Clinical Efficacy and Human Factors Validation Testing for Prescription Home Use of the Erchonia Corporation THL™ for Providing Relief of Tinnitus Symptoms
Phase: NA
Conditions: Tinnitus
Sponsor: Erchonia Corporation

Erchonia® THL ™ 
A placebo-controlled, randomized, double-blind 
evaluation of the effect of the Erchonia® THL ™ for 
providing temporary relief from the symptoms of 
tinnitus 
Version 3.0  
April 13, 2022 
Appendix B: Clinical Efficacy Testing

TABLE OF CONTENTS 
 
 
STUDY INFORMATION..................................................................................................................................................................... 2 
SPONSOR ........................................................................................................................................................................................ 2 
CLINICAL CONSULTANT ................................................................................................................... Error! Bookmark not defined. 
MONITOR ......................................................................................................................................................................................... 2 
PRINCIPAL CLINICAL INVESTIGATOR ............................................................................................................................................ 2 
PURPOSE OF STUDY ...................................................................................................................................................................... 2 
EXPECTED RESULTS ...................................................................................................................................................................... 2 
STUDY DESIGN ................................................................................................................................................................................ 2 
SUBJECT GROUPS .......................................................................................................................................................................... 3 
DOUBLE BLIND DESIGN .................................................................................................................................................................. 3 
RANDOMIZATION............................................................................................................................................................................. 4 
SUBJECTS ........................................................................................................................................................................................ 4 
STUDY PROCEDURE ....................................................................................................................................................................... 5 
STUDY TEST BATTERY ................................................................................................................................................................... 5 
BASELINE VARIABLES .................................................................................................................................................................... 5 
OUTCOME ASSESSMENT TOOLS .................................................................................................................................................. 6 
STUDY PROCEDURE PROTOCOL .................................................................................................................................................. 8 
STUDY QUALIFICATION .................................................................................................................................................................. 9 
STUDY QUALIFICATION EVALUATION ........................................................................................................................................... 9 
PRE-PROCEDURE EVALUATION PHASE ..................................................................................................................................... 10 
AT-HOME PROCEDURE ADMINISTRATION PHASE .................................................................................................................... 11 
PROCEDURE ADMINISTRATION................................................................................................................................................... 11 
PROCEDURE ADMINISTRATION PHASE MEASURES ................................................................................................................. 13 
POST-PROCEDURE ACTIVITIES ................................................................................................................................................... 13 
ADVERSE EVENTS ........................................................................................................................................................................ 14 
PRIVACY AND CONFIDENTIALITY ................................................................................................................................................ 14 
MONITORING OF THE CLINICAL STUDY ...................................................................................................................................... 14 
INFORMED CONSENT ................................................................................................................................................................... 20 
CASE REPORT FORMS ................................................................................................................................................................. 20 
 
 
APPENDIX D: THL™ PROPER USE REFERENCE GUIDE 
APPENDIX K: TINNITUS FUNCTIONAL INDEX (TFI) 
APPENDIX L: THE TINNITUS FUNUCTION INDEX: DEVELOPMENT OF A NEW CLINICAL MEASURE 
FOR CHRONIC, INTRUSIVE TINNIUTS  
APPENDIX M: RESEARCH SUBJECT INFORMATION AND CONSENT FORM  
APPENDIX N: CASE REPORT FORMS 
APPENDIX O: RECRUIMENT ADVERTISEMENTS  
 
 
 
 
 
 
 
 
 
 
 
 

STUDY INFORMATION 
 
SPONSOR 
Erchonia Corporation 
650 Atlantis Rd.  
Melbourne, FL  32904 
 
Contact: Mr. Steven Shanks, President 
Telephone: 321-473-1251 
E-mail: sshanks@erchonia.com 
  
REGULATORY AND CLINICAL CONSULTANT 
219 East Harbor 
Hendersonville, TN 37075 
Contact: Elvira Cawthon Principal Consultant 
Telephone: 615-447-5150 
E-mail: elvira@reginsight.com 
 
MONITOR 
Erchonia Corporation 
650 Atlantis Rd.  
Melbourne, FL  32904 
 
Contact: Travis Sammons 
Telephone: 321-473-1251 ext. 501 
E-mail: tsammons@erchonia.com 
 
PRINCIPAL CLINICAL INVESTIGATOR 
 
Paige Haberman, Au.D 
2415 High School Ave #300 
Concord, CA 94520 
Office: 925-676-8420 
 
 
PURPOSE OF STUDY 
The purpose of this clinical study is to determine the effectiveness of the Erchonia® THL™, 
manufactured by Erchonia Corporation (the Company), for prescription home use in providing 
relief of tinnitus symptoms when used by individuals in their own homes.  
 
 
EXPECTED RESULTS 
Following completion of the study procedure administration protocol with the Erchonia® THL ™, 
it is anticipated that compared with baseline, a significantly greater proportion of subjects in the 
test group than in the placebo group will show a 13-point or greater reduction in total score on the 
TFI at study endpoint evaluation relative to baseline. 
 
 
STUDY DESIGN 
 
This clinical study is a double blind, placebo-controlled, randomized design evaluation of the effect 
of the Erchonia® THL™ for prescription home use application in providing temporary relief from 
the symptoms of tinnitus.  

 
 
This proposed clinical study design is based on the outcome of Pre-sub Q211668 agreed upon 
between Erchonia Corporation (Sponsor) and the FDA pertaining to a clinical study evaluating 
the effectiveness of the Erchonia 405 nm laser for the relief of the symptoms of tinnitus. 
 
 
SUBJECT GROUPS  
 
Subjects enrolled in the clinical study will not have been enrolled in the Human Factors Validation 
Testing study. 
 
Each enrolled subject will be randomized to the test procedure group or to the placebo procedure 
group of the clinical study, as follows: 
 
Test procedure group: Subjects randomized to the test procedure group will self-administer the 
study procedures with the active (true) Erchonia® THL™ laser in his or her own home.  
 
Control procedure group: Subjects randomized to the control procedure group will self-administer 
the study procedures with a ‘fake’ (placebo) Erchonia® THL™ laser in his or her own home.   
 
The ‘fake’ (placebo) laser device will appear to the subject to be an active device but will not 
produce any therapeutic light output. The placebo laser device is designed to have the same 
physical appearance as the actual (active) laser device, including the appearance of any visible 
and invisible light output. Therefore, both the test and control devices emit light when activated 
that is indistinguishable to the subject. As the laser light does not put out any notable degree of 
heat or noise, these are also not distinguishing factors for subjects between the active and control 
devices.  
 
Regardless of whether the subject self-administers the study procedures with the actual or the 
fake laser device, all subjects will be required to adhere to all phases of the entire protocol design.   
 
DOUBLE BLIND DESIGN  
This clinical study is a double-blind design, such that neither the subject nor the investigator is 
aware of whether the subject has been provided with the active or the placebo Erchonia® THL™ 
device. Unblinding will occur after the final data set has been fully analyzed  
 
The blinding procedure is as follows:  
 
1) Each device is identified by an arbitrary number (serial number) and will be preassigned by 
the Sponsor to Group A which corresponds to the actual (test) THL™ devices or Group B 
which corresponds to the ‘fake’ devices. The serial number to device group translation will be 
maintained by the Sponsor until the final study data set analysis is complete 
2) Each subject is randomly assigned to Procedure Group A or to Procedure Group B using the 
computer-generated randomization sequence stored and maintained confidentially at the 
Sponsor’s work site.  
3) Each subject will be assigned a device serial number by the Sponsor, which translates to 
Group A or Group B based on the subject’s group randomization. The subject and the site 
personnel will not be aware of any grouping at all. The devices will only be identified by serial 
number. 
 

 
4) The fake (placebo) Erchonia® THL™ is designed to have the same physical appearance as 
the actual Erchonia® THL™, including the appearance of any visible and invisible light output. 
Therefore, both the test and sham devices emit light when activated that is indistinguishable 
to both the subject and to the investigator. As the laser light does not put out any notable 
degree of heat or noise, these are not distinguishing factors for subjects between the two 
groups. 
 
 
RANDOMIZATION 
 
Subject randomization occurs following attainment of subject consent. Subject allocation to 
procedure group will be via variable block randomization with varying block sizes of two, four and 
six used at random to minimize the likelihood of predicting the next procedure group assignment. 
 
Randomization will be attained using computer generation sequence methodology, ensuring that 
the randomization methodology and the generated allocation sequence is concealed from the 
subjects.  
 
Concealment will be insured as follows: 
 
(ii) Each computer-generated randomization sequence is unique and will therefore not be able 
to be replicated. 
(iii) Randomization will occur to either ‘Procedure Group A’ or to ‘Procedure Group B’ rather than 
to a test or placebo group, and only the Sponsor  will know which assignment (A or B) 
corresponds to the active device and which corresponds to the fake device. Unblinding will 
not occur until the final study data set analysis is complete. 
 
 
SUBJECTS  
 
Recruitment 
Subjects will be recruited from the test site and online advertisements for individuals who have 
Tinnitus. Subject recruitment material found in Appendix O. 
 
Compensation  
A subject will receive financial compensation of $150 for his or her participation in this clinical 
study. 
 
A subject will not be charged for the cost of use of the Erchonia® THL™ Laser or for the cost of 
any other evaluations or measurements that occur as part of his or her participation in the study. 
 
Sample Size Determination  
 
In the determination of sample size, the following parameters have been established for the 
purpose of assessing efficacy of the Erchonia® THL™ in this clinical study: 
 
 Individual subject success criteria defined as a 13-point or greater reduction in total score on 
the Tinnitus Functional Index (TFI) from baseline to study endpoint evaluation.  
 Overall study success criteria defined as a minimum 35% difference between the test device 
group and the placebo device group in the proportion of individual successes.  
 It is anticipated that about 55% of subjects in the test device group and about 20% of subjects 
in the placebo device group will meet the individual success criteria, and 

 Intended application of a two-tailed test with an alpha value of 0.05 and Power of 0.8. 
 
 
In consideration of the above parameters established for the purposes of sample size calculation, 
the sample size of 29 subjects per procedure group (test group and placebo group, separately) 
has been determined using the following reference calculator: Hypothesis Testing: Categorical 
Data - Estimation of Sample Size and Power for Comparing Two Binomial Proportions in Bernard 
Rosner's Fundamentals of Biostatistics. 
 
It is anticipated that about one-twentieth of subjects overall may withdraw from the study prior to 
completion for various reasons. Therefore, the following formula is used to determine the final 
needed starting sample size for each group: 
 
Final sample size = sample size X 1/(1-d); where d = # expected dropouts/# subjects enrolled. 
Final sample size = 29 X 1/(1-0.083) 
Final sample size = 29 X 1/0.917 = 29 X 1.0905 = 31.62, rounded to 32 subjects per group. 
 
Therefore, a minimum starting sample size of 32 subjects in each procedure group is needed to 
ensure sufficient numbers remain at the end of the trial (29 subjects per group) for any significant 
difference found between groups to be considered statistically valid and representative of the 
general population being sampled. This results in a total of 64 subjects being enrolled in this study 
across both study procedure groups.  
 
Justification for Sample Size Determination 
 
The parameters selected for sample size determination are based on the industry-standard 
reference article: Tinnitus handicap inventory for evaluating treatment effects: which changes are 
clinically relevant?  Otolaryngol Head Neck Surg. 2011 Aug;145(2):282-7. Zeman F1, Koller 
M, Figueiredo R, Aazevedo A, Rates M, Coelho C, Kleinjung T, de Ridder D, Langguth 
B, Landgrebe M. 
 
Additional details with respect to the reference values in this article are contained in the Statistical 
Analysis section below. 
 
STUDY PROCEDURE 
 
STUDY TEST BATTERY 
 
The following are the study assessment tools to be used and the variables to be recorded in this 
clinical study.  
 
 
BASELINE VARIABLES 
 
A. Tinnitus Variables 
 
 Diagnosed etiology of tinnitus, if known. Responses: presbyacusis, noise-induced, unknown.  
 Number of months/years since tinnitus onset. 
 
B. Medication and Treatment  
 

 Prior treatment approaches for tinnitus reduction: Record all prior treatments, whether 
conventional or alternative, tried by the subject for tinnitus reduction. 
 Concomitant Medication and Therapy Use: Record all over-the-counter and prescription 
medications currently used for any indication (other than the management of tinnitus 
symptoms)  
 
C. Hearing Aid Use: yes/no 
D. Subject Demographics: Subject age, gender, and ethnicity. 
 
OUTCOME ASSESSMENT TOOLS 
 
PRIMARY OUTCOME MEASURE ASSESSMENT TOOL:  
 
Tinnitus Functional Index (TFI) (Appendix K) 
The Tinnitus Functional Index (TFI) is commonly used in both clinical and research settings for 
tinnitus measurement due to its responsiveness to treatment-related change, validity for scaling 
the overall severity of tinnitus, and comprehensive coverage of multiple domains of tinnitus 
severity (Meikle et al., 2011). The self-report questionnaire, consists of 25 items with a response 
option on an 11-point Likert scale from 0–10 
The calculation of overall TFI score is as follows:  
(1) Sum all valid answers  (maximum possible score = 250 if the respondent were to rate all 25 
TFI items at the maximum value of 10).  
(2) Divide (1) by the number of questions for which the sum of the valid answers was based to 
yield the respondent's mean item score.  
(3) Multiply (2) by 10 to attain  the respondent's overall TFI score (0-100 range). 
 
Total TFI score can be categorized as Level of Tinnitus Severity as follows: 
 
TFI 0 to 17: Not a problem 
TFI 18 to 31: Small problem 
TFI 32 to 53: Moderate problem 
TFI 54 to 72: Big Problem 
TFI 73 to 100: Very big problem 
 
 
 
DIAGNOSTIC, SECONDARY, and SAFETY OUTCOME ASSESSMENT TOOLS 
 
Audiometric Testing: Degree of Hearing Loss 
 
 
Audiometric testing will be performed as follows: 
 
• Pure tone air conduction testing for the frequencies of 250 Hz, 500 Hz, 1 kHz, 2 kHz, 4 kHz, 
8kHz, 12 kHz, 16 kHz, and 20 kHz  
• Pure tone bone conduction testing for the frequencies of 250 Hz, 500 Hz, 1 kHz, 2 kHz, 4 kHz, 
and 8kHz. 
 

Audiometric testing will be performed using standardized, calibrated equipment that is held 
constant across all subjects at the test site and administered according to standard industry 
procedures and protocols. 
 
The audiogram results will be used for two purposes in this study: 
 
(i) Calculation of pure tone average (PTA) as a part of Study Qualification evaluation. 
 
Pure Tone Average (PTA) is calculated as follows: PTA = (500 Hz dB + 1 kHz dB + 2 kHz dB) 
/ 3. 
 
(ii) For tracking of changes in PTA and hearing levels across study duration from 250 Hz through 
20 kHz for efficacy and safety evaluation. 
 
Tympanometry 
Tympanometry is an objective test of middle-ear function. It is an acoustic evaluation of the 
condition of the middle ear eardrum (tympanic membrane) and the conduction bones by creating 
variations of air pressure in the ear canal. Tympanometry, together with audiometry, assists in 
distinguishing between sensorineural and conductive hearing loss,  
The test is performed by inserting the tympanometer probe in the ear canal. The instrument 
changes the pressure in the ear, generates a pure tone, and measures the eardrum responses 
to the sound at different pressures. This produces a series of data measuring how admittance 
varies with pressure, which is plotted as a tympanogram: 
Tympanograms are categorized according to the shape of the plot. A normal tympanogram shows 
normal pressure in the middle ear with normal mobility of the eardrum and ossicles and is labelled 
Type A. Type B tympanograms indicate (a) fluid in the middle ear, (b) perforation of the tympanic 
membrane or patent pressure equalization tube, or (c) a tumor in the middle ear. Type C 
tympanograms are consistent with negative pressure in the middle ear space resulting from 
compromised eustachian tube function and a retracted tympanic membrane. 
A Type A tympanogram accompanied by hearing loss where the air conduction and bone 
conduction levels on an audiogram are comparable is consistent with a sensorineural hearing 
loss. 
A Type B or Type C tympanogram accompanied by hearing loss where there is a gap / difference 
between the air conduction and bone conduction thresholds on the audiogram at all or some 
frequencies is consistent with a conductive or mixed hearing loss. 
 
Otoscopic Exam of the Ears 
 
Otoscopy is a clinical procedure used to examine the structures of the ear, particularly the external 
auditory canal, tympanic membrane, and middle ear. Otoscopy is performed using a standard 
otoscope, a tool that shines a beam of light to help visualize and examine the condition of the ear 
canal and eardrum. The otoscopic exam is performed by gently pulling the auricle upward and 
backward to move the acoustic meatus in line with the canal.  
 
The appearance of a normal healthy middle ear is as follows: 
 
• 
Auditory canal: Some hair, often with yellow to brown cerumen. 

• 
Ear drum:  
− Pinkish gray in color; shiny, translucent and in neutral position. 
− Intact; no bulging or retraction. 
− Malleus lies in oblique position behind the upper part of drum. 
 
Observations from the otoscopic examination of the ear will be recorded, taking into consideration 
the following factors and any other of consideration: 
 
• 
External auditory canal:  
- Hair (none, some, excessive)  
- Cerumen:  
• color (yellow, brown) 
• amount: minimal, normal (≤ 50%); impacted (> 50%)  
 foreign body (yes/no) 
- Discharge or drainage (yes/no) 
 
• 
Tympanic membrane 
- Color (pinkish-grey, red, white, yellow) 
- Translucency (transparent, opaque)  
- Position of the drum (retracted, neutral, or bulging)  
- Perforation / scars (yes/no) 
- Cone of light observed (yes/no) 
 
• 
Position of the malleus handle: normal (behind the upper part of the drum); other 
 
 
Subject Satisfaction with Study Outcome 
 
The subject is asked to rate how satisfied he or she is with any change in his or her overall tinnitus 
following completion of the laser administration procedures with the Erchonia® THL™ by using 
the 5-point Likert scale presented below to respond to the following question: “Overall, how 
satisfied or dissatisfied are you with any change in your tinnitus following the study procedures 
with the study laser device?”  
• Very Satisfied 
• Somewhat Satisfied 
• Neither Satisfied nor Dissatisfied 
• Not Very Satisfied 
• Not at All Satisfied   
 
BLINDING EFFICACY EVALUATION TOOLS 
 
Subject Perceived Group Allocation and Rationale 
 
The subject records whether he or she believes to have received the study procedures with the 
true or fake Erchonia® THL™ and records verbatim his or her reasoning or rationale for this 
perceived determination. 
 
 
STUDY PROCEDURE PROTOCOL 
 

STUDY QUALIFICATION 
 
SIGNING OF INFORMED CONSENT FORM 
The site investigator will commence by presenting and reviewing the items in the informed 
consent form with the potential participant and answer any questions he or she may have. To 
proceed, the individual must willingly sign the informed consent form.  
 
 
ASSIGNMENT OF SUBJECT IDENTIFICATION NUMBER 
The subject is assigned a unique subject identification number based upon his or her order of 
entry into the study. 
 
Additional information about the informed consent and subject ID number assignment is contained 
in a later section of the protocol titled, “SAFETY AND CONFIDENTIALITY ISSUES.” 
 
SUBJECT RANDOMIZATION TO PROCEDURE GROUP  
 
Following signing of the consent form and prior to study qualification evaluation, a subject is 
randomly assigned to Procedure Group A or to Procedure Group B, following the methodology 
outlined above in the STUDY DESIGN section of the protocol.  
 
STUDY QUALIFICATION EVALUATION 
A suitably qualified and licensed health professional (study investigator) will perform the study 
qualification evaluation, at the test site. To be eligible for study participation a subject must 
satisfy the following qualification criteria. 
 
 The study inclusion and exclusion criteria have been separated into two parts: Part 1 and Part 
2. This is done to avoid lengthy study tool evaluations (TFI & Audiometric Test) that are involved 
in Inclusion and Exclusion Part 2, if the subject does not first meet all the Inclusion Part 1 and / 
or Exclusion Part 1 criteria. 
 
INCLUSION CRITERIA PART 1 
 
To be eligible for study participation, a subject must satisfy each of the following criteria. 
 
 Bilateral tinnitus  
 Current diagnosis of subjective tinnitus  
 18 years of age or older 
 Able to read and write English 
 Constant tinnitus on-going over at least the past 6 months 
 Willing to abstain from other tinnitus-related treatments, except existing hearing aid use, 
throughout the study duration.    
 
EXCLUSION CRITERIA PART 1 
 
A subject who satisfies any of the following criteria will be excluded from study participation: 
 

 Tympanosclerosis 
 Meniere’s disease 
 Acoustic neuroma(s) 
 Current and consistent use of ototoxic medication(s) 
 Presbycusis 
 Thyroid disease 
 Skull fracture 
 Traumatic brain injury (TBI) 
 Significant depression or other significant mental health condition that in the opinion of the 
study investigator may interfere with the individual’s ability to participate in the study. 
 Syphilis 
 Retrocochlear tumor(s) 
 Pregnant, possibly pregnant, or breastfeeding. 
 Open wounds (sores, cuts, ulcers, etc.) on or around the ears or neck 
 Cancerous growths or being treated for cancerous growths on or around the ears or neck 
 Previous experience self-administering laser therapy 
 Difficulty with hand dexterity sufficient to impact ability to administer treatments with the 
laser such as from severe arthritis in the hands, Multiple Sclerosis, Cerebral Palsy, 
Parkinson’s Disease, Huntington’s Disease, etc. 
 
INCLUSION CRITERIA PART 2 
 
 
A subject that satisfies both the Inclusion Part 1 and Exclusion requirements will proceed to 
Inclusion Criteria Part 2: 
 
 Tinnitus Functional Index (TFI) total score of 32 to 72, inclusive (Level 3 or 4) 
 
Conduct of the following evaluations: 
 
• 
Audiometric Testing: calculation of PTA for each ear 
• 
Tympanometry 
• 
Otoscopic Examination of the Ears 
• 
 
Based on the outcome of the above evaluations:  
 
 Pure Tone Audiometry (PTA) is ≤ 60 dB (Moderate or less) for each of the right and left ears 
 No hearing loss or sensorineural hearing loss only, bilaterally. 
 
 
EXCLUSION CRITERIA PART 2 
 
 Impacted cerumen, foreign bodies, or tubes in one or both ears 
 Perforation of the eardrum in one or both ears 
 Discharge and/or drainage from one or both ears 
 
 
PRE-PROCEDURE EVALUATION PHASE 
 

The pre-procedure evaluation phase commences the same day following successful study 
qualification. The pre-procedure evaluation will be performed at the test site and the following will 
be recorded by the site investigator as outlined in the STUDY TEST BATTERY section above. 
 
BASELINE VARIABLES 
 
 Tinnitus Variables 
 Existing hearing aid use 
 Medication and Treatment  
 Subject Demographics 
 
PRE-PROCEDURE OUTCOME ASSESSMENTS  
 
The Pre-Procedure outcome measures can be taken from the “Study Qualification Evaluation” 
measures if each are performed on the same day.  
 
 Tinnitus Functional Index (TFI)  
 Audiometric Test: calculation of PTA for each ear 
 Tympanometry 
 Otoscopic Examination of the Ears 
 
 
AT-HOME PROCEDURE ADMINISTRATION PHASE 
 
A fully-qualified enrolled subject will be provided by the study site, a device serial number, which 
translates to Group A or Group B based on the subject’s group randomization. The subject and 
the site personnel will not be aware of any grouping at all. The devices will only be identified by 
serial number (see Randomization). The device will include a THL™ Proper Use Reference Guide 
(Appendix D).  
 
 
PROCEDURE ADMINISTRATION   
   
 The procedure administration phase extends over 4 consecutive weeks.  
 The subject self-administers one procedure administration with the Erchonia® THL ™ (A or B) 
on each consecutive day of the 4-week procedure administration phase for a total of 28 self-
administered procedures.  
 Each procedure administration lasts 5 minutes each ear, for a total treatment time of 10 
minutes.  
 Each procedure is self-administered by the subject in his or her own home. 
 
 
 
 
PROCEDURE ADMINISTRATION PROTOCOL 
 
The subject will need to follow the instructions in the Erchonia THL ™ Proper Use Reference 
Guide to correctly self-administer a procedure. These instructions read as follows: 
 
1. Turn the THL ™ device on by pressing and holding the “Power Switch” for 3 seconds. 

2. Ensure the green POWER ON indicator light is lit. 
3. Put on the laser safety goggles provided. 
4. Once the safety goggles are on, start the laser treatment by pressing the “START” icon on the 
treatment screen. Note: The protocol software is factory set and cannot be changed. 
5. Ensure the laser indicator light is lit. 
 
6. Hold the THL ™ laser light diode about 1 inch above your right ear and about 4 inches from 
your skin. 
 
7. In a slow continuous sweeping motion, move the THL ™ down the right side of your neck. 
 
8. Once you reach the bottom of your neck, in a slow continuous sweeping motion. move the THL 
™ up your neck back to where you started, about 1 inch above your right ear, making sure to 
keep the laser about 4 inches away from the surface of your skin the whole time. This process 
is shown in the diagram below. 
 
 
 
 
 
 
9. Continue this up and down sweeping motion on the right side for the whole 5 minutes of 
treatment. 
 
10. Once the 5 minutes is done, the treatment will automatically stop. The “Time Remaining” display 
shows 0:00 and the laser lights and the laser indicator light will turn off.  
 
11. Next, repeat steps 4 through10 for your left side (left ear and left side of neck) as shown in the 
diagram below.   
 
 
 
 
 
 
 
 
 
 
 
 

12. After you have treated both your right and left ears for a total treatment time of 10 minutes, the 
treatment session is complete, and you may remove the safety googles. 
PROCEDURE ADMINISTRATION PHASE MEASURES 
 
DAILY TREATMENT ADMINISTRATION LOG  
 
The study site will provide the subject data capture forms to record each day when they have 
administered a treatment with the Erchonia® THL ™ Laser. The subject will provide the study 
investigator the completed “Treatment administration log” following the 4-week treatment 
procedure administration phase. 
 
 
WEEKLY ASSESSMENTS 
 
Once a week, the site staff may call and/or contact the subject by e-mail to check on compliance, 
to verify that no adverse events had occurred, and to answer any questions the subject may have.    
 
4 WEEK EVALUATION: TREATMENT END 
 
Following completion of the entire 4 weeks of study procedure administrations with the Erchonia® 
THL ™, the following will be recorded by the site investigator as outlined in the STUDY TEST 
BATTERY section above. 
 
 Tinnitus Functional Index (TFI)   
 Audiometric Test: Degree of Hearing Loss 
 Tympanometry 
 Otoscopic Examination of the Ears 
 Subject Satisfaction With Study Outcome 
 Subject Perceived Group Allocation and Rationale 
 
 
 
POST-PROCEDURE ACTIVITIES 
    
2 Weeks Post-Procedure: STUDY ENDPOINT 
 
Two weeks following the completion of the 4-week treatment administration phase, the following 
will be recorded by the site investigator) as outlined in the STUDY TEST BATTERY section above. 
These recordings will form the study endpoint data set from which change from baseline will be 
evaluated with respect to assessing study outcome. 
 
 Tinnitus Functional Index (TFI) 
 Audiometric Test: Degree of Hearing Loss 
 Tympanometry 
 Otoscopic Examination of the Ears 
 Subject Satisfaction With Study Outcome 
 Subject Perceived Group Allocation and Rationale 

 
 
ADVERSE EVENTS  
 
The subject will be instructed to notify the PI any time that a potential adverse event has been 
experienced. It is unlikely and not expected that any adverse events will result from 
implementation of this clinical study protocol. Prior clinical trials using low level laser light have 
not typically yielded any adverse events or reactions. However, potential adverse events that may 
feasibly occur from application of the Erchonia® THL™ include, but are not necessarily limited to 
skin irritation, discoloring, rash, indentations, and infection. 
 
PRIVACY AND CONFIDENTIALITY 
 
Records for each subject in this clinical study will be maintained in separate files in a locked filing 
cabinet at the respective test site. The investigator at the test site will be responsible for ensuring 
that all records for a subject pertaining to his or her participation in the clinical study are stored in 
that subject’s file at all times other than when information is being recorded on them.   
 
Copies of all of the subject case report forms will be made and supplied to Regulatory Insight, Inc. 
and Erchonia Corporation. Regulatory Insight, Inc. and Erchonia Corporation will maintain these 
copies in a separate clinical study file that is kept in a locked filing cabinet at their respective 
premises. The original records will be maintained at the respective test sites. 
 
Subjects’ identities will be kept confidential by assigning each subject a unique de-identified 
subject ID upon acceptance into the study. The subject ID will comprise the investigator’s two 
initials (first and last name initials) and a three-digit number that will be based upon the subject’s 
order of entry into the clinical study. For example, under Study Investigator John Black, the third 
subject enrolled in the study would have a subject ID of JB003.  
 
 
MONITORING OF THE CLINICAL STUDY 
 
A Clinical Trial Monitoring Plan will be in place to ensure on-going compliance and accuracy of 
procedures throughout the trial. 
 
STATISTICAL ANALYSIS 
 
BASELINE VARIABLES EVALUATION  
 
A. Tinnitus Variables 
 
Baseline tinnitus variables of tinnitus etiology, and time since tinnitus onset will be summarized 
descriptively (mean and standard deviation, and categorically, as applicable) and compared for 
differences between procedure groups and test sites, as applicable. Any identified differences will 
be explored with respect to impact on study outcome. 
 
B. Medication and Treatment  
 
Subjects’ prior treatment approaches for tinnitus reduction and baseline concomitant medication 
and therapy use will be summarized categorically and compared for differences between 

procedure groups and test sites. Any identified differences will be explored with respect to impact 
on study outcome. 
 
C. Hearing Aid Use 
 
Subjects’ use of hearing aids will be summarized descriptively. Any identified differences will be 
explored with respect to impact on study outcome. 
D. Subject Demographics:  
 
Demographics of age, gender and ethnicity will be summarized descriptively (mean and standard 
deviation, and categorically, as applicable) and compared for differences between procedure 
groups and test sites. Any identified differences will be explored with respect to impact on study 
outcome. 
 
PRIMARY EFFICACY OUTCOME MEASURE: CHANGE IN TOTAL SCORE ON THE TINNITUS 
FUNCTIONAL INDEX(TFI) FROM BASELINE TO STUDY ENDPOINT   
 
Primary efficacy outcome measure for this clinical study is a statistically significant difference in 
the proportion of subjects between test and control groups who achieve a clinically meaningful 
decrease in total score on the TFI from baseline to study endpoint.    
The TFI has been highly recommended to be used in both clinical and research settings for 
tinnitus measurement because of its responsiveness to treatment-related change, validity for 
scaling the overall severity of tinnitus, and comprehensive coverage of multiple domains of tinnitus 
severity (Meikle et al., 2011). 
The following abstract pertains to a reference study that served to establish the industry-standard 
minimal clinically relevant difference of change in TFI total score from pre- to post-intervention as 
13 points. This reference has been cited and supported through numerous subsequent 
prospective and retrospective trials and analyses and is considered industry-wide. 
 
 
Meikle MB, Henry JA, Griest SE, Stewart BJ, Abrams HB, McArdle R, Myers PJ, Newman CW, 
Sandridge S, Turk DC, Folmer RL, Frederick EJ, House JW, Jacobson GP, Kinney SE, Martin 
WH, Nagler SM, Reich GE, Searchfield G, Sweetow R, Vernon JA. The tinnitus functional index: 
development of a new clinical measure for chronic, intrusive tinnitus. Ear Hear. 2012 Mar-
Apr;33(2):153-76.  
Objectives: Chronic subjective tinnitus is a prevalent condition that causes significant distress 
to millions of Americans. Effective tinnitus treatments are urgently needed but evaluating them 
is hampered by the lack of standardized measures that are validated for both intake assessment 
and evaluation of treatment outcomes. This work was designed to develop a new self-report 
questionnaire, the Tinnitus Functional Index (TFI), that would have documented validity both for 
scaling the severity and negative impact of tinnitus for use in intake assessment and for 
measuring treatment-related changes in tinnitus (responsiveness) and that would provide 
comprehensive coverage of multiple tinnitus severity domains.  
Design: To use preexisting knowledge concerning tinnitus-related problems, an Item Selection 
Panel (17 expert judges) surveyed the content (175 items) of nine widely used tinnitus 
questionnaires. From those items, the Panel identified 13 separate domains of tinnitus distress 

and selected 70 items most likely to be responsive to treatment effects. Eliminating redundant 
items while retaining good content validity and adding new items to achieve the recommended 
minimum of 3 to 4 items per domain yielded 43 items, which were then used for constructing TFI 
Prototype 1.Prototype 1 was tested at five clinics. The 326 participants included consecutive 
patients receiving tinnitus treatment who provided informed consent-constituting a convenience 
sample. Construct validity of Prototype 1 as an outcome measure was evaluated by measuring 
responsiveness of the overall scale and its individual items at 3 and 6 mo follow-up with 65 and 
42 participants, respectively. Using a predetermined list of criteria, the 30 best-functioning items 
were selected for constructing TFI Prototype 2.Prototype 2 was tested at four clinics with 347 
participants, including 155 and 86 who provided 3 and 6 mo follow-up data, respectively. 
Analyses were the same as for Prototype 1. Results were used to select the 25 best-functioning 
items for the final TFI.  
Results: Both prototypes and the final TFI displayed strong measurement properties, with few 
missing data, high validity for scaling of tinnitus severity, and good reliability. All TFI versions 
exhibited the same eight factors characterizing tinnitus severity and negative impact. 
Responsiveness, evaluated by computing effect sizes for responses at follow-up, was 
satisfactory in all TFI versions. In the final TFI, Cronbach's alpha was 0.97 and test-retest 
reliability 0.78. Convergent validity (r = 0.86 with Tinnitus Handicap Inventory [THI]; r = 0.75 with 
Visual Analog Scale [VAS]) and discriminant validity (r = 0.56 with Beck Depression Inventory-
Primary Care [BDI-PC]) were good. The final TFI was successful at detecting improvement from 
the initial clinic visit to 3 mo with moderate to large effect sizes and from initial to 6 mo with large 
effect sizes. Effect sizes for the TFI were generally larger than those obtained for the VAS and 
THI. After careful evaluation, a 13-point reduction was considered a preliminary criterion 
for meaningful reduction in TFI outcome scores.  
Conclusions: The TFI should be useful in both clinical and research settings because of its 
responsiveness to treatment-related change, validity for scaling the overall severity of tinnitus, 
and comprehensive coverage of multiple domains of tinnitus severity.  
The complete article is contained in Appendix L. 
 
Based on this established reference, the following criteria are established to determine efficacy 
of self-application of the Erchonia® THL™ to relieving the symptoms of tinnitus in adults. 
 
Subjects Meeting Individual Success Criteria 
Individual subject success criteria is defined as a 13-point or greater decrease in total TFI score 
at study endpoint relative to baseline. 
 
Overall Study Success Criteria.  
Overall study success criteria is defined as at least a 35% difference between procedure groups, 
comparing the proportion of individual successes in each group. It is anticipated that about 55% 
of subjects in the test group will meet the individual success criteria and about 20% of subjects in 
the control group will meet the individual success criteria.  
 
Each of the three following studies utilized the Tinnitus Functional Index (TFI) as the primary 
efficacy outcome with the minimal clinically relevant difference of change in TFI total score from 
pre- to post-intervention defined as 13 points as per the reference article cited above by Meikle, 
MB, et al. (2012).  
 

The table below presents the number and percentage of individual subjects who attained or 
exceeded the MCID of a 13-point change in TFI total score pre- to post-treatment for each of the 
three randomized controlled trials (RCTs) for subjects in each of the active and sham/placebo 
groups. The differences in these proportions between treatment groups ranged from 25% to 
34%, with the differences of 30% and 34% each determined to be statistically significant at 
p<0.05 and p<0.005, respectively. These RCTS therefore support the overall success criteria of 
a 35% difference between treatment groups implemented in the current study as being both 
statistically significant and clinically meaningful and highly conservative. The individual group 
anticipated proportions of 20% and 55% for placebo and active treatment groups, respectively is 
further supported by the outcome of the Folmer, RL et al. (2015) study listed below.  
 
Study 
Active Group: 
n attaining 
individual 
MCID/Total n 
Placebo Group: 
n attaining 
individual 
MCID/Total n 
Difference 
between 
groups  
p-value 
Robert L. Folmer, PhD; Sarah 
M. Theodoroff, PhD; Linda Casiana, MS, CCRP et al; 
Yongbing Shi, MD, 
PhD; Susan Griest, MPH; Jay Vachhani, AuD 
Repetitive Transcranial Magnetic Stimulation Treatment 
for Chronic Tinnitus: A Randomized Clinical Trial 
JAMA Otolaryngol Head Neck Surg. 2015;141(8):716-
722.  
18/32 = 56%; 
7/32 = 22%; 
34% 
<0.005 
Maxwell, Kenneth S.∗; Robinson, James M.; Hoffmann, 
Ines; Hou, Huiying J.; Searchfield, Grant; Baguley, 
David M.; McMurry, Gordon; Piu, Fabrice†; Anderson, 
Jeffery J. 
Intratympanic Administration of OTO-313 
Reduces Tinnitus in Patients With Moderate to Severe, 
Persistent Tinnitus: A Phase 1/2 Study 
Otology & Neurotology: December 2021 - Volume 42 - 
Issue 10  
6/14 = 43%; 
2/16 = 13%; 
31% 
<0.05 
Theodoroff, S.M., Griest, S.E. & Folmer, R.L. 
Transcranial magnetic stimulation for tinnitus: using the 
Tinnitus Functional Index to predict benefit in a 
randomized controlled trial. Trials 18, 64 (2017).  
18/25 = 51% 
9/35 = 26% 
25% 
Not 
reported 
 
Hypotheses 
 
 Null Hypothesis: There will be no statistically significant difference in the proportion of 
individual successes, as defined, between the test and control groups. 
 
 Alternative Hypothesis: There will be a statistically significant difference in the proportion of 
individual successes, as defined, between the test and control groups, to the effect of 35% or 
greater. 
 
 
PRIMARY EFFICACY OUTCOME STATISTICAL EVALUATION METHODS 
 

 Intent to Treat (ITT) Principle: Primary efficacy analysis will be according to the intent to treat 
(ITT) principle; wherein subjects will be included in the analysis if they were randomized to 
study procedure group and had a valid baseline (pre-procedure) visit including recording of the 
TFI.  
 
 Missing data will be handled through multiple imputation analysis is a strategy to handle 
missing values in a clinical trial wherein each missing value is replaced with a set of plausible 
values that represent the uncertainty about the right value to impute. Multiple imputation does 
not attempt to estimate each missing value through simulated values, but rather to represent 
a random sample of the missing values. This process results in valid statistical inferences 
that properly reflect the uncertainty that results from missing values, such as valid confidence 
intervals for parameters. 
Multiple imputation inference involves three distinct phases: 
 
1. The missing data are filled in m times to generate m complete data sets. 
2. The m complete data sets are analyzed by using standard statistical procedures. 
3. The results from the m complete data sets are combined for the inference. 
 
Multiple imputation usually assumes that the data are missing at random (MAR). That is, for a 
variable Y, the probability that an observation is missing depends only on the observed 
values of other variables, not on the unobserved values of Y. 
 
 Per-Protocol Analysis will also be performed for the set of all subjects who were randomized 
to procedure group and completed the study according to the full protocol.  
 
 Primary analysis of efficacy will be according to intent to treat (ITT) analysis through the 
application of: 
 
1) Fisher's exact test to compare the proportion of individual successes between the test 
and the control groups, considering that randomization has been diligently conducted and 
important covariates between the two groups are well balanced. 
 
2) Parametric ANCOVA model analysis with the mean change from baseline to study 
endpoint in TFI score as the dependent variable, procedure group as the independent 
variable of interest and baseline TFI score as a covariate. A two-tailed significance level of 
5% will be considered statistically significant.  
  
 Covariates: The following potential covariate baseline variables will be adjusted, as applicable, 
through application of an ANCOVA analysis for the continuous variables and linear regression 
analysis for categorical variables. 
 
 Baseline Audiometric Test: PTA 
 Age, gender, ethnicity 
 Tinnitus etiology and duration 
 Use/non-use of hearing aids   
 
  
ADDITIONAL SUPPORTIVE EVALUATIONS  
 

The following exploratory qualitative trending within and between procedure groups will be 
conducted descriptively across all applicable assessments at baseline, treatment endpoint (4 
weeks), and 2 weeks post-procedure evaluations, without claims of statistical significance: 
 
a. mean changes in total TFI scores and categories across and between procedure groups 
across all three evaluations of pre-treatment, treatment end, study endpoint, and post-
treatment. 
b. 
changes in audiometric evaluations, including PTAs. 
COMPLIANCE EVALUATION  
 
Subject’s self-reported compliance with treatment administration will be evaluated. Deviations in 
compliance will be reported and evaluated with respect to impact on study outcome evaluation.  
 
BLINDING EFFICACY EVALUATION  
 
Blinding efficacy evaluation will be conducted through analysis of findings from the Subject 
Perceived Subject Group Allocation and Rationale responses, recorded at completion of the 
procedure administration phase (study endpoint). 
 
Statistical evaluation of blinding efficacy will be performed as follows: 
 
(i) The percentage of subjects who correctly perceived their procedure group assignment and 
the percentage of subjects who did not correctly perceive their procedure group assignment 
will be calculated. 
(ii) The Fischer’s Exact categorical analysis technique for comparison of proportion of 
successes (accurate procedure group assignment determination) and failures (inaccurate 
procedure group assignment determination) between subject groups will be performed for 
each of the subject. 
(iii) Qualitative analysis confirmation: Evaluation of the comments provided by the subject in 
the rationale section to explain the guess at group assignment will be evaluated and 
interpreted as follows to either support or negate the numerical findings:   
 
 Positive blinding efficacy will be supported through qualitative assessment of comments 
provided to support perceived group assignment that pertain to the determination being 
based on treatment efficacy or lack thereof, e.g.: ‘I barely notice my tinnitus anymore, so 
I believe I got the real treatment’ or ‘I haven’t noticed any change in my tinnitus, so I believe 
I got the fake treatment.’ 
 Blinding will be determined to have failed if comments provided to support perceived group 
assignment pertain to factors such as sensation/visual clues, such as ‘I saw/didn’t see a 
light go on’. 
 
SAFETY ANALYSES  
 
Safety analyses will be based on all subjects who were randomized to the test or to the placebo 
procedure group. Safety will be assessed by evaluating and comparing frequency and incidence 
of observed and/or reported adverse events between test and placebo procedure groups. A chi-
square test with a continuity correction will be performed to compare the percentage of subjects 
who had adverse events between test and placebo group subjects.  
  
Additionally, safety will be assessed through tracking of the following across study duration: 

 
a. 
changes in audiometric evaluations, including PTAs. 
b. 
Changes in tympanogram type. 
c. 
Changes in otoscopic evaluation findings. 
INFORMED CONSENT 
• Informed consent will be an agreement between the individual investigator and each subject, 
having the capacity to understand and make an informed decision. Consent will be obtained 
prior to each potential subject’s participation in this clinical study. 
• Each subject participating in this clinical study will be made aware of the fact that his or her 
participation involves research and the intent of the research, the expected duration of his or 
her participation and a description of the procedures that will be followed.   
• Each subject will be made aware of the reasonably expected benefits he or she might receive, 
as well as any risks or potential discomfort that are involved.   
• Each subject will also be made aware of alternative treatments available to him or her.   
• Each subject will be made aware that his or her records will remain confidential, but that the 
FDA and the IRB has the right to inspect his or her records.   
• Each subject will be told that his or her participation in the clinical study is voluntary, without 
force or influence from the investigator or sponsor. 
• Each subject will be given the name and method of contacting the appropriate person(s) to 
answer his or her questions about the research and in the event of a research-related injury. 
 
The informed consent form that will be used to collect the data from each subject in this clinical 
study can be found in Appendix M. 
 
CASE REPORT FORMS 
The case report forms that will be used to collect the data from each subject in this clinical study 
can be found in Appendix N. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
 
 
 
 
 
 
 
 
 
 
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