Use of Endpoint Adjudication to Improve Quality and Validity – A CSRC White Paper in AHJ

Clinical Safety Research Consortium (CSRC) paper in the American Heart Journal (AHJ)

Use of endpoint adjudication to improve the quality and validity of endpoint assessment for medical device development and post marketing  evaluation: Rationale and best practices. A report from the cardiac safety research consortium


Jonathan H Seltzer, MD, MA, MBA
Ted Heise, Phd, RAC
Peter Carson, MD
Jo Carol Hiatt, MD, MBA
Pascal Vranckx, MD, PhD
Thomas Christen, MD, PhD
Donald E Cutlip, MD


This white paper provides a summary of presentations, discussions and conclusions of a Thinktank entitled “The Role of Endpoint Adjudication in Medical Device Clinical Trials”. The think tank was cosponsored by the Cardiac Safety Research Committee, MDEpiNet and the US Food and Drug Administration (FDA) and was convened at the FDA’s White Oak headquarters on March 11, 2016. Attention was focused on tailoring best practices for evaluation of endpoints in medical device clinical trials, practical issues in endpoint adjudication of therapeutic, diagnostic, biomarker and drug-device combinations, and the role of adjudication in regulatory and reimbursement issues throughout the device lifecycle. Attendees included representatives from medical device companies, the FDA, Centers for Medicare and Medicaid Services (CMS), endpoint adjudication specialist groups, clinical research organizations, and active, academically based adjudicators.

The manuscript presents recommendations from the think tank regarding

(1) rationale for when adjudication is appropriate,

(2) best practices establishment and operation of a medical device adjudication committee and

(3) the role of endpoint adjudication for post market evaluation in the emerging era of real world evidence.

(Am Heart J 2017;190:76-85.)

MDEpiNet Think Tank I: Active Surveillance

June 1, 2016

Capitalizing on the National/International Infrastructure to Develop Methods for 21 Century Active Surveillance


Event Recordings

8:00-8:15 Opening Remarks Program Leaders:
Sharon-Lise Normand, Harvard
Frederic Resnic, Lahey
Danica Marinac-Dabic, FDA
8:15-9:30 Plenary Session: Harnessing Real World Evidence for Active Surveillance:
Moderators: Kathleen Hewitt, ACC and Ben Moscovitch, Pew
Electronic Patient Data Linkage to EHR– Harlan Krumholz, Yale (30 min)
Legal Environment– Robert Portman, Powers, Pyles, Sutter & Verville (30 min)
Audience Questions (15 min)
09:30-10:50 Session 1: Envisioning Active Surveillance
This session will describe what is meant by active surveillance today for devices and what it should include in the future.
Moderator: Joseph Ross, Yale
1) Regulatory Perspective: Thomas Gross, FDA (15 min)
2) Small company perspective: Jeff Dunkel, Titan Spine (15 min)
3) Large company perspective: Richard Kuntz, Medtronic (15 min)
4) Public Health Perspective: Dale Nordenberg, Novasano Health & Science (15 min)
11:05-12:20 Session 2: Case Studies in Medical Device Surveillance: Today
This session will focus on understanding specific examples of medical device surveillance. Each example to be a focused presentation including goal, approach, findings, and lessons learned.
Moderator: Michael Matheny, Vanderbilt
Example 1: Device surveillance using national registries – Frederic Resnic, Lahey (15 min)
Example 2: Device surveillance using integrated health care delivery system – Guy Cafri, Kaiser (15 min)
Example 3: Canadian Pilot – Mark Roche, ONC (15 min)
Audience Discussion: Led by Moderator (30 min)
13:20-14:55 Session 3: Device Surveillance Methodology Efforts Today: Where are the Gaps?
This session will identify the gaps by discussing strengths and weaknesses in the Session 2 Case studies (including scalability, sustainability, methodological consensus, alert/signal communication (to regulators, manufacturers, providers, patients) and operational control.
Moderators: Sharon-Lise Normand, Harvard and Jesse Berlin, J&J
Panel Members: Roseann White – Duke, Vahan Simonyan – FDA, Myoung Kim – J&J, Daniel Caños – CMS
15:10–16:10 Session 4: Prioritizing Methodology Developments
This session will begin development of recommendations regarding the intersecting priorities of specific surveillance models.
Moderators: Danica Marinac-Dabic, FDA and Harlan Krumholz, Yale
Panel Members: Theodore Lystig – Medtronic, Libbe Englander – Pharm3r, Liz Paxton – Kaiser, Michael Matheny – Vanderbilt, Patient representative (TBA)
16:10-16:45 Closing Remarks: Sharon-Lise Normand, Harvard, Frederic Resnic, Lahey and Danica Marinac-Dabic, FDA
1) Review key next steps,
2) Identify authorship teams for white papers,
3) Announce next meeting and timeline.

National and International Postmarket Research and Surveillance Implementation: Achievements of the International Consortium of Orthopaedic Registries Initiative

Journal The Journal of Bone and Joint Surgery
Authors Sedrakyan, Art; Paxton, Elizabeth; Graves, Stephen; Love, Rebecca; Marinac-Dabic, Danica
Year Published 2014
Link to publication

Nearly every American will be exposed to a medical device during his or her life, and tens of millions of people will be treated with an implantable device. However, regulatory and public health systems in the United States and internationally have critical gaps. The U.S. Food and Drug Administration (FDA) has released a national medical device postmarket surveillance plan, in which the agency identifies as a main priority the goal of promoting the development of national and international medical device registries for selected products. Another top priority of the FDA is the creation of a unique device identification (UDI) system for medical devices in response to a 2007 federal law.

The International Consortium of Orthopaedic Registries: Overview and Summary

Journal The Journal of Bone and Joint Surgery
Authors Sedrakyan, Art; Paxton, Elizabeth; Phillips, Charlotte; Namba, Robert; Funahashi, Tadashi; Barber, Thomas; Sculco, Thomas; Padgett, Douglas; Wright, Timothy; Marinac-Dabic, Danica
Year Published 2011
Link to publication

The United States Food and Drug Administration (FDA) Center for Devices and Radiological Health (CDRH) monitors both mandatory and voluntary post-market reporting to identify adverse events and problems associated with medical devices. Although the manufacturers of medical devices are required to report deaths, injuries, and malfunctions directly to the FDA, the device users are required to report these events to the manufacturer and are required to report only deaths to the FDA. Voluntary reporting systems such as the MedWatch program, the MAUDE (Manufacturer and User Facility Device Experience) database, and the MedSun (Medical Product Safety Network) enhanced surveillance network2,3 provide nationwide medical device surveillance in the U.S. However, these reporting systems have important weaknesses, such as incomplete, inaccurate, or nonvalidated data, reporting biases related to event severity, concerns that reporting may result in adverse publicity or litigation, and general underreporting of events. Most importantly, denominator data are missing, which makes evaluation of the incidence or prevalence of a safety-related event impossible.