A Prospective, Non-Randomized Study to Evaluate Treatment Outcome of Nasal Airway Obstruction Using the Aerin Medical Vivaer™ Stylus
Phase: NA
Conditions: Nasal Obstruction
Sponsor: Aerin Medical

2/11/19

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TABLE OF CONTENTS 
 
1.0 
PROTOCOL SYNOPSIS ................................................................................................. 4 
2.0 
OVERALL OBJECTIVES ................................................................................................. 6 
2.1 
Primary outcome variable(s) ........................................................................................ 6 
2.2 
Secondary outcome variable(s).................................................................................... 6 
3.0 
Background and Rationale .............................................................................................. 7 
4.0 
Procedures ...................................................................................................................... 9 
4.1 
Research Design ......................................................................................................... 9 
4.2 
Study Size ................................................................................................................... 9 
4.3 
Inclusion Criteria .......................................................................................................... 9 
4.4 
Exclusion Criteria ........................................................................................................10 
4.5 
Subject recruitment .....................................................................................................10 
4.6 
Measurement / Instrumentation...................................................................................10 
4.7 
Study Phases ..............................................................................................................12 
4.8 
Internal Validity ...........................................................................................................15 
4.9 
Data Analysis ..............................................................................................................15 
5.0 
SUBJECT REIMBURSEMENT .......................................................................................16 
6.0 
STUDY WITHDRAWAL ..................................................................................................16 
7.0 
ADVERSE EVENTS .......................................................................................................17 
8.0 
RISK – BENEFIT ASSESSMENT ...................................................................................17 
8.1 
Potential Risks ............................................................................................................17 
8.2 
Potential Benefit ..........................................................................................................18 
8.3 
Minimization of Anticipated Risks ................................................................................19 
8.4 
Potential Risks to Patient Confidentiality .....................................................................19 
9.0 
QUALITY ASSURANCE AND SUPERVISION BY AUTHORITIES .................................19 
10.0 
STUDY MANAGEMENT .................................................................................................19 
11.0 
INVESTIGATIONAL DEVICE MANAGEMENT ...............................................................20 
12.0 
REQUIRED DOCUMENTS FROM THE INVESTIGATOR (PRIOR TO STUDY START) 20 
13.0 
TRAINING ......................................................................................................................20 
14.0 
ETHICAL CONSIDERATIONS .......................................................................................21 
15.0 
PROTECTION OF PATIENT CONFIDENTIALITY ..........................................................21 
16.0 
DATA COLLECTION ......................................................................................................21 
17.0 
SOURCE DATA VERIFICATION ....................................................................................21 
18.0 
STUDY SUSPENSION OR EARLY TERMINATION .......................................................22 

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19.0 
SITE CLOSE-OUT .........................................................................................................22 
20.0 
RESPONSIBILITIES.......................................................................................................22 
21.0 
SPONSOR MAINTENANCE OF STUDY RECORDS .....................................................23 
22.0 
INVESTIGATOR MAINTENANCE OF STUDY RECORDS .............................................23 
23.0 
INVESTIGATOR REPORTS ...........................................................................................24 
24.0 
DATA MANAGEMENT ...................................................................................................24 
24.1 
Data Entry ...............................................................................................................24 
24.2 
Data Cleaning .........................................................................................................25 
24.3 
Data Back-up ..........................................................................................................25 
24.4 
Confidentiality and Security .....................................................................................25 
24.5 
Final Report .............................................................................................................25 
24.6 
Publication Policy ....................................................................................................25 
25.0 
DEFINITIONS AND ACRONYMS ...................................................................................25 
 
 
 
 
 
 
 
 
 
 
 

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1.0 PROTOCOL SYNOPSIS 
 
Study Title:  
A Prospective, Non-Randomized Study to Evaluate Treatment 
Outcome of Nasal Airway Obstruction Using the Aerin Medical 
Vivaer Stylus 
 
Study Device:  
 
Aerin Medical Vivaer Stylus 
 
Device Description: 
The Vivaer Stylus is a disposable handheld device capable of 
delivering bipolar radiofrequency energy to tissue. 
 
Proposed Indication:  
The Vivaer Stylus is indicated for the treatment of nasal obstruction 
by the modification of submucosal tissue including cartilage in the 
internal nasal valve area. 
 
Study Objective:  
The main objective of this research is to evaluate the outcome of   
treating nasal airway obstruction with the Aerin Medical Vivaer 
Stylus 
 
Study Design:  
Prospective, non-randomized study to evaluate treatment outcome 
of nasal airway obstruction using the Aerin Medical Vivaer stylus 
 
 
 
Subject Population:  
Male and female subjects who present with symptoms associated 
with chronic nasal obstruction 
 
Study Procedures:  
Subjects will have both nasal valves treated in a single treatment 
session.  Follow-Up and Study Exit will be at 90 Days, Post-
Procedure. No repeat ("touch-up") procedures will be permitted 
during the 90 day follow-up period. 
 
Study Endpoints:  
Primary Endpoint variable(s) – The primary symptom outcome 
variables include self-reported Nasal Obstruction Symptoms 
Evaluation (NOSE) score and Visual Analog Scale (VAS) of nasal 
obstruction. One-way ANOVA with repeated measures will be used 
to compare post-treatment vs. baseline measurements and 
determine the effectiveness of the treatment. 
 
The primary independent endpoint variables include several 
categories: 1) variables that index general disease severity 
(Computerized Tomography (CT) staging and endoscopic 
examination score 2) peak inspiratory flow measurements of nasal 
physical resistance. 
 
Secondary outcome variables will include age, gender, race, 
duration of the disease, and medical and smoking histories.  The 
potential confounding effect of the secondary outcome variables will 
be examined. 
 
Study Evaluations:   
 
 
1. Nasal Obstruction Symptoms Evaluation (NOSE) score 
2. Visual Analog Scale (VAS) of nasal obstruction  

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3. Endoscopic examination (video and pictures), Lund-Kennedy 
endoscopic scores  
4. Peak nasal inspiratory flow 
5. Cone beam CT scan (clinical or research)  
6. Sino-Nasal Outcome Test (SNOT-22) 
7. Computational modeling of nasal airflow based on CT scan of 
each visit. 
 
  
Study Size:  
Up to 20 patients meeting the inclusion/exclusion criteria will be 
recruited.  
 
Anticipated Duration: 
Enrollment completion/Q2 2019; Follow-Up completion/Q3 2019 
 
Study Visits:   
 
Phase 1 - Pre-Admission Evaluation/Patient Consent 
 
  
 
 
Phase 2 – Baseline/Treatment 
 
Phase 3 – Follow-Up 90 Days Post-Procedure / Study Exit 
 
Study Eligibility Criteria:  
 
 
 
 
 
Inclusion Criteria: 
Eligible subjects will meet all the following: 
1. Age 18 to 75 years (inclusively) 
2. Willing and able to provide informed consent 
3. Willing and able to comply with the subject-specific 
requirements outlined in the study protocol 
4. Complaints of nasal obstruction for at least 1 year  
5. Failed maximum medical therapy (4-6 weeks of steroids) 
6. Nasal Obstruction Symptom Evaluation (NOSE) score of 
> 60 at Baseline  
7. Nasal valve is a primary or significant contributor to the subject's 
nasal obstruction as determined by the study investigator 
(based on clinical presentation, physical examination, nasal 
endoscopy, etc.) and the subject has a positive response to any 
of the following temporary measures (based on patient history 
or during office exam): 
a. Use of external nasal dilator strips (e.g., Breathe Right 
Strips) 
b. Q-Tip test (manual intranasal lateralization) 
c. Use of nasal stents 
d. Cottle Maneuver (manual lateral retraction of the cheek) 
 

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Exclusion Criteria:  
Subjects will not be enrolled if they meet any of the following:  
1. Prior surgical treatment of the nasal valve 
2. Rhinoplasty, septoplasty, inferior turbinate reduction or other 
surgical nasal procedures within the past three (3) months 
3. Severe and/or chronic sinusitis, recurrent sinusitis, or allergies 
leading to nasal obstruction and currently requiring oral 
corticosteroid therapy 
4. Severe case of any of the following: septal deviation, turbinate 
hypertrophy, polyps, or ptotic nose tip believed to be the primary 
contributor to the subject’s nasal obstruction symptoms and 
warranting surgical intervention 
5. Known or suspected allergies or contraindications to the 
anesthetic agents and/or antibiotic medications to be used 
during the study procedure session 
6. Known or suspected to be pregnant, or is lactating 
7. Other medical conditions which in the opinion of the investigator 
could predispose the subject to poor wound healing or 
increased surgical risk. 
 
 
2.0 OVERALL OBJECTIVES 
 
The study will evaluate the outcome of nasal obstruction treated with the Vivaer Stylus, and also 
attempt to use computational aerodynamics simulation and sensory measurements to identify 
and predict patients’ treatment outcome. The ability to envisage variables that will lead to best 
outcome may have potential to assist patients and clinicians in planning effective, well-informed, 
personalized treatment/surgery strategies. 
 
2.1 Primary outcome variables 
 
The primary symptom outcome variables include self-reported Nasal Obstruction Symptoms 
Evaluation (NOSE) score and VAS of nasal obstruction.  
 
The primary independent objective variables include several categories: 1) variables that 
index general disease severity (Computerized Tomography (CT) staging and endoscopic 
examination score), 2) peak inspiratory flow measurements of nasal physical resistance. 
 
2.2 Secondary outcome variables 
 
Secondary outcome variables will include age, gender, race, duration of the disease, and 
medical and smoking histories. The potential confounding effect of the secondary outcome 
variables will be examined. 
 
 

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3.0 BACKGROUND AND RATIONALE 
 
The nasal valve area (V) represents the narrowest segment of the nasal airway. It is defined as 
the area bounded by the caudal end of the upper lateral cartilage (ULC), cartilaginous nasal 
septum (S) and head of the inferior turbinate (T) (Figure 1). The nasal valve angle is the angle 
between the upper lateral cartilage and the nasal septum.  Anatomical studies have shown that 
this angle classically ranges between 10° and 15° in the nose of Caucasian individuals. The nasal 
valve is a critical site for nasal resistance and for nasal obstruction symptoms. One of the most 
common causes of nasal obstruction is internal nasal valve dysfunction wherein the upper lateral 
cartilage moves towards the septum, increasing airway resistance and leading to nasal 
obstruction.  
 
Figure 1. Nasal Anatomy 
                                              (from Weaver 20121, Figure 1) 
 
Airway remodeling in the nasal valve region may have significant benefit for patients with a narrow 
nasal valve.  Over-the-counter remedies such as external breathing strips can provide patients 
with temporary relief. However, a long-term solution to chronic nasal airway obstruction 
associated with the nasal valve usually involves extensive surgery. One of the common surgical 
procedures targeting the nasal valve is the implantation of alar batten grafts; i.e., curved cartilage 
supports placed into areas of the nasal valve area to enlarge and strengthen it. Although batten 
graft surgical outcomes are generally successful, the procedure requires the harvesting of a 
cartilage graft from another anatomic site, a difficult and time-consuming procedure. Overall, 
current surgical therapy on the nasal valve is efficacious, but is invasive and associated with long 
recovery periods and the risk of complications, e.g., hemorrhage.  
 
The use of radiofrequency energy has been common for decades in the fields of otolaryngology, 
neurosurgery, cardiology, urology and general surgery.  For instance, radiofrequency turbinate 
reduction (RFTR) uses radiofrequency to create heat within the submucosal tissue of the turbinate, 
reducing tissue volume with minimal impact on surrounding tissues. Numerous studies have 
demonstrated that radiofrequency therapy in the nasal passage can be safe and effective in 
improving nasal obstruction and in preserving nasal function.2,3  
 
The Aerin Medical Vivaer System an investigational device that is capable of delivering bipolar 
radiofrequency energy to improve nasal breathing by modifying soft tissues of the nasal valve. 
The System is comprised of the Vivaer Stylus (Figure 2), a disposable handheld device capable 
of delivering bipolar radiofrequency energy to tissue, and a radiofrequency generator (Figure 3). 
 
 

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Figure 2. Vivaer Stylus 
 
 
The Vivaer Stylus consists of a handle, shaft and treatment tip. An array of bipolar electrodes is 
positioned on a non-conductive tip which is attached to the handle via a non-conductive shaft. A 
temperature sensor (thermocouple) is located on the tip to monitor tissue temperature. The Stylus 
is attached to a temperature-controlled radiofrequency generator via a flexible cable. The Vivaer 
Stylus modifies the soft tissues of the nasal valve through the use of low doses of radiofrequency 
energy. The low-power radiofrequency generates heat within the submucosal tissue, creating a 
coagulation lesion. As the lesion heals, the tissue retracts and stiffens, slightly widening the nasal 
valve area. This decreases the nasal airflow resistance thereby improving inflow of air through 
the nose (as demonstrated in earlier pre-clinical and pilot studies). The procedure requires local 
anesthesia only, and is much less invasive than current surgical approaches. 
 
This clinical study plans to use computational fluid dynamics (CFD) and various sensory testing 
techniques to examine the factors contributing to patients’ outcome after Aerin treatment. The 
efficacy and safety of the Vivaer Stylus treatment will be recorded. 
 
 
 
Figure 3. Aerin Console 
 
 
 
②Connector 
①Cable 
③Stylus 
Handle 
④Stylus  
Shaft
⑤Stylus Tip 
⑦Tip/Face 
⑥Electrodes 
⑧Thermocouple 

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4.0 PROCEDURES 
 
4.1 Research Design 
 
The study will be conducted by the Department of Otolaryngology, The Ohio State University 
School of Medicine, in conjunction with Aerin Medical.  This study is a prospective, case series 
design, involving a group of patients with chronic nasal obstruction symptoms. The study is a 
longitudinal design, involving two test sessions: one at baseline (pre-treatment) and one at 90 
days post-treatment.   
 
4.2 Study Size 
 
Up to Twenty (20) patients meeting the inclusion/exclusion criteria will be recruited.  
 
4.3 Inclusion Criteria 
 
Eligible subjects will meet all the following: 
1. Age 18 to 75 years (inclusively) 
2. Willing and able to provide informed consent 
3. Willing and able to comply with the subject-specific requirements outlined in the study 
protocol 
4. Complaints of nasal obstruction for at least 1 year  
5. Failed maximum medical therapy (4-6 weeks of steroids) 
6. Nasal Obstruction Symptom Evaluation (NOSE) score of > 60 at Baseline  
7. Nasal valve is a primary or significant contributor to the subject's nasal obstruction as 
determined by the study investigator (based on clinical presentation, physical 
examination, nasal endoscopy, etc.) and the subject has a positive response to any of 
the following temporary measures (based on patient history or during office exam): 
a. Use of external nasal dilator strips (e.g., Breathe Right Strips) 
b. Q-Tip test (manual intranasal lateralization) 
c. Use of nasal stents 
d. Cottle Maneuver (manual lateral retraction of the cheek; see Figure 4) 
 
 
 
 
Figure 4. Cottle Maneuver 
 

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Figure 4 demonstrates the Cottle Maneuver as the patient or the physician temporarily lifts 
and lateralizes the skin around the nose and cheek, increasing the nasal valve angle, and 
potentially increasing nasal airflow. A positive response can be an indicator that the patient 
will respond well to an increase in nasal valve angle. 
 
The Q-Tip test is another evaluation of potential positive response. A Q-tip is placed gently 
within the nares against the lateral nasal wall at the location of the narrowest nasal valve 
region and is pushed outward lightly to expand the nasal valve angle. A positive response to 
this maneuver may also predict the potential benefit of nasal valve correction. 
 
4.4 Exclusion Criteria  
 
Subjects will not be enrolled if they meet any of the following:  
1. Prior surgical treatment of the nasal valve 
2. Rhinoplasty, septoplasty, inferior turbinate reduction or other surgical nasal 
procedures within the past three (3) months 
3. Severe and/or chronic sinusitis, recurrent sinusitis, or allergies leading to nasal 
obstruction and currently requiring oral corticosteroid therapy 
4. Severe case of any of the following: septal deviation, turbinate hypertrophy, polyps, or 
ptotic nose tip believed to be the primary contributor to the subject’s nasal obstruction 
symptoms and warranting surgical intervention 
5. Known or suspected allergies or contraindications to the anesthetic agents and/or 
antibiotic medications to be used during the study procedure session 
6. Known or suspected to be pregnant, or is lactating 
7. Other medical conditions which in the opinion of the investigator could predispose the 
subject to poor wound healing or increased surgical risk. 
 
4.5 Subject recruitment    
 
Patients will be primarily recruited from the clinical population being seen by physicians as 
part of their practice in the Department of Otolaryngology, The Ohio State University School 
of Medicine. In order to ensure the subject population has adequate access to the recruitment 
materials, IRB approved flyers will be available in the patient waiting area, and on the 
department’s website / Facebook page.  
 
4.6 Measurement / Instrumentation 
 
Endoscopic Examination 
Patients will receive endoscopic examination as part of their standard clinical care. The 
severity of disease will be scored based on endoscopic examination (Lund-Kennedy 
endoscopic scores).   
 
Study Procedures 
Each visit is expected to last 2-3 hours and may include the following procedures. (These 
procedures are routinely performed for research purposes; however, none of them should be 
considered standard clinical care. The differences will be explained to the participants during 
the consent process.) 
 

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1.  All participants will be asked to fill out a medical history questionnaire, as well as the 
Sino-Nasal Outcome Test (SNOT-22) questionnaire, the NOSE score and the Visual 
Analog Scale for nasal obstruction. The SNOT-22 and NOSE are two commonly used 
validated outcome questionnaires to evaluate change in rhinosinusitis and/or nasal 
obstruction symptoms in patients. The VAS is a self-rating of nasal obstruction on a 
linear scale (range 0-10; 0 being completely clear and 10 being completely blocked) 
using both nostrils and then with the left and right nostril separately.  
 
2. Peak nasal inspiratory flow: A mask attached to a spirometer is fitted tightly on each 
subject´s face without touching the nose. The subject is instructed to inhale as strongly 
as possible, and the peak flow rate is then recorded. The test will be repeated three 
(3) times and the results averaged. For unilateral recording, one nostril is blocked with 
a tape, so that the subject can only inhale through the other nostril.  
 
3.  Research CT scans: The subject may receive a CT scan for non-clinical purposes with 
a cone beam office CT scanner (3D Accuitomo 170, J. Morita USA, Inc.) at the 
Department of Otolaryngology at The Ohio State University School of Medicine. This 
scan has a radiation dosage of roughly 12% that of a conventional head CT scan with 
a significantly lower associated health risk, while retaining excellent air-mucus contrast 
for CFD modeling. The recruitment strategy will reduce the need for research CTs and 
unnecessary radiation by recruiting patients who have been prescribed a sinus CT 
clinically, which will serve as the subject’s baseline CT. Furthermore, if a post-
treatment/surgery CT scan is clinically necessary for a patient after enrollment, it will 
be scheduled for the subject’s second study visit. Through these measures, the need 
for research CT scans will be reduced to limit the number of research CT scans for all 
patients to one (1). 
 
4. CFD Modeling: 3D numerical nasal models that are suitable for numerical simulation 
of nasal airflow and odorant transport will be constructed based on each 
subject/patient’s CT scan and according to the method described by Zhao8. In brief, 
first the interface between the nasal mucosa and the air is delineated (using AMIRA) 
on the CT scans. Then, the nasal cavity air space is filled with tetrahedral elements 
(ICEMCFD). A finer mesh (prism layer) is created near the mucosal surface to more 
accurately model the rapidly changing near-wall air velocity and odorant concentration. 
Next, inspiratory and expiratory quasi-steady laminar nasal airflow8,9 is simulated 
(Fluent©, Ansys Inc, USA) by applying a physiologically realistic pressure drop 
between the nostrils and the nasal pharynx. By varying the pressure drop and 
computing the changes in total airflow through the nose, the total nasal resistance can 
be determined, a numerical method of rhinomanometry. Through simulation, the 
following variables will be obtained: numerical nasal resistance, nasal mucosal cooling 
rate, and nasal airflow distribution patterns. 
 
5. Adverse Event Evaluation – Subjects will be asked about possible side effects or 
adverse experiences related to the study procedure. All events will be documented on 
the proper Adverse Event Log and Adverse Event Case Report Form.  Anticipated 
observations related to the study procedure will be tabulated, but will not be 
categorized as adverse events unless they require mitigation by the treating physician 
or are greater in severity, duration or degree of incidence than anticipated.  Refer to 
Table 2 for a listing of anticipated observations as well as anticipated frequency, 
severity and duration. 

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7. Medications – Updates to current medications or any new or changed medications will 
be requested at each follow-up visit.  The medication log will be updated to reflect any 
changes.  In addition, any medications required as a result of intervention related to 
the study procedure will be documented and will correlate with the Adverse Event 
Case Report Form. 
    
8. General Health Survey Subject will be asked to complete the SF-36 before and after 
treatment. The SF-36 is one of the most widely used generic measures of health-
related quality of life and has been shown to discriminate between subjects with 
different chronic conditions and between subjects with different severity levels of the 
same disease. The SF-36 has also demonstrated sensitivity to significant treatment 
effects in a variety of patient populations.  
 
 
4.7 Study Phases 
The study will be conducted in three phases as subjects are consented and evaluated for 
eligibility, treated and followed until study exit:  
 
Phase 1 - Pre-Admission Evaluation/Patient Consent 
Phase 2 – Baseline/Treatment 
Phase 3 – Follow-Up 90 Days (+/- 15 days) Post-Procedure / Study Exit 
 
The assessments to be performed during each phase are listed in Table 1. 
 
Pre-Admission Evaluation/Patient Consent 
Patients presenting with symptoms associated with nasal airway obstruction will be 
approached with the study and asked if they are willing to volunteer participation.  Patients 
will initially be asked about duration of symptoms and conservative measures used for their 
condition.  Any known concomitant nasal conditions and past nasal surgeries will be discussed 
to understand if they are potential candidates for the study.   
 
 
 
 
 
 
 
 
 
 
 
 
 

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Table 1.  Schedule of Assessments 
Assessments 
Screening / Evaluation 
Baseline/Study Procedure  
Immediately Post-Treatment 
90 day Follow-Up / Study Exit 
    (+/- 15 days) 
Informed Consent 
X 
 
 
 
Demographics and Medical History  
X 
 
 
 
Physical Exam and Vital Signs  
 
X 
 
 
Medication Review 
 
X 
 
X 
SF-36 Quality of Life Questionnaire 
 
X 
 
X 
NOSE Score 
X 
 
 
X 
Study Procedure 
 
X 
 
 
Endoscopic Assessment of treatment area 
(with representative still photographs) 
 
X 
X 
X 
Cone beam CT scan (clinical or research)  
 
X 
 
X 
Sino-Nasal Outcome Test (SNOT-22) 
 
X 
 
X 
Peak Nasal Inspiratory Flow (PNIF) 
 
X 
 
X 
Visual Analog Scale (VAS) of nasal 
obstruction  
 
X 
 
X 
Adverse Event review 
 
 
X 
X 
Pregnancy test (if female of child bearing 
potential) 
 
X 
 
 
 
 
Informed Consent 
Informed consent will be obtained as outlined in 21 CFR Part 50 and the Good Clinical 
Practice: Consolidated Guidance (ICH, April 1996).  
 
A research study member at the approved study site will speak with the study candidate about 
the purpose of the study and investigational research.  Explanation of the study background, 
study procedure, follow-up visit schedule, and study procedure risks and benefits will be 

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reviewed in detail with the patient.  Patients will be given the time they need to read through 
the study information and informed consent document and to ask as many questions as 
necessary to make them comfortable with the study and the requirements.  A patient willing 
to participate after undergoing the informed consent process will then be asked to sign the 
consent form and given a copy.  The original will be kept on file.  
 
For those potential candidates who agree to participate in the study by signing the IRB 
approved Informed Consent Form (ICF), a baseline evaluation will be conducted.  Subjects 
will be considered enrolled once they arrive at the study clinic to undergo the procedure.  At 
this time a subject identification number will be assigned along with the subject binder. 
 
During the baseline and follow-up visits, the procedures listed below will occur  
1. Endoscopic examination (video and pictures), Lund-Kennedy endoscopic scores  
2. Peak nasal inspiratory flow 
3. Cone beam CT scan (clinical CT at baseline; clinical or research CT at 90-day follow-
up visit)  
4. Nasal Obstruction Symptom Evaluation (NOSE) scale  
5. Sino-Nasal Outcome Test (SNOT-22) 
6. Visual analogue scale (VAS) rating severity of nasal obstruction  
7. Computational modeling of nasal airflow based on CT scan of each visit.  
 
During the baseline visit, data collection will be performed first, and then the Aerin Vivaer 
Treatment will be provided in the clinic by the physician. The styluses used in this study will 
be manufactured and supplied by the sponsor.  
 
During the treatment, 0.5 ml of local anesthesia (lidocaine 1% with epinephrine 1:100,000) 
will be injected into the target tissue. The Vivaer stylus will be inserted into the nose and the 
electrode-containing tip will be positioned against the target tissue.  
 
Subjects will have both nasal valves treated in a single study procedure session.  Each nostril 
will be treated at up to 3 non-overlapping positions along the upper lateral nasal valve region.  
 
Treatment settings to be used are: 
Temperature ...............60C 
Power .................... 4 Watts 
Treatment Time ..... 18 secs 
Cooling Time ......... 12 secs 
 
Accurate positioning will be confirmed by observing the temperature change on the RF 
generator screen as the stylus tip comes in contact with the target tissue.  
 
No repeat ("touch-up") procedures will be permitted during the 90-day follow-up period.   
 
Immediate Post-Procedure Care (prior to leaving the clinic) 
At the discretion of the physician, the following care and instructions may be provided: 
• 
Apply petroleum jelly to the treatment area as needed.  

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• 
The patient should be instructed not to manipulate the treatment site for 24 hours with 
the exception of any necessary hemostasis.     
 
Study subjects will be reminded of their next follow-up visit and will be scheduled within the 
study window (90  15 days).   
Adverse events (AEs) may occur during the treatment phase or during the follow-up phase.  
Adverse events occurring during the baseline assessment will be documented in the subject’s 
medical record but will not count as related to the device or procedure.  Each adverse event 
will be recorded and judged by the Investigator as to its relationship and level of relatedness 
to the device and/or procedure.  In addition, the Investigator will identify the date of onset, 
severity and duration.  All adverse events will be monitored until they are adequately resolved 
or explained.   
4.8 Internal Validity 
 
The participating physicians will ensure that the recruitment material is well distributed to all 
potential subject/patient populations. In the recruitment process, they will specifically 
emphasize to all potential subjects/patients that whether or not they agree to participate will 
not have any impact on their continuing treatment and interactions at the Department of 
Otolaryngology, The Ohio State University School of Medicine. 
 
4.9 Data Analysis 
 
Treatment effectiveness  
Outcome variables: patient’s ratings of nasal obstruction via a VAS and NOSE score as well 
as the SNOT-22 questionnaire and peak inspiratory flow rate. One-way ANOVA with repeated 
measures will be used to compare post-treatment vs. baseline measurements and determine 
the effectiveness of the treatment. 
 
 
Hypothesis:  
Nasal valve region airflow and airflow induced cooling is critical for patients’ subjective nasal 
patency. 
 
Many publications suggest that sensory feedback is as important to perception of nasal 
obstruction as nasal resistance.  For example: Topical or oral application of menthol produces 
the illusion of decongestion and improved nasal airflow without actually altering nasal 
resistance10. Topical application of local anesthetics results in an artificial sensation of nasal 
obstruction, presumably due to blocking of the trigeminal afferents11.  
 
The Ohio State University (OSU) staff have published a series of studies6,12,13 with 
individualized Computational Fluid Dynamics models and demonstrated that nasal cooling 
during breathing at the nasal valve region and the nasal trigeminal nerve sensitivity are key 
to the perception or absence of nasal obstruction. The combination of these variables can 
predict the subject’s ratings (excellent, normal and moderately obstructed) with 89.3% 
success. It is likely that nasal valve width and shape may have an optimal range in order to 
achieve both low nasal resistance and high regional mucosal cooling (see Fig. 5). This study 
will examine a broad list of factors that may contribute to patients’ subjective outcomes, not 
just limited to nasal resistance alone, that include CFD simulation of nasal airflow, mucosa 
cooling and mucosa sensitivity responding to that cooling. 
 

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Figure 5. Computational simulation of nasal cooling 
a) high regional cooling, no complaints 
b) low nasal cooling with moderate ratings of nasal obstruction 
 
Spearmen correlation and multiple regression will be used to screen for independent 
variables that significantly correlate with dependent variables, as well as potential non-linear 
relationships between the variables. Other potential confounding factors (e.g., age, duration 
of the disease, smoking history) will also be examined. The Holm Bonferroni correction will 
be applied to control for multiple comparisons. Finally, statistical learning methods such as 
linear discrimination analysis (LDA) and logistic regression will be applied for classification 
and discrimination of patient symptom categories (e.g., symptom-free, moderate and severe 
nasal obstruction) based on significant independent variables.  
 
 
5.0 
SUBJECT REIMBURSEMENT 
Subjects may be reimbursed for their time and travel and any expenses associated with each 
study visit, as allowed by study site policies.  Subjects will not be reimbursed for those scheduled 
study visits that they do not attend.   
 
 
6.0 
STUDY WITHDRAWAL 
Subjects may be terminated or withdrawn from the study for the following reasons: 
• 
Voluntary withdrawal – the subject voluntarily chooses not to further participate in the 
study 
• 
*Lost to follow-up – the subject is more than one month late (beyond the late visit window) 
to a study visit and 3 documented attempts to contact the subject are unsuccessful.  A 
subject who misses a study visit but attends a subsequent visit will no longer be 
considered lost to follow-up. 
• 
*In the physician’s opinion, it is not in the best interest of the subject to continue study 
participation. 
• 
Subject death.   
 
*Where possible, subjects will be followed for safety to study completion.  Safety follow-up will 
include a review of adverse events (AEs).  A safety follow-up assessment may be performed 
either via a phone or email contact or a physician visit.   
 
Any study subject who does not attend the scheduled follow-up visit should be contacted by site 
personnel to determine the reason for the missed appointment.  The reason for the missed visit 
should be determined and documented in the subject’s study records.  All subjects enrolled 

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(including those withdrawn or lost to follow-up) shall be accounted for with appropriate 
documentation. 
 
 
7.0 
ADVERSE EVENTS 
Adverse events (AEs) may occur during the treatment phase or during the follow-up phase.  
Adverse events occurring after the baseline assessment but before the treatment procedure will 
be documented in the subject’s medical record but will not count as related to the investigational 
device or procedure.   
Each adverse event will be recorded in the corresponding subject’s CRF.  The Investigator will 
make a judgement as to its relationship and level of relatedness to the study device and/or study 
procedure.  In addition, the Investigator will identify the date of onset, severity and duration of the 
AE.  All adverse events will be monitored until they are adequately resolved or explained.  If a 
subject reaches the 90-day follow-up visit and is experiencing a new or ongoing adverse event, 
the study sponsor should be contacted to discuss the need and/or methods for continued 
surveillance of the event. 
The Investigator must submit to the Sponsor a report of any Serious Adverse Event (SAE), 
Serious Adverse Device Effect (SADE) or Unanticipated Adverse Device Effect (UADE) within 24 
hours of knowledge of the event. 
Sponsor Contact:   Scott Wolf, MD  
Telephone:   
 
(650) 605-3579 
Facsimile:     
 
(650) 605-3579 
Email:  
 
scott@aerinmedical.com  
 
 
In addition, the Investigator will report adverse events to the reviewing IRB (as applicable) 
according to the local reporting requirements. 
 
 
8.0 
RISK – BENEFIT ASSESSMENT 
8.1 Potential Risks 
Potential risks associated with the use of the Vivaer System do not differ from those of the 
commonly used devices and procedures to treat nasal obstruction discussed previously, but 
due to the non-surgical nature of the therapy, small treatment area, low-power delivery and 
lack of need for general anesthesia, the overall risk to the patient may be less than from 
other procedures such as RF turbinoplasty, septoplasty and/or functional rhinoplasty.   
 
Potential risks associated with the use of the Vivaer System and/or the associated local 
anesthetics are outlined below.  Subjects will be monitored closely as part of this study to 
allow for detection of symptoms, should they be present.  This, in turn, should allow for early 
treatment or intervention, if necessary.  
 
While there were no reports of these events in the previous feasibility study of this system, 
the following are adverse events or side effects that may occur as a result of the treatment:  
• 
Infection 

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• 
Bleeding (other than intra-treatment at treatment sites and greater than anticipated 
by the investigator) 
• 
Mucosal changes  
• 
Scar formation leading to nasal obstruction  
• 
Sensory changes at treatment site  
• 
Vasovagal response secondary to the procedure 
 
Table 2 provides a list of anticipated observations that are expected in and around the 
treatment area.  For reference, the incidence (reported as percentage of treated nostrils) 
observed in the previous feasibility study is also provided.  These observations will be 
assessed and recorded at study visits if they occur but, being anticipated as a result of the 
procedure, will not be considered adverse events unless they require mitigation by the 
treating physician or are greater in severity, duration or degree of incidence than anticipated.  
If one of these types of observations is deemed to be an adverse event, it should be 
recorded on the study Adverse Event CRF. 
 
Table 2.  Treatment Area Observations (Feasibility Study) 
Observation 
Post-Procedure 
(% treated nostrils) 
30-Day Follow-Up 
(% treated nostrils) 
90-Day Follow-Up 
(% treated nostrils) 
Inflammation / redness 
Mild  
55.9 
Mild  
10.7 
Moderate    1.8 
Mild  
3.7 
Swelling, edema 
Mild  
64.4 
Mild  
16.1 
Moderate    3.6 
Mild  
3.7 
Blanching 
 
Mild  
66.1 
Moderate   3.4 
Mild 
3.6 
Mild  
3.7 
Numbness 
Mild  
5.1 
No reports 
No reports 
Bruising around orbital area 
No reports 
No reports 
No reports 
Soreness, pain 
Mild  
15.3 
Mild  
3.6 
Moderate   21.8 
No reports 
Bleeding at anesthetic 
injection site 
Mild  
5.3  
No reports 
No reports 
Bleeding at treatment site 
Mild  
3.4 
No reports 
No reports 
Nasal obstruction from tissue 
edema 
Mild  
45.8 
Mild  
5.4 
Moderate    1.8 
No reports 
Disruption of mucosal flow / 
crusting 
Mild  
1.7 
Mild  
10.7 
Moderate    1.8 
No reports 
 
 
8.2 Potential Benefit 
Potential benefit, associated with the use of the Vivaer System, is to offer a safe, minimally 
invasive treatment method to improve nasal breathing.  Improved nasal breathing may have 
a positive effect on quality of life and health.   
 

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8.3 Minimization of Anticipated Risks 
Risks associated with the Vivaer System are minimized by design.  In addition, risks will 
be minimized through the use of an Investigator with a high degree of experience in nasal 
surgical and minimally invasive procedures.  The Investigator will receive sponsor-led 
training in proper use of the device, prior to study initiation and as warranted throughout the 
study.  The sponsor will monitor the study for any trends that would indicate a safety issue.   
8.4 Potential Risks to Patient Confidentiality  
In all clinical studies, confidentiality of protected health information may be breached due to 
study-related activities beyond those of routine clinical care.  This risk will be minimized by 
not collecting personally identifying information on Case Report Forms (CRFs) or other 
study-related documentation to be provided to the study sponsor.   
 
9.0 
QUALITY ASSURANCE AND SUPERVISION BY AUTHORITIES 
This study will be conducted in accordance with elements of E6 Good Clinical Practice 
Consolidated Guidance, ICH, April 1996, abbreviated requirements of 21 CFR 812.2(b) for Non-
significant Risk (NSR) device studies, the Declaration of Helsinki, the Belmont Report, and IRB 
requirements. 
 
All documents and data shall be produced and maintained in such a way to assure control of 
documents and data to protect the patient’s privacy as far as reasonably practicable.  The Sponsor 
and representatives of the FDA or other regulatory authorities are permitted to inspect the study 
documents (e.g., study protocol, CRFs, and original study-relevant medical records/files) as 
needed.  All attempts will be made to preserve patient confidentiality.  
 
The clinical site is subject to audit by study sponsor personnel or designee for protocol adherence, 
accuracy of CRFs and compliance with applicable regulations.  Any evident pattern of non-
compliance with respect to these standards will be cause for corrective action. 
 
The study protocol, data-recording procedures, data handling as well as study reports are subject 
to an independent clinical Quality Assurance audit by the study sponsor, its designee, or health 
authorities. 
 
 
10.0 
STUDY MANAGEMENT 
This study will be conducted in accordance with elements of E6 Good Clinical Practice 
Consolidated Guidance, ICH, April 1996, Abbreviated Requirements of 21 CFR 812 for NSR 
device studies, the Declaration of Helsinki, the Belmont Report and any conditions imposed by 
the reviewing IRB or US FDA or other regulatory agency.   
 
The study sponsor has the overall responsibility for the conduct of the study according to all 
applicable regulatory requirements.  The study sponsor will have certain direct responsibilities 
and will delegate other responsibilities to the Principal Investigator.  The study sponsor and 
Principal Investigator will ensure that the study is conducted according to all applicable regulations.  
All personnel to participate in the conduct of this clinical trial will be qualified by education and / 
or experience to perform their tasks.   
 

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The study sponsor, Investigator or any person acting for or on behalf of a sponsor or Investigator 
shall act in accordance the applicable standards, guidelines and regulations. 
 
 
11.0 
INVESTIGATIONAL DEVICE MANAGEMENT 
The Vivaer System is investigational and is not approved for commercial use in the United 
States.  The investigator shall maintain adequate records of the receipt and disposition of all 
investigational devices.  When trial enrollment is complete, the investigator shall return any 
unused devices to the sponsor or their designee.  The device will only be used as part of this 
clinical trial in eligible patients and will be used according to its intended use.  A copy of the 
Instructions for Use (IFU) accompanies each study device. 
 
 
12.0 
REQUIRED DOCUMENTS FROM THE INVESTIGATOR (PRIOR TO STUDY START) 
At a minimum, the following documents will be provided by the investigational site to the study 
sponsor: 
• 
Signed Investigator Agreement  
• 
Signed Clinical Investigational Plan (CIP) Signature Page 
• 
IRB approval   
• 
IRB approved Informed Consent Form (ICF) 
• 
Investigator and Co-Investigator’s current Curriculum Vitae 
• 
Investigator and Co-Investigator’s current Medical Licenses 
 
A site may not begin study participation until all of the above listed documents have been provided 
to the study sponsor. 
 
 
13.0 
TRAINING 
The Vivaer System is intended for use by experienced medical personnel.  The Investigator will 
be provided training by the study sponsor in the use of the device to familiarize them with the use 
of the Vivaer System prior to their participation in the clinical study. 
Each study center will undergo protocol initiation including but not limited to a review of the 
following: 
• 
Procedures for obtaining Informed Consent 
• 
Procedures for completing Informed Consent Form 
• 
Device usage instructions  
• 
Reporting requirements 
• 
CRF completion and correction procedures 
• 
Vivaer System overview 
• 
Protection of patient confidentiality 
 

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14.0 
ETHICAL CONSIDERATIONS 
The rights, safety and well-being of clinical investigation subjects shall be protected consistent 
with the ethical principles outlined in the Declaration of Helsinki.  This shall be understood, 
observed and applied at every step in this clinical investigation.  
 
It is expected that all parties will share in the responsibility for ethical conduct in accordance with 
their respective roles in the investigation.  The Sponsor and the Investigator shall avoid improper 
influence or inducement of the patient, study monitor, clinical investigator or other parties 
participating in or contributing to the clinical investigation.   
 
 
15.0 
PROTECTION OF PATIENT CONFIDENTIALITY 
At all times throughout the clinical investigation, confidentiality will be observed by all parties 
involved.  All data shall be secured against unauthorized access.  Privacy and confidentiality of 
information about each patient shall be preserved in the reports and in any publication.  Each 
patient participating in this study will be assigned a unique identifier.  All CRFs will be tracked, 
evaluated, and stored using only this unique identifier.   
The investigational site will maintain a confidential study patient list (paper or electronic) 
identifying all enrolled patients.  This list will contain the assigned study patient’s unique identifier 
and name.  The Site Principal Investigator (PI) bears responsibility for keeping this list confidential.  
This list will not be provided to the study sponsor and is only to be used at the study center. 
Monitors and auditors will have access to the study patient list and other personally identifying 
information of study patients to ensure that data reported in the CRF corresponds to the person 
who signed the ICF and the information contained in the original source documents.  Such 
personal identifying information may include, but is not limited to the patient’s name, address, 
date of birth, gender, race and medical record number.   
 
NOTE:  The patient’s name, medical record number or address will NOT be recorded in the 
monitor’s visit report or the database; demographic data that may be recorded includes age, race, 
and gender.   
Any source documents copied for monitoring purposes by the Sponsor will have patient 
identifiable information redacted and be identified by using the assigned patient’s unique identifier 
in an effort to protect patient confidentiality.   
 
 
16.0 
DATA COLLECTION 
Study data will be collected using standardized Case Report Forms (CRFs).  The CRFs are 
designed to accommodate the specific features of the trial design.  Modification of CRFs will only 
be made if deemed necessary by the study sponsor.   
 
17.0 
SOURCE DATA VERIFICATION 
At a minimum, source data verification will be performed on all primary endpoint, secondary 
endpoint and safety data for each patient enrolled in this study. 
 

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18.0 
STUDY SUSPENSION OR EARLY TERMINATION 
The study can be discontinued at the discretion of the Site PI or Sponsor for reasons including, 
but not limited to, the following: 
• 
Occurrence of adverse events unknown to date in respect to their nature, severity, or 
duration, or the unexpected incidence of known adverse events 
• 
Obtaining new scientific knowledge that shows that the study is no longer valid or 
necessary 
• 
Insufficient recruitment of patients 
• 
Unanticipated adverse device effect (UADE) presenting an unreasonable risk to patients 
(Sponsor may terminate the study immediately) 
• 
Persistent non-compliance with the protocol 
• 
Persistent non-compliance with IRB or regulatory requirements 
 
If the study is discontinued or suspended prematurely, the Sponsor shall promptly inform the 
clinical investigator(s) / investigational centers of the termination or suspension and the reason(s) 
for this.  The IRB shall also be informed promptly and provided with the reason(s) for the 
termination or suspension by the Sponsor or by the Site PI / investigational center.  Regulatory 
authorities and the personal physicians of the patients may also need to be informed if deemed 
necessary.   
 
 
19.0 
SITE CLOSE-OUT  
At the time of the site close-out visit, the site monitor or designee will collect all outstanding study 
documents, ensure that the Investigator’s files are accurate and complete, review record retention 
requirements with the Investigator, make a final accounting of all study supplies, and ensure that 
all applicable requirements are met for the study.  The observations and actions made at this visit 
will be documented in a final closeout report.   
 
 
20.0 
RESPONSIBILITIES 
Aerin Medical Inc. is the manufacturer of the Vivaer System and the Sponsor of this study.  The 
study Sponsor has the overall responsibility of the study and will work to ensure compliance with 
the Investigational Plan, elements of Good Clinical Practice: Consolidated Guidance (ICH, April 
1996), signed study agreements and 21 CFR 812.2(b), Abbreviated Requirements.   
The sponsor will be responsible for, but not limited to, conducting the following tasks:  
• 
Select qualified Investigators 
• 
Select qualified monitors and other contract study personnel 
• 
Provide the Investigational Plan and any subsequent amendments 
• 
Sign the protocol  
• 
Provide appropriate information and device training to Investigators and study site staff  

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• 
Promptly inform the Investigators and where applicable any regulatory authorities and the 
Institutional Review Board, if the study is prematurely terminated or suspended and the 
reason for the termination or suspension 
• 
Provide protocol initiation training to include review of the Vivaer System instructions for 
use, the Investigational Plan, CRF completion guidelines, and guidelines for obtaining 
informed consent 
• 
Coordinate ongoing communication with CRO(s), consultants and study sites to resolve 
any problems concerning the protocol or data collection.  Every effort will be made to 
ensure compliance with the protocol 
• 
Retain ownership of all clinical data generated in this study, and control the use of the data 
for purposes of regulatory submissions to the US and other regulatory agencies 
• 
Protect patient confidentiality  
• 
Collect, store and keep secure, at a minimum, the following documents: 
• 
A current Curriculum Vitae and medical license of each Investigator 
• 
The name of the institutions where the study will be conducted 
• 
The IRB opinion and / or approval, in writing, and relevant correspondence 
• 
Correspondence with authorities (as required) 
• 
Investigator Agreement  
• 
CIP Signature Page 
• 
Appropriate insurance certificates (as necessary) 
• 
IRB approved ICF 
• 
Names / contact information for study monitor(s) 
• 
Copies of signed and dated CRFs 
• 
Records of any adverse events and adverse device effects 
• 
Statistical analyses and underlying supporting data 
• 
Final report 
 
 
21.0 
SPONSOR MAINTENANCE OF STUDY RECORDS 
The Sponsor will be responsible for maintaining study records per 21 CFR 812.140(b) and 
Good Clinical Practice: Consolidated Guidance (ICH, April 1996), Section 8. 
 
The Sponsor will be responsible for monitoring the investigation per 21 CFR 812.46 and Good 
Clinical Practice: Consolidated Guidance (ICH, April 1996), Section 5.18. 
 
The Sponsor will be responsible for reporting per 21 CFR 812.50(b). 
 
 
22.0 
INVESTIGATOR MAINTENANCE OF STUDY RECORDS 
The Site PI will be responsible for maintaining study records per 21 CFR 812.140(a) and Good 
Clinical Practice: Consolidated Guidance (ICH, April 1996), Section 4.9. 
 
The Site PI will allow auditing of their clinical investigation procedure(s). 

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Each investigator will provide a completed Financial Disclosure prior to study initiation and upon 
request at later time points in the study. 
The Investigator is responsible for maintaining medical and study records for every patient 
participating in the clinical study (including information maintained electronically such as digital 
imaging).  The study center will also maintain original source documents from which study-
related data are derived, which may include, but are not limited to: 
• 
Clinic progress notes recording patient’s medical history and medications 
• 
Medical records regarding AEs, including treatment and clinical outcome  
• 
Results of diagnostic examinations 
• 
Notes of phone calls and/or correspondence indicating investigational site’s attempts to 
contact and follow a study patient at the required follow-up visits until such time a subject 
is determined to be lost-to-follow-up. 
 
The Investigator must ensure that all study patient records are stored for at least 2 years after the 
latter of the following two dates: the date on which the investigation is terminated or completed, 
or the date that the records are no longer required for purposes of supporting a premarket 
approval application or a notice of completion of a product development protocol.  To avoid error, 
the study site should contact the study sponsor prior to the destruction of study records to ensure 
that they no longer need to be retained.  In addition, the study sponsor should be contacted if the 
Investigator plans to leave the investigational site so that arrangements can be made for the 
handling or transfer of study records. 
 
 
23.0 
INVESTIGATOR REPORTS 
The Site PI will be responsible for reporting per 21 CFR 812.150(a) and according to applicable 
IRB requirements and Good Clinical Practice: Consolidated Guidance (ICH, April 1996), Section 
4.11. 
NOTE:  Reports must identify patients using the study’s unique identifier to protect patient’s 
confidentiality. 
The primary responsibility of the investigator is to protect the welfare of the study subjects. Other 
responsibilities, including adherence to the protocol, are defined in the Investigator Agreement. 
 
 
24.0 
DATA MANAGEMENT 
Data will be handled as applicable, per Good Clinical Practice: Consolidated Guidance (ICH, April 
1996), Section 5.5. To ensure proper tracking of Case Report Forms, a tracking system will be 
utilized.   
 
24.1 Data Entry 
Qualified personnel assigned by the principal investigator and/or the sponsor will perform 
data entry.   
 

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24.2 Data Cleaning  
All CRF pages will be subject to initial inspection for omitted data, gross data inconsistencies, 
illegible data and deviations.  Any deficiencies or deviations will be reviewed and any 
necessary action determined (e.g., data query, communication to the study center).   
 
Intermittent data review will be performed and any discovered errors will be reported to the 
study site using the data correction and query process (as necessary).  The study site will 
be expected to review the query, make any necessary corrections or comments, and return 
to Data Management where the correct response will be entered.  The data cleaning cycle 
will be repeated until all data are considered clean.  
 
24.3 Data Back-up 
Incremental computer data backup will be performed on a regular basis.  All hard copies of 
Case Report Forms and media will be stored in a secure location.   
 
24.4 Confidentiality and Security 
Passwords will be issued to appropriate personnel to insure confidentiality and protection of 
data.   
 
24.5 Final Report 
A final report will be completed, even if the study is prematurely terminated.  
 
24.6 Publication Policy 
At the conclusion of the trial, the results may be prepared and presented at a major 
meeting(s).  
 
 
25.0 
DEFINITIONS AND ACRONYMS 
Adverse Events 
Adverse Event (AE) – any untoward medical occurrence in a subject (ISO 14155).   
NOTE:  This definition does not imply that there is a relationship between the adverse event 
and the device under investigation. 
 
Serious Adverse Event (SAE) – an adverse event that (ISO 14155): 
• 
led to a death, 
• 
led to a serious deterioration in the health of the subject,  
• 
resulted in a life-threatening illness or injury, 
• 
resulted in a permanent impairment of a body structure or a body function, 
• 
required hospitalization or prolongation of existing hospitalization, 
• 
resulted in medical or surgical intervention to prevent permanent impairment to body 
structure or function, 
• 
led to fetal distress, fetal death, a congenital abnormality, or birth defect.  
 
Adverse Device Effect (ADE) – any untoward and unintended response to a medical device (ISO 
14155) 

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NOTE: This includes any event resulting from insufficiencies or inadequacies in the 
instructions for use or the deployment of the device.  This definition also includes any event 
that is a result of user error. 
 
Serious Adverse Device Effect (SADE) – an adverse device effect that has resulted in any of the 
consequences characteristic of a serious adverse event or that might have led to any of these 
consequences if suitable action had not been taken or intervention had not been made or if 
circumstances had been less opportune (ISO 14155). 
 
Anticipated Adverse Device Effect (AADE) – an adverse device effect which by its nature, 
incidence, severity or outcome has been previously identified in the previously identified in nature, 
severity, or degree of incidence in the investigational plan or application  
 
Unanticipated Adverse Device Effect (UADE) – any serious adverse effect on health or safety or 
any life-threatening problem or death caused by, or associated with, a device, if that effect, 
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 problem associated with a device that relates to the rights, safety, or welfare 
of subjects (21 CFR 812.3.s and ISO 14155). 
NOTE: The occurrence of a diagnostic or elective surgical procedure for a pre-existing 
condition, unless the condition becomes more severe or increases in frequency, would not be 
considered procedure or device-related. 
 
Adverse Device Effect (ADE) 
See Adverse Events. 
 
Case Report Form (CRF) 
Printed, optical or electronic document designed to record all of the protocol required information 
to be reported to the sponsor on each trial subject 
 
Confidentiality 
Prevention of disclosure, to other than authorized individuals, of a sponsor’s proprietary 
information or a subject’s identity (GCP Consolidated Guidance). 
 
Institutional Review Board (IRB) 
An independent body constituted of medical, scientific and nonscientific members, whose 
responsibility is to ensure the protection of the rights, safety and well-being of human subjects 
involved in a trial by, among other things, reviewing, approving, and providing continuing review 
of trials, of protocols and amendments, and of the methods and material to be used in obtaining 
and documenting informed consent of the trial subjects (GCP Consolidated Guidance). 
 
Good Clinical Practice (GCP) 
An international quality standard for conducting clinical trials that is provided by International 
Conference on Harmonisation (ICH) to protect trial subjects rights, safety, and welfare, as well as 
provide integrity to the overall study data.  
 
Informed Consent 
The process by which a subject voluntarily confirms his or her willingness to participate in a 
particular trial, after having been informed of all aspects of the trial that are relevant to the subject’s 
decision to participate.  Informed consent is documented by means of a written, signed and dated 
consent form (GCP Consolidated Guidance). 

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Informed Consent Form (ICF) 
A document disclosing the risks, benefits, and alternatives of a clinical trial and documents the 
subject’s voluntary willingness to participate in a clinical trial.  
 
Monitoring 
The act of overseeing the progress of a trial, and of ensuring that it is conducted, recorded and 
reported in accordance with the protocol, standard operating procedures (SOPs), and the 
applicable regulatory requirements. 
 
Serious Adverse Device Effect (SADE)  
See Adverse Events. 
 
Serious Adverse Event (SAE) 
See Adverse Events. 
 
Source Data 
All information in original and identified records and certified copies of original records of clinical 
findings, observations, or other activities in a clinical investigation, necessary for the 
reconstruction and evaluation of the clinical investigation.  Source data are contained in source 
documents (ISO 14155 and GCP Consolidated Guidance). 
 
Source Documents  
Original documents, data and records (ISO 14155).   
NOTE:  This may be, for example, hospital records, laboratory notes, pharmacy dispensing 
records, copies or transcriptions certified after verification as being accurate copies, 
photographic negatives, radiographs, and records kept at the pharmacy, at the laboratories, 
and at medico-technical departments involved in the clinical investigation. 
 
Standard Operating Procedure (SOP) 
Detailed, written instructions to achieve uniformity of the performance of a specific function 
 
Unanticipated Adverse Device Effect (UADE) 
See Adverse Events. 
 

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Weaver EM. Nasal valve stabilization. Operative Techniques in Otolaryngology 
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Sapci T, Sahin B, Karavus A, Akbulut UG. Comparison of the effects of radiofrequency 
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functions. Laryngoscope 2003;113:514-9. 
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Hytonen ML, Back LJ, Malmivaara AV, Roine RP. Radiofrequency thermal ablation for 
patients with nasal symptoms: a systematic review of effectiveness and complications. 
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Wysocki CJ, Cowart BJ, Radil T. Nasal trigeminal chemosensitivity across the adult life 
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Frasnelli J, Albrecht J, Bryant B, Lundstrom JN. Perception of specific trigeminal 
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Zhao K, Blacker K, Luo Y, Bryant B, Jiang J. Perceiving nasal patency through mucosal 
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Zhao K, Scherer PW, Hajiloo SA, Dalton P. Effect of anatomy on human nasal air flow 
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Keyhani K, Scherer PW, Mozell MM. Numerical simulation of airflow in the human nasal 
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Eccles R, Jones AS. The effect of menthol on nasal resistance to air flow. J Laryngol 
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Jones AS, Crosher R, Wight RG, Lancer JM, Beckingham E. The effect of local 
anaesthesia of the nasal vestibule on nasal sensation of airflow and nasal resistance. Clin 
Otolaryngol Allied Sci 1987;12:461-4. 
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Zhao K, Jiang J, Blacker K, et al. Regional peak mucosal cooling predicts the perception 
of nasal patency. Laryngoscope 2014;124:589-95. 
13. 
Zhao K, Jiang J. What is normal nasal airflow? A computational study of 22 healthy 
adults. International forum of allergy & rhinology 2014;4:435-46.