In January 2005, the oversight responsibility of the Post-Approval Studies Program was transferred to the Division of Epidemiology (DEPI) of the Office of Surveillance and Biometrics (OSB)/Center for Devices and Radiological Health (CDRH).
The CDRH Post-Approval Studies Program encompasses design, tracking, oversight, and review responsibilities for studies mandated as a condition of approval of a premarket approval (PMA) application, protocol development product (PDP) application, or humanitarian device exemption (HDE) application. The program helps ensure that well-designed post-approval studies (PAS) are conducted effectively and efficiently and in the least burdensome manner.
CDRH has established an automated, internal tracking system that efficiently identifies the reporting status of active PAS studies ordered since January 1, 2005 based on study timelines incorporated in study protocols and agreed upon by the CDRH and applicants. This system represents CDRH's effort to ensure that all PAS commitments are fulfilled in a timely manner.
In addition, CDRH launched this publicly available webpage to keep all stakeholders informed of the progress of each PAS. The webpage displays general information regarding each PAS, as well as the overall study status (based on protocol-driven timelines and the adequacy of the data) and the applicant's reporting status for each submission due.
The primary goal of the study is to evaluate the incidence of post-procedure significant leg
pain for the ExAblate treatment of uterine fibroids using enhanced sonication. Leg pain analysis will test non-inferiority of the ExAblate test group versus an incidence reference of 7%, allowing for a non-inferiority delta of 10%.
Study Population Description
Pre or peri-menopausal women who are not pregnant or breastfeeding, ages 18 and over, are
seeking treatment for fibroid symptoms will be evaluated and invited to participate in the study.
A total of one hundred and fifteen (115) patients will be enrolled and treated. This
study analysis of post-procedure significant leg pain will be based on the incidence of 7 percent suggested by FDA. Per FDA suggested sample calculation based on the non-inferiority one-sided alpha of 0.025, the sample estimate based on assumptions of type I error (alpha) = 0.025, type II error (beta (power)) = 0.86, an incidence of 7%, a non-inferiority delta of 0.10 resulted in a required sample size of 96. Allowing for a dropout rate of 20% results in a sample size of N = 115-
Safety data will be collected, including the type, frequency, and severity of adverse events (see
Attachment A for more details).
Followup Visits and Length of Followup
Patients will be followed at one week and one month.
Final Study Results
Actual Number of Patients Enrolled
115 subjects enrolled and treated
Actual Number of Sites Enrolled
Patient Followup Rate
94% at 1-month
Final Safety Findings
There was a substantially higher occurrence of pain in the post-approval study (PAS) compared to
the pivotal study. In the pivotal study the most common adverse events were as follows: abdominal pain (38.5%); Other pain (12.8%); and positional back pain (10.1%). Sonication-related pain in the leg and back were relatively less common (7.3% and 3.7%, respectively). Pain was also a common adverse event in the post-approval study and occurred more frequently than in the pivotal trial. The most commonly occurring types of pain in the PAS were as follows: sonication-related abdomen pain (52.1%); sonication-related leg pain (28.9%); and sonication-related back pain (14.9%). The most common adverse events were back/buttock/leg pain, abdominal pain, and skin pain (all sonication-related). Of the 366 adverse events, 306 (84%) were mild or moderate and 60 (16%) were severe. The most common severe adverse events were Pain Abdomen Sonication-related, Pain Back/Buttock/Leg - Sonication-related, and Skin Pain Sonication-related. Seventy-six percent of all adverse events resolved on the day of treatment, and 88% of all events resolved within 10 days of treatment.
Final Effectiveness Findings
No effectiveness endpoints in this study
Study Strengths and Weaknesses
High follow-up rate of 94%. Multi-center design increases representativeness of the study sample. Limitations The high screen failure
rate limits the generalizeability of the PAS findings to women with uterine fibroids at large. Short follow-up period of 1 month.