One June 9, 2003, the Obstetrics and Gynecology Devices Panel met in a 2-hour, closed session, and in a 2-hour open session. In the open session, FDA and NIH briefed the panel about post-market studies and adverse events related to the OxiFirst™ Fetal Oxygen Saturation Monitoring System. Nellcor Puritan Bennett (the manufacturer) also presented information.
- The post-market “Dystocia Study” has been completed. This study was designed to investigate why, in the pivotal clinical trial, the cesarean section rate for the indication of dystocia was higher among patients whose labor was monitored with OxiFirst compared with patients who were monitored only with fetal heart rate data. Based on this study, the investigators concluded that significantly non-reassuring fetal heart rate predicts Cesarean for dystocia among nulliparous patients having normally oxygenated fetuses in a setting of standardized labor management. FDA has just received this report.
- The “FOX” (Fetal Oximeter Study), which aims to determine if fetal pulse oximetry affects overall cesarean delivery rates, is ongoing. In this study, being conducted by the NICHD Maternal Fetal Medicine Network, 1250 patients have been recruited out of a projected 10,000 patients at 14 centers. The study will not be completed for at least 2-3 years.
- The “General Use” study, intended to determine the effect of widespread, uncontrolled, routine use of fetal oxygen saturation monitoring on cesarean delivery rates, is accruing patients very slowly. Furthermore, study results thus far indicate that the rates of cesarean deliveries change too quickly to measure how they are impacted by fetal oxygen saturation monitoring. This study will be difficult to complete.
- In response to 14 post-market adverse event reports (including 3 stillbirths or immediate neonatal deaths), changes have been made to the guidelines for use of fetal oxygen saturation monitoring. In February, 2003, Nellcor issued a "Dear Customer" letter with this information.
On June 10, the panel met in an open session to discuss the pre-market approval application (PMA P020031) from Microsulis for their Microwave Endometrial Ablation (MEA) System. This device is indicated for abnormal uterine bleeding due to benign causes in premenopausal women for whom childbearing is complete.
The panel considered the sponsor’s prospective, randomized, controlled clinical trial in which 210 women were treated with MEA and 107 women were treated with rollerball endometrial ablation (REA). The study design required women enrolled in the study to be followed for a total of three years post-procedure (twelve months premarket and an additional two years postmarket). The definition of success was a reduction in pictorial blood assessment chart (PBAC) score for menstrual flow from >185 to <75 at 12 months after treatment. Intent-to-treat success rates were 87.0% for MEA and 83.2% for REA.
The panel also considered the 27 serious adverse events that have been reported in non-U.S. commercial experience since 1998. In at least 14 events, injuries occurred in the absence of uterine perforation; 11 of these 14 events led to bowel resection. In response to these events, the Sponsor proposed the following requirements: preceptorship for new users; pre-operative ultrasound on all patients to confirm a minimal uterine wall thickness of 10 mm; hysteroscopy on all patients after cervical dilation and prior to insertion of the MEA applicator. The Sponsor has also proposed exclusion of any dilatation and curettage (D&C) at the time of the procedure.
In closing remarks near the end of the afternoon, FDA highlighted that the PMA review was very much in progress. Review issues related to the critical 10 mm minimum uterine wall thickness are still under consideration, including thermal modeling, resolution of diagnostic ultrasound, labeling, and training program.
The panel voted 9-0 to recommend that the PMA was approvable with the following conditions:
- There will be a statistical analysis for non-inferiority, including confidence intervals, based on the true intent-to-treat groups.
- Preceptorship will be done by experienced physicians; there will be no mechanical preparation done with the procedure; all patients will have hysteroscopic examination after dilatation.
- All patients will have a minimum myometrium thickness of 10 mm, as measured by ultrasound; measurements will include the cornua; ideally, transvaginal ultrasound will be used.
- Users will be required to have experience in diagnostic hysteroscopy.
- The labeling will be modified to reflect the above requirements.
Contact: Joyce M. Whang, Ph.D., Executive Secretary, 301-594-1180, x127
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