Robotic Prostatectomy Artificial Intelligence Low Pressure Pain Study Trial - "The Monitoring of Patients Outcomes Intraoperatively and Perioperatively Using the Airseal and Stryker Insufflator Undergoing Robotic Assisted Laparoscopic Prostatectomy at a Pressure and Stability of Pneumoperitoneum of 8 mmHg"
Phase: NA
Conditions: Prostate Cancer (Adenocarcinoma), Prostate Cancer (Post Prostatectomy), Prostate Cancer Surgery, Prostate Cancers, Prostate Neoplasm, Prostatectomy
Sponsor: East and North Hertfordshire NHS Trust

 
Protocol: Robotic Prostatectomy Artificial Intelligence Low Pressure Pain (RALP) Trial RD No: RD2024-
75 
Version [1.1] Date [20.01.2025] 
 
              
 
 
 
 Confidential 
 
 
 
Page 1 of 36 
 
 
 
 
 
 
 
 
 
 
 
       
 
 
 
 
              
Robotic Prostatectomy Artificial Intelligence Low Pressure 
Pain Study Trial  -  “The monitoring of patients outcomes 
intraoperatively and perioperatively using the Airseal and 
Stryker insufflator undergoing Robotic Assisted 
Laparoscopic Prostatectomy at a pressure and stability of 
pneumoperitoneum of 8 mmHg”. 
 
 
 
Short Title: Robotic Prostatectomy Artificial Intelligence 
Low Pressure Pain (RALP) Trial 
 
 
 
 
 
 
Protocol Reference/RD no: RD2024-75 
Version number: 1 
Version date: 18/11/2024 
Study Chief Investigator:  
Study Sponsor:  
IRAS ID: 346481 
 
 
 
 
This protocol has regard for the HRA guidance 
 
CONFIDENTIAL 
 
These comments are confidential and may not be communicated to any third party without permission 
from the Sponsor. 
 

 
Protocol: Robotic Prostatectomy Artificial Intelligence Low Pressure Pain (RALP) Trial RD No: RD2024-
75 
Version [1.1] Date [20.01.2025] 
 
              
 
 
 
 Confidential 
 
 
 
Page 2 of 36 
 
Robotic Prostatectomy Artificial Intelligence Low Pressure Pain Study Trial  -  “The 
monitoring of patients outcomes intraoperatively and perioperatively using the Airseal 
and Stryker insufflator undergoing Robotic Assisted Laparoscopic Prostatectomy at a 
pressure and stability of pneumoperitoneum of 8 mmHg”. 
 
Robotic Prostatectomy Artificial Intelligence Low Pressure Pain (RALP) Trial 
 
Protocol RD Number: 
RD2024-75 
IRAS ID:  
346481 
REC Number: 
 
ISRCTN Number: 
 
Date: 
18/11/2024 
Amended: 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
Protocol: Robotic Prostatectomy Artificial Intelligence Low Pressure Pain (RALP) Trial RD No: RD2024-
75 
Version [1.1] Date [20.01.2025] 
 
              
 
 
 
 Confidential 
 
 
 
Page 3 of 36 
 
Protocol Synopsis 
 
Study Title 
Robotic Prostatectomy Artificial Intelligence Low Pressure Pain Study 
Trial  -  “The monitoring of patients outcomes intraoperatively and 
perioperatively using the Airseal and Stryker insufflator undergoing 
Robotic Assisted Laparoscopic Prostatectomy at a pressure and 
stability of pneumoperitoneum of 8 mmHg”. 
Short Title 
Robotic Prostatectomy Artificial Intelligence Low Pressure Pain 
(RALP) Trial 
Type of Trial 
A prospective, randomized, controlled, open label, human clinical 
study designed to evaluate pain related to the use of the AirSeal® 
Insufflation System (AIS) vs a Stryker PneumoClear Insufflator for the 
management of pneumoperitoneum. 
Study Period 
Each subject will be enrolled in the study from day of consent until 
their standard of care 30-day, post-procedure, follow-up appointment. 
Objectives 
In this trial, 40 patients undergoing robotic prostatectomies will be 
randomised to have either the AIRSEAL® Insufflation System (AIS) or 
the Stryker PneumoClear Insufflator devices used to maintain 
pneumoperitoneum during surgery. Data relating to intra-operative 
and post-operative pain will be collected. This data will be used to 
identify any differences in outcomes between the two arms of the trial. 
 
The main aim of this feasibility study will be to inform the feasibility 
and design of a subsequent definitive full-scale trial. The feasibility 
trial will collect data about recruitment, study conduct, and 
assessment methods.  
 
Outcome measures 
The main aim of this feasibility study will be to inform the feasibility 
and design of a subsequent definitive full-scale trial. The feasibility 
trial will collect data about recruitment, study conduct, and 
assessment methods. The objectives of the feasibility are to  
• Assess recruitment rates  
• Evaluate whether the study can run in line with the study protocol  
• Identify the feasibility of collecting clinical data  
• Evaluate treatment-based adverse events, serious adverse events, 
anticipated adverse device effects, unanticipated adverse device 
effects and all device deficiencies and use errors, regardless of 
relationship to an adverse event  
• Estimate the likely magnitude of the effect of the intervention. To 
allow for estimation of the sample size for the full trial  
 
The subsequent large scale, multi-center trial following this feasibility 
trial will focus on severity of pain during and immediately after surgery 
in the recovery room and then by 6-hour increments, measured by a 0 
– 10 Numeric Rating Scale (NRS) and a PMD-200 nociception non-
invasive monitor as the primary outcome 
 
Secondary outcomes include: 

 
Protocol: Robotic Prostatectomy Artificial Intelligence Low Pressure Pain (RALP) Trial RD No: RD2024-
75 
Version [1.1] Date [20.01.2025] 
 
              
 
 
 
 Confidential 
 
 
 
Page 4 of 36 
 
 
Pre-Operative  
1. Pre-op vitals including height and weight  
2. Pre-op labs  
 
Intra-operative  
1. Insufflation Pressure  
2. Estimated blood loss  
3. Blood transfusion (intra-operative)  
4. Procedure time (initial incision to closure)  
5. Surgeon-determined need to increase IAP beyond “study pressure”  
6. Administration of transversus abdominis plane block  
7. Urine output  
8. Anesthetic/pain medication administration  
9. MedaSense PMD-200 monitor for pain documentation  
10. Intraoperative Peak Airway Pressure every 15 minutes  
11. Intraoperative End Tidal Carbon Dioxide (ETCO2) every 15 
minutes  
 
Post-Operative 
During hospital discharge, all subjects will be evaluated for incidence 
and severity of pain using a 0-10 numeric rating scale (NRS) and 
records of medication use and a PMD-200 monitor. These data will be 
captured in the Case Report Forms.  
 
Recovery room:  
1. Time in recovery room  
2. Post-op pain incidence and severity (abdominal) NRS  
3. Pain medications  
4. Post- op labs (CBC, Chem-7) per standard of care  
5. Vital signs 24 hr  
 
Discharge:  
1. Post-op pain incidence and severity (abdominal) NRS  
2. Presence or absence of postoperative nausea or vomiting  
3. Pain medications  
4. Length of hospital stay  
5. Pain Interference and Pain Intensity short form surveys  
6. Any complications that were observed. Post-operative 
complications through 30 days, reported using Clavien-Dindo 
Classification, including 30-day mortality  
7. Return to operating room within 24 hour  
8. Readmission to hospital within 30 days  
 
Classification, including 30-day mortality  
All Adverse Events (intra-operative and post-operative through 30 
days):  
1. Adverse Events  

 
Protocol: Robotic Prostatectomy Artificial Intelligence Low Pressure Pain (RALP) Trial RD No: RD2024-
75 
Version [1.1] Date [20.01.2025] 
 
              
 
 
 
 Confidential 
 
 
 
Page 5 of 36 
 
2. Serious Adverse Events  
3. Anticipated Adverse Device Effects  
4. Unanticipated Adverse Device Effects  
5  All device deficiencies and use errors, regardless of relationship to 
an adverse event 
Study Design and 
Methodology 
Patients under the care of the urology department at the Lister 
Hospital, Stevenage will be listed in clinic for a robotic prostatectomy. 
If patients meet the eligibility criteria for the trial, they will be 
approached and informed of the RALP clinical trial during their clinic 
consultation, by a member of the clinical team (likely a urological 
consultant).  
 
Patients will be provided with a patient information sheet informing 
them of the aims and methodology of the trial. Members of the 
research department will be able to answer any outstanding questions 
patients might have.  
 
Written informed consent will be obtained from eligible patients (n=40) 
willing to participate in the trial. If patients consent, their GP will 
subsequently be written to and informed of their involvement in the 
trial.  
 
Pre-Operative data collection:  
Within 30 days of a subject’s scheduled procedure, members of the 
research department at Lister hospital will obtain a medical history 
and record the subject’s demographic (age, race, sex and date of 
birth) and baseline information (height, weight, and systolic/diastolic 
blood pressure). Within 30 days prior to the planned procedure date, 
obtain serum blood tests per standard of care. These will typically 
include:  
• FBC • Renal function test • CRP  
This data, along with all subsequent trial related data will be 
anonymised and subsequently inputted into a database created by the 
Centre for Health Services and Clinical Research at the University of 
Hertfordshire.  
 
Preoperative Randomization:  
Randomization will be done electronically via a database which is 
facilitated by the University of Hertfordshire. Patients will be 
randomized 1:1 to either AIS (at 8 mmHg) or Stryker PneumoClear 
Insufflator Arm 1: AIRSEAL® Insufflation System (AIS) – 8 mmHg 
Arm 2: Stryker PneumoClear Insufflator - 8 mmHg. 
 
Methods and Procedure: 
Patients will undergo their robotic assisted prostatectomy with the use 
of either the AIRSEAL® Insufflation System (AIS) or Stryker 
PneumoClear Insufflator depending on which arm of the trial they 
have been randomized to. Patients will be blinded to the intervention 

 
Protocol: Robotic Prostatectomy Artificial Intelligence Low Pressure Pain (RALP) Trial RD No: RD2024-
75 
Version [1.1] Date [20.01.2025] 
 
              
 
 
 
 Confidential 
 
 
 
Page 6 of 36 
 
(AIRSEAL® Insufflation System (AIS) or Stryker PneumoClear 
Insufflator). Both systems are commonly used devices across many 
NHS trusts and there is currently no evidence comparing patient 
outcomes between use of the two devices.  
 
This study will be conducted at one site by one surgeon performing 40 
total procedures. Study subjects will be prepared for surgery per 
standard institutional policy and practice. Standard operative 
procedures will be followed.  
 
Case Report Forms will be also be used to collect data relating to pre-
operative, intra-operative and post-operative outcomes. This data will 
relate to outcomes such as intra-operative pain, post operative pain 
scores, medication use, duration of hospital stay, presence of nausea 
or vomiting etc...  
 
The final patient follow up will be in a clinic appointment 30 days 
following their operation. Ongoing post-operative outcomes will be 
assessed (pain scores, medication use, adverse events etc...). 
 
Data will be inputted on the database which is subsequently 
processed and statistically analysed and reviewed. Differences in 
outcomes between the two arms of the trial may be identified.  
 
Once the aforementioned data has been processed and reviewed, 
results may be published and also distributed to those trial 
participants who wished to receive ongoing information and results 
from the trial.  
 
The outcomes of this research will be used to inform future research 
such as a full scale trial with a larger number of patients and larger 
volume of data 
Indication 
We hope to use results from this initial single-center RCT to inform 
future, larger scale, multi-center research on this topic. Research into 
this field has the potential to benefit patients by reducing intra and 
post-operative pain, reduce reliance on pain medications and reduce 
lengths of hospital admissions. This is especially important given 
there is a global issue with long term analgesia abuse. 
Planned Trial sites 
Single site – Lister Hospital, Corey Mills Lane, Stevenage 
No of Participants 
40 
Eligibility Criteria 
Inclusion criteria: 
1.Patient indicated for non-emergent robotic Prostatectomy surgery 
2.Patients (or appropriate legal representatives) able to provide 
written informed consent to participate in the study  
3.Males, aged 18 to 75 years  
4.Have no significant psychopathology that could limit the subject's 
ability to understand the procedure, comply with medical, surgical, 
and/or behavioural recommendations and office visits  

 
Protocol: Robotic Prostatectomy Artificial Intelligence Low Pressure Pain (RALP) Trial RD No: RD2024-
75 
Version [1.1] Date [20.01.2025] 
 
              
 
 
 
 Confidential 
 
 
 
Page 7 of 36 
 
5.Are American Society of Anaesthesiologists (ASA) Class I, II, or III); 
 
Exclusion criteria: 
1.Patient participation in a different investigational clinical study within 
90 days before screening and for the duration of this trial (unless 
previously approved by the investigator and Sponsor);  
2.Patients requiring any surgical procedure in addition to 
Prostatectomy and or / Pelvic Lymph node dissection  
3.Previous pelvic surgery or previous malabsobtion or restrictive 
procedures performed for the treatment of obesity  
4.Inability to provide informed consent  
5.Unable or unwilling to attend follow-up visits and examinations  
6.Uncontrolled hypertension (=/>Systolic: 180 mmHg/Diastolic: 120 
mmHg) and/or diabetes mellitus (Blood sugar level: >200 mg/dL)  
7.Patients who fall into American Society of Anesthesiologists (ASA) 
Class ≥ IV  
8.History of chronic alcohol or drug abuse within 2 years of the 
screening visit  
9.Chronic renal failure or on dialysis  
10.Significant complicating medical history or immunocompromised 
11.History or presence of pre-existing autoimmune connective tissue 
disease, e.g., systemic lupus erythematosus or scleroderma 
12.Immunocompromised such as that resulting from chronic oral 
steroid use, chemotherapeutic agents, or immune deficiency 
disorders;  
13.Any medical condition which precludes compliance with the study 
14.Subjects with any other clinically significant unstable medical 
disorder, life threatening disease, or conditions that, in the opinion of 
the investigator, may jeopardize the subject's well-being and/or the 
soundness of this clinical study or which would contra-indicate a 
surgical procedure.  
15.Previous or current history of being on regular analgesia / pain 
killers 
Treatment 
Robotic assisted prostatectomy using either the AIRSEAL® 
Insufflation System (AIS) or Stryker PneumoClear Insufflator. 
Assessment 
Schedule 
Patients initially assessed for trial eligibility in outpatient urology clinics 
where they are approached and informed about the trial. If a patient 
consents to take part in the trial then they will have their pre-operative 
assessment within 30 days of their planned robotic prostatectomy.  
Statistical 
Methodology and 
analysis 
Data analysis will be undertaken by Professor Neil Spencer at the 
Department of Applied Statistics at the University of Hertfordshire. Full 
details of the data analysis plan can be found in section 7.3 of the 
protocol. 
 
 
 
 
 

 
Protocol: Robotic Prostatectomy Artificial Intelligence Low Pressure Pain (RALP) Trial RD No: RD2024-
75 
Version [1.1] Date [20.01.2025] 
 
              
 
 
 
 Confidential 
 
 
 
Page 8 of 36 
 
 
 
 
 
 

 
 
Protocol: Robotic Prostatectomy Artificial Intelligence Low Pressure Pain (RALP) Trial RD No: XXXX 
 
 
 
 
 
Version [1.1] Date [18.11.2024] 
 
              
 
 
 
 Confidential 
Page 9 of 36 
 
 
Study Glossary 
 
Commonly used abbreviations 
 
AE 
Adverse Event 
CI 
Chief Investigator 
CRF 
Case Report Form 
CRO 
Contract Research Organisation 
DMC 
Data Monitoring Committee 
GAfREC 
Governance Arrangements for NHS Research Ethics 
GCP 
Good Clinical Practice  
GP 
General Practitioner  
HRA 
Health Research Authority 
ICF 
Informed Consent Form 
ISF 
Investigator Site File 
ISRCTN 
International Standard Randomised Controlled Trials Number     
Main REC 
Main Research Ethics Committee 
NHS R&D 
National Health Service Research & Development   
NIHR 
National Institute for Health Research 
NIMP 
Non-Investigational Medicinal Product 
PI 
Principal Investigator 
PIS 
Participant Information Sheet 
QA 
Quality Assurance 
QC 
Quality Control 
RCT 
Randomised Control 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  
WHO                                                    World Health Organisation

 
Protocol: Robotic Prostatectomy Artificial Intelligence Low Pressure Pain (RALP) Trial RD No: RD2024-75 
Version [1.1] Date [20.01.2025] 
 
              
 
 
 
 Confidential 
 
 
 
Page 10 of 36 
 
 
Table of Contents 
PAGE 
NO. 
Title Page  
Protocol Signature Page 
Trial Administration 
Protocol Synopsis 
Study Glossary 
  
 
 
 
 
 
 
 
1. INTRODUCTION 
1.1 Background 
1.2 Preclinical/Clinical Data 
1.3 Rationale 
2. STUDY OBJECTIVES AND DESIGN 
2.1 Objectives 
2.1.1 Primary objective 
2.1.2 Secondary objectives 
2.2 Endpoints/outcomes 
2.2.1 Primary Endpoint/outcome 
2.2.2 Secondary Endpoint/outcome 
2.3 Study Design 
 
2.3.1 Number of subjects 
 
2.3.2 Study Duration 
 
2.3.3 End of Study 
3. SUBJECT SELECTION AND RECRUITMENT  
3.1 Inclusion Criteria 
3.2 Exclusion Criteria 
3.3 Subject Recruitment and Screening 
3.4 Randomisation Procedure 
4. SUBJECT  WITHDRAWAL 
4.1 General Withdrawal Criteria 
5. STUDY PROCEDURES AND SCHEDULE OF ASSESSMENTS 
5.1 Informed consent 
5.2 Trial Procedures by Visit 
5.3 Screening and Baseline assessments 
5.4 Study assessments and procedures 
5.5 Follow up  
5.6 End of study procedures  
6. SAFETY REPORTING  
6.1 Definitions 
 
 6.1.1 Adverse Event (AE) 
 
 6.1.2 Serious Adverse Event (SAE) 
                         6.1.3 Disease related Events/outcomes NOT qualifying as SAEs 
 
 6.1.4 Pre existing conditions 
6.2 Investigator Assessments 
6.2.1 Seriousness 
6.2.2 Causality 
 
 
6.2.3 Expectedness 
6.3 Reporting of AEs and SAEs 
 
 
6.3.1 Pregnancy 
 
 
6.3.2 Notification Procedure 
 
 
6.3.3 Medical Monitoring 
 
 
 
 
 
 
 
 
 
 

 
Protocol: Robotic Prostatectomy Artificial Intelligence Low Pressure Pain (RALP) Trial RD No: RD2024-75 
Version [1.1] Date [20.01.2025] 
 
              
 
 
 
 Confidential 
 
 
 
Page 11 of 36 
 
 
 
6.3.4 Hospitalisation, Prolonged Hospitalisation or Surgery 
 
 
6.3.5 Post study AEs 
 
 
6.3.6 Abnormal Laboratory values 
 
 
6.3.7 Lack of efficacy 
 
 
6.3.8 New Cancers 
 
 
6.3.9 Deaths 
7. STATISTICS AND DATA ANALYSIS 
7.1 Sample Size determination 
7.2 Statistic Methods 
8. DATA HANDLING AND RECORD KEEPING 
8.1 Confidentiality 
8.2 Source Documents 
8.3 Case Report Form 
8.4 Data handling and record keeping 
8.5 Records Retention 
9. STUDY MONITORING, AUDITING AND INSPECTING 
9.1 Study Monitoring Plan 
9.2 Auditing and Inspecting 
9.3 Source Data Verification  
      10. REGULATORY OBLIGATIONS AND COMPLIANCE 
10.1 Protocol compliance 
10.2 Notification of Serious Breaches to GCP and/or the protocol  
      11. STUDY FINANCES 
11.1 Funding Source 
11.2 Conflict  
       14. INDEMNITY 
       15. PUBLICATION PLAN 
        
APPENDICES 
Appendix 1 – Patient Information Leaflet  
Appendix 2 – Informed Consent Document 
Appendix 3 – GP letter 
 
 
 

 
Protocol: Robotic Prostatectomy Artificial Intelligence Low Pressure Pain (RALP) Trial RD No: RD2024-75 
Version [1.1] Date [20.01.2025] 
 
              
 
 
 
 Confidential 
 
 
 
Page 12 of 36 
 
Content 
 
1 INTRODUCTION 
 
1.1 Background and Rationale 
 
Rapid advances in minimally invasive surgical techniques drive continual technological 
improvements in surgical tools and equipment.  The benefits of laparoscopic surgery in 
terms of reduced complications, minimally invasiveness, patient comfort and reduced 
recovery time have been well established to the point that laparoscopic surgery is now the 
standard of care for procedures such as radical prostatectomies.   
Laparoscopic surgical technique depends upon the establishment of pneumoperitoneum 
through insufflation of the abdomen in order to achieve sufficient working space, visualization 
of target organs and tissue, and surgical access.  Insufflation and surgical access are 
achieved through the use of trocars and systems that pump CO2 into the abdominal cavity 
during the duration of surgery.  Conventional trocars include a mechanical rubber valve or 
seal that minimizes the loss of gas pressure. 
The AirSeal® System consists of an insufflation, filtration, and recirculation system (AirSeal® 
iFS), a triple lumen filtered tube set, and a valve free trocar (AirSeal® Access Port). The 
device enables peritoneal access with a novel mechanism to maintain pneumoperitoneum 
without a mechanical seal.  Specifically, the AirSeal® System creates a pressure barrier 
within the proximal housing of the cannula which acts as an invisible seal to maintain 
pneumoperitoneum during the course of surgery.  It utilizes a re-circulation and filtration 
control unit (AirSeal® iFS) designed specifically for the AirSeal® Access Port to create and 
maintain the pressure barrier.   
The AirSeal® System has applications in abdominal minimally invasive surgical procedures 
to establish a path of entry for laparoscopic instruments. The system provides high flow 
insufflation, stable pneumoperitoneum, and further limits loss of intra-abdominal pressure 
compared with conventional systems (source). 
The insufflation and recirculation system (AirSeal® iFS) are reusable and the AirSeal® 
Access Port and triple lumen filtered tube set are designed as single patient use devices. 
The 1st generation AirSeal® System received FDA 510(k) clearance in 2007 and the current 
system received FDA 510(k) Clearance in May 2011. Since that time, the AirSeal™ system 
has been used routinely in centers throughout the United States and UK. Initial evidence in 
the literature has reported that the use of the AirSeal System results in a reduction of 
operative time, CO2 consumption, CO2 elimination, and CO2 absorption. Additionally, the 
AirSeal was reported to maintain the stability of pneumoperitoneum better than Stryker’s 
PneumoSure and Storz’s THERMOFLATOR insufflators when challenged with leakage and 
suction in a lab-based study. There is, however, a lack of in vivo evidence investigating intra-
operative and post-operative pain when comparing two insufflators that are readily available 
on the market and are already in common use across various NHS Trusts (AirSeal and 
Stryker PneumoSure). 

 
Protocol: Robotic Prostatectomy Artificial Intelligence Low Pressure Pain (RALP) Trial RD No: RD2024-75 
Version [1.1] Date [20.01.2025] 
 
              
 
 
 
 Confidential 
 
 
 
Page 13 of 36 
 
This study is designed to evaluate post-operative pain in relation to the use of the AirSeal 
Insufflation System (AIS) versus Stryker PneumoClear Insufflator.  The study is 
hypothesised to demonstrate superiority of the AIS during laparoscopic/robotic surgery in 
relation to the degree of post-operative abdominal pain.  In addition to this primary endpoint, 
additional key effectiveness and safety outcomes will be evaluated.  These outcomes include 
ease of anesthesia management, recovery time, time to hospital discharge, and additional 
safety outcomes including any insufflation device related complications.   
 
2 STUDY OBJECTIVES AND DESIGN 
 
2.1 Objectives 
 
2.1.1 Primary objective:  
 
The main aim of this feasibility study will be to inform the feasibility and design of a subsequent 
definitive full-scale trial. The feasibility trial will collect data about recruitment, study conduct, 
and assessment methods. The objectives of the feasibility are to  
• Assess recruitment rates  
• Evaluate whether the study can run in line with the study protocol  
• Identify the feasibility of collecting clinical data  
• Evaluate treatment-based adverse events, serious adverse events, anticipated adverse 
device effects, unanticipated adverse device effects and all device deficiencies and use errors, 
regardless of relationship to an adverse event  
• Estimate the likely magnitude of the effect of the intervention. To allow for estimation of the 
sample size for the full trial  
 
The subsequent large scale, multi-center trial following this feasibility trial will focus on severity 
of pain during and immediately after surgery in the recovery room and then by 6-hour 
increments, measured by a 0 – 10 Numeric Rating Scale (NRS) and a PMD-200 nociception 
non-invasive monitor as the primary outcome. Here it is hypothesized that the outcomes such 
as intra and post-operative pain in the AirSeal Insufflation System (AIS) arm of the trial will be 
superior to the Stryker PneumoClear Insufflator arms of the trial.  
 
2.1.2 Secondary objectives: 
 
To confirm the feasibility in collecting data relating to the following secondary 
outcomes: 
Pre-Operative  
1. Pre-op vitals including height and weight  
2. Pre-op labs  
 
Intra-operative  
1. Insufflation Pressure  
2. Estimated blood loss  

 
Protocol: Robotic Prostatectomy Artificial Intelligence Low Pressure Pain (RALP) Trial RD No: RD2024-75 
Version [1.1] Date [20.01.2025] 
 
              
 
 
 
 Confidential 
 
 
 
Page 14 of 36 
 
3. Blood transfusion (intra-operative)  
4. Procedure time (initial incision to closure)  
5. Surgeon-determined need to increase IAP beyond “study pressure”  
6. Administration of transversus abdominis plane block  
7. Urine output  
8. Anesthetic/pain medication administration  
9. MedaSense PMD-200 monitor for pain documentation  
10. Intraoperative Peak Airway Pressure every 15 minutes  
11. Intraoperative End Tidal Carbon Dioxide (ETCO2) every 15 minutes  
 
Post-Operative 
During hospital discharge, all subjects will be evaluated for incidence and severity of 
pain using a 0-10 numeric rating scale (NRS) and records of medication use and a 
PMD-200 monitor. These data will be captured in the Case Report Forms.  
 
Recovery room:  
1. Time in recovery room  
2. Post-op pain incidence and severity (abdominal) NRS  
3. Pain medications  
4. Post- op labs (CBC, Chem-7) per standard of care  
5. Vital signs 24 hr  
 
Discharge:  
1. Post-op pain incidence and severity (abdominal) NRS  
2. Presence or absence of postoperative nausea or vomiting  
3. Pain medications  
4. Length of hospital stay  
5. Pain Interference and Pain Intensity short form surveys  
6. Any complications that were observed. Post-operative complications through 30 
days, reported using Clavien-Dindo Classification, including 30-day mortality  
7. Return to operating room within 24 hour  
8. Readmission to hospital within 30 days  
 
Classification, including 30-day mortality  

 
Protocol: Robotic Prostatectomy Artificial Intelligence Low Pressure Pain (RALP) Trial RD No: RD2024-75 
Version [1.1] Date [20.01.2025] 
 
              
 
 
 
 Confidential 
 
 
 
Page 15 of 36 
 
All Adverse Events (intra-operative and post-operative through 30 days):  
1. Adverse Events  
2. Serious Adverse Events  
3. Anticipated Adverse Device Effects  
4. Unanticipated Adverse Device Effects  
5  All device deficiencies and use errors, regardless of relationship to an adverse event 
 
 
2.2 Endpoints/outcomes 
 
2.2.1 Primary Endpoints/outcomes: 
 
As this is primarily a feasibility trial, the primary endpoint will have been achieved once all 
intra-operative and post-operative pain related data (including the 30 day post-op outcomes) 
has been collected and analysed. This data may or may not show a statistically significant 
difference in patient’s pain when comparing the the AirSeal Insufflation System (AIS) and the 
Stryker PneumoClear Insufflators (conventional insufflator system - CIS). 
The hypotheses for the primary endpoint of an 11-point NRS abdominal pain score are as 
follows: 
Null hypothesis H0: mean AIS pain score ≥ mean CIS pain score 
Alternative hypothesis Ha: mean AIS pain score < mean CIS pain score 
A Mixed Model Repeated Measures (MMRM) analysis encompassing the multiple in-hospital 
pain scores per subject will be performed to compare the AIS and CIS groups.  Since a 
portion of the subjects will report no pain, the data will be analyzed primarily in the rank 
transformed scale and secondarily in the regular scale. 
 
2.2.2 Secondary Endpoints/outcomes:  
 
The complete collection of all data relating to the secondary outcomes. This data is grouped 
into sub-categories including, pre-operative, intra-operative, post-operative, recovery room, 
discharge and classification, including 30-day mortality. See section 2.1.2 for further 
information. 
 
2.3 Study Design 
 
A prospective, randomized, controlled single-center clinical study designed to evaluate post-
operative pain related to the use of the AirSeal® Insufflation System (AIS) and Stryker 
PneumoClear Insufflator for the management of pneumoperitoneum.  Subjects will be 
randomized in a 1:1 treatment device to control ratio into one of two (2) different study arms: 
Arm 1: AIRSEAL® Insufflation System (AIS) – 8 mmHg 
Arm 2: Stryker PneumoClear Insufflator (conventional insufflator system) 
The study is designed and powered to demonstrate superiority of the AIS over CIS in terms 
of post-operative abdominal pain. 
Secondary outcome measures include procedure time, length of recovery room stay, length 
of hospital stay, number of times insufflator settings are adjusted and severity of 

 
Protocol: Robotic Prostatectomy Artificial Intelligence Low Pressure Pain (RALP) Trial RD No: RD2024-75 
Version [1.1] Date [20.01.2025] 
 
              
 
 
 
 Confidential 
 
 
 
Page 16 of 36 
 
postoperative nausea/vomiting.  These outcomes will be evaluated in a qualified population 
undergoing robotic prostatectomy. 
 
Patients under the care of the urology department at the Lister Hospital, Stevenage will be 
listed in clinic for a robotic prostatectomy. If patients meet the eligibility criteria for the trial, 
they will be approached and informed of the RALP clinical trial during their clinic 
consultation, by a member of the clinical team (likely a urological consultant). Patients will be 
provided with a patient information sheet informing them of the aims and methodology of the 
trial. Members of the research department will be able to answer any outstanding questions 
patients might have. 
 
Written informed consent will be obtained from eligible patients (n=40) willing to participate in 
the trial. If patients consent, their GP will subsequently be written to and informed of their 
involvement in the trial. 
 
Pre-Operative data collection: 
Within 30 days of a subject’s scheduled procedure, members of the research department at 
Lister hospital will obtain a medical history and record the subject’s demographic (age, race, 
sex and date of birth) and baseline information (height, weight, and systolic/diastolic blood 
pressure). Within 30 days prior to the planned procedure date, obtain serum blood tests per 
standard of care. These will typically include: 
• FBC 
• Renal function test 
• CRP 
This data, along with all subsequent trial related data will be anonymised and subsequently 
inputted into a database created by the Centre for Health Services and Clinical Research at 
the University of Hertfordshire.  
 
Preoperative Randomization: 
Randomization will be done electronically via a database which is facilitated by the University 
of Hertfordshire. Patients will be randomized 1:1 to either AIS (at 8 mmHg) or Stryker 
PneumoClear Insufflator. 
Arm 1: AIRSEAL® Insufflation System (AIS) – 8 mmHg 
Arm 2: Stryker PneumoClear Insufflator - 8 mmHg 
 
Methods and Procedure 
Patients will undergo their robotic assisted prostatectomy with the use of either the 
AIRSEAL® Insufflation System (AIS) or Stryker PneumoClear Insufflator depending on 
which arm of the trial they have been randomized to. Patients will be blinded to the 
intervention (AIRSEAL® Insufflation System (AIS) or Stryker but it is not feasible to blind the 
surgeon in the trial. 
 
 
This study will be conducted at one site by one surgeon performing 40 total procedures. 
Study subjects will be prepared for surgery per standard institutional policy and practice. 
Standard operative procedures will be followed.  
 
Case Report Forms will be also be used to collect data relating to pre-operative, intra-
operative and post-operative outcomes. This data will relate to outcomes such as intra-

 
Protocol: Robotic Prostatectomy Artificial Intelligence Low Pressure Pain (RALP) Trial RD No: RD2024-75 
Version [1.1] Date [20.01.2025] 
 
              
 
 
 
 Confidential 
 
 
 
Page 17 of 36 
 
operative pain, post operative pain scores, medication use, duration of hospital stay, 
presence of nausea or vomiting etc... The final patient follow up will be in a clinic 
appointment 30 days following their operation. Ongoing post-operative outcomes will be 
assessed (pain scores, medication use, adverse events etc...). 
 
Data will be inputted on the database which is subsequently processed and statistically 
analysed and reviewed. Differences in outcomes between the two arms of the trial may be 
identified.  
 
Once the aforementioned data has been processed and reviewed, results may be published 
and also distributed to those trial participants who wished to receive ongoing information and 
results from the trial. 
 
The outcomes of this research will be used to inform future research such as a full scale trial 
with a larger number of patients and larger volume of data. 
 
  
 
2.3.1 Number of subjects 
 
40 patients. 
 
2.3.2 Study Duration 
 
Each subject will be enrolled in the study from day of consent until their standard of care 
30-day, post-procedure, follow-up appointment. It is expected that this will take up to 12 
month to commence and complete with follow up 
 
2.3.3 End of Study 
 
End of study is defined as the point at which all 40 patients involved in the trial have 
undergone, and completed their 30 day post-operative follow up.  At this point there is no 
further follow up or data collection required for study participants. 
 
The sponsor will inform the REC within 90 days of the ‘end of trial’ that the study has 
closed. 
 
Following the submission of end of trial notification to the REC, the sponsor should ensure 
that end of trial report is submitted within 12 months of this notification. 
 
In circumstances of early termination of the trial or temporary halt by the sponsor, the 
sponsor will notify the REC within 15 days of the decision and a detailed, written 
explanation for the termination/halt will be given. 
 
 
3    SUBJECT SELECTION AND RECRUITMENT  
 
3.1 Inclusion Criteria 
 

 
Protocol: Robotic Prostatectomy Artificial Intelligence Low Pressure Pain (RALP) Trial RD No: RD2024-75 
Version [1.1] Date [20.01.2025] 
 
              
 
 
 
 Confidential 
 
 
 
Page 18 of 36 
 
1.Patient indicated for non-emergent robotic Prostatectomy surgery 
2.Patients (or appropriate legal representatives) able to provide written informed consent to 
participate in the study  
3.Males, aged 18 to 75 years  
4.Have no significant psychopathology that could limit the subject's ability to understand the 
procedure, comply with medical, surgical, and/or behavioural recommendations and office 
visits  
5.Are American Society of Anaesthesiologists (ASA) Class I, II, or III);  
 
3.2 Exclusion Criteria 
 
1.Patient participation in a different investigational clinical study within 90 days before 
screening and for the duration of this trial (unless previously approved by the investigator 
and Sponsor);  
2.Patients requiring any surgical procedure in addition to Prostatectomy and or / Pelvic 
Lymph node dissection  
3.Previous pelvic surgery or previous malabsobtion or restrictive procedures performed for 
the treatment of obesity  
4.Inability to provide informed consent  
5.Unable or unwilling to attend follow-up visits and examinations  
6.Uncontrolled hypertension (=/>Systolic: 180 mmHg/Diastolic: 120 mmHg) and/or diabetes 
mellitus (Blood sugar level: >200 mg/dL)  
7.Patients who fall into American Society of Anesthesiologists (ASA) Class ≥ IV  
8.History of chronic alcohol or drug abuse within 2 years of the screening visit  
9.Chronic renal failure or on dialysis  
10.Significant complicating medical history or immunocompromised 11.History or presence 
of pre-existing autoimmune connective tissue disease, e.g., systemic lupus erythematosus or 
scleroderma 12.Immunocompromised such as that resulting from chronic oral steroid use, 
chemotherapeutic agents, or immune deficiency disorders;  
13.Any medical condition which precludes compliance with the study 14.Subjects with any 
other clinically significant unstable medical disorder, life threatening disease, or conditions 
that, in the opinion of the investigator, may jeopardize the subject's well-being and/or the 
soundness of this clinical study or which would contra-indicate a surgical procedure.  
15.Previous or current history of being on regular analgesia / pain killers 
 
3.3 Subject Recruitment and Screening 
 
Potential participants in this trial will be identified when seen in their routine outpatient 
urology clinic appointment. During this clinic appointment patients will be being listed for a 
robotic prostatectomy. If patients are considered to meet the eligibility criteria for the trial, 
they will subsequently be approached and invited onto the trial. The identification process 
will be carried out by a member of the urology clinical team at Lister hospital. 
 
3.4 Randomisation Procedure  
 
Randomisation will be done electronically via an electronic   database which is facilitated by 
the University of Hertfordshire. Patients will be randomized 1:1 to either AIS (at 8 mmHg) or 
Stryker PneumoClear Insufflator Arm 1: AIRSEAL® Insufflation System (AIS) – 8 mmHg Arm 

 
Protocol: Robotic Prostatectomy Artificial Intelligence Low Pressure Pain (RALP) Trial RD No: RD2024-75 
Version [1.1] Date [20.01.2025] 
 
              
 
 
 
 Confidential 
 
 
 
Page 19 of 36 
 
2: Stryker PneumoClear Insufflator - 8 mmHg. 
  
 
4    SUBJECT WITHDRAWAL  
 
Patients will be withdrawn from the trial and will not receive the intervention (AIRSEAL® 
Insufflation System (AIS) or Stryker PneumoClear Insufflator) if they no longer meet the 
eligibility criteria. If a patient no longer meets the inclusion criteria or meets the exclusion 
criteria in the time period between enrollment into the trial and the intervention date (day of 
robotic prostatectomy), they will then be withdrawn from the trial. 
 
 
5   STUDY PROCEDURES AND SCHEDULE OF ASSESSMENTS 
 
5.1 Informed consent 
 
All subjects for this study will be provided with a patient information sheet and a consent 
form describing this study and providing sufficient information for subjects to make an 
informed decision about their participation in this study.  This consent form will be submitted 
with the protocol for review and approval by the REC/HRA for the study.  The formal consent 
of a subject, using the REC/HRA -approved consent form, must be obtained before that 
subject is submitted to any study procedure.  This consent form must be signed by the 
subject or legally acceptable surrogate, and the investigator-designated research 
professional obtaining the consent.  
 
Consent to participate in the study will be obtained by a member of the urology research 
team that is qualified to take consent. This person will be GCP trained, suitably qualified and 
experienced, and have been delegated this duty by the CI/PI on the delegation log. This will 
most commonly be done by Professor Nikhil Vasdev. 
 
It is the responsibility of the Investigator, or a person delegated by the Investigator to obtain 
written informed consent from each subject prior to participation in the trial, following 
adequate explanation of the aims, methods, anticipated benefits and potential hazards of the 
study.  
 
Adequate time must be given for consideration by the patient before taking part. The PI must 
record when the patient information sheet (PIS) has been given to the patient. [If the amount 
of time between the PIS being given and the date of consent is less than 24 hours, the PI 
needs to explain the rationale for this].  
 
The Investigator or designee will explain the patients are under no obligation to enter the trial 
and that they can withdraw at any time during the trial, without having to give a reason. 
 
No study procedures will be conducted prior to taking consent from the participant. Consent 
will not denote enrolment into trial.  
 
A copy of the signed Informed Consent form will be given to the participant.  The original 
signed form will be retained at the study site and a copy placed in the medical notes. 

 
Protocol: Robotic Prostatectomy Artificial Intelligence Low Pressure Pain (RALP) Trial RD No: RD2024-75 
Version [1.1] Date [20.01.2025] 
 
              
 
 
 
 Confidential 
 
 
 
Page 20 of 36 
 
 
If new safety information results in significant changes in the risk/benefit assessment, the 
consent form will be reviewed and updated if necessary and subjects will be re-consented as 
appropriate 
 
Where the participant population is likely to include a significant proportion of participants 
who cannot read or write, require translators or have cognitive impairment, appropriate 
alternative methods for supporting the informed consent process should be employed. 
Details of alternative methods for supporting informed consent should be provided. This may 
include allowing a witness to sign on a participant’s behalf (in the case of problems with 
reading or writing), or allowing someone to date the form on behalf of the participant, or 
providing Participant Information Sheets in other languages or in a format easily understood 
by the participant population (in the case of minors or cognitive impairment). 
 
Patients lacking capacity will not be recruited into the study. 
 
 
 
5.2 Trial Procedures by Visit 
 
Area of Activity 
Specific Activity                                                                         Undertaken by                                        
Patient approached and invited to participate in study 
Patients seen in Urology outpatient clinic at 
Lister Hospital and listed for a robotic 
prostatectomy. Patient will be approached here 
and informed about the study and given a PIS.  
Local Urology Consultant at ENHT 
(East and North Hertfordshire NHS 
Trust). 
Consent Processes 
Written informed consent taken from patient 
agreeing to participate in the study. 
Member of the Local Urology 
research team able to take consent. 
Study Set Up 
Patients (n=40)  randomised to two arms. 
Patient's baseline characteristics and pre-
operative data collected, anonymised and 
stored on encrypted Trust IT systems. Stryker 
PneumoClear Insufflator purchased/rented in 
order to compare to Airseal infufflator. 
Member of the Local Urology 
research team. 
Study Monitoring 
Study commences where patients undergo their 
radical prostatectomy using one of the two 
insufflators being randomised to them during 
the trial. Pre-operative, intra-operative and 
post-operative data relating to the primary and 
secondary outcomes of the study collected, 
anonymised and stored on encrypted Trust IT 
systems.  
Members of the local clinical team 
involved in pre-op, intra-op and 
post-operative care. Ranging from 
Research nurses and doctors, to 
consultant urological surgeons, the 
surgical team and the nursing team.  
Study Close Down 
Study data is sent to the University of 
Hertfordshire's Department of Applied Statistics 
where is is statistically analysed . Results are 
returned to the clinical research team to 
interpret and publish. Adverse events within 30 
days post-operation will be documented and 
published. Patients will be followed up for a 
total of 12 months whereafter the trial data will 
be archived.  
University of Hertfordshire 
Department of Applied Statistics 
and clinical research team involved 
in the trial at Lister Hospital. 
  

 
Protocol: Robotic Prostatectomy Artificial Intelligence Low Pressure Pain (RALP) Trial RD No: RD2024-75 
Version [1.1] Date [20.01.2025] 
 
              
 
 
 
 Confidential 
 
 
 
Page 21 of 36 
 
 
Table 2. Schedule of assessments 
 
Within 1 month 
Before 
Procedure 
 
Day of 
Procedure 
Post-Procedure/ 
Prior to Hospital 
Discharge 
One week 
(7±2 days) 
Follow- up 
30- day  
(30±2 days) 
Follow- up 
Study Initiation 
X 
 
 
 
 
Demographics/Medical History 
X 
 
 
 
 
Physical Examination 
X 
 
 
X 
 
X 
Clinical Status Evaluation 
X 
 
 
 
X 
Study Exit 
 
 
 
 
X 
Laboratory Tests*: 
X 
 
 
 
 
Inclusion / Exclusion Criteria 
Assessment 
X 
 
 
 
 
Informed Consent 
X 
 
 
 
 
Randomization and Intent to Treat 
 
X 
 
 
 
Endpoints: 
 
X 
X 
X 
X 
Adverse Events 
 
X 
X 
X 
X 
Incidence and severity of pain 
 
 
X 
X 
X 
(NRS) Pain Scale 
X 
 
X 
X 
X 
PMD-200 monitor 
X 
X 
X 
X 
X 
*Only standard of care – no special testing required specific to this study. 
 
 
 
5.3  Screening and Baseline assessments  
 
Investigators will maintain a screening log that will record the date of informed consent, the 
date of screening, the enrollment status (enrolled/excluded) and the reason for exclusion for 
all screen failures. 
 
Within 30 days of a subject’s scheduled procedure, obtain a medical history and record the 
subject’s demographic (age, race, sex and date of birth) and baseline information (height, 
weight, and systolic/diastolic blood pressure).  Within 30 days prior to the planned procedure 
date, obtain serum blood tests per standard of care.  These will typically include: 
• 
FBC 
• 
Renal function test 
• 
CRP 
 
Once it has been determined that the subject meets all eligibility criteria, and written 
informed consent has been obtained, the subject is eligible for randomization. 
 
 
5.4 Study assessments and procedures 
 
 

 
Protocol: Robotic Prostatectomy Artificial Intelligence Low Pressure Pain (RALP) Trial RD No: RD2024-75 
Version [1.1] Date [20.01.2025] 
 
              
 
 
 
 Confidential 
 
 
 
Page 22 of 36 
 
This study will be conducted at one site by one surgeon performing 40 total procedures.  
Study subjects will be prepared for surgery per standard institutional policy and practice.  
Standard operative procedures will be followed.   
If a technical malfunction of the AirSeal® iFS or AirSeal® Access Port was to occur, the 
surgeon should replace each with the corresponding AirSeal® part.  The same replacement 
practice should be followed for the Stryker PneumoClear insufflator.  Switching to the other 
insufflation system should occur only by necessity. 
All ports will be placed according to standard of care (SOC).  All clinical decisions will be 
made per standard institutional practice and policy.   
Once pneumoperitoneum has been established and all trocars have been placed, intra-
abdominal pressure will be set to the specified values. 
Data collection methods are described below. 
Postoperative data will be collected regarding incidence and severity of pain, medication 
use, anesthesia related parameters and length of recovery and hospital stay.   
Surgical Technique 
Standard of Care (SOC) 
Treatment Arm Guidelines: 
The AirSeal Insufflation System should be used as per the procedure in the Instructions for 
Use (IFU).   
To achieve the study goals all patients in all study arms need the following data to be 
collected intraoperatively using the following methods: 
Pre-Operative: 
1. Pre-op vitals including height and weight  
2. Pre-op labs  
 
Intra-operative: 
1. Insufflation Pressure  
2. Estimated blood loss  
3. Blood transfusion (intra-operative)  
4. Procedure time (initial incision to closure)  
5. Surgeon-determined need to increase IAP beyond “study pressure”  
6. Administration of transversus abdominis plane block  
7. Urine output  
8. Anesthetic/pain medication administration  
9. MedaSense PMD-200 monitor for pain documentation  
10. Intraoperative Peak Airway Pressure every 15 minutes  
11. Intraoperative End Tidal Carbon Dioxide (ETCO2) every 15 minutes  

 
Protocol: Robotic Prostatectomy Artificial Intelligence Low Pressure Pain (RALP) Trial RD No: RD2024-75 
Version [1.1] Date [20.01.2025] 
 
              
 
 
 
 Confidential 
 
 
 
Page 23 of 36 
 
 
Post-Operative: 
During hospital discharge, all subjects will be evaluated for incidence and severity of pain 
using a 0-10 numeric rating scale (NRS) and records of medication use and a PMD-200 
monitor. These data will be captured in the Case Report Forms.  
 
Recovery room:  
1. Time in recovery room  
2. Post-op pain incidence and severity (abdominal) NRS  
3. Pain medications  
4. Post- op labs (CBC, Chem-7) per standard of care  
5. Vital signs 24 hr  
 
Discharge:  
1. Post-op pain incidence and severity (abdominal) NRS  
2. Presence or absence of postoperative nausea or vomiting  
3. Pain medications  
4. Length of hospital stay  
5. Pain Interference and Pain Intensity short form surveys  
6. Any complications that were observed. Post-operative complications through 30 days, 
reported using Clavien-Dindo Classification, including 30-day mortality  
7. Return to operating room within 24 hour  
8. Readmission to hospital within 30 days  
 
Classification, including 30-day mortality  
All Adverse Events (intra-operative and post-operative through 30 days):  
1. Adverse Events  
2. Serious Adverse Events  
3. Anticipated Adverse Device Effects  
4. Unanticipated Adverse Device Effects  
5  All device deficiencies and use errors, regardless of relationship to an adverse event 
 
5.5 Follow-up 
 
Each subject will be enrolled in the study from day of consent until their standard of care 30-
day, post-procedure, follow-up appointment. Following this last follow up appointment, the 

 
Protocol: Robotic Prostatectomy Artificial Intelligence Low Pressure Pain (RALP) Trial RD No: RD2024-75 
Version [1.1] Date [20.01.2025] 
 
              
 
 
 
 Confidential 
 
 
 
Page 24 of 36 
 
study will run for a further 12 months in order to follow up on any subsequent adverse events 
during this time period. 
 
5.6 End of study procedures 
 
The sponsor will notify the main REC of the end of a trial within 90 days of its completion. 
This will be the date of the last visit/data item of the last patient undergoing the trial. 
 
 
 
6    SAFETY REPORTING 
 
 
6.1 Definitions 
 
6.1.1 Adverse Event (AE) 
 
An adverse event (AE) is any symptom, sign, illness or experience that develops or worsens 
in severity during the course of the study.  Inter-current illnesses or injuries should be 
regarded as adverse events.  Abnormal results of diagnostic procedures are considered to 
be adverse events if the abnormality: 
 
• 
results in study withdrawal 
• 
is associated with a serious adverse event 
• 
is associated with clinical signs or symptoms 
• 
leads to additional treatment or to further diagnostic tests 
• 
is considered by the investigator to be of clinical significance 
 
6.1.2 Serious Adverse Event (SAE) 
 
A serious adverse event is any AE that is:  
 
• 
Fatal 
• 
life-threatening 
• 
requires or prolongs hospital stay 
• 
results in persistent or significant disability or incapacity 
• 
a congenital anomaly or birth defect 
• 
an important medical event 
 
6.1.3 Disease related Events/outcomes NOT qualifying as SAEs 
 
An event which is part of the natural course of the disease under study (i.e., disease 
progression) should not be reported as an SAE.  However, if the progression of the 
underlying disease is greater than that which would normally be expected for the subject, or 
if the investigator considers that there was a causal relationship between treatment with 
study intervention or protocol design/procedures and the disease progression, then it must 
be reported as an SAE. 

 
Protocol: Robotic Prostatectomy Artificial Intelligence Low Pressure Pain (RALP) Trial RD No: RD2024-75 
Version [1.1] Date [20.01.2025] 
 
              
 
 
 
 Confidential 
 
 
 
Page 25 of 36 
 
Important medical events are those that may not be immediately life threatening, but are 
clearly of major clinical significance. They may jeopardise the subject, and may require 
intervention to prevent one of the other serious outcomes noted above.  
 
    
6.1.4 Pre existing conditions 
 
A pre-existing condition is one that is present at the start of the study.  A pre-existing 
condition should be recorded as an adverse event if the frequency, intensity, or the character 
of the condition worsens during the study period. 
 
At screening, any clinically significant abnormality should be recorded as a pre-existing 
condition.  At the end of the study, any new clinically significant findings/abnormalities that 
meet the definition of an adverse event must also be recorded and documented as an 
adverse event. 
 
6.2 Investigator Assessments 
 
 
6.2.1 Seriousness 
 
When an AE/AR occurs the investigator responsible for the care of the patient must first 
assess whether the event is serious using the definitions given above. If the event is serious 
and not exempt from expedited reporting, then an SAE form must be completed. 
 
6.2.2 Causality 
 
The Investigator must assess the causality of all adverse events in relation to the trial 
therapy using the definitions in the table below. There are 5 causality categories: unrelated, 
unlikely, possible, probable and definitely related. If the causality assessment is unrelated or 
unlikely to be related then for reporting purposes the event will not be regarded as an 
adverse reaction to trial therapy. If the causality is assessed as possible, probable or 
definitely related then for reporting purposes the event is classified as an adverse reaction.
 
 
 
Table 3. 
Definitions of Causality 
 
Relationship Description 
Unrelated 
There is no evidence of any causal relationship 
Unlikely 
There is little evidence to suggest there is a causal relationship (e.g. the 
event did not occur within a reasonable time after administration of the trial 
intervention). There is another reasonable explanation for the event (e.g. 
the patient’s clinical condition, other concomitant treatment). 
Possible 
There is some evidence to suggest a causal relationship (e.g. because the 
event occurs within a reasonable time after administration of the trial 
intervention). However, the influence of other factors may have contributed 
to the event (e.g. the patient’s clinical condition, other concomitant 
treatments). 
Probable 
There is evidence to suggest a causal relationship and the influence of 
other factors is unlikely. 

 
Protocol: Robotic Prostatectomy Artificial Intelligence Low Pressure Pain (RALP) Trial RD No: RD2024-75 
Version [1.1] Date [20.01.2025] 
 
              
 
 
 
 Confidential 
 
 
 
Page 26 of 36 
 
Definitely 
There is clear evidence to suggest a causal relationship 
 
6.2.3 Expectedness 
 
Expected SAEs for the disease and trial intervention should be listed in the protocol. 
Investigators must file the current version of the Expected Adverse Events list in the safety 
reporting section of their Investigator File. 
 
 
6.2.4 Grading  
 
Insert relevant grading information including version of CTCAE to be used. 
 
6.3 Reporting of AEs and SAEs 
 
At each contact with the subject, the investigator must seek information on adverse events 
by specific questioning and, as appropriate, by examination.  Information on all adverse 
events should be recorded immediately in the source document, and also in the appropriate 
adverse event module of the case report form (CRF).  All clearly related signs, symptoms, 
and abnormal diagnostic procedures results should recorded in the source document, 
though should be grouped under one diagnosis. Methods to detect the presence of adverse 
events may take one or more of the following: 
 
➢ 
Information volunteered by the patient or carer. 
➢ 
Open-ended and non-leading verbal questioning of the patient at every visit 
such as the following: “How are you feeling? Have you had any (other) medical 
problems since your last visit?” 
➢ 
Observation by the investigational team, other care providers or relatives. 
 
All adverse events occurring during the study period must be recorded.  The clinical course 
of each event should be followed until resolution, stabilisation, or until it has been determined 
that the study treatment or participation is not the cause.  Serious adverse events that are 
still ongoing at the end of the study period must be followed up to determine the final 
outcome.  Any serious adverse event that occurs after the study period and is considered to 
be possibly related to the study interventnion or study participation should be recorded and 
reported immediately. 
 
A serious adverse event must be reported to the study sponsor within 24 hours of the event.  
A Serious Adverse Event (SAE) form must be completed by the investigator and faxed to the 
study sponsor within 24 hours.  The investigator will keep a copy of this SAE form on file at 
the study site.   
 
At the time of the initial report, the following information should be provided: 
 

 
Protocol: Robotic Prostatectomy Artificial Intelligence Low Pressure Pain (RALP) Trial RD No: RD2024-75 
Version [1.1] Date [20.01.2025] 
 
              
 
 
 
 Confidential 
 
 
 
Page 27 of 36 
 
• 
Study identifier 
• 
Study Center 
• 
Subject number 
• 
A description of the event 
• 
Date of onset 
• 
Current status 
• 
Whether 
study 
treatment 
was 
discontinued 
• 
The 
reason 
why 
the 
event 
is 
classified as serious 
• 
Investigator 
assessment 
of 
the 
association between the event and 
study treatment 
 
This should include a copy of the completed Serious Adverse Event form, and any other 
diagnostic information that will assist the understanding of the event.  Significant new 
information on ongoing serious adverse events should be provided promptly to the study 
sponsor. 
 
6.3.1 Notification Procedure 
 
• 
The SAE form must be completed by the Investigator (consultant named on the 
signature list and delegation of responsibilities log who is responsible for the patient’s 
care), with due care being paid to the grading, causality and expectedness of the event 
as outlined above. In the absence of the responsible investigator the form should be 
completed and signed by a member of the site trial team.  
• 
All unexpected SAEs not defined in protocol or related documents in ENHT sponsored 
trials (including non-ENHT patients) must be reported to the R&D Office using the 
ENHT Adverse Event Report Form and a copy of the local/ trial specific form used for 
REC/HRA notification. 
 
➢ 
Initial SAE reports must be faxed within one working day of the investigator’s 
knowledge of the event. 
➢ 
Follow-up Patients must be followed-up until clinical recovery is complete and 
laboratory results have returned to normal or baseline, or until the event has 
stabilised. Follow-up should continue after completion of protocol treatment if 
necessary. Follow-up information should be noted on a further SAE form by 
ticking the box marked ‘follow-up’ as information becomes available. Extra, 
annotated information and/or copies of test results may be provided separately. 
The patient must be identified by trial number, date of birth and initials only. The 
patient’s name should not be used on any correspondence. 
 
6.3.2 Medical Monitoring 
 
 
It is the responsibility of the Principal Investigator to oversee the safety of the study at his/her 
site.  This safety monitoring will include careful assessment and appropriate reporting of 
adverse events as noted above, as well as the construction and implementation of a site 
data and safety-monitoring plan.  Medical monitoring will include a regular assessment of the 
number and type of serious adverse events and suspected unexpected serious adverse 
events. 
 
 6.3.3 Hospitalisation, Prolonged Hospitalisation or Surgery 
 

 
Protocol: Robotic Prostatectomy Artificial Intelligence Low Pressure Pain (RALP) Trial RD No: RD2024-75 
Version [1.1] Date [20.01.2025] 
 
              
 
 
 
 Confidential 
 
 
 
Page 28 of 36 
 
Any adverse event that results in hospitalisation or prolonged hospitalisation should be 
documented and reported as a serious adverse event unless specifically instructed 
otherwise in this protocol.  Any condition responsible for surgery should be documented as 
an adverse event if the condition meets the criteria for an adverse event.  
 
Neither the condition, hospitalisation, prolonged hospitalisation, nor surgery are reported as 
an adverse event in the following circumstances: 
 
➢ 
Hospitalisation or prolonged hospitalisation for diagnostic or elective surgical 
procedures for a pre-existing condition.  Surgery should not be reported as an 
outcome of an adverse event if the purpose of the surgery was elective or 
diagnostic and the outcome was uneventful. 
➢ 
Hospitalisation or prolonged hospitalisation required to allow efficacy 
measurement for the study 
➢ 
Hospitalisation or prolonged hospitalisation for therapy of the target disease of 
the study, unless it is a worsening or increase in frequency of hospital 
admissions as judged by the clinical investigator. 
 
            Examples where an AE is NOT to be reported: 
 
➢ 
Medical or surgical procedure (e.g., endoscopy, appendectomy). Note, the 
condition that leads to the procedure is an AE. 
➢ 
Situations where an untoward medical occurrence did not occur (social and/or 
convenience admission to a hospital). 
➢ 
Anticipated day-to-day fluctuations of pre-existing disease(s) or condition(s) 
present or detected at the start of the study that do not worsen. 
➢ 
The disease/disorder being studied or expected progression, signs, or 
symptoms of the disease/disorder being studied unless more severe than 
expected for the subject’s condition. 
 
 
6.3.4 Post study AEs 
 
All unresolved adverse events should be followed by the investigator until the events are 
resolved, the subject is lost to follow-up, or the adverse event is otherwise explained.  At the 
last scheduled visit, the investigator should instruct each subject to report any subsequent 
event(s) that the subject, or the subject’s personal physician, believes might reasonably be 
related to participation in this study.  The investigator should notify the study sponsor of any 
death or adverse event occurring at any time after a subject has discontinued or terminated 
study participation that may reasonably be related to this study.  The sponsor should also be 
notified if the investigator should become aware of the development of cancer or of a 
congenital anomaly in a subsequently conceived offspring of a subject that has participated 
in this study.  
 
6.3.5 Abnormal Laboratory values 
 

 
Protocol: Robotic Prostatectomy Artificial Intelligence Low Pressure Pain (RALP) Trial RD No: RD2024-75 
Version [1.1] Date [20.01.2025] 
 
              
 
 
 
 Confidential 
 
 
 
Page 29 of 36 
 
A clinical laboratory abnormality should be documented as an adverse event if any one of 
the following conditions is met:  
 
• 
The laboratory abnormality is not otherwise refuted by a repeat test to confirm the 
abnormality 
• 
The abnormality suggests a disease and/or organ toxicity 
• 
The abnormality is of a degree that requires active management; e.g. modification of 
intervention, more frequent follow-up assessments, further diagnostic investigation, 
etc. 
Abnormal laboratory findings (e.g., clinical chemistry, haematology, urinalysis) or other 
abnormal assessments that are judged by the investigator as clinically significant will be 
recorded as AEs or SAEs if they meet the definition of an AE or SAE. 
 
Clinically significant abnormal laboratory findings or other abnormal assessments that are 
detected during the study or are present at Baseline and significantly worsen following the 
start of the study will be reported as AEs or SAEs.  However, clinically significant abnormal 
laboratory findings or other abnormal assessments that are associated with the disease 
being studied, unless judged by the investigator as more severe than expected for the 
subject’s condition, or that are present or detected at the start of the study and do not 
worsen, will not be reported as AEs or SAEs. 
 
 
6.3.6 Lack of efficacy 
 
When there is a deterioration in the condition for which the study treatment is being used, 
there may be uncertainty as to whether this is lack of efficacy or an AE. In such cases, 
unless the reporting physician considers that study treatment contributed to the deterioration 
or local regulations state to the contrary, the deterioration would be considered a lack of 
efficacy. 
 
 
6.3.7 New Cancers  
The development of a new primary cancer should be regarded as an SAE. New cancers are 
those that are not the primary reason for the administration of the study treatment and have 
been identified after the patient’s inclusion in this study. 
 
6.3.8 Deaths 
 
All deaths that occur during the study, or within the protocol defined follow up period 
after the administration of the last intervention, must be reported as follows:  
 
➢ 
Death clearly the result of disease progression should be reported to the study 
monitor at the next monitoring visit and should be documented in the CRF but 
should not be reported as an SAE. 
➢ 
Where death is not due (or not clearly due) to progression of disease under 
study, the AE causing the death must be reported to the study monitor as an 
SAE within 24 hours. The report should contain a comment regarding the co-

 
Protocol: Robotic Prostatectomy Artificial Intelligence Low Pressure Pain (RALP) Trial RD No: RD2024-75 
Version [1.1] Date [20.01.2025] 
 
              
 
 
 
 Confidential 
 
 
 
Page 30 of 36 
 
involvement of progression of disease, if appropriate, and should assign main 
and contributory causes of death. 
➢ 
Deaths with an unknown cause should always be reported as an SAE and a 
post-mortem may be helpful in the assessment of the cause of death. 
 
 
7 STATISTICS AND DATA ANALYSIS  
 
7.1 Sample Size determination 
 
Sample size estimation is performed conservatively assuming a single measurement per 
subject for the primary endpoint of pain assessed by a 0-10 NRS. With multiple 
measurements for some subjects, the actual power should be slightly higher.  Based on pilot 
data, a true 1-point reduction in mean abdominal pain NRS is assumed for AIS as compared 
to CIS; the common standard deviation is estimated to be 2.6.  With 40 evaluable subjects, 
20 for each treatment arm, the power for observing a statistically significant AIS benefit (i.e. 
2-sided p<0.05 by t test) is approximately 0.85. 
 
Please note that the findings from this study will inform future, larger scale, multi-center trials 
into this topic. 
 
7.2 Statistic Methods 
 
Data Analysis Plan 
The data analysis plan has been planned in order to conform to best current statistical 
practice and the reporting of analyses in accordance with the relevant sections of the 
CONSORT 2010 Statement and Checklist (Schulz et al., 2010). It is anticipated that it will 
also enable reporting to conform to the updated CONSORT 2024 Statement (when that is 
released) or will be enhanced in response to it. Analysis will be on a “per protocol” basis as 
departures from the randomised allocation (which will be fully reported) are not a matter of 
participant adherence to study protocol. 
 
Descriptive Statistics 
Summary statistics regarding the conduct of the trial will be presented, including the 
numbers of participants randomly assigned, drop-outs and exclusions, separately for each 
arm of the trial, along with dates of recruitment and follow-up. 
 
Baseline demographic and relevant clinical characteristics will be presented for participants 
in each arm of the trial. The number of participants in each group in subsequent analyses will 
be given, along with details of any changes of groups that might have occurred since the 
original assignments. 
 
Primary Outcomes 
The primary effectiveness outcome is the pain associated with use of the two insufflator 
devices. Pain will be measured during and immediately after surgery in the recovery room 
and then by 6-hour increments, measured by a 0 – 10 Numeric Rating Scale (NRS) and a 
PMD-200 nociception monitor. 
 

 
Protocol: Robotic Prostatectomy Artificial Intelligence Low Pressure Pain (RALP) Trial RD No: RD2024-75 
Version [1.1] Date [20.01.2025] 
 
              
 
 
 
 Confidential 
 
 
 
Page 31 of 36 
 
Summary descriptive statistics for these outcomes will be given for each arm of the trial and 
modelling undertaken, as described below. Confidence intervals and both absolute and 
relative effect sizes will be reported where appropriate. 
 
For the measure of pain obtained using the PMD-200 nociception monitor, longitudinal 
analysis of covariance will be used as the method of analysis. Incorporation of a baseline 
measure into the analysis will be undertaken in accordance with the recommendations 
contained in Twisk et al. (2018), including the use of a random effect to allow for the 
correlation between the baseline and non-baseline measurements at the individual level. 
Random effects will also be included to allow for different surgeons undertaking operations. 
For the NRS, it is the intention to again used longitudinal analysis of covariance with the pain 
measure as a continuous variable. However, if the distribution of the pain measure is such 
that it is more appropriate to treat it as an ordinal categorical variable, then the analysis will 
take that approach. 
 
For both analyses, adjustment for differences between the two arms of the trial will be 
undertaken by the inclusion of potential confounding covariates. 
For testing of significance, the residuals of the fitted models will be examined to assess the 
reasonableness of assumptions. In the event of assumptions being untenable, robust 
methods such as bootstrapping will be used. 
 
Secondary Outcomes 
Secondary measures relate to the procedure being undertaken (e.g. procedure time, number 
of times insufflator settings adjusted) and post-operative measures (e.g. length of recovery 
room stay, length of hospital stay, severity of postoperative nausea/vomiting). 
Summary descriptive statistics for these outcomes will be given for each arm of the trial and 
modelling undertaken, as described below. Confidence intervals and both absolute and 
relative effect sizes will be reported where appropriate. 
 
For variables which can be regarded as continuous in nature, analysis of covariance will be 
carried out, including the use of a random effect to allow for different surgeons undertaking 
operations. Adjustment for differences between the two arms of the trial will be undertaken 
by the inclusion of potential confounding covariates. 
 
While some secondary outcomes (e.g. procedure time) may clearly be regarded as 
continuous, it will be necessary to explore the distribution of others (e.g. length of recovery 
room stay, length of hospital stay) to ascertain whether it might be more appropriate to 
derive ordered categorical variables and analyse these. In this case, the analysis of 
covariance will again be used, employing methods suitable for an ordered category 
response. 
 
Secondary measures which are counts (e.g. number of times insufflator settings adjusted) 
will be analysed using methods for count data, with these methods being chosen in a 
manner recommended by Jakobsen et al. (2015). 
 
For testing of significance, the residuals of the fitted models will be examined to assess the 
reasonableness of assumptions. In the event of assumptions being untenable, robust 
methods such as bootstrapping will be used. 
 

 
Protocol: Robotic Prostatectomy Artificial Intelligence Low Pressure Pain (RALP) Trial RD No: RD2024-75 
Version [1.1] Date [20.01.2025] 
 
              
 
 
 
 Confidential 
 
 
 
Page 32 of 36 
 
Other variables which are categorical in nature will be analysed using methods appropriate 
to the variables under consideration, such as chi-square tests and/or exact tests.  
 
Ancillary analyses 
Where ancillary analyses of undertaken of other outcomes or where subgroups are 
analysed, it will be made clear that these are not pre-specified. The rationale for undertaking 
these analyses will be given. 
 
Software 
It is anticipated that R statistical software will be used to undertake the analyses for the trial. 
The individual R packages and version numbers that are used for analyses will be reported. 
 
Departures from protocol, exclusions and serious adverse events 
Any departures from protocol which occur will be fully reported, as will the reasons for any 
exclusion of participants and any serious adverse events. 
 
8 DATA HANDLING AND RECORD KEEPING 
 
8.1 Confidentiality 
 
Confidentiality of subjects will be maintained throughout the Study. A unique identification 
code will be assigned to each subject participating in this Study. Any data that may be 
published in abstracts, scientific journals, or presented at medical meetings will reference a 
unique subject code and will not reveal the subject’s identity. The Sponsor or their 
representative will make every reasonable effort to protect the confidentiality of the subjects 
participating in the Study. 
 
The trial protocol will be applied to ensure there is no breach of any duty of confidentiality 
owed to patients, service users or any other person in the process of identifying potential 
participant as per the Good Clinical Practice (GCP) guidelines. All physical patient data will 
be stored securely in lockers in the research office at Lister hospital, Stevenage. All 
electronic data will be stored securely on password protected and encrypted NHS Trust 
computers or a secure University of Hertfordshire database with password protection and 
prior pseudoanonymisation. All data processed will be done my members of the research 
department who are up to date with their GCP training. 
 
8.2 Source Documents 
 
The Principal Investigator must maintain detailed source documents on all Study subjects 
who are enrolled in the Study or who undergo screening.  Source documents include subject 
medical records, hospital charts, clinic charts, Investigator’s subject Study files, as well as 
the results of diagnostic tests (e.g., laboratory tests). 
The following minimum information should be recorded in the subject’s medical records: 
• 
The date the subject entered the Study and the subject number 
• 
The Study protocol number and the name of the Sponsor 
• 
The date that informed consent was obtained 
• 
Evidence that the subject meets Study eligibility requirements (e.g., medical history, 
Study procedures and/or evaluations) 
• 
The dates of all Study related subject visits 

 
Protocol: Robotic Prostatectomy Artificial Intelligence Low Pressure Pain (RALP) Trial RD No: RD2024-75 
Version [1.1] Date [20.01.2025] 
 
              
 
 
 
 Confidential 
 
 
 
Page 33 of 36 
 
• 
Evidence that required procedures and/or evaluations were completed 
• 
Use of any concurrent medications 
• 
Documentation of specific device used, if any 
• 
Occurrence and status of any Adverse Events 
• 
The date the subject exited the Study, and a notation as to whether the subject 
completed the Study or was discontinued, including the reason for discontinuation. 
 
8.3 Case Report Form 
 
The study case report form (CRF) is the primary data collection instrument for the study.  All 
data requested on the CRF must be recorded.  All missing data must be explained.  If a 
space on the CRF is left blank because the procedure was not done or the question was not 
asked, write “ND”.  If the item is not applicable to the individual case, write “NA”.  All entries 
should be printed legibly in black ink.  If any entry error has been made, to correct such an 
error, draw a single straight line through the incorrect entry and enter the correct data above 
it.  All such changes must be initialed and dated.  DO NOT ERASE OR WHITE OUT 
ERRORS.  For clarification of illegible or uncertain entries, print the clarification above the 
item, then initial and date it. 
 
8.4 Data handling and record keeping 
 
Standard security for secure storage of data on NHS computer network. Anonymised paper 
and manual files are safely stored in a locked office within Research Offices in the research 
Department. Electronic records of anonymised participants will be safely stored in 
designated NHS computers. These will be password protected. The database will be created 
and maintained by the University of Hertfordshire but access to data in the database is 
restricted by role and only those who are required to have access to personal data (i.e. the 
clinical research team) will be able to see it. Access to the database will require individual 
logins and access to specific data in the database is restricted by role. 
After the study duration, all paper records will be sent for storage to archive in line with the 
Trust Research SOPs. This research data will be held by the Health Records Department at 
East and North Hertfordshire NHS Trust. As per Trust policy, data relating to patients 
involved in clinical trials will be stored for 5 years before being disposed of. Further 
information relating to the storage of research data can be found in the East and North 
Hertfordshire NHS Trust's policy on Health Records Management. 
Electronic archiving of study documents and the study database will be initiated by the CI no 
earlier than one year after publication of the study. Identifiable information will be removed 
from the study database before archiving. The electronic archive will be stored on secure 
servers at the University of Hertfordshire 
 
8.5 Records Retention 
 
• 
Archiving for this study will be carried out according to gSOP-17 
• 
Destruction of essential documents will require authorisation from the Sponsor 
• 
Archiving will be authorised by the Sponsor following submission of the end of study 
report 

 
Protocol: Robotic Prostatectomy Artificial Intelligence Low Pressure Pain (RALP) Trial RD No: RD2024-75 
Version [1.1] Date [20.01.2025] 
 
              
 
 
 
 Confidential 
 
 
 
Page 34 of 36 
 
• 
all essential documents will be archived for 5 years after completion of trial.  
 
9  STUDY MONITORING, AUDITING AND INSPECTING 
 
9.1 Study Monitoring Plan 
 
This study will be monitored according to the monitoring plan.  The investigator will allocate 
adequate time for such monitoring activities.   
 
The Investigator will also ensure that the monitor or other compliance or quality assurance 
reviewer is given access to all the above noted study-related documents and study related 
facilities and has adequate space to conduct the monitoring visit. 
 
The monitoring plan will depend on the type of trial and the Sponsor will be provide some 
monitoring assistance as detailed in gSOP-12, but it is important that the Investigator 
ensures that the data in relation to this study is accurate and verifiable and that patient safety 
is maintained throughout the trial duration regardless of sponsor monitoring activities. 
 
9.2 Auditing and Inspecting 
 
The investigator will permit study-related audits, and inspections by the IEC, the sponsor, 
government regulatory bodies, and R&D Compliance and Quality Assurance groups of all 
study related documents (e.g. source documents, regulatory documents, data collection 
instruments, study data etc).  The investigator will ensure the capability for inspections of 
applicable study-related facilities (e.g. diagnostic laboratory) 
 
Participation as an investigator in this study implies acceptance of potential inspection by 
government regulatory authorities and R&D Compliance and Sponsor Quality Assurance 
offices.  
 
 
9.6 Source Data Verification 
 
Source Documents are original documents, data and records (e.g. hospital records, clinical 
and office charts, laboratory notes, memoranda, x-rays, subject files and records kept at the 
pharmacy, recorded data from automated instruments etc.). Source Data is considered all 
information in original records and certified copies of clinical findings, observations, or other 
activities in the trial. Source Data are contained in Source Documents (original records or 
certified copies). 
 
The following items must be available for Source Data Verification (SDV) in source 
documents other than the CRF: 
 
o Date of conducting Informed Consent 
o Gender 
o Statement that the patient is participating in the /study 
o Data for evaluation of eligibility criteria 
o Relevant medical history and diagnosis 

 
Protocol: Robotic Prostatectomy Artificial Intelligence Low Pressure Pain (RALP) Trial RD No: RD2024-75 
Version [1.1] Date [20.01.2025] 
 
              
 
 
 
 Confidential 
 
 
 
Page 35 of 36 
 
o Screening Number and Patient Number 
o Administration of study intervention 
o All study visit dates  
o Adverse Events or absence of Adverse Events 
o Concomitant Therapy including changes (if applicable) 
o Date and reason for exclusion or withdrawal (if applicable) 
 
Source data verification should be performed before the statistical database is cleaned and 
then locked for analysis. 
 
10. REGULATORY OBLIGATIONS AND COMPLIANCE 
 
This study is to be conducted according to EU and international standards of Good Clinical 
Practice and International Conference on Harmonisation guidelines, applicable government 
regulations and Ethics policies and procedures. 
 
This protocol and any amendments will be submitted to a properly constituted Independent 
Ethics Committee (IEC), in agreement with local legal prescriptions, for formal approval of 
the study conduct.  The decision of the IEC concerning the conduct of the study will be made 
in writing to the investigator and a copy of this decision will be provided to the sponsor before 
commencement of this study.  The investigator should provide a list of IEC members and 
their affiliate to the sponsor. 
 
Before any site can enroll patients into the trial, the Chief Investigator/Principal Investigator 
or designee will apply for NHS confirmation of capacity and capability from the site’s 
Research & Development (R&D) department. 
 
10.1 Protocol compliance  
 
• 
Prospective, planned deviations or waivers to the protocol are not allowed and must not 
be used e.g. it is not acceptable to enroll a subject if they do not meet the eligibility 
criteria or restrictions specified in the trial protocol 
• 
Accidental protocol deviations can happen at any time. They must be adequately 
documented on the relevant forms and reported to the Chief Investigator and Sponsor 
immediately.  
• 
Deviations from the protocol which are found to frequently recur are not acceptable, will 
require immediate action and could potentially be classified as a serious breach. 
 
10.2 Notification of Serious Breaches to GCP and/or the protocol  
 
A “serious breach” is a breach which is likely to effect to a significant degree – 
(a) the safety or physical or mental integrity of the subjects of the trial; or 
(b) the scientific value of the trial 
The sponsor will be notified immediately of any case where the above definition applies 
during the study conduct phase. 

 
Protocol: Robotic Prostatectomy Artificial Intelligence Low Pressure Pain (RALP) Trial RD No: RD2024-75 
Version [1.1] Date [20.01.2025] 
 
              
 
 
 
 Confidential 
 
 
 
Page 36 of 36 
 
 
11. STUDY FINANCES 
 
 
11.1 Funding Source 
 
£100,000 funding from ConMed Corporations, 6455 S. Yosemite St. Suite 800, Greenwood 
Village, Colorado, 80111. 
 
11.2 Conflict  
 
ConMed Corporation is funding this study and manufactures the AirSeal Insufflator, however, 
none of the study investigators have any conflicts of interest in the trial. 
 
Any investigator who has a conflict of interest with this study (patent ownership, royalties, or 
financial gain greater than the minimum allowable by their institution, etc.) must have the 
conflict reviewed by a properly constituted Conflict of Interest Committee with a Committee-
sanctioned conflict management plan that has been reviewed and approved by the study 
sponsor prior to participation in this study.   
 
 
12. INDEMNITY 
 
NHS indemnity scheme will apply as this is a NHS sponsored study. 
 
11. PUBLICATION PLAN 
 
Confidentiality of subjects will be maintained throughout the Study. Any data that may be 
published in abstracts, scientific journals, or presented at medical meetings will reference a 
unique subject code and will not reveal the subject’s identity. The Sponsor or their 
representative will make every reasonable effort to protect the confidentiality of the subjects 
participating in the Study. 
Following cessation of the trial, the results will be published and also distributed to 
those trial participants who wished to receive ongoing information and results from the trial.  
 
APPENDICES   
Appendix 1 -  Patient Information Leaflet, V1.0 09.09.2024  
Appendix 2 -  Informed Consent Form V1.0 09.09.2024  
Appendix 3 – GP Letter V1.0 09.09.2024 
 
 
 
.