Conditions: Knee Osteoarthritis
Keywords: Non-Steroidal Anti-Inflammatory Drugs Sustained Acoustic Medication Low-Intensity Continuous Ultrasound
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 60
Healthy volunteers: yes

Brief summary:
The purpose of this study is to evaluate the usability of the ultrasound devices and common pain relief gel. The ability of the three treatment approaches to reduce pain, stiffness, and functionality as measured by NRS scale and the Western Ontario and McMaster Universities Arthritis Index (WOMAC) will be evaluated.

Detailed description:

Arms:
arm 1: Patients receive treatment from the wired SAM Ultrasonic Diathermy Device for 4 hours at least 5 days a week for 8 weeks combined with 2.5% diclofenac patch. The SAM device emits continuous ultrasound at 3 megahertz (MHz) frequency and 0.132 watts/cm2 intensity. arm 2: Patients receive treatment from the wireless SAM Ultrasonic Diathermy Device for 1 hour at least 5 days a week for 8 weeks combined with 2.5% diclofenac patch. The SAM device emits continuous ultrasound at 3 megahertz (MHz) frequency and 0.132 watts/cm2 intensity. arm 3: Patients apply topical 1% diclofenac gel three times per day, at least 5 days per week for 8 weeks.

Interventions: intervention 1: Sustained Acoustic Device with 2.5% Diclofenac Patch intervention 2: 1% Diclofenac Topical Gel
Intervention descriptions: intervention 1: Patients apply the SAM Ultrasonic Diathermy Device daily for 1-4 hours of continuous therapeutic ultrasound at 3 megahertz(MHz) frequency and 0.132 Watts/cm@ with 2.5% Diclofenac patches. intervention 2: Topical pain-relief gel

Protocol document:
Prot_SAP_002.pdf: 
Version 1.1 - May 2021 
 
1
 
 
UPLOAD 4/07/2025 
 
PROTOCOL & SAP  
 
Sports and Orthopedic Physical Therapy 
 
Orthopedic Foundation 
 
Medical Pain Consultants 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


Version 1.1 - May 2021 
 
2
Study Protocol 
 
HF-01-2021 
 
NCT05050448 
 
Comparative Usability Evaluation of Sustained 
Acoustic Medicine Devices and Topical Gel for 
Knee Pain Related to Osteoarthritis 
 
May 20st 2021 
 
 


Version 1.1 - May 2021 
 
3
1.0 Background and Scientific Rationale  
1.1 Background Information 
ZetrOZ’s Ultrasonic Diathermy medical device is intended for use as a 
portable and wearable medical device which, when applied to various areas 
of the body, applies Low Intensity Therapeutic Ultrasound (LITUS) to deep 
tissues. The Food and Drug Administration has approved claims for such 
devices that fall under 21 CFR part 1050.10 including pain reduction, 
treatment of muscle spasm and joint contracture, and increasing local 
circulation. ZetrOZ has received FDA 510(k) clearance and has received 
CE marking for the Ultrasonic Diathermy Device. A new geriatric-improved 
wireless power pack with 2.5% diclofenac patch will be evaluated for 
usability (easy to open, apply and remove), and compared to functionality of 
the wired power pack and standard over-the-counter pain relief gel.  
 
Approximately 50 million people in the United States suffer from some form 
of arthritis pain, and Osteoarthritis is the most common form of the disease. 
The prevalence of osteoarthritis is greater among women than men, 
increases with age, and affects all race/ethnicity groups. As the aging 
population expands, the costs associated with treating osteoarthritis 
increase significantly. In a study of medical spending, the U.S. Centers for 
Disease Control and Prevention found that between 1997 and 2003, 
arthritis costs in the U.S. rose from $65 to $81 Billion, and average 
prescription prices doubled from $899 per person in 1997 to $1,635 in 
2003. 
 
Osteoarthritis affects articular cartilage, the smooth fibrous connective 
tissue essential for smooth movement and cushioning of the joint. As the 
disease progresses, the cartilage becomes thinner and may completely 
wear away. Inflammation of the synovial membrane, the lining that 
surrounds the knee joint and contains the synovial fluid, is often a result of 
these changes. Osteoarthritis can form in any joint but is more common in 
weight bearing joints such as the knee and hip, and results in joint space 
narrowing, severe pain and loss of mobility. 
 
 
1.2 Product and Investigational Product Description(s) 
Ultrasound Devices (Groups 1 & 2): Low intensity therapeutic ultrasound 
(LITUS) will be delivered in this study using ZetrOZ’s Ultrasonic Diathermy 
Device called sam®. The device packages consist of a Power Controller, 2 
Applicators (ultrasound generators), Ultrasound Coupling Bandages 2.5% 
Diclofenac Ultrasound Gel, Charger and User Manual. 
 
Pain Gel (Group 3): Topical Pain Relief Diclofenac 1% Gel will be provided 
by generic from (Walgreens or CVS) with dosing card and package insert.   
 
1.3 Hypotheses 
It is hypothesized that users of the LITUS device (sam®) device(s) will be 
able to successfully apply and remove the device(s) daily to the knee. It is 
hypothesized that users of the wireless sam® device will find application of 


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LITUS easier than wired-LITUS and topical pain relief gel. It is hypothesized 
that treatment with the LITUS device(s) (sam®) will yield similar 
improvements in pain and stiffness in subjects with knee Osteoarthritis.   
 
1.4 Potential Risks to Subjects 
The risks of using ultrasound devices to administer physical therapy are 
well established and include: burn, itching and/or pain. These risks 
decrease when using lower intensity ultrasound, as in this study. The 
Ultrasound Diathermy Device uses existing technology to deliver ultrasound 
therapy in a portable and convenient fashion. The subjects will be given the 
chance to ask any questions regarding the trial procedures, requirements, 
and purposes. Once the subjects are fully informed of the possible risks 
and benefits of participation in the study and all of their questions have 
been satisfactorily answered, they will be required to sign the informed 
consent form in order to participate in the study. All subjects must give 
consent themselves and no legally authorized representatives will be 
accepted on their behalf. 
 
The 1% diclofenac pain relief gel used in this study is widely available over 
the counter for arthritis pain. It is well understood that this alcohol-based 
pain gel may cause allergic reactions, especially in people allergic to aspirin 
and with sensitive skin. Possible subject risks include hives, skin reddening, 
blisters, swelling and rash. There is also the possibility of stomach bleeding, 
liver problems, heart attack and stroke from pain relief gel use, however this 
is highly unlikely. Overall, the safety profile of topical pain relief gel is well 
understood for patients with arthritis pain. 
 
2.0 Study Objectives and Design  
2.1 Objectives 
The primary objective of this study is to evaluate the usability of the new 
wireless power pack for proper design, and compare it for ease of daily use 
with a wired version of the same device and common pain relief gel.   
 
Secondary objectives are to evaluate the ability of the three treatment 
approaches to reduce pain, stiffness as measured by NRS scale and the 
Western Ontario and McMaster Universities Arthritis Index (WOMAC) 
 
2.2 Study Design 
2.2.1 General Study Design 
This study is designed as a three arm parallel assignment study. 
After screening and enrollment, subjects will self-administer 
treatment daily for 8 consecutive weeks. 
 
2.2.2 Study Design Schematic 
 


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3.0 Study Population 
3.1 General Characteristics of the Proposed Subject Population(s) 
This study will enroll subjects with physician confirmed knee Osteoarthritis 
pain. The long duration wearable therapeutic ultrasound treatment has 
multiple benefits likely to aid the patients enrolled in this study with knee 
Osteoarthritis pain. Acoustic waves mechanically stimulate tissue, triggering 
biological effects including the down regulation of inflammatory cytokines, 
increased transport kinetics, protein synthesis, and extracellular matrix 
deposition. It is therefore hypothesized that the ZetrOZ’s wearable device 
has the potential to provide sustained OA symptom management. Over the 
counter pain gel is widely used for arthritis pain relief and is used as a 
usability control for comparative purposes. 
 
3.2 Anticipated Number of Research Subjects 
 
Enrollment will be monitored at the assumed rates of Screen Failures and 
Discontinuation may be found to differ in this study from historical controls. 
The objective is to screen and enroll towards a target of 60 completed 
subjects. 
 
Subjects to be Screened 
95 
Assumed Screen Fail Rate 
30% 
Subjects to be Enrolled (sign ICF) 
66 
Assumed Discontinuation Rate 
10% 
Total Number Completers (complete 8-wk treatment phase) 
60 
 
3.3 Inclusion Criteria 
Subjects to be enrolled in the trial will: 
• 
Have physician-diagnosed mild to moderate knee OA (OARSI atlas grades 
1-2)  
• 
Fulfill the American College of Rheumatology clinical and radiological 
diagnostic criteria for knee OA 
• 
Are between 35-80 years of age 


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• 
Report a frequent pain score between 3-7 (range: 0-10) during the week 
preceding enrollment 
• 
Report that knee pain negatively affects quality of life 
• 
Are willing not to use any cream, gel, or topical solution during the 
administration of treatment other than the approved ultrasound gel 
provided to the subject at the initiation of the study 
• 
Are deemed appropriate by their physician or by the study site physician to 
participate.  
• 
Be willing and able to self-administer treatment daily within their place of 
residence or during normal daily activity, excluding bathing, showering, or 
other water activities which may result in submersion of the study device. 
• 
Not use or initiate opioid and/or non-opioid analgesic medications. 
• 
Be willing to discontinue any other interventional treatment modalities on 
the knee during the study period (e.g., transcutaneous electrical nerve 
stimulation, electronic muscle stimulation, traditional ultrasound). 
 
3.4 Exclusion Criteria 
A potential subject will be excluded from participation in this study if he or she: 
• 
Cannot successfully demonstrate the ability to put on and take off the 
device. 
• 
Displays any condition which, in the judgment of the investigator, would 
make participation in the study unacceptable including, but not limited to, 
the subject’s ability to understand and follow instructions. 
• 
Participated in a clinical trial for an investigational drug and/or agent 
within 30 days prior to screening. 
• 
Is pregnant. 
• 
Is a prisoner. 
• 
Is non-ambulatory (unable to walk). 
• 
Has a pacemaker. 
• 
Has a malignancy in the treatment area. 
• 
Has an active infection, open sores, or wounds in the treatment area. 
• 
Has impaired sensation in the treatment area, such as caused by 
chemotherapy or anesthesia. 
• 
Has a known neuropathy (disease of the brain or spinal nerves). 
• 
Has a hereditary disposition (tendency) for excessive bleeding 
(hemorrhage). 
• 
Have knee replacement, other surgical intervention, or hyaluronidase 
injection in the affected knee in the past 6 months 
• 
Are currently taking steroids 
• 
Have any contraindication to radiograph 
• 
Have a secondary cause of arthritis (metabolic or inflammatory) 
 
4.0 Study Procedures 
4.1 Subject Recruitment  
It is planned at one site to enroll subjects into this trial. Therefore, based on 
the assumptions presented in Section 3.2, we will need to screen 
approximately 95 subjects to meet the target enrollment number of 66 


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subjects, and support a target completion number of 60. The target 
enrollment period for this study is 6 months.  
 
4.1.1 Subject Compensation 
Subjects will be compensated up to $250 for participation in the study. 
Subjects will not be compensated for the initial screening/enrollment visit, 
but will get $250 for completing three virtual meetings and Visit 2 (exit). 
 
4.2 Screening Procedures 
Subjects will come to the clinic to be screened for inclusion in the study. 
The investigator or a sub-investigator will review the Eligibility Screening 
Checklist with the subject. All subjects must have physician-diagnosed mild 
to moderate knee OA (OARSI atlas grades 1-2). 
 
4.3 Study Treatment 
4.3.1 Treatment Groups 
Subjects will participate in three treatment arms. All LITUS devices are 
manufactured by ZetrOZ Systems (Trumbull, CT). The wired 3 MHz device 
was FDA cleared in November 2013 and March 2020, and is marketed in 
the United States under the brand name sam®. The wireless battery pack 
removes the wire from the sam® device and connects directly to the 3 MHZ 
applicator. All study subjects will apply 2 applicators affixed to the coupling 
bandages to their knee on the medial and lateral sides as shown in the 
figure below. The applicators are connected via a Y-adapter to a single 
power controller in the wired version, and with two small wireless power 
controllers connected directly to the applicators in the wireless version. The 
subjects will activate the device for each daily treatment.  
 
 
 
 
 
 
 
 
This device delivers continuous 
ultrasound with a maximum acoustic 
power output of 1.3 W/cm2 ±20% 
when 2 applicators are used. The 
frequency is 3 MHz ± 20%. The 
maximum treatment duration 
permitted is 4 hours per day. 
 
LITUS treatment protocol: subjects will self-administer the LITUS therapy 
for up to 4 hours per day at least 5 days per week (and up to 7 days) for the 
8-week study. 
 
Pain Gel treatment protocol: Pain relief gel (Generic version) will be applied 
2g, 3x per day at least 5 days per week (and up to 7 days) for the 8-week 
study.   
Sample  
Applicator Placement 


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4.3.2 Randomization   
All study kits will be labeled with a color coded sticker located under the 
foam of the kit. The color coded stickers correspond to a specific 
treatment arm of the study, which will be recorded by the Regulatory team 
at ZetrOZ. The Regulatory team will act as a non-research member of the 
sponsor, and will record kit and component serial numbers, as well as the 
color of the sticker in a locked Excel document. A spreadsheet of kit 
numbers will be provided to the Clinical Trials team at ZetrOZ who will 
utilize the randomization function in Excel to associate a kit number with a 
subject number. Therefore, the ZetrOZ clinical team will have no 
knowledge of the treatment arm assigned to a subject.  
 
4.3.3 Breaking the Blind 
Not Applicable 
 
4.3.4 Treatment Adherence/ Study Compliance 
Treatment compliance will be assessed by review of daily diaries, virtual 
meetings and count of remaining bandages and pain-gel quantity at the 
end of the study. The Research Coordinator will remind the subjects of 
the treatment protocol and retrain them on use of the device or 
application of pain gel if necessary. Study in person and virtual visits 
should be completed within 3 days of the specified time in the Schedule 
of Assessments (Section 4.6). 
 
 
4.4 Follow-Up Procedures 
4.4.1 Procedures to Assess Usability and Efficacy  
Usability and Efficacy will be assessed at the end of the study. 
Subjects will maintain a Daily Diary at home, which will be a 
printed booklet that they will complete manually daily throughout 
the study period.  
 
Daily Diary 
Subjects will complete a Daily Diary throughout the 8-week 
treatment period to collect usability and pain ratings before and 
after treatment. 
 
Numeric Rating Scale (NRS) 
Subject-reported rating of pain severity, 0 = no pain, 10 = worst 
pain imaginable  
 
Western Ontario and McMaster Universities Arthritis 
Index (WOMAC) 
Subject reported rating of pain, stiffness and function validated for 
knee Osteoarthritis. 
 
Exit Assessment 


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At the conclusion of the trial, each subject will be asked to 
complete an exit assessment form which solicits the subject’s 
feedback on their use of the device, and satisfaction with therapy. 
 
4.4.2 Procedures to Assess Safety  
Adverse events will be recorded at each study visit and virtual 
meeting. 
 
4.5 Use of Non-Study Drugs and Procedures 
Not Applicable. Not Allowed. 


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4.6 Schedule of Assessments 
 
 
1 - Visit window: ±3 days 
2 - Research coordinator should review subject diaries to ensure completeness, and evidence that subject is using the device per 
protocol.  
5.0 Data Management and Analysis 
5.1 Outcome Measures and Data Analysis Plan 
Visit Number
V1
V1
W2
W4
W6
V2 W8
Visit Type
Screening
Start 
Treatment
Virtual 
Check
Virtual 
Check
Virtual 
Check
End of 
Treatment
/Early 
Terminati
on (3)
Week (1)
0
0
2
4
6
8
Inclusion/Exclusion 
Criteria
x
Informed Consent
x
Medical history
x
Treatment history
x
Device Assignment Form
x
Physical Examination
x
Confirm baseline pain >4 
week preceding 
x
Train Subject on sam 
Device or Pain Gel
x
Confirm subject and put 
on and take off device
x
WOMAC Scale
x
x
Adverse Events
x
x
x
x
x
Protocol Deviations
x
x
x
Distribute Daily Diary
x
Review/Collect Daily Diary
x
x
x
x
Assess Compliance (2)
x
Distribute study marterials 
sam Device or gel 
x
Distribute Patches
x
Issue Subject 
Compensation and Signed 
Receipt
x
Collect sam Device and 
Unused Study Supplies
x
Exit Assessment 
Questionnaire 
x


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Change in NRS pain score from baseline will be analyzed for pre and post-8 week 
treatment and WOMAC (pain, stiffness, and functional change) will be evaluated 
on week 0 and week 8. Data will be analyzed using t-tests and repeated measure 
ANOVAs. 
 
6.0 Risk Analysis 
6.1 Adverse Event Recording and Reporting  
6.1.1 Adverse Event Definitions 
Adverse effect. Any untoward medical occurrence in a clinical study of an 
investigational device; regardless of the causal relationship of the 
problem with the device or, if applicable, other study treatment or 
diagnostic product(s). 
 
Associated with the investigational device or, if applicable, other study 
treatment or diagnostic product(s).  There is a reasonable possibility that 
the adverse effect may have been caused by the investigational device 
or, if applicable, the other study treatment or diagnostic product(s). 
 
Disability.  A substantial disruption of a person’s ability to conduct normal 
life functions. 
 
Life-threatening adverse effect.  Any adverse effect that places the 
subject, in the view of the investigator-sponsor, at immediate risk of death 
from the effect as it occurred (i.e., does not include an adverse effect that, 
had it actually occurred in a more severe form, might have caused death). 
 
Serious adverse effect. Any adverse effect that results in any of the 
following outcomes: death, a life-threatening adverse effect, inpatient 
hospitalization or prolongation of existing hospitalization, a persistent or 
significant disability/incapacity, or a congenital anomaly/birth defect. 
 
• 
Hospitalization shall include any initial admission (even if less than 24 
hours) to a healthcare facility as a result of a precipitating clinical 
adverse effect; to include transfer within the hospital to an intensive 
care unit.  Hospitalization or prolongation of hospitalization in the 
absence of a precipitating, clinical adverse effect (e.g., for a 
preexisting condition not associated with a new adverse effect or with 
a worsening of the preexisting condition; admission for a protocol-
specified procedure) is not, in itself, a serious adverse effect.   
 
Unexpected adverse effect.  Any adverse effect, the frequency, specificity 
or severity of which is not consistent with the risk information described in 
the clinical study protocol(s) or elsewhere in the current IDE application, 
as amended. 
 
Unanticipated adverse device effect.  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 


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investigational plan or IDE 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. 
 
6.1.2 Eliciting Adverse Effect Information 
Clinical study subjects will be routinely questioned about adverse 
effects at study visits and virtual meetings. 
 
6.1.3 Recording and Assessment of Adverse Effects 
All observed or volunteered adverse effects (serious or non-
serious) and abnormal test findings, regardless of treatment 
group, if applicable, or suspected causal relationship to the 
investigational device or, if applicable, other study treatment or 
diagnostic product(s) will be recorded in the subjects’ case 
histories.  For all adverse effects, sufficient information will be 
pursued and/or obtained so as to permit 1) an adequate 
determination of the outcome of the effect (i.e., whether the effect 
should be classified as a serious adverse effect) and; 2) an 
assessment of the casual relationship between the adverse effect 
and the investigational device or, if applicable, the other study 
treatment or diagnostic product(s).    
 
Adverse effects or abnormal test findings felt to be associated with 
the investigational device or, if applicable, other study treatment or 
diagnostic product(s) will be followed until the effect (or its 
sequelae) or the abnormal test finding resolves or stabilizes at a 
level acceptable to the investigator-sponsor. 
 
6.1.3.1 
Causality and Severity Assessment 
The investigator-sponsor will promptly review documented 
adverse effects and abnormal test findings to determine 1) 
if the abnormal test finding should be classified as an 
adverse effect; 2) if there is a reasonable possibility that 
the adverse effect was caused by the investigational 
device or, if applicable, other study treatment or diagnostic 
product(s); and 3) if the adverse effect meets the criteria 
for a serious adverse effect. 
 
If the investigator-sponsor’s final determination of causality 
is “unknown and of questionable relationship to the 
investigational device or, if applicable, other study 
treatment or diagnostic product(s)”, the adverse effect will 
be classified as associated with the use of the 
investigational device or study treatment or diagnostic drug 
product(s) for reporting purposes.  If the investigator-
sponsor’s final determination of causality is “unknown but 
not related to the investigational device or, if applicable, 
other study treatment or diagnostic product(s)”, this 
determination and the rationale for the determination will 
be documented in the respective subject’s case history. 


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6.1.4 Reporting of Adverse Effects to the FDA   
The investigator-sponsor will submit a completed Form FDA 3500 
A to the FDA’s Center for Devices and Radiological Health for any 
observed or volunteered adverse effect that is determined to be 
an unanticipated adverse device effect.  A copy of this completed 
form will be provided to all participating sub-investigators.   
 
The completed Form FDA 3500 A will be submitted to the FDA as 
soon as possible and, in no event, later than 10 working days after 
the investigator-sponsor first receives notice of the adverse effect. 
 
If the results of the sponsor-investigator’s follow-up evaluation 
show that an adverse effect that was initially determined to not 
constitute an unanticipated adverse device effect does, in fact, 
meet the requirements for reporting; the investigator-sponsor will 
submit a completed Form FDA 3500 A as soon as possible, but in 
no event later than 10 working days, after the determination was 
made. 
 
For each submitted Form FDA 3500 A, the sponsor-investigator 
will identify all previously submitted reports that that addressed a 
similar adverse effect experience and will provide an analysis of 
the significance of newly reported adverse effect in light of the 
previous, similar report(s). 
 
Subsequent to the initial submission of a completed Form FDA 
3500 A, the investigator-sponsor will submit additional information 
concerning the reported adverse effect as requested by the FDA. 
 
6.1.5 Reporting of Adverse Effects to the Responsible IRB 
In accordance with applicable policies of the Institutional Review 
Board (IRB), the investigator-sponsor will report, to the IRB, any 
observed or volunteered adverse effect that is determined to meet 
all of the following criteria: 1) associated with the investigational 
device or, if applicable, other study treatment or diagnostic 
product(s); 2) a serious adverse effect; and 3) an unexpected 
adverse effect.  Adverse event reports will be submitted to the IRB 
in accordance with the respective IRB procedures.  
 
Applicable adverse effects will be reported to the IRB as soon as 
possible and, in no event, later than 10 calendar days following 
the investigator-sponsor’s receipt of the respective information.  
Adverse effects which are 1) associated with the investigational 
drug or, if applicable, other study treatment or diagnostic 
product(s); 2) fatal or life-threatening; and 3) unexpected will be 
reported to the IRB within 24 hours of the investigator-sponsor’s 
receipt of the respective information.  
 
Follow-up information to reported adverse effects will be submitted 
to the IRB as soon as the relevant information is available.  If the 


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results of the sponsor-investigator’s follow-up investigation show 
that an adverse effect that was initially determined to not require 
reporting to the IRB does, in fact, meet the requirements for 
reporting; the investigator-sponsor will report the adverse effect to 
the IRB as soon as possible, but in no event later than 10 
calendar days, after the determination was made. 
 
7.0 Monitoring Procedures 
Monitoring of the clinical study for clinical protocol compliance will be conducted 
periodically (i.e., at a minimum of annually) by the ZetrOZ clinical team. The sponsor-
investigator will permit direct access to the study monitors and appropriate regulatory 
authorities to the study data and to the corresponding source data and documents to 
verify the accuracy of these data. 
 
8.0 Additional Records and Reports   
8.1 Data Handling and Record-keeping 
A Case Report Form (CRF, see Appendix) will be completed at each study 
visit for each subject enrolled into the clinical study.  The investigator-
sponsor will review, approve and sign/date each completed CRF; the 
investigator-sponsor’s signature serving as attestation of the investigator-
sponsor’s responsibility for ensuring that all clinical and laboratory data 
entered on the CRF are complete, accurate and authentic.   
 
ZetrOZ’s clinical research team will work with each site to ensure accurate 
completion of CRFs reconciling illegible entries, missing data, and 
conflicting data entries.  
 
Source Data are the clinical findings and observations, laboratory and test 
data, and other information contained in Source Documents.  Source 
Documents are the original records (and certified copies of original 
records); including, but not limited to, hospital medical records, physician or 
office charts, physician or nursing notes, subject diaries or evaluation 
checklists, pharmacy dispensing records, recorded data from automated 
instruments, x-rays, etc.  When applicable, information recorded on the 
CRF shall match the Source Data recorded on the Source Documents.   
 
 
8.2 Record Maintenance and Retention 
The investigator-sponsor will maintain records in accordance with Good 
Clinical Practice guidelines; to include: 
 
• 
IRB correspondence (including approval notifications) related to the 
clinical protocol; including copies of adverse event reports and annual or 
interim reports; 
• 
Current and past versions of the IRB-approved clinical protocol and 
corresponding IRB-approved consent form(s) and, if applicable, subject 
recruitment advertisements. 


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15
• 
Signed Investigator’s Agreements and Certifications of Financial Interests 
of Clinical Investigators; 
• 
Curriculum vitae (investigator-sponsor and clinical protocol sub-
investigators); 
• 
Certificates of required training (e.g., human subject protections, Good 
Clinical Practice, etc.) for investigator-sponsor and listed sub-
investigators; 
• 
Instructions for on-site preparation and handling of the investigational 
device and/or study treatment or diagnostic product(s), and other study-
related materials (i.e., if not addressed in the clinical protocol); 
• 
Decoding procedures for blinded trials; 
• 
Master device list; 
• 
Signed informed consent forms; 
• 
Completed Case Report Forms; signed and dated by investigator-
sponsor; 
• 
Source Documents or certified copies of Source Documents; 
• 
Monitoring visit reports; 
• 
Copies of investigator-sponsor correspondence to sub-investigators, 
including notifications of adverse effect information; 
• 
Subject screening and enrollment logs; 
• 
Subject identification code list; 
• 
Device accountability records, including documentation of device disposal 
and returns to sponsor; 
• 
Final clinical study report. 
 
Site-subject identification numbers will be assigned to all subjects to de-
identify the associated clinical data. A master subject ID log will be 
maintained by ZetrOZ separately from clinical trial data. The master log will 
contain the assigned site-subject identification number matched to each 
subject’s full name, gender, and date-of-birth. The site-subject ID will be 
generated by a two-digit site ID separated by a dash from the subject 
number at that site. Subjects’ names or other directly identifiable 
information will not be used in any reports, publication or other disclosures 
of clinical study outcomes. 
 
The investigator-sponsor will retain the specified records and reports for up 
to 2 years after the marketing application is approved for the investigational 
device; or, if a marketing application is not submitted or approved for the 
investigational drug, until 2 years after investigations under the IDE have 
been discontinued and the FDA so notified. 
 
 


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9.0 References 
 
Therapeutic ultrasound for osteoarthritis, Cochrane Review, 20 January 2010. 
http://www.cochrane.org/CD003132/MUSKEL_therapeutic-ultrasound-for-osteoarthritis