Comparison of Alignment Achieved Using Single-Use Versus Reusable Instrumentation in Total Knee Arthroplasty (TKA): A Prospective, Non-Randomized Multi-center Investigation
Phase: NA
Conditions: Osteoarthritis, Post-traumatic Arthritis
Sponsor: DePuy Orthopaedics

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

DePuy Synthes Joint Reconstruction 
CLINICAL RESEARCH 
 
 
CLINICAL INVESTIGATION PLAN (CIP) 
 
 
                                                                              TITLE 
Comparison of Alignment achieved using Single-Use versus Reusable Instrumentation in Total Knee 
Arthroplasty (TKA): A Prospective, Non-Randomized Multi-Center Investigation. 
 
This document is a confidential communication of DePuy Synthes Joint Reconstruction. The recipient 
agrees that no unpublished information contained herein will be published or disclosed without prior 
written approval of DePuy Synthes Joint Reconstruction except that this document may be disclosed to 
appropriate oversight authorities or duly authorized representatives of the U.S. Food and Drug 
Administration or other responsible regulatory authorities under the condition that they are requested to 
keep it confidential. 
 
Clinical Investigation 
 Plan Number: 
10002 
Country: 
Worldwide Study 
CIP Prepared By: 
 
 
 
 
 
CIP Version: 
Revision B 
Clinical Investigation Sponsor: 
DePuy Synthes Joint Reconstruction 
a division of DePuy Orthopaedics, Inc. 
PO Box 988 
700 Orthopaedic Drive 
Warsaw, IN   46581-0988 
 
 
 
 
 
 
 
 
 

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PROTOCOL SIGNATURE PAGE 
 
 
 
Comparison of Alignment achieved using Single-Use versus Reusable Instrumentation in Total Knee 
Arthroplasty (TKA): A Prospective, Non-Randomized Multi-Center Investigation. 
PROTOCOL 10002  
Document 
 
 
Type/Revision 
Protocol/Exhibit  
Effective Date 
 
Original                 #1 
  Protocol/Exhibits Rev A 
May 28, 2015 
Administrative     #2                               Protocol/Exhibits Rev B 
February 19, 2018 
 
Principal Investigator:  
 
I have read this protocol and agree to conduct this clinical investigation in accordance with the 
design and specific provisions outlined herein. 
 
I understand the protocol and I understand I am solely responsible to ensure the investigation is 
conducted in accordance with Good Clinical Practices (GCP), applicable country regulations, the 
Declaration of Helsinki, the signed clinical study contract with DePuy Synthes Joint Reconstruction, 
and with the protocol outlined herein.  
 
I will conduct this study as outlined therein and will make reasonable effort to complete the study 
within the time period designated by DePuy Synthes Joint Reconstruction. 
 
I will provide copies of the protocol and all pertinent information to all individuals responsible to 
me who will assist in the conduct of this study. I will discuss this material with them to ensure they 
are fully informed regarding the device and the conduct of the study.  
 
I will fulfill the requirements of my Institutional Review Board (IRB)/Ethics Committee (EC), or other 
oversight committee, to ensure complete and continual oversight of this clinical investigation.   I 
will use an Informed Consent Document approved by DePuy Synthes Joint Reconstruction and my 
reviewing IRB/EC.  
 
I agree to report all information or data in accordance with the protocol and I agree to report any 
serious adverse events, device related adverse events, or procedure related adverse events as 
defined in this protocol to DePuy Synthes Joint Reconstruction and comply with all adverse events 
reporting requirements of my reviewing IRB/EC. 
 
I agree to permit DePuy Synthes Joint Reconstruction, its authorized representatives, my reviewing 
IRB/EC, and any regulatory authority/body access to all records relating to the clinical investigation.  
 

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The below signature confirms I have read and understood this protocol and its associated 
amendments or attachments, and will accept respective revisions or amendments provided by 
DePuy Synthes Joint Reconstruction. 
 
 
_______________________________________                        _______________ 
Principal Investigator 
 
 
 
 
         Date 
 
 
 
 
 
 

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Table of Contents 
 
COMPARISON OF ALIGNMENT ACHIEVED USING SINGLE-USE VERSUS REUSABLE INSTRUMENTATION IN TOTAL KNEE 
ARTHROPLASTY (TKA): A PROSPECTIVE, NON-RANDOMIZED MULTI-CENTER INVESTIGATION. ............................................ 2 
PROTOCOL 10002 .............................................................................................................................................. 2 
1 
LIST OF ABBREVIATIONS .....................................................................................................................7 
2 
SUMMARY ..........................................................................................................................................9 
 
TIME AND EVENTS TABLE............................................................................................................................ 11 
3 
INTRODUCTION ................................................................................................................................ 12 
 
BACKGROUND .......................................................................................................................................... 12 
4 
RATIONALE ....................................................................................................................................... 14 
 
STUDY RATIONALE ..................................................................................................................................... 14 
 
STUDY DESIGN RATIONALE ......................................................................................................................... 14 
 
RATIONALE OF ENDPOINTS ......................................................................................................................... 14 
 
RATIONALE OF STUDY POPULATION .............................................................................................................. 14 
5 
SUBJECT DEFINITION ......................................................................................................................... 15 
 
INCLUSION CRITERIA .................................................................................................................................. 15 
 
EXCLUSION CRITERIA.................................................................................................................................. 15 
 
DEFINITION OF SUBJECT ENROLLMENT .......................................................................................................... 16 
6 
OBJECTIVES AND HYPOTHESIS ........................................................................................................... 17 
 
PRIMARY OBJECTIVE .................................................................................................................................. 17 
 
SECONDARY OBJECTIVES ............................................................................................................................ 17 
 
EXPLORATORY OBJECTIVES .......................................................................................................................... 17 
 
HYPOTHESIS ............................................................................................................................................. 17 
7 
STUDY DESIGN .................................................................................................................................. 18 
8 
PROTOCOL ........................................................................................................................................ 19 
 
THE SEQUENCE OF EVENTS FOR A SUBJECT ARE AS FOLLOWS: ............................................................................ 19 
 
SUBJECT ENROLLMENT ............................................................................................................................... 19 
8.2.1 
Subject Screening .......................................................................................................................... 19 
8.2.2 
Subject Informed Consent ............................................................................................................. 20 
8.2.3 
Subject Identification Numbering .................................................................................................. 22 
 
STUDY PROCEDURES .................................................................................................................................. 22 
8.3.1 
Subject Evaluation Tools ................................................................................................................ 22 
8.3.2 
Pre-operative Management .......................................................................................................... 22 
8.3.3 
Intra-operative Management ........................................................................................................ 23 
8.3.4 
Post-operative Management ........................................................................................................ 24 
8.3.5 
Radiographic Procedures ............................................................................................................... 24 
8.3.6 
Management of Bias ..................................................................................................................... 25 
 
PROCESS FOR DISCONTINUATION OF SUBJECT PARTICIPATION .......................................................................... 25 

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8.4.1 
Preoperative Screen Failures/Withdrawals ................................................................................... 25 
8.4.2 
Intra-operative Withdrawal .......................................................................................................... 26 
8.4.3 
Enrollment Replacement Rules ...................................................................................................... 27 
8.4.4 
Postoperative Withdrawal ............................................................................................................ 27 
8.4.5 
Revisions / Reoperations ............................................................................................................... 28 
8.4.6 
Minimization of Subjects Lost to Follow-up .................................................................................. 29 
9 
RISK ANALYSIS .................................................................................................................................. 31 
 
ADVERSE EVENT DETERMINATION ................................................................................................................ 31 
 
NON-REPORTABLE ADVERSE EVENTS - SPONSOR ONLY .................................................................................. 31 
 
STUDY RELATED RISKS / REPORTABLE ADVERSE EVENTS .................................................................................. 31 
 
MINIMIZATION OF RISK .............................................................................................................................. 33 
 
BENEFIT ANALYSIS ..................................................................................................................................... 33 
 
ADVERSE EVENT ........................................................................................................................................ 33 
9.6.1 
Categories and Definitions ............................................................................................................ 33 
 
ADVERSE EVENT REPORTING GUIDELINES ...................................................................................................... 35 
9.7.1 
AE Reporting by Site to the Sponsor .............................................................................................. 35 
9.7.2 
Institutional Review Board (IRB) / Ethics Committee (EC) Reporting. ........................................... 39 
9.7.3 
Regulatory reporting requirements ............................................................................................... 39 
10 STATISTICAL METHODOLOGY ............................................................................................................ 40 
 
STUDY DESIGN ...................................................................................................................................... 40 
 
TREATMENT ASSIGNMENT ...................................................................................................................... 40 
 
LEVELS OF SIGNIFICANCE ......................................................................................................................... 40 
 
INTERVAL WINDOWS ............................................................................................................................. 40 
 
HANDLING OF MISSING DATA .................................................................................................................. 41 
 
PRIMARY AND SECONDARY ENDPOINTS ..................................................................................................... 41 
 
HYPOTHESES ......................................................................................................................................... 41 
 
ANALYSIS SETS ...................................................................................................................................... 42 
 
SAMPLE SIZE JUSTIFICATION .................................................................................................................... 42 
 
ANALYSIS PLAN ..................................................................................................................................... 43 
 
INTERIM ANALYSIS ................................................................................................................................. 44 
11 DEVICE DESCRIPTION ........................................................................................................................ 45 
 
INSTRUMENTS ....................................................................................................................................... 45 
11.1.1 
Reusable Instruments .................................................................................................................... 45 
11.1.2 
The ATTUNE Single Use Instruments (SUI) .................................................................................... 45 
 
IMPLANTS ............................................................................................................................................ 45 
12 INVESTIGATOR RESPONSIBILITIES AND GOOD CLINICAL PRACTICES .................................................... 48 
 
IRB/ ETHICS COMMITTEE APPROVAL ........................................................................................................ 48 
 
INFORMED CONSENT .............................................................................................................................. 48 
 
PROTECTED HEALTH INFORMATION .......................................................................................................... 48 
 
SUBJECT DISCONTINUATION FROM THE CLINICAL INVESTIGATION .................................................................. 49 
 
SOURCE DOCUMENTATION AND DATA RETENTION ...................................................................................... 49 
 
RECORD OF DEVICE INVENTORY ............................................................................................................... 50 
 
CASE REPORT FORM COMPLETION AND DATA SUBMISSION .......................................................................... 50 

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PROTOCOL ADHERENCE .......................................................................................................................... 51 
 
CIP AMENDMENTS ................................................................................................................................ 51 
 
INVESTIGATOR REPORTING RESPONSIBILITIES ............................................................................................. 51 
 
INVESTIGATOR SITE FILE.......................................................................................................................... 53 
 
REGULATORY REQUIREMENTS .................................................................................................................. 53 
 
INVESTIGATOR STUDY TERMINATION ........................................................................................................ 53 
13 SPONSOR OBLIGATIONS .................................................................................................................... 54 
 
IRB/EC APPROVAL ................................................................................................................................ 54 
 
INVESTIGATOR TRAINING, PRE-INVESTIGATIONAL VISIT ................................................................................ 54 
 
STUDY MONITORING .............................................................................................................................. 54 
SPONSOR OVERSIGHT WILL BE MAINTAINED PER SPONSOR POLICIES AND PROCEDURES.  ON SITE MONITORING WILL BE DONE AT 
THE DISCRETION OF THE SPONSOR. SHOULD A MONITORING VISIT BE REQUIRED, THE SPONSOR WILL WORK WITH THE SITE TO 
DETERMINE THE DATE(S). ...................................................................................................................................... 54 
DURING THE VISIT, THE SPONSOR AND AUTHORIZED SPONSOR REPRESENTATIVES SHALL BE GIVEN ACCESS TO ALL STUDY RECORDS, 
TO INCLUDE STUDY SUBJECT  MEDICAL RECORDS. ....................................................................................................... 54 
 
LABELING ............................................................................................................................................. 54 
 
SPONSOR STUDY TERMINATION ............................................................................................................... 54 
 
SPONSOR REPORTING RESPONSIBILITIES .................................................................................................... 55 
 
FINANCIAL AGREEMENT .......................................................................................................................... 55 
 
PUBLICATION POLICY AND PUBLIC DISCLOSURE .......................................................................................... 55 
 
INSURANCE ........................................................................................................................................... 55 
14 REFERENCES ..................................................................................................................................... 56 
15 CLINICAL INVESTIGATIONAL PLAN EXHIBITS....................................................................................... 58 
 

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1 
LIST OF ABBREVIATIONS 
ADE 
     
Adverse Device Effect 
AE 
     
Adverse Event  
AP 
     
Anterior-Posterior 
BS  
      
ENBritish Standard European Norm 
21 CFR     
Code of Federal Regulation:  Title 21 
CE 
 
Conformité Européenne 
CIP 
 
Clinical Investigational Plan 
CR  
 
Cruciate Retaining 
CRF 
 
Case Report Form (paper) 
 
DVT 
 
Deep Vein Thrombosis  
EC 
 
Ethics Committee 
eCRF 
 
Electronic Case Report Form 
 
EMEA  
Europe/Middle East/ Asia-Pacific 
EU 
 
European Union 
FB 
 
Fixed Bearing 
FDA 
 
Food and Drug Administration 
GCP 
 
Good Clinical Practice 
HTO 
 
High Tibial Osteotomy 
ICD 
 
Informed Consent Document 
IRB 
 
Institutional Review Board 
ISO 
 
International Organization for Standardization 
IRR 
 
Independent Radiographic Reviewer                           
ITT 
 
Intent To Treat 
MEDDEV 
Medical Device Guidance Document(s) 
NIDJD  
Non-inflammatory Degenerative Joint Disease 
OR 
 
Operating Room 
PHI 
 
Personal Health Information 
PI 
 
Principal Investigator 
PMCF  
Post-Market Clinical Follow-up  
Post-op  
Post-operative 
PP 
 
Per Protocol Analysis 

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Pre-op  
Pre-operative 
RUI 
 
Reusable Instruments 
SADE 
 
Serious Adverse Device Effect 
SAE 
 
Serious Adverse Event 
SAS® 
 
Statistical Analysis System 
SUI 
 
Single Use Instruments 
TKA 
 
Total Knee Arthroplasty 
UADE  
Unanticipated Adverse Device Effect 
UK 
 
United Kingdom 
US 
 
United States 
USADE  
Unanticipated Serious Adverse Device Effect 
UTO 
 
Upper Tibial Osteotomy (See also HTO) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
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2 
SUMMARY 
TITLE: 
Comparison of Alignment achieved using Single-Use versus Reusable 
Instrumentation in Total Knee Arthroplasty (TKA): A Prospective, Non-
Randomized Multi-Center Investigation. 
Short Title: 
SUI vs. RUI 
Protocol 
Number: 
10002 
Treatment 
Device: 
Single Use Instruments (SUI) for implantation of ATTUNE® primary TKA. Four 
implant configurations are permitted:  Cruciate Retaining Fixed Bearing (CR FB),  
Cruciate Retaining Rotating Platform (CR RP), Posterior Stabilizing Fixed Bearing 
(PS FB) and Posterior Stabilizing Rotating Platform (PS RP) configurations.  Each site 
will be restricted to using either Cruciate Retaining configurations or Posterior 
Stabilizing Configurations for both treatment and control groups. 
Control 
Device: 
Reusable Instruments (RUI) for implantation of ATTUNE primary TKA.  Four  
implant configurations are permitted:  Cruciate Retaining Fixed Bearing (CR FB),  
Cruciate Retaining Rotating Platform (CR RP), Posterior Stabilizing Fixed Bearing 
(PS FB) and Posterior Stabilizing Rotating Platform (PS RP) configurations. Each site 
will be restricted to using either Cruciate Retaining configurations or Posterior 
Stabilizing Configurations for both treatment and control groups. 
Intended 
Use: 
The intended use for the instrumentation and device, applicable to this study, is as 
follows: 
Candidates for total knee replacement include patients with severely painful 
and/or severely disabling Non-inflammatory Degenerative Joint Disease (NIDJD) 
resulting from osteoarthritis (OA) or post-traumatic arthritis. 
Primary 
Objective: 
To determine whether the mechanical axis alignment achieved with SUI 
instrumentation is non-inferior to the alignment achieved  with RUI 
instrumentation.   
Secondary 
Objectives 
• 
To compare individual component alignment achieved with SUI vs. RUI of 
individual components in the frontal and sagittal planes, specifically: distal 
femoral varus-valgus (FM), proximal tibial varus-valgus (TM),  femoral 
component flexion and tibial slope.  
• 
To compare the type and frequency of  adverse events 
Study 
Design: 
Prospective, comparative, sequential, non-randomized, multi-center, controlled 
study design.  Level of evidence: Level IIIA 
Number of 
Sites: 
4  Centers Worldwide                                    
Subject 
Population: 
Male and female Subjects who are candidates for primary, total knee arthroplasty 
between 22 and 80 years of age, inclusive, with noninflammatory degenerative 
joint disease (NIDJD) resulting from osteoarthritis (OA) or post-traumatic arthritis.   
Sample Size: 
A total of 88 Subjects will be enrolled in the investigation (44 treatment Subjects 
and 44 control Subjects). 
                                                          
A Levels of Evidence for Primary Research Question 
 

 
 
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TITLE: 
Comparison of Alignment achieved using Single-Use versus Reusable 
Instrumentation in Total Knee Arthroplasty (TKA): A Prospective, Non-
Randomized Multi-Center Investigation. 
Study 
Duration: 
The estimated duration of this study is 13 months: 8 months for enrollment and 5 
months for post-operative follow-up. 
Procedure 
Schedule: 
Demographic data will be collected preoperatively.  Surgical data will be collected 
intraoperatively.   Post–operatively, radiographic data will be collected at 
approximately 90 days. 
Safety: 
All adverse events will be collected from the time of surgery through to the end of 
the study or the time when that Subject is withdrawn from the study. A listing of 
expected, procedure-related, early postoperative adverse events (AEs) will be 
provided and such events will not need to be recorded.The type and frequency of 
recorded AEs will be analyzed. 
 
 

 
 
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
Time and Events Table 
Event / Visit 
Pre-Op 
Surgery 
Post-Op 
Required Timing (days) 
-180d to 
include day 
0 
0 
30 -150 
Discuss Study with Subject  
Yes 
 
 
Screening Log  
Yes 
 
 
Informed Consent 
Yes 
 
 
Enrollment  
Yes 
 
 
Complete Subject History eCRF 
C 
 
 
Surgical Procedure 
x
Complete Operative Details eCRF 
x
Complete Device Log eCRF 
 
 
C 
C 
 
Radiographs 
x
Hip to Ankle Long Film 
 
 
 
  R* 
x
AP View 
R 
 
R 
x
Lateral View 
 
 
R 
Complete Adverse Event eCRF 
 
A  
A
Complete End of Study/Withdrawal  
A 
A 
C 
Advise the Subject when they will next be seen 
Yes 
Yes 
 
C= Case Report Form to be completed and submitted in the Electronic data capture system 
R= Radiograph obtained and submitted 
R*, For the purposes of this investigation this radiograph will only be performed when 
the Subject can achieve full leg extension (±5°). 
A= As needed 
 
 

 
 
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3
INTRODUCTION 

Background 
Alignment 
 
Successful total knee arthroplasty relies on proper positioning of prosthetic components to restore 
the mechanical axis of the lower extremity. It is widely accepted that proper alignment is an important 
factor in the success and longevity of total knee arthroplasties [1-4]. Mechanical axis alignment is 
defined as the line drawn from the center of the femoral head through the center of the knee and 
ankle. The knee is in proper alignment when these three points are collinear in the frontal plane [1] . 
Many authors have observed that the correct alignment of the lower limb is correlated with clinical 
success in total knee arthroplasty [2-7].  
 
Operating Room (OR) Efficiency                                                                                                                         
In this era of capitated reimbursement and managed care, cost containment is assuming greater 
importance in health care. Consequently, operating room efficiency has become higher priority for 
many institutions [8]. As patient volume increases and hospital resources are strained the OR can 
become a bottleneck in providing efficient, high quality patient care.  Optimizing OR performance 
without compromising safe and high-quality health care for patients is an important goal. 
There are a number of studies aimed at increasing operating room efficiency and controlling operating 
room costs while striving to provide high-quality, technologically advanced surgical services.  Often 
the focus is on streamlining the existing steps that are involved in delivering patient care 
preoperatively, intraoperatively, and postoperatively [10]. This need for improved delivery of care is 
further critical when one recognizes the increasing number of patients needing TKA. Improved surgical 
instruments are one factor that may improve OR efficiency and an  approach is to introduce Single-
Use instruments.  
 
An important aspect of the delivery of surgical care is the time required to prepare the operating room 
prior to the procedure as well as the turnover time at the conclusion of the surgery.  Preparation 
timeline for every surgical procedure is at risk from various delays.  Unwanted delays have occurred 
related to unavailable sterile instruments,  holes found in the sterile wrap of sterilized instruments, 
the time required to flash sterilize an instrument requested last minute, etc.   Prepackaged sterilized 
Single-Use instruments may help to resolve some of these unwanted delays.  Additionally, when single 
use instruments are combined with preoperative templating to define implant sizing, there should be 
a substantial reduction in the quantity of instruments brought to the OR (Figure 1). Single use 
instruments provide a completely clean and sterile instrument for every patient, which is used once 
and disposed of, removing the need for lengthy decontamination processes[13].   
 
 
 

 
 
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Figure 3-1: ATTUNE TKA Instrumentation (left to right):Reusable instrumentation; and  Single Use 
instrumentation shown 
   
    
 

 
 
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4
RATIONALE 

Study Rationale 
A pre-requisite for SUI adoption is to confirm that  the mechanical axis alignment achieved with                  
single use instruments is non-inferior to the alignment achieved with ATTUNE reusable instruments .    

Study Design Rationale 
The study was designed as comparative, sequential, non-randomized, multi-center, such that each 
site has an equal number of Subjects in each treatment group, SUI and RUI. The follow-up period of 
approximately 90 days was selected due to the time required for most Subjects to be able to achieve 
full leg extension (within ± 5°), a requirement for obtaining suitable weight-bearing hip-to-ankle 
radiographs for analysis of alignment.  The mechanical axis alignment will be assessed at the 3 month 
follow-up by independent radiographic review.  The sequential design (that is at each site all RUI cases 
will be completed before doing any of the SUI cases) is set up to ensure that with the control group 
(RUI), current status of OR efficiency is captured rather than this being influenced by any efficiencies 
learned from use of the SUI. 
 

Rationale of Endpoints 
Successful total knee arthroplasty relies on proper positioning of prosthetic components to restore 
the mechanical axis of the lower extremity. It is widely accepted that proper alignment is an important 
factor in the success and longevity of total knee arthroplasties [1-4].  A goal of 0° ± 3° mechanical axis 
alignment was chosen because the Investigators in this study confirmed they regularly aim for this 
target.    
 

Rationale of Study Population 
Subjects with NIDJD and determined to be suitable for a cemented, primary TKA with the ATTUNE 
implant are targeted as this study is on surgical instruments to implant a cemented, primary ATTUNE 
implant.   Narrowing the indications to exclude inflammatory arthritis was done to have more 
homogeneity in the population, including bone quality that could possibly influence bone resections 
with the two instrument types. 
 

 
 
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5
SUBJECT DEFINITION 
Male and female Subjects, aged 22-80 years, inclusive, with Non-Inflammatory Degenerative Joint 
Disease (NIDJD) resulting from osteoarthritis (OA) or post-traumatic arthritis and suitable candidates 
for primary, total knee arthroplasty using an ATTUNE system are eligible for enrollment in this study. 
 
Subjects who do not meet all of the inclusion criteria or meet any of the exclusion criteria are 
automatically excluded from study consideration and participation.  Subjects, who meet all entry criteria 
and are properly consented, may be excluded from participation because of:  
x
Surgeon preference/medical opinion (under very limited conditions not to introduce Investigator 
bias). 
x
Withdrawal of consent from study participation.  

Inclusion Criteria 
Subjects meeting all of the following specific criteria will be considered for participation in the study:  
 
a) Subjects with severely painful and/or severely disabling Non-inflammatory Degenerative Joint 
Disease (NIDJD) resulting from osteoarthritis (OA) or post-traumatic arthritis. 
 
b) Subject is male or female and between the ages of 22 and 80 years old, inclusive.  
 
c) Subject requires a primary total knee replacement and is considered by the Investigator to be 
suitable for the specific knee prosthesis identified in the protocol.   
 
d) Subject, who, in the opinion of the  Investigator, is suitable for implantation using either RUI 
or SUI instrumentation.  
 
e) Subject is able to speak and read English to facilitate comprehension of the Informed Consent 
Document.  
 
f) Subject has given voluntary, written informed consent to participate in this clinical 
investigation and has authorized the transfer of his/her information to DePuy Synthes Joint 
Reconstruction. 
 
g) Subject, in the opinion of the Investigator, is able to understand this clinical investigation and 
is willing and able to perform all study procedures and follow-up visits and co-operate with 
investigational procedures. 
 

Exclusion Criteria 
Subjects will be excluded from participation if they meet any of the following criteria:  
 
a) The Subject has, in the opinion of the Investigator, a severe deformity that will hinder 
achieving a mechanical axis alignment target of 0°  ±   3°. 

 
 
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b) The Subject has, in the opinion of the Investigator, an existing condition that would 
compromise their participation and follow-up in this study.   
 
c) The Subject has, in the opinion of the Investigator, a flexion deformity that will not allow 
for 0° extension postoperatively.  
 
d) The Subject is a woman who is pregnant or lactating. 
 
e) The Subject, in the opinion of the Investigator, is a drug or alcohol abuser (in the last 5 
years) or has a psychological disorder that could affect follow-up care or treatment 
outcomes. 
 
f) The Subject has participated in a clinical investigation with an investigational product in 
the last 3 months. 
 
g) The Subject is currently involved in any personal injury litigation, medical-legal or worker’s 
compensations claims. 
 
h) The Subject has previous prosthetic knee replacement  (any type including 
unicompartmental, total knee arthroplasty, patellofemoral arthroplasty or ipsilateral 
UTO/HTO) of the affected knee or a previous patellectomy.  
 
i)
The Subject presents with ankylosis of the hip joint on the side to be treated. 
 
j)
The Subject had a contralateral TKA and that knee was previously entered into the study.B 
 
k) The Subject requires simultaneous bilateral total knee replacements.C 
 
l)
Any case in which Computer-Assisted Surgery (CAS) or TruMatch (or any other type of 
Custom Patient Instruments) is to be used, or any additional instrumentation are to be 
used for bone resections that are not provided as part of the ATTUNE RUI or SUI 
Instrument kits. 
 
m) The Subject requires a device not specified in the protocol or the surgeon determines that 
the ATTUNE Knee System is not a suitable treatment. 

Definition of Subject Enrollment 
As described in additional detail in Section 8.2 a patient will be considered enrolled when they have: 
 
9 Provided written informed consent to participate in this Investigation, which includes authorization 
of the release of their Personal Health Information (PHI).   
                                                          
B Having both knees from one Subject in the study could confound the data. 
C As the study involves measuring the time taken for stages of surgery a simultaneous bilateral 
procedure would confound this dataset (would always take longer) 

 
 
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6
OBJECTIVES AND HYPOTHESIS 

Primary Objective 
To determine whether the mechanical axis alignmentD achieved with SUI instrumentation is non-
inferior to the alignment achieved with RUI instrumentation.  Mechanical axis alignment is defined as 
the line drawn from the center of the femoral head through the center of the knee and ankle and will 
be measured from weight bearing long-leg (51”) Anteroposterior (AP) radiographs, taken 
approximately 90 days post-op (when subject has reached full knee extension) and read by an 
independent radiographic reviewer.  
 

Secondary Objectives 
x
To compare alignment achieved with SUI vs. RUI of individual components in the frontal and 
sagittal planes, specifically: distal femoral varus-valgus (FM) , proximal tibial varus-valgus 
(TM),  femoral component flexion and tibial slope. 
x
To compare the type and frequency of  adverse events, from the time of surgery through to 
withdrawal of a subject or the end of the study (includes serious adverse events, and device 
and/or procedure-related adverse events), between the SUI and RUI instrument groups. 
 

Exploratory Objectives 
x
To compare SUI and RUI operating room times from OR set-up through OR clean down as 
detailed in Table 8-3 of Section 8.3.3. 
x
To determine whether SUI provides opportunity to reduce the incidence of minor procedural 
obstacles during the time in the OR.  
x
To compare Surgeon satisfaction of SUI instrumentation to RUI instrumentation. 
 
The primary and secondary clinical endpoints and the relevant statistical analyses are described in 
Section 10.6 
 

Hypothesis 
Hypothesis: If Single Use Instruments are used to implant an ATTUNE Total Knee, the alignment 
achieved will be non-inferior to that achieved with Reusable Instruments for the same procedure. 
 
See Section 10.7 for further details on study hypotheses. 
                                                          
D During preparation of this protocol discussions with the sites to be involved in this study  confirmed 
that all 4  sites regularly plan to achieve 0° ±  3° mechanical axis alignment. Exceptions to this are only 
in rare cases of  extreme deformity. The study has therefore been designed with this in mind and 
collection of pre-operative  plans are not required for the study. 
 

 
 
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7 
STUDY DESIGN 
This study is designed as a prospective, comparative, sequential, non-randomized, multi-center, 
controlled clinical investigation.  
 
There will be 4 centers worldwide that will recruit a total of 88 Subjects (44 Treatment Subjects and 
44 Control Subjects).  A complete description of the methods for determining sample size is contained 
in Section 10.9. Initially, the Subjects will be evenly distributed across the four sites; therefore it is 
expected that each site will recruit 22 Subjects (11 Control followed sequentially by 11 Treatment 
Subjects).  In between the Control and Treatment Subjects, a learning curve is permitted for the use 
of SUI. 
 
• 
The Control group will consist of 44 Subjects, 11 per site and the surgical procedure for these 
Subjects will be performed using Reusable Instruments (RUI).  
• 
The Treatment group will consist of 44 Subjects, 11 per site and the surgical procedure for 
these Subjects will be performed using Single Use Instruments (SUI).  
 
At each site the 11 Control Subjects will be enrolled and operated on prior to performing the first 
surgery in the Treatment group. For a given site, either Cruciate Retaining or Posterior Stabilising 
configurations will be used; consistent with their standard of care.  Within a given CR site, the 
Investigator may choose to implant either the CR FB or CR RP.  Similarly, within a given PS site, the 
Investigator may choose to implant either the PS FB or PS RP.  Randomization is not being applied in 
this study in order to isolate and learn if there are changes in OR efficiency with SUI under normal 
operating room procedures. 
 
One surgeon at each site will complete all RUI and SUI surgical cases including the learning curve. No 
Sub-Investigators will be permitted to perform surgery  to avoid possible confounding issues with 
varying surgical process.  All sites will have previously completed their learning curve with the ATTUNE 
Primary Implant implanted using RUI prior to enrolling the 1st patient. Then after the completion of 
all RUI study cases, a learning curve will be permitted for the use of SUI.  The duration of the SUI 
learning curve is anticipated to be approximately 5 cases and is at the discretion of the Principal 
Investigator. These early cases that are within the learning curve will not be enrolled into this study 
at each site.   
 
Both resurfaced patellae and non-resurfaced patellae are permitted in this investigation, consistent 
with site standard of care. TruMatch technology or any other type of Custom Patient Instruments are 
not permitted.  Similarly Computer-Assisted Surgery (CAS) is not permitted within the study. The 
procedures must be performed using only the instrumentation provided (SUI or RUI) and standard 
surgical methods, without additional tools that could confound the key research question of this study 
(for example, instrumentation that helps perform bone resections). 
 
The Sponsor will monitor overall project enrollment. Cohort reallocation during the RUI phase only 
may be done in order to maintain project timelines. The Sponsor  can authorize a shift of a group of 
Subjects from one site to another to maintain project timelines.   For example, the Sponsor can reduce 
the cohort of a slow-enrolling RUI site to a faster-enrolling RUI site and the faster-enrolling RUI  site 
will assume responsibility for the reallocated RUI cohort and the same number of SUI Subjects.  

 
 
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8
PROTOCOL 

The sequence of events for a Subject are as follows: 
x
If the Patient is thought to be generally eligible, the Patient is invited to participate and the 
informed consent procedure is followed 
x
The Subject is screened for eligibility against the Protocol Inclusion/Exclusion criteria 
x
If the Subject meets the Protocol Inclusion/Exclusion criteria, a subject history is taken 
x
Within 180 days from initiating the consent procedure TKA surgery is performed during which 
operative details, timepoints of key stages of the procedure, instrument and device details, 
and any intraoperative complications are captured on eCRFs for submission and subsequent 
analysis. 
x
Approximately 90 days (+/-60 days) post-surgery weight bearing long-leg (51”) 
Anteroposterior (AP) radiographs are taken and any postoperative complications collected.  
Radiographs are to be anonymized and sent to the Independent Radiographic Reviewer (IRR) 
for analysis. 

Subject Enrollment            
No study-related procedure or form associated with this study can be completed until written 
informed consent is obtained for that Subject. (see Section 5.3 Definition of Subject Enrollment). 
8.2.1
Subject Screening 
All Patients who present with NIDJD affecting the knee, and are candidates for primary, cemented 
TKA, and who generally meet the study requirements, will be screened for eligibility and will be listed 
on the Screening and Enrollment Log in order to document that the Subject selection was unbiased. 
The date of screening, the results of screening (included or not) and the primary reason for not 
including the patient (e.g., does not satisfy eligibility criteria, not interested in participating) will be 
recorded on this log. The original log is to be retained at the Site and a copy sent to the Sponsor 
regularly during enrollment.  A flowchart demonstrating the screening process and definition of 
enrollment is illustrated in Figure 8-1. 
 
Eligible Patients who agree to participate in the study will be required to sign an Informed Consent 
Document prior to any study related procedures being done.  After signing the Informed Consent,  
study Subjects are defined as “enrolled” and site will complete the non-standard of care pre-
operative data collection. 
 
It is expected that complete data collection will be obtained for all enrolled Subjects, with the only 
exception being a Subject who is subsequently withdrawn. See Section 8.4 Discontinuation of Subject 
Participation (Withdrawal) for details. 
 
 

 
 
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8.2.2 
Subject Informed Consent 
In compliance with BS EN ISO 14155, and the Declaration of Helsinki, no Subject shall be enrolled in 
an investigation without provision of adequate informed consent.  The Principal Investigator is 
responsible for ensuring that no Subject is included in the study without adequate informed consent 
being provided.  Failure to obtain and properly document this process is in violation of BS EN ISO 
14155, the Declaration of Helsinki, and this study protocol.   
All informed consent documents (ICD) must have favorable opinion of the IRB/EC (Section 12.1).  
Consent of a Subject needs to be from the subject themselves and documented on an Informed 
Consent Document in the primary language of the Subject.   
 
Screening, consenting and enrollment are illustrated in Figure 8-1.  The Investigator or trained 
designee preliminarily screens to determine if a patient generally meets the eligibility criteria for the 
study (item 2 in flowchart, Figure 8-1).  If so, the Investigator or trained designee shall offer study 
participation to those patients (item 3 in flowchart, Figure 8-1). If the patient agrees to participate 
s/he signs the informed consent document.   
 
               Table 8-1: Key Elements of Consent Process 
Key Element of Consent Process (item 4 of flowchart) 
The Investigator or designee shall confirm the Subject understands each of the following 
points of the study: 
 
• 
The purpose of the study, 
• 
The potential risks or adverse events that are posed by their treatment, 
• 
The potential risks or adverse events directly related to study participation, 
• 
Possibility of failure and the need for subsequent treatment(s), 
• 
Alternative procedures/treatments available to the Subject, 
• 
Requirements of the study including rehabilitation and follow-up visits, 
• 
All of the Subject’s rights as a participant in the clinical investigation. 
 
Following the explanation of the study intent, the Investigator or trained designee shall 
offer to answer any of the Subject’s questions.  If the Subject then agrees to participate, 
his or her willingness must be documented via a signature and date on the IRB/EC’s 
approved ICD and this document countersigned and dated by the person taking consent. 
 
 
Upon successful completion of consent process, the Patient is enrolled and is identified as a Study 
Subject (items 5 in flowchart, Figure 8-1).  The Investigator or trained designee will assess eligibility 
per Sections 5.1 & 5.2 (item 6 in flowchart, Figure 8-1). 
 
Acquiring Consent on Day of Surgery:  If the Informed Consent Document signatures are acquired on 
the day of surgery, a time stamp on the signature page is required to support that consent was 
obtained from the study Subject prior to any treatment related and/or mood altering medications 
being administered.  A time stamp is not required where consent is obtained on a day prior to surgery.   
 
 

 
 
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Figure 8-1: Screening and Enrollment Process 
 
1) Review Surgical 
Schedule
2) Based on prelim info, 
does Subject generally meet 
eligibility criteria?
3) Invite Subject to participate in Study & 
Document Subject on 
Screening & Enrollment Log 
4) Consent Process 
Successful?
6) Subject meets all 
Eligibility criteria?
YES
NO                 
YES- collect pre-op clinical data
8) Continue Post-op 
Follow-up 
NO
No documentation 
needed
          
 
Document as Screen Failure in Screening & 
Enrollment Log
YES
5) Subject Enrolled – Subject 
Identification Number Allocated
7) Surgery 
completed with 
assigned 
instruments
YES
Complete 
Withdrawal CRF
NO                 
NO
Replace Subject
NO
 
 

 
 
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8.2.3
Subject Identification Numbering 
The database assigns Subject ID numbers after consent is obtained.  
 
Each site is identified uniquely , e.g., 01-, 02- through 04, followed by 0001 for the first Subject, at the 
site, 0002 for the second Subject, and so on. For example, the first (3) three Subjects enrolled at Site 
#1 will be identified as 01-0001, 01-0002, 01-0003. Together the Site number and the Subject number 
will then become the unique identifier of the Subject and will be recorded on each page of the eCRF 
and on the Subject Screening & Enrollment Log.  
 
In the instance of a Subject being enrolled, a number assigned and subsequently the Subject is 
deemed ineligible prior to receiving the ATTUNE knee, the Subject will be recorded as a screen failure 
on the screening/enrollment log. Once a Subject identification number is assigned, it may not be 
reused.  Refer to Sections 8.4 Discontinuation of Subject Participation and 8.4.1 Enrollment 
Replacement Rules. 
 

Study Procedures 
This section is applicable to individuals who have undergone screening, have signed an Informed 
Consent Document, and have otherwise been found eligible to participate in this study per the 
Protocol’s Inclusion/Exclusion criteria. This section details the pre-operative, operative, and post-
operative management of Subjects. Visit evaluations include  radiographic evaluations. Sample Case 
Report Forms (CRFs) are located in Exhibit A.  eCRFs must be submitted to DePuy Synthes Joint 
Reconstruction as outlined in Section 12.7 Case Report Form Completion and Data Submission.                                        
8.3.1
Subject Evaluation Tools 
No Patient Reported Outcome Measures are included in this study. 
8.3.2
Pre-operative Management 
Prior to surgery, the evaluations in Table 8-2 must be completed for each enrolled Subject.  The 
interval for obtaining pre-op assessments is - 180 days to day 0 (day of surgery) as designated on the 
Time & Events Table 2.1. The pre-surgery management of each Subject enrolled in this investigation 
will be according to the standards of care used at the study site.  
 
Table 8-2: Pre-operative Data Collection and eCRF 
Evaluation 
Details of Evaluation 
Subject History 
For all Subjects the Investigator or designee must confirm consent has been 
given, record the Subject’s demographic details and details of their previous 
medical history, and confirm eligibility on Subject History eCRF.   
Radiographs 
Pre-operative radiographs will be obtained.  
 
 

 
 
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8.3.3
Intra-operative Management 
The surgical process is to follow site standard of care. 
This investigation allows the Investigator to follow their current standard of care with respect to 
patellar resurfacing. Specifically the Investigator can choose to: 
x
Resurface the patella 
x
Leave the patella unresurfaced. 
 
This investigation does NOT permit the Investigator to use TruMatch (or any other PSI 
instrumentation) or CAS for any Subjects, whether they are in the RUI or SUI arms of the study. 
 
Products supplied by DePuy Synthes must be used in accordance with the manufacturer’s instructions 
unless an alternative technique is medically necessary.  
 
Each Investigator or designee will collect information as noted in Table 8-3 below. The detailed 
surgical procedure is provided in Exhibit B.  Data collection will begin at the time the OR is being set 
up for a study Subject procedure and will continue until the room is cleaned up and ready for the next 
case. 
 
 Table 8-3: Intra-operative Data Collection and eCRFs 
Evaluation 
Details of Evaluation 
Operative Details 
eCRF 
For all Subjects, detailed surgical information and time information 
relating to the duration of 4 key elements of the surgical procedure 
will be recorded on the Operative Details eCRF.   These 4 elements 
are OR Set Up, Anesthetic, Surgery & Clean Down. Definitions of each 
element will be provided as part of the training for individuals who 
will be capturing time data. Note there is likely to be overlap in time 
between some of these elements (possible scenario illustrated 
below). 
 
1. OR Set Up
2. Anesthesia
3. Surgery
4. Clean Down
 
 
In addition to the start and stop times for the 4 key elements, the 
occurrence of various incidents that can introduce delays or 
interruptions to the surgical flow will also be recorded.  

 
 
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Evaluation 
Details of Evaluation 
Device Log 
eCRF 
For all Subjects, each component used during the procedure should 
be documented on the Device Log eCRF.  The required product codes 
and catalog numbers can be found on pre-printed labels provided in 
the sterile implant boxes.     
Retain a copy of each label to facilitate data entry into the eCRF 
Intra-operative 
Complications 
(if applicable) 
Adverse Event eCRF 
In the event of an intraoperative complication, an Adverse Event 
eCRF is completed. An intra-operative complication is defined as a 
complication that occurs between the start of anesthesia and up to 
the time the Subject is moved to the recovery room. Complete a 
separate form  for each intra-operative complication.   
8.3.4 
Post-operative Management 
Immediate post-operative management is at the discretion of the  Principal Investigator and should 
follow each Site’s standard of care.  
 
The one(1) postoperative study follow-up visit will be conducted according to the Time and Events 
Table 2.1.   Each Investigator or designee will collect information as noted in Table 8-4 below.  At this 
visit radiographs will be collected as detailed in the Radiographic Protocol (Exhibit F). An independent 
radiographic reviewer (IRR) will evaluate all radiographs. Copies of the evaluations will be available to 
Investigators upon request.  
 
 Table 8-4: Post-operative Data Collection and eCRFs 
Evaluation 
Details of Evaluation 
Radiographs 
For all Subjects post-operative radiographs will be obtained.   
End of Study 
Completion or 
Subject 
Withdrawal 
For all Subjects the Investigator or designee must complete an End of 
Study/Subject Withdrawal eCRF to confirm the Subject is no longer in the 
study.  
Post-operative 
Complication(s) 
(if applicable) 
 
In the event of a post-operative complication an Adverse Event eCRF is 
completed. A post-operative complication is defined as a complication that 
occurs at any time from the time the Subject is in the recovery room up 
through the time a Subject withdrawal form is submitted ending the Subject’s 
study participation. Complete a separate form  for each post-operative 
complication.  
 
8.3.5 
Radiographic Procedures 
Weight bearing long-leg, hip-to-ankle (51” = 129.54 cm) Anteroposterior (AP) radiographs will be 
taken, as well as standard AP and lateral view radiographs, following the detailed instructions 
presented in the Radiographic Protocol (Exhibit F).  While Patellar Skyline/Merchant view radiographs 
may be standard of care at some sites, they are not a requirement of the study and they do not need 
to be submitted to the IRR.    All radiographs must be de-identified by the site prior to making them 
available for review by the Independent Radiographic Reviewer (IRR). 

 
 
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8.3.6
Management of Bias 
To avoid potential bias and ensure consistency, an Independent Radiographic Reviewer (IRR) will be 
used to evaluate the post-op 90 day radiographs. This is an open investigation by design. Only the 
independent radiographic reviewer will be blinded regarding the instrumentation. The X-ray images 
will be provided with all Subject PHI information removed prior to assessment by the IRR. Data from 
the IRR radiographic evaluations (not the Investigators) will be used for determination of radiographic 
success criteria. Details of the radiographic assessment and means of submitting radiographs for 
review are detailed in Exhibit F, the Radiographic Protocol. 

Process for Discontinuation of Subject Participation 
A Subject is considered enrolled after signing the Informed Consent Document, as described in Section 
5.3, Definition of Valid Subject Enrollment.  Subject participation may discontinue through screen 
failure, withdrawal, or death. In all instances of Subject discontinuation after obtaining Informed 
Consent, an End of Study/Withdrawal eCRF is required to be submitted to the Sponsor supporting the 
study Subject’s study discontinuation/withdrawal.   
 
8.4.1
Preoperative Screen Failures/Withdrawals 
 
A Subject may withdraw consent at any time during the study, even before surgery. The Investigator 
may withdraw the Subject preoperatively for safety reasons due to eligibility, for example, a patient 
may become pregnant during the window between giving consent and the planned surgery.  
 
In all instances when a Subject is declared a screen failure, the Subject Screening and Enrollment Log 
must be updated to reflect that Subject’s removal/withdrawal from the study.  Occasionally, a screen 
failure (after obtaining consent) will also require and an End of Study/Withdrawal eCRF submitted to 
DePuy Synthes.  Please refer to table 8-5 for further guidance. 
 
 

 
 
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Table 8-5: Pre-operative Screen Failure/Withdrawal examples 
Screen Failure   
Potential Subjects determined to be ineligible for study participation 
preoperatively, and should not be implanted with study device. 
Before consent and before surgery,  
patient is determined to be ineligible 
Update Screening/Enrollment Log  as 
“Screen Failure” and document 
reason 
Do not 
continue 
After consent and before surgery,  
Subject is determined to be ineligible 
Update Screening/Enrollment Log  as 
“Screen Failure” and document 
reason  
Submit Subject History and End of 
Study/Withdrawal eCRFs  to 
Sponsor 
Do not  
Continue 
Subject Withdrawal   Potential Subject withdraws consent prior to receiving the study implant.  
After consent but before surgery,  
patient withdraws consent 
Update Screening/Enrollment Log   
as “Withdrawal” and document 
reason 
Submit Subject History and End of 
Study/Withdrawal eCRFs  to 
Sponsor 
Do not 
continue 
8.4.2
Intra-operative Withdrawal 
The Investigator may withdraw the Subject intraoperatively for safety reasons, for example, it may 
become clear that the patient is not suited to receive the implant to be used for the study or the 
surgeon did not used the assigned instruments for whatever reason.  Please refer to table 8-6 for 
further guidance. 
 
 
 

 
 
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Table 8-6: Intraoperative Withdrawal example 
Intraoperative   Withdrawal: Potential Subjects to be withdrawn from study participation 
intraoperatively. 
Intraoperatively 
determined to be 
ineligible (example, 
ATTUNE primary implant 
not suitable) 
Update Screening/Enrollment Log  as “Intraoperative 
Withdrawal” and document reason 
Submit Subject History,  and End of 
Study/Withdrawal eCRFs  to Sponsor 
Inform Subject that they were withdrawn  
Do not 
continue 
Intraoperatively the 
assigned instruments are 
not used  to perform the 
proximal tibia and/or 
distal femoral resections 
Update Screening/Enrollment Log as “Intraoperative 
Withdrawal” and document reason   
Submit Subject History, Operative Details, Device 
Log and End of Study/Withdrawal eCRFs  to 
Sponsor.  Submit Adverse Event as applicable. 
Inform Subject that they were withdrawn 
Do Not 
continue 
Intraoperatively the 
ATTUNE  implant is 
attempted but not 
retained 
Update Screening/Enrollment Log  as “Intraoperative 
Withdrawal” and document reason 
Submit Subject History, Operative Details, Device 
Log and End of Study/Withdrawal eCRFs  to 
Sponsor. 
Submit Adverse Event as applicable. 
Inform Subject that they were withdrawn 
Do Not 
continue 
 
8.4.3
Enrollment Replacement Rules 
Since Subjects are enrolled at the time of consent, any Subject that is withdrawn preoperatively or 
intraoperatively prior to receiving the study implant will be replaced with subsequent Subjects.  
Overall, the number of Subjects who received an ATTUNE implant using a study device (with either 
the RUI or SUI instrumentation), across all sites must meet the sample size of 88. 
8.4.4
Postoperative Withdrawal 
A postoperative withdrawal is a Subject who has signed the Informed Consent Document, has 
received an ATTUNE implant using a study device (with either the RUI or SUI instrumentation), and is 
later withdrawn from study participation (i.e., withdrawal of consent, revision, death, etc.). Please 
refer to table 8-7 for further guidance.  
 
All data obtained up to the date of withdrawal will be included in the clinical analysis.   
 
 

 
 
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Table 8-7: Post-operative Withdrawal Examples 
Example 
Action 
Follow-Up 
Subject 
withdraws 
consent  
• 
Study site documents Subject’s request 
for withdrawal from study. 
• 
Complete End of Study/Withdrawal 
eCRF  
• 
Update Screen/Enrollment Log. 
Do not continue 
Death 
• 
Complete Adverse Event eCRF 
• 
Complete End of Study/Withdrawal 
eCRF 
• 
Update Screen/Enrollment Log 
Do not continue 
Revision  
See Section 8.4.5 and Table 8-8 Revision/Re-
Operation Examples 
Do not continue if metal tibial 
base or femoral component 
revised.  Continue to follow if 
neither the metal tibial or 
femoral components have been 
revised.  
8.4.5 
Revisions / Reoperations 
A revision is defined as a surgical procedure of the affected knee where one or more of the TKA 
components (femoral and/or tibial base, polyethylene insert, or patella polyethylene resurfacing 
component) are removed.  Should it be necessary for the Subject to undergo a revision of either the 
femoral or metal tibial base components between the date of the enrollment and the completion of 
the study data acquisition, the Subject is to be withdrawn from study participation.  Thus, both an 
Adverse Event (AE) eCRF and an End of Study eCRF would be completed.  If possible, long leg x-rays 
should be captured prior to revision to permit analysis of the primary objective. 
 
A re-operation is defined as any surgical procedure of the affected knee in which no TKA components 
are removed.  These subjects are not to be withdrawn.  An Adverse Event (AE) eCRF must be 
completed.  Several examples for revision/reoperations are shown in Table 8-8.   
 
 
 

 
 
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Table 8-8: Revision/Re-operation Examples 
Revision 
A surgical procedure of the affected knee where one or more of the TKA 
components (femoral and/or tibial base, polyethylene insert, or patella 
polyethylene resurfacing component) are removed.    
 
If either femoral or metal tibial base components are revised, the Subject is to 
be withdrawn from study participation. 
Example 
Actions 
Follow Up 
Removal or revision of either metal tibial 
base and/or femoral component 
Complete Adverse Event eCRF  
Complete End of Study/Withdrawal 
eCRF 
Do not 
continue 
Tibial polyethylene exchange  
Complete Adverse Event eCRF  
Continue 
Revision of a patella which was resurfaced 
in the index TKA 
Complete Adverse Event eCRF 
Continue 
 
 
 
Re-operation 
Any surgical procedure of the affected knee in which no TKA components 
(femoral and/or tibial base, polyethylene insert, or patella polyethylene 
resurfacing component) are removed. 
Example 
Actions 
Follow Up 
Irrigation & debridement without tibial 
insert exchange 
Complete Adverse Event eCRF 
 
Continue 
Resurfacing of previously unresurfaced 
patella 
Complete Adverse Event eCRF 
 
Continue 
8.4.6 
Minimization of Subjects Lost to Follow-up 
Although follow-up compliance is essential to study quality, some Subjects may not be able or willing 
to return for follow-up evaluations as prescribed in the protocol.  Given the short duration of follow-
up in this study, this is not expected to occur often.   
 
Sites should make every effort to ensure complete follow-up whenever possible through phone calls 
and written requests to a Subject.  Each Investigator will maintain a record of communications and/or 
attempts at communications in the source documentation. This record will be used to obtain an 
indication or report on the current status of the study device (e.g., still in place and functioning 
satisfactorily; painful; revised; etc.).   
 
A Subject can be classified as “lost-to-follow-up” and  withdrawn from the study only after the visit 
window has closed and the site has documented in the medical record at least two (2) unsuccessful 
attempts of contact.   Please refer to table 8-9 for further guidance.  
 
 

 
 
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Table 8-9: Recommended Contact Attempts 
If 
Then 
A response is not received from phone calls 
the Investigator should send a  letter to the 
Subject explaining the follow-up agreement per 
the informed consent. 
A response is not received from the Investigator’s 
letter and/or all attempts to contact the Subject 
are unsuccessful or the Subject is contacted and 
chooses to withdraw from the study 
the End of Study/Withdrawal eCRF will be 
completed and will specify why the Subject is no 
longer participating in this study. 

 
 
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9
RISK ANALYSIS 

Adverse Event Determination 
Adverse Event determination will be done by the Principal Investigator, or appropriate designee. 

Non-Reportable Adverse Events - Sponsor ONLY 
There are immediate post-operative events that are changes from the baseline condition of the 
Subject, but are expected events resulting from the surgery. If these events occur, they should be 
recorded in the Subject’s medical record per standard medical practice, but it is not necessary to 
report them as AEs in the eCRF or to the Sponsor (please refer to Exhibit E-2 for listing of Non-
reportable AEs).   

Study Related Risks / Reportable Adverse Events 
Any surgical procedure poses a potential risk and the procedures undertaken as part of this clinical 
investigation are no exception.  
 
The surgical risks associated with the use of the Single Use Instruments for implanting the ATTUNE 
cemented primary TKA system are similar to those with the Re-usable instruments for implanting the 
ATTUNE cemented primary TKA system when used for the same clinical indication.   Additionally, the 
surgical risks are the same whether or not the Subject participates in this study for a number of 
reasons:  
 
x
It is assumed that the Investigator and patient have mutually decided that primary TKA is an 
appropriate treatment for the patient’s condition and that the patient would have a TKA 
whether or not they choose to take part in this study; 
x
The same implant is used with both RUI and SUI instrumentation; 
x
Both types of instruments have to meet the same design control requirements/standards 
prior to market availability as do all surgical instruments on the market; 
x
Participating Investigators in this study are already implanting the ATTUNE TKA system with 
the re-usable instruments and will obtain training on the single use instruments prior to 
enrolling study Subjects. 
 
Study related risks are categorized as those anticipated to be related to general surgical risks, total 
knee arthroplasty risks, or those potential risks associated with the study implant system. 
Unanticipated Adverse Events may occur as well.   
 
This protocol requires each site to report AEs, SAEs, ADEs, and SADEs to their respective IRB/EC per 
their IRB/ECs respective requirements 
 
A summary of risks is described below, please refer to the printed IFU for additional details (Exhibit 
D). 
 
A. General Surgical Risks  

 
 
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General surgical risks and post-operative adverse events can occur with any surgery and include, but 
are not limited to:   
• 
Anesthetic complications/reactions 
• 
Bleeding and/or excessive blood-loss 
• 
Transfusion reaction 
• 
Post-operative infection 
• 
Vascular injury  
• 
Delayed wound healing 
• 
Deep vein thrombosis (DVT) 
• 
Nerve injury 
• 
Death 
 
B. Risks Associated with Total Knee Arthroplasty Procedure/Study Device/Instruments  
 
Potential adverse events associated with primary total knee arthroplasty include, but are not limited 
to: 
• 
Early or late loosening of the prosthetic component(s) 
• 
Tibial subsidence 
• 
Bending, cracking, fracture, deformation of the prosthetic components 
• 
Excessive wear of the polyethylene articulating surface 
• 
Progressive bone resorption (osteolysis) as a result of foreign-body reaction to wear debris 
• 
Early or late infection 
• 
Delayed wound healing or wound dehiscence 
• 
Pain 
• 
Dislocation or joint instability of the knee 
• 
Subluxation of the knee 
• 
Flexion contracture 
• 
Varus-valgus deformity 
• 
Malalignment 
• 
Decreased range of motion 
• 
Leg length discrepancy 
• 
Soft tissue impingement or damage 
• 
Bone fracture(s) 
• 
Nerve damage 
• 
Localized swelling 
• 
Vascular injury 
• 
Temporary or permanent neuropathies 
• 
Cardiovascular disorders including venous thrombosis, pulmonary embolism, or myocardial 
infarction 
• 
Histological reactions resulting in inflammation 
• 
Metal sensitivity 
• 
Corrosion of metal components (the significance and long-term implications are uncertain 
and await further clinical evidence and evaluation) 
• 
Re-usable or single use instrument breakage 

 
 
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
Minimization of Risk 
Risks have been minimized by designing the  device under evaluation (total knee arthroplasty surgical 
instruments) to be similar to commercially available total knee arthroplasty surgical instruments used 
for the same indication. The ATTUNE surgical instruments have been functionally tested to verify 
performance characteristics and biocompatibility.  In addition, only trained orthopaedic surgeons with 
expertise in treating this condition will participate in this study. 
Investigators should refer to the ATTUNE implant system package insert for additional information 
and instructions for use (Appendix D) and the surgical technique (Appendix B). 
 
The Sponsor will further minimize the identified and/or emergent risks throughout the study, by 
reviewing the reported complications and adverse effects.  All SAEs, SADEs, ADEs, UADEs and USADEs 
will be reviewed and evaluated by the Medical Monitor assigned to this project. 
 

Benefit Analysis 
There are no potential benefits to study Subjects from participation in this study. The knowledge 
gained from this investigation may help future TKA patients. 

 Adverse Event  
9.6.1
Categories and Definitions 
Table 9-1: Adverse Event Categories 
ADVERSE 
EVENTS 
Non-Device 
Related 
Device- and/or Procedure-related 
Non-Serious 
Adverse Event 
(AE) 
Adverse Device Effect 
(ADE) 
Serious 
Serious Adverse 
Event 
(SAE) 
Serious Adverse Device Effect 
(SADE) 
Anticipated 
Unanticipated 
Anticipated Serious 
Adverse Device Effect 
(ASADE) 
Unanticipated Serious 
Adverse Device Effect 
(USADE) 
 
Table 9-2: Adverse Event Definitions 
Term 
Details 
Adverse Event 
(AE) 
Any untoward medical occurrence, unintended disease or injury, or untoward 
clinical signs (including abnormal laboratory findings) in subjects, users or other 
persons, whether or not related to the investigational medical device.  
 
Adverse Event is synonymous with complication or medical event. 

 
 
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Term 
Details 
Serious 
Adverse Event 
(SAE) 
 
An Adverse Event that: 
leads to death, 
leads to a serious deterioration in the health of the subject that 
o resulted in a life –threatening illness or injury, 
o resulted in an impairment of a body structure or a body function,  
  required in-patient hospitalization or prolongation of existing  
  hospitalization, resulted in medical or surgical intervention to prevent 
  permanent impairment to body structure or a body function, leads to  
  fetal distress, fetal death or a congenital abnormality or birth defect. 
 
Note:  Planned hospitalization for a pre-existing condition, or a procedure 
required by the CIP, without serious deterioration in health, is not considered a 
serious adverse event. 
Adverse 
Device Effect 
(ADE) 
An adverse event related to the use of an investigational medical device. This 
definition includes any event resulting from insufficiencies or inadequacies in the 
instructions for use or the deployment of the device. This definition includes any 
event that is a result of a user error. 
Anticipated 
AE 
An effect which by its nature, incidence, severity or outcome has been previously  
   identified in the Instructions for Use for the medical device. 
Anticipated 
Adverse 
Device Effect 
(AADE) 
An adverse event related to the use of an investigational medical device is 
previously identified in nature, severity, or degree of incidence in the current 
version of the Instructions for Use.  This definition includes any event resulting 
from insufficiencies or inadequacies in the instructions for use or the deployment 
of the device. This definition includes any event that is a result of a user error. 
Unanticipated 
Adverse 
Device Effect 
(UADE) 
An adverse event related to the use of an investigational medical device not 
previously identified in nature, severity, or degree of incidence in the current 
version of the risk analysis report.  This definition includes any event resulting 
from insufficiencies or inadequacies in the instructions for use or the deployment 
of the device. This definition includes any event that is a result of a user error. 
Serious 
Adverse 
Device Effect 
(SADE) 
An adverse event related to the use of an investigational medical device that has 
resulted in any of the consequences characteristic of a serious adverse event.  
 
Anticipated 
Serious 
Adverse 
Device Effect 
(ASADE) 
 
A serious adverse device effect which by its nature, incidence, severity or 
outcome has been identified in the current version of the Instructions for 
Use/risk analysis report.  This definition includes any event resulting from 
insufficiencies or inadequacies in the instructions for use or the deployment of 
the device. This definition includes any event that is a result of a user error. 

 
 
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Term 
Details 
Unanticipated 
Serious 
Adverse 
Device Effect 
(USADE) 
 
A serious adverse device effect which by its nature, incidence, severity or 
outcome has not been identified in the current version of the risk analysis.  This 
definition includes any event resulting from insufficiencies or inadequacies in the 
instructions for use or the deployment of the device. This definition includes any 
event that is a result of a user error. 
 
Site 
Awareness 
(Date of AE 
Awareness) 
The day, month and year that the study site becomes aware of information from 
any source that reasonably suggests that an Adverse Event has occurred.  
 
Note: This date may or may not correspond to the date of onset.  The date of 
awareness is critical to reporting timelines (see Section 9.8). 

Adverse Event Reporting Guidelines 
9.7.1
AE Reporting by Site to the Sponsor 
For AEs to be reported through this protocol, a record including details of site awareness, the nature, 
onset, duration, seriousness, relationship to the device, relationship to the procedure, treatment 
given (if any) and outcome, will be entered into the subject’s eCRF.   
 
For this study, only serious AEs and those AEs related or possibly related to either the device and/or 
the procedure are to be reported to the SPONSOR (Please see Figure 9-1).  
   
The outer circle (Figure 9-1) represents all AEs that could possibly be observed.  For this protocol, not 
all AEs are required to be reported.  The below list are the reportable AE’s that must be recorded on 
the eCRF and submitted to the Sponsor by entering into EDC per the reporting timelines detailed 
below:   
 
 
x
Any AE classified as ‘Serious’ (SAEs, SADEs, SUADEs) to include Serious procedure related AEs 
– report to Sponsor as soon as able but no later than 72 hours from site awareness*. 
x
All UADEs – report to Sponsor as soon as able but no later than 72 hours from site 
awareness*. 
x
All non-Serious Device Related (ADE) – report to Sponsor as soon as able but no later than 2 
weeks from site awareness*. 
x
All non-Serious Procedure Related AEs, except for selected events (see Exhibit E-2: Non-
reportable list) -  report to Sponsor as soon as able but no later than 2 weeks from site 
awareness*. 
 
*NOTE:  Not meeting the above reporting timelines to the Sponsor will result in a protocol 
deviation.  
 

 
 
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 Figure 9-1: Adverse Event Reporting for this Study Protocol 
 
 
 
 
 
Pre-existing medical conditions or symptoms reported prior to the surgical event are not to be 
recorded as AEsE.  The only exception would be in the event there is an exacerbation of a pre-existing 
medical condition or symptom(s) in the post-operative time frame, then an AE must be reported.   
  
AEs are reported beginning from surgery and until Subject participation has ended (study completed 
or consent withdrawn). AEs must be followed to resolution, or until the study completion or consent 
withdrawal. When a Subject ends participation in the study (either study completion or consent 
withdrawal) an AE must be designated either as “resolved” (end date must be provided), or as 
“ongoing.” 
 
Subjects should be encouraged to report AEs spontaneously and may volunteer AE information at any 
time. At each evaluation, the Investigator will determine whether a study reportable AE has occurred. 
If it is determined that such an AE has occurred, the Investigator should obtain all the information 
required to complete the appropriate AE form eCRF. If an event occurs at an outside institution, the 
Investigator should attempt to obtain, if possible, required AE information. 
 
The Investigator will record the nature, severity, treatment and outcome of the AE, and will determine 
their association to the device and/or the study procedure. 
                                                          
E An example could be pre-existing contralateral knee osteoarthritis with a planned TKA intervention 
after the index knee surgery. 
 

 
 
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
Determination of AE Severity 
Refers to the intensity of the symptoms experienced by the study subject and can be used with any 
event, without regard to whether or not the adverse event is classified as Serious. 
 
Please refer to Table 9-3 in determining intensity of symptoms of the reportable AE. 
 
Table 9-3: Definitions of Severity of AEs 
Term 
Description 
Severe 
Symptoms 
The intensity of the symptoms  are severe and poorly tolerated, requiring 
intervention, and significantly affect activities of daily life; or place the Subject 
at immediate risk or harm. 
Moderate 
Symptoms 
The intensity of the symptoms are moderate.  Intervention is either noninvasive 
or not indicated.  Activities of daily living can be sustained.   
Mild Symptoms The intensity of the symptoms are mild, transient or  asymptomatic.  
Intervention is not indicated. Clinical or diagnostic observations only and no 
impairment of normal activity. 

Determination of Relationship to Device and/or Procedure 
The determination whether the AE is related to the device and/or procedure will be based upon 
whether a causal relationship between the device or procedure and the AE is at least a reasonable 
possibility, i.e., the relationship cannot be ruled out. A causal relationship cannot be ruled out if, in 
the medical judgment of the Investigator, the effect follows a reasonable temporal association with 
the use of the device and/or is confirmed by the improvement of the effect upon discontinuation of 
the clinical use of the device, and/or the effect is not reasonably explained by the Subject’s clinical 
state.  
 
Please refer to Table 9-4 in determining if an AE is related to the study device or procedure. 
 
 Table 9-4: Definitions of Device-Relatedness and Procedure Relatedness for AEs 
Term 
Description 
Definitely 
The relationship between study device or procedure and event does exist 
and is confirmed upon further investigation by the Investigator 
Probably  
The relationship between study device or procedure may exist if other 
causes are unlikely 
Possibly 
The relationship between study device or procedure could exist; however, 
other causes are possible 
Remote 
Possibility 
There is minimal chance that a relationship exists between the study device 
and/ or procedure  
Definitely Not 
There is definitely no relationship between study device or procedure and 
the event 

 
 
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The AE Reporting flowchart (Figure 9-2) illustrates a series of questions a site must consider when 
determining whether a given clinical observation must be reported and which AE’s do not need to be 
reported for this CIP.   
 
 
 
Figure 9-2: AE Reporting Flowchart 
 
NO
NO
YES
YES
YES
NO
NO
Clinical Observation
NEW CONDITION
Is it serious?
New condition 
Or pre-existing 
condition?
Report to DePuy 
within 72 hrs of site 
awareness
& Ethics Comm
(per local requirements)
PRE-EXISTING
Exacerbation of 
previous 
condition?
DO NOT REPORT
Is AE related to device 
or procedure?
YES
Is observation included on 
“Do Not Report List”?
(Exhibit E)
Report to DePuy 
within 2 weeks of site 
awareness
& Ethics Comm
(per local requirements)
 
 
 

 
 
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9.7.2 
Institutional Review Board (IRB) / Ethics Committee (EC) Reporting. 
This protocol requires each site to report AEs, SAEs, ADEs, SADEs and UADEs to their respective 
IRB/EC, per their IRB/EC’s respective requirements. 
9.7.3 
Regulatory reporting requirements  
Device related AEs will be reviewed by DePuy Synthes and reported if applicable to the appropriate 
regulatory body.  

 
 
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10 STATISTICAL METHODOLOGY 
Statistical analysis will be performed using SAS (SAS Institute Inc., SAS Campus Drive, Cary, North 
Carolina 27513) software version 9.3 or higher.  Any further software that may be necessary will be 
described in the final study report.  
 
 Study Design 
This study is a prospective, comparative, sequential, non-randomized, multi-center, controlled clinical 
investigation; see Section 7 for further details on study design.  Reassignment of Subjects from one 
site to another may occur under circumstances defined in Section 7. The schema defined for 
reassigning Subjects is designed to keep RUI and SUI treatment groups balanced and to minimize 
potential bias.  
 
 Treatment Assignment 
See Section 7. 
 
Randomization will not be employed in this study.  Each site will consecutively enroll all RUI cases 
prior to enrolling consecutive SUI cases.     
 
 Levels of Significance 
Unless otherwise stated, confidence intervals will be 2-sided 95% confidence intervals, and p-values 
below 0.05 will be deemed to be statistically significant. Unless otherwise stated, there will be no 
adjustment of significance levels because of testing multiple hypotheses. 
 Interval Windows 
The pre-operative window will be from 180 days prior to surgery up to the day of surgery, which is 
defined to be Day 0. The 3 month post-operative interval will be defined as 90 days plus or minus 60 
days.  
 
Table 10-1: Interval Windows 
Follow-up [days] 
Pre-Op 
Surgery 
Immed 
Post-op 
3 Month 
-180 to  0 
0 
1 to 29 
30 to 150 
 

 
 
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 Handling of Missing Data 
Subjects with no post-op alignment data at 3 Months post-op will be considered missing at random. 
Only actual Subject data which is collected will be utilized in analyses; no imputation of missing data 
will be performed. 
 Primary and Secondary Endpoints 
The primary endpoint in this study is mechanical axis alignment, and the primary endpoint analysis 
will be to determine whether the alignment achieved with SUI instrumentation is non-inferior to the 
alignment achieved with RUI instrumentation. Mechanical axis alignment is defined as the angle 
between the line drawn from the center of the femoral head through the center of the knee and  line 
drawn from the knee center to the ankle center.  Mechanical axis alignment will be measured from 
weight bearing long-leg (51”) Anteroposterior (AP) radiographs, taken approximately 90 days post-op 
(when Subject has reached full knee extension, within 5 degrees) and read by an independent 
radiographic reviewer. The non-inferiority margin was set at 1.5o because the study team felt this was 
the maximum non-meaningful difference when thinking about absolute mechanical axis alignment 
differences between the RUI and SUI groups. A standard deviation between 1.5o to 2o is anticipated 
based on previous studies conducted by the sponsor that had the same primary endpoint (Protocol 
ID #’s 04023, 08003).  
 
The secondary endpoints are as follows: 
 
x
To compare alignment achieved with SUI vs. RUI of individual components in the frontal and 
sagittal planes, specifically: distal femoral varus-valgus (FM) , proximal tibial varus-valgus 
(TM),  femoral component flexion and tibial slope. 
To compare the type and frequency of  adverse events, from the time of consent through to 
withdrawal of a Subject or the end of the study (includes pre-operative, intraoperative and 
early postoperative device-related adverse events), between the SUI and RUI instrument 
groups. 
 
Exploratory endpoints 
x
To compare SUI and RUI operating room times.  Specifically the duration of the four key steps 
in the procedure (possibly overlapping) will be compared.  See Table 8-3. 
x
To determine whether SUI provides opportunity to reduce the incidence of minor procedural 
obstacles during the time in the OR.  
x
To compare Surgeon satisfaction of SUI instrumentation to RUI instrumentation. 
 Hypotheses 
The null (Ho) and alternate (HA) hypotheses are as follows:  
Ho: μSUI ≥ μRUI + 1.5o 
HA: μSUI < μRUI + 1.5o, 
where μRUI is the absolute value of mechanical axis alignment angle sample mean of Subjects being 
operated upon using reusable instruments (RUI), and μSUI is the absolute value of mechanical axis 
alignment angle sample mean of Subjects being operated upon using single use instruments (SUI). 
 

 
 
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 Analysis Sets 
Below is a flow chart showing the analysis sets. 
 
Figure 10-1:  Analysis Populations Flowchart 
 
 
The primary analysis dataset will be the Per Protocol population. 
 
Adverse event comparisons will be conducted using the Safety population. 
 
 Sample Size Justification  
The primary endpoint will be a non-inferiority test of absolute value mechanical axis alignment, 
comparing single use instrument results with reusable alignment results.  
 
A standard deviation of  1.870o for this absolute value of mechanical axis was established in a previous 
DePuy Study (ID # 04023). Assuming that this is a good estimate, a sample size of 35 per group will 
yield statistical power of 95% for a 1-sided test with a non-inferiority margin of 1.5o and α = 0.05.  This 
power estimate was calculated with the following SAS code:  
 
 
6DIHW\3RSXODWLRQ
All cases that received the Attune device and the assigned instruments were used.  

&RQVHQWHG(QUROOHG3RSXODWLRQ
All cases consented to participate in this study 
3HU3URWRFRO3RSXODWLRQ
All cases from the Safety Population that did not have major protocol violations.  
,QFOXVLRQ([FOXVLRQ9LRODWLRQV
1 ".QHHV
PLQXV
$VVLJQHGLQVWUXPHQWVZHUHQRWXVHG
1 ".QHHV
PLQXV
'LGQRWUHFHLYHWKH$WWXQHGHYLFH
LQFOXGLQJFDVHVWKDWGLGQRWKDYHVXUJHU\
1 ".QHHV
PLQXV
Demographic & Adverse Event Analysis 
Adverse Event Narrative of cases that 
drop out of Safety Population 
Primary, Secondary, and Exploratory Analysis 

 
 
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Figure 10-2: SAS Code for Power Estimation 
proc power;   
twosamplemeans 
 
meandiff= 1.5        
 
stddev=1.87       
 
groupweights=(1 1)    
 
power= .         
 
alpha=0.05            
 
sides=1           
 
ntotal=70;        
run; 
 
This sample size is increased to 44 per group to account for attrition and possible problems with xray 
quality. 
Analysis Plan  
The primary endpoint is a non-inferiority test of mean absolute mechanical axis angle, comparing 
single use and reusable instrument results with a non-inferiority margin of 1.5o using a 1-sided 
independent means t-test and α = 0.05.  The primary endpoint analysis null hypothesis will be rejected 
and non-inferiority will be concluded if the 1-sided upper 95% confidence limit for μSUI - μRUI is less 
than 1.5o.   
 
Preoperative demographics will be compared to determine whether differences exist between 
treatment groups. Age and BMI will be compared using two-tailed independent means t-tests. Gender 
distribution will be compared with a Fisher’s exact test. 
 
Secondary analyses include: 
x
Tests of differences for individual component alignment in the frontal and sagittal planes, 
specifically: distal femoral varus-valgus (FM), proximal tibial varus-valgus (TM),  femoral 
component flexion and tibial slope using (independent means two-tailed t-tests). 
x
The types and frequencies of adverse events will be tabulated for all enrolled knees. The 
proportion of each complication will be compared using a Fisher’s Exact Test (2 x 2 only) and 
Chi-square. 
 
Exploratory analyses will be conducted to see if SUI improves OR efficiency compared to conventional 
(RUI) instruments.  Exploratory analyses will also be conducted to investigate OR step times,  inter-
site differences in OR times, and issues that potentially introduced delays or interruptions in the 
surgical flow.   
 
The Following Table presents a summary of the planned statistical tests:  
 
 
 

 
 
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Table 10-2: Planned statistical comparisons 
Comparison 
Purpose 
Expected Result 
Mean absolute mechanical axis non-
inferiority 
Primary efficacy 
SUI Non-inferior to RUI 
Demographic comparisons 
Test comparability 
No difference 
Distal Femoral Varus-Valgus (FM) 
Secondary efficacy 
No difference 
Proximal Tibial Varus-Valgus (TM) 
Secondary efficacy 
No difference 
Femoral flexion  
Secondary efficacy 
No difference 
Tibial slope 
Secondary efficacy 
No difference 
OR Efficiency 
Exploratory Analysis 
No difference  
Interim Analysis  
No interim analyses are planned for the purpose of stopping the study early. 
 

 
 
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11 DEVICE DESCRIPTION  
All products used in this CIP have the appropriate regulatory approval, FDA clearance/approval for 
commercial distribution and bear the CE mark.  The ‘devices’ under study are the surgical instruments. 
 Instruments 
The instruments to be used in this study are detailed below. Different sets of instruments will be used 
for each treatment group of this study. Please refer to Exhibit B, Surgical technique for details. 
11.1.1 Reusable Instruments 
The ATTUNE Reusable Instruments (INTUITION), as used on the Control group, will be used on multiple 
patients, going through a process of decontamination and sterilization after each surgical procedure 
in preparation for the next procedure. Reusable instruments are manufactured from a combination 
of engineering grade polymers and metals and are supplied non-sterile.   
11.1.2 The ATTUNE Single Use Instruments (SUI)  
The ATTUNE Single-Use Instruments (SUI), which are also referred to as SOLO, as used on the 
Treatment group, will be used on a single patient and then disposed of. Single-Use instruments are 
manufactured from engineering grade polymers and supplied sterile packed to hospitals.  Kits consist 
of 5 packs, which contain all of the necessary instruments to perform a Total Knee Arthroplasty.  The 
pack details are outlined in Table 11-1 below. Once a procedure is complete the packs of instruments 
are disposed of in clinical waste.  Details of the Packs and their function are outlined below. 
Table 11-1:  Detailed Instrument Information by Pack 
Single Use Instruments:  Complete set is delivered in 5 Packs 
1 – Primary Cuts    
      & Sizing 
Indication:  Enables distal femoral and proximal tibial cuts, plus sizing of both 
femur and tibia. 
2 – Tibial  
      Preparation  
Indication: Provided in 6 sizes, with one pack being opened once the patient 
anatomy is defined. 
3 – Femoral  
      Finishing 
Indication: Provided for both CR and PS configurations, each available in 6 
sizes. The specific size and configuration dictates which pack is opened. 
4 – Patella  
      Preparation 
Indication:  Used to size the patella and fix the patella implant component. 
5 – Pin Pack 
Indication:  Used for pinning throughout the procedure. 
 Implants 
All components will be cemented.  The implants specified in Table 11-2  below will be used for all 
study Subjects during this investigation. The intended purpose, indications, contraindications and 
population are described in the Instructions for Use (IFU), see Exhibit D. Product codes for each 
component are provided in Exhibit C.   

 
 
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Table 11-2: Detailed Device Information for ATTUNE Implants 
Device 
Component 
Component offerings 
 
Details 
Femoral 
Components 
Cruciate 
Retaining 
(CR) 
ATTUNE femoral components are available in cruciate retaining (CR) and posterior stabilized 
(PS) configurations. The femoral components are manufactured from cast Co-Cr-Mo alloy 
conforming to ASTM standard F-75. They are available in lefts and rights. Fourteen sizes are 
available including standard sizes 1-10 and narrow sizes: 3N, 4N, 5N, 6N. Femoral 
components are sterilized using gamma irradiation. They are available for cemented use 
only.    
The PS femoral components have a cam mechanism that articulates with a corresponding 
spine on the PS tibial insert.  
Posterior 
Stabilized 
(PS) 
Tibial Bases 
Fixed 
Bearing 
(FB) 
The FB tibial bases are manufactured from Co-Cr-Mo alloy conforming to ASTM standard F-
75. The proximal surface has a universal locking feature that is used for securing the FB tibial 
insert and permits up-sizing and downsizing. Ten sizes are available including 1-10.  The FB 
base is offered only in a keeled cemented version. The cemented components have a blasted 
finish to provide for enhanced cement fixation. FB Tibial Bases are sterilized using gamma 
irradiation. They are available for cemented use only.     
Rotating 
Platform 
(RP) 
The RP tibial bases are manufactured from Co-Cr-Mo alloy conforming to ASTM standard F-
75. The metal bases have a hollow, conical intramedullary stem. The flat superior surface of 
the base has a central hole continuous with the hollow conical medullary stem which receives 
the conical spike of the RP tibial insert components. The RP tibial insert component is not 
secured to the metal base, but rotates axially to maintain congruent contact with the femoral 
prosthesis.  Ten sizes are available including 1-10.  The RP base is offered only in a keeled 
cemented version. The RP base articulates with the RP CR and RP PS tibial inserts. The 
cemented components have a blasted finish to provide for enhanced cement fixation. RP 
Tibial Bases are sterilized using gamma irradiation. They are available for cemented use only.   
Tibial Inserts 
Fixed 
Bearing 
(FB) 
Cruciate 
Retaining 
(CR) 
The CR and PS tibial inserts are manufactured from UHMWPE and are available 
in sizes 1-10 and thicknesses from 5, 6, 7, 8, 10, 12, 14, 16, 18mm.  Additional 
thicknesses 20 & 22mm are available for the PS inserts. The distal surface has 
features that secure the insert to the FB tibial base.  Tibial inserts are sterilized 
using gas plasma sterilization.  The PS insert has a spine which articulates with 
the cam on the corresponding PS femoral component. 
Posterior 
Stabilized 
(PS) 
Rotating 
Platform 
(RP 
Cruciate 
Retaining 
(CR) 
CR and PS inserts are manufactured from UHMWPE and are available in sizes 1-
10 and thicknesses from 5, 6, 7, 8, 10, 12, 14, 16, 18mm.  Additional thicknesses 
20 & 22mm are available for the PS inserts.  RP inserts should be the same size 
as the selected femoral component.  The RP inserts articulate with the RP 
primary bases and should be within 2 sizes of the RP tibial base. Tibial inserts 
are sterilized using gas plasma sterilization.  The CR RP insert can be used with 
or without an intact PCL.   The PS insert has a spine which articulates with the 
cam on the corresponding PS femoral component. 
Posterior 
Stabilized 
(PS) 
Patellae 
Medial 
Offset 
Patellar components are manufactured from UHMWPE. They are available in two styles, 
medialized dome and medialized anatomic. They are available in 5 sizes with proportionally 
increasing thicknesses from 8.5 to 10.5 mm. They are available for cemented use only.  
Anatomic 
Bone 
Cement 
FOR US SITES:  DePuy CMW Antibiotic impregnated bone cement is not cleared for use in primary joint 
replacement in the United States and will constitute a protocol violation if it is used. See Figure 11-1 for 
guidance.  

 
 
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Figure 11-1 : Flowchart depicting regional considerations for permitted bone cement selection 
Study Site
Based in US?
Does Site use DePuy 
Synthes Bone Cement for 
Standard of Care?
Site Follow 
Standard of Care 
for Bone Cement 
Selection
Site MUST NOT 
use antibiotic 
bone cement
YES, US Site
YES
NO
NO, OUS Site

 
 
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12 INVESTIGATOR RESPONSIBILITIES AND GOOD CLINICAL PRACTICES  
In conducting this medical device clinical investigation the Investigator is responsible for:  
x
Ensuring that a clinical investigation is conducted according to the Declaration of Helsinki, 
applicable local regulations, the signed Clinical Trial Agreement, and the Clinical Investigation 
plan;    
x
Protecting the rights, safety, and welfare of Subjects under the Investigator’s care; and 
x
Ensuring the integrity of the data.  
 
Prior to the initiation of this clinical investigation, the Principal Investigator at each site globally will 
approve this Clinical Investigation Plan (CIP) by signing the signature page. This signature confirms 
that the clinical investigation will be performed in compliance with the CIP. 
 IRB/ Ethics Committee Approval 
All Principal Investigators must submit to their institution’s IRB/EC for initial review a copy of the 
clinical investigational plan (CIP) and a sample Informed Consent Document (ICD) provided by the 
Sponsor.  Many institutions request modification of the ICD to satisfy specific institutional 
requirements.  The use of a modified or unique Informed Consent Document is permitted provided 
that the document is reviewed and approved by the Sponsor.  Additionally, all translated consent 
forms require IRB/EC approval.  
 
All Principal Investigators must submit the Clinical Investigation for continuing review and any other 
additional required submissions to their IRB/EC according to their IRB/EC’s policies and procedures.  
 
Initial approval/favorable opinion and all continuing review approvals must be documented; originals 
of correspondence and approvals are to be filed by the Investigator and copies forwarded to the 
Sponsor.  
 Informed Consent   
The Principal Investigator is responsible maintaining source documents evidencing informed consent 
was obtained on study Subjects prior to their participation in the study.   
 
If an Investigator performs any study-specific data collection without obtaining informed consent, the 
Investigator will report such use to the Sponsor and the reviewing IRB/EC within 5 working days. 
For further details and a description of the Informed Consent process, please refer to Section 8.2.2, 
Subject Informed Consent. 
 Protected Health Information 
The Principal Investigator is responsible to inform study Subjects their personal data will be collected, 
processed, and confidentially maintained in accordance with local data privacy regulation and law. 
 
United States:  The Principal Investigator is responsible for taking the necessary steps to collect, 
process, and maintain confidentiality of the study Subject’s personal data in accordance with data 
protection legislation including the Health Insurance Portability and Accountability Act of 1996 

 
 
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(HIPAA). Subjects will be asked to sign an Authorization for Release of Personal Health Information 
(PHI) for the purpose of this investigation. This authorization may be combined with the ICD 
depending on local IRB preference.   
 
European Union:  The Principal Investigator is responsible for taking the necessary steps to collect, 
process, and maintain confidentiality of the study Subject’s personal data in accordance with 
provisions of the national transposition of the EU Data Protection Directive 95/46/EC or local 
equivalent legislation, for Investigational sites outside of the US. Data protection consent will be 
obtained from the Subjects as part of the informed consent process.   
 
Results from the Clinical Investigation may be published. However, Subject confidentiality will be 
maintained at all times and it will not be possible to identify individual Subjects from any data 
presented. 
 Subject Discontinuation from the Clinical Investigation   
Any Subject is entitled to discontinue/withdraw from this clinical investigation for any reason without 
obligation and/or prejudice to further treatment. In addition, the  Investigator may decide for reasons 
of medical prudence, to withdraw a subject.  
The  Investigator will clearly document the date and reason(s) for the Subject’s discontinuation from 
this clinical investigation in the eCRF and submit to DePuy Synthes Joint Reconstruction. 
Please refer to Section 8.4 Process for Discontinuation of Subject Participation for further details. 
 Source Documentation and Data Retention 
Each Investigator will maintain a complete, current and accurate case history (Source Documentation 
records) on each Subject according to the usual procedure at the Site. Case histories medical records, 
including progress notes, hospital charts, nurses’ notes, etc.  
Additional documents to be retained  include: 
x
Signed original Informed  Consent Form,  
x
Executed Authorization for Release of Personal Health Information (may be combined with 
Informed  Consent Form based on local IRB requirements) – not required outside USA.  
x
Completed Source Worksheets(if used), 
x
Results of relevant diagnostic and laboratory tests, 
x
Intraoperative and post-operative  complications and treatment, and 
x
Any other relevant information or documentation pertaining to the condition of the Subject. 
 
The Investigator should retain copies of all documents pertaining to this clinical investigation (for at 
least 5 years in the United Kingdom and for at least 3 years in the United States after this clinical 
investigation is completed, or according to institutional policy if longer.  In addition, if the Investigator 
moves/retires, etc., s/he should provide DePuy Synthes Joint Reconstruction with the name and 
address of the person who will be responsible for the Subjects’ clinical investigation related records.
 
The investigator agrees that the Sponsor’s employees or designees will have the right to audit and 
review pertinent medical records relating to this clinical trial. 

 
 
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 Record of Device Inventory  
Not applicable as this is a post-market study on an FDA cleared/CE marked product.  
 Case Report Form Completion and Data Submission 
Data will be captured within an electronic data capture system. 
Electronic Case Report Forms (eCRFs) will be used to collect and submit all Subject data once a Subject 
is enrolled in the study. Investigative study sites are asked to enter Subject data into the eCRFs 
preferably within 4 weeks from the time the Subject was seen for their scheduled study visit. 
 
Role-specific training on eCRF completion are included  via Learning modules and  are required to be 
completed by the Investigator(s) and study support staff prior to initiating Subject enrollment. 
 
The eLearning will be assigned by the Clinical Operations representative and training signoff 
documented within the EDC system.  
  
The personal data recorded on all documents, including copy documents, and within the EDC system, 
will be regarded as confidential. The Investigator will be responsible for the timing, completeness and 
accuracy of the details entered within the electronic data capture system.   All data entered in the 
database must have source documents in the Subject’s medical records.  
 
There are no patient-reported outcome measures used in this study.  
 
The protocol required data may be entered directly into the respective eCRF within the electronic 
data capture system by the Investigator or designee.   The respective eCRFs must be fully completed 
for each Subject.  The Investigator’s electronic signature will be obtained within the EDC system once 
all study data has been entered, cleaned, and coded (and at interim analysis if applicable).   Signoff 
can occur on a per form or per casebook level.  Any changes to the data will break the Investigator’s 
signature and signoff will need to be obtained again on the relevant data. 
 
Paper Source Worksheets may be provided and may be used (optional) to supplement data points 
that are not typically collected in the medical record..  These data will then be required to be 
transferred directly to the eCRF within the electronic data capture system for submission to the 
Sponsor.  If paper Source Worksheets are used, they must be stored in the Subject’s research record, 
as these will be considered source documents, please refer to Section 12.5.  Any errors on paper forms 
should be crossed out with a single stroke, initialed and dated. Typing correction fluid must not be 
used.  
 
The Investigator must record the Subject’s participation in this clinical investigation in the Subject’s 
clinic notes.  In addition, the Investigator must keep a separate list of all Subjects entered into this 
clinical investigation showing each Subject’s name, date of birth and assigned Subject number (for 
identification purposes).  A Patient Information log will be provided in the Investigator Site File for this 
purpose and remain at the site. 
 
The Investigator should retain copies of all documents pertaining to this clinical investigation 
(including source documentation, the informed consent document and any other documents to 

 
 
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identify the Subjects) for at least 5 years after this clinical investigation is completed.  In addition, if 
the Investigator moves/retires, etc., he should provide DePuy Synthes Joint Reconstruction with the 
name and address of the person who will be responsible for the Subjects’ clinical investigation related 
records. 
 
Data queries will be generated by the system at the time of data entry, if applicable.  Resolution of 
the queries will be the responsibility of the Investigator and investigation team members. Following 
completion of all data queries on each eCRF, the Investigator will be responsible for reviewing and 
confirming agreement to the data within the system. 
 
The platform software has been validated in accordance with 21 CFR Part 11, European Commission’s 
Directive on Data Protection and US Safe Harbor Certification. Prior to being released for data entry, 
validation of the study level components (i.e., data entry screens, associated edit checks and work 
flow) will be conducted in accordance with approved user acceptance testing procedures. Access to 
this system will be controlled so that only authorized users will have the ability to enter into the 
system. The system is considered a closed system according to 21 CFR Part 11 Electronic Records; 
Electronic Signatures.   
 
 Protocol Adherence 
The Investigator (s) agree to conduct the study in accordance with this protocol.  Prior to beginning 
the study, the Investigator (s) must sign the  protocol signature page. 
 
An Investigator must not make any changes in a study without first receiving approval from the 
Sponsor and IRB/EC, except when necessary to eliminate apparent immediate hazards to a Subject. 
 
With the exception of emergency situations, no deviations to this CIP will be permitted.  In the event 
of an emergency situation, the Principal Investigator must notify their DePuy Synthes clinical 
operations contact immediately.  A full written report of the situation must be forwarded to the 
IRB/EC who approved the original CIP and DePuy Synthes Joint Reconstruction within 10 working days 
of the event.  
 
 CIP Amendments 
If it becomes necessary to amend the Clinical Investigation then the nature of the amendment will be 
agreed between the Sponsor and the Principal Investigator(s) and this will be recorded with a 
justification for the amendment.  The appropriate IRB/EC, will be informed of any amendments.  
 
 Investigator Reporting Responsibilities 
In fulfillment of study related requirements, the Investigator is responsible for preparing and 
submitting complete, accurate, and timely reports as described below.  

 
 
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Table 12-1: Investigator Reporting Responsibilities 
Report 
Description 
Action 
Withdrawal of 
IRB/EC approval 
The Investigator will promptly notify the Sponsor of a 
withdrawal of approval by the reviewing IRB/EC or of the 
Investigator’s part in an investigation within 2 weeks. 
Preferably 
within 2 weeks 
Progress Report  
If required by your IRB/EC, the Investigator is responsible 
for submitting progress reports on the investigation to 
the reviewing IRB/EC. 
As required per 
your IRB/EC 
Reports of 
deviations from the 
investigational plan  
The Investigator will notify the Sponsor of any deviation 
from the Investigational Plan as soon as able.  
 
The Investigator will notify the IRB/EC of any deviation 
from the Investigational Plan per the IRB/EC 
requirements. 
Per IRB/EC 
requirements; 
at least annually 
Other 
The Investigator will, upon request of a reviewing IRB/EC 
or Sponsor, provide accurate, complete, and current 
information about any aspect of the investigation. 
As requested 
 
The Principal Investigator may delegate a qualified associate(s) to complete one or more of the above 
functions. However, the Principal Investigator retains the overall responsibility for Subject safety, 
proper conduct of the study including obtaining Subject Informed Consent, compliance with this study 
plan, and the collection of all required data. 
 
 
 

 
 
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Investigator Site File 
Each Investigator and all personnel from the investigational site must maintain accurate, complete, 
and current information about all aspects of this Clinical Investigation. This includes documentation 
relating to the Investigator’s participation, Subject information and correspondence: electronic, 
written, and verbal, relating to any aspect of the clinical investigation.  
 
The records are maintained in the Investigator Site File consisting of, but not limited to, 
correspondence with other participating Investigators, the reviewing IRB/ EC, and the Sponsor.  
 
Upon receipt of copies of changes or revision updates to the Clinical Investigation Plan (otherwise 
known as the Study Protocol) from the Sponsor, the Investigator will add the updated document and 
Revision Log to the Investigator File. The outdated version will be filed. 
Regulatory Requirements  
This clinical investigation is a post-marketing surveillance study to obtain additional data. The devices 
are FDA cleared/approved and CE marked products cleared for sale by the appropriate regulatory 
authority in the country(ies) in which this clinical investigation is to be conducted.   
Investigator Study Termination 
The Investigator may prematurely terminate the clinical investigation at any time. Should this be 
necessary, the procedures will be arranged on an individual clinical investigation basis after review 
and consultation by both parties. In terminating the clinical investigation, the Sponsor and the  
Investigator will assure that adequate consideration is given to the protection of the Subject’s 
interests, all documentation is archived per Section 12.5 and the appropriate bodies such as the 
IRB/EC are informed as appropriate.   

 
 
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13  SPONSOR OBLIGATIONS 
 IRB/EC Approval 
The Sponsor requires this Clinical Investigation Plan to be submitted to the IRB/EC for initial review 
and approval before implementation at each site.  Additionally, all protocol amendments must be 
submitted to the IRB/EC for review and approval before implementation. 
 
Each site is required to submit a copy of the IRB/EC initial approval.  Additionally, US sites are required 
to submit a copy of the IRB renewal(s), typically annually, to the Sponsor for filing in the study’s Trial 
Master File.  The site is to maintain the original documentation of the initial approval and annual 
renewals in the site’s Investigator Site File.   
 Investigator Training, Pre-Investigational Visit 
Prior to enrolling Subjects in this study, the Investigator and/or appropriate site personnel will be 
trained on the study protocol to include: 
x
the general aspects of study administration, 
x
all procedures in the protocol, and 
x
the procedure for e-data acquisition and transmission. 
 
The Sponsor will be offering hands on training to supplement professional education of the surgeon 
on the implant and surgical instruments, as needed.   
  Study Monitoring 
Sponsor oversight will be maintained per Sponsor policies and procedures.  On site monitoring will be 
done at the discretion of the Sponsor. Should a monitoring visit be required, the Sponsor will work 
with the site to determine the date(s).   
During the visit, the Sponsor and authorized Sponsor representatives shall be given access to all study 
records, to include study Subject  medical records.    
All study Subjects are required to sign the Informed Consent Document allowing access to and release 
of their personal health information.  
 Labeling 
Refer to Exhibit D for Product Labeling. 
 Sponsor Study Termination 
The Sponsor may prematurely terminate or suspend the clinical investigation as a whole or at an 
individual investigational site for significant and documented reasons.  Reasons for premature 
termination or suspension include, but are not limited to safety, inadequate recruitment, Principal 
Investigator issues, device related problems, alignment with business strategy or administrative 
issues. 

 
 
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In the event of the study being terminated, any enrolled Subjects that have not yet had the surgical 
procedure would be treated as per their surgeon's standard practice using implants and instruments 
of the surgeon's choice. All enrolled Subjects who have received an ATTUNE implant within the study 
would continue to be cared for by their surgeon according to his/her standard of care. No further 
study-related procedures or data collection would occur.  
 Sponsor Reporting Responsibilities 
The Sponsor is responsible for preparing and submitting complete, accurate and timely reports per 
Section 9.6.3. 
 Financial Agreement 
Funding of the clinical investigation will be  detailed in  a separate agreement between the Sponsor 
and the Institution where the clinical investigation is being conducted and the Principal Investigator 
(where permitted by the Institution). 
 Publication Policy and Public Disclosure 
The Sponsor is committed to publication of this study.  A multi-center publication will be completed 
prior to allowing individual sites to publish their own data.  Authorship decisions will be aligned with  
the International Committee of Medical Journal EditorsF.  All manuscripts including data from this 
study will be reviewed and approved by the Sponsor, and each author, prior to any submission. All 
authors must disclose financial or personal affiliations that could be considered conflicts of interest. 
  
The sponsor will register this study  on www.clinicaltrials.gov per  FDAAA regulations.   
 Insurance 
The Sponsor will secure and maintain in full force and effect, throughout the duration of the Clinical 
Investigation, clinical trial insurance in line with national regulations. The type of insurance for each 
participating site is detailed within the respective Clinical Trial Agreement or equivalent which will be 
executed before the start of Subject recruitment at that site. 
 
 
 
 
 
 
 
                                                          
F http://www.icmje.org/ 
 

 
 
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14 REFERENCES  
 
1. Krackow K.A. Serpe L. Phillips M.J. Bayers-Thering M. Mihalko W.M.  A new technique for 
determining proper mechanical axis alignment during total knee arthroplasty: Progress 
toward computer-assisted TKA.Orthopedics.  22(7)(pp 698-702), 1999. Date of Publication: 
1999. 
2. Wasilewski RC, Galante JO, Leighty R, Natarajan RN, Rosenberg AG. Wear patterns on 
retrieved polyethylene inserts and their relationship to technical considerations during total 
knee arthroplasty. Clin Orthop; 299: 31-43, 1994. 
3. Chauhan SK. Scott RG. Breidahl W. Beaver RJ. Computer-assisted knee arthroplasty versus a 
conventional jig-based technique. A randomised, prospective trial. J Bone Joint Surg,, 86 
B(3):372-7, 2004 Apr 
4. Stulberg SD, Loan P, Sarin V: Computer-assisted navigation in total knee replacement: Results 
of an initial experience in thirty-five patients. J Bone Joint Surg, 24-A Supplement 2: 90-98, 
2002. 
5. Barrack et al: Component Rotation and Anterior Knee Pain after TKA. Clin Orthop Rel Res,392: 
46-55, 2001. 
6.  Berger RA, Rubash HE, Seel MJ, Thompson WH, Crossett LS. Determining the rotational 
alignment of the femoral component in total knee arthroplasty using the epicondylar axis. 
Clin Orthop Rel Res, 286:40-7, 1993. 
7. Ishii Y. Ohmori G. Bechtold J.E. Gustilo R.B. Extramedullary versus intramedullary alignment 
guides in total knee arthroplasty.Clinical Orthopaedics and Related Research.  (318)(pp 167-
175), 1995. Date of Publication: 1995. 
8. Overdyk F.J. Harvey S.C. Fishman R.L. Shippey F. Successful strategies for improving operating 
room efficiency at academic institutions. Anesthesia and Analgesia.  86(4)(pp 896-906), 1998. 
Date of Publication: Apr 1998. 
9. Weinbroum A.A. Ekstein P. Ezri T.Efficiency of the operating room suite. American Journal of 
Surgery.  185(3)(pp 244-250), 2003. Date of Publication: 01 Mar 2003. 
10. David M. Friedman, Suzanne M. Sokal, Yuchiao Chang, David L. Berger.  Increasing Operating 
Room Efficiency Through Parallel Processing. Ann Surg. 2006; January; 243(1): 10–14. 
11. Ricketts D. Patterson M. Harries W. Hitchin D. Hartley J. An orthopedic theatre timings survey. 
Annals of the Royal College of Surgeons of England.  76(3)(pp 200-204), 1994. Date of 
Publication: 1994. 
12. Frost 
& 
Sullivan. 
European 
Markets 
for 
Orthopaedic 
Surgical 
Instruments. 
www.researchandmarkets.com Jan 2007. 
13. www.healthcareaz.org/resources/res.aspx/Resource/resourceFilename/529/single_use-
instruments.pdf 
14. Morrison J.M, Jacobs V.R: Replacement of Expensive, Single-use Instruments With Old-
fashioned Surgical Techniques for Improved Cost-effectiveness in Laproscopic Hysterectomy.  
15. Hamaguchi T, Noguchi-Shinohara M,  Nakamura Y, Sato T, Kitamoto T. Opthalmic Surgery in  
Prion Diseases. Emergency Infectious Diseases. Vol.13. No.1. January 2007. 
16. Lau H: Endoscopic Extrapeitoneal Inguinal Hernioplasty: Single-use and Reusable Instruments. 
2006.15.109-115. 
 

 
 
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17. International Standard Organization 14155.  Second Edition 2011-2-01.  Clinical investigation 
of medical devices for human subjects – Good clinical practice. 

 
 
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15 CLINICAL INVESTIGATIONAL PLAN EXHIBITS 
Exhibit 
Description of Exhibit  
A 
Sample Case Report Forms 
B 
Surgical Technique 
C 
Implant Product Codes  
D 
Instructions for Use (IFU)  
E 
Adverse Events:  Tips & Pearls 
• 
Listing of Non-reportable Adverse Events 
• 
Preferred Terms for Select TKA Related Adverse Events 
• 
Flowchart for AE reporting 
F 
Radiographic Protocol