A Prospective, Multicenter Study to Evaluate Functional Outcome After Knee Replacement
Phase: NA
Conditions: Osteoarthritis
Sponsor: Restor3D

 
 
 
 
A Prospective, Multicenter Study to Evaluate 
Functional Outcome After Knee Replacement 
 
Protocol 12-005 v 5.0 AD 
27 March 2017 
 
 
SPONSOR: 
ConforMIS, Inc. 
600 Technology Park Drive, 4th Floor, Billerica, MA 01821 
 
Contact: 
Marc Quartulli, VP, Clinical Affairs 
Ph: 781.345.9191  
marc.quartulli@conformis.com 
 
 
ConforMIS internal use: CD-00006 v5.0 AD
NCT02494544

 
 
ConforMIS, Inc. 
Protocol 12-005 Revision 5.0 AD 
27 March 2017 
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Confidential and Proprietary 
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Table of Contents 
 
1. 
INTRODUCTION, BACKGROUND & OBJECTIVE ............................................. 4 
2. 
DEVICE DESCRIPTION .......................................................................................... 4 
3. 
STUDY DESIGN....................................................................................................... 5 
4. 
ECONOMIC SUBSTUDY ........................................................................................ 6 
5. 
FUNCTIONAL TESTING ........................................................................................ 6 
6. 
STUDY DURATION ................................................................................................ 7 
7. 
STUDY ENDPOINTS ............................................................................................... 7 
7.1.  Primary Endpoints ............................................................................................ 7 
7.2.  Secondary Endpoints ........................................................................................ 7 
8. 
INCLUSION AND EXCLUSION CRITERIA ......................................................... 7 
8.1.  Inclusion Criteria .............................................................................................. 7 
8.2.  Exclusion Criteria ............................................................................................. 7 
9. 
SITE SELECTION .................................................................................................... 8 
10.  ENROLLMENT ........................................................................................................ 9 
11.  SCHEDULE OF EVALUATIONS BY VISIT.......................................................... 9 
11.1. Preoperative Visit (Up to 4 months prior to Surgery) .................................... 10 
11.2. Surgery Visit (Day 0) ...................................................................................... 10 
11.3. 90 Days Follow-up Visit (± 14 days) .............................................................. 10 
11.4. 180 Days Follow-up Visit (± 21 days) ............................................................ 11 
11.5. Year 1, 2, and 5 Follow-up Visits (± 2 months) ............................................. 11 
11.6. Year 3, 4, 6, 7, 8, and 9 Follow-up Visits (± 3 months) ................................. 12 
11.7. Year 10 Follow-up Visit (± 4 months) ............................................................ 12 
11.8. Early Termination Visit .................................................................................. 13 
12.  SAFETY REPORTING ........................................................................................... 13 
13.  DATA MANAGEMENT......................................................................................... 14 
14.  MONITORING ........................................................................................................ 15 
15.  STATISTICAL METHODS .................................................................................... 15 
16.  SUBJECT PROTECTION ....................................................................................... 17 
17.  ETHICAL CONSIDERATIONS ............................................................................. 17 
18.  REPORTS ................................................................................................................ 17 
19.  LITERATURE ......................................................................................................... 18 
20.  APPENDIX A – Schedule of Evaluations ............................................................... 24 
21.  APPENDIX B – Functional Testing Instructions .................................................... 25 
22.  APPENDIX C – U.S. Economic Sub-Study ............................................................ 29 
23.  APPENDIX D – CONSORT Data Reporting Guidelines ....................................... 30 
 
 
 

 
 
ConforMIS, Inc. 
Protocol 12-005 Revision 5.0 AD 
27 March 2017 
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Confidential and Proprietary 
Nothing herein is to be disclosed without the prior express written permission of ConforMIS, Inc. 
 
 
 
A Prospective, Multicenter Study to Evaluate 
Functional Outcome After Knee Replacement 
 
 
Protocol Number: 12-005 Version 5.0 AD 
Date:    27 March 2017 
Contact:  Marc Quartulli 
 
      VP Clinical Affairs 
 
      781.345.9191 
                Marc.Quartulli@conformis.com 
 
 
Protocol Signature Page 
This is to acknowledge that I have received the above-identified protocol, that I 
have read and understood its content, and that I agree to conduct the clinical trial 
in accordance with the procedures outlined therein. 
 
 
Investigator Approval: 
_____________________________________ 
                                     Signature 
 
 
 
 
Date 
 
                                _____________________________________ 
                                     Print Name 

 
 
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Protocol 12-005 Revision 5.0 AD 
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1. INTRODUCTION, BACKGROUND & OBJECTIVE 
 
Osteoarthritis or other degenerative changes or injury can cause damage to the structures in the 
knee, causing pain, discomfort, and lessening the quality of life.  Knee replacement, or knee 
arthroplasty, is a common surgical procedure performed to relieve the pain and disability 
resulting from osteoarthritis. In general, the surgery consists of replacing the diseased or damaged 
joint surfaces of the knee with metal and plastic components shaped to allow continued motion of 
the knee.   
 
Today, over 600,000 patients undergo total knee replacement each year in the United States, a 
number that is projected to increase greatly over the next 20 years (Kurtz 2007).  Total knee 
replacement has been performed since 1964 and has been shown to be an effective, long-lasting 
procedure with good survivorship of the implants for patients with osteoarthritis.  Despite the 
excellent survivorship, there are still a significant percentage of patients that remain dissatisfied 
with their results.  Studies reveal that 14- 39% of patients report some level of dissatisfaction with 
their knees post-surgery (Noble 2006; Bourne 2010; Suda 2010).  
 
This study is designed to compare outcome data for patients undergoing surgery with the iTotal® 
Cruciate Retaining (CR) Knee Replacement System (KRS) versus those who are undergoing 
surgery with Off-the-Shelf (OTS) systems. 
 
To compare outcomes of these two study groups, this study will include the routine office 
questionnaires such as the 2011 Knee Society Knee Scoring System © (KSS) and the Knee Injury 
and Osteoarthritis Outcome Score (KOOS).  However, literature suggests that these 
questionnaires fail to capture the change in functional activities post total knee replacement 
(Mizner 2010).  It has been noted that patients “dramatically overestimate their functional ability 
early after surgery” (Mizner 2010).  The Mizner study showed that there was an increased use in 
assistive devices and a decrease in functional testing scores post-surgery, while the patient 
reported outcome scores failed to show worsening.  To capture these changes, this study will also 
conduct multiple functional tests on all patients pre- and post-surgery.  
 
The functional tests used in this study are commonly used as an objective method to assess 
patients’ functional status.  The testing is designed to closely mimic daily activities that the 
patients are familiar with.  In this study, the patient will have a pre-operative visit to serve as a 
baseline, and then will be retested at predefined post-operative intervals.  The patient will perform 
the same group of functional tests pre- and post-operatively using methods that are summarized 
below in section 4 and in Appendix B. 
 
2. DEVICE DESCRIPTION 
 
The iTotal CR Knee Replacement System (hereafter referred to as the "iTotal CR") is a patient-
specific tricompartmental faceted posterior cruciate ligament (PCL) retaining knee replacement 
system. The iTotal CR is a semi-constrained cemented knee implant which consists of a femoral, 
tibial and patellar component.  
 
Using computed tomography (CT) and a combination of proprietary and off-the-shelf software a 
patient-specific implant is designed, that best meets the geometric and anatomic requirements of 
the specific patient. The femoral component is manufactured from cobalt chromium molybdenum 

 
 
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("CoCrMo") alloy. The tibial component includes a metal tray manufactured from CoCrMo alloy 
and polyethylene inserts. The polyethylene inserts may be manufactured from either UHMWPE 
or a highly cross-linked Vitamin E infused polyethylene (iPoly XE™).  The patellar component is 
also manufactured from either UHMWPE or from a highly cross-linked Vitamin E infused 
polyethylene (iPoly XE).  
 
Several key features of the iTotal CR are listed below: 
 
Disposable, patient-specific instrumentation   
 
Simple, reproducible surgical technique  
 
Potential for less post-operative pain and shorter post-operative recovery time 
 
The control will be one of three off-the-shelf CR systems:   
 
DePuy Synthes:  Attune 
 
Zimmer:  Persona 
 
Stryker:  Triathlon 
 
For all procedures, the patella will be resurfaced using the patella implant available through the 
respective manufacturer. 
3. STUDY DESIGN 
 
This is a prospective, blinded, multi-center study that will be conducted in the US, UK, and 
Germany. The study will include a minimum of 450 and a maximum of 600 subjects across up to 
20 sites with up to 225 min- 300 max subjects in the iTotal CR arm and 225 min- 300 max 
subjects in the off-the-shelf total knee arm.  An additional 25% may be enrolled to account for 
subject discontinuation. 
 
Subjects will be consecutively recruited in groups of 10, alternating between study arms until 
enrollment is completed.  Once a series of 10 is recruited (subject signed consent and completed 
pre-op questionnaires), then the next series of 10 is to be recruited. 
 
To ensure that enrollment in each arm remains relatively even, sites assigned odd site numbers 
will begin by enrolling off-the-shelf subjects and even numbered sites will begin by enrolling 
ConforMIS subjects.  Subjects will be implanted with either an iTotal CR or an off-the-shelf 
cruciate retaining total knee replacement.      
 
The person administering the functional tests will be blinded.  The blind will be maintained for at 
least one year in order to maintain an objective assessment of each patient’s function.  
Investigators and study staff will make every attempt to maintain the blind by limiting access to 
study data, x-rays, and other evaluations. 
 
For all surgeries, the preferred surgical approach is to make an incision that is midline or slightly 
medial to midline, followed by a parapatellar arthrotomy, or a subvastus arthrotomy with prior 
written approval from Sponsor.  The surgeon must use the same approach for all study subjects. 
 
For surgical technique, the off-the-shelf goal is to obtain mechanical alignment. 

 
 
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4. ECONOMIC SUBSTUDY 
 
This study will include a prospective economic analysis of US sites if contracted by the Sponsor.  
Please refer to Appendix C for complete description.   
5. FUNCTIONAL TESTING 
 
Each subject enrolled in the study will be asked to perform a series of functional tests under static 
and dynamic conditions that they routinely encounter during their daily lives.  These tests 
include: 
 
1. The Timed “Get-up and Go” Test (TUG) is a functional test that physical therapists have 
been using since the late 1980s to assess balance in elderly people (Mathias 1985; 
Podsiadlo 1991; Nordin 2006; Wall 2000).  This is a quick test where no special 
equipment is needed to quantify functional mobility.  The test will involve a standard 
chair, a walkway long enough for a subject to walk 3 meters and turn around, a 
stopwatch, and an administrator to observe and time the subject.  The test administrator 
will instruct the subject to “go” and start the stopwatch.  The subject will rise from the 
chair, walk 3 meters, turn around, walk back to the chair, and sit down again.  Once the 
subject’s buttocks touch the seat, the stopwatch will be stopped by the test administrator.  
The subject will be instructed to walk as quickly as they feel safe and comfortable.  
Assistive devices are allowed only if the subject does not feel safe or cannot do this test 
without the assistive devices.  The test administrator will take note if an assistive device 
was used during the test.  There will be 3 timed trials.  The average will be used for data 
analysis.   
 
2. The 8 Meter Walk is a functional test that measures locomotion.  “Locomotion refers to 
the act of moving from one place to another place, reflecting ambulation ability including 
walking distance, velocity and quality of gait” (National Institutes of Health 2012).  In 
this test, the distance of 4 meters will be marked by a cone.  The subject will begin at one 
end of the walkway.   The test administrator will instruct the subject to “go” and start the 
stopwatch.  The subject will walk towards the cone, around the cone, and back to the 
starting location at the pace that they normally walk.  Once the subject is back at the 
starting point, the stopwatch will be stopped by the test administrator.  There will be 3 
timed trials.  The average will be used for data analysis. 
 
3. The Timed Up and Down Stairs Test (TUDS) is a functional test that “demands more 
balance, coordination, strength and muscle control than walking demands” (Lepage 1998; 
Zaino 2004).  This test will involve a stopwatch and a flight of stairs with rails.  A usual 
set of stairs is 12 steps that are 18cm high with a depth of 28cm.  The flight of stairs used 
during testing must have a minimum of 4 steps.  The subject will stand at the bottom of 
the stairs.  The test administrator will voice the command “go” and start the stopwatch.  
The subject will walk as quickly as they feel safe and comfortable to the top of the stairs, 
turn around, and come back down the stairs.  Once the subject is safely back down with 
both feet back on the landing, the test administrator will stop the stopwatch.  The subject 
may use the rail, but the preference is to do this test without the use of a rail.  Assistive 
devices are allowed only if the subject does not feel safe or cannot do this test without the 
assistive devices.  The test administrator will take note if the rail or an assistive device 
was used during the test.  Again, the subject will be instructed to move as quickly as they 

 
 
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feel safe and are comfortable.  There will be 3 timed trials.  The average will be used for 
data analysis. 
 
The Aggregated Locomotor Function (ALF) score is formed by summating the mean of the 
above three timed tests (McCarthy 2004).   Suggested instructions are located in Appendix B. 
6. STUDY DURATION 
 
The study subjects will be required to complete follow-up visits at predetermined intervals for 10 
years post-implantation. The in-office follow-up visits will occur at 90 days, 180 days, 1 year, 2 
years, 5 years, and 10 years post-implantation. The remaining follow-up data collected at years 3, 
4, 6, 7, 8, and 9 may be collected via phone call, mail, or email and does not require an in-office 
visit. 
7. STUDY ENDPOINTS 
 
7.1. Primary Endpoints 
The primary functional endpoint will be measured by the Aggregated Locomotor Function 
(ALF) score (TUG, 8 Meter Walk, and TUDS activities) and/or its components at 1 Year 
post-implantation. 
 
7.2. Secondary Endpoints 
The study secondary endpoints are: 
1. The 2011 Knee Society Knee Scoring System© (KSS) and/or its subscales at 1 Year 
post-implantation 
2. The Knee Injury and Osteoarthritis Outcome Score (KOOS) 
3. Incidence of major procedure–related and device-related complications, including 
revision rates 
4. Post-operative limb alignment  
8. INCLUSION AND EXCLUSION CRITERIA 
 
Per CONSORT data reporting guidelines, all patients considered for this study will be tracked on 
a log documenting their eligibility, and enrollment status. For further details, please refer to 
Appendix D. 
 
8.1. Inclusion Criteria 
1. Clinical condition included in the approved Indications For Use for the iTotal CR 
2. Osteoarthritis, as confirmed by the investigator’s assessment of disease status at 
screening visit that warrants a TKR procedure.  Disease status is determined by 
Clinical and Radiographic assessment 
3. Willingness to participate in the clinical study, to give informed consent and to attend 
all follow-up visits 
4. > 18 years of age 
 
8.2. Exclusion Criteria 
1. Subject will require a simultaneous bilateral procedure 

 
 
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2. Lower extremity surgery (orthopaedic or ligament injury) on either limb to the hip, 
ankle, feet occurring or expected to occur within 1 year of surgery on the evaluated 
knee 
3. Severe (> 15º) fixed valgus or varus deformity 
4. Severe (> 15º) extension deficit 
5. Severe instability due to advanced loss of osteochondral structure 
6. Loss of bone or musculature, osteoporosis, neuromuscular or vascular compromise in 
the area of the joint to be operated on to an extent that the procedure is unjustified 
7. Insufficient bone stock on the femoral or tibial surfaces 
8. Contralateral knee replacement occurring or expected to occur within 6 months of 
surgery on the evaluated knee 
9. BMI > 40 
10. Active malignancy (defined as a history of any invasive malignancy – except non-
melanoma skin cancer), unless patient has been treated with curative intent and there 
have been no clinical signs or symptoms of the malignancy for at least 5 years 
11. Poorly controlled diabetes (defined as HbA1c >7 or surgeon discretion) 
12. Immunocompromised 
13. Other physical disability affecting the hips, spine, or contralateral knee that limits 
function 
14. Disabling chronic pain with narcotic dependence 
15. Compromised PCL or collateral ligament 
16. Prior history of failed implant surgery of the joint to be treated, including 
Unicompartmental Knee Arthroplasty (UKA), or Bicompartmental Knee 
Arthroplasty (BKA) 
17. Prior history of failed High Tibial Osteotomy (HTO) 
18. Participation in another clinical study which would confound results 
19. Inability to complete the protocol in the opinion of the clinical staff due to safety or 
other reasons 
9. SITE SELECTION 
 
All sites will be selected by a Site Selection Committee based on a set of defined criteria. The 
Site Selection Committee will be led by Clinical Affairs. The site selection criteria includes but is 
not limited to: 
 
Interest in participating in the study as demonstrated by responsiveness 
 
Demonstrated technical and surgical skills with iTotal CR device - Investigator must have 
completed a cadaver training at minimum prior to enrolling their first subject 
 
Sufficient patient volume to expect timely subject enrollment  
 
Ability to adhere to the standards of Good Clinical Practice (GCP) and Good 
Documentation Practice (GDP) 
 
Clinical study experience and resources that demonstrate good compliance with study 
requirements and timely, complete documentation of subject follow-up 
 
Willingness to allow personnel from ConforMIS (or its designate) access to the hospital 
records, Investigator’s study records, data and patient files as they pertain to the study 
 
During the study, an oversight committee comprised of three individuals:  the Lead Study 
Principle Investigator in the U.S., a second study investigator, and a statistician will review site 

 
 
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performance and data integrity.  This committee will determine if the data collected is consistent 
with the cohort, and meets the minimum enrollment threshold for the study.  
 
If a site has not enrolled a minimum of 20 subjects into the study, data may be excluded from 
analysis.  Likewise, if data quality is inadequate or data is incomplete, the committee may 
exclude a site’s data.   
10. ENROLLMENT 
 
Potential subjects will be identified by the Investigator or study staff based on patients’ clinical 
and radiographic assessments during regular medical care. The Investigator or study staff will 
provide study information and the approved Informed Consent Form to all eligible subjects, 
(determined via Inclusion/Exclusion criteria), as well as answer any questions about the study.   
 
Once the consent form is signed, the subjects will be assigned a unique subject identification 
number through the EDC system.  Once they complete the first set of pre-operative 
questionnaires, they will be assigned to one of two treatment arms: A) Treatment with the iTotal 
CR or B) Treatment with an off-the-shelf knee replacement.  The site will be instructed to 
consecutively enroll 10 subjects per treatment arm, alternating between each arm, until 
enrollment is completed.   
 
The subject identification number will be comprised of a five digit number starting with a two 
digit site number assigned by ConforMIS at the Site Initiation followed by a three digit subject 
number, assigned chronologically for the entire study. For example, at site 01, the first subject 
enrolled will receive number 01-001, followed by 01-002, 01-003, etc.  
 
The Investigator and/or study staff will assess the subject against the Inclusion and Exclusion 
criteria to determine eligibility. Eligibility includes clinical assessments, radiographic 
assessments, and a review of the subject’s medical history. The radiographic assessments should 
include: 
1. Knee x-ray: 3 views – AP, lateral, sunrise or Merchant 
2. Three foot standing x-ray (full length, full weight-bearing film): AP view 
 
If the subject is not eligible to participate in the study, the subject will not be enrolled and is 
considered a screen failure. All screen failures will be tracked by the site manually in a tracking 
spreadsheet and electronically in a clinical database. Subject identification numbers for screen 
failures will not be re-used.  
 
The following Case Report Forms will be completed for all screen failures: 
 
SUBJECT INFORMATION/MEDICAL HISTORY 
 
INCUSION/EXCLUSION CRITERIA 
 
If the subject is eligible to participate in the study, they will be assigned to a treatment arm and 
will be considered enrolled when they are implanted with a device. 
11. SCHEDULE OF EVALUATIONS BY VISIT 
 
A table displaying the Schedule of Evaluations is in Appendix A.  Regardless of treatment arm 
assigned, subjects will complete each visit in the schedule of evaluations below. 

 
 
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11.1. 
Preoperative Visit (Up to 4 months prior to Surgery) 
Many of the screening assessments required to ensure subject eligibility are also considered 
the pre-operative assessments. The results of the assessments will be captured on the 
following Screening/Pre-operative Case Report Forms: 
 
SUBJECT INFORMATION / MEDICAL HISTORY 
 
CONCOMITANT MEDICATIONS 
 
PAIN MEDICATIONS 
 
INCLUSION/EXCLUSION CRITERIA 
 
KNEE SOCIETY SCORE (Surgeon portion)  
 
 
The subject will complete the following function tests and questionnaires to assess pain and 
function as part of their preoperative assessment: 
 
THE KNEE INJURY AND OSTEOARTHRITIS OUTCOME SCORE (KOOS) 
 
KNEE SOCIETY SCORE (Subject portion) 
 
TIMED “GET UP AND GO” 
 
8 METER WALK 
 
TIMED UP AND DOWN STAIRS  
 
X-rays: 
 
3 views – AP, lateral, sunrise or Merchant 
 
Three foot standing x-ray (full length, full weight-bearing film): AP view 
11.2. 
Surgery Visit (Day 0) 
The Investigator will surgically implant either the iTotal CR in compliance with the 
ConforMIS surgical training and Instructions for Use, or the off-the-shelf TKR per their 
surgical training and the manufacturer’s Instructions for Use.  
 
The site will complete the following Case Report Forms: 
 
SURGICAL SUMMARY  
 
DISCHARGE SUMMARY  
 
CONCOMITANT MEDICATIONS (optional) 
 
PAIN MEDICATIONS 
 
ADVERSE EVENTS (if any occur during surgery through discharge from hospital)   
 
X-rays: None 
11.3. 
90 Days Follow-up Visit (± 14 days) 
At the 90 days follow-up visit, the Investigator or study staff will perform a post-operative 
knee assessment and identify any adverse events that have occurred since the subject was 
discharged from the hospital.   The site will also collect the Uniform Billing (UB) form from 
their billing department if contracted with the Sponsor to participate in the Economic Sub-
study. 
 
The site will complete the following Case Report Forms: 
 
FOLLOW UP 
 
KNEE SOCIETY SCORE (Surgeon portion) 

 
 
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 
CONCOMITANT MEDICATIONS (optional) 
 
PAIN MEDICATIONS 
 
ADVERSE EVENTS (if any) 
o REVISION FORM (if necessary) 
 
The subject will complete the following function tests and questionnaires to assess post-
operative pain and function: 
 
THE KNEE INJURY AND OSTEOARTHRITIS OUTCOME SCORE (KOOS) 
 
KNEE SOCIETY SCORE (Subject portion) 
 
TIMED “GET UP AND GO”  
 
8 METER WALK 
 
TIMED UP AND DOWN STAIRS 
 
X-rays: 
 
3 views – AP, lateral, sunrise or Merchant* 
 
Three foot standing x-ray (full length, full weight-bearing film): AP view* 
*(Depends on hospital standards.  Protocol requires only one set of post-op x-rays at either 
90 or 180 days) 
11.4. 
180 Days Follow-up Visit (± 21 days) 
At the 180 days follow-up visit, the Investigator or study staff will perform knee assessments 
and identify any adverse events that have occurred since the last visit.  
 
The site will complete the following Case Report Forms: 
 
FOLLOW UP  
 
KNEE SOCIETY SCORE (Surgeon portion) 
 
CONCOMITANT MEDICATIONS (optional) 
 
PAIN MEDICATIONS 
 
ADVERSE EVENTS (if any) 
o REVISION FORM (if necessary) 
 
The subject will complete the following function tests and questionnaires to assess post-
operative pain and function: 
 
THE KNEE INJURY AND OSTEOARTHRITIS OUTCOME SCORE (KOOS) 
 
KNEE SOCIETY SCORE (Subject portion) 
 
TIMED “GET UP AND GO”  
 
8 METER WALK 
 
TIMED UP AND DOWN STAIRS  
 
X-rays: 
 
3 views – AP, lateral, sunrise or Merchant* 
 
Three foot standing x-ray (full length, full weight-bearing film): AP view* 
*(depends on hospital standards.  Protocol requires only one set of post-op x-rays at either 90 or 
180 days) 
11.5. 
Year 1, 2, and 5 Follow-up Visits (± 2 months) 

 
 
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At the 1 year, 2 year, and 5 year follow-up visits, the Investigator or study staff will perform a 
knee assessment and identify any adverse events that have occurred since the subject’s last 
visit.  
 
The site will complete the following Case Report Forms: 
 
FOLLOW UP 
 
KNEE SOCIETY SCORE (Surgeon portion) 
 
CONCOMITANT MEDICATIONS (optional) 
 
PAIN MEDICATIONS 
 
ADVERSE EVENTS (if any) 
o REVISION FORM (if necessary) 
 
The subject will complete the following function tests and questionnaires to assess post-
operative pain and function: 
 
THE KNEE INJURY AND OSTEOARTHRITIS OUTCOME SCORE (KOOS) 
 
KNEE SOCIETY SCORE (Subject portion) 
 
TIMED “GET UP AND GO”  
 
8 METER WALK 
 
TIMED UP AND DOWN STAIRS  
 
X-rays: None 
11.6. 
Year 3, 4, 6, 7, 8, and 9 Follow-up Visits (± 3 months) 
On the anniversary of the implant surgery for years 3, 4, 6, 7, 8, and 9, the Investigator or 
study staff will assess the subject for complications or adverse events, and specifically to 
determine if the iTotal CR or off-the-shelf total knee has been revised. It is not necessary for 
the subject go to the clinic for a visit, as the site can obtain the data via direct communication 
with them (such as via telephone or email).   
 
The site will complete the following Case Report Form: 
 
FOLLOW UP 
 
ADVERSE EVENTS (if any) 
o REVISION FORM (if necessary) 
 
X-rays: None 
11.7. 
Year 10 Follow-up Visit (± 4 months) 
On the 10 year anniversary of the implant surgery, the Investigator or study staff will assess 
the subject to determine if the iTotal CR or off-the-shelf total knee has been revised.  
 
The site will complete the following Case Report Form: 
 
FOLLOW UP 
 
KNEE SOCIETY SCORE (Surgeon portion) 
 
CONCOMITANT MEDICATIONS (optional) 
 
PAIN MEDICATIONS 
 
ADVERSE EVENTS (if any) 
 
REVISION FORM (if necessary) 
 

 
 
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The subject will be asked to complete the following function tests and questionnaires to 
assess long term post-operative pain and function. Note that the subject should return to the 
clinic to complete these questionnaires.   
 
THE KNEE INJURY AND OSTEOARTHRITIS OUTCOME SCORE (KOOS) 
 
KNEE SOCIETY SCORE (Subject portion) 
 
TIMED “GET UP AND GO” 
 
8 METER WALK 
 
TIMED UP AND DOWN STAIRS 
 
X-rays: None 
11.8. 
Early Termination Visit 
In the event that the study subject ends their participation in the study prior to the 10 year 
visit, the investigator or designated study staff will complete the following CRFs: 
 
SUBJECT DISPOSITION 
 
CONCOMITANT MEDICATIONS (optional) 
 
PAIN MEDICATIONS 
 
ADVERSE EVENTS (if any) 
o REVISION FORM (if necessary) 
 
The Investigator or designated study staff will make every attempt to complete the following 
evaluations: 
 
THE KNEE INJURY AND OSTEOARTHRITIS OUTCOME SCORE (KOOS) 
 
KNEE SOCIETY SCORE (Subject and Surgeon portion) 
 
TIMED “GET UP AND GO” 
 
8 METER WALK 
 
TIMED UP AND DOWN STAIRS 
12. SAFETY REPORTING 
 
All Adverse Events (AEs) that are at least possibly related to the knee replacement device or 
procedure will be recorded by the site from surgery on the Adverse Event CRF and should be 
reported to Sponsor within 5 working days of site becoming aware of the event. In addition, all 
Serious Adverse Events (SAEs) and Unanticipated Adverse Device Effects (UADEs) must be 
reported to ConforMIS or designee via telephone (781-345-9001) or email (clinical-
affairs@conformis.com) as soon as possible once discovered by the site. SAEs should be reported 
to ConforMIS within 3 working days, and UADEs should be reported to ConforMIS within 2 
working days. The Investigator and investigative site will also be responsible for required 
reporting to the site’s Institutional Review Board / Independent Ethics Committee (IRB/IEC) for 
all AEs, SAEs, and UADEs. 
 
In the communications to ConforMIS or the IRB, include the protocol number and subject ID 
either in the subject of the email or the beginning of the call.  ConforMIS will confirm receipt of 
the AE/SAE.  If possible, include the AE/SAE CRF and supporting documents to ConforMIS as 
soon as possible. 
 
For the purposes of this protocol, for the first 90 days following surgery, all AEs categorized 
as Possible, Probable or Definite in relationship to the device or procedure should be 

 
 
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recorded.  At day 91, only those AEs categorized as Possible, Probable, or Definite in 
relationship to the device, as deemed by the investigator, will be recorded.  Those events 
that are Unlikely or Not Related to the device and procedure will not be collected.  Please 
see definitions below. 
 
All SAEs will be recorded regardless of relationship to the device or procedure. 
 
ConforMIS will be responsible for safety reporting as required by applicable regulatory bodies. 
 
Adverse Event: Any untoward or unfavorable medical occurrence associated with the use of a 
medical product in a human patient, including any abnormal sign, symptom, or disease.  Report 
only those AEs with Possible or above, relationship. 
 
Definite: 
Clear-cut temporal association and no other possible cause. 
Probable: 
Clear-cut temporal association and a potential alternative etiology 
are not apparent. 
Possible: 
Temporal association is less clear and other etiologies are also 
possible. 
Unlikely: 
Temporal association and the nature of the event is such that the 
study device is not likely to have had any association with the 
observed event (cause and effect relationship improbable but not 
impossible) 
Not Related: 
There is no temporal association and/or evidence exists that the 
event is definitely related to another etiology 
 
Serious Adverse Event: Any undesirable experience associated with the use of a medical product 
in a patient in which the patient outcome is: death, a life-threatening event, inpatient 
hospitalization or prolongation of existing hospitalization, a persistent or significant 
disability/incapacity, a congenital anomaly/birth defect or requires intervention to prevent 
permanent impairment or damage. 
Unanticipated Adverse Device Effect (21 CFR 812.3): 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), 
instructions for use, informed consent or any other unanticipated serious problem associated with 
a device that relates to the rights, safety, or welfare of patients. 
13. DATA MANAGEMENT 
 
Each site will be responsible for accurate, complete, and timely collection/recording of data using 
the CRF (or EDC system) provided. Data will be stored in a validated and secure database for 
analysis. ConforMIS will periodically review all data, and specifically adverse event data to 
determine interim revision rates, frequency of serious adverse events and patient outcomes. If 

 
 
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missing data fields or incorrect data are identified, the site may be contacted to provide the 
missing/correct data. 
 
ConforMIS or a designee will provide Case Report Forms (paper and/or electronic) to the study 
sites, along with access the to the EDC system. 
 
14. MONITORING 
 
ConforMIS or designee will monitor clinical sites using risk-based monitoring to review source 
data, study conduct, and compliance to the protocol. Each site will be monitored shortly after 
beginning enrollment to ensure early identification and resolution of any issues. After the initial 
monitoring visit, the site will be monitored at a frequency determined by ConforMIS or designee 
based on a variety of variables including but not limited to the risk of the site, rate of enrollment, 
the number of issues identified that require follow-up, changes in site personnel, etc.  
15. STATISTICAL METHODS  
  
All statistical processing will be performed using SAS® Version 9.3 or later unless otherwise 
stated.   
 
For continuous variables, descriptive statistics will include n (number of subjects), mean, 
standard deviation (SD), median, minimum, and maximum. For categorical variables, the number 
and percentage of subjects in each category will be presented. Appropriate inferential statistics 
will be used for the primary and secondary efficacy variables.   
 
Populations 
The safety population will be comprised of all subjects for whom the procedure is initiated. 
 
The Full Analysis Set (FAS) will be comprised of all subjects for whom the procedure is 
completed. 
 
The Per-Protocol (PP) population will include all subjects in the FAS who complete the 1 Year 
visit without significant protocol violations.  The PP population will not include subjects who 
meet any of the following criteria: 
 
Violated inclusion/exclusion criteria, without sponsor waiver; 
 
Did not attend the 1 Year visit 
 
Out of window at the 1 Year visit by +/- 2 months 
 
Have undergone a procedure to the contralateral knee which may impact the follow-up 
assessments  
 
Additional criteria may be added to the list to accommodate for unforeseen events that occur 
during the conduct of the study that impact efficacy assessments. The PP population will be 
determined prior to data base lock. 
 
Demographic and Baseline Characteristics 
Demographic variables (e.g. age, gender, ethnicity, race) and baseline characteristics will be 
recorded in the CRF. For continuous variables, comparisons between treatment groups will be 

 
 
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conducted with an analysis of variance (ANOVA). A Cochran-Mantel-Haenszel (CMH) test will 
be used for testing categorical variables. 
 
Efficacy Analysis 
 
Primary Efficacy Analysis 
The absolute change from baseline to 1 Year for each primary endpoint will be analyzed using an 
analysis of covariance (ANCOVA) with factor of treatment (iTotal CR, OTS) and the respective 
baseline score as a covariate.  The least squares means will be presented along with the observed 
means. 
 
Secondary Efficacy Analyses 
Secondary endpoints will be analyzed as follows: 
 
 
The absolute change from baseline to 1 Year for each subscale of KSS will be analyzed 
using an analysis of covariance (ANCOVA) with factor of treatment (iTotal CR, OTS) 
and the respective baseline score as a covariate.  The least squares means will be 
presented along with the observed means. 
 
The absolute change from baseline to 1 Year for each subscale of KOOS will be analyzed 
using an analysis of covariance (ANCOVA) with factor of treatment (iTotal CR, OTS) 
and the respective baseline score as a covariate.  The least squares means will be 
presented along with the observed means. 
 
Post-operative limb alignment will be dichotomized as in and out of “safe zone” (+/- 3 
degrees neutral mechanical axis alignment).  The proportion of subjects in each study arm 
summarized and compared using a CMH test. 
 
Safety Analysis 
Procedure-related and device-related adverse events (AEs) occurring during the study will be 
recorded. For the safety population, AEs will be summarized by study arm, the number of 
subjects reporting AEs, severity, relationship to procedure, relationship to device, and 
seriousness. 
 
In addition to overall AE summaries, AEs will be summarized for the following study periods: 
 
Day of procedure to 6 months post procedure 
 
Annual summaries (1 Year, 2 Year, etc.) from day of procedure 
 
All serious adverse events (SAEs) will be summarized by study arm, severity, relationship to 
procedure, and relationship to device.  SAEs will also be listed by subject.  
 
All information pertaining to AEs noted during the study will be listed by subject.  
 
The Fisher’s Exact test will be used to compare the proportion of subjects in each study arm who 
have the following: 
 
procedure-related AEs  
 
device-related AEs  
 
revision procedures 
 
Missing Efficacy Data Imputation 

 
 
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The last observation carried forward (LOCF) method will be used to impute missing efficacy 
data.   
 
Sample Size Determination 
A total sample size of a minimum of 450 and a maximum of 600 subjects will be prospectively 
enrolled in a consecutive fashion, to each arm of the study (approximately 225-300 in the iTotal 
CR arm and 225-300 in the OTS arm). To ensure that enrollment in each arm remains relatively 
even, sites assigned odd site numbers will begin by enrolling off-the-shelf subjects and even 
numbered sites will begin by enrolling ConforMIS subjects.  Based on data from a previous 
study, it is expected that a minimum of 450 and a maximum of 600 total subjects will provide 
greater than 80% power for the primary functional endpoint. 
 
16. SUBJECT PROTECTION 
 
Data will be de-identified on forms and in the clinical database, and subjects will be identified 
only by a code or subject number. All information and data sent to ConforMIS or designee 
concerning patients or their participation in this study will be considered confidential, and 
confidentiality shall be observed by all parties involved at all times during the study. All data 
used in analysis and reports will be used without identifiable reference to the subject. All data 
will be secured against unauthorized access. The Investigator and investigative site will be 
responsible for compliance with all local privacy regulations. 
17. ETHICAL CONSIDERATIONS 
 
The protocol and Informed Consent Form must be approved by a central IRB or the IRB/IEC for 
the institution where the study is conducted. Each subject shall give informed consent in a form 
and manner that meets all IRB/IEC requirements. All subjects must be informed that the device is 
available commercially and that participation in the clinical study is not required for them to be 
treated with the device.  Investigators shall agree to conduct the study in compliance with the 
provisions of the Declaration of Helsinki and with ICH/GCP Standards. 
 
In compliance with the Food and Drug Administration Amendments Act of 2007 (FDAAA), this 
study will be listed in www.clinicaltrials.gov. 
18. REPORTS  
 
A final study report shall be prepared and provided to all investigative sites for submission to 
their IRB/IEC.  The final study report will be made a permanent record in the ConforMIS 
document control system. 
 
 

 
 
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19. LITERATURE 
 
1. American Thoracic Society.  ATS Statement: Guidelines for the Six Minute Walk Test.  
American Journal of Respiratory and Critical Care Medicine.  2002; 166: 111-117. 
2. Bourne RB, et.al. Patient satisfaction after total knee arthroplasty: Who is satisfied and 
who is not?. Clin Orthop Relat Res. 2010 468:57–63. 
3. Fitz W. Unicompartmental Knee Arthroplasty with Use of Novel Patient-Specific 
Resurfacing Implants and Personalized Jigs. J Bone Joint Surg Am. 2009; 91:69-76. 
4. Kurtz S, et. al. Projections of Primary and Revision Hip and Knee Arthroplasty in the 
United States from 2005 to 2030. J Bone Joint Surg Br. 2007; 89:780-85. 
5. Lepage C, et. Al.  Association between characteristics of locomotion and accomplishment 
of life habits in children with cerebral palsy.  Physical Therapy.  1998; 78:458-469. 
6. Mathias S, et.al.  Balance in Elderly Patients: The “Get-up and Go” Test.  Arch Phys Med 
Rehabil 1985; 67:  387-399. 
7. Mizer R, et. al.  Measuring Functional Improvement After Total Knee Arthroplasty 
Requires Both Performance-Based and Patient-Report Assessments:  A Longitudinal 
Analysis of Outcomes.  The Journal of Arthroplasty.  2010; Article in Press (0) June 9, 
2010. 
8. McCarthy C, et. Al.  The reliability, validity and responsiveness of an aggregated 
locomotor function (ALF) score in patients with osteoarthritis of the knee.  
Rheumatology.  2004; 43: 514-517. 
9. National Institutes of Health.  NIH Toolbox Training Manual. National Institutes of 
Health and Northwestern University. 2012. Retrieved from 
http://www.healthmeasures.net/images/nihtoolbox/Training-Admin-
Scoring_Manuals/NIH_Toolbox_Training_Manual-English_9-25-12.pdf 
10. Noble PC, et al. The John Insall Award: Patient expectations affect satisfaction with total 
knee arthroplasty. Clin Orthop Relat Res. 2006 452:35–43. 
11. Nordin E, et. al.  Timed “Up & Go” test:  Reliability in older people dependent in 
activities of daily living- focus on cognitive state.  Physical Therapy.  2006; 86: 646-655. 
12. Podsiadlo D, et. Al.  The Timed “Up & Go”: A test of basic functional mobility for frail 
elderly persons.  The American Geriatrics Society 1991; 39: 142-148. 
13. Steffen TM, et. al.  Age and gender related test performance in community-dwelling 
elderly people: Six-minute walk test, Berg Balance Scale, timed up & go test, and gait 
speeds.  Physical Therapy.  2002; 82: 128-137. 
14. Suda A, et. al.  Are patients’ expectations of hip and knee arthroplasty fulfilled?  A 
prospective study of 130 patients.  Orthosupersite.  2010.  www.orthosupersite.com.  
15. Wall JC, et. al.  The timed get-up-and-go test revisited: Measurement of the component 
tasks.  Journal of Rehabilitation Research and Development.  2000; 37(1): 109-114. 
16. Zaino, C, et. al.  Timed up and down stairs test:  Preliminary reliability and validity of a 
new measure of functional mobility.  Pediatric Physical Therapy.  2004; 90-98. 
 
 

 
 
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PROTOCOL HISTORY 
 
Protocol 
Version 
Protocol Date 
Updated by: 
Changes Made: 
1.0 AA 
13 November 2013 
Shirley Mak-Parisi
Initial release 
2.0 AA 
06 April 2015 
Shirley Mak-Parisi
Added protocol signature page 
Throughout protocol- iTotal CR KRS 
was shortened to iTotal CR 
Throughout protocol- updated the 
reference structure from footnotes to 
MLS format. 
Study design: added UK 
Added Economic sub study to protocol 
and appendix 
Functional testing:  Updated tests to be 
listed in the order that they will be 
performed. 
Deleted the Berg and 6minute walk 
Added 8 meter walk 
Added ALF details 
Updated primary and secondary 
endpoints 
Enrollment, randomization:  Updated 
the alternative way of randomizing a 
patient.   
Throughout protocol:  Deleted 6 weeks 
Added 90 days and updated 6 months to 
180 days 
Safety reported:  added the sentence 
“for the first 90 days, ALL AEs should 
be recorded.  At day 91” this is to 
capture all AEs in the first 90 days for a 
patient. 
Monitoring: added risk based 
monitoring 
Worksheets:  Updated and renamed 
“instructions” 
Updated:  “Patients” to “Subjects” 
throughout the protocol 
Removed all references to the Patient 
Satisfaction Survey, Berg Balance and 
Forgotten Joint Score 
Changed section 9 (schedule of 
evaluations by visit) to indicate that 
both types of radiographic evaluation 

 
 
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can occur at either the 90 days or 180 
days visit. 
Fixed Appendix A to indicate the 
change described above concerning 
radiographic evaluations, and indicated 
that the Follow-up CRF is to be 
completed at the 90 days visit, as well 
as an Adverse Events/Revision form if 
applicable. 
Stats section updated to reflect protocol 
updates 
3.0 AB 
14 October 2015 
Tyler Halloran 
Updated Marc Quartulli’s job title. 
Under Study Design (section 3), 
surgical approach was updated to allow 
for other approaches. 
Changed the name of section 7.1 from 
“Primary Endpoint” to “Primary 
Endpoints”. 
In section 7.1, Primary Endpoints, 
further detailed the components 
comprising the ALF score. 
Updated section 8, Site Selection, to 
section 9, in turn correcting an overall 
issue with the numbering throughout 
the remainder of the protocol. 
Updated AE language (section 12) so 
that only AEs that are at least possibly 
related to the device or procedure are 
captured in the first 90 days post-op. 
Updated Appendix A, combining 
Onsite and Remote Follow Up and 
altering the spacing/positioning. 
Updated Appendix B to clarify 
instructions. 
Added Appendix D, CONSORT Data 
Reporting Guidelines, and an 
explanation in Section 8, 
Inclusion/Exclusion Criteria, how sites 
will log all patients considered for the 
study. 
Updated the Table of Contents. 

 
 
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4.0 AC 
30 April 2016 
Shirley Mak-Parisi
Updated versioning to 4.0 AC in all 
headers and footers and protocol 
signature page. 
Under Study Design (section 3), 
surgical approach was defined and 
updated to allow for only medial 
parapatellar or subvastus approach. 
Under schedule of evaluation section, 
for concomitant medications, added the 
word “(optional)” for all time points 
except for screening. 
Under Appendix A, added an “*” to 
radiographic evaluation (long leg) row 
to indicate that this is to occur at the 90 
Days or 180 Days visit. 
Updated Functional Testing Worksheet 
in Appendix B to make changes to 
CRF, including shading and a typo. 
Appendix C updated SAS version to 
match main protocol 
5.0 AD 
27 March 2017 
Shirley Mak-Parisi
Updated the title from:  “A Prospective, 
Randomized, Multicenter Study to 
Evaluate the ConforMIS iTotal (CR) 
Knee Replacement System versus Off-
the-Shelf Replacement” to “A 
Prospective, Multicenter Study to 
Evaluate Functional Outcome After 
Knee Replacement” 
Throughout document, oxford comma 
used 
Updated ConforMIS address 
Added ConforMIS internal use ID 
Deleted randomization throughout the 
protocol 
Deleted the use of patient specific 
instrumentation. 
Updated the study design to reflect no 
randomization. 
Deleted double blinding.  Only 
functional tester is blinded.  Updated 
throughout protocol. 
Updated N 

 
 
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Updated language for economic study. 
Only sites who are contracted with 
ConforMIS will take part. 
Updated timed “Get-up and Go” test 
definition to clarify the length of the 
walk. 
Updated 8 meter walk with the correct 
reference.  National Institutes of Health 
instead of McCarthy. 
Updated the Timed Up and Down Stairs 
Test to include a minimum of 4 steps in 
a flight of stairs. 
Deleted the patient reported outcomes 
as a primary endpoint. 
Added KSS as a secondary endpoint.  
Updated statistical analyses with KSS 
information. 
Updated exclusion criteria to provide 
clarity.  Deleted “Other lower extremity 
surgery within 1 year” to “Lower 
extremity surgery (orthopaedic or 
ligament injury) on either limb to the 
hip, ankle, feet occurring or expected to 
occur within 1 year of surgery on the 
evaluated knee” 
Updated exclusion criteria to provide 
clarity.  Changed “Contralateral knee 
replacement surgery within the past 6 
months” to “Contralateral knee 
replacement occurring or expected to 
occur within 6 months of surgery on the 
evaluated knee” 
Added instructions on how a site will 
consecutively enroll subjects. 
Administrative changes to provide 
clarity. 
Clarified Safety reporting.  Added 
phone number and email along with 
instructions of what needs to be 
included in the communications to the 
sponsor and the IRB. 
Updated efficacy analysis 

 
 
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Updated the sample size determination 
paragraph 
Updated Appendix A to reflect changes 

 
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20. APPENDIX A – Schedule of Evaluations 
Evaluation 
Screening/ 
Pre-Op 
Surgery 
90 Days 
Follow-up 
180 Days 
Follow-up 
Year 1, 2, 5 
Follow-up 
Year 3, 4, 6, 7, 8, 9 
Follow-up 
Year 10 
Follow-up 
Visit window 
Up to 4 
months 
prior to 
surgery 
N/A 
± 14 days 
± 21 days 
± 2 months 
± 3 months 
± 4 months 
Inclusion/Exclusion Criteria 
X 
 
 
 
 
 
 
Subject Information & Medical 
History 
X 
 
 
 
 
 
 
Pain Medications & Concomitant 
Medications‡ 
X 
X 
X 
X 
X 
 
X 
Knee Society Score (KSS) 
X 
 
X 
X 
X 
 
X 
Knee Injury & Osteoarthritis 
Outcome Score (KOOS) 
X 
 
X 
X 
X 
 
X 
Functional Testing 
X 
 
X 
X 
X 
 
X 
Radiographic Evaluation * 
X 
 
X† 
X† 
 
 
 
Surgical & Discharge Summary 
 
X 
 
 
 
 
 
Adverse Events & Serious Adverse 
Events  
 
X 
X 
X 
X 
X 
X 
Follow Up 
 
 
X 
X 
X 
X 
X 
Subject Disposition 
 
 
 
 
 
 
X+ 
 
‡ The collection of Concomitant Medications is optional after the Pre-operative visit 
*Radiographic evaluation includes: Knee x-ray 3 views- AP, lateral, sunrise or Merchant; Long Leg x-ray (full length flim with full weight bearing)- AP view  
†Post-operative radiograph can be performed at 90 or 180 days depending on hospital standard 
+ Subject Disposition to be completed either at the 10 year visit or when the subject withdraws from the study

 
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21. APPENDIX B – Functional Testing Instructions 
 
 
 
Timed Get Up and Go Test 
  
 
Equipment needed: Arm chair, tape measure, tape, stopwatch, and cone 
Test Set Up: 
1. Place a chair in an area with adequate space for the patient to walk and turn around. 
2. Measure 30.5 cm (12 inches; 1ft) in front of the chair and place a piece of tape there. 
3. From the piece of tape, measure 3 meters (118 inches; 9ft & 10 in) and place another piece of tape 
at the end. 
4. Place the cone on top the piece of tape at the 3 meter mark (ensure the middle of the cone is 
aligned with the center of the tape. 
Test Instructions: 
1. The subject should begin the test sitting comfortably in the chair with their feet on the ground.  
The subject is allowed to use the arm rests during the sit and stand movements.  The subject is 
allowed to use assistive devices such as a cane or walker.  If the subject uses the arm rests or an 
assistive device, please record this on the form. 
2. Instruct the subject using the following command: 
- 
“On the word ‘GO’ you will stand up, walk to the cone, walk around the cone, and then walk 
back towards the chair to sit down.  Walk as quickly as you feel safe.” 
3. Stopwatch instructions: 
- 
Start timing when you say “GO.” 
- 
Stop timing when the subject is completely seated (same as starting position). 
4. There will be 3 individually timed tests. 
 

 
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8 Meter Walk 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Equipment needed: Stopwatch, cone, tape measure, and tape 
Test Set Up:  
1. Place a piece of tape as a starting point in an area with adequate space for the patient to walk and 
turn around. 
2. Measure 4 meters from that point and place a second piece of tape at that location. 
4 meters = 
13.12 Feet 
157.48 Inches 
13 Feet and 1.48 inches 
400 Centimeters 
4.37 Yards 
2.35 Smoot 
3. Place the cone on top the piece of the second piece of tape. 
Test Instructions: 
1. The subject should stand at the first piece of tape. 
2. Instruct the subject using the following command: 
- 
“On the word ‘GO’ you will walk to the cone, walk around the cone, and then walk back 
towards first piece of tape.  Walk as quickly as you feel safe.” 
3. Stop watch instructions: 
- 
Start timing when you say “GO.” 
- 
Stop timing when the subject’s second foot touches the first piece of tape. 
4. There will be 3 individually timed tests. 
 
 
4 meters = 
13.12 Feet 
157.48 Inches 
13 Feet and 1.48 inches 
400 Centimeters 
4.37 Yards 
2.35 Smoot

 
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Timed Up & Down Stairs Test 
 
 
Equipment needed: Stopwatch, Flight of Stairs 
Test Set Up:  
1. Count the number of steps and record this on the form.  Count the steps in one direction.  For 
example, in the diagram above, there are 5 steps.  The flight of stairs used in this test must have a 
minimum of 4 stairs. 
2. If possible, please use the same flight of stairs for all subjects. 
Test Instructions: 
1. The subject should stand at the bottom of the flight of stairs. 
2. Instruct the subject using the following command: 
- 
“I am going to ask you to stand at the bottom of the stairs so that your first step is up.  My 
commands will be ‘ready, set, GO’.  Then you are going to walk as quickly as you feel safe 
and comfortable to the top of the stairs, turn around, and come back down.  You may use the 
rail, but if you can go without the rail, please try to do so.” 
3. Stop watch instructions: 
- 
Start timing when you say “GO.” 
- 
Stop timing when the subject’s second foot touches the landing at the bottom of the stairs. 
4. At the end of each test, ask the subject about their pain level during the test, their confidence, and 
their comfort in completing another trial. 
5. If the subject answers “no” concerning their comfort in completing the stairs, then do not have 
them attempt the stairs again. 
6. There will be 3 individually timed tests if the subject if the subject feels comfortable completing 
each test. 
 
 
 
 

 
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Time Point (check one):   Pre‐op 
 90 Days 
 180 Days   Year 1 
 Year 2 
 Year 5 
 Year 10 
 
Trial 
Get Up & Go Time 
(mm:ss.ms) 
Get Up & Go Rest 
Time 
(mm:ss.ms)
Arms 
Used? 
Circle Pain Level After Each Trial
1 
 
___ ___ : ___ ___ . ___ ___ 
 
___ ___ : ___ ___ . ___ ___ 
Y      N 
0   1   2   3   4   5   6   7   8   9   10 
2 
 
___ ___ : ___ ___ . ___ ___ 
 
___ ___ : ___ ___ . ___ ___ 
Y      N 
0   1   2   3   4   5   6   7   8   9   10 
3 
 
___ ___ : ___ ___ . ___ ___ 
 
___ ___ : ___ ___ . ___ ___ 
Y      N 
0   1   2   3   4   5   6   7   8   9   10 
Did the subject require a rest between the Chair and Walking activities? 
Y 
N
 
Trial 
Walking Time 
(mm:ss.ms) 
Walking Rest Time
(mm:ss.ms) 
Circle Pain Level After Each Trial
1 
 
___ ___ : ___ ___ . ___ ___ 
 
___ ___ : ___ ___ . ___ ___ 
0   1   2   3   4   5   6   7   8   9   10 
2 
 
___ ___ : ___ ___ . ___ ___ 
 
___ ___ : ___ ___ . ___ ___ 
0   1   2   3   4   5   6   7   8   9   10 
3 
 
___ ___ : ___ ___ . ___ ___ 
 
___ ___ : ___ ___ . ___ ___ 
0   1   2   3   4   5   6   7   8   9   10 
Did the subject require a rest between the Walking and Stairs activities? 
Y 
N
 
Trial 
Stairs Time 
(mm:ss.ms) 
Stairs Rest Time
(mm:ss.ms) 
Rails 
Used? 
Circle Pain Level After Each Trial
1 
 
___ ___ : ___ ___ . ___ ___ 
 
___ ___ : ___ ___ . ___ ___ 
Y      N 
0   1   2   3   4   5   6   7   8   9   10 
How confident were you in your ability to 
complete the Stairs during that trial? 
Very  Somewhat  Not Very 
Not At All 
Do you feel comfortable completing the Stairs a second time? 
Y 
N
2 
 
___ ___ : ___ ___ . ___ ___ 
 
___ ___ : ___ ___ . ___ ___ 
Y      N 
0   1   2   3   4   5   6   7   8   9   10 
How confident were you in your ability to 
complete the Stairs during that trial? 
Very  Somewhat  Not Very 
Not At All 
Do you feel comfortable completing the Stairs a third time? 
Y 
N
3 
 
___ ___ : ___ ___ . ___ ___ 
 
___ ___ : ___ ___ . ___ ___ 
Y      N 
0   1   2   3   4   5   6   7   8   9   10 
How confident were you in your ability to 
complete the Stairs during that trial? 
Very  Somewhat  Not Very 
Not At All 
Number of Steps (in staircase): ______ 
Observations: ______________________________________________________________ 
 
 

 
ConforMIS, Inc. 
Protocol 12-005 Revision 5.0 AD 
27 March 2017 
Page 29 of 30 
Confidential and Proprietary 
Nothing herein is to be disclosed without the prior express written permission of ConforMIS, Inc. 
22. APPENDIX C – U.S. Economic Sub-Study 
 
A cost comparison between the groups will be performed.  Each site will obtain the Uniform 
Billing (UB) forms from their billing department.  These forms will have the following 
information for analysis: 
 
Length of stay  
 
Blood transfusions throughout the stay (number of units and type of transfusions) 
 
Patient discharge disposition 
 
Patient comorbidities 
 
Readmission to hospital and 30-day readmission rate 
 
 
Additionally, in the case report forms, the following information will be collected for analysis: 
 
Number of trays used  
 
Instances of compromised tray sterility 
 
Procedure and device related adverse events 
 
Primary outcome: 
Economic Outcomes as measured by collected hospital data and Uniform Billing (UB) forms 
 
Statistics: 
All statistical processing will be performed using SAS® Version 9.3 or later unless otherwise 
stated.     
 
No imputations will be made for missing observations.  Continuous variables will be summarized 
with sample size, mean, standard deviation, median, minimum, maximum, and 95% confidence 
intervals, as appropriate.  Categorical variables will be summarized with frequency counts, 
percentages, and 95% confidence intervals, as appropriate.     
 
Demographic Evaluations & Cost Analysis 
Demographic variables (age, gender, ethnicity, and race) will be recorded in the database and 
summarized using descriptive statistics.  For continuous variables, comparisons between treatment 
groups will be conducted with an analysis of variance (ANOVA). A Chi-square test will be used 
for testing categorical variables. 
 
 

 
ConforMIS, Inc. 
Protocol 12-005 Revision 5.0 AD 
27 March 2017 
Page 30 of 30 
Confidential and Proprietary 
Nothing herein is to be disclosed without the prior express written permission of ConforMIS, Inc. 
23. APPENDIX D – CONSORT Data Reporting Guidelines 
 
 
 
 
 
CONSORT 2010 Flow Diagram 
Assessed for eligibility (n=  ) 
Excluded  (n=   ) 
   Not meeting inclusion criteria (n=  ) 
   Declined to participate (n=  ) 
   Other reasons (n=  ) 
Analysed  (n=  ) 
 Excluded from analysis (give reasons) (n=  ) 
Lost to follow-up (give reasons) (n=  ) 
Discontinued intervention (give reasons) (n=  ) 
Allocated to intervention (n=  ) 
 Received allocated intervention (n=  ) 
 Did not receive allocated intervention 
(give reasons) (n=  ) 
Lost to follow-up (give reasons) (n=  ) 
Discontinued intervention (give reasons) (n=  ) 
Allocated to intervention (n=  ) 
 Received allocated intervention (n=  ) 
 Did not receive allocated intervention (give 
reasons) (n=  ) 
Analysed  (n=  ) 
 Excluded from analysis (give reasons) (n=  ) 
Allocation
Analysis 
Follow‐Up 
Randomized (n=  ) 
Enrollment