**SUMMARY MINUTES**

**OF THE**

**ORTHOPEDIC AND REHABILITATION DEVICES PANEL**

**MEDICAL DEVICES ADVISORY COMMITTEE**

# OPEN SESSION 

**JULY 20, 2000**

**Gaithersburg Holiday Inn**

**2 Montgomery Village Avenue**

**Gaithersburg, MD**

**ORTHOPEDIC AND REHABILITATION DEVICES PANEL ROSTER**

**July 20, 2000**

Barbara Boyan, Ph.D.

Chair

Albert J. Aboulafia, M.D.

Voting Member

Velia Butcher, J.D.

Consumer Representative

Edward Y. Cheng, M.D.

Voting Member

Maureen Finnegan, M.D.

Deputized Voting Member

Robert Goldman, M.D.

Deputized Voting Member

Kinley Larntz, Ph.D.

Deputized Voting Member

Peter A. Lewin, Ph.D.

Deputized Voting Member

Glenn B. Pfeffer, M.D.

Deputized Voting Member

John A. Robinson, M.D.

Deputized Voting Member

Raymond Silkaitis, Ph.D.

Industry Representative

Douglas G. Wright, M.D.

Deputized Voting Member

Michael J. Yaszemski, M.D., Ph.D.

Voting Member

**FDA Personnel**

Hany Demian, M.S.

Panel Executive Secretary

Celia Witten, M.D., Ph.D.

Director, Division of General and Restorative Devices

Sankar Basu, Ph.D.

Physicist, Office of Device Evaluation

Gerry Gray, Ph.D.

Division of Biostatistics

Neil R. P. Ogden

Branch Chief, General Surgery Devices Branch

**OPEN SESSION**

**Panel Executive Secretary Hany Demian** called the session to order at
9:40 a.m. After reading the deputization of temporary voting member
statement, he deputized Doctors Larntz, Lewin, Robinson, Goldmman,
Pfeffer, Wright, Finnegan, Li and Lyons. He then read the conflict of
interest statement and added that Doctors Cheng, Larntz, Wright and Li
could participate fully in the panel proceedings. Additional matters
were considered for Doctors Boyan, Yaszinski, Cheng and Li, and they
also could participate fully in all discussions. The panel members
introduced themselves.

**Panel Chair Dr.Barbara Boyan** reviewed the agenda for the day and
noted there was a quorum of voting members present in this session.

**Dr. Celia Witten, Director of General and Restorative Devices**
presented Dr. Boyan with a plaque for her five year service on the
panel. She then gave Dr. Silkaitis a certificate of appreciation for his
service from 1997 to 2000. She noted that the new Director of the Office
of Device Evaluation is Dr. Bernard Statland.

## OPEN PUBLIC HEARING

No one came forward from the audience to address the panel.

Summarizing three letters supporting this device for the treatment of
plantar fasciitis, **Panel Executive Secretary**, **Mr. Demian** stated
that the OssaTron is an alternative to surgery with little risk of side
effects from the procedure.

## OPEN COMMITTEE DISCUSSION

Premarket Approval Application P990086: HealthTronics OssaTron
Lithotriptor for the Treatment of Heel Pain

## Sponsor Presentation

**Marie Marlow, Vice President of Clinical and Regulatory Affairs for**
**HealthTronics**, introduced the OssaTron, an extracorporeal shock
device to be used in the treatment of chronic heel pain syndrome. She
added that extracorporeal shock wave devices have been used for many
years in the treatment of kidney stones.

**Dr. Schultheiss, Director of Sales and Marketing of HealthTronics in
Switzerland**, reviewed the functional components and technical
properties of the device, technical and bench testing, and clinical and
non-clinical testing. He emphasized that the power settings are much
higher for lithotripsy than for treatment of heel pain syndrome.

**Marie Marlow** presented the clinical study results. The study was a
multi-center, randomized double blind placebo controlled trial that
evaluated the safety and effectiveness of this device and the durability
of the results of this treatment. The patients were evaluated at twelve
weeks, six months and twelve months. Ms. Marlow reviewed the treatment
procedure and the evaluation criterion. After identifying the
complications from the treatment, she pointed out that pain and mild
numbness or tingling were the most commonly reported complications.

**George DeMuth, President of StatTech Services**, provided the
statistical analyses. He reviewed the four criteria for successful
treatment and found that the investigator assessment of the heel pain
was the most sensitive criterion. The OssaTron was statistically a more
effective treatment than the placebo treatment and the effect was
sustained.

**Marie Marlow** concluded that a single treatment was safe and
effective. One treatment was sufficient in most patients. When
re-treatment was used, approximately the same success rate occurred as
with the first treatment. The complications of the procedure were
temporary and resolved spontaneously. She concluded the talk with
proposed labeling that included indications, contraindications and
precautions.

**Panel Chair Dr. Boyan** requested that questions be held until after
the FDA presentation.

## FDA Presentation

**Dr. Sankar Basu** presented the physics of this device. After he
described the method of energy generation, he delineated the
histopathological change at various energy densities. The energies
produced by the OssaTron are below the energy employed in stone breaking
lithotriptors. A large amount of experience has been accumulated already
with shock wave technology.

**Neil R. P. Ogden** presented the clinical data for the OssaTron. He
reviewed the indications for use, study design, and inclusion and
exclusion criteria. The FDA believes that "chronic heel pain syndrome"
is equivalent to plantar fasciitis. The trial design and the provided
data do not permit analyses of re-treatment results or the durability of
the treatment due to insufficient sample size and inadequate follow-up.
The variation in complications between treated and placebo groups is not
significant. The sponsor did not include plantar fascial tears in their
presentation of treatment complications.

**Dr. Gerry Gray** listed the four success criteria used in the clinical
trials: independent assessment of heel pain; self-assessment of heel
pain; activity score; and the use of pain medication. When the
therapeutic results between OssaTron and the Sham (Placebo) are compared
using the above criteria, OssaTron is significantly statistically
superior. The difference between these treatment modalities is due to
the increased sensitivity in independent pain evaluation and a higher
rate of responders in the OssaTron group. Predictive factors for overall
success includes age, baseline heel pain, duration of heel pain and back
pain.

## Panel Clinical Review

**Preclinical Review: Dr. Lewin** stated that the study followed the FDA
guidelines, and in general the study seemed to be solid.

**Clinical Review:** Since Dr. Robinson was impressed with the 12 week
assessment and with the Sham controls, he found the 12 week data to be
convincing; however the remaining data was not convincing to him.

**Statistical Review: Dr. Larntz** thought that the study focused on the
12 week outcomes and that one cannot make conclusions about patient
outcomes after six months in this study. He felt that 12 weeks was not a
long enough follow up for these patients. The fact that patients were
missing at the 12-week follow up was problematic for him. Another
problem in the study was that patients in the repeat treatment were
self-selected and therefore the trial followed the patient successes.

## Panel Questions

Dr. Richard Alvarez, Dr. John Ogden and Marie Marlow answered most of
the questions raised by the panel. When the panel questioned how the
device worked, Dr. Ogden stated that no one knew exactly the
explanation, however, research was being conducted on the molecular
level. In answer to concerns about future training programs, the company
representatives stated that similar training would be used as was
developed with the 50 nonrandomized patients.

Another concern was that peripheral neuropathy and vascular
insufficiency should be more precisely and objectively evaluated on the
follow up visits. In addition, more precise patient documentation should
be obtained on the patients who did not return.

The panel felt that patients who have osteoporosis should be included in
the study. Ms. Marlow revealed that early studies of osteoporotic
patients demonstrated increased bone density after treatment with
OssaTron at higher energy settings than those used in the application.

The panel also had concerns about the standardization of the injection
site for local anesthetic and local blocks. Ms. Marlow verified that no
patient included in the study had cortisone injections during the time
of the study. Cancer patients will be offered this treatment at some
future time. She went on to add that the application of this treatment
is with the patient with chronic heel pain , decreased vascularity,
increased fibrosis and fluid in the tissues.

Two other questions were raised. Would it be appropriate to use this
treatment on patients with failed surgery? What medical personnel should
use the machine?

## FDA Panel Questions

Mr. Ogden read the FDA questions to the panel.

1.  Although different complications were observed with the OssaTron
    treatments than with the Sham treatments, the panel felt that the
    side effects were not consequential with this device.

2.  From the data presented at this meeting, the consensus was that the
    use of the Ossa Tron provided clinically significant results.

3.  The OssaTron should be used in the treatment of patients with
    proximal plantar fasciitis.

Ms. Marlow discussed the profile and outcome of the patients who had
persistent pain after one OssaTron treatment. She stated that the
company made no claims about persistence of pain relief. Most patients
with chronic proximal fasciitis recover on their own over a period of
five years.

**Panel Chair Dr. Boyan** adjourned the meeting for a lunch break at
12:30 p.m. The meeting reconvened at 1:10 p.m.

## Open Public Session

No one came forward to discuss the device.

**Panel Executive Secretary Hany Demian** read the voting rules and
options. Dr. Robinson made a motion to approve OssaTron with no
conditions, and Dr. Yaszinski seconded the motion. The motion passed by
a vote of six to four. The voting members stated the reason for their
votes.

**Panel Chair Dr. Boyan** adjourned the meeting at 1:25 p.m.

> I certify that I attended the Open Session of the Orthopedic and
> Rehabilitation Devices Panel Meeting on July 20, 2000, and that this
> summary accurately reflects what transpired.
>
> [\_\_\_\_/s/\_\_\_Hany
> Demian\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_]{.underline}
>
> Hany Demian, M.S.
>
> Executive Secretary
>
> I approve the minutes of the meeting as recorded in this summary.
>
> \_\_[/s/ Barbara D. Boyan]{.underline} \_
>
> Barbara Boyan, Ph.D.
>
> Chair
>
> Summary minutes prepared by Lynne Blei

### 8916 Burdette Road

> Bethesda, MD 20817
>
> \(301\) 365-4031
>
> **ORTHOPEDIC AND REHABILITATION DEVICES PANEL ROSTER II**
>
> **July 20, 2000**
>
> Barbara Boyan, Ph.D.
>
> Chair
>
> Albert J. Aboulafia, M.D.
>
> Voting Member
>
> Velia Butcher, J.D.
>
> Consumer Representative
>
> Edward Y. Cheng, M.D.
>
> Voting Member
>
> Maureen Finnegan, M.D.
>
> Deputized Voting Member
>
> Kinley Larntz, Ph.D.
>
> Deputized Voting Member
>
> Stephen Li, Ph.D.
>
> Deputized Voting Member
>
> John Lyons, M.D.
>
> Deputized Voting Member
>
> Raymond Silkaitis, Ph.D.
>
> Industry Representative
>
> Michael J. Yaszinski, M.D., Ph.D.
>
> Voting Member

#### FDA Personnel

> Hany Demian, M.S.
>
> Panel Executive Secretary
>
> Celia Witten, M.D., Ph.D.
>
> Director, Division of General and Restorative Devices
>
> Peter Allen, M.S.
>
> Engineer, Orthopedic Devices Branch
>
> Harry Bushar, Ph.D.
>
> Statistician, Division of Biostatistics
>
> **OPEN SESSION**

The meeting was called to order at 1:43 p.m. by **Panel Chair Dr.
Barbara Boyan**, who stated that this session of the panel would be
considering the premarket approval application (PMA) of Howmedica
Osteonics' ABC and Trident Systems. She asked the panel to introduce
themselves.

##### OPEN COMMITTEE DISCUSSION

> **Premarket Approval Application P000013 Howmedica Osteonics ABC and
> Trident Systems**
>
> **Sponsor Presentation**
>
> **Beth Staub, Vice President of Quality Assurance, Regulatory Affairs
> and Clinical** **Research** introduced the ABC and the Trident
> Systems. **Michael Manley, Ph.D., Chief Scientific** **Officer**,
> introduced the speakers.
>
> **Thomas McCarthy, Hip Project Manager, System III**, reviewed the
> Study Control and next detailed the difference between the ABC
> (Aluminum Bearing Couple) Systems and the Trident System as a
> permanently assembled Titanium sleeve around the ceramic cup. He
> emphasized that only the ceramic inserts are under investigation in
> these systems.
>
> **Michael Bushelow, Assistant Director of Device Evaluation**,
> iterated that the inserts, which are under consideration for this
> trial, far exceeded FDA standards in all strength testing.
> Furthermore, the bone stresses generated at the fixation interfaces
> were acceptable.
>
> **James D'Antonia, M.D., Principal Investigator**, described the
> surgical techniques and cited some specific patient cases.
>
> **Dr. Manley** presented the clinical data noting that in this study
> the mean age was less than 55 years, the majority of patients were
> male, and most of the patients carried the diagnosis of
> osteoarthritis. The patient satisfaction was high both for the ABC
> Devices and for the Control Device. After Dr. Manley reviewed the
> changes on the post-operative radiographs, he concluded that the study
> revealed equivalent performance of hips with the ABC Devices and the
> Control Device.
>
> He next turned to the Trident results that were equivalent to or
> better than the ABC results. The operative site adverse event rate was
> lower with the Trident System than with the ABC Systems or Control
> System. Furthermore, the Trident System provided multiple revision
> options.
>
> **Dr. D'Antonio** addressed the first Panel Question regarding
> chipping in the ABC inserts. In general, chipping is not of clinical
> concern, if the liner is not left in a canted position. Beth Staub
> stated that with proper labeling, training and education this question
> should not be a persistent problem. Ms. Staub addressed the question
> of the Trident Systen after seven weeks of clinical trials noting that
> the ABC and Trident Systems are very similar and that Trident exceeded
> ABC in almost all tests. Ms. Staub stated that if the Trident System
> were approved at this time, the ABC and Trident cases would be
> followed together with the Control Group for an additional two years.

**FDA Presentation**

**Lead Reviewer Peter Allen** noted the difference in the ABC Systems
was an exterior hydroxyapatite coating on the acetabular shell of System
II. The Titanium sleeve on the Alumina ceramic insert helps prevent
chipping in the Trident System. It is the ceramic or ceramic couple that
makes these systems investigational.

The FDA found the pre-clinical testing adequate and has no further
issues with this portion of the trial. Efficacy studies showed virtually
no difference between the two ABC Device scores and the Control Device
scores. The major concern with the ABC Systems was chipping, especially
during surgery. The secondary end points including patient satisfaction
and results of the Health Status Questionnaire show no difference
between the three systems.

The Trident System , an updated version of the ABC Systems, shows early,
comparable results with the ABC Systems and Control System, without the
adverse event of chipping.

**Statistical Reviewer Harry Bushar** reported that the ABC Clinical
Trial was a prospective, controlled, randomized, multi-center study with
two study arms. The Trident Clinical Trial has borrowed the Control
System from the ABC Study. In regard to safety, the Trident System has
had fewer adverse events than the ABC Systems by reducing chipping to
zero. The effectiveness or failure rates are comparable between the
Control Study and the ABC Study.

Mr. Allen ended the FDA presentation by summarizing the three FDA panel
questions.

###### Panel Clinical Review

**Pre-clinical Reviewer Dr. Li** started his review by stating that
ceramic on ceramic devices had three problems: fracture, loosening of
the acetabulum and impingement. He feels that the problem of ceramic
fracture has been solved. Over time there has been a reduction of
osteolysis with these devices, however this problem may not be solved.
One of the gravest problems is corrosion of Titanium after five to seven
years.

This trial did extensive mechanical testing under a single condition,
and therefore, additional tests should be done under non-optimal
conditions. A general issue is mal-alignment or canting of the liner in
the shell. Chipping of the liner is an indication of mal-alignment. In
some literature, mal-alignment is said to occur in 30% of cases. The
current literature regards the metal polyethelene device as standard,
however there is little accumulated knowledge about ceramic on ceramic
devices.

He questioned whether the study should combine data from liners with and
without hydroxyapatite coatings. Further, should the Trident System use
data from the ABC tests?

In summary, Dr. Li felt that these devices appear to be safe. The
question remains of what criteria should by used in the future to
evaluate ceramic on ceramic devices.

**Primary Clinical Reviewer Dr. Lyons** found ceramic devices clinically
attractive due to the smoothness of the surface and inertness of the
material. Problems arise with the brittleness of the material,
specifically chipping at the periphery of the cup. Training on
implantation techniques becomes a primary issue to minimize this
problem.

Disclosure to surgeons is needed so that the surgeon understands options
with these three devices. For instance, Trident is easier to revise at
surgery. Since monitoring is crucial to collecting data on these
devices, post market surveillance is an important issue. Retrieval of
these devices for additional testing could contribute to better
understanding of performance and failure.

**Statistical Reviewer Dr. Larntz** stated the Howmedica Osteonics made
a nice statistical presentation, however nothing is known about the
long-term failure rate of the Trident System. If one considered only
short term adverse events, one would chose Trident.

A five-minute break was taken at 3:43 p.m.

###### Panel Questions

The panel had concerns about the difficulty of implantation and removal
of the ceramic liner at surgery.

They questioned the importance of canting of the assembly and
association with chipping. In the discussion the point was made that
Titanium wears faster than ceramic material.

They returned to the difficulty of predicting the future performance of
the Trident System.

If chips occur in the post-operative period, are there any untoward
biological effects? How would a physician or patient decide which system
to use? The underlying question for discussion was, is this product
better than what is available on the market?

Dr. Witten clarified for the panel that they would be voting on an
entire system and not just the ceramic on ceramic interface.

###### FDA Questions

Mr. Allen read Question l.

Dr. Lyons felt slipping was not a concern since it could be overcome
with training on liner implantation. Ion leaching from Alumina over time
could be a clinical problem.

On Question 2, the panel continued to be concerned that the data from
the ABC Systems could not predict the future performance of the Trident
System.

In answer to Question 3, most panel members felt a five year follow up
study was indicated. Dr Li mentioned that ceramic on ceramic devices
fail in five years.

Howmedica Osteonics representatives answered the three FDA questions.
Dr. D'Antonio noted that the ABC System had an extraction device and
that osteolysis was a persistent problem with hip replacement in young
patients.

###### PANEL VOTE

**Executive Secretary Hany Demian** read the voting instructions to the
panel.

Dr.Lyons made a motion for Trident and ABC Systems approval with
conditions. Dr. Aboulafia seconded the motion.

The motion passed with a five to two vote. The conditions were discussed
and unanimously agreed upon as follows:

1.  Warnings to surgeons

2.  Disclosures concerning the different systems

3.  Education

4.  Post market surveillance at the end of 5 years to include retrieval
    analysis

5.  Monitoring of surgeons.

Dr. Witten advised that requesting new clinical data was not equivalent
to adding conditions. If the panel was advising a company how to put the
product in approvable form , that was not the same as voting for
approval with conditions.

Dr. Finnegan made a motion to strike down the current motion and moved
to separate the ABC and Trident Systems. The motion was seconded. Dr.
Lyons accepted the motion to strike down his original motion, and he
made a new motion to accept the ABC System with conditions. Dr.
Aboulafia seconded the motion. Dr. Boyan repeated the conditions for the
ABC System and asked for a vote of approval with the above mentioned
conditions. The panel voted unanimously to approve this motion.

The panel members iterated reasons for their votes.

Dr. Lyons made a motion to approve the Trident System with conditions,
and Dr. Aboulafia seconded it. A discussion followed. The motion was
defeated with three for and four against the motion.

Dr. Finnegan made a motion for non-approvability, and Dr. Cheng seconded
the motion. The motion passed with a four to three vote. Every panel
member discussed their vote and added their suggestion to make the
product approvable. Persistent questions remain: corrosion of Titanium,
performance in two to five years, additional wear testing, and the
performance of the new interface.

**Executive Secretary Hany Demian** thanked all the participants of the
panel and adjourned the meeting at 5:23 p.m.

> I certify that I attended the Open Session of the Orthopedic and
> Rehabilitation Devices Panel Meeting on July 20, 2000, and that this
> summary accurately reflects what transpired.
>
> [\_\_\_\_/s/\_\_\_Hany
> Demian\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_]{.underline}
>
> Hany Demian, M.S.
>
> Executive Secretary
>
> I approve the minutes of the meeting as recorded in this summary.
>
> \_\_[/s/ Barbara D. Boyan]{.underline} \_
>
> Barbara Boyan, Ph.D.
>
> Chair
>
> Summary minutes prepared by Lynne Blei

### 8916 Burdette Road

> Bethesda, MD 20817
>
> \(301\) 365-4031