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U.S. Department of Health and Human Services

Post-Approval Studies (PAS)

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The FDA has the authority to require sponsors to perform a post-approval study (or studies) at the time of approval of a premarket approval (PMA), humanitarian device exemption (HDE), or product development protocol (PDP) application. Post-approval studies can provide patients, health care professionals, the device industry, the FDA and other stakeholders information on the continued safety and effectiveness (or continued probable benefit, in the case of an HDE) of approved medical devices. This database allows you to search Post-Approval Study information by applicant or device information.

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VON Registry

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Study Status Completed
Application Number P040025 / PAS001
Date Current Protocol Accepted 12/20/2006
Study Name VON Registry
General Study Protocol Parameters
Study Design Active Surveillance
Data Source Sponsor Registry
Comparison Group No Control
Analysis Type Descriptive
Study Population Neonate: 1-28 days, Infant: 29 days-2 yrs
Detailed Study Protocol Parameters
Study Design Description This is a prospective observational study, using the Vermont Oxford Network (VON) Registry, Burlington, Vermont: this is a non-profit voluntary collaboration of health care professionals dedicated to improving the quality and safety of medical care for newborn infants and their families, established in 1988. The sponsor will provide each hospital that purchases a Cool-Cap with information on the existing VON. This network maintains a dataset including information about the care and outcomes of high-risk newborn infants. The sponsor explains to the hospitals that purchases the device how to join the VON, who to contact, and an explanation of how their participation can help in monitoring the use of this new treatment. The VON is independently establishing a registry for infants with symptoms of hypoxic ischemic encephalopathy (HIE). Patients receiving the Cool-Cap for HIE will be included in this registry. VON will collect data for this registry through a software module added to the system currently used by their members to report data for their other registries.
Study Population Description Study population is as per device indication. The device is indicated for use in fullterm infants with clinical evidence of moderate to severe hypoxic-ischemic encephalopathy (HIE)*. Cool-Cap provides selective head cooling with mild systemic hypothermia to prevent or reduce the severity of neurologic injury associated with HIE.
Sample Size No sample size or power calculations are provided in the protocol.The sponsor expects that participation in the registry will be a subset of all Cool-Cap customers/patients. It is expected that a reasonable percentage of hospitals will already be a member of this registry and will participate.
Data Collection Data to be collected on infants treated with the Cool-Cap will include the following information. Demographic and Admission data: sec, race / ethnicity, measurements at birth (weight, head circumference, length), gestational age, gestational category (AGA, LGA, SGA <10%), date of birth, time of birth, inborn or transfer, method of delivery, multiple births, delivery complications, NICU admit temperature, Apgar scores, CFM / aEEG Score, Sarnat Stage, cord pH, base deficit, assisted ventilation, cooling start date/time, cooling stop date/time, stop date/time, restart date/time, duration, and reason for any interruptions of cooling that exceed 30 minutes. Data that reports the occurrence of potential serious adverse events due to hypothermia as defined in the clinical trial protocol. This would include: - Major cardiac arrhythmia (such as ventricular tachycardia, ventricular fibrillation or acquired conduction block), - Major venous thrombosis not related to an infusion line,- Severe hypotension despite full inotrope support and volume correction,Data that reports the occurrence of adverse events encountered in the clinical trial. This would include:- Clinical seizures during rewarming,- Abnormal EKG (minor cardiac arrhythmia or prolonged QT interval),- Scalp edema,- Sclerema neonatorum,Data that will provide information on the infant's condition when discharged from the hospital would include:- Discharge Date,- Discharge Diagnosis or Cause of Death
Follow-up Visits and Length of Follow-up The sponsor will discontinue participation in the registry, and reporting of data, after 5 years.
Interim or Final Data Summary
Interim Safety Information As of the 36-month PAS report, finalized tabulation of results for the year 2008, including infants for whom the 3-day treatment began January 1, 2008 through December 31, 2008. In addition to 76 infants in 2007, a total of 129 infants from 8 hospitals are included, a relevant increase from the 49 infants from 4 hospitals reported in the initial tabulation. The last report also provides initial tabulation of results for the year 2009: 69 infants were included from 7 hospitals for whom the 3-day treatment began January 1, 2009 through November 12, 2009. The overall number of infants included in the report is 274.
Actual Number of Patients Enrolled 551
Actual Number of Sites Enrolled 16
Patient Follow-up Rate 100%
Final Safety Findings Infants in the current registry had higher rates of adverse events including minor cardiac arrhythmias, seizures, and scalp edema than those in the randomized clinical trial; this trend does not appear to change over time. The sponsor has provided explanations on the observed difference, which was mainly due to the longer observational period and different definitions of adverse events in PAS contrast to the PMA data
Final Effect Findings Effectiveness findings were not reported.
Study Strengths & Weaknesses Although important data was collected about patient characteristics and adverse events for these infants during their NICU hospitalization, the registry may not be able to provide any useful information in assessing device performance (safety and effectiveness) under actual conditions

of use because of its following limitations: (1) lack of valid comparison group; (2) potential selection bias due to the lack of baseline information on infants who may receive the device but whose data were not entered in the registry; (3) no continued follow-up for premarket and continued access patients who have already received the device; (4) failure to obtain data on infants after discharge from the NICU; and (5) no long-term follow-up with neurodevelopmental assessments.

Recommendations for Labeling Changes The sponsor was asked to update their labeling to reflect the changes in clinical practice of therapeutic hypothermia for neonatal HIE based on the final PAS


VON Registry Schedule

Report Schedule
Date Due
FDA Receipt
Applicant's Reporting Status
1 year report 12/20/2007 12/20/2007 On Time
2 year report 12/19/2008 12/17/2008 On Time
3 year report 12/19/2009 12/16/2009 On Time
4 year report 12/19/2010 12/16/2010 On Time
5 year report 12/19/2011 12/14/2011 On Time
6 year report-final report 12/19/2012 11/02/2012 On Time

Contact Us

Julie Unger
Project Manager, Post-Approval Studies Program
Food and Drug Administration
10903 New Hampshire Ave
WO66-4206v Silver Spring, MD

Phone: (301) 796-6134
Fax: (301) 847-8140

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