Clinical Study of Laser Analgesia in Cavity Preparations
Phase: NA
Conditions: Tooth Pain
Sponsor: Chen Laser Institute

  
 
18-CHEN-101  
APPROVED 13Dec2018 to 12Dec2019 
CLINICAL STUDY PROTOCOL 
 
Clinical Study of Laser Analgesia in Cavity Preparations 
using the Er,Cr:YSGG Laser  
 
 
Protocol #:  
 
Dr. William Chen 
4168 Nameoki Road, Granite City, Illinois 62040 
(618) 931-2025 
 
9-Sep-2018 
 
PROTOCOL VERSION HISTORY 
Version 
Date (dd-mmm-yyyy) 
Initial 
9-Sep-2018 
Amendment 
N/A 
 
ETHICS AND REGULATORY COMPLIANCE STATEMENT 
The procedures set forth in this protocol are designed to ensure that the sponsor(s) and 
principal investigator(s) abide by the International Conference on Harmonization (ICH) 
current Good Clinical Practice (cGCP) guidelines, current Good Laboratory Practice (cGLP) 
guidelines, the Declaration of Helsinki, and applicable local regulatory requirements and 
laws in the conduct, evaluation, and documentation of this study. 

 
  
Protocol Name 
Laser Analgesia 
Protocol Number 
 
Investigational Product Name 
Laser Analgesia in Cavity Preparations 
Date: (dd-mmm-yyyy) 
06-Sept-2018 
Author 
Dr. William Chen 
 
PROTOCOL HISTORY 
Version 
Date (dd-mmm-yyyy) 
Description 
V1  
06-Sept-2018 
Initial Release 
V2 
 
 
 
PROTOCOL APPROVALS 
Name 
Signature 
Date 
(dd-mmm-yyyy) 
Department 
 
eSignature 
eDate 
 
 
eSignature 
eDate 
 
 
eSignature 
eDate 
 
 
 

 
  
CONTACT INFORMATION 
Sponsor 
Dr. William Chen 
Primary Study Contact, Principal 
Investigator 
 
Dr. William Chen 
Project Team Lead 
Regulatory Affairs 
Dr. William Chen 
Dr. William Chen 
Study Monitor 
Unanticipated Adverse Device Events 
Dr. William Chen 
Dr. William Chen 
Legal Affairs 
Protocol Author:  
Dr. William Chen 
Dr. William Chen 
Sub-investigators: Kendra Stevenson, 
Melissa Layne 
 
Coordinating Investigator and Principal Investigators   
An updated list of Principal Investigators (PI), investigation sites, and institutions will be 
maintained separately. The definitive list will be provided in the clinical study report. 
 

 
  
PROTOCOL SIGNATURE PAGE 
 
 
Clinical Study of Laser Analgesia in Cavity Preparations 
using the Er,Cr:YSGG Laser 
 
 
As an Investigator for this Study, I have read the Clinical Trial Protocol. I agree to make 
available to the Sponsor, Dr. William Chen (or its designee), original source documents and 
all regulatory documents pertaining to this Study. I agree to cooperate fully with the Sponsor 
with the conduct of study-related audits. 
 
By my signature below, I agree to conduct this Study in accordance with the Clinical 
Trial Protocol, current Good Clinical Practice (cGCP) and Good Laboratory Practice 
(cGLP) guidelines, obligations as set forth in Title 21 CFR Parts 812, 54, 56 and 11 (as 
applicable), and any applicable regulatory laws. I will make no changes to protocol-
defined procedures without written permission from the Sponsor.   
 
I understand that Investigational Use Products may be used only for the purposes explicitly 
described in this protocol.  
 
I further agree to treat the results of this Study as confidential information and will not 
submit the results of the Study for publication without prior written authorization from the 
Sponsor.  
 
 
 
 
 
William Chen 
 
 
 9/19/18 
PRINTED NAME 
 SIGNATURE 
 DATE 
 
 

 
  
SYNOPSIS 
Title of Study 
Clinical Study of Laser Analgesia in Cavity Preparations using 
the Er,Cr:YSGG Laser 
Objectives 
 
To show there is laser analgesia. Restorative dental procedures 
potentially can be performed without needle injection first.  
 
Planned Number of 
Subjects and Duration 
of Involvement 
 The planned number will be forty-eight patients. The duration 
will last till all patients are done. 
Patient Population 
 
Patients included in the study are adults 19-65 years old who had 
at least two cavity preparations of the same type, with the same 
approximate size lesion. Excluded patients include children, 
people with language barriers, pregnant women, immune 
compromised patients compromised (No bronchitis, no sinus 
infection, no ear infection, ect…), patients with heart disease, 
uncontrolled hypertension, cardiac arrhythmia, and patients 
whose teeth amalgam restorations were in close proximity to the 
lesion. 
Investigational Product 
Name 
Clinical Study of Laser Analgesia in Cavity Preparations using 
the Er,Cr:YSGG Laser 
Methodology Overview 
 
 The study involves using the Er,Cr:YSGG Laser to perform 
cavity preparation without giving any injection anesthesia. This 
study is going to be done to show there is laser analgesia. 
 
 
 

 
  
ABBREVIATIONS 
 
 
 
 
 
 
 
 
US/USA 
United States of America 

 
  
TABLE OF CONTENTS 
1 
INTRODUCTION ....................................................................................................... 10 
2 
DESCRIPTION OF THE INVESTIGATIONAL PRODUCT ..................................... 10 
2.1 
Overview ................................................................................................................. 10 
2.2 
Proposed Intended Use Statement .......................................................................... 11 
3 
STUDY OBJECTIVES ................................................................................................ 11 
4 
STUDY OVERVIEW ................................................................................................... 12 
4.1 
Study Approach ...................................................................................................... 12 
4.2 
Study Duration ........................................................................................................ 13 
5 
STUDY POPULATION ............................................................................................... 13 
5.1 
Sample Size and Target Study Population .............................................................. 13 
5.1.1 
Sample size ..................................................................................................................... 13 
5.1.2 
Study population ............................................................................................................. 14 
5.1.3 
Alignment with intended study population ..................................................................... 14 
5.1.4 
Alignment with intended use of the device .................................................................... 14 
5.2 
Recruitment Methods .............................................................................................. 14 
5.2.1 
Recruitment for Laser Analgesia Study .......................................................................... 14 
5.2.2 
Duration of study activities ............................................................................................. 14 
5.3 
Patient Selection...................................................................................................... 14 
6 
STUDY MATERIALS ................................................................................................. 15 
6.1 
Investigational Product ........................................................................................... 15 
6.1.1 
Identity of the investigational product and accessories .................................................. 15 
6.1.2 
Safety issues ................................................................................................................... 15 
6.1.3 
Handling, storage, accountability ................................................................................... 15 
6.1.4 
Required training ............................................................................................................ 16 
6.1.5 
External studies ............................................................................................................... 16 
6.2 
Other Study Materials ............................................................................................. 16 
6.2.1 
Materials to be provided by study site ............................................................................ 16 
6.2.2 
Materials to be provided by external testing facilities .................................................... 16 
6.3        Concent Procedures ................................................................................................ 16 
7 
STUDY PROCEDURES .............................................................................................. 17 
7.1 
Workflow ................................................................................................................ 17 
7.2 
Study Data ............................................................................................................... 18 
7.2.1 
Collection of data ............................................................................................................ 18 
7.3 
Randomization and Blinding .................................................................................. 18 

 
  
7.4 
Procedures for Study Closure ................................................................................. 18 
7.4.1 
Routine study close-out .................................................................................................. 18 
7.4.2 
Suspension or premature termination of the study ......................................................... 19 
8 
DATA QUALITY ASSURANCE ................................................................................. 19 
9 
STATISTICAL METHODS ........................................................................................ 19 
9.1 
Determination of Sample Size ................................................................................ 19 
9.2 
Bias Minimization ................................................................................................... 20 
9.3 
Planned Analyses .................................................................................................... 20 
10 ADVERSE EVENT REPORTING .............................................................................. 20 
10.1 
Non-Device-Associated Adverse Events ................................................................ 20 
10.2 
Device-Associated Adverse Events ........................................................................ 21 
10.2.1 Definition of an unanticipated adverse device effect (UADE) event ............................. 21 
10.2.2 Reporting of device-associated adverse events .............................................................. 21 
10.3 
Sponsor Contact for Serious Adverse Event Reporting .......................................... 21 
11 RISK ANALYSIS ........................................................................................................ 21 
11.1 
Potential Risks of the Investigational Product and Clinical Investigation .............. 21 
11.2 
Potential Benefits of the Investigational Product and Clinical Investigation ......... 22 
11.3 
Minimization of Risks............................................................................................. 22 
12 INVESTIGATOR RESPONSIBILITIES..................................................................... 22 
12.1 
Site Qualification and Study Oversight .................................................................. 22 
12.2 
Case Report Forms/Electronic Data Records ......................................................... 22 
12.3 
Access to Source Documents .................................................................................. 23 
12.4 
Financial Disclosure................................................................................................ 23 
12.5 
Deviations from the Study Protocol ........................................................................ 23 
12.6 
Record Retention .................................................................................................... 23 
12.7 
Publication Policy ................................................................................................... 24 
13 ETHICS AND COMPLIANCE ................................................................................... 24 
13.1 
Investigational Device Exemption .......................................................................... 24 
13.2 
Informed Consent and De-Identification ................................................................ 24 
13.2.1 Prospectively collected data ........................................................................................... 24 
13.3 
IRB Review ............................................................................................................. 24 
13.4 
Confidentiality of Data and Patient Records .......................................................... 25 
14 REFERENCES ................................................................... Error! Bookmark not defined. 
 

 
  
LIST OF TABLES 
Table 1. 
Inclusion/Exclusion Criteria for Enrollment of Subjects .................................... 15 
 
LIST OF FIGURES 
No table of figures entries found. 

 
  
1 
INTRODUCTION 
General dentistry can be stressful to both the patient and the doctor due to the fear of 
the needle before most dental procedures. One of the main benefits of using Lasers is pain 
reduction and anti-inflammation. In some of the references, scientists use electrodes inserted 
in the brain of cats or rabbits. They have also placed electrodes in the pulp of teeth to 
measure action potentials as pain is perceived or attenuated. They were able to show that pain 
causes action potential formed and pain reduction (analgesia) causes diminishing effects on 
the action potential. However, this is not practical in human study. Using the Visual Analog 
Scale (VAS) is a good way in gauging the patient’s experience of the procedures. Small, 
medium, and large sized cavity preparations all to be measured. Effort is made to standardize 
the amount of cutting with each technique. The study is aimed to show if there is Laser 
Analgesia and if the use of Low Level Laser Therapy makes a difference in providing better 
analgesia.  
2 
DESCRIPTION OF THE INVESTIGATIONAL PRODUCT  
2.1 
Overview  
Lasers have been used in several areas of medicine for a long time, even becoming a 
standard of care for many medical specialties, ophthalmology, dermatology, urology. In 
dentistry, the clinical use of lasers began in the 1980s. In search of the ideal wavelength for 
all dental needs, several manufacturers developed different systems and each had their own 
benefits and limitations. Overtime and research, it has been understood how these different 
lasers act on the bio-physical aspect, and that there wasn’t one laser that could answer all our 
needs in dentistry [3]. Lasers work by emitting a wavelength of high energy light, which 
when focused on a certain skin condition that will create heat and destroy diseased cells. 
These lasers have a very high affinity for tissues containing water. Work performed by 
Ohshiro and Calderhead showed that an Er:YAG laser can be used to achieve laser analgesia 
based on the concept that Low Level Laser Therapy (LLLT) may occur simultaneously with 
high level laser treatment [1]. Laser analgesia does not produce a profound lack of sensation 
as is the case with using an injection anesthesia. It has been shown in vivo studies that LLLT 
can produce an analgesic effect on nerves that innervate the oral cavity by using a near or 
middle infrared laser [2, 3, 11, 12, 13, 14, 15]. It is theorized that LLLT decreases the firing 
frequency of nociceptors (pain receptors), particularly the afferent axons from nociceptors 
that are of low velocities. The LLLT affects only selective target fibers. As a result, The 
LLLT produces an analgesic effect, but not an anesthetic effect.  
Laser specific to this study is Er,Cr:YSGG (Erbium, Chromium: Yttrium, Scandium, 
Gallium, garnet) which is a waterlase iplus laser from Biolace, Inc. Irvine, CA. This laser is 
the markets best-selling all-tissue laser that is minimally invasive and used for dentistry. It 
features expanded and enhanced capabilities such as the Surefire delivery system and 
REPAIR protocols to give patients the best experience and for practice growth. Waterlase 

 
  
iplus offers complete versatility across all tissue types. It is engineered to provide a 
refreshing, comfortable patent experience when compared to traditional tools. It is cleared for 
over 80 different indication for soft tissue, hard tissue and bone. This is more than any other 
dental laser out there. Waterlaser iplus leads to results by empowering dentists to offer the 
best possible dental experience with single-visit, multi-quadrant, minimally invasive 
dentistry.  This system is reliable, durable and flexible for any dental practice.  
Er, Cr:YSGG laser system (2790nm, middle infrared) for cavity preparation and caries 
removal without the need of injection is one of the most attractive advantages of using the 
laser [4 , 5, 16, 17, 18, 19].  Due to the plentiful amount of water and air cooling in the 
Er:Cr:YSGG laser, there is no temperature change on the surface.[6] There is already the 
benefit of no side effect of heat on the surface of treatment. Different techniques are being 
used to achieve cavity preparation with the Er:Cr:YSGG laser system with no injection 
anesthesia [7]. The results claimed by using the different techniques are generally presented 
based on anecdotal evidence. One group of users may use one setting, typically at higher 
power levels, to perform the entire cavity preparation. A few of these high power examples 
are 6 Watts at 20 Hz, 4.5 Watts at 15 Hz, or 3 Watts at 10 Hz. Another group of users may 
use a moderate power setting to perform the entire cavity preparation such as 4.5 Watts at 20 
Hz, 3.5 Watts at 15 Hz, or 2.5 Watts at 10 Hz and the setting is used. A third group of users 
use different settings for each step of the cavity preparation. They start out using relatively 
lower power such as 2 Watts, 30 Hz at a new lesion on the occlusal surface. The power is 
incrementally raised over time until ablation of the tooth takes place. After the cavity is 
removed, a lower power setting is used to finish and smooth the final preparation. The setting 
used is 2 Watts at 30 Hz. The users of these different techniques all claim they could perform 
cavity preparations without giving injection anesthesia and the patients are comfortable. 
Because of the multiple variables involved in cavity preparation and causes of 
discomfort, the study will focus on specific parameters that may induce an analgesic effect. 
There are multiple variables in choice of power and frequencies that different users select for 
cavity preparation. In this study, we will focus on specific parameters and cavity preparations 
in small lesions (1.5mm X 1.5mm X 2mm) and in medium (2mm X 2m X 2.5mm) / large 
lesions (3.5mm X 2.5mm X 3mm ).   
 
2.2 
Proposed Intended Use Statement 
The intended use is to find out if there is laser analgesia and if LLLT makes a difference in 
providing better analgesia to patients. 
3 
STUDY OBJECTIVES 
The principal objective of this study is to prove the phenomenon of laser analgesia. 
Traditionally before a cavity preparation is performed, the doctor will use local anesthetic 
(Needle Injection) before using rotary instrument to do a cavity preparation. The study 
involves using the Er,Cr=YSGG Laser to perform cavity preparation without giving any 
injection anesthesia. VAS (Visual Analog Scale) will be used to have patients rate the laser 

 
  
cavity preparation procedure to show there is laser analgesia. On each patient subject that has 
two similar size cavities of the same classification, either Class I or Class V, on similar teeth. 
Two different laser protocols will be used. One includes Low Level Laser Therapy (LLLT) 
to condition the pulp producing analgesia before using higher power to perform the cavity 
prep. The other protocol will skip the LLLT setting and prepare the cavity with the higher 
power to perform the cavity prep. The design of the study is to find out if there is laser 
analgesia and if LLLT makes a difference in providing better analgesia. The VAS forms 
from each procedure will be used to show there is laser analgesia and potentially cavity 
preparations can be performed by using the laser without the need to give injection anesthesia 
first. 
4 
STUDY OVERVIEW 
4.1 
Study Approach 
Treatment. Preconditioning and cavity preparation are done using the Er:Cr:YSGG laser, 
Waterlase MD (mfg: Biolase Technology Inc, Irvine CA), and the gold hand piece with an 
MG6 fiber tip, trunk fiber, contra-angle hand piece. Preconditioning. Preconditioning is 
preformed using laser desensitization. One tooth will be randomly selected, and 
preconditioning will be performed using LLLT on the tooth with minimal tooth ablation. The 
LLLT settings that will be used for preconditioning are 0.25 Watts, 50 Hz, 0% water, 0% air, 
H mode. Following this a fiber-optic tip will be aimed perpendicular to the surface of the 
cervical portion of the tooth, ensuring that a 2mm distance will be maintained between the 
end of the fiber optic tip and the surface. The fiber-tip will be used to generate a 2mm line. 
The cavity on the second tooth will be prepared for without laser preconditioning. Lesion 
Preparation – small preparations. Small preparations are to be performed as follows. The 
Waterlase MD is set to 4.5W, 15 Hz, 65% air, and 60% water and the cavity is prepared 
according to the preferred technique. If patients indicate sensitivity, the procedure will be 
halted, patients fill out the VAS form and anesthetic will be offered. For patients who refuse 
anesthetic, the procedure will be continued at the same settings. Lesion Preparation – small 
to medium preparations. Small to medium preparations will be performed as follows. The 
Waterlase MD will be set to 2W, 15 Hz, 65% air, and 60% water and the cavity will be 
prepared according to the preferred technique. If patients indicate sensitivity, the procedure 
will be halted, patients fill out the VAS form and anesthetic will be offered. For patients who 
refuse anesthetic, the procedure will be continued at the same settings. 
 
Restoration. Overall VAS Score. Up to 3 intra-operative VAS measurements are recorded. If 
a patient feels even the slightest amount of pain during the procedure, they will be instructed 
to raise their hand and the treatment will be paused. The patient is then asked to fill in the 
VAS form before the procedure will be continued. After conclusion of the cavity preparation, 
patients will be asked to mark one last VAS rating indicating the overall pain of the 
procedure. Patients that do not raise their hand throughout the entirety of the procedure will 
be given an overall VAS rating of zero. Data for each patient will be recorded and analyzed 
in this way. 

 
  
Explanation of VAS analysis 
The VAS scale will be presented to the patients using a standard explanation 
(zero, indicating no pain at all, to 100, representing the ‘worst pain patient had ever 
felt’). Patients will be asked to place a vertical line on the VAS scale to indicate 
his/her discomfort status. They are encouraged to stop the treatment if they encounter 
any pain. The number of hand raises, as defined by the protocol, will be recorded and 
analyzed (small and medium/large preparations are analyzed separately), represent 
the number of times during the procedure the patient felt sufficient discomfort to stop 
the procedure. 
 
VAS data will be assessed by the following assumptions: The 'lower' the average 
score, the 'better' the mode of treatment. Once the patient marks their vertical line on 
the scale, a precise measurement, in millimeters, was taken from the “zero” line of the 
VAS scale to where the patient marked their line. 
 
 
 
 
 
 
 
 
 
 
 
4.2 
Study Duration 
The duration of this study will be conducted until all data is collected from the number of 
participants needed to complete this study. 
5 
STUDY POPULATION 
5.1 
Sample Size and Target Study Population 
5.1.1 
Sample size 
The total number of individual subjects is expected to reach approximately forty-eight 
patients. This estimate is based on the number of teeth that possibly will need to have this 
surgery out of the people that come to the office. 
No Pain 
Moderate 
Pain 
Worst 
Pain 

 
  
5.1.2 
Study population  
The study population will be representative patients that include adults 19-65 years old who 
had at least two cavity preparations of the same type, with the same approximate size lesion. 
Excluded patients include children, pregnant women, immune compromised patients, patients 
with heart disease, uncontrolled hypertension, cardiac arrhythmia, patients whose teeth 
amalgam restorations were in close proximity to the lesion, decay that has reached the pulp 
where potential for root canal therapy, patients of different language difficulty, and special/ 
vulnerable patient populations will be excluded. Contradictions in device labeling is also 
include in the exclusion. 
 
5.1.3 
Alignment with intended study population  
The study population includes patients likely to benefit from using LLLT to make a 
difference in providing better analgesia.  
 
5.1.4 
Alignment with intended use of the device 
The study involves using the Er,Cr=YSGG Laser to perform cavity preparation without 
giving any injection anesthesia. On each patient subject that has two similar size cavities 
of the same classification, either Class I or Class V, on similar teeth. Two different laser 
protocols will be used. One includes Low Level Laser Therapy (LLLT) to condition the 
pulp producing analgesia before using higher power to perform the cavity prep. The 
other protocol will skip the LLLT setting and prepare the cavity with the higher power 
to perform the cavity prep. 
5.2 
Recruitment Methods 
5.2.1 
Recruitment for Laser Analgesia Study 
Eligible patients will be invited to participate in the study, subject to Dr. William Chen 
recruitment goals. They will be informed of the possible risks of the procedure and will be 
required to give informed consent before study-specific procedures can proceed. Each subject 
will be informed that no personally relevant clinical information will be derived from the 
collected data.  
5.2.2 
Duration of study activities 
This study is anticipated to continue until the desired number of patients have had the study 
completed on them. In the event that additional studies are going to be conducted, new 
protocols will be developed specifically for those studies. 
 
5.3 
Patient Selection 
The eligibility criteria for prospective enrollment of subjects are shown in Table 1.  

 
  
Table 1. 
Inclusion/Exclusion Criteria for Enrollment of Subjects  
Inclusion criteria 
The study population will be representative patients that include 
adults 19-65 years old who had at least two cavity preparations of the 
same type, with the same approximate size lesion. Small & Medium 
size cavities 
Exclusion criteria 
Excluded patients include children, pregnant women, immune 
compromised patients, patients with heart disease, uncontrolled 
hypertension, cardiac arrhythmia, patients whose teeth amalgam 
restorations were in close proximity to the lesion, decay that has 
reached the pulp where potential for root canal therapy, patients of 
different language difficulty, and special/ vulnerable patient 
populations will be excluded. 
 
Participant 
Withdrawal 
Criteria 
Your participation in this study is voluntary. It is up to you to decide 
whether or not to take part in this study. If you decide to take part in 
this study, you will be asked to sign a consent form. After you sign 
the consent form, you are still free to withdraw at any time and 
without giving a reason. Withdrawing from this study will not affect 
the relationship you have, if any, with the researcher. If you withdraw 
from the study before data collection is completed, your data will be 
returned to you or destroyed. 
6 
STUDY MATERIALS 
6.1 
Investigational Product 
6.1.1 
Identity of the investigational product and accessories 
• Waterlase MD (mfg: Biolace Technology Inc, Irvine CA) 
• Waterlase MD accessories and consumables ( MG6 fiber tips, trunk fiber, contra- 
angle hand piece) 
• Case Report Forms 
6.1.2 
Safety issues 
If patient complains of having pain, raising hand signal, injection anesthesia will be given as 
an option to finish the procedure but will not be included in the study. 
 
6.1.3 
Handling, storage, accountability 
All the information collected though this study will go through Dr. William Chen. All files 
will all be stored in the office. Everyone involved in this study will accept responsibility for 

 
  
all the documents and results of this study. 
 
6.1.4 
Required training 
All involved people have been properly trained to work with the patients and around the laser 
by Dr. William Chen. 
 
6.1.5 
External studies 
In the event that plans are made to conduct additional studies, new protocols describing the 
relevant handling, storage, accountability, and training procedures will be prepared 
specifically for those studies.  
6.2 
Other Study Materials 
6.2.1 
Materials to be provided by study site 
• Study notebooks to maintain study documents, including signed ICFs, all applicable 
information, and additional forms to be collected and retained by the study institution 
during the course of the study.  
6.2.2 
Materials to be provided by external testing facilities  
None 
 
6.3 
Consent Procedures 
This study will be held in the office of Dr. Chen. There will be no extra costs to participate in 
the study.The consent procedures will be read in office and there will be an opportunity to 
ask questions. Participation is voluntary. Once the consent form is read signed, and all 
questions are asked and the participant is aware of everything that will be done the consent 
form will be collected and he/she is ready to move forward with the study.  

 
  
7 
STUDY PROCEDURES 
7.1 
Workflow 
This study will consist of two procedures. Both procedures will be performed on the same 
patient. Both procedures are cavity preparations. The tooth is chosen and the first procedure 
is started. The first one will be done with LLLT protocol prior to using the higher power to 
perform the cavity preparations. The second preparation will be done without LLLT first and 
thus using the higher power laser for cavity preparation from the beginning.  
Laser Preconditioning: 
A. Laser Desensitization/ preconditioning procedure 
a. Randomly select one tooth to have laser preconditioning performed on 
it 
• Preconditioning is using some LLLT on the tooth 
without expecting much, if any, ablation of the tooth. 
• For preconditioning, the setting is 0.25 Watt, 50Hz, 0% 
water, 0% air, H mode. 
b. Aim fibre-optic tip perpendicular to the surface of cervical portion of 
tooth 
c. Ensure that a 2mm distance between the end of the fiver optic tip and 
the surface is maintained 
d. Go back and forth with the fibre-tip over a 2mm line for the number of 
seconds indicated  
e. Prep the cavity on the first tooth (settings to follow) 
f. Prep the cavity on the second tooth, without laser preconditioning 
Preparation of Lesion: 
               A. Laser ablation- Small Preparation 
a. Waterlase MD settings: 4.5W, 15Hz, 65% air, 60% water 
b. Prepare cavity preparation using preferred technique 
c. If the patient indicates sensitivity, 
• Halt the procedure 
• Have the patient mark the VAS form, 
• Offer anaesthetic; if refused, continue using the same settings 
                B. Laser ablation- Small and Medium Preparation 
a. Waterlase MD settings: 2W, 15Hz, 65% air, 60% water 
b. Prepare cavity preparation using preferred technique 
c. If the patient indicates sensitivity, either 
• Halt the procedure 

 
  
• Have the patient mark the VAS form, 
• Offer anaesthetic; if refused, continue using the same settings 
Restoration:  
▪ Overall VAS Score: Up to 3 intra-operative VAS measurements are recorded. 
If a patient feels even the slightest amount of pain during the procedure, they 
are instructed to raise their hand and the treatment would be paused. The 
patient will then be asked to fill in the VAS form. The procedure could then 
be continued. After the conclusion of the cavity preparation, the patients are 
asked to mark one last VAS rating indicating the overall pain of the 
procedure.  
 
7.2 
Study Data 
Patients included in the study are adults 19-65 years old who had at least two cavity 
preparations of the same type, with the same approximate size lesion. Excluded patients 
include children, people with language barriers, pregnant women, immune compromised 
patients compromised (No bronchitis, no sinus infection, no ear infection, ect…), patients 
with heart disease, uncontrolled hypertension (high blood pressure), cardiac arrhythmia, and 
patients whose teeth amalgam restorations were in close proximity to the lesion. 
 
When approved to be in the required parameters subject to the appropriate requirements, the 
paperwork will be read, signed and collected from each eligible subject. Once all the 
paperwork is filled out the study will then be started. 
7.2.1 Collection of data  
7.3 
Randomization and Blinding   
The patient information (including name, age ect.) will not be associated with the results of 
the study that will be included in future articles. Dr. William Chen will only have record and 
know what results go with what patients so confidentiality is kept.  
 
7.4 
Procedures for Study Closure 
7.4.1 
Routine study close-out 
The study will end when Dr. William Chen has obtained all data necessary. Study close-
out will follow Dr. William Chen standard procedures and may include, but is not limited 
to, review of regulatory documents, collection of completed case report forms, 
reconciliation of study records, removal or destruction of ancillary study supplies, and 

 
  
informing the Investigator of remaining obligations (e.g., record retention, final report 
submission to the IRB, financial disclosure updates, etc.).  
7.4.2 
Suspension or premature termination of the study  
This study may prematurely terminate at any time because of a regulatory authority 
decision, a change in opinion of the IRB, or at the discretion of the Investigator or 
Sponsor. If this trial is temporarily suspended or prematurely discontinued, Dr. William 
Chen will notify the Investigator(s) and provide instructions. If the study is temporarily 
suspended, Dr. William Chen will provide guidance on timing and procedures for 
resuming the study. If the study is prematurely discontinued, all study materials must be 
collected and all study forms completed to the extent possible.  
8 
DATA QUALITY ASSURANCE  
The study site will be responsible for the accuracy of the data collected. 
9 
STATISTICAL METHODS 
9.1 
Determination of Sample Size 
The total number of individual subjects is expected to reach approximately forty-eight 
patients.  This estimate is based on the number of teeth that need to be done. 
 
n =        c2*N*p*(1-p)____      
      (A2*N) + (c*2p*[1-p]) 
 
n = the sample size required 
N = the target population (50) 
p = is the average proportion of records expected to meet the various criteria (1-p) is the 
average proportion of records not expected to meet the criteria if unknown choose 50% you 
do not want more than 50% you actually prefer to be way under but it is always better to 
estimate higher so you make sure you get enough results for your study. 
A =is the margin of error deemed to be acceptable (2.5%) 
c =is a mathematical constant defined by the Confidence Interval chosen ie (how sure we 
need to be of the result)  
To be 95% sure of the result the constant c = 1.96 which is always given. 
 
A narrower margin of error requires a larger sample size. Our margin of error is 2.5%. 
 
n =        1.692*50*.50*(1-.50) _______      
      (.0252*50) + (1.96*2.50*[1-.50]) 
 
n = 48.42 
Which will get our result of about 48 
patients
 

 
  
9.2 
Bias Minimization 
All subjects meeting the specified eligibility criteria will be enrolled in the study until all 
spots are filled up. 
9.3 
Planned Analyses 
The clinical study report will contain only information necessary to prove this phenomenon. 
 
Statistical analysis will include the VAS forms from each procedure which will be used to 
show there is laser analgesia and potentially cavity preparations can be performed by using 
the laser without the need to give injection anesthesia first. The VAS form is used to show 
how much pain they are in and if any.  All patient data will remain anonymous during 
analyses to maintain patient confidentiality. 
 
10 ADVERSE EVENT REPORTING  
10.1 
Non-Device-Associated Adverse Events 
Adverse events occurring during the enrollment period should be documented by the 
Investigator in progress notes, but will not be collected or analyzed unless considered serious 
by the Investigator.  
 
Serious adverse events (SAEs) encountered during study enrollment will be documented by 
the Investigator and reported immediately upon discovery. SAEs are defined under current 
Good Clinical Practice (cGCP) guidelines as events that result in one or more of the 
following: 
• life-threatening illness or injury;  
• permanent impairment of a body structure or a body function;  
• medically necessary in-patient hospitalization;  
• medical or surgical intervention necessary to prevent permanent impairment 
to body structure or function; or  
• fetal distress, fetal death, or congenital abnormality. 
 
SAEs will be reported using an Unanticipated Adverse Device Effects (UADE) form, which 
serves the dual role of capturing pertinent SAE information per industry guidelines and 
capturing device information pertinent to medical device standards. Other serious events that 
affect the rights, safety, or welfare of subjects must also be documented on the UADE form 
and must be reported immediately to the Investigator’s IRB according to that IRB’s policies. 
 
All adverse events that happen during this study will be treated seriously according to the 
appropriate policies, which should be none, will be documented in the patient’s medical 
record using the UADE form and will be reported immediately to the Investigator’s IRB 
according to that IRB’s policies. Also, a Follow-up will be implemented for AEs that cause 
interruption or discontinuation of the study, or those that are present at the end of study 
treatment as appropriate. 

 
  
10.2 
Device-Associated Adverse Events  
10.2.1 
Definition of an unanticipated adverse device effect (UADE) event 
A UADE event, as defined by cGCP guidelines, is any SAE, life-threatening problem, or 
death caused by or associated with a device (or with the process of evaluating a device) if 
that SAE, problem, or death was not previously identified in nature, severity, or degree of 
incidence in the investigational plan or application (including a supplementary plan or 
application), or any other unanticipated, serious, device-associated problem that relates to the 
rights, safety, or welfare of subjects or operators using the investigational product system or 
the comparator product system. 
10.2.2 
Reporting of device-associated adverse events 
Monitoring of adverse events (AEs) is critical to the patient’s safety (i.e., human subjects 
protection) and data integrity. 
 
Per this investigational plan, study subjects are not expected to experience any device-
associated adverse events. 
 
If instrument operators or research staff employed by the Sponsor experience any adverse 
events associated with study-specific use of the investigational device, the events will be 
processed according to the standard complaint investigation and handling policies, which 
may include recording of the event in the product’s design history file.   
10.3 
Sponsor Contact for Serious Adverse Event Reporting 
 
11 RISK ANALYSIS 
11.1 
Potential Risks of the Investigational Product and Clinical Investigation 
The procedures used in this study are experimental. However, there is no more of a risk 
during this study than there would be during any other cavity preparations performed by Dr. 
Chen. If you are having any pain during the procedure, we ask that you please signal us by 
raising your hand. We will stop the procedure and use injection anesthesia as an option to 
finish the procedure. You may decline to answer any or all questions and you may terminate 
your involvement at any time if you choose with no penalty. 
Dr. William Chen 
 4168 Nameoki Road, Granite City, Illinois 62040 
(618) 931-2025 

 
  
11.2 
Potential Benefits of the Investigational Product and Clinical Investigation 
Subjects are expected to benefit in the way of having better care for their teeth over going to 
your average dentist. One of the main benefits of using Lasers is pain reduction and anti-
inflammation. 
 
The studies made possible by the data collected in this study are expected to prove the 
phenomenon of laser analgesia.  
11.3 
Minimization of Risks 
Although the risk to subjects participating in the study is anticipated to be minimal, the 
clinician, at his/her discretion, will not collect data from those individuals for whom 
collection is judged to pose an unusually high risk of physical or mental harm or discomfort. 
 
Participation in this study poses no risk to study personnel other than that normally 
encountered during standard practice. These risks will be minimized by adherence to the 
following guidelines: 
 
• Personnel should wear appropriate personal protective equipment to avoid contact of 
the eyes or skin with hazardous materials or products derived from biological sources.  
12 INVESTIGATOR RESPONSIBILITIES 
12.1 
Site Qualification and Study Oversight 
The PI is responsible for general administration of the study.  
Before the study, the PI must: 
• Obtain approval to conduct the study from the study site’s IRB; 
• Sign the Protocol Signature Page him/herself and have all sub-investigators sign  
• Provide financial disclosures for themselves and all sub-investigators participating in 
study conduct, per Title 21CFR 54 (see Section 12.4 below).  
 
During the study, the PI must ensure that: 
• The study is conducted ethically;  
• Case report forms (CRFs), including Subject ICFs, are provided with each transfer of 
data requiring informed consent 
• All other study forms are completed as instructed. 
 
12.2 
Case Report Forms/Electronic Data Records 
As used in this protocol, the term CRF should be understood to refer to either a paper form or 
an electronic data record or both, depending on the data collection method(s) used. 

 
  
 
Original CRFs are the sole property of Dr. William Chen and should not be made available in 
any form to third parties, except for authorized representatives of Dr. William Chen or 
appropriate regulatory authorities.  
 
It is the PI's responsibility to ensure completion, review, and approval of all CRFs. CRFs 
must be signed by the PI or by an authorized staff member. These signatures serve to attest 
that the information contained on the CRFs is true. At all times, the PI has final personal 
responsibility for the accuracy and authenticity of all clinical and laboratory data entered on 
the CRFs.  
12.3 
Access to Source Documents 
Dr. William Chen or its agents and appropriate regulatory authorities shall be granted direct 
access to all study-related documents to perform verification that the protocol and all 
applicable current Good Laboratory Practices (cGLPs), Good Clinical Practices (GCPs), and 
regulations are being followed and to confirm that study documents are complete and 
accurate. It is important that Investigator and their relevant personnel be made available 
during monitoring visits and any audits or inspections, and that sufficient time is allotted for 
the process.  
12.4 
Financial Disclosure 
Investigators must provide sufficient, accurate financial information in accordance with local 
regulations Investigators are responsible for providing information concerning their relevant 
financial interests during the course of the study and for 1 year after completion of the study. 
Conflicts of interest should be disclosed as required by law.  
 
12.5 
Deviations from the Study Protocol 
An Investigator may not deviate from the study protocol unless the deviations are necessary 
under emergency circumstances to protect the rights, safety, or well-being of human subjects 
or the scientific integrity of the clinical investigation. These deviations must be documented 
and promptly reported to Sponsor and, if applicable, to the IRB providing oversight of the 
study. Protocol deviations may result in corrective and preventive actions and/or 
disqualification of the Investigator.  
12.6 
Record Retention 
To enable evaluations and/or audits from regulatory authorities, the PI and all sub-
investigators agrees to retain all study records, including copies of all CRFs, all forms, and 
source documents, for 3 years following completion of the project dependent upon the study 
data.  
 

 
  
12.7 
Publication Policy 
The results of this study will be submitted for publication.  The PI agrees that any publication 
of data from this study will comply with publication policy, the instructions to authors 
outlined by the editor of the journal or conference proceedings where the data is to be 
published, and the spirit of recommendations made in the good publication practice 
guidelines (GPP3) of the International Society of Medical Publication Professionals.  
13 ETHICS AND COMPLIANCE 
13.1 
Investigational Device Exemption 
Although exempt from IDE regulations as noted in Title 21 CFR 812.2(c), the conduct and 
performance of this study will be in accordance with applicable Sponsor and Investigator 
responsibilities as described in Title 21 CFR 809 and Title 21 CFR 812. 
13.2 
Informed Consent and De-Identification  
13.2.1 
Prospectively collected data 
All subjects will be given a copy of the IRB-approved ICF to review before their study 
participation begins. The Investigator will explain all aspects of the study in lay language and 
answer all of the potential participant’s questions regarding the study. If the participant 
decides to participate in the study, s/he will be asked to sign and date the ICF. Subjects who 
refuse to participate or who withdraw from the study will be treated without prejudice. 
13.3 
IRB Review 
The PI is required to obtain IRB oversight of the research study. Performance of the study 
may not begin until written evidence of IRB approval has been provided. 
 
The conduct and performance of this study will be in accordance with applicable Sponsor 
and Investigator responsibilities as described in Title 21 CFR 812 and other Good Clinical 
Practice guidance.  
 
IRB/Ethics Committee oversight will be required as human subjects or data from humans are 
being used. This protocol and the associated informed risks document(s) (if applicable) must 
be submitted to the IRB for review and approval. Performance of the study at a given site 
may not begin until written evidence of IRB oversight has been provided. IRB Review and 
approval must comply with Title 21 CFR 812 Subpart D. 

 
  
13.4 
Confidentiality of Data and Patient Records 
The study institution shall keep all records associated with this study for at least 3 years, as 
specified in Section 12.6. Investigators will keep all records associated with this study for at 
least 3 years. 
13.4.1 Provisions to Protect the Privacy Interests of Participants 
The PI and/or study institution shall provide sufficient information to allow the IRB to 
evaluate the researcher’s provisions to maintain the confidentiality of data. 
 
Privacy data will be maintained in accordance with HIPAA, other applicable policies, and 
local law.  
 
14. REFERENCES 
1. Ohshiro T, Calderhead RG. Development of low reactive-level laser therapy and its 
present status. (Japan Medical Laser Laboratory, Tokyo). J Clin Laser Med Surg. 1991 
Aug;9(4):267-75. 
 
2. “Erbium YAG Laser Treatment.” Peutz-Jeghers Syndrome | DermNet New Zealand, 
www.dermnetnz.org/topics/eryag-laser-treatment/.In-text Citation 
 
3. Robert, Marc. “Clinical Crown Lengthening Using a Er,Cr:YSGG Dental Laser; A 
Minimally Invasive Technique.” Oral Health Group, 2014, 
www.oralhealthgroup.com/features/clinical-crown-lengthening-using-a-er-cr-ysgg-dental-
laser-a-minimally-invasive-technique-marc/. 
 
6. Eversole, L.r., I. Rizoiu, and Kimmel. "Pulpal Response To Cavity Preparation By An 
Erbium, Chromium:ysgg Laser-Powered Hydrokinetic System." The Journal of the American 
Dental Association 128.8 (1997): 1099-106. Web. 
 
7. Chen, William. “The Clinical Applications for the Er:Cr:YSGG Laser System.” St. Louis, 
Mo. Chen Laser Institute, (2011). 
 
11. Orchardson R, Whitters CJ. Effect of HeNe and pulsed Nd:YAG laser irradiation on 
intradental nerve responses to mechanical stimulation of dentine. (Division of Neuroscience, 
Institute of Biomedical and Life Sciences, University of Glasgow, Glasgow, Scotland, United 
Kingdom. r.orchardson@bio.gla.ac.uk) Lasers Surg Med. 2000;26(3):241-9. 
 

 
  
12. Orchardson R, Peacock JM, Whitters CJ. Effects of pulsed Nd:YAG laser radiation on 
action potential conduction in nerve fibres inside teeth in vitro. (Institute of Biomedical and 
Life Sciences, University of Glasgow, UK. R.Orchardson@bio.gla.ac.uk). J Dent. 1998 Jul-
Aug:26(5-6):421-6. 
 
13. Orchardson R, Peacock JM, Whitters CJ. Effect of pulsed Nd:YAG laser radiation on 
action potential conduction in isolated mammalian spinal nerves. (Institute of Biomedical and 
Life Sciences, University of Glasgow, Scotland, United Kingdom. 
R.Orchardson@bio.gla.ac.uk). Lasers Surg Med, 1997;21(2):142-8. 
 
14. Takamori K, A histopathological and immunohistochemical study of dental pulp and 
pulpal nerve fibers in rats after cavity preparation using Er:YAG laser. (Department of 
Pedodontics, Nihon University School of Dentistry at Matsudo, Matsudo, Japan) J Endod. 
2000 Feb;26(2):95-9. 
 
15. Nair PN, Baltensperger MM, Luder HU, Eyrich GK. Pupal response to Er:YAG laser 
drilling of dentine in health human third molars. (Department of Oral Structural Biology, 
Center of Dental and Oral Medicine, University of Zurich, Switzerland. 
nair@zzmk.unzich.ch) Lasers Surg Med. 2003;32(3):203-3.