### SUMMARY MINUTES

### MEETING OF THE OBSTETRICS AND GYNECOLOGY DEVICES 

### 

### ADVISORY PANEL

**OPEN SESSION**

**June 9, 2003**

Gaithersburg Hilton

Gaithersburg, MD

Obstetrics and Gynecology Devices Advisory Panel Meeting

**Open Session June 9, 2003**

**Attendees**

**Chairperson**

Mary Jo O'Sullivan, M.D.\
University of Miami/Jackson Memorial Hospital

**Executive Secretary**

Joyce M. Whang, Ph.D.\
Division of Reproductive, Abdominal, and Radiological Devices

**Voting Members**

Machelle Allen, M.D.

NYU School of Medicine

Carol L. Brown, M.D.

Weill-Cornell Medical College

Memorial Sloan-Kettering Cancer Center

Charles C. Coddington, III, M.D.

Department of Obstetrics and Gynecology Denver Health Medical Center

Ralph B. D'Agostino, Ph.D.

Mathematical Statistics Department

Boston University

Gary S. Eglinton, M.D.

Department of Obstetrics and Gynecology

New York Hospital Medical Center at Queens

Evelyn R. Hayes, Ph.D.

College of Health and Nursing Sciences, University of Delaware

Jay D. Iams, M.D.

Department of Obstetrics and Gynecology

Ohio State University

Kinley Larntz, Ph.D.

School of Statistics, University of Minnesota

Michael Neuman, M.D., Ph.D.

Joint Program of Biomedical Engineering

University of Memphis

Kenneth L. Noller, M.D.

Department of Obstetrics and Gynecology

Tufts University Medical School

Susan M. Ramin, M.D.

Department of Obstetrics and Gynecology and Reproductive Sciences

University of Texas--Houston Medical School

Nancy C. Sharts-Hopko, Ph.D.

College of Nursing, Villanova University

Jonathan W. Weeks, M.D.

Suburban Hospital, Maternal-Fetal Medical Center

Louisville, KY

Deborah A. Wing, M.D.

Department of Obstetrics and Gynecology

Women's and Children's Hospital and USC Medical Center

Robert N. Wolfson, M.D., Ph.D.

Specialists in Women's Health

Colorado Springs

## Consumer Representative

Kleia R. Luckner, J.D., M.S.N.

The Toledo Hospital

## Industry Representative

Mary Lou Mooney, R.A.C.

SenoRx, Inc.

## FDA Participants

Nancy C. Brogdon

Director, Division of Reproductive, Abdominal, and Radiological Devices

Colin Pollard

Chief, Obstetrics and Gynecology Devices Branch

Danica Marinac-Dabic, M.D., M.M.Sc.

Office of Surveillance and Biometrics

**CALL TO ORDER**

**Panel Chair Mary Jo O'Sullivan, M.D.,** called the open session to
order at 2:49 p.m. and asked the panel members to introduce themselves.
**Panel Executive Secretary Joyce Whang** noted that upcoming panel
meetings have been tentatively scheduled for September 8 and 9 and
November 3 and 4, 2003. The panel has four new voting members: Evelyn R.
Hayes, Ph.D., Hugh Miller, M.D., Jonathan W. Weeks, M.D., and Kenneth L.
Noller, M.D. in addition, Charles C. Coddington, III, M.D., and Deborah
A. Wing, M.D., are new panel consultants.

Dr. Whang then read the conflict of interest statement. A full waiver
had been granted to Michael Neuman, M.D., Ph.D., who reported interests
in firms at issue in matters unrelated to the day's agenda. Hugh Miller,
M.D., reported past interests in firms at issue in matters unrelated to
the first session's agenda and could participate fully in the panel's
first session. However, due to conflicts of interest in matters related
to the second session's agenda, Dr. Miller was excluded from the second
session.

# BRANCH UPDATE

**Colin Pollard, chief, Chief, Obstetrics and Gynecology Devices
Branch,** introduced new FDA branch staff to the panel and updated the
panel on the activities of the branch since the last panel meeting.
Three original PMAs have been approved: the Essure System for permanent
birth control (November 2002); the Philips fetal pulse oximeter (January
2003); and the FemCap device, a barrier contraceptive (March 2003). The
Essure device was approved with conditions including postapproval
studies. The sponsor will continue to follow up with patients in phase 2
of the clinical trial and the pivotal study as well as conduct a smaller
study to look at bilateral placement rates in the general population.

Using a new regulatory tool called *early collaboration,* the Agency has
reached regulatory agreement on the pivotal clinical trial for
Medispectra, an optical system intended to serve as an adjunct to
colposcopy for detection and localization of diseased cervical tissue.
In October 2002, the Agency approved a 510(k) for the Embosphere for
uterine fibroid embolization, a nonsurgical alternative for women with
symptomatic uterine fibroids. The company will follow clinical trial
subjects for 3 years. In addition, In March 2003 the Agency did a *de
novo* reclassification of the BreastView system, a breast lesion
documentation system. Finally, the Agency oversaw the voluntary market
withdrawal of Intergel, an adhesion barrier product that is applied
immediately after pelvic surgery and before surgical closure.

Mr. Pollard stated that the purpose of the meeting was to update the
panel on the status of postapproval studies on the OxiFirst intrapartum
fetal pulse oximeter.

# OPEN PUBLIC HEARING

No comments were made.

# 

# OXIFIRST POSTAPROVAL STUDIES AND ADVERSE EVENTS 

**Danica Marinac-Dabic, M.D., M.M.Sc., Office of Surveillance and
Biometrics,** presented an update on FDA's post-market surveillance
activities related to the OxiFirst fetal Oxygen Saturation Monitoring
System. She reviewed the original approval decision and outlined the
issues that needed to be addressed in the postapproval studies for
Nellcor's OxiFirst device, which include the indications, cesarean
section rates, maternal infection rates, duration for which oxygen
saturation can remain below 30 percent before the risk of fetal injury,
adequacy of labor, and neonatal outcomes.

The postapproval plan has evolved into three separate studies: a General
Use Study, a Dystocia Study, and a Fetal Oximeter (FOX ) Trial.

From July 2000 to June 2003, an estimated 15,000 patients were
monitored, and 14 adverse events were reported. The adverse events
resulted in three deaths and nine injuries; two of the events involved
device malfunctions. Five of the adverse event reports indicated clear
deviation from the clinical guidelines.

A September 2001 ACOG committee opinion may have affected the use of the
device; the opinion stated that the committee could not endorse use of
the device because doing so could increase the cost of care without
improving clinical outcomes. In October 2002, Nellcor stopped active
marketing of the device and is now servicing only existing customers.
Dr. Dabic reminded the panel that the 14 adverse event reports came from
passive surveillance, meaning that it is highly likely that adverse
events are underreported.

The sponsor submitted a PMA supplement to change the labeling for the
device; it was approved in November 2002. The changes expanded the
definitions of "ominous" FHR and added a footnote stating that it is not
necessary to wait for more than 7 minutes of prolonged deceleration
before initiating intervention, even with reassuring FSpO~2~. The
labeling changes also stated that when FSpO~2~ is not available, the
fetus should be managed by FHR and clinical signs alone; that OxiFirst
is to be used as an adjunct to FHR monitoring, and that FHR
classification and clinical management tables accompanying the device
are recommendations.

In February 2003, the company sent a "Dear Doctor" letter to clinical
users of the device; the letter informed clinicians of the labeling
changes. FDA also sent a letter to the National Institute of Child
Health and Human Development (NICHD); it highlighted the issues in the
Dear Doctor letter and stated that the changes do not undermine the
results of the pivotal trial. When used according to the labeling, the
device is safe and effective for its intended use.

Dr. Dabic then summarized the status of the three studies. The General
Use Study is currently on hold because the usage rate is 1 percent of
all births; therefore, accrual of study participants is not proceeding
at the anticipated pace. The final report for the Dystocia Study, which
involved 274 patients at 5 sites, is in preparation. The FOX Trial,
which is being conducted by the NICHD Maternal Fetal Medicine Unit
(MFMU), is under way; current enrollment is 1,026, and the anticipated
sample size is approximately 10,000. The study is expected to last 2 to
3 years.

**Catherine Y. Spong, M.D.,** **chief, Pregnancy and Perinatology Branch
of the National Institutes of Health,** described the NICHD FOX study.
The aim of the study is to determine whether fetal pulse oximetry
affects the total Cesarean delivery rate. Participant recruitment began
in May 2002; more than 6,000 patients have been screened, 38 percent of
whom were ineligible. The consent rate is 30 percent. The mean age of
participants is 23.2 years and the mean education is 12.2 years; 6.6
percent are smokers. A total of 49.3 percent are white, and 29.6 percent
are Hispanic/Latino.

**David Swedlow, M.D., consultant to Nellcor Puritan Bennett,** began by
showing the numbers of monitors and sensors shipped over time. He noted
that clinicians who were using the OxiFirst device use it at same rate
as before the ACOG statement. Adverse events occurred during early use,
but as experience increased, events have tapered off. The sponsor
introduced new software and guidelines for use in fall 2002. All NICHD
sites are using the new software.

The Dystocia Study is testing the hypothesis that significantly more
nonreassuring FHR patterns identify patients at an increased risk for
dystocia given an adequate trial of labor in a setting of fetal
well-being defnied by normal fetal pulse oximetry. The study divided FHR
into two classes: intermittent, mildly nonreassuring (Class I) and
persistent, progressive, moderate to severe nonreassuring (Class II).
The study found that significantly more patients in Class II than in
Class I had cesarean delivery, confirming the hypothesis. The two groups
were not significantly different on a number of other variables.

The General Use Study was designed to address the concern that
widespread uncontrolled use of FSpO2 could increase the C-section rate.
A prospective 3-site study has been initiated to compare C-section rate
with the use of Oxifirst to historical rates. However, C-section rates
have changed in the time needed to initiate the study. The useage rate
has turned out to be about 1%, which is much less than the 30% projected
when the study was designed. At the current rate of accrual, it would
take three decades to complete.

Panel members asked clarifying questions on various aspects of the
methodology of the three studies. Ms. Brogdon noted that the Agency has
to decide whether to cancel certain conditions of approval. Panel
members noted that it has been difficult for the company to comply with
the conditions and that no decision could be made before the NICHD trial
ends.

# ADJOURNMENT 

Dr. O'Sullivan thanked the participants and adjourned the meeting at
4:08 p.m.

> I certify that I attended this open session of the Obstetrics and
> Gynecology Devices Advisory Panel Meeting on June 9, 2003, and that
> these minutes accurately reflect what transpired.
>
> \_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_
>
> Joyce M. Whang, Ph.D.
>
> Executive Secretary

I approve the minutes of this meeting

as recorded in this summary.

\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_

Mary Jo O'Sullivan, M.D.

Chairperson

> *Summary prepared by*
>
> Caroline G. Polk
>
> Polk Editorial Services
>
> 1112 Lamont St., NW
>
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> cpolk@earthlink.net