.  
6.4.5 Subsequent assessments 
 
Once informed consent has been taken, each participant will have their height, weight, waist 
and chest size measured and recorded, along with their gender. Participants will be asked to 
remove any belts or large objects that may interfere with the study. The following will then be 
repeated 3 times for each set of pillows: Each participant will be given instructions and be 
asked to lie down on the pillows (adjusting the position of the pillows to suit their height if 
necessary). The participant will then be given a short period of time (~1 minute) to get 
comfortable. The pressure mat data recording will then start, and the co-investigator will press 
down on the pressure mat at the approximate location of anatomical landmarks. The participant 
will continue to lie on the pillow for approximately 3 further minutes to allow pressure 
measurements to be taken. The participant will be asked to stand up and will be given a short 
rest period (~30 seconds) before being asked to reposition themselves back on the pillows and 
get comfortable.  
 
Following this the participant will be given a period of time to recover while the pillows are 
changed to either standard hospital pillows or the novel proning pillows (the order will be 
randomized). They will then be asked to lie down again, get comfortable and have pressure 
measurements taken in the same way as before. 
No follow-up assessments will take place. 
6.5 
Definition of End of Trial  
Refer to section 15. 

 
Proning Pillow Study Protocol 
version 2.0  Date 11th January 
2022 
 
Page 14 of 25 
 
 
6.6 
Discontinuation/ Withdrawal of Participants from Study Treatment 
Each participant has the right to withdraw study at any time.  In addition, the investigator may 
discontinue a participant from the study at any time if the investigator considers it necessary 
for any reason including:  
• 
Non-compliant with the established protocol by moving excessively during the testing 
• 
Ineligibility (either arising during the study or retrospective having been overlooked at 
screening) 
• 
Significant protocol deviation 
• 
Significant non-compliance with study requirements 
• 
An adverse event which requires discontinuation of the study medication or results in 
inability to continue to comply with study procedures 
• 
Consent withdrawn 
Withdrawn participants will be replaced. 
The reason for withdrawal will be recorded in the CRF.   
If the participant is withdrawn due to an adverse event, the investigator will arrange for follow-
up visits or telephone calls until the adverse event has resolved or stabilised.   
 
6.7 
Source Data 
 
CRF entries will be considered source data if the CRF is the site of the original recording (e.g., 
there is no other written or electronic record of data). In this study the CRF will be used as the 
source document for weight, height, waist and chest size, and gender. 
 
 All documents will be stored safely in confidential conditions. On all study-specific documents, 
other than the signed consent, the participant will be referred to by the study participant code, 
not by name. 
7. 
TREATMENT OFSTUDY PARTICIPANTS 
7.1 
Description of Study Intervention(s) 
The standard pillows used in the ICU were the Sleepsia Bamboo Pillows, 508mm x 660.4mm 
x 127mm. Each pillow would be placed under the pelvis and chest.  

 
Proning Pillow Study Protocol 
version 2.0  Date 11th January 
2022 
 
Page 15 of 25 
 
 
The novel Proning Pillow System is a CE marked device manufactured by Putnam Health Co 
Ltd (Eastern wood Road, Langage Industrial Estate, Plympton, Devon, England, PL7 5ET) that 
includes two separate pillows for the chest and pelvis:  
Ortho Solutions chest pillow 800 x 300 x 180 mm 
Ortho Solutions Pelvic pillow 700 x 300 x 180 mm 
 
 
 
 
 
 
 
 
 
Chest pillow 
Pelvic pillow 
 
 
 
In each case, a pressure mat (BoditTrak Pro standard, CE 0413) will be placed on each pillow 
(chest and pelvis). The participant will lie on top of the pillows. The pressure mat will be 
connected to a laptop which will capture the data using the BodiTrak Pro software. 
  

 
Proning Pillow Study Protocol 
version 2.0  Date 11th January 
2022 
 
Page 16 of 25 
 
 
7.2 
Maintenance and storage of device 
The pillows, bed and pressure mat will be wiped clean with disinfectant wipes (approved by 
the Infection Prevention and Control Team) between participants.  The pillows will be stored 
in Aintree hospital.  
7.3  
Concomitant Medication (if applicable)  
N/A 
8. 
SAFETY REPORTING 
Definitions for DD, AE, ADE, SAE and SADE are in Section 19. 
8.1 Reporting of AE 
All AEs occurring during the study observed by the investigator or reported by the participant, 
whether or not attributed to the device under investigation, will be reported, without undue 
delay, to the Chief Investigator and LUHFT R&D and recorded on the hospital incident 
reporting system, in the source data (medical notes) and the CRF.  Any questions concerning 
adverse event reporting should be directed to the Chief Investigator in the first instance. 
8.2 Reporting of DDs/SAEs/SADEs/USADEs 
All SAEs, SADEs, and USADEs will be reported to the sponsor/legal representative, Chief 
Investigator and LUHFT R&D immediately; regardless of relationship to the device.  DDs that 
might have led to an SAE if suitable action had not been taken, intervention had not been 
made or if circumstances had been less fortunate are similarly reported. All SAEs, SADEs and 
USADEs will be recorded on the hospital incident reporting system, in the source data (medical 
notes) and the CRF. 
Reports of related and unexpected SAEs should be submitted to the Research Ethics 
Committee (REC)within 15 days of the Chief Investigator becoming aware of the event, using 
the SAE report form for non-CTIMPs published on the HRA website1. 
All reporting to LUHFT R&D should be by email to RGT@rlbuht.nhs.uk giving as much 
information about the incident as possible, and should be signed by the PI or Co-investigator. 
The LUHFT SADE reporting form should be used for LUHFT sponsored studies. 
 
1 https://www.hra.nhs.uk/approvals-amendments/managing-your-approval/safety-reporting/, accessed 
16/Aug/2021 

 
Proning Pillow Study Protocol 
version 2.0  Date 11th January 
2022 
 
Page 17 of 25 
 
 
The LUHFT R&D Department will undertake an initial review of the information and ensure it 
is reviewed by LUHFT. Events will be followed up until resolution, any appropriate further 
information will be sent by the research team in a timely manner. 
Reporting to the MHRA will be done in liaison with the Chief Investigator. 
8.3: Annual Reports 
In addition to the above reporting the Chief Investigator will submit once a year, throughout 
the trial, or on request a progress/safety report to the REC and R&D.  
9. 
STATISTICS 
9.1 
Description of Statistical Methods 
A model-based approach will be used to test the hypothesis. This approach considers 
complexities such as repeated measurements, unbalanced observations and determination of 
the magnitude of effects. The model incorporates the measured peak pressure for each 
participant at each anatomic location (chest and pelvis) and the two different pillow systems 
(new and standard).  
9.2 
The Number of Participants 
Based on the complexity of the model used to test the experimental hypotheses, and the fact 
that the sample size should be of the order of 10 times the number of parameters estimated 
by the model [Harrell], we estimate a sample size of 50 is required. 
9.3 
The Level of Statistical Significance and Model Validation 
Considering the small sample size and the complexity of the model, a significance level of 0.01 
will be considered for rejection of the null hypotheses of no difference between peak pressures, 
with the aim to control the false discovery rate [Harrell]. However, since it is generally 
recognised that statistical significance alone doesn’t necessarily provide a realistic picture of 
the underlying processes generating the data [Harrell], other measures of quality of the 
statistical inference will be reported, namely approximate confidence intervals, Akaike 
Information Criterion, and analysis of residuals. 
9.4 
Procedure for Accounting for Missing, Unused, and Spurious Data. 
The chosen statistical methods can be applied even with unbalanced observations (i.e. 
outcomes need not be observed for all possible combinations of the experimental factors pillow 
and position) [Pinheiro]. Due to the nature of the experimental design and the type of 

 
Proning Pillow Study Protocol 
version 2.0  Date 11th January 
2022 
 
Page 18 of 25 
 
 
measurements involved, no missing, unused, or spurious data are expected. 
9.6 
Procedures for Reporting any Deviation(s) from the Original Statistical Plan 
Any deviation(s) from the original statistical will be described and justified in protocol and/or in 
the final report, as appropriate. 
9.7 
Inclusion in Analysis 
All eligible participants 
10. 
DIRECT ACCESS TO SOURCE DATA/DOCUMENTS 
Direct access will be granted to authorised representatives from the sponsor, host institution 
and the regulatory authorities to permit trial-related monitoring, audits and inspections. 
11. 
QUALITY CONTROL AND QUALITY ASSURANCE PROCEDURES 
The study will be conducted in accordance with the current approved protocol, ICH GCP, 
relevant regulations and standard operating procedures.  
Regular monitoring will be performed according to ICH GCP. Data will be evaluated for 
compliance with the protocol and accuracy in relation to source documents. Following written 
standard operating procedures, the monitors will verify that the clinical trial is conducted and 
data are generated, documented and reported in compliance with the protocol, GCP and the 
applicable regulatory requirements.  
12. 
ETHICS 
12.1 
Declaration of Helsinki 
The Investigator will ensure that this study is conducted in accordance with the principles of the 
Declaration of Helsinki.  
12.2 
ICH Guidelines for Good Clinical Practice 
The Investigator will ensure that this study is conducted in full conformity with relevant 
regulations and with the ICH Guidelines for Good Clinical Practice R2 
12.3 
Approvals  
The protocol, informed consent form, participant information sheet and any proposed 
advertising material will be submitted to the Health Research Authority. Local approvals will be 
sought from participating NHS organisations and the sponsor.   

 
Proning Pillow Study Protocol 
version 2.0  Date 11th January 
2022 
 
Page 19 of 25 
 
 
The Chief Investigator will submit and, where necessary, obtain approval from the above parties 
for all substantial amendments to the original approved documents.    
12.4 
Participant Confidentiality 
The study staff will ensure that the participants’ anonymity is maintained.  The participants will 
be identified only by a participants ID number on the CRF and any electronic database.  All 
documents will be stored securely and only accessible by trial staff and authorised personnel. 
The study will comply with the Data Protection Act 2018 which requires data to be anonymised 
as soon as it is practical to do so.   
 
12.5 
Other Ethical Considerations 
N/A 
13. 
DATA HANDLING AND RECORD KEEPING 
Data will be processed under the terms of UK data protection law (including the UK General 
Data Protection Regulation (UK GDPR) and the Data Protection Act 2018). 
All study data will be entered on a password-protected Microsoft Excel spreadsheet.  Once all 
data has been captured, the spreadsheet will be locked as read-only to protect the integrity of 
the data.  
All pseudonymous data will be stored on a laptop and on the Clinical Engineering LUHFT 
departmental network.  
The participants will be identified by a study specific participants number and/or code in any 
database.  The name and any other identifying detail will NOT be included in any study data 
electronic file. A copy of the final published results of the study will be sent to the participants 
should they wish. 

 
Proning Pillow Study Protocol 
version 2.0  Date 11th January 
2022 
 
Page 20 of 25 
 
 
14. 
FINANCING AND INSURANCE 
LUHFT ICU will loan a set of pillows for this study. The pressure mats will be supplied by the 
Posture and Mobility Service in Bryn-y-Neuadd hospital. 
NHS bodies are legally liable for the negligent acts and omissions of their employees. If you 
are harmed whilst taking part in a clinical trial as a result of negligence on the part of a member 
of the study team this liability cover would apply. 
Non-negligent harm is not covered by the NHS indemnity scheme. LUHFT, therefore, cannot 
agree in advance to pay compensation in these circumstances. In exceptional circumstances 
an ex-gratia payment may be offered.  
15. 
END OF STUDY DEFINITION 
End of study definition would be when the set of number of participants have been recruited 
and completed all elements of the study and data has been analysed. 
 
16. 
PUBLICATION POLICY 
Authors will be defined as those who have made: 
• 
Substantial contributions to the conception or design of the work; or the acquisition, 
analysis, or interpretation of data for the work; AND 
• 
Drafting the work or revising it critically for important intellectual content; AND 
• 
Final approval of the version to be published; AND 
• 
Agreement to be accountable for all aspects of the work in ensuring that questions related 
to the accuracy or integrity of any part of the work are appropriately investigated and 
resolved. 
Contributors who have contributed materially to the paper but whose contributions do not 
justify authorship will be described clearly in acknowledgements 
17. 
ARCHIVING 
Following analysis, data will be fully anonymised then stored in electronic format in Clinical 
Engineering LUHFT departmental network for at least 15 years. The data will be stored for 
future ethically approved studies. Archiving will be in line with the sponsor’s Standard 
Operating Procedures.  

 
Proning Pillow Study Protocol 
version 2.0  Date 11th January 
2022 
 
Page 21 of 25 
 
 
18. 
REFERENCES 
Guérin, C. et al. Prone positioning in severe acute respiratory distress syndrome. N. Engl. J. 
Med. 368, 2159–2168 (2013). 
F. E. Harrell, Jr. Regression Modeling Strategies, 2nd edition. Springer, 2015. 
J. C. Pinehiro, D. M. Bates. Mixed-effects Models in S and S-Plus. Springer, 2000. 
 

 
Proning Pillow Study Protocol 
version 2.0  Date 11th January 
2022 
 
Page 22 of 25 
 
 
19. 
APPENDIX 
19.1 Definitions 
19.1.1 Device Deficiency (DD) 
This is the inadequacy of a medical device with respect to its identity, quality, durability, 
reliability, usability, safety or performance.  Device deficiencies include malfunction, use error 
and inadequate labelling. 
19.1.2 Adverse Event (AE): 
Any untoward medical occurrence, unintended disease or injury or any untoward clinical signs 
(including an abnormal laboratory finding) in subjects, users or other persons, whether or not 
related to the investigational medical device and whether anticipated or unanticipated. 
This includes events related to the investigational device or the comparator and events related 
to the procedures involved (any procedure in the study protocol).  For users or other persons, 
i.e. where the medical occurrence, unintended disease or injury is not in the subject, this 
definition is restricted to events related to the use of investigational medical devices or 
comparators. 
No potential AEs are identified. 
19.1.3: Adverse Device Effect (ADE) 
Adverse event related to the use of an investigation medical device.  This includes AEs 
resulting from insufficient or inadequate instructions for use, deployment, implantation, 
installation, or operation, or any malfunction of the investigational medical device.  This 
includes the comparator if the comparator is a medical device. 
All AEs judged by either the reporting medically qualified professional or the sponsor as having 
a reasonable suspected causal relationship to the device qualify as ADEs.  For guidance on 
causality assessment, refer to MEDDEV 2.7/3 Clinical Investigations: Serious Adverse Event 
Reporting Under Directive 90/385/EEC and 93/42/EEC.   
 
19.1.4: Serious Adverse Event (SAE):  
SAE is an adverse event that led to any of the following: 
• 
death  

 
Proning Pillow Study Protocol 
version 2.0  Date 11th January 
2022 
 
Page 23 of 25 
 
 
• 
foetal distress, foetal death or congenital abnormality or birth defect including 
physical or mental impairment.  
• 
serious deterioration in the health of the subject, users or other persons as defined by 
one or more of the following: 
o a life-threatening illness or injury 
o a permanent impairment of a body structure or a body function including 
chronic diseases  
o in-patient or prolonged hospitalisation 
o medical or surgical intervention to prevent life-threatening illness or injury, or 
permanent impairment to a body structure or a body function 
Planned hospitalisation for a pre-existing condition, or a procedure required by the Study 
Protocol, without serious deterioration in health, is not considered a serious adverse event. 
19.1.5: Serious Adverse Device Effects (SADE):  
Adverse device effect that has resulted in any of the consequences of a SAE.  This includes 
device deficiencies that might have led to a SAE if (a) suitable action had not been taken or 
(b) intervention had not been made or (c) if circumstances had been less fortunate.  These are 
handled under the SAE reporting system.All cases judged by either the reporting medically 
qualified professional or the sponsor.  
 
19.1.6: Unanticipated Serious Adverse Device Effect (USADE):  
Any serious adverse device effect which by its nature, incidence, severity or outcome has not 
been identified in the current risk assessment. 
 
 
19.2 Description of Statistical Methods 
Suggested statistical approach in more detail. 
A model-based approach to hypothesis testing will be applied. This allows incorporation of 
complexities such as repeated measurements, nested classification factors, unbalanced 
observations, and determination of the magnitude of effects [Harrell]. The chosen model 
belongs to the family of linear mixed-effects models [Pinheiro], and it is formulated as follows: 

 
Proning Pillow Study Protocol 
version 2.0  Date 11th January 
2022 
 
Page 24 of 25 
 
 
 
𝐲𝑖𝑗= 𝐗𝑖𝑗𝛃+ 𝐙𝑖,𝑗𝐛𝑖+ 𝐙𝑖𝑗𝑏𝑖𝑗+ 𝜖𝑖𝑗,      𝑖= 1, … , 𝑀,   𝑗= 1,2 
 
𝐛𝑖~𝑁(0, 𝛙1),   𝑏𝑖𝑗~𝑁(0, 𝜎2
2),   𝜖𝑖𝑗~𝑁(0, 𝜎2𝐈) 
 
where 𝐲𝑖𝑗 is the measured peak pressures for subject 𝑖 from a sample of size 𝑀, at anatomic 
location 𝑗 (corresponding to chest and pelvis.) The fixed-effects treatment contrast matrices 𝐗𝑖𝑗 
encode the experimental factor pillow type (new versus standard). 𝐙𝑖,𝑗 represents the design 
matrices of the level-1 random effects for subject 𝑖 on the measurements for anatomic location 
𝑗 within subject 𝑖. 𝐙𝑖𝑗 represents the design matrices of the level-2 random effects for anatomic 
location 𝑗 within subject 𝑖. The normally distributed 𝐛𝑖 are assumed to be independent for 
different 𝑖; and the normally distributed 𝑏𝑖𝑗 are assumed to be independent for different 𝑖 or 𝑗 
and to be independent from 𝐛𝑖; finally, the within-group errors 𝜖𝑖𝑗 (which represent all the 
variability which is not explained by the model) are assumed to be independent for different 𝑖 
or 𝑗 and to be independent from the random effects. The parameters to be estimated by the 
above model are represented by the 2-vector 𝛃, the variance 𝜎2
2, and the entries of the 2x2 
matrix 𝛙1 (it should be noted that since the latter is a covariance matrix which is forced to be 
positive definite by construction, only 2 entries need to be estimated.) The total number of 
parameters is therefore 5. 
19.2.1 The Number of Participants 
Due to the lack of available information in published sources to determine the effect sizes 
required for sample size calculation, and due to the complexity of the experimental design, no 
formal power analysis is possible.  
However, a heuristic approach will be applied [Harrell] based on the complexity of the model 
used to test the experimental hypotheses, namely that the sample size should be of the order 
of 10 times the number of parameters estimated by the model. With the previous definition of 
the model complexity, we estimate the sample size to be of the order of 𝑀= 50.  
19.2.2 The Level of Statistical Significance and Model Validation 
Considering the small sample size and the complexity of the model, a significance level of 0.01 
will be considered for rejection of the null hypotheses of no difference between peak pressures 
(as represented by parameter β2), with the aim to control the false discovery rate [Harrell]. 
However, since it is generally recognised that statistical significance alone doesn’t necessarily 
provide a realistic picture of the underlying processes generating the data [Harrell], other 

 
Proning Pillow Study Protocol 
version 2.0  Date 11th January 
2022 
 
Page 25 of 25 
 
 
measures of quality of the statistical inference will be reported, namely approximate confidence 
intervals, Akaike Information Criterion, and analysis of residuals. 
19.2.3 Procedure for Accounting for Missing, Unused, and Spurious Data. 
The chosen statistical methods can be applied even with unbalanced observations (i.e. 
outcomes need not be observed for all possible combinations of the experimental factors pillow 
and position) [Pinheiro]. Due to the nature of the experimental design and the type of 
measurements involved, no missing, unused, or spurious data are expected.