Determinants of Post-operative Pain and Quality of Life Following Root Canal Treatment: A Prospective Clinical Study
Conditions: Post-operative Pain, Quality of Life
Sponsor: University of Edinburgh

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Non-CTIMP Study Protocol 
Study title: Pain following root canal treatment 
 
 
The University of Edinburgh and Lothian Health Board 
ACCORD 
The Queen’s Medical Research Institute 
47 Little France Crescent 
Edinburgh 
EH16 4TJ 
Funder 
NHS Lothian & University of Edinburgh 
Sponsor number 
AC21057 
REC Number 
21/YH/0180 
Project registration 
If applicable trials should be registered on a publically 
accessible database. ACCORD can provide log-in 
credentials for clinicaltrials.gov. Please email 
resgov@accord.scot to arrange 
Version Number and Date 
Version 1.0 15 June 2021 

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CONTENTS 
1 
INTRODUCTION ............................................................................................................... 8 
1.1 
BACKGROUND ....................................................................................................... 8 
1.2 
RATIONALE FOR STUDY ...................................................................................... 8 
2 
STUDY OBJECTIVES ...................................................................................................... 9 
2.1 
OBJECTIVES ........................................................................................................... 9 
2.1.1 
Primary Objective ................................................................................................ 9 
2.1.2 
Secondary Objectives ......................................................................................... 9 
2.2 
ENDPOINTS ............................................................................................................ 9 
2.2.1 
Primary Endpoint ................................................................................................ 9 
2.2.2 
Secondary Endpoints ......................................................................................... 9 
3 
STUDY DESIGN ............................................................................................................... 9 
4 
STUDY POPULATION ..................................................................................................... 9 
4.1 
NUMBER OF PARTICIPANTS ................................................................................ 9 
4.2 
INCLUSION CRITERIA ............................................................................................ 9 
4.3 
EXCLUSION CRITERIA .......................................................................................... 9 
5 
PARTICIPANT SELECTION AND ENROLMENT ......................................................... 10 
5.1 
IDENTIFYING PARTICIPANTS ............................................................................. 10 
5.2 
CONSENTING PARTICIPANTS ............................................................................ 10 
5.2.1 Withdrawal of study participants .................................................................... 10 
5.3 
Co-enrolment ........................................................................................................ 10 
6 
STUDY ASSESSMENTS ................................................................................................ 10 
6.1 
STUDY ASSESSMENTS ....................................................................................... 10 
6.2 
LONG TERM FOLLOW UP ASSESSMENTS ...................................................... 11 
6.3 
STORAGE AND ANALYSIS OF SAMPLES ......................................................... 11 
7 
DATA COLLECTION ...................................................................................................... 11 
7.1 
Source Data Documentation ............................................................................... 11 
7.2 
Case Report Forms .............................................................................................. 11 
8 
STATISTICS AND DATA ANALYSIS ............................................................................ 11 
8.1 
SAMPLE SIZE CALCULATION ............................................................................ 11 
8.2 
PROPOSED ANALYSES ...................................................................................... 11 
9 
ADVERSE EVENTS........................................................................................................ 11 
10 
OVERSIGHT ARRANGEMENTS ................................................................................... 12 
10.1 
INSPECTION OF RECORDS ................................................................................ 12 
10.2 
RISK ASSESSMENT ............................................................................................. 12 
10.3 
STUDY MONITORING AND AUDIT ...................................................................... 12 
11 
GOOD CLINICAL PRACTICE ........................................................................................ 13 
11.1 
ETHICAL CONDUCT ............................................................................................. 13 
11.2 
INVESTIGATOR RESPONSIBILITIES .................................................................. 13 
11.2.1 Informed Consent.............................................................................................. 13 
11.2.2 Study Site Staff .................................................................................................. 13 
11.2.3 Data Recording .................................................................................................. 13 

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11.2.4 Investigator Documentation ............................................................................. 13 
11.2.5 GCP Training...................................................................................................... 13 
11.2.6 Confidentiality .................................................................................................... 14 
11.2.7 Data Protection .................................................................................................. 14 
12 
STUDY CONDUCT RESPONSIBILITIES....................................................................... 14 
12.1 
PROTOCOL AMENDMENTS ................................................................................ 14 
12.2 
MANAGEMENT OF PROTOCOL NON COMPLIANCE ....................................... 14 
12.3 
SERIOUS BREACH REQUIREMENTS ................................................................. 15 
12.4 
STUDY RECORD RETENTION............................................................................. 15 
12.5 
END OF STUDY..................................................................................................... 15 
12.6 
CONTINUATION OF TREATMENT FOLLOWING THE END OF STUDY .......... 15 
12.7 
INSURANCE AND INDEMNITY ............................................................................ 15 
13 
REPORTING, PUBLICATIONS AND NOTIFICATION OF RESULTS .......................... 16 
13.1 
AUTHORSHIP POLICY ......................................................................................... 16 
14 
REFERENCES ................................................................................................................ 16 

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LIST OF ABBREVIATIONS 
Insert abbreviations as required 
This is not an exhaustive list. 
Any additional abbreviations used within the protocol must also be added here. 
 
ACCORD 
Academic and Clinical Central Office for Research & Development - Joint office for The University 
of Edinburgh and Lothian Health Board 
CI 
Chief Investigator 
CRF 
Case Report Form 
GCP 
Good Clinical Practice 
ICH 
International Conference on Harmonisation 
PI 
Principal Investigator 
QA 
Quality Assurance 
REC 
Research Ethics Committee 
SOP 
Standard Operating Procedure 

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1.0 INTRODUCTION 
1.1 
BACKGROUND 
 
Pain is a very subjective sensation that has be defined as an unpleasant sensory and 
emotional experience associated with actual or potential tissue damage (Rosenberg, 
1998). Root canal treatment is the process of eliminating pain by removing inflamed 
or dead pulpal tissues, cleaning and shaping the root canal system, to allow for the 
placement of a restoration that prevents microleakage. Pain following root canal 
treatment (RCT) is an unpleasant outcome for both dentists and patients. It is 
multifactorial, which could be mediated by cognitive, emotional as well as motivational 
factors, that may also be related to personal characteristics (Weich et al., 2008). The 
causes of pain following RCT include mechanical, chemical and/ or microbial injury to 
the pulpal or the tissues surrounding the roots. Other factors may include inadequate 
cleaning and shaping, over-instrumentation and extrusion of debris, irrigant, intracanal 
medication, tooth type and position, gender as well as age (ElMubarak et al., 2010; 
Watkins et al., 2002; Ali et al., 2012; Torabinejad et al., 1988; Morse et al., 1986; Imura 
and Zuolo, 1995; Siqueira, 2003; Walton et al., 2003; Mattscheck et al., 2001). 
Patient’s bite (occlusion) may also play an important role in triggering pain following 
RCT. Occlusal adjustment has been reported to prevent post-operative pain in teeth 
which underwent RCT (Rosenberg et al., 1998). 
 
 
Pain can either be tooth-related (odontogenic) or not tooth-related (non-odontogenic). 
The tooth-related pain following RCT can be further subdivided into intra-appointment 
flare-up, immediate post-operative pain, intermediate post-operative pain (within the 
first three months after treatment) and long-term post-operative pain (persistent pain 
lasting longer than 6 months to years after treatment) (Nixdorf et al., 2010). Intra- 

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appointment flare-up is the presence of severe pain and swelling of the soft tissues 
and the oral mucosa with regards to the root-treated tooth, occurring within a few hours 
to a few days after treatment, which usually would result in patients coming in for an 
unscheduled emergency appointment (Udoye & Aguwa, 2010; Iqbal et al., 2009; Yu 
et al., 2012; Gotler et al., 2012; Mattscheck et al., 2001; Walton & Fouad; 1992; Shah 
et al., 2011; Pasqualini et al., 2012; Ehrmann et al., 2003 and Thesis et al., 2008). 
 
The objective of RCT has always been to eradicate as much microorganisms as 
possible from the root canal system, creating an environment that is favourable for 
healing to take place (Orstavik et al., 1991; Sjogren et al., 1997; Siqueira et al., 2000). 
It also facilitates retention of teeth, to remain in function (Gilheany et al. 1994, Ørstavik 
& Pitt Ford, 1998). Nonetheless, pain following root canal treatment has been reported 
to be within 3% to 69.3%, mainly experienced within the first 24 to 48 hours (Ince et 
al., 2009; Gomes et al., 2017; Bourreau et al., 2015; Sing and Garg, 2012; Oginni and 
Udoye, 2004; Albashaireh and Alnegrish, 1998; Risso et al., 2008; Ng et al., 2004; 
Glennon et al., 2004; ElMubarak et al., 2010; Siqueira et al., 2002; Bhagwat and 
Mehta, 2013; Fava 1995). On the other hand, studies reported 5% - 25% incidence of 
persistent pain, lasting for 6 months or longer (Nixdorf et al., 2010; Nixdorf et al., 2015, 
Nixdorf et al., 2016, Philpott et al., 2019). Regardless of the mild to moderate possibility 
of pain occurring following root canal treatment, it is a poor indicator of a successful 
outcome of root canal treatment. 

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1.2 
RATIONALE FOR STUDY 
Although numerous studies have been conducted regarding pain following root canal 
treatment, there still appears to be contradicting results in the outcome as well as pain 
management, mainly due to the differences in the study protocols and small sample 
size. 
 
 
Findings from this study is aimed at evaluating incidence of immediate post-operative 
pain, be it for primary RCT or re-treatment cases. Additionally, it is also aimed for 
clinicians to understand the possible factors of root canal treatment that may be related 
to immediate post-operative pain. As a result, clinicians will be able to accurately 
diagnose the pain and appropriate treatment planning can be carried out. Patients will 
also be better educated in managing their symptoms, which includes the consumption 
of appropriate pain medication. It is also hoped that the validation of the pain 
assessment tool used in this study will help dental practitioners to record pain more 
easily. 

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2.0 
STUDY OBJECTIVES 
 
2.1 
OBJECTIVES 
 
2.1.1 The primary objectives of this study are: 
(i) to evaluate the incidence of post-operative pain after RCT at 24H, 48H and 7 days 
(ii) to evaluate the factors affecting post-operative pain 
 
(iii) to evaluate the quality of life (QoL) following RCT at 24H, 48H and 7 days 
 
 
 
2.1.2 The secondary objective include: 
(i) to evaluate the duration of post-operative pain 
(ii) to evaluate the severity of post-operative pain 
 
 
2.2 
Endpoints 
2.2.1 Primary endpoints 
 
(i) Patient decided to extract the tooth undergoing root canal treatment 
(ii) Patient does not want to continue with root canal treatment in Edinburgh Dental 
Institute 
 
 
2.2.2 Secondary endpoints 
(i) Tooth had procedural errors (such as perforation or ledge) that would affect the 
accuracy of the results of this study 
(ii) The tooth was filled (obturated) to an unsatisfactory level; extremely short (> 2mm) 
or extruded (> 2mm) 

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3.0 STUDY DESIGN 
 
This study is a prospective clinical study, which evaluates pain following the 
completion of non-surgical root canal treatment and re-treatment cases. The study is 
planned to take place from July 2021 until June 2022. Patient cohort would be patients 
referred to Edinburgh Dental Institute for root canal treatment. Root canal treatment 
and re-treatment cases will be performed by Postgraduate Trainees (Years 1,2 and 3) 
in Endodontology and Prosthodontics, core trainees, specialist registrars in the 
Restorative Departments and staff members of the Restorative Department, 
Edinburgh Dental Institute. (Please refer to Appendix 1) 
 
Patients who are deemed suitable for this study, screened by clinicians on duty during 
Restorative New Patient Clinic, will be invited to participate in this study. They will be 
given the Patient Information Sheet (PIS) at the beginning of the session and will be 
given time to decide on whether to participate in the study or not. If a suitable patient 
happens to not have the PIS and consent form during the 1st treatment visit, the 
patient will be provided with the PIS and consent form during the 1st treatment visit 
and will be given up to 24H to decide on participating the study or not. The pre- 
operative assessment, which will include pain assessment will be conducted as per 
normal routine prior to the commencement of RCT. At 24H (+/- 2H) the Principal 
Investigator will call the patient to follow-up. If the patient has agreed to participate in 
the study, the 24H post-operative pain and quality of life assessment will be conducted 
at the same time. Once patients have agreed to participate, they will be required to 
provide written consent which will be attached together with the PIS. On the first 
treatment day, patients will be required to answer a pre-operative Pain Assessment 
Questionnaire (Appendix 3), which will be answered in the presence of the clinician 
treating the patient, before the commencement of RCT. The Pain Questionnaire is the 
combination of Numeric Rating Scale (NRS) and Modified Verbal Rating Scale (VRS) 
adapted from previous published studies, with the addition of question on the presence 
of pre-operative pain duration. The pre-operative questionnaire will incorporate 
questions on pain intensity, the need, name and dosage of painkillers used by the 
patient on that day, and the last dose taken (in hours) as well as the duration of pain 
felt, as the longer the duration of pre-operative pain felt has been associated with 

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higher incidence of post-operative pain (Polycarpou et al., 2005). Also, pre-operative 
pain felt within the last 24 hours prior to root canal treatment has been associated with 
higher probability of post-operative pain (Arias et al., 2013). 
 
 
 
Following the completion of treatment, patients will be provided with post-operative 
Pain Assessment Questionnaire (Appendix 4), for the evaluation of post-operative 
pain. A copy of the pain questionnaire will be given to the patients which will be used 
as a guide when the pain history is obtained. This will be carried out verbally via phone 
by the main investigator of the study (NAF). Patients will not be required to return the 
forms to the institute. 
 
In addition to pain evaluation, this Pain Questionnaire also incorporates the intake of 
painkillers taken. In the event that painkillers are taken by patients for pain control, 
patients are required to record the pain intensity before the consumption of painkillers, 
apart from recording the dosage and frequency of painkillers taken. Patients will be 
advised on the standard painkiller regimen as a post-operative instruction after the 
completion of RCT. Painkiller consumption is also an indirect measure of post- 
operative pain intensity, hence, that is why this has been added to the Pain 
Assessment Questionnaire. Apart from pain assessment, post-operative quality of life 
(POQoL) post-treatment will also be assessed, based on questionnaire adapted from 
Pasqualini et al., 2016. (Appendix 5). 
 
Patients will be given the liberty to pull out from the study at any time, throughout the 
duration of the study. Similarly, the investigator will also be able to remove patients 
from the study, throughout the duration of the study, in the event that the teeth being 
root-treated were faced with complications that may alter the accuracy of the study. 
Withdrawal or removal will be recorded in the ‘Withdrawal/ Removal Form’. 
 
In terms of clinical notes required, a clinical template of the most important information 
required will be provided for all clinicians performing root canal treatment/ retreatment, 
in order for a standardized record to be obtained (Appendix 6). The clinical notes 
should include: 

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1. Any additional special tests done/ repeated 
 
 
2. Assessment of soft tissues for signs of infection 
 
 
3. Assessment of the tooth of concern: 
(i) Type and quality of pre- existing restoration 
(ii) Tenderness to palpation 
(iii) Tenderness to percussion 
(iv) Mobility 
(v) Periodontal pocket depth 
 
4. Additional sensibility tests conducted 
(i) EPT 
(ii) Cold test 
 
5. Diagnosis on the first treatment visit 
 
 
6. Whether any treatment has been carried out prior to having treatment initiated at 
Edinburgh Dental Institute (EDI) 
 
* At the end of the treatment notes template, a sentence on providing patients with 
pre-operative and post-operative questionnaires will be added as a reminder to the 
clinicians. This will also be re-emphasized verbally to the nurses and clinicians in 
charge. 

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4.0 
Study Population 
4.1 
Number of participants: 
150 participants 
 
Participant population: 
All patients referred to Restorative Department, Edinburgh Dental Institute for root 
canal treatment treated by postgraduate trainees in Endodontology and 
Prosthodontics (Years 1,2,3), Core Trainees and Specialist Registrars in the 
Restorative Department as well as staff members of Edinburgh Dental Institute. 
 
Number of sites involved: 
Only patients seen in the Restorative department of EDI will be included. 
Length of recruitment period: 
September 2021 until March 2022 
 
4.2 Criteria 
 
Inclusion Criteria 
Exclusion Criteria 
All teeth requiring primary root canal 
treatment 
Surgical root canal treatment 
All teeth requiring root canal re-treatment Patients on long term analgesics and 
steroids 
Age 18 – 100 years old (completely 
formed apex) 
Primary teeth 
Permanent teeth 
Teeth with procedural errors either being 
referred for the management or created 
during the procedure 
Periodontal pocket depth < 4mm and 
with mobility within normal limits 
Traumatized teeth 
Teeth with open apices 
Periodontally involved teeth 
Cases with hypochlorite accident 
Short or extruded root canal obturation 
Cases 
whereby 
patency 
was 
not 
achieved 
Patients with the ability to give informed 
consent 

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5.0 
PARTICIPANT SELECTION AND ENROLMENT 
 
5.1 
Identifying participants 
1. 
Who will identify the participants? 
Clinicians working on the Restorative New Patient Clinic 
 
2. 
Details of the first approach: 
- Patients referred to Edinburgh Dental Institute requiring root canal treatment or 
retreatment within the inclusion criteria will be invited to join the research 
- Patients will be given the Patient Information Sheet (PIS), by the clinicians seeing 
them during the New Patient clinic and will be given time to consider their participation 
- Patients can either decide on the same day before the end of their appointment 
during the New Patient clinic and provide with written consent or to bring back the PIS 
during the first treatment visit 
 
 
5.2 
Consenting Participants 
1. 
The consent process 
 
- 
Patients will be given the Patient Information Sheet (PIS), by the clinicians 
seeing them during the New Patient clinic and will be given time to consider 
their participation 
 
Patients will be informed on the procedure of the research study, which will 
include routine root canal treatment, that patient requires. The only additions to 
the procedure would be the inclusion of pre-operative pain questionnaire prior 
to the commencement of the treatment as well as the post-operative pain and 
immediate post-operative quality of life (QoL) assessment at 24H, 48H and 7 
days. 
 
- 
Patients can either decide on the same day before the end of their appointment 
during the New Patient Clinic and provide with written consent or to bring back 
the PIS during the first treatment visit. The written consent will be attached 
together with the PIS. If the patient decides to participate in the study during the 
New Patient Clinic, the clinician attending to the patient on that day will be taking 
the consent. If the patient takes a longer time to decide and brings back the 
consent form during the first treatment visit, the clinician in-charge in providing 
the treatment will be taking the consent. 

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2. 
Possible limitations 
 
- 
Participants will be informed in the PIS and consent form that phone calls will 
be made at 24 hours, 48 hours and 7 days (+/- 2 hours) post-operative to 
assess pain experience after root canal treatment as well as the quality of life 
after treatment 
 
5.2.1 
Withdrawal of Study Participants 
Participants are free to withdraw from the study at any point or a participant can be 
withdrawn by the Investigator. If withdrawal occurs, the primary reason for withdrawal 
will be documented in the participant’s case report form, if possible. The participant 
will have the option of withdrawal from: 
 
(i) All aspects of the trial but continued use of data collected up to that point . To 
safeguard rights, the minimum personally-identifiable information possible will be 
collected. 
 
(ii) Details required for withdrawal from study include: 
(a) Reason for withdrawing 
(b) Treatment level at which patient withdraw or has been withdrawn by the Principal 
Investigator 

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6.0 
STUDY ASSESSMENTS 
6.1 
Study assessments 
This study will begin with: 
1. Assessment of the eligibility criteria during Restorative New Patient Clinic, seen by 
clinicians on duty during the New Patient clinical sessions 
2. If patient is found suitable for the study, the patient will be invited to participate in 
this study and will be given the Patient Information Sheet (PIS) and consent form on 
the same day of the New Patient clinic 
3. The patients will be given time to consider their participation and can either return 
the consent form on the same day of their New Patient clinic appointment, whereby 
they will be given time during the gap between before going to Radiology Department 
for pre-operative radiograph(s) and return the consent form once they come back from 
the Radiology Department or during the first treatment visit. Written consent will be 
obtained upon returning the consent form and the patients will be given a study number 
based on numerical order (1,2,3 etc…) 
 
4. On the first treatment day, patients will be given the pre-operative Pain Assessment 
Questionnaire (a modified version adapted from VRS and NRS) 
5. After the completion of treatment, the patients will be given post-operative Pain 
Assessment Questionnaire (a modified version adapted from VRS and NRS) and post- 
operative quality of life (QoL) questionnaire. Patients will be called at 24 hours, 48 
hours and 7 days after treatment for the assessment. 

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Assessment 
Screening 
Treatment 
Day 
24H 
48H 
1 week 
Assessment of 
eligibility criteria & 
PIS 
X 
Written informed 
consent 
X* 
X* 
Pre-operative pain 
assessment 
X 
Post-operative 
pain assessment 
X 
X 
X 
Post-operative 
quality of life 
(POQoL) 
X 
X 
X 
Table 1: Research study plan in table form 
*Written consent can either be obtained on the screening day or 1st treatment 
visit. 

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7.0 DATA COLLECTION 
Detailed data to be collected: 
1. The Principal Investigator (NAF) will go through TRAK diaries to check for 
Restorative New Patient Clinic Sessions 
- The Principal Investigator will provide the clinicians on New Patient Clinic with PIS 
and consent forms 
- The Principal Investigator will follow-up with these clinicians at the end of the day to 
collect all returned consent forms as well as to keep track of patients who have brought 
back the consent forms and are due to return them during the first treatment 
appointment 
2. Since most patients will be placed in the waiting list after the New Patient Clinic 
appointment, before being assigned a clinician for the root canal treatment, the 
Principal Investigator will use the ‘watch’ feature on TRAK to keep track of the suitable 
patients that have been recruited during the New Patient Clinic to take note of the 
clinician that will be assigned to the patient 
 
3. Once the patients have been assigned a clinician, the Principal Investigator will go 
through the TRAK diaries of the clinicians involved in providing RCT, for the collection 
of the consent forms and distribution of pre-operative, post-operative pain assessment 
questionnaires and PoQOL questionnaires. 
 
4. The main investigator will create a document containing details of patients who have 
agreed to participate in the study, which will be securely saved on K-drive 
5. The main investigator will call patients to assess post-operative pain at 24H, 48H 
and 7 days, as well as the assessment of post-operative quality of life (QoL) at the 
same time frame 
 
6. The main investigator will also need to record any withdrawals from the study 
 
Time points for collection: 
- 
Pre-operative pain on treatment day before commencement of treatment 
- 
Post-operative pain and quality of life (QoL) at 24H, 48H, 7 days 
Data collector: 
- 
Principal Investigator (NAF) 
Details of standardized tools used: 
1. Pre-operative pain assessment questionnaire 
2. Post-operative pain assessment questionnaire 
3. Post-operative quality of life (POQoL) assessment 
Method to maximize completeness of data: 

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1. Patients will be contacted via phone to assess post-operative pain and quality of life 
- Questionnaires used have been validated for verbal/ phone call assessment 
 
 
 
7.1 
Source of data documentation 
 
The source of data will be from: 
i) Pre-operative pain assessment questionnaire 
ii) Post-operative pain assessment at 24H, 48H and 7 days 
iii) Post-operative quality of life (POQoL) assessment at 24H, 48H and 7 days 
 
 
7.2 
Case report forms 
 
The pain assessment questionnaires will be paper-based which will be stored securely 
in a pin-locked locker in the Postgraduate room on Level 4 of Edinburgh Dental 
Institute 

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8.0 DATA MANAGEMENT 
8.1.1 Personal data collection 
 
The following personal data will be collected as part of the research: 
1. Name 
2. CHI number 
3. Gender 
4. Age 
5. Address 
6. Updated phone number 
• All data will be stored on a password protected document saved on NHSL 
computers under the K drive. Patient identifiable information will not be copied or 
transferred from these computers. All the analysis of the data will be carried out 
on NHSL computers. 

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8.1.2 Data Information Flow 
 
 
 
Assess suitability, distribute PIS and consent form during New Patient Clinic 
(by respective clinicians on duty) 
 
 
 
Details of patients with PIS will be recorded by the Principal Investigator and 
will be safely stored in the K-drive. 
Once the consent form has been returned and consent obtained, the Principal 
Investigator will record relevant data of the patients participating in the study 
 
 
 
 
Patient's data collection 
 
Name 
CHI Number 
Updated phone 
number 
Gender 
Age 
Address 
 
 
 
 
Pre-operative pain assessment data will be recorded into Excel sheet with 
patient's study number only (numerical order) 
Data will be stored safely in the K-drive 
 
 
 
 
Post-operative pain and quality of life (QoL) assessment data at 24H, 48H and 
7 days will be recorded into Excel sheet with patient's study number only 
Data will be stored safely in the K-drive 
 
 
 
 
Personal data of participants will be removed from K-drive after the completion 
of study or once patients have withdrawn from the study 

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8.1.3 Transfer of Data 
Data collected or generated by the study (including personal data) will not be transferred to 
any external individuals or organisations outside of the Sponsoring organisation(s). 
 
 
8.1.4 Data Controller 
The University of Edinburgh and NHS Lothian. 
 
 
 
8.1.5 Data Breaches 
 
Any data breaches will be reported to the University of Edinburgh and NHS Lothian 
Data Protection Officers who will onward report to the relevant authority according to 
the appropriate timelines if required. 

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9.0 
STATISTICS AND DATA ANALYSIS 
9.1 
Sample Size Calculation 
Power analysis – NA 
Sample size – 150 
Effect size – NA 
Dropout rates – 20% 
 
 
9.2 
Proposed Analyses 
 
Detail the variables to be used for assessment and how these will be reported (e.g. 
means, standard deviations, medians etc.) Write detailed plans for analyses of primary 
and secondary outcome measures including: 
Summary measures to be reported 
The data will be analysed via logistic regression analysis. Each factor will first be 
analysed via the single-logistic regression analysis. The multiple-logistic regression 
analysis will then be conducted to compare the factors with each other 
 
Method of analysis 
Logistic regression analysis 
 
Plans for handling missing, unused and spurious data, non-compliers and 
withdrawals 
NA as the data will most likely not be used then 
 
Plans for pre-defined subgroup analyses 
Logistic regression analysis 
 
Statement regarding use of intention to treat analysis 
The intention to treat analysis will not be utilized as the study involves routine root 
canal treatment/ retreatment. Regardless of the case suitability, the patients will 
still be treated 
 
Details of any interim analysis 
NA 

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10 
ADVERSE EVENTS 
This study is a low-risk study, a normal clinical procedure of routine root canal 
treatment for patients requiring the treatment. It does not involve intervention with new 
materials or technology. 
 
However, this study does evaluate the incidence of pain following root canal treatment. 
Therefore, patients will receive standardized post-operative instructions after the 
completion of root canal treatment. This post-operative instruction follows the SDCEP 
guidelines as well as adapted from Menhinick et al., 2004. If ever required, this will be 
re-emphasized during the follow-up phone calls. 

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11 
OVERSIGHT ARRANGEMENTS 
 
11.1 
INSPECTION OF RECORDS 
Investigators and institutions involved in the study will permit trial related monitoring 
and audits on behalf of the sponsor, REC review, and regulatory inspection(s). In the 
event of audit or monitoring, the Investigator agrees to allow the representatives of the 
sponsor direct access to all study records and source documentation. In the event of 
regulatory inspection, the Investigator agrees to allow inspectors direct access to all 
study records and source documentation. 
 
11.2 
STUDY MONITORING AND AUDIT 
The ACCORD Sponsor Representative will assess the study to determine if an 
independent risk assessment is required. If required, the independent risk assessment 
will be carried out by the ACCORD Quality Assurance Group to determine if an audit 
should be performed before/during/after the study and, if so, at what frequency. 
 
Risk assessment, if required, will determine if audit by the ACCORD QA group is 
required. Should audit be required, details will be captured in an audit plan. Audit of 
Investigator sites, study management activities and study collaborative units, facilities 
and 3rd parties may be performed. 

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12.1 
ETHICAL CONDUCT 
The study will be conducted in accordance with the principles of the International 
Conference on Harmonization Tripartite Guideline for Good Clinical Practice (ICH 
GCP). Before the study can commence, all required approvals will be obtained 
and any conditions of approvals will be met. 
 
 
12.2 
INVESTIGATOR RESPONSIBILITIES 
The Investigator is responsible for the overall conduct of the study at the site and 
compliance with the protocol and any protocol amendments. In accordance with the 
principles of ICH GCP, the following areas listed in this section are also the 
responsibility of the Investigator. Responsibilities may be delegated to an appropriate 
member of study site staff. 
 
12.2.1 Informed Consent 
The Investigator is responsible for ensuring informed consent is obtained before any 
protocol specific procedures are carried out. The decision of a participant to participate 
in clinical research is voluntary and should be based on a clear understanding of what 
is involved. 
Participants must receive adequate oral and written information – appropriate 
Participant Information and Informed Consent Forms will be provided. The oral 
explanation to the participant will be performed by the Investigator or qualified 
delegated person, and must cover all the elements specified in the Participant 
Information Sheet and Consent Form. 
The participant must be given every opportunity to clarify any points they do not 
understand and, if necessary, ask for more information. The participant must be given 
sufficient time to consider the information provided. It should be emphasized that the 
participant may withdraw their consent to participate at any time without loss of 
benefits to which they otherwise would be entitled. 
The participant will be informed and agree to their medical records being inspected by 
regulatory authorities and representatives of the sponsor(s). 
The Investigator or delegated member of the trial team and the participant will sign 
and date the Informed Consent Form(s) to confirm that consent has been obtained. 
The participant will receive a copy of this document and a copy filed in the Investigator 
Site File (ISF) and participant’s medical notes (if applicable). 

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12.2.2 Study Site Staff 
The Investigator must be familiar with the protocol and the study requirements. It is 
the Investigator’s responsibility to ensure that all staff assisting with the study are 
adequately informed about the protocol and their trial related duties. 
 
12.2.3 Data Recording 
The Principal Investigator is responsible for the quality of the data recorded in the CRF 
at each Investigator Site. 
 
12.2.4 Investigator Documentation 
The Principal Investigator will ensure that the required documentation is available in 
local Investigator Site files ISFs. 
 
12.2.5 GCP Training 
 
- The Principal Investigator has attended a GCP training on 18/5/2021 
 
For non-CTIMP (i.e. non-drug) studies all researchers are encouraged to undertake 
GCP training in order to understand the principles of GCP. However, this is not a 
mandatory requirement unless deemed so by the sponsor. GCP training status for all 
investigators should be indicated in their respective CVs. 
 
12.2.6 Confidentiality 
 
All laboratory specimens, evaluation forms, reports, and other records must be 
identified in a manner designed to maintain participant confidentiality. All records must 
be kept in a secure storage area with limited access. Clinical information will not be 
released without the written permission of the participant. The Investigator and study 
site staff involved with this study may not disclose or use for any purpose other than 
performance of the study, any data, record, or other unpublished information, which is 
confidential or identifiable, and has been disclosed to those individuals for the purpose 
of the study.. Prior written agreement from the sponsor or its designee must be 
obtained for the disclosure of any said confidential information to other parties. 
 
12.2.7 Data Protection 
All Investigators and study site staff involved with this study must comply with the 
requirements of the appropriate data protection legislation (including the General Data 
Protection Regulation and Data Protection Act) with regard to the collection, storage, 
processing and disclosure of personal information. 
Computers used to collate the data will have limited access measures via usernames 
and passwords. 

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Published results will not contain any personal data and be of a form where individuals 
are not identified and re-identification is not likely to take place 
 
 
STUDY CONDUCT RESPONSIBILITIES 
 
 
12.3 
PROTOCOL AMENDMENTS 
Any changes in research activity, except those necessary to remove an apparent, 
immediate hazard to the participant in the case of an urgent safety measure, must be 
reviewed and approved by the Chief Investigator. 
Amendments will be submitted to a sponsor representative for review and 
authorisation before being submitted in writing to the appropriate REC, and local R&D 
for approval prior to participants being enrolled into an amended protocol. 
 
12.4 
MANAGEMENT OF PROTOCOL NON-COMPLIANCE 
Prospective protocol deviations, i.e. protocol waivers, will not be approved by the 
sponsors and therefore will not be implemented, except where necessary to eliminate 
an immediate hazard to study participants. If this necessitates a subsequent protocol 
amendment, this should be submitted to the REC, and local R&D for review and 
approval if appropriate. 
Protocol deviations will be recorded in a protocol deviation log and logs will be 
submitted to the sponsors every 3 months. Each protocol violation will be reported to 
the sponsor within 3 days of becoming aware of the violation. All protocol deviation 
logs and violation forms should be emailed to QA@accord.scot 
Deviations and violations are non-compliance events discovered after the event has 
occurred. Deviation logs will be maintained for each site in multi-centre studies. An 
alternative frequency of deviation log submission to the sponsors may be agreed in 
writing with the sponsors. 
 
12.5 
SERIOUS BREACH REQUIREMENTS 
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 participants of the trial; or 
(b) the scientific value of the trial. 
If a potential serious breach is identified by the Chief investigator, Principal Investigator 
or delegates, the co-sponsors (seriousbreach@accord.scot) must be notified within 24 
hours. It is the responsibility of the co-sponsors to assess the impact of the breach on 
the scientific value of the trial, to determine whether the incident constitutes a serious 
breach and report to research ethics committees as necessary. 
 
12.6 
STUDY RECORD RETENTION 

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All study documentation will be kept for a minimum of 3 years from the protocol defined 
end of study point. When the minimum retention period has elapsed, study 
documentation will not be destroyed without permission from the sponsor. 
 
12.7 
END OF STUDY 
The end of study is defined as the last participant’s last visit. 
The Investigators or the co-sponsor(s) have the right at any time to terminate the study 
for clinical or administrative reasons. 
The end of the study will be reported to the REC, and R+D Office(s) and co-sponsors 
within 90 days, or 15 days if the study is terminated prematurely. The Investigators will 
inform participants of the premature study closure and ensure that the appropriate 
follow up is arranged for all participants involved. End of study notification will be 
reported to the co-sponsors via email to resgov@accord.scot 
A summary report of the study will be provided to the REC within 1 year of the end of 
the study. 
The patients will continue to receive all planned treatment even after the completiong 
of the study. They will also be routinely reviewed at 6 months after the completion of 
the root canal treatment, as this is the practice in the Restorative Department, 
Edinburgh Dental Institute. 
 
 
 
12.8 
INSURANCE AND INDEMNITY 
The co-sponsors are responsible for ensuring proper provision has been made for 
insurance or indemnity to cover their liability and the liability of the Chief Investigator 
and staff. 
The following arrangements are in place to fulfil the co-sponsors' responsibilities: 
• 
The Protocol has been designed by the Chief Investigator and researchers 
employed by the University and collaborators. The University has insurance 
in place (which includes no-fault compensation) for negligent harm caused by 
poor protocol design by the Chief Investigator and researchers employed by 
the University. 
• 
Sites participating in the study will be liable for clinical negligence and other 
negligent harm to individuals taking part in the study and covered by the duty 
of care owed to them by the sites concerned. The co-sponsors require 
individual sites participating in the study to arrange for their own insurance or 
indemnity in respect of these liabilities. 
• 
Sites which are part of the United Kingdom's National Health Service will have 
the benefit of NHS Indemnity. 
• 
Sites out with the United Kingdom will be responsible for arranging their own 
indemnity or insurance for their participation in the study, as well as for 
compliance with local law applicable to their participation in the study. 

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13.0 
REPORTING, PUBLICATIONS AND NOTIFICATION OF RESULTS 
13.1 
Authorship Policy 
Ownership of the data arising from this study resides with the study team. 

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14.0   REFERENCES 
1. Paul A. Rosenberg, Peter J. Babick, Leon Schertzer, Anthony Leung. The effect of 
occlusal reduction on pain after endodontic instrumentation. Journal of Endodontics, 
Volume 24, Issue 7, 1998, Pages 492-496 
ISSN 0099-2399 
https://doi.org/10.1016/S0099-2399(98)80054-X. 
 
2. ElMubarak, A., H., Abu-bakr, N., H., & Ibrahim, Y., E. (2010). Postoperative pain in 
multiple-visit and single-visit root canal treatment. Journal of Endodontics 36(1): 36- 
39. 
doi: https://doi.org/10.1016/j.joen.2009.09.003 
 
3. Ali, S. G., Mulay, S., Palekar, A., Sejpal, D., Joshi, A., & Ghufran, H. (2012). 
Prevalence of and factors affecting post-obturation pain following single visit root canal 
treatment in Indian population: A prospective randomized clinical trial. Contemp. Clin. 
Dent, 3(4): 459-463. doi: 10.4103/0976-237X.107440: 10.4103/0976-237X.107440 
 
4. Watkins, C., A., Logan, H., L., & Kirchner, H., L. (2002). Anticipated and 
experienced pain associated with endodontic therapy. Journal of the American Dental 
Association 133, 45–54. 
5. Torabinejad, M., Kettering, J., D., McGraw, J., Cummings, R., R., Dwyer, T., G., & 
Tobias, T. (1988). Factors associated with endodontic interappointment emergencies 
of teeth with necrotic pulps. J. Endod; 14: 261-266 
 
6. Morse, D., R., Koren, L., Z., Esposito, J., V., Goldberg, J., M., Sinai, I., H., & Furst, 
M., L. (1986). Asymptomatic teeth with necrotic pulps and associated periapical 
radiolucencies: relationship of flare-ups to endodontic instrumentation, antibiotic 
usage and stress in three separate practices at three different time periods. Parts 1– 
5. Int J Psychosom;33:5–87. 
 
7. Imura, N., & Zuolo, M., L. (1995). Factors associated with endodontic flare-ups: a 
prospective study. Int Endod J; 28:261–5. 
8. Siqueira, J., F. (2003). Microbial causes of endodontic flare-ups. Int Endod J; 
36:453-63. 
 
9. Walton, R., E., Holton, I., F., & Michelich, R. (2003). Calcium Hydroxide as an 
intracanal medication: effect on posttreatment pain. Journal of Endodontics; 29(10): 
627-629 
10. Mattscheck, D., J., Law, A., S., & Noblett, W., C. (2001). Retreatment versus initial 
root canal treatment: factors affecting posttreatment pain. Oral Surg Oral Med Oral 
Pathol Oral Radiol Endod.; 92:321-24. 
 
11. Iqbal, M., Kurtz, E., & Kohli, M. (2009). Incidence and factors related to flare-ups 
in a graduate endodontic programme. Int Endod J.; 42:99–104. 

Pain following root canal treatment <PfRCT> 
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12. Marbach, J., J., Hulbrock, J., Hohn, C., & Segal, A., G. (1982). Incidence of 
phantom tooth pain: an atypical facial neuralgia. Oral Surgery, Oral Medicine, and Oral 
Pathology 53, 190–3. 
 
13. Law, A., S., & Lilly, J., P. (1995). Trigeminal neuralgia mimicking odontogenic 
pain. A report of two cases. Oral Surgery, Oral Medicine, Oral Pathology, Oral 
Radiology, and Endodontics 80, 96–100. 
14. Nixdorf, D., R., Law, A.,S., & John, M., T., et al. (2015). Differential diagnoses for 
persistent pain after root canal treatment: a study in the National Dental Practice- 
based Research Net- work. Journal of Endodontics 41, 457–63. 
 
15. Alonso, A., A., & Nixdorf, D., R. (2006). Case series of four different headache 
types presenting as tooth pain. Journal of Endodontics 32, 1110–3. 
 
16. Nixdorf, D., R., Moana-Filho, E., J., & Law, A., S., et al. (2010). Frequency of 
persistent tooth pain after root canal therapy: a system- atic review and meta-analysis. 
Journal of Endoddontics 36, 224–30. 
 
17. Udoye, C., H., & Aguwa, E. (2010). Flare - up incidence and related factors in 
adults. J Dent Oral Hyg; 2:19-22. 
 
18. Yu, V., S., Messer, H.,H., Yee, R., & Shen, L.(2012). Incidence and impact of 
painful exacerbations a cohort with post-treatment persistent endodontic lesions. J 
Endod; 38:41-6. 
 
19. Gotler, M., Bar-Gil, B., & Ashkenazi, M. (2012). Postoperative pain after root canal 
treatment: a prospective cohort study. Int J Dent;2012:310467. 
20. Walton, R., & Fouad, A. (1992). Endodontic interappointment flare - ups: a 
prospective study of incidence and related factors. J Endod;18:172-7. 
 
21. Shah, S., I., Qayyum, Z., Shah, S., A., Khan, S., & Pasha, F. (2011). Prophy- lactic 
use of antibiotics to prevent flare - up in endodontic treatment. Pakist Oral Dental 
J;31:427-31. 
22. Pasqualini, D., Mollo, L., Scotti, N., Cantatore. G., Castellucci, A., Migliaretti, G., 
et al. (2012). Postoperative pain after manual and mechanical glide path: a 
randomized clinical trial. J Endod;38:32-6. 
 
23. Ehrmann, E., H., Messer, H., H., & Adams, G., G.(2003). The relationship of 
intracanal medicaments to postoperative pain in endo- dontics. Int Endod J;36:868- 
75. 
24. Thesis, I., Faivishevsky, V., Fuss, Z., & Zukerman, O. (2008). Flare - ups after 
Endodontic Treatment: A Meta - Analysis of Literature. J Endod;10:1177-81. 

Pain following root canal treatment <PfRCT> 
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32 
 
 
25. Orstavik, D., Kerekes, K., & Molven, O. (1991). Effects of extensive apical reaming 
and calcium hydroxide dressing on bacterial infection during treat- ment of apical 
periodontitis: a pilot study. International Endodontic Journal;24(1):1–7 
 
26. Sjogren, U., Figdor, D., Persson, S., & Sundqvist, G. (1997). Influence of infection 
at the time of root filling on the outcome of endodontic treatment of teeth with apical 
periodontitis. International Endodontic Journal;30(5):297–306. 
27. Siqueira, J., F., Favieri, A., Gahyva, S., M., Moraes, S., R., Lima, K., C., & Lopes, 
H., P. (2000). Antimicrobial activity and flow rate of newer and established root canal 
sealers. Journal of Endodontics;26(5):274–7. 
 
28. Gilheany, P., A., Figdor, D., & Tyas, M., J. (1994). Apical dentin permeability and 
microleakage associated with root end resection and retrograde filling. Journal of 
Endodontics; 20(1): 22–26. 
29. Ince, B., Ercan, E., Dalli, M., Dulgergil, C., T., Zorba, Y., O., & Colak, H. (2009). 
Incidence of postop- erative pain after single- and multi-visit endodontic treatment in 
teeth with vital and non-vital pulp. Eur J Dent;3:273–279. 
 
30. Gomes, M., S., Böttcher, D., E., Scarparo, R., K., et al. (2017). Predicting pre- and 
postoperative pain of endodontic origin in a southern Brazilian subpopulation: an 
electronic database study. Int Endod J 50:729– 739. https://doi.org/10.1111/iej.12684 
 
31. Bourreau, M., L., S., Soares, A., D., J., & Souza-Filho, F., J., D. (2015). Evaluation 
of postoperative pain after endodontic treatment with foraminal enlargement and 
obturation using two auxiliary chemical protocols. Rev Odontol UNESP; 44: 157-162. 
32. Singh, S., & Garg, A. (2012). Incidence of post-operative pain after single visit and 
multiple visit root canal treatment: a randomized controlled trial. J Conserv Dent; 15: 
323. 
 
33. Oginni, A., O., & Udoye, C., I. (2004). Endodontic flare-ups: comparison of 
incidence between single and multiple visit procedures in patients attending a Nigerian 
teaching hospital. BMC Oral Health; 4: 1. 
34. Albashaireh, Z., & Alnegrish, A. (1998). Postobturation pain after single- and 
multiple-visit endodontic therapy. A prospective study. J Dent; 26: 227-232. 
 
35. Risso, P., D., A., Cunha, A., Araujo, M., & Luiz, R. (2008). Postobturation pain and 
associated factors in adolescent patients undergoing one- and two-visit root canal 
treatment. J Dent; 36: 928-934. 
36. Ng, Y., L., Glennon, J., Setchell, D., & Gulabivala, K.(2004). Prevalence of and 
factors affecting post-obturation pain in patients under- going root canal treatment. Int 
Endod J; 37: 381-391. 

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37. Glennon, J., Ng, Y., L., Setchell, D., & Gulabivala, K.(2004). Prevalence of and 
factors affecting postpreparation pain in patients undergoing two-visit root canal 
treatment. Int Endod J; 37: 29-37. 
 
38. Siqueira, J., F., Roˆ c ̧  as, I., N., Favieri, A., Machado, A., G., Gahyva, S., M., 
Oliveira, J., C., et al. (2002). Incidence of postoperative pain after intra- canal 
procedures based on an antimicrobial strategy. J Endod; 28: 457e460. 
39. Bhagwat, S., & Mehta, D. (2013). Incidence of post-operative pain following single 
visit endodontics in vital and non-vital teeth: an in vivo study. Contemp Clin Dent; 4: 
295. 
 
40. Fava, L. (1995). Single visit root canal treatment: incidence of post- operative pain 
using three different instrumentation techniques. Int Endod J; 28: 103e107. 
 
41. Philpott, R., Gulabivala, K., Lesson, R., & Ng, Y.-L. (2019). Prevalence, predictive 
factors and clinical course of persistent pain associated with teeth displaying periapical 
healing following nonsurgical root canal treatment: a prospective study. International 
Endodontic Journal; 52: 407-415. 
 
42. Arias, A., de la Macorra, J. C., Hidalgo, J. J., & Azabal, M. (2013). Predictive 
models of pain following root canal treatment: a prospective clinical study. Int Endod 
J, 46(8), 784-793. https://doi.org/10.1111/iej.12059 

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APPENDIX 1 - Study design 
 
Assessment of suitable patients from Restorative New Patient Clinic by 
clinicians on duty 
 
 
Suitable patients (based on inclusion criteria) requiring RCT will be 
invited to participate in this research study 
 
 
Patient Information Sheet (PIS) and consent forms will be given to 
patients during the New Patient Clinic 
 
 
Patients will be given time to decide. The 2 options are: 
1.  Read the PIS and provide with a decision after coming back from 
Radiology Department (for patients requiring new radiographs) 
2. Return the consent form during the first treatment visit 
 
 
Obtaining written consent 
- 
Written consent will be attached together with the PIS 
 
 
Treatment Day 1 
Distribution of Pre-operative Pain Assessment Questionnaire to patient 
prior to commencement of treatment (by clinician providing the 
treatment) 
 
Treatment Day 1 
Commencement of root canal treatment 
(By Postgraduate Trainees in Endodontology, Prosthodontics Years 
1,2,3, Core Trainees and Specialist Registrars in Restorative Department 
and the Staff Member of the Restorative Department, Edinburgh Dental 
Institute) 
 
 
Distribution of Post-operative Pain Assessment Questionnaire & Post- 
operative Quality of Life (PoQOL) Questionnaire upon completion of root 
canal treatment 
 
 
Patients will be called by the Principal Investigator (NAF) at 24H, 48H 
and 7 days to assess post-operative pain & post-operative quality of life 

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APPENDIX 2 – Treatment Notes Template 
Management for today: 
1. Any additional special tests done/ repeated 
 
2. Assessment of soft tissues for signs of infection 
 
 
3. Assessment of the tooth of concern: 
(i) Type and quality of pre- existing restoration 
(ii) Tenderness to palpation 
(iii) Tenderness to percussion 
(iv) Mobility 
(v) Periodontal pocket depth 
 
 
4. Additional sensibility tests conducted 
(i) EPT 
(ii) Cold test 
 
 
5. Diagnosis on the first treatment visit 
 
6. A not on whether any treatment has been carried out prior to having treatment 
initiated at EDI 
 
7. Treatment sequence 
8. Radiographic outcome 
 
 
Note: Please distribute post-operative pain assessment & post-operative quality of life assessment questionnaires to patients. Thank you 
 
 
 

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