Prospective Multicenter Post Approval Study of the LPS-Flex Mobile Bearing Knee
Phase: NA
Conditions: Osteoarthritis, Traumatic Arthritis, Avascular Necrosis of the Femoral Condyle, Moderate Varus, Valgus, Flexion Deformities
Sponsor: Zimmer Biomet

 
 
 
Prospective Multicenter Post Approval Study of the  
LPS-Flex Mobile Bearing Knee 
 
 
 
Protocol # 07-100 
 
 
 
 
Clinical Study Protocol 
 
 
 
May 15, 2007 
Revised August 29, 2007 
Revised January 30, 2008 
Revised February 6, 2008 
Revised April 29, 2008 
Revised June 11, 2008 
Final Revision August 12, 2008 
Amendment I February 14, 2014 
Revised April 18, 2014 
Revised August 6, 2014 
 
 
 
Zimmer, Inc. 
PO Box 708 
Warsaw, IN  46581-0708 
 
 
 
 
 
 
 
 
This protocol contains CONFIDENTIAL information and should be restricted in its 
distribution 

Prospective Multicenter Post Approval Study of the LPS-Flex Mobile Bearing Knee        Protocol # 07-100 
August 12, 2008 
Amendment I January 2, 2014 
 
Table of Contents 
 
1. Protocol Summary 
 
 
 
 
 
 
 
1 
2. Introduction 
 
 
 
 
 
 
 
 
2 
3. Objective 
 
 
 
 
 
 
 
 
3 
4. Study Design 
 
4.1   Additional Data Sources  
 
 
 
 
3 
5. Patient Selection Criteria 
 
 
 
 
 
 
4 
5.A. Patient Eligibility Criteria 
 
 
 
 
4 
5.B. Contraindications 
 
 
 
 
 
5 
6. Study Procedures 
 
 
 
 
 
 
 
6 
6.A. Inclusion of Patient 
 
 
 
 
 
6 
6.B. Operative Procedures 
 
 
 
 
 
6 
6.C. Follow-Up Procedures  
 
 
 
 
7 
7. Plan to Minimize Loss to Follow-up  
 
 
 
 
8 
8. Data Collection 
 
 
 
 
 
 
 
10 
8.A. General Instructions 
 
 
 
 
 
10 
8.B. Device Outcome Case Report Forms 
 
 
 
10 
8.C. Data Collection Schedule 
 
 
 
 
12 
8.D. Quality Assurance and Control  
 
 
           12 
9. Statistical Procedures  
 
 
 
 
 
 
12 
10. Management of Incurrent Events 
 
 
 
 
          19 
10.A. Device Failure/Replacement Procedure 
 
           19 
10.B. Patient Withdrawal 
 
 
 
 
           20 
10.C. Modifications to this Protocol  
 
 
           20 
11. Requirements Prior to Study Initiation 
 
 
 
           20 
12. Informed Consent 
 
 
 
 
 
 
           21 
13. Annual Reporting to the FDA 
 
 
 
 
           21 
14. Completion of Study  
 
 
 
 
 
           21 
15. Device Retrieval 
 
 
 
 
 
 
 
22 
16. Retention of Records  
 
 
 
 
 
           22 
17. Additional Data Source 
 
 
 
 
 
 
24 
18. References 
 
 
 
 
 
 
            
25 
 
  
 

 
Page 1 of 28 
1. Protocol Summary 
 
The objective of Post Approval Study (PAS) is to assess the long-term performance 
of the NexGen® LPS-Flex Mobile Bearing Knee in the treatment of patients with 
severe knee pain or degenerative knee disease.  The target population of 400 cases 
will be from two parallel groups.  
 
Group 1 will consist of approximately 300 patients already implanted with either the 
LPS-Flex Fixed Bearing Knee (control population) or the LPS-Flex Mobile Bearing 
Knee device during the IDE study from approximately 10 sites.  These patients will 
be involved in long-term follow-up through 10 years.   
 
Group 2 will consist of approximately 100 new patients who are eligible for a total 
knee replacement, have been chosen to receive the LPS-Flex Mobile Bearing Knee 
and meet the study eligibility criteria.  The clinical and radiographic data collection 
will be the same for both groups.   
 
The Knee Society Knee Score will be used for both groups to evaluate clinical 
parameters such as functional ability, level of pain and range of motion. The SF-12 
will be used to assess patient’s quality of life status.  Radiographic views will be 
obtained at the immediate postoperative interval (A/P view only) and at each post-
operative follow-up interval (A/P and lateral views).  In addition to the independent 
radiographic evaluation at each post-operative follow-up interval, patient 
improvement in Knee Society and SF-12 scores will be characterized as the change in 
postoperative scores from the preoperative values, and will be summarized at 6 
weeks, 6 months and at annual increments up to 5 years for Group 2 and at 5, 6, 8 and 
10 years for Group 1.   
 
Adverse events will serve as clinical study endpoints, and will be summarized over 
the long-term follow-up period (over the 6 year period beginning at 4 years (if 
applicable) and extending to 10 years from the date of primary knee replacement 
surgery) for Group 1, and over the first 5 postoperative years for Group 2.   
 
The length of follow up for Group 1 will begin with protocol approval at 
approximately 4 to 5 years from the date of the primary knee replacement surgery 
date and will extend through 10 years from the primary surgery date.  A number of 
patients have reached the 4 and/or 5 year post-operative time point during the period 
between the submission of the PMA and the launching of the post approval study at 
which time data was not required to be collected per the IDE protocol.  If the 4 and/or 
5 year data was collected during this period as part of the surgeons standard of care, 
the patient informed consent will request permission to collect this retrospective data 
for use in the post approval study.  The length of follow-up for Group 2 will extend 
through 5 years from the date of primary knee replacement surgery.    
 
 
 

 
Page 2 of 28 
 
2. Introduction 
 
Total knee arthroplasty, TKA, is a medical procedure where the entire knee joint is 
replaced with a prosthetic device.  Since the first total condylar implant procedure in 
1974,1 TKA has become a widely accepted orthopaedic procedure.  Each year, 
approximately 478,000 TKR surgeries are performed in the United States for end-
stage arthritis of the knee joint.  
 
Major indications of TKA include osteoarthritis, rheumatoid arthritis, juvenile 
rheumatoid arthritis, osteonecrosis, and other types of inflammatory arthritis.3  The 
TKA surgical procedure involves resurfacing the knee joint by removing diseased 
bone and cartilage on the surface of the femur, tibia, and patella and implanting an 
artificial device. 
 
Clinical experience has highlighted the need to minimize wear of polyethylene and 
transmission of contact stresses to biological interfaces in total knee replacement 
applications.1,9,21  It has long been recognized that the wear rate of the articulating 
surfaces is correlated with the contact pressures imposed upon them during 
movement.1,21,  It is difficult, however, to increase the congruency of the tibiofemoral 
articulation surfaces without detrimentally affecting knee kinematics and increasing 
contact stress transmission to an unacceptable level.8,13 
 
In the natural knee joint, incongruency of the opposing surfaces of the femoral 
condyles and tibial plateau is accommodated by the menisci, which serve to spread 
the applied load and thus reduce contact pressure.  In the case of artificial knee 
replacements, it is possible to achieve the same effect by allowing one of the bearing 
surfaces, typically the tibial articulating surface, to move relative to the other.  The 
advantage of allowing the tibial articulating surface, or (meniscal bearing surface), to 
move, is that it allows the possibility to retain knee conformity while also maintaining 
a good range of natural movement and thereby reduce contact pressure. 
 
The LPS-Flex Mobile Bearing Knee is designed specifically to optimize congruency 
between the femoral and tibial articulating surfaces over the entire range of motion, 
while providing movement of the tibial articular surface to maintain optimal 
kinematics.  Congruency is important over the entire range of motion because the 
highest contact pressures are often encountered at significant flexion angles when 
climbing and descending stairs, and rising out of a chair.  In the literature, it has been 
demonstrated that in high flexion, the tibia will have a tendency to rotate up to 25º.23  
The articular surface of the LPS-Flex Mobile Bearing is designed to permit free 
rotation about the tibial baseplate trunnion up to 25º of internal or external rotation 
(total possible rotation is 50º).  The tibial/femoral conformity is thus maximized 
throughout the entire range of motion continuum. 
 
The LPS-Flex Mobile Bearing Knee is a meniscal bearing total knee replacement, 
designed to accommodate posterior cruciate ligament resection.  The device is 

 
Page 3 of 28 
designed for use with bone cement only for fixation of all components, which include 
the femoral, tibial and patellar implant devices. 
 
 
3. Objective 
 
The objective of PAS is to assess the long-term performance of the NexGen® LPS-
Flex Mobile Bearing Knee in the treatment of patients with severe knee pain or 
degenerative joint disease, in comparison with the LPS-Flex Fixed Bearing Knee.. 
Outcome data will be collected to evaluate: 
 
 Pre and post-operative status of affected knee. 
 Alleviation of pain in the knee joint 
 Restoration of function 
 Radiographic findings 
 Quality of life 
 Revision, removal or secondary surgery; 
Procedure-related complication and device-related adverse events. 
 
 
4. Study Design 
 
This is a prospective, multi-center, parallel group, active and historically controlled 
post approval study comparing the clinical performance of the LPS-Flex Mobile 
Bearing Knee with the LPS-Flex Fixed Bearing Knee.  Group 1 consists of patients 
who received either the LPS-Flex Fixed Bearing Knee or the LPS-Flex Mobile 
Bearing Knee  during the active IDE, completed the two arm randomized actively 
controlled IDE study and has provided written consent to participate in the post 
approval study.  Group 2 patients will be enrolled into a single arm, historically 
controlled, short- term study (5 years) and will consist of those patients who are 
eligible to receive the LPS-Flex Mobile Bearing Knee and will have the device 
implanted by orthopaedic surgeons experienced in primary total knee replacement.   
 
The post approval study will be offered to all Group 1 patients who participated in the 
IDE portion of the study and agree to participate in the post approval study.  For those 
patients willing to consent to continued follow-up, visits will occur at the following 
post-operative intervals: Years 5, 6, 8, & 10.  All data will be recorded on the Study 
Case Report Forms (CRFs) which will be provided to each site. As stated in Section 
1, if the 4 and/or 5 year data was collected during the period between the submission 
of the PMA and the launching of the post approval study as part of the surgeons 
standard of care, a request will be made to the patient in the informed consent 
requesting permission to collect this retrospective data for use in the post approval 
study. The retrospective data will include any data collected by the investigator per 
his/her standard of care.  If the data collected includes all data points as specified in 
the IDE, this information will be transferred onto the post approval case report forms 

 
Page 4 of 28 
and reported as part of the post approval study.  If the data collected includes any of 
the data points as specified in the IDE, this information will be transferred onto the 
post approval case report forms and flagged to be analyzed separate from the study 
data.  
 
Patients in Group 2 will be selected according to the Patient Eligibility Criteria set out 
in Section 5.  Data on pain, function, deformity, radiographic parameters, and 
complications will be collected.   Patients undergoing primary total knee arthroplasty 
which require a bilateral procedure will also be eligible for inclusion into Group 2.   
Follow-up examinations will be made at 6 weeks, 6 months, 1 year, 2 year, 3 year, 4 
year, and 5 year intervals.     
 
Up to 5 new sites will contribute subjects to Group 2 of the post approval study of the 
LPS-Flex Mobile Bearing Knee Prosthesis.  Surgeon selection will be based on the 
following criteria:  1) the surgeon is willing to conduct this research study in 
accordance to the protocol and applicable federal regulations, 2) the surgeon 
identifies staff to assist him/her to conduct the research and collect the required data 
and 3) an adequate patient population exists to support study enrollment 
requirements.  This number of centers will permit assessment of the consistency of 
outcomes across a variety of investigators.  Each site will enroll approximately 20 
patients.  The enrollment period may be 12 months or longer to assure an adequate 
number of cases at each site. 
 
4.1 
Additional Data Sources 
 
Additional data sources (i.e. Australian Registry) will be requested annually to 
provide further information on the long term safety and efficacy of the NexGen 
LPS Flex Mobile Bearing Knee, in comparison with the LPS-Flex Fixed 
Bearing Knee.  Please refer to Section 17 for further details regarding the 
acquisition and use of this data.  
 
 
5. Patient Selection Criteria/Recruitment Strategy 
 
In order to avoid possible ascertainment bias, the investigator agrees to screen all 
presenting total knee replacement patients against the patient eligibility and 
contraindication criteria and to offer enrollment to all consecutive patients (Group 2) 
that satisfy the criteria. The investigator also agrees to provide an informed consent to 
these presenting patients, who satisfy the patient eligibility and contraindication 
criteria as specified below.  
 
 Patients must meet the following criteria to be eligible for participation.  
 
5.A. 
Patient Eligibility Criteria 
 

 
Page 5 of 28 
Enrollment into Group 2 of the PAS will be offered to all patients who present with 
severe knee pain and disability due to: 
 
 Osteoarthritis (OA)  
 Primary and secondary traumatic arthritis 
 Avascular necrosis of the femoral condyle  
 Moderate varus, valgus, or flexion deformities (i.e. valgus/varus 
deformity of ≤15˚, fixed flexion deformity of ≤10˚) 
 
5.B. 
Contraindications 
 
▪ 
Contraindications include: 
1. 
Previous history of infection in the affected joint and/or 
local/systemic infection that may affect the prosthetic joint. 
2. 
Insufficient bone stock on femoral or tibial surfaces. 
3. 
Skeletal immaturity 
4. 
Neuropathic arthropathy 
5. 
Osteoporosis or any loss of musculature or neuromuscular disease 
that compromises the affected limb. 
6. 
A stable, painless arthrodesis in a satisfactory functional position 
7. 
Severe instability secondary to the absence of collateral integrity 
▪ 
Total knee arthroplasty is contraindicated in patients who have rheumatoid 
arthritis (RA) and an ulcer of the skin or a history of recurrent breakdown 
of the skin because their risk of postoperative infection is greater.  RA 
patient using steroids may also have increased risk of infection.  Late 
infections in RA patients have been reported 24+ months postoperative. 
▪ 
Patient is a poor compliance risk, i.e., history of ethanol or drug abuse, or 
mental handicap that would compromise patient compliance with respect 
to rehabilitation or follow-up.  
▪ 
Patient is not willing or able to give informed consent to participate in the 
follow-up program. 
▪ 
Patient is not willing to return for all scheduled follow-up appointments as 
defined by this protocol. 
 
Participation in Group 1 will be offered to all subjects enrolled in the LPS 
Flex Mobile IDE study.  Of the IDE study participants, it is anticipated that 
approximately 150 procedures implanted with the LPS-Flex Mobile Bearing 
Knee and approximately 150 procedures implanted with the LPS-Flex Fixed 
Bearing Knee will be included in this arm of the study.  Group 1 subjects are 
subjects: 1) without preoperative diagnoses of rheumatoid arthritis, 2) 
implanted with a study device, 3) completed the (IDE) study, 4) will agree to 
be consented for the post approval study and 5) are willing to be re-evaluated 
for their ability to comply with the follow-up schedule specific to the post-
market approval study.  All patients from the IDE study cohort will be 
followed unless any of the following occurs: 1) refusal to provide informed 

 
Page 6 of 28 
consent to participate in the PAS, 2) death, or 3) voluntarily withdrawal from 
participation.    
 
Group 2 will consist of approximately 100 unilateral procedures which are 
implanted with the LPS-Flex Mobile Bearing Knee, have signed the 
informed consent, and are evaluated using the patient 
eligibility/contraindication criteria specific to the post-market approval study.  
Group 2 patients will have a shorter period of follow-up, and will be 
followed until death, revision (or re-revision), withdrawal, or 5 years 
whichever comes first.  All procedures requiring contralateral knee 
replacement will be placed into an ancillary bilateral study arm, and reported 
on in a separate summary of bilateral study procedures.  All procedures 
requiring revision surgery will be placed into a revision study arm, and 
reported on in a separate summary of revision study procedures. 
 
 
6. Study Procedures 
 
6.A. 
Inclusion of Patient 
 
For each consecutive patient in Group 2 presenting as a candidate for total 
knee replacement, the inclusion and contraindication criteria of Section 5 
should be reviewed. If all patient selection criteria are satisfied, the patient 
informed consent process will be completed.  No preoperative information can 
be collected until the patient informed consent has been signed.  A 
preoperative patient questionnaire, health status patient questionnaire, and 
preoperative clinical evaluation will be obtained for Group 2.  
 
The investigator or designee will discuss with the IDE patients continuing into 
Group 1 of the post approval study, the importance of returning for follow-up 
visits at the required intervals.  If during this discussion the patient is 
identified as a poor compliance risk, (i.e., history of ethanol or drug abuse, or 
mental handicap that would compromise patient compliance with respect to 
extended follow-up), this patient would be excluded from the study.  Patients 
having a history of drug and/or alcohol abuse or who are mentally 
handicapped could have the potential to report inaccurate data during the 
follow-up visits and/or could be considered a high risk for non-compliance 
which could inadvertently bias the study.  For this reason, these patients will 
be excluded from the study.  Any baseline information and clinical results of 
these excluded patients at the end of the IDE will be provided in the PAS 
status report. Once the patient is deemed appropriate for continuing into 
Group 1, the patient informed consent process will be completed.  Study 
information will not be collected until the patient informed consent has been 
signed.   
 
 

 
Page 7 of 28 
6.B. 
Operative Procedures 
 
Details of the surgical procedures for Group 2 will be recorded on the CRFs 
provided.  Surgical procedures for Group 2 will follow the same procedures 
that were required for the Group 1 patients enrolled into the IDE phase of the 
study. 
 
All surgical procedures will be performed under aseptic conditions using the 
procedure specified in the appropriate surgical technique manual. 
 
All LPS-Flex Mobile Bearing Knee components will be implanted using bone 
cement of the investigators choice.  The surgical technique for implantation of 
the LPS-Flex Mobile Bearing Knee is included in Appendix 6 of the protocol.   
 
Three separate surgical techniques standard and MIS are available for 
implantation of the LPS-Flex Mobile Bearing Knee, with the choice of 
technique related to surgeon preference for specific instrumentation.  The 
techniques include intramedullary instrument, epicondylar instrument and 
Multi-Reference™ 4-in-1 Femoral Instrumentation surgical techniques.  All of 
the instruments used to implant this device are currently available for 
implantation of the NexGen Complete Knee Solution device.   
 
The Operative Information form and Surgical Device Information form will 
be completed for Group 2 at the time of surgery or immediately thereafter.  
Similarly, the Immediate Postoperative Evaluation form will be completed as 
soon as possible after the surgery, but prior to the 6 week follow-up visit.  The 
case report forms to be completed at each event and interval can be found in 
Appendix 1 of the protocol.  
 
6.C. 
Follow-Up Procedures 
 
Data needed to complete the functional evaluation and the radiographic 
evaluation will be collected for both groups in the study.   
 
Group 1: Postoperatively at 4 years (if applicable), 5 years (if 
applicable), 6 years, 8 years and 10 years. 
 
Group 2: Postoperatively at 6 weeks, 6 months, 1 year, 2 years, 3 years , 
4 years, and 5  years .  
 
Acceptable windows for follow-up for both groups are as follows: 6 weeks ±2 
weeks, 6 months ± 1-month and yearly ± 2 months.  There will be a minimum 
of 5 years of follow-up for each case in Group 2, although some patients may 
fail to achieve the minimum 5 year follow-up due to death, withdrawal from 
the study, or identified as lost to follow-up.  If provided with a second, LPS-
Flex Mobile Bearing Knee bilateral implant, patients will be asked to 

 
Page 8 of 28 
complete two patient questionnaires, and data for each knee implanted will be 
evaluated on separate case report forms.  This information will be analyzed 
separately from patients with unilateral knee replacement.   All patient data 
will be used in the analysis of re-operation rates, pain scores, deformity 
scores, radiographic indications, and complication rates for as long as the 
patient is in the study.  This will remain true until lost to follow-up, or the 
study is closed.   
 
 
Follow-up 
Intervals 
Group 
Follow-up 
Windows 
Months Post-op 
Range 
6 weeks  
Group 2 
± 2 weeks 
4 - 8 weeks 
6 month  
Group 2 
± 1 month 
5 – 7 months 
1 year 
Group2 
± 2 months 
10 – 14 months 
2 year 
Group 2 
± 2 months 
22 – 26 months 
3 year 
Group 2 
± 2 months 
34 – 38 months 
4 year 
Group 1 (if applicable) 
Group 2 
± 2 months 
46 – 50 months 
5 year 
Group 1 (if applicable) 
Group 2 
± 2 months 
58 – 62 months 
6 year 
Group 1 
± 2 months 
70 – 74 months 
8 year 
Group 1 
± 2 months 
96 – 98 months 
10 year 
Group1 
± 2 months 
118 – 122 months 
 
Radiographs (A/P and lateral views) for Group 1 will be required at each 
postoperative interval as specified in the protocol.  Radiographs for Group 2 will be 
required at the preoperative interval (A/P and lateral views), at the immediate 
postoperative interval (A/P view only) and at each postoperative interval (A/P and 
lateral views) as specified in the protocol.  All radiographs (Group 1 and Group 2) 
will be reviewed by the investigator at each interval and a Radiographic Review Form 
will be completed.  If a significant radiographic event is identified, a Significant 
Radiographic Event form will be completed.  An independent radiographic review 
will be performed on Group 1 and Group 2 at all PAS post-operative follow-up 
intervals.  (See Section 8B).   
 
 
7. Plan to minimize Loss to Follow-up 
 
Patient follow-up is extremely important for the conduct of a sound clinical study.  
The expectation of the FDA is to obtain an 80% follow-up rate by the end of this 

 
Page 9 of 28 
study.  In an effort to minimize lost to follow-up study subjects, the following 
recommendations and/or study requirements are essential to ensure proper patient 
selection and compliance.  
  
All Group 2 patients will be selected according to patient eligibility criteria detailed 
in Section 5 and are expected to return for all follow-up visits. Patients from both 
groups will be counseled during the informed consent process on the importance of 
returning for follow-up visits.  Patients who are not willing to return for study 
required follow-up visits and/or are not willing to comply with the follow-up schedule 
will be excluded from enrollment in the study.  In addition, if a patient is a poor 
compliance risk, (i.e., history of ethanol or drug abuse, or mental handicap that would 
compromise patient compliance with respect to extended follow-up) that patient will 
be excluded from the study.   Patients having a history of drug and/or alcohol abuse 
or who are mentally handicapped could have the potential to report inaccurate data 
during the follow-up visits and/or could be considered a high risk for non-compliance 
which could inadvertently bias the study.  For this reason, these patients will be 
excluded from the study.  Any baseline information and clinical results of these 
patients at the end of the IDE will be provided in the PAS status report.   
 
In addition to proper patient selection, patient due notices will be sent to the sites on a 
regular basis in order to track each study participant and monitor adherence to the 
required follow-up visit timeframes.  The patient due listings will facilitate scheduling 
the patients for their return office visits.  If during the course of the study it is 
determined that a patient is experiencing a financial hardship that prevents the patient 
from returning for follow-up visits, Zimmer should be notified to discuss possible 
financial assistance which may be available to the patient.    
 
Attempts to contact patients will be documented on the Study Completion form.  It is 
recommended that the first three attempts be made by telephone.  If a response is not 
received from the phone calls, a letter from the investigator should be sent to the 
patient explaining their agreement per the informed consent to comply with the 
follow-up intervals as stated in the protocol.  If a response is not received from this 
letter to the patient, the final recommendation would be to send a certified letter to the 
patient.  If no response is received from the certified letter, the patient will be deemed 
lost to follow-up and a study completion form will be completed. 
 
In addition, patient contact information of two additional sources will be requested 
from the patient and collected on the Confidential Patient Information form.  If the 
patient is unable to be located either by direct contact to the patient or the two 
additional sources listed on the Confidential Patient Information form, the National 
Death Index will be used to determine whether the patient has died.  If the patient 
should decide to withdrawal from study participation, the Study Completion form will 
include documentation for the reason of withdrawal.  It will also have a question 
which requests permission to contact the patient at the end of the study to assess the 
experience with the device.   
 

 
Page 10 of 28 
Should these recommendations and/or requirements fail to achieve the FDA required 
80% follow-up compliance for Group 1 at the 10 year time point, the follow-up 
requirements for Group 2 will continue until the patients reach the ten year post-
operative interval.  These patients will be expected to continue annual post-operative 
follow-up visits at 5, 6, 8 and 10 years.  The consent for Group 2 will include the 
following statement to allow for additional follow-up out to the 10 year time point.  
“You will be required to complete follow-up visits at 6 weeks, 6 months, and annually 
out to 5 years.  However, if at the end of the 5 year period, additional data is required 
to fulfill FDA requirements, you may be asked to continue annual post-operative 
follow-up visits at year 6, 8, and 10.”    
 
 
8. Data Collection 
 
8.A. 
General Instructions 
 
Bilateral cases will require the completion of two separate sets of case report 
forms (CRFs) and thus will have two separate identification numbers.  
 
The CRFs should be completed in black ink. 
 
Data corrections should be made by striking out the incorrect entry with a 
single line and initialing and dating the change(s), and the correct response 
marked alongside.  
 
All questions on the forms should be answered. If the information is not 
available, the supporting information shall be documented in the general 
comments section of the CRF. This will help to reduce the number of data 
queries generated for data that may not be available. Consistent occurrences 
of missing/incomplete data may prevent thorough and proper analysis of the 
study data. 
 
8.B. 
Device Outcome Case Report Forms  
 
Pre-operative Assessment (consisting of five different CRFs – 
Demographic Evaluation, Patient Questionnaire, Physical Exam, Knee 
Assessment and Health Status Questionnaire (SF-12)) will include 
demographics, relevant medical & surgical history, diagnosis, clinical 
evaluation (Knee Society Knee Score) and quality of life evaluation (SF-12) 
 
Operation Details (consisting of three different CRFs – Operative 
Information, Surgical Device Information, and Immediate Postoperative 
Evaluation) will include procedure and device information, length of stay 
and details of any perioperative complications.  
 

 
Page 11 of 28 
Group 1 patients will return for follow-up visits at 4 years (if applicable), 5 
years (if applicable), 6 years, 8 years and 10 years.  Group 2 will return for 
follow-up visits at 6 weeks, 6 months, 1 year, 2 years, 3 years, 4 years, and 5 
years.  There are three clinical assessment forms (Patient Questionnaire, 
Physical Exam and Knee Assessment), a Significant Radiographic Event 
form and an SF12 (Health Status Questionnaire) form allocated for each 
routine follow-up visit, with additional forms as required (i.e., Independent 
Radiograph Review, Concomitant Medical Events/Complication Report 
form, Protocol Deviation form, and Study Completion form.)  
 
Independent Radiograph Review will be performed on all required post-
operative follow-up intervals for both Group 1 and Group 2.  The findings of 
independent radiographic review will be captured on the Independent 
Radiograph Evaluation form.  If the findings of the independent reviewer are 
different from that of the investigator review, the independent review will be 
considered the final determination.   
 
Adverse Events/Adverse Device Effects/Complications Reporting will 
include a description of all complications, onset date, type of event, severity, 
relation to the device, treatment and outcome. One Concomitant Medical 
Events/Complications Report form is completed for each complication 
identified during the course of the study.  
 
Study Completion forms will be completed if one of the following events 
occurs:  
1) Patient completes study follow up,  
2) Patient withdraws from the study,  
3) Patient death,  
4) Patient is lost to follow up,  
5) The patient undergoes revision of the study implant (or revision implant 
where warranted), (Please Note: these patients will be classified as a 
failure and moved into the Revision arm of the study) or  
6) Other reason such as senility or dementia.  
The form will include the date of study completion, study completion status, 
(e.g. patient expired, lost to follow-up, withdrawal of consent, implant 
revision, etc.) and questions regarding if the device is still in place and if the 
patient is experiencing any complications at date of last contact. 
 
Revision Study Subjects 
Any study subject who undergoes a revision procedure during the course of 
this post-approval study will be terminated from their respective group and 
moved into the revision arm of the study, per request of the FDA.  
 
Revision information will be collected on the Reoperation/Device Removal 
form and include the following information:   
1) Component removed,  

 
Page 12 of 28 
2) Reoperation information consisting of reason for removal, date of 
removal, new components implanted, disposition of device,  
3) Re-operative findings, and  
4) IRB notification.   
 
The revision surgery information will be collected on the Revision 
Operative Information form and the Revision Surgical Device 
Information form which will be completed at the time of surgery, or 
immediately thereafter.   The Revision Immediate Postoperative 
Evaluation form will be completed as soon as possible after the 
surgery, but prior to the 6 week follow-up visit.  The post-operative 
follow-up intervals after revision surgery will be at 6 week, 6 month, 
and annually thereafter until the study has been completed.  The case 
report forms to be completed at each revision event and interval can 
be found in Appendix 1 of the protocol.  
 
8.C. 
Data Collection Schedule 
 
Completed Case Report Forms should be sent directly to the Clinical Affairs 
Department at Zimmer for data entry, validation and analysis.  Please see 
Appendix 2 of the clinical protocol for a detailed data collection matrix.  
 
8.D. 
Quality Assurance and Control 
 
Study Monitors from the Zimmer Clinical Affairs Department will visit sites 
on a periodic basis and will require either direct or indirect access to patient 
records for monitoring purposes.  
 
Study data will be summarized and reported to the participating centers on an 
annual basis.  Confidentiality of individual site data will be strictly 
maintained. 
 
 
9.  Statistical Procedures 
 
9.A.  Analysis Objectives 
 
The statistical analysis has four major objectives:   
(1) to evaluate the ability to replicate the short-term efficacy and the safety 
of the LPS-Flex Mobile Bearing Knee prosthesis observed in the 
original IDE study population in a prospective cohort which 
corresponds to its continued use in routine clinical practice (Group 2);  
(2) to evaluate the long-term efficacy and the safety of the LPS-Flex 
Mobile Bearing Knee prosthesis (Group 1);  

 
Page 13 of 28 
(3) to evaluate the combined midterm efficacy and safety of the LPS-Flex 
Mobile Bearing Knee prosthesis from the combination of two 
prospective sequential cohorts (Group 1 and Group 2); and  
(4) to summarize the short-term (e.g., generally less than 5 years) efficacy 
and safety in the small subcohort of primary TKAs from Group 1 and 
Group 2 who undergo revisions during the post approval study.   
 
To achieve these objectives, we will evaluate safety and efficacy through:   
(1) A comparison of a clinical success endpoint between unilateral 
primary procedures in the short-term LPS-Flex Mobile Bearing Knee 
cohort  (Group 2) at the 2+ year postoperative clinical assessment with 
the full unilateral primary IDE LPS-Flex Fixed Bearing Knee 
representing per-protocol procedures cohort at the 2+ year 
postoperative clinical assessment;  
(2) A comparison of short-term LPS-Flex Mobile Bearing Knee cohort 
(Group 2) at the 2+ year postoperative clinical assessment with the full 
unilateral primary IDE LPS-Flex Mobile Bearing Knee representing 
per-protocol procedures cohort at the 2+ year postoperative clinical 
assessment. 
(3) A comparison of a clinical success endpoint between the primary 
unilateral LPS-Flex Mobile Bearing Knee and the LPS-Flex Fixed 
Bearing Knee long-term cohort (Group 1) at the 10+ year 
postoperative clinical assessment;  and  
(4) A comparison of clinical success in the mid-term 5+ year postoperative 
clinical assessment between the combined LPS-Flex Mobile Bearing 
Knee (Group 1 + Group 2) and the full unilateral primary IDE LPS-
Flex Fixed Bearing Knee historical control representing per-protocol 
procedures cohort which also includes all IDE per-protocol procedures 
which were not enrolled in Group 1 by carrying their last postoperative 
clinical assessments forward to 5 years.   
Results of one-sided statistical tests will be given in the statistical 
analysis because it is of interest to know if the patient outcomes with 
the LPS-Flex Mobile Bearing Knee are not worse than those observed 
in the LPS-Flex Fixed Bearing Knee.  In addition, 
 (5) Safety and efficacy parameters will be provided for primary TKAs 
that undergo revision (Group 1 and Group 2) during the post approval 
study at the time of clinical assessment.  Safety and efficacy will be 
evaluated for each cohort (and their combination at 5+ years) and 
results will be compared between the LPS-Flex Mobile Bearing Knee 
and the LPS-Flex Fixed Bearing Knee.  
 
Analyses of clinical success will also be accompanied by sensitivity analyses 
which will report clinical success rates for subgroups defined by study device:  

 
Page 14 of 28 
(1) Investigative site; 
(2) Baseline symptoms (Knee Scores);  
(3) Subcohort (Group 1, Group 2, and IDE procedures not enrolled in 
Group 1);  
(4) Patient age;  
(5) A 5+ Year results restricted to subjects enrolled in Groups 1 and 2 (i.e., 
without carrying forward results of all IDE subjects that did not enroll 
in Group 1);  
(6) Missing data imputed as failures (regardless of device group);   
(7) Missing data imputed as failures for the LPS-Flex Mobile Knee group 
and successes for the LPS-Flex Fixed Bearing Knee group;   
(8) Missing data imputed as successes for the LPS-Flex Mobile Knee 
group and failures for the LPS-Flex Fixed Bearing Knee group;   
(9) Various proportions of missing data imputed as failures (regardless of 
device).   
Sensitivity analyses are intended to assess the consistency of the results with the 
LPS-Flex Mobile Bearing Knee prosthesis and the LPS-Flex Fixed Bearing Knee 
under different conditions. 
 
 
9. B. 
Variables for Analysis 
 
Variables to be studied include: 
 
1. Baseline Data 
 
a. Age 
b. Sex  
c. Symptomatic side 
d. Diagnosis 
e. Medical history 
f. Preoperative clinical and functional analysis (Knee Scores) 
g. Operative time 
 
2. Follow-up Data 
 
a. Functional analysis (Knee Scores) 
b. Radiographic analysis 
c. Complications 
d. Implant Survival 
e. Quality of Life (SF-12) 
 
Surgical procedures followed to 10 years (Group 1) will be evaluated 
postoperatively at 4 years (if applicable), 5 years (if applicable), 6 years, 8 
years, and 10 years.  Procedures followed to 5 years (Group 2) will be 

 
Page 15 of 28 
evaluated preoperatively, perioperatively, and in follow-up at 6 weeks, 6 
months, 1 year, 2 years, 3 years, 4 years, and 5 years. 
 
Randomization Scheme 
 
Patients in Group 2 will not be randomized in the post-approval study, but will 
be required to provide informed consent, meet inclusion criteria, and be free 
from attributes represented in contraindication criteria for inclusion.  Patients 
in Group 1 were randomized and implanted with a study device prior to the 
post approval study. 
 
Sample Size Justification 
 
Sample size serves to characterize safety and efficacy through separate 
assessments which each are measures of clinical success.  Success will be 
assessed from implant survival, as well as, from clinical, functional, 
radiographic, and safety evaluations.   
 
Success for each clinical endpoint will be evaluated separately for each 
procedure at key time points.  Each procedure which meets all the criteria for 
clinical success will be classified as a clinical success.  
 
The following are the five (5) criteria for classification of a procedure as a 
clinical success: 
 Knee Society assessment score greater than/equal to 70 points 
 Knee Society function score greater than/equal to 70 points 
 No intended, actual, or planned revision and/or removal of any component 
of the knee system 
 Absence of severe knee related complications 
 An absence of subsidence of greater than or equal to 2 millimeters and an 
absence of both osteolysis and radiolucencies greater than or equal to 2 
millimeters as determined by independent radiographic reviewer 
 
If one or more of the above criteria are unmet, the procedure will be classified 
as a failure to achieve clinical success. 
 
Sample size was based on independent Blackwelder1 test of clinical success 
proportions for non-inferiority by a comparison of proportions of primary 
unilateral procedures implanted with the LPS-Flex Mobile Bearing Knee 
versus unilateral procedures implanted with the LPS-Flex Fixed Bearing 
Knee.  Clinical success at the 5 year postoperative assessment will correspond 
to assessments made at follow-up visits conducted at the 58 postoperative 
month or beyond for both device groups.  The LPS-Flex Mobile Bearing Knee 
estimate will be obtained from the combination of clinical results obtained 
from both Group 1 and Group 2, as well as subjects in the original IDE group 
that were not enrolled into Group 1.  All LPS-Flex Mobile Bearing Knee 

 
Page 16 of 28 
procedures that were not enrolled in Group 1 will be included in analysis, and 
will have their last postoperative clinical assessments carried forward (LOCF) 
to 5 years.  The LPS-Flex Fixed Bearing Knee estimate will be obtained from 
clinical assessments performed on Group 1, and will include all subjects in the 
original IDE group that were not enrolled into Group 1.  LPS-Flex Fixed 
Bearing Knee procedures not enrolled into Group 1 will have their last 
postoperative clinical assessments carried forward (LOCF) to 5 years for 
completeness.  This comparison will therefore consist of all eligible unilateral 
procedures.  The equivalence of clinical success will be tested using a two-
group proportion test.   
 
In addition to the comparison  of clinical success of all eligible unilateral 
procedures at the 5 year postoperative assessment, the equivalence of clinical 
success will be assessed in secondary analyses at each key protocol-specified 
scheduled postoperative clinical assessments using a two-group proportion 
test following the article by Blackwelder.1  Primary unilateral LPS-Flex 
Mobile Bearing Knee procedures will be compared with the LPS-Flex Fixed 
Bearing Knee with restriction to Group 1 procedures at 10 years using FOCB 
(first observation carried backwards).  Clinical success will be compared 
between primary unilateral Group 2  LPS-Flex Mobile procedures at 2 years 
and the historical rate in primary unilateral LPS-Flex Fixed Bearing Knee 
procedures obtained in the IDE study at 2 years.  Two year comparisons will 
be performed using FOCB (or LOCF if FOCB unavailable).     
 
The null (Ho) and alternative (H1) hypotheses for testing equivalence are 
represented by: 
 
Ho:  PLPS-Flex Fixed Bearing   P LPS-Flex Mobile Bearing +  
 
H1:  P LPS-Flex Fixed Bearing <  P LPS-Flex Mobile Bearing +  
 
where, PLPS-Flex Mobile Bearing is the clinical success rate for the LPS-Flex Mobile 
Bearing Knee, PLPS-Flex Fixed Bearing is the clinical success rate for the LPS-Flex 
Fixed Bearing Knee, and  is the minimum difference of practical 
interest.  The clinical success endpoint is dichotomous in nature and as a result 
will be evaluated independently by a two-sample t-test which employs a 
normal approximation to the binomial distribution.     
 
Sample size determination for the comparison of clinical success rates 
between the LPS-Flex Mobile Bearing Knee and the LPS-Flex Fixed Bearing 
Knee at 5 years was completed using a one-sided alpha (Type I) error rate of 
5%, and was based on the 2 Year clinical success rate reported in the 
regulatory submission (IDE G000157) for the LPS-Flex Mobile Bearing Knee 
(67.7%, Volume 11 page 04329).    Sample size was computed with 
consideration of imbalances between the number of procedures implanted 
with the LPS-Flex Mobile Bearing Knee in Group 1 and Group 2 and the 

 
Page 17 of 28 
control implanted with the LPS-Flex Fixed Bearing Knee in Group 1.  A 2:1 
ratio of the LPS-Flex Mobile Bearing to LPS-Flex Fixed Bearing Knee 
unilateral procedures was used in the estimation of sample size.    
 
Specifically, Blackwelder’s method was modified to allow for imbalances in 
sample size.  The following formula was used for the one-sided two-group 
proportion test: 
 
 




)
(
*
2
*
(
*
)
1(
*
(3
)
(
2
2
1
1







Z
Z
P
P
n
Size
Sample
 
 
Where
2
exp
control
erimental
P
P

 is the average clinical success rates for the LPS-Flex 
Fixed Bearing Knee (Pcontrol ) and the LPS-Flex Mobile Bearing Knee (Pexperimental ) 
under the alternative hypothesis. 
 
Table 1: Power analyses for the comparison of clinical success rates at 5+ Years in the Post-
Approval Study 
Primary 
Endpoint 
Type I 
Error 
() 
Difference 
(δ) 
Power 
(%) 
Estimate of 
Success in 
control 
N  
LPS-Flex 
Mobile 
Knee 
N  
LPS-Flex 
Fixed 
Bearing 
Knee 
Clinical 
Success 
0.05 
15% 
90 
67.7% 
274 
137 
Clinical 
Success 
0.05 
15%‡ 
96.7 
67.7% 
268‡ 
134‡ 
Clinical 
Success 
0.05 
10% 
62.9 
67.7% 
274 
137 
Clinical 
Success 
0.05 
10%‡ 
80 
67.7% 
268‡ 
134‡ 
‡ Sample size determined using additional estimates obtained from the LPS-Flex Mobile Bearing Knee 
IDE study for per-protocol endpoints at 2+ Years follow-up using a modification of the sample size 
formula provided in Fundamentals of Clinical Trails (Friedman, Furberg, and DeMets, PSG Publishing, 
1985, page 90) : 


2
2
1
1
0
0
2
2
*
2
)])
1(
*
[
)]
1(
*
2
[
*
(
))
1(
*
3
*
(



p
p
p
p
Z
p
p
Z
N






 
Where p(bar) represents the average of p0  the clinical success rate in the LPS-Flex Fixed Bearing Knee, 
and p1  the clinical success rate in the LPS-Flex Mobile Bearing Knee,.     
The use of the observed clinical success rate in the LPS-Flex Mobile Bearing Knee (69.9%) resulting in an 
average rate of clinical success of 68.6%, and adjustment of the non-inferiority margin (10%) to 
accommodate the 2.2% greater rate of clinical success observed in the LPS-Flex Mobile Bearing Knee (i.e., 
adjusted to 12.2% for the 10% margin and 17.2% for the 15% margin) for sample size estimation..  

 
Page 18 of 28 
Based on the modification of Blackwelder’s sample size algorithm, a fixed sample 
size of 137 implants in the LPS-Flex Fixed Bearing Knee and 274 in the 
combined LPS-Flex Mobile Bearing Knee study groups (Group 1 + Group 2)  at 
the 5 year postoperative assessment has 90%  power to detect a difference in 
clinical success rates of 15% (δ) or greater at a 1-sided alpha (Type I) error level 
of 0.05, assuming a clinical success rate in the LPS-Flex Fixed Bearing Knee of 
69.4 percent.  With additional considerations, a sample size of 153 implants in the 
LPS-Flex Fixed Bearing Knee and the combined LPS-Flex Mobile Bearing Knee 
study groups (Group 1 + Group 2) also has 80% power to detect a difference in 
clinical success rates of 10% at a one-sided alpha (Type I) error level of 0.05.   
Analyses at the 5 year assessment will ensure an adequate number of procedures 
are available using an imputation of the first assessment beyond 58 months 
backwards (FOCB).  If the 5 year postoperative assessments are unavailable, then 
the last postoperative clinical assessment will be carried forward (LOCF).   
 
9.C. General Statistical Methods 
 
At study completion, all cases will be evaluated for compliance with the patient 
selection criteria and follow-up procedures.  A case may be dropped from the 
final analysis for any of the following reasons: 
i. Patient is lost to follow-up 
ii. Patient withdraws prior to final follow-up 
iii. Patient does not meet patient eligibility criteria 
iv. 
One or more components were improperly implanted (i.e., subjects 
enrolled but not implanted with a study device at primary knee 
surgery will not be included) 
v. Patient did not comply with follow-up procedures 
 
Any cases dropped from the primary analysis will be evaluated and reported 
separately. 
 
Data tabulation and summarization will be presented to help in the evaluation of 
the importance differences in clinical success rates.  One-sided statistical 
comparisons will be performed at an alpha (Type I) error level which will not be 
adjusted (for multiplicity) and will equal to 5 percent in the test of the null 
hypothesis of non-inferiority.  Tests of the primary hypothesis will be carried out 
by computing the 95% confidence limit for differences in clinical success rates (
control
al
experiment
P
P

) between the LPS-Flex Mobile Bearing Knee (experimental) 
and the LPS-Flex Fixed Bearing Knee (control), and declaring non-inferiority, if 
the lower bound of the one-sided 95% confidence limit is greater than the non-
inferiority margin (-10%) The non-inferiority of the LPS-Flex Mobile Bearing 
Knee as compared to the LPS-Flex Fixed Bearing Knee will also be assessed at a 
non-inferiority margin of -10%.  Details concerning the specific testing 
procedures to be used are reported below. 
 

 
Page 19 of 28 
Point estimates of means or rates will be reported for many results. Confidence 
intervals are used when it is important to evaluate the uncertainty of an estimate 
or hypothesis test.  In particular, a null hypothesis may not be rejected even 
though it is false, and a confidence interval can then be used to give a range for 
the plausible size of the undetected difference. 
 
Secondary analyses will be chosen to be appropriate for the scale and distribution 
of the measures being analyzed:  discrete categorical, discrete ordinal, continuous 
non-Gaussian, and continuous Gaussian.   
 
Most of the measures analyzed are discrete in nature.  This includes patient 
classification measures, such as diagnosis, as well as several components of the 
symptom, function, and physical examination evaluation.  Most of the 
components of the function and physical examination are ordinal and will be 
analyzed as ordinal measures. 
 
Comparisons of distributions of dichotomous variables between a subcohort and 
the historical control will be performed using Fisher's exact test.  Comparisons of 
distributions of polychotomous variables between a subcohort and the historical 
control will be performed using a likelihood ratio Chi-square test.   
 
Comparisons of distributions of continuous variables between a subcohort and the 
historical control will be performed by a comparison of averages using Student’s 
t-test.  Significance will be inferred at a 2-sided alpha (Type I) error level of 0.05.  
The assumption of equal study group sample variances will be assessed using an 
F-test (folded), at an alpha (Type I) error level of 0.05.  If the assumption of equal 
sample variances is unmet, then a non-parametric Wilcoxon rank sum test will be 
performed, and significance will be inferred at a 2-sided alpha (Type I) error level 
of 0.05.    
 
9.D. Specific Analyses 
 
Preoperative, baseline, and perioperative characteristics of the subcohort and 
historical controls will be compared between study device groups.  Those factors 
that are found to significantly differ at an unadjusted alpha (Type I) error level of 
0.05 between the two groups will be considered in a secondary adjusted logistic 
regression analysis of clinical success which accounts for significant 
demographic, baseline, and perioperative differences through the use of 
propensity scores.  Specifically, baseline and demographic variables will be used 
to estimate probabilities of study device group assignment, and the probabilities 
or propensity scores will be used as an adjustment variable in a secondary 
adjusted logistic regression analysis of clinical success measures.  Demographic, 
baseline, and perioperative characteristics will also be summarized by study 
device for each cohort (Group 1, Group 2, and IDE procedures not enrolled in 
Group 2).  

 
Page 20 of 28 
Distributions of available outcomes (Knee Society function and assessment, 
radiographic parameters, etc.) at each scheduled time of clinical assessment in the 
short-term arm of the study (Group 2) will be compared between primary 
unilateral LPS-Flex Mobile Bearing Knee procedures and the historical control of 
primary unilateral LPS-Flex Fixed Bearing Knee at the 6 Week, 6 Month, 1 Year, 
and 2+ year postoperative assessments, and parameters will also be summarized 
for Group 2 procedures that undergo revision at each time point.  Distributions of 
available outcomes (Knee Society function and assessment, radiographic 
parameters, etc.) will be compared between the LPS-Flex Mobile Bearing Knee 
and the LPS-Flex Fixed Bearing Knee at each scheduled time of clinical 
assessment (4 year, 5 year, 6 year, 8 year, and 10+ years) for primary unilateral 
procedures enrolled in the long-term phase of the study (Group 1), and parameters 
will also be summarized for Group 1 procedures that undergo revision at each 
time point.     
 
Revision rates for each cohort or historical control will be estimated using the 
Kaplan-Meier product limit method.  The Kaplan-Meier curves will be plotted 
over the relevant period of follow-up, and the survival curves will be compared 
using the log rank and Wilcoxon rank sum tests. 
 
Adverse events will be summarized by study device and group as patient adverse 
events (counted once per patient per type) and, separately, as adverse events 
(counted overall).  Adverse event rates will be compared between the subcohort 
and the historical control using Fisher’s exact test at a two-sided alpha (Type I) 
error level of 0.05.  In addition, time-course of adverse events summaries will be 
performed for patient adverse events and adverse events.   
 
 
10. Management of Intercurrent Events 
 
10.A. 
Device Failure / Replacement Procedure 
 
Total knee revision procedures, should they be necessary, must be recorded 
on the Concomitant Medical Events/Complications Report and the 
Reoperation/Device Removal CRF.  A full explanation of the cause and 
treatment is needed.  The Study Completion CRF should also be completed. 
 
The revision patients will be moved into the Revision Arm of the study and 
follow-up will continue until the study is completed as stated in Section 8b.   
 
Standard total knee replacement and revision methods will be used in the 
event of a device failure requiring revision of one or more total knee 
components.  Clinical and radiographic information, and a detailed operative 
report will be gathered on all revision cases. 
 
10.B. 
Patient Withdrawal 

 
Page 21 of 28 
 
Subjects have the right to withdraw from the study at any time.  The reason 
for the withdrawal will be documented on the Study Completion case report 
form.  In the event of withdrawal, investigators should request permission to 
contact the study subject at the end of study to find out if the patient had a 
revision or if the device is still in place.  This contact will occur at the 10 
year follow-up for Group 1 and at the 5 year follow-up for Group 2.  
 
10.C. 
Modifications to this Protocol 
 
Neither the investigator nor Zimmer will proceed to modify this protocol 
without mutual agreement. 
 
After agreement to initiate the modification (in the form of a protocol 
amendment), the investigator agrees not to institute this modification until 
instructed to do so by the Zimmer monitor.  It will be necessary to obtain 
FDA and IRB approval prior to implementation of any changes in the 
protocol that may affect the scientific soundness or the rights, safety, or 
welfare of the patients involved. 
 
11. Prior to Initiation of the study 
 IRB Protocol Approval 
 
A copy of the Institutional Review Board (IRB) approval containing the 
protocol version, the IRB meeting date and the provisions for periodic review in 
compliance with FDA regulations should be submitted to Zimmer.   
 
 Informed Consent 
 
A copy of the final, date stamped (if applicable) IRB approved Informed 
Consent form must be submitted to Zimmer.  If the IRB requires a document 
differing from that provided in the investigational plan, a specimen copy of the 
Informed Consent should be submitted by the investigator to Zimmer for review 
and approval by Zimmer and if necessary, the FDA.  Informed consent must be 
obtained for each case prior to study enrollment.   
 
 Clinical Investigator Agreement 
 
A signed Clinical Trial Agreement (CTA) must be submitted to Zimmer.  An 
investigator will not be permitted to participate in this clinical investigation until 
the CTA is fully executed and received by the Zimmer Clinical Affairs 
Department.   
 
 
 

 
Page 22 of 28 
12. Informed Consent 
 
Patients should be made aware that their data will be included in a computerized 
database for this study.  
 
Any additional information required about this study should be obtained from the 
Zimmer Clinical Affairs Study Manager at:   
 
Kim Rowe 
1800 West Center Street 
Warsaw, Indiana 46580 
Tel: 574-372-4843 
Fax: 574-372-4710 
 
 
13. Annual Reporting to the FDA  
 
Zimmer will submit an Interim Study Status Report to the FDA every six months 
for the first two years of the study and annually thereafter until a Final Study Report 
has been submitted. These reports will include information required by FDA 
guidance document entitled: Procedures for Handling Post-Approval Studies 
Imposed by PMA Order dated August 1, 2007 or otherwise directed by the FDA.  
 
14. 
Completion of Study 
 
The investigator will complete and report the results of the study in satisfactory 
compliance with the protocol within 6 months of last patient follow-up.  
 
It is agreed that either the investigator or sponsor may terminate this study before 
the above date, provided a written notice is submitted at a reasonable time in 
advance of intended termination.  Upon receipt of this written notification by either 
party, it is understood that no additional patients will be entered into the study. 
 
After conclusion of the study, Zimmer will prepare a clinical summary which will 
include tabulations of the data reported. 
 
15. Device Retrieval 
 
In the event of a revision, all components revised should be returned to Zimmer for 
analysis.  The investigator must notify the study manager prior to the return of any 
device.  There are three types of returned devices:  1) unused; 2) used, non-
contaminated (i.e., the outer package has been opened or the seal has been broken, 
but the device has not been implanted; and 3) used, contaminated (i.e., those which 
have been implanted in human subjects).   
 

 
Page 23 of 28 
For used, contaminated devices, immerse the implant in 10 percent neutral buffered 
formalin, label the implant container to identify the investigator, patient, date of 
removal, and that the implant is from a clinical study case.  Properly prepared 
specimens are to be sent to: 
  
 
Zimmer, Inc. 
 
Attention:  Product Service Department 
 
1777 West Center Street 
 
Boggs Industrial Park 
 
Warsaw, Indiana 46580 
 
Once the analysis is complete, a copy of the report will be maintained in the study 
subject records by Zimmer Clinical Affairs and a copy will also be sent to the 
Investigator for his study records.   
 
A summary of all detailed explant reports will be provided to the FDA in the 
Annual Reports.  
 
 
16. Retention of Records 
 
Federal law requires that a copy of all correspondence with Zimmer, study 
monitor’s, IRB’s, the FDA, or another investigator, and all records which support 
case reports of this study must be retained in the files of the investigator for a 
minimum of two years following written notification by Zimmer that the clinical 
trial has been completed or has been discontinued.  
 
17. Additional Data Source   
 
Purpose 
The intent is to utilize data from the Australian Orthopaedic Association National Joint 
Registry (AOANJRR) external registry data in order to supplement existing internal data 
submitted as required for the Prospective Multicenter Post Approval Study of the LPS-
Flex Mobile Bearing Knee (P060037). 
History  
On August 12, 2008, the LPS-Flex Mobile Bearing Knee Post Approval Study Protocol 
was approved and the study launched as a condition of approval for the LPS-Flex Mobile 
Bearing Knee System. 
The post approval study is comprised of two groups: Group 1 was to include 
approximately 300 patients (both mobile bearing and fixed bearing) who were enrolled in 
the IDE study and eligible to participate in the post approval study.  These patients were 
to be followed until the completion of 10-year follow-up visits.  However, of the original 
fifteen (15) sites participating in the IDE study, only nine (9) sites agreed to participate in 
this post approval study, representing 161 mobile and 146 fixed bearing subjects eligible 
for study participation, or a total of 307 potential study participants from Group 1.  As of 

 
Page 24 of 28 
10/1/2013, enrollment in Group 1 is 144 subjects (76 fixed bearing, 68 mobile bearing).  
All sites in Group 1 are in year 10 of follow-up for those participating patients, with all 
sites completing 10-year follow-up in 2014. 
Failure of Group 1 sites to reach the desired compliance rate for Zimmer to meet the 
conditions of approval for the post approval study may bias the post-approval study 
results and decrease the statistical precision of the difference between the LPS-Flex 
Mobile Bearing Knee and the LPS-Flex Fixed Bearing Knee. Data received from the 
AOANJRR will be used to supplement data being collected in the post-approval study. 
This supplements Zimmer data to further demonstrate safety, efficacy and a low revision 
rate for the LPS-Flex Mobile Bearing device in over 4,000 knees. 
Group 2 consists of 3 new surgeons who are to enroll a total of 120 patients.  These 
patients are to be implanted with the LPS-Flex Mobile Bearing Knee and followed until 
the completion of 5-year follow-up.  As of 10/1/2013, enrollment in Group 2 is 119 
subjects.  
 
Comparison of Data  
 
Objective 
Group 1 participation includes 144 patients (76 fixed bearing and 68 mobile bearing) who 
have consented to participate in the post approval study and have returned for follow-up 
evaluations.  In order to meet the FDA’s PAS requirements, external registry data will be 
used to supplement current clinical data being collected.  The supplemental data will be 
obtained annually from the Australian Orthopaedic Association National Joint Registry 
(AOANJRR).  The AOANJRR collects data on revision procedures and calculates 
revision rates by device fixation, type of revision and revision diagnosis on the requested 
brand name product and compares it to all total knees of the same or similar category 
performed in Australia.  The NexGen LPS-Flex Mobile Bearing Knee System was 
approved for commercial use in Australia on July 18, 2003.  
 
Data Acquisition 
On October 1 of each year, Zimmer will request data for the catalog numbers with 
descriptions (see Appendix D) for ad-hoc reports from the AOANJRR utilizing the 
required form (See Appendix E) and requesting specific data available (primary 
diagnosis, gender, reason for revision) for comparison with data collected as part of the 
post approval study.  Only those component combinations approved in the PMA 
Application P060037 will be analyzed to obtain current survivorship data for submission 
with the annual report.  Fixed Bearing Components cleared in 510(k) K062768 will be 
reported as well, because these components were used as the Control Group in the 
original IDE.   
 
The AOANJRR is a Level 1 Registry and as such, endpoints available for data submitted 
to Sponsor are limited to revision rates.  Per policy of AOANJRR, only verified data 
published in the current year’s registry will be released for reporting purposes (i.e. data 
published as of December 31, 2013 will be reported in the 2014 annual report).   Please 
review Appendix A for a copy of the data collection tool used by the AOANJRR.   As 

 
Page 25 of 28 
requested by FDA, Sponsor has provided in Appendix B the “Introduction” section from 
the 2013 Australian Registry detailing how the data is collected, validated and 
survivorship estimates are calculated.  Included in Appendix C is an example of the 
reports from AOANJRR for both the mobile bearing knee components as well as the 
fixed bearing knee components. 
 
The expected reports from the AOA NJRR will include the following: 
 Revision Rates 
 Primary Diagnoses  
 Type and Reason for Revision 
 Demographic 
▪ 
Gender 
▪ 
Age (categorical only) 
 
Data Analysis  
Due to the manner in which AOANJRR reports and categorizes age in the registry, age 
comparison cannot be made.  Sponsor will compare revision rates, primary diagnoses, 
types of revisions and gender for mobile bearing subjects obtained from AOANJRR with 
mobile bearing subjects’ data currently collected for the post approval study.  The 
following are the methods Zimmer intends to use to compare results from the PAS group 
and the AOA NJRR data: 
 Revision rates will be presented for each year where the number of cases at 
risk exceeds fifty (50).  The cumulative percent revision at a certain time is 
the complement (in probability) of the Kaplan-Meier survivorship function 
at that time, multiplied by 1001. The two survival distributions will be 
statistically compared using the log-rank test.  Statistical inference will be 
inferred at a Type I error rate of 5%. 
 Types of revisions will be compared between the LPS Flex Mobile PAS 
data and the AOANJRR using a Likelihood Ratio Chi-Square test.  
Statistical inference will be inferred at a Type I error rate of 5%. 
 Primary diagnosis will be compared between the LPS Flex Mobile PAS data 
and the AOANJRR using a Likelihood Ratio Chi-Square test.  Statistical 
inference will be inferred at a Type I error rate of 5%. 
 Gender will be compared between the LPS Flex Mobile PAS data and the 
AOANJRR using the Fishers Exact test.  Statistical inference will be 
inferred at a Type I error rate of 5%.  No p-values will be adjusted for 
multiplicity. 
 
However, data analyses of the AOANJRR data will not be possible due to the restricted 
access to the registry’s raw data.   
 
Indications for use of the LPS-Flex Mobile Bearing and LPS-Flex Fixed Bearing devices 
are the same for US as well as Australia. 
 
                                                          
1 Australian Orthopaedic Association National Joint Replacement Registry. Annual Report. Adelaide:AOA; 2013, pg 5 

 
Page 26 of 28 
IRB Protocol Amendment Approval 
This amendment will be submitted for review and approval to all Group 1 and Group 2 
participating IRB’s.  A copy of each IRB’s approval for this amendment will be 
submitted to Sponsor.  
 
Informed Consent 
Patients enrolled in the post approval study have signed informed consents detailing the 
study requirements and are aware their data will be included in a computerized database 
by Sponsor for this study.   Since this amendment does not affect data already submitted 
and reported to Sponsor, nor will this amendment affect patient safety or well-being, 
subjects will not be required to sign a new consent. 
 
The AOANJRR supplemental data will be included with all Post Approval Study Annual 
Reports as required by FDA.   The Final Study Report will include the AOANJRR data 
as well as a comparison of the data as described in the Data Analysis Section on page 24 
of this amendment. 
 
 

 
Page 27 of 28 
18. 
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Bert, J. M., M.D., “Delayed Failure of Meniscal Bearing Elements in Total 
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13. Cohen, M., et al., “Meniscal-Bearing Unicompartmental Knee 
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