MEMORANDUM

Reclassification Petition: Clinical Consult Review

 

To:      Orthopaedic Advisory Panel

From:  Orthopaedic Devices Branch, Division of General, Restorative and Neurological Devices;

Date:   April 26, 2004           

Subject:  Reclassification Petition: Mobile Bearing Knee Prostheses       

 ____________________________________________________________________________________

 

Summary: 

This reclassification petition presents data to support the petition for reclassification of all mobile bearing unicondylar, bicondylar condylar and tricompartmental knees from Class III to Class II.  This includes clinical data from IDE and outcome studies, peer reviewed journal articles and meta- analysis comparison analyses between fixed and mobile bearing systems related to adverse events and effectiveness outcomes. The sponsor believes that this information provides strong evidence of the safety and efficacy of mobile bearing knees, and that the risks associated with these devices are now adequately defined. Before a decision can be made whether reclassification from Class III (Premarket Approval Application) to Class II (Special Controls) is justified, further information and clarification is needed.

 

Background:

Reclassification is requested from Class III to Class II.  

There are numerous mobile bearing knee designs on the market worldwide

designed to increase contact area and /or to reduce implant-to-bone interface stresses by allowing mobility of the polyethylene bearing on the tibial plate in order to potentially reduce long-term wear.

 

Regulatory History of the Device Class

FDA issued a Proposed Rule classifying 77 orthopedic devices on July 2, 1982 (47 FR 29052), and the Final Rule on September 4, 1987 (52 FR 33686). The Final Rule established twelve separate categories of implantable knee prostheses (21 CFR 888.3480 through 888.3590). Each of the twelve types of knee prostheses described were assigned to either Class II or Class III depending on system attributes such as fixation method, level of constraint, and degree of resurfacing (e.g., patellofemorotibial versus femoral).

 

None of the categories, however, describes the type of total knee replacement system that has come to be known as the mobile bearing knee.

 

The question of reclassification of mobile bearing knees from Class III (Premarket Approval) to Class II (Special Controls) was considered by an FDA Advisory Committee on January 13, 1998. At that time, the panel's recommendation was to retain the Class III designation for all tricompartmental and unicompartmental mobile bearing knees with the exception of recommending reclassification of tricompartmental mobile bearing knees

that are cemented and have a rotating/translating base. The panel also recommended post-market surveillance for those mobile bearing knees reclassified to Class II. The FDA subsequently chose to recommend submission of a new reclassification petition for the entire class of mobile bearing knees, rather than reclassify specific subcategories.

 

Device History

The first mobile bearing knee designs were introduced in the late 1970's. The Oxford Unicondylar knee (Biomet, Inc., Warsaw, IN) was the first to utilize a mobile bearing to reduce contact stress while also reducing implant-to-bone interface stress. Since those early implants, several generations of mobile bearing knees have followed, and today there are nearly 50 unicondylar and bi-condylar implant designs with either platform-style or meniscal bearing design of the polyethylene articulating surface on the international market. There are numerous variations in the directional mobility of the polyethylene, type of constraint of the polyethylene, and treatment of the PCL.  The first mobile bearing knee to be approved by the FDA for sale in the U.S. was the Low Contact Stress (LCS) Rotating Platform Knee (J&J DePuy, Warsaw, IN). PMA approval for this knee was received in 1985, and since then five other mobile bearing knees have been approved in the U.S.

 

Reclassification of several types of knees from Class III to Class II was considered by an FDA Advisory Panel on January 13, 1998 ("Petition for Reclassification, Patello-Femoral-Tibial Metal/Polymer/Metal/Polymer/Metal Biologically Fixed Prosthesis, submitted by the Orthopedic Surgical Manufacturers Association, July 25, 1997). Mobile bearing knees were included in that petition. At that time, the Panel believed there was insufficient evidence to provide reasonable assurance of safety and efficacy for the entire class of mobile bearing knees. They recommended reclassification only of tricompartmental mobile bearing knees that are cemented and have a rotating/translating base. However, they recommended the retention of Class III designation for all other tricompartmental and unicompartmental mobile bearing knees.

 

 At this time 6 devices are available in the US:

• Low Contact Stress (LCS) Rotating Platform

• P.F.C. Sigma Rotating Platform

• P.F.C. Sigma Stabilized Rotating Platform

• Low Contact Stress (LCS) Meniscal Bearing

• Low Contact Stress (LCS) Unicompartmental Knee

• Oxford Meniscal Unicompartmental Knee

 

Intended Use:

The intended use differs depending on the subtype.

 

The mobile bearing total knee, fixed with or without bone cement is indicated for:

• Patients with knee pain and disability due to rheumatoid arthritis, osteoarthritis, traumatic arthritis, polyarthritis, collagen disorders and/or avascular necrosis of the femoral condyle

• Post-traumatic loss of joint configuration (particularly when there is patellofemoral erosion, dysfunction, or prior patellectomy)

• Moderate valgus, varus, or flexion deformities

• The salvage of previously failed surgical attempts if the knee can be satisfactorily balanced and stabilized at the time of surgery

 

The mobile bearing unicompartmental Knee, fixed with or without bone cement is indicated for:

• Patients with knee pain and disability due to osteoarthritis or traumatic arthritis

• Previous tibial condyle or plateau fractures with loss of anatomy or function

• Varus or valgus deformities

• Use with an intact Anterior Cruciate Ligament (ACL)

• Revision of previous unicompartmental arthroplasty procedures

 

Device Description/Principle of Operation:

This class of devices includes two subtypes: bicondylar knee joint patellofemorotibial metal/polymer mobile bearing cemented or porous coated uncemented prosthesis" and

Unicondylar knee joint femorotibial (uni-compartmental) metal/polymer mobile bearing

cemented or porous coated uncemented prosthesis"

 

The defining feature of a mobile bearing knee is the presence of a moving polyethylene bearing that articulates with both the femoral condyle and the tibial tray.  It is theorized that mobile bearing knee designs potentially reduce polyethylene wear by their highly conforming surface that disperses contact forces over a large area. The mobility in the polyethylene bearing, which reduces implant-to-bone interface stresses, may prevent implant loosening, which has been attributed to high interface stresses in highly conforming fixed bearing knee designs.

 

Mobile bearing knees are available in PCL-retaining, PCL-sacrificing and PCL stabilizing designs. In general, knees with only rotating mobility utilize a PCL sacrificing or PCL-stabilizing design, while multidirectional platform knees generally are PCL-retaining.

 

These devices can be further categorized by the type of bearing surface (Platform, bicondylar meniscal bearing, and unicondylar meniscal bearing), type of constraint and type of fixation (cemented , porous coated uncemented).

Bearing Surface included:

independently in arced tracks that run anteriorly and posteriorly in the fixed, metal

tibial component

compartment of the knee is replaced. The polyethylene may run in a track as

described above, or may move freely, held in place only by its reciprocal shape and

the tension of the surrounding ligaments.

 

Past experience and literature have shown that the use of cement has improved results and higher failure rates are associated with non cemented use.  In light of this information, it should be considered whether we can  include uncemented (porous coated) devices with cemented devices (i.e. do we have enough data to feel comfortable that special controls will predict safe use).

 

Type of Constraint (prevention of bearing dislocation)

Unconstrained designs have very low constraint forces over the entire range of normal (physiologic) displacements.

Semi-constrained designs have near physiologic constraint that rises over the range of normal displacements.

Constrained designs have constraint forces that exceed physiologic levels and rise sharply over the range of displacements

 

Characterization of the Directional Mobility of the Bearing Surfaces:

 Nine knee designs were tested in a dynamic testing system in which compressive load was applied as the knee was rotated or moved in the A/P or M/L direction. Torque or shear forces were measured and plotted against displacement, thus characterizing the ability of the knee design to constrain displacement during gait. The nine designs were then characterized as "unconstrained", "semiconstrained", and "constrained". Of the nine designs evaluated, all demonstrated unconstrained motion in the rotational direction and all the mobile bearing designs

demonstrated unconstrained mobility within a total of 15 degrees internal/external rotation. Relative to M/L mobility, the designs tested were evenly divided between semi-constrained and constrained mobility. Constrained and semiconstrained M/L mobility is characteristic of both mobile and fixed bearing knee designs, and does not adversely affect clinical performance.  Analysis of A/P mobility revealed a wide range of constraint, with unconstrained designs prevailing. In order to achieve joint stability with the lower level of constraint, competent soft tissue, including balanced collaterals and/or the PCL are necessary.

 

• Congruence:

Fully congruent mobile bearing knees are those that have a high degree of conformity between the femoral condyle and the polyethylene bearing surface, over a wide range of flexion (approximately 120 degrees). accomplished by providing a constant sagittal femoral radius, limited by posterior impingement of the tibial component. A fully congruent prostheses has a large contact area between the femoral condyle and the bearing surface, disperses contact forces, thereby theoretically resulting in reduced polyethylene wear.

 

Gait congruent or partially congruent mobile bearing knees have large contact areas in the first 20 degrees of flexion. The contact area decreases with flexion due to a decreasing sagittal radius. These prostheses maximize contact areas in the low end of the flexion range, while decreasing the sagittal radius to improve flexion range.

The term "functionally congruent” is used to mean that a device has a single femoral radius for up to 75 degrees of flexion.

 

Summary of Unpublished IDE data

 

BIOMET

TRAC PS

Rotating

Platform

OXFORD

UNICOND Phase II

Meniscal Bearing

S&N

GEN II

Rotating P,

Multidirectional P

PROFIX

RP

MP

STRYKER

HO SCORPIO PS

RP

ZIMMER

MOBILE BEARING

KNEES

MP

ZIMMER

NEXTGEN

LPS FLEX

RP

Type

P, MC, Rand

P,MC

P,MC,R

P,MC,R

P,MC,R

P,MC, NR

P,MC,R

#enrolled

130 (all cemented)

125 knees(all cemented)

107 pts

109/119 cemented

94/104knees uncemented

15 hybrid

59

50 cement

9 hybrid

62

179

61cemented

1 yr

103

104/125

106 pt

 

41 pts @ 7 weeks; (6 mo 12pts)

145

81/123(65%)

2 yr (%)

89

 

3

 

 

51%

 

3 yr

333

 

 

 

 

 

 

4 yr f/u

6

 

 

 

 

 

 

Mean F/U

2.2 yr

4.8

1 yr

9 mo

3 mo

1.5 yr

 

Age Mean

65 (40-87)

62 (34-85)

64-65

64

63

65

62

KSS/HSS

Good-Excellent

KSS

1 yr     77.4%

2 yr     83.7%

3 yr     85%

4 yr     100%

HSS

95.2

95

14% required walking support

 89= ave KSS

KSS 92%

75% 6mo

KSS 89.7

89.3

KSS 84%

Revisions

7

16 (7?)

survivor ship 94% @ 6 yrs

88% cumulative @ 6yrs

2(1yr)

0

0

3

0

Reasons

-Poly  (multiple) dislocation(11)

-Insert subluxation (1)

-Pt dislike

-Poly dislocation(4%)

-Deep infection

-Lat  compartmt

degeneration

-Aseptic loosening :femur and tibia

-poly wear

-patellar complication

-RA onset

-Auto Accident

-Patella Dislocat

-improper alignment

-meniscal cyst

1 pt death

-deep infection(1yr)

-poly subluxation(3 mo)

-Fracture

-Fibroarthrosis

-RSD

 

-Wound healing probs

medial epicondyle avulsion

IPL disruption

-deep infection

-pain

-PCL insufficiency

 

Rev Rate (sponsor)

5.4%

15.4

1.7

 

 

1.7

 

*Note that in all of the studies 85-100% of patients had OA as a primary diagnosis.

 

International Studies

 

Zimmer MOBILE BEARING KNEES

NexGen LPS-Flex

# enrolled

1,254

390

Insall Categories

A

B

C

A

B

C

1 yr

447/552 (80%)

223/256

143/213 (81%)

80/86

24/30

55/60

2 yr (%)

223/256 (87%)

117/140 .(83.6%)

74/100  (74%)

15/15

3/5  (60%)

4/4

Mean F/U

33% at 2 yrs

 

 

 

 

 

KSS/HSS

Good-Excellent

81%

85.7

87%

83.8%

67%

74%

93%

100

79

67

91

100

Revisions

8 total  0.6%

2 total

Reasons

-Patellar complications

-Fixed flexion deformity/stiffness

-unspecified

Complication rate 3.6%

Deep infection (3 mo)

Instability (6 mo)

 

Data from two international clinical outcomes studies provide robust evidence of the clinical success of mobile bearing knees in general usage. These data sets represent a variety of surgical skills among numerous surgeons, in numerous countries, from general patients not limited by inclusion/exclusion criteria. Currently, 2 year data is

available from a total of 243 patients.  The published data is summarized in Volume 2, Appendix 3.

 

Overall Summary

The sponsor provides summaries of studies grouped by mobile bearing knees types.  Even within these groupings, the results are variable and very few prospective randomized controlled studies are reviewed, particularly those comparing mobile bearing knees to fixed bearing total knee arthroplasty out comes. Patient population varies as do indications ( Unicondylar vs. bicondylar)  Although retrospective studies are useful as they provide longer term information, the data collected retrospectively has inherent flaws due in large part to missing information and the need for interpretation.  Thus this data should be reviewed with some caution.  It is difficult to group all the different types of mobile bearing knees into one group as they appear to have very variable results, even within the same group.   The FDA believes the mechanics and adverse events may be unique for tricompartmental (patellofemorotibial) mobile bearing knees as compared to bicompartmental (femorotibial)and therefore recommend that a separate category be proposed rather than grouping these two types of devices together.

 

Multidirectional platform devices

This consists of 2 prospective (none randomized) and 2 retrospective studies which discuss 4 different devices implanted in 425 patients/491 knees (includes bilateral) with a major diagnosis of osteoarthritis (>70%).  Follow-up averaged 4.1 years  in the range of  2-8 years with variable patient follow-up percentages( as low as 35%) .    The outcomes results are variable and range from poorer results for the Accord device (Duffy) at 5 years  with 16% severe pain, mean knee score 60/100 and function score 42/100 and 58% survivorship at 10 yrs.,  to better results for the Rotaglide (Polyzoides) with pain in less than 3% of the patients(knee scores not reported). Knee scores in the other 2 studies range from 155-188/200. Some of the patients in these reviews were excluded if they had a revision.

Multidirectional Platform Devices Meta analysis

reference

Duffy & Philipson

Kaper et. Al.

Morgan-Jones et. al.  prospective

Polyzoides et. al.

 

retrospective

Device Name

Accord TKA

Self Aligning I

 

Rotaglide TKA

Knees/patients

74/61

35% f/u

172/141   OA

75/62

170 cemented

Age mean (range)

68-69

71 (47-90)

67

66

Deaths

16 pts (20 knees)

41

 

 

Lost to f/u

6

1 @ 5 yrs

 

 

Revisions/surg

25

(19 instability) 34%

15 (8.1%)

0

0

Complications

Infection

Aseptic loosening

Poly wear

Fractures

Stiffness

Pain

Dislocations

Lysis

Instability

 

1

8

2

 

 

 

3

8

19

 

4

4

2

4

1

1

No dislocation, subluxation, breakage, subsidence or osteolysis

1 patella replacement

No platform dislocation

No mechanical implant failures

1ptw/fracture@6 wks

 

NSS (mean)

60

35% good –excellent, fxn 4% good to excellent

KSS pre 81

        Post -155

KSS pre 96

         Post 188

95%  BritishOA score good/excellent

Function score

42

ROM    0o

Post      111o

ROM 2yr 133o

 

Survivorship

10yr= 58%

91.7 % (poly wear =98.8%

 

 

F/U (mean)

5 yrs, 4 mo

5.6 yrs (5-8yrs)

2.5 yrs

2-5 yrs

Comment

Poor as compared to conventional TKA  16% severe pain

Pt satisfaction = 94%

 

 

 

Rotating platform Devices

This consists of 2 prospective (one randomized) and 2 retrospective studies which discuss 1 device (LCS) implanted in 744 patients/939 knees (includes bilateral) with a major diagnosis of osteoarthritis (>70%).  Follow-up averaged 1-12 years with variable patient follow-up percentages( as low as 55%) .    The outcomes results are variable. Knee scores were not reported in one study, but range from KSS clinical of 90-91/100 (165/200) to 159/200 . 10% of knees had pain in one study.  Survivorship ranged from 88-94% in 2 retrospective studies at 14 and 11 years.  Revision rate from 3 studies range from 0-7%.

Rotating Platform Devices

Reference

Callaghan et.al.

Grodzki et. al.

Sorrells

Sorrells  retro

Device Name

LCS

PFC/LCS

LCS

LCS

Knees/patients

119/86

 

665/521

1117/9

Age mean (range)

70

73

70

56

Deaths

18

 

 

15/18 knees

Lost to f/u

5 knees

 

 

26 knee/25 pt

Revisions/surg

0

 

13 (2%)

8 (6.8%)

Complications

Infection

Aseptic        

      loosening

Osteolysis

Poly wear

Fractures

Stiffness

Pain

Dislocation

Malpositioning

Laxity

Sublux/subside

 

 

 

0

0

 

 

 

0

No information because article was in German

 

4

 

 

 

1

 

 

2

7

6

1

1/1

 

1

 

 

1

2

 

 

 

2

4

NSS (mean)

 

PFC =130

LCS =160

98% good to excellent at 11 yrs

85% good-excellent

Function score

ROM ave:

0-102o

 

 

 

Survivorship

100%

*

94.7%

88.1%@14yr

F/U (mean)

 

1 yr

1-11 yrs

8.5 yrs

Comment

Avoidance of a flexion gap thought to account for no dislocation/

osteolysis from backside wear

 

 

 

* blank spaces indicate that information was not available in reference

 

Meniscal Bearing Devices

This consists of 5 prospective (one randomized) and 3 retrospective studies which discuss 2 devices (LCS) implanted in 1666 knees (includes bilateral) with a major diagnosis of osteoarthritis (>70%).  Follow-up averaged 1-11.5 years with variable patient follow-up percentages( as low as 60%).  The outcomes results are variable. Knee scores were not reported in one study, but range from KSS clinical of 70-94/100.  Survivorship 93-99% in 5 retrospective studies..  Revision rate from 5 studies range from 1-9%. In the one randomized study the mobile bearing knees and fixed knees were similar.

 

Meniscal Bearing Devices

Reference

Bert

Hartford

Jordan

Jordan

Kim

Minns

Muller

RosenbergHenderson

Device Name

LCS

 

LCS prosp

LCS Uncement

LCS/AMK

Minns Meniscal

LCS unresurfaced patella

LCS/PCR

Knees/patients

43/

139/104

80 cement

50unceme

9 hybrid

160/141

473/375

120 bilat

165

RA and OA (57%)

436

35/27

Age mean (range)

63

66

68 yr    OA pts

68

65

67

 

72

Deaths

0

37 knees

66knees

39(34 after 24 mo)

0

 

 

3

Lost to f/u

 

47 knees

 

63

4

 

 

4

Revisions/surg

4 (9.3%)

10

2(0.8%)

18(3.8%)

2/2(1.7%)

8

 

1 (2.9%)

Complications

Infection

Aseptic       

      loosening

 

 

 

Fractures

Dislocation

 

Sublux/subside

 

 

 

 

 

 

 

 

 

3

 

5

 

 

 

1

 

 

7(hi in uncement

27%/31% loosening femur/tibia

 

2

 

 

 

 

 

 

 

 

1

 

 

 

4:3-2wk,1-6mo

1

 

5

1

8

 

 

 

 

 

4/2

 

 

 

 

Fractures

 

 

 

7

 

 

 

 

NSS (mean)

91% good-excellent

 

 

92/93

94.4/93.3

75% excellent 9%fair

NJOHS =90 @ 5yr

83 (14PTS)

60(5=Fair)

Function score

 

 

 

 

ROM =123/121

Flexion 89-103o

Dec instability

Dec flexion def

 

 

Survivorship

 

93%

99.5%

94.6% (8yrs)

98%

 

 

97%

F/U (mean)

1 yr

7.8 yr

12 yr

2-10 (4.7)

7.4

0-5yr

 

?

Comment

Proper measurement of flexion gap critical to prevent dislocation of elements

 

 

 

 

 

 

 

 

Combination of Rotating Platform and meniscal Bearing in same study

This consists of 3 prospective (none randomized) and 7 retrospective studies which discuss 6 devices implanted in  8433 knees (includes bilateral) with a major diagnosis of osteoarthritis (>70%).  Follow-up averaged 20 months-13.5 years with variable patient follow-up percentages.    The outcomes results are variable. Survivorship is 90-100% in at 5-10 yrs.  Revision rates range to 8%.


 

Combination of Rotating Platform and meniscal Bearing in same study  details on table Vol. 2, Appendix 3,p.240

 

Reference

Buechel

Buechel

/Pappas

Callaghan (8 reports)

Keblish

Keblish

Munzinger

Papchristou

Sanchez

Sotelo

Steil et al

Weissinger

Thompson

Device

Name

NJLCS

NJLCS

LCS/

Oxford

LCS

LCS

Moveable-bearing w/ anatomic femoral groove

LCS

Oxford 9 pts

Endo-model

18 pts

LCS

LCS

147

Meniscal

44 Rot Plat

LCS

LCS

Knees

/patients

373/282

357:   149 cemented

208 uncement

MB=140

RP= 217

 

963/918 (MC)

275 personal series

104/52

bilateral

1 side patella resurface

88 uncementd

16 cement

235

 

101 pts

290/250

42/41

33/31

Age mean (range)

68

62

35-90

68

69

68

63-72

66

69

65.8

73

Deaths

 

1

42

 

0

0

0

0

35

1

 

Lost to f/u

 

 

 

 

 

131 less than 2yr

 

 

99

 

 

Revisions

/surg

1

15 (4%)

65

9 (personal  3.3%)

1

8 (3%)

3 total

2 Oxford

(22%)

1 endo

8 /(8%)

5 (5.4%)

0

 

Infection

3

7

 

 

 

1

1

1

 

 

1

Aseptic    loosening   

3

6

 

4

 

 

2

1

 

 

 

Osteolysis

3(1.8%)

0

 

 

 

 

 

2

 

 

 

Poly wear

 

 

 

3

 

 

 

1

 

 

 

Fractures

1

2

 

 

 

 

 

 

 

 

 

Stiffness

 

 

 

 

 

 

 

 

 

 

 

Pain

 

 

 

 

 

 

 

 

 

 

 

Dis

location

5

MB=.7%

RP= 3.2%

Most common

 

 

1Patellar probs responsible for comps

 

2

 

 

 

Sublux/

subside

 

 

 

4

 

 

 

 

 

 

 

Fractures

1

2+

1 trauma

 

2 patellar

 

 

 

 femur

 

 

 

NSS

(mean)

PCR 68% excellent

CRP 47%

cement

85% excellent

11.5% poor

uncement

92% excellent

6% poor

 

Cemented

LCS-96% excellent

Uncement

LCS-97%

excellent

89.9 mean

95% excellent/good 4.2 yr

 

93

 

 

Dec pain

All to 21

pain free

12

occasional

Function score

 

 

 

 

 

 

 

78 ave

 

 

Dec ROM

Survivor

ship

 

 

 

 

 

 

 

 

97.5%MB 7 yrs

100% RP

 

 

F/U

(mean)

20 yr

91mo/52mo

5-11 yrs

2-8yr

5.24 yr

 

 

5.2yr

 

21 mo

20 mo

Comment

 

 

 

 

Nonresurf

patella same as resurfaced patella

Acceptable results re: -degree of stability - pain relief

 

 

IM alignmt flexi/extgap balancing  impt

 

 


 

Unicondylar Meniscal Bearing

This consists of 12 prospective (one randomized) and 8 retrospective studies which investigates 3 devices (LCS, Oxford, Lotus) implanted in 2385 knees (includes bilateral) with a major diagnosis of osteoarthritis (>90% in all except one study).  Several studies had small sample sizes (<60 pts) Follow-up averaged 2-11 years with variable patient follow-up percentages.(some less than 50%)    The outcomes results are variable, 47-98% success.  In one study, RA patients had better outcomes than the OA patients Survivorship 66 (6 yrs)-100% in at 5-10 yrs.  Revision rates are high in several studies, reported range 0 to 30%.  In this grouping, successful results were associated with specific patient inclusion and exclusion criteria, and patient anatomy.

 

Unicondylar Meniscal Bearing

REF

Device

Pts/Knee

Age

Revision

F/U

KSS

Fxn

Survivorship

Complications

Argenson

oxford

552

 

45(8.2%)

14

 

 

92%

 

Barrett

Oxford bicompart

62 pts

RA 46%

OA 54%

75

4 (7%)

4.5 yr

83% pain relief

ROM:

93-103o

93-73o

 

4 DVT

2 Dislocation

2 aseptic loosening

5 infxn

Bourne

Oxford Meniscal

Oxford Kinematic I

67

 

66

67

20 (30%)

 

3

5.5 yr

82

 

88

 

9 deaths

15 aseptic loosening

2 patellofemoral syn

1 dislocatn

1 infexn

 

Carr

25 bilateral medial compartment

121/96

 

69

1(0.8%)

44.4 mo

75% pts no pain

ROM 95-106

99.1% @ 9yrs

1 death

Loosening

displacement

Cohen

NJOHS

 

21/20

60

1

10 yrs

16 good-excellent

 

2 death

Aseptic loosening

Goodfellow

Oxford Uni Meniscal

103/85

 

70 OA

9 rev (9.2%)

36 mo

92% No pain

 

5 deaths

4 Aseptic loosening

2 Lysis

3 dislocn

2 infexn

Subluxation

ACL absence greater incidence of failure

Goodfellow O’Conner

Oxford

125/107

67

8 rev

4 failures

49 mo

89% pain free

Flexion deformity

Flexion worse post op

1death

1 infxn

5disloc

6Aseptic loosening

2lysis

 

Goodfellow

Uni

25/22

67 OA, AVN,fx

1

21 mo

92% no –mild pain

Flexion worse post op

 

1Loosning tibia

Gunther

Oxford Uni

53/51

68

11 (21%)

5.2 yr

53% report pain w/activity

 

Bearing dislocation greater in lateral compartment

6 Bearing dislocation

1Plateau fracture

Harding

Oxford I, II

50/50

 

14 (28%)

 

 

 

I 66%

II 86%

100% if indications met?

Poor outcome if ACL deficient

Keyes

Oxford Unicompartmental

 

 

0

5 yr

97.5% good -excellent

 

100%

 

Kumar

Oxford

Uni

100/

71

7 (7%)

11yr

Pre 62

Post 91

Pre 45

Post 71

85%

Aseptic loosening

McLardy

Smith

Oxford Uni

475/

<60

>60

 

10yr

 

 

94%

95%

 

Murray

Uni congruous mobile poly bearings

143/114

70

5 rev (3.5%)

7.6

 

 

98% 10yr

dislocations

Price

Oxford Uni

40 MIS

20 conv

40ABD TKA

57-91

 

 

 

 

 

 

Rees

Oxford UCA

631/507

primary and failed HTO

70

19 1o (3.1%)

5 HTO

 

 

 

96% 10yr

66%

Uni UCA should not be used in failed HTO

Sherman

Bilateral Bicompartmental Oxford Meniscal

/32

63

5

51 mo

Pain relief in all but one

No improvements in  ROM

 

Infection

Aseptic loosening

Bearing dislocation

Svard

Oxford Meniscal B uni

124/

70

6 (4.8%)

12.5

 

 

95% 10yr

Bearing dislocation

Vorlat

Oxford Uni

41/39

62

3

5 yrs

87

 

 

Infection

4 “other”

Weale

Oxford

31/28

70

2

 

 

Oxford scale 36.5/48

 

Aseptic loosening

Weale

Oxford Uni

56

80.3

2

1.4

25/28 good or excellent

 

 

 

Witvoet

Lotus

 

 

18 19%

4.6

71.9% good

28% poor

 

 

Poly wear

Radiolucencies

Poor techniques/indications

 

The sponsor provides results of review articles which report on large samples grouped together and summarized with survivorship rates (section VIII) of over 2500 knees over a 5-17 years evaluation of survivorship, with a range of survival for those prosthetics of  93% to 100% over this time.  The sponsor states that over 46 knees (Section XI) are available for review, however it appears that the article chosen include only two or three designs.

 

Review of testing shows that the amount of displacement permitted in the anterior-posterior and medial and lateral directions is highly variable

 

Meta analysis  (Vol. 1 Section VIII p. 68, Vol2, Appendix 4, p.272)  [see statisticians review, “problems” and analysis below]

 

The sponsor presents the result of a meta analysis of 21 studies reporting the outcome of 22 cohorts which enrolled a total of 2,490 patients (2,870 knees).The mean enrollment per study was 138, greater than 10 patients per study was allowed however.  Mean follow-up was 6 years for these patients, The mean age for these patient was 66 years with a slight majority of women(62.3%),  The majority of patients had Osteoarthritis (82%) and 13% were bilaterally implanted.  The outcome of the meta analysis was compared to a review of over 9000 patients with fixed bearing knees reported by Callahan, et al.

 

This table was provided as a summary.  The rate of revision was higher in the mobile bearing knees at 6.4% vs. 3.8% for fixed bearing knees. Two particular mobile bearing knees  have a high rate of revision (30%): the oxford phase I and the Accord TKA, which are both, according to the sponsor no longer used.  The mean percentage of patients with good or excellent outcomes following mobile bearing knees replacement is 90.3% which was similar to the percentage reported in Callahan’s review (89.3%) and lower than the fixed bearing group when comparing improvement in a global rating scale outcomes. 91% vs. 100%.  “The range of the percentage of patients with good or excellent outcomes following mobile bearing knee replacement was 35% to 100%.” Vol.2 Appendix 4, p. 277.

 

Meta analysis results :Comparison of mobile bearing knees vs. fixed bearing knees  (Vol. 1 Section VII, p.68)

 

Mobile bearing knees outcome result

Mobile bearing knees outcome result excluding Oxford phase I and Accord knee

Tricompartmental Fixed bearing knee outcome result

(Callahan et.al.)

# knees

2870

2729

9879

Weighted mean yrs of f/u

6.0

6.4

4.1

# cohorts analyzed

22

20

154

Weighted mean% good/excellent

90.3

93.4

89.3

% improvement in global rating scale

91.4

91.4

100

Weighted mean postoperative global rating scale score

87.8

89

86.6

Weighted mean % knees with any revision

6.4

5.1*

3.8

*The revision rate described in these studies is 30%.

 

The sponsor provided a survival meta-analysis which compared mobile bearing knees to fixed bearing knees based on survival estimates and reports reviewed by Callahan.  Estimates of implant survival were extracted from 37 articles (1989-2002) Implants were grouped into categories: 21 were mobile bearing knees and 16 were fixed bearing.  From these 111 survival estimates were extracted: 40 mobile bearing knees  and 71 fixed bearing.  The survival rates were “reduced” by the sponsor, when multiple survival estimates were provided for a unique device, data was reduced retaining the estimate with the most consistent definition of “revision” and the longest length of follow-up.

 

Mobile bearing knees and Fixed bearing implant survival compared

 

Overall survival

Mobile bearing knees

Fixed Bearing Knees

Mean follow-up

12-17 years

12.5 yrs

17.2 yrs

WLS estimate

0.9198

0.9263

0.9133

 

Survival meta analysis

There were 21 articles which summarized survival for devices which were grouped into a mobile bearing category and 16 grouped into a fixed bearing category. From these a total of 111 survival estimates were extracted, with 40 mobile bearing device group estimates, and 71 fixed bearing device group estimates. For each implant, information on the average period of follow-up and the total number of knee implants was tabulated.

 

There are several problems with the performance of this meta-analysis:

Judgments were made as to which survival reports to include “Since the number of survival estimates appearing in a given publication ranged from 1 to 30, data was reduced allowing only one estimate for each unique device (or set of similar devices within the mobile or fixed bearing group) from each article. When multiple

survival estimates were provided for a unique device, data was reduced retaining the estimate with the most consistent definition of revision and the longest length of follow-up.”

Reporting style was also problematic. Authors reported data using the patient or knee as

the unit of analysis. The number of “cases” or number of knees was used for this meta analysis. The data abstraction was completed by a research professional who was educated in the data abstraction requirements. Only variables that were consistently reported across the majority of studies could be analyzed. Difficulties in abstracting data resulted from two types of missing data. The first came when authors did not mention a variable of interest

in a study. The data abstractor could not determine if the variable was absent from the study or if it was not reported. The second difficulty arose when the variable of interest was mentioned as part of a subset of enrolled patients, but were not mentioned in number or stratified in the results.

 

The second problem involved the author’s choice of global knee-rating system and the method of reporting used for the scores. To allow comparison across studies, the mean preoperative and postoperative global knee-rating scale score using a 100-point scale was used.

The reporting of complications also showed variability. To allow comparison across studies, perioperative complication data were not collected. Complication data that was collected included the following categories: knees with any complication, knees with any revision, knees with revision for mechanical failure, knees with revision for aseptic loosening, and knees with revision for septic loosening. The anatomic portion of this classification scheme identified the prostheses by treatment of the posterior cruciate ligament (sparing, sacrificing, or both  sparing/sacrificing of PCL used in same study). When an article reported across more than one anatomic

classification and provided patient characteristics for each group, the data were treated as two separate articles. When an article reported data across more than one classification but did not provide patient characteristics for each group, the study was considered as a mixed group of prostheses.

 

The sponsor does a meta analysis of the new device class based on studies with greater than 15 patients enrolled per study reporting on this device, (randomized, non randomized and uncontrolled series, single investigator, multicenter are all reported in one large group).  They then use these results and compare it to another meta analysis already completed on another class of devices in which studies were included if 15 patients were enrolled and outcomes were measured by a global out come scale ( not necessarily all the same scale within and between the studies) Then the sponsor took the two meta analyses and compared the mean numbers for follow-up, revision, device survivorship and good to excellent results, without defining what patient inclusion/exclusion criteria were, what the criteria for revision are and what scales were used to rate good to excellent out come in a global scale.

 

For a meta-analysis, all the demographic and study design, assessment issues also have to be considered and it does not appear that these are completed for both analyses  The conclusion is that the device classes have the same outcomes.  However, the sponsor only provided 3 actual randomized studies in which a representative device from each class were compared prospectively under controlled conditions, and the meta analysis was not properly performed. Nonetheless the number of patients implanted is large and the results varied, the summary may be misleading by providing one mean for all devices.  This may be better characterized by summarizing subgroup results.

 

Risk to Health

Risks may be identified from:

                1.             The proposed and final classification rules (based on the Classification

                                Panel’s recommendation)

                2.             Review of the literature

                3.             Review of the MDR’s

                4.             Labeling for the device 

 

MDR ( Volume 1, section IX)

A search of the MDR reports found 385 MDR, 365 were of one manufacturer.

Injuries: 333

Malfunctions: 29

Death : 1

Other: 2

This table was constructed from the sponsor’s data listing in summary by type

Type of event

LCS Posterior

Stabilized

LCS Rotating Platform

LCS Meniscal Bearing

LCS Unknown type

LCS Femoral

LCS Tibial

LCS Patella

Loosening

3

18

 

1

3

4

2

Metal/poly separation

 

 

 

 

 

 

25

Bearing Fracture

 

3

35

4

 

 

2

Effusion

10

1

 

1

 

 

1

Incorrect bearing

 

1

 

 

 

 

 

Physician error

 

 

 

 

1

 

 

Impingement and Swelling

4

 

 

 

 

 

 

Infection

2

 

 

 

1

 

1

Unknown

2

1

1

1

 

 

1

Pain and Swelling

46

 

 

2

 

 

 

Broken Post

1

 

 

 

 

 

 

Patella spin out

 

 

 

 

 

 

2

Poly wear

 

11

11

 

 

 

3

Revision

1

 

 

 

 

 

 

Painful ROM

1

 

 

 

 

 

 

Poly defect

3

 

 

 

 

 

 

Subluxation

 

 

1

 

 

 

 

Bearing Failure

 

2

11

 

 

 

1

Patella locked

 

 

 

 

 

 

1

Impingement/wear

1

2

 

 

 

 

 

Fractured meniscal bearing

 

 

2

 

 

 

 

Loosening with debris

 

1

 

 

 

 

 

Fractured Poly

 

1

 

 

 

1

5

Allergic Reaction

 

 

 

2

 

 

 

Pain

15

1

1

 

2

2

 

Failed tibia

1

 

 

 

 

 

1

Pain/inflammation

1

 

 

 

 

 

 

Catastrophic Poly failure

 

 

1

 

 

 

 

Pain bilateral revisions

5

 

 

 

 

 

 

Bearing dislocations

 

5

 

 

1

 

 

Bleeding patella

 

 

 

 

 

 

1

Patella/(avulsion ) fracture

1

 

 

 

 

 

4

Stiffness ROM

2

 

 

 

 

 

 

Bearings disintegrated

 

 

1

 

 

 

 

Metallosis

 

 

1

 

 

 

 

Porocoat separation

 

 

 

 

1

 

 

Bent bearing track

 

 

 

 

 

2

 

Poly crumbled

 

1

 

 

 

 

 

Knee prosthesis failure

 

1

2

1

 

 

3

Package defect

 

 

 

 

1

 

 

Poly pitted

 

 

 

1

 

 

 

Implant defect

 

 

 

 

 

 

2

Mislabeled

1

 

3

1

 

 

 

Malpositioned

 

1

 

 

 

 

 

Implant did not fit

 

 

1

 

 

 

 

Unknown revision

 

 

 

 

 

1

1

 

Although the sponsor provides a list of the MDRs of the one device that is marketed in the US,  similar information is not available for mobile bearing knees devices in use outside the US.  Although literature articles provide some information, many do not report a complete profile of the adverse events.

 

Risks associated with knee surgery include infection, Pulmonary embolism, gastrointestinal and genitourinary problems.  Those associated with the device are listed above.  Risks were grouped into 3 general categories:

·         Infection

·         Adverse tissue reaction

·         loss or reduction of joint function/revision

The sponsor provided two tables which evaluated patient risk using the engineering tool, “Failure Modes and Effects Analysis” (FMEA).( Volume 1, Section X, pp. 85-93) The first table, contains the hazards common to both fixed and mobile bearing knees while the second contains the additional hazards specific to mobile bearing knees, exclusively.  Potential hazards are listed within each category, as applicable. Potential effects from those hazards and an initial risk assessment are presented.

 

Each hazard in these tables has provided one or more solutions or actions designed to reduce the potential risk to the patient. An assessment of the final risk after those solutions/actions are implemented is presented. In addition, special controls are identified for each of the hazards.  

 

However, because the mechanics and designs are significantly different , the testing demonstrated the safe use of fixed bearing knees may not be applicable to the mobile bearing designs.

 

The sponsor contends that many of the identified risks can be mitigated by material standards, proper device design, labeling and by controlling the device quality through Good Manufacturing Practices (GMP) Quality System Regulations (QSR). Numerous FDA guidance documents, ISO standards, and ASTM standards are available to provide specific guidance regarding materials, testing and labeling.

 

There are two risks that the sponsor believes are unique to mobile bearing knees and not common with fixed bearing knees.  These are:   the potential for the mobile bearing to rotate beyond design objectives, and the potential for greater wear due to an additional articulating surface are hazards related to the design of mobile bearing knees. For these two risks, there are no recognized standard testing methods to predict the modes of failure associated with these risks.

 

The sponsor also provides the following in support of the reclassification: (Volume 1, Section X)

• a review of the requirement for various types of special controls, including a complete listing of FDA guidance  

   documents, ISO Standards, and ASTM Standards that apply to knee prostheses.

• A breakout of guidance documents and standards, assigning each to one of the three general categories of risk

   (infection, adverse tissue reaction, and loss or reduction of joint function).

• Proposed Labeling for mobile bearing knees: a listing of indications, contraindications, warnings, and adverse

    events relevant to mobile bearing knees, including total knees and unicondylar knees.

    Also, included is proposed package insert content that includes information on total and unicondylar knees.

• Tests and test methods suggested for mobile bearing knees.

 

In the summary of risks a sponsor is charged with the task of providing a summary of the following information:

                1.             The incidence rate

                2.             Cause

                3.             Sequelae of the risk

                4.             Information demonstrating that the stated risk is not a potential

                                hazard of the device, if available.

 

Wear is defined through various bench studies, in-vivo explants are not presented and the results of bench testing is compared to hip wear data not knee data.  There are studies which review explants and there are several studies which characterize poly wear in fixed bearing knees which should be included.  The biomechanical characteristics are summarized in the preclinical review.

 

Known Potential Benefits

The potential benefits of the device include decreased pain and improved function; however it is not yet proven that these devices are better or even completely equivalent to a well functioning fixed bearing knee.  There are few published randomized controlled studies which examine the outcomes and risks of the fixed and mobile bearing knees side by side.  In some other reports, the survival rate of mobile bearing knees are slightly lower than fixed bearing knees, the patients are not more active and the revision rate slightly higher, showing that prevention of mechanical failure is not higher.  The theoretical advantage of a longer device life in younger, active patients is not proven as most studies the patients have a mean age of 65 or greater.  There are some studies which have shown that the contact stresses of fixed bearing knees may be equivalent to those of mobile bearing knees and few explant studies have validated that reduced wear actually occurs in situ in each type.  Osteolysis similarly has not been shown to be different in the mobile bearing knees designs.  (AAOS instructional course lectures:  Callahan, C.  Mobile Bearing Knees: Concepts and Results, 2001.)


That having been said, the sponsor does provide multiple retrospective and non randomized studies which report good to excellent clinical results for the majority of study patients.

 

Labeling: (Section X)

Indications

The data may not support indications for steroid dependent RA or valgus, varus and flexion deformities. Instability of the knee in general should be excluded.  There is no information to assist a physician to choose a Mobile bearing knees over a fixed bearing prosthesis, particularly in the indications statement, as this has not been properly studied

For the unicondylar knee indication should be correctable varus and valgus deformities is misleading.  This should be further clarified that both should not be present

 

____________________________________________________________________________________________

The memo that follows summarizes the submission and the responses to FDA’s deficiencies from a clinical perspective. 

 

Summary

This reclassification presents data to support the petition for reclassification of all mobile bearing unicondylar, bicondylar condylar and tricompartmental knees from Class III to Class II.  This includes clinical data from IDE and outcome studies, peer reviewed journal articles and meta- analysis comparison analyses between fixed and mobile bearing systems related to adverse events and effectiveness outcomes. The sponsor believes that this information provides strong evidence of the safety and efficacy of mobile bearing knees, and that the risks associated with these devices are not adequately defined. Before a decision can be made whether reclassification from Class III (Premarket Approval Application) to Class II (Special Controls) is justified, further information and clarification is needed.  The sponsor provides responses to the requests for further information as requested in the FDA letter dated February 2004.

 

Responses to deficiencies: 

1a. The sponsor provided Appendix 1a with multiple articles on wear, including back side wear not present in the original petition.  It includes a synopsis of articles on wear defined by these articles.

Review:   This response is adequate and the sponsor provides an adequate review of current literature.  It serves to corroborate the premises that:

 

Deficiency 1.b&c.

The sponsor has filled out the table FDA presented as requested to facilitate review of this reclassification petition. It states the representative mobile bearing knees, the biomechanical advantages and disadvantages, survivorship[(survivorship for each mobile bearing knee device type was calculated by averaging the survival estimate and mean follow-up reported in the article. Each article included had a minimum follow-up period of 5 years. If multiple definitions of survival were included, the most conservative definition was used.)   With the exclusion of this poor performer (Thackeray,UK), all mobile bearing device groups report  >90% survivorship (note: some of the groups have a small sample size).]

 

Response continued: Risks and special controls [OSMA divided them into two groups:

1-       risks and special controls that are common to fixed and mobile bearing knees, and for which there are no special issues related to mobile bearing design features.

Categories: sterility, biocompatibility, metal sensitivity, metal corrosion and separation of the porous coating from the metal substrate. These generic risks and related special controls were discussed in the original petition and were not included in Table 1.c.  This is adequate as the sponsor has already provided these previously

Risks and special controls includes those that have unique considerations when applied to mobile bearing knees when compared to the same special control applied to fixed bearing knees. For example, wear testing of mobile bearing knees needs to account for additional articulating surface wear and for rotational movement. Section Appendix 1.c. also includes a section entitled “Special Controls with Unique Mobile bearing knees Considerations”. This text provides descriptions of each special control, with an explanation of how the control will provide reasonable assurance of safety and effectiveness. In addition, the applicable FDA guidance, ASTM and/or ISO

documents are listed for each special control. Where no standard test method has been defined, OSMA has recommended a test method.

 

Test

Rationale

Current Standard

Suggested

Wear Test

-Simulate sliding Rolling and rotational mvmts

ASTM 1715

ISO 14243

 

 

 

- address backside wear

In vitro simulator/gravimetric analysis

Volume of wear scar

Observed changes to engraving marks

Particulate analysis

Determine risk of Osteolysis due to particulate

ASTM F-2025

ISO 14243-2

 

Spin Out test

 

None

ASTM F-1223

Tibial Tray Fatigue Test

 

ASTM F-1800

ISO 14879-1

 

Dissociation /Binding Test

 

None

Component interlock Strength Testing

SC guidance PF & FT M/P porous coated Uncemented Prosthesis

Overhang Deformation Test

 

none

ASTM F-1715

ISO 14243-1

Contact Area/ StressEvaluation (load damage)

 

None

Contact Area guidance Semi Constrained knees

ASTM F-1715

ISO 14243

PatelloFemoral Lateral Stability test

 

None

Lateral stability of the PF joint testing

PE Metal shear Fatigue and static Tensile strength test

 

 

Static Tensile Pull-off and shear Fatigue Testing

ASTM F-1672

Patello Femoral Contact Stress(load Damage and Patellar wear

 

None

ASTM F-1715

ISO 14243-1

Wear test of stop

 

None

ASTM 1715

ISO 14243-1

Labeling, Surgical Technique surgeon training

 

None

21 CFR 801,820 and ISO 6018

 

d. The sponsor provides Table 1.d. (see Appendix 1.d.) which provides a summary comparing the various mobile bearing knee device groups with fixed bearing devices.  And Supplement 1.d., which lists the clinical outcome details of each study that was utilized to provide the data in table 1.d.

 

Review: The sponsor has provided the information as requested, however because the sample size is small no statistical conclusions can be reached.  It is note worthy that only few mobile bearing knee designs are approved in the US and those are the subject of the reclassification petition. 

 

This table overstates the revision rate of Fixed Bearing Knees.  In the recent NIH consensus the overall prosthesis failure rate is given as 1% per year or 10% at 10 years.   It is worth noting that the revision rate of mobile bearing knees is not less than that of fixed bearing devices.