Attachment 1.pdf

Attachment 1: Amendment 3

RFP NHLBI-HV-12-03

Minutes

NHLBI Pumps for Kids, Infants, and Neonates (PumpKIN) Contractors’ Meeting February 24, 2011

February 24, 2011, 8:00 AM-2:30 PM Pooks Hill Marriott, Grand Ballroom – Salons A-B 5151 Pooks Hill Road, Bethesda, MD 20814

Agenda Item: Opening Remarks and Introductions, Timothy Baldwin, Ph.D., Project Officer, NHLBI

Following introductions, Dr. Baldwin, the PumpKIN Program PO, reviewed the NHLBI Pediatric Circulatory Support Program, initial year of PumpKIN Program including the pre-clinical awards, and plans for future years including the RFP for the DCCC and the protocol development activities.

Agenda Item: Scientific Presentations, NHLBI PumpKIN Program Progress Updates

The PediaFlow Pediatric Ventricular Assist Device Harvey Borovetz, Ph.D., University of Pittsburgh

Infant and Child-size Jarvik 2000 hearts Robert Jarvik, M.D., Jarvik Heart, Inc.

Integrated Pediatric Cardiopulmonary Assist System (pCAS) Mark Gartner, Ph.D., Ension, Inc.

Pedi-PumpLung (PediPL) Bartley Griffith, M.D., University of Maryland

Each of the contractors reported on the progress made by each of their teams towards accomplishing the deliverables of the contract. These included HUD designations, pre- IDE meetings with the FDA, development activities, design freezes, and results from the necessary pre-clinical in vitro and in vivo testing and results.

Agenda Item: Scientific Presentations, Clinical Updates

Pediatric VADs: Indications for Use, Demographics, and Developments David Morales, M.D., Texas Children’s Hospital and W. Robert Morrow, M.D., University of Arkansas

ECMO in Pediatric Patients: Indications for Use, Demographics, and Developments Peter Wearden, M.D., Ph.D., University of Pittsburgh

Dr. Morales and Dr. Wearden provided updates on the state of use and clinical results of both ECMO (Dr. Wearden) and VADs (Dr. Morales) used in pediatric patients. These included demographics and statistics of overall use of these two types of devices over the past 10-15 years, r morbidity and mortality results, and recent on pending improvements to the devices.

Agenda Item: FDA Panel Discussion/Question-Answer

Bram Zuckerman, MD, Donna Lochner, Matthew Hillebrenner, Sonna Patel-Raman, PhD, Eric Chen, Francesca Joseph, MD, Shreya Mehta, John Laschinger, MD

The FDA panel above provided answers and engaged in a discussion with the attendees about the following questions.

1. Please educate us about the differing levels of "evidence" necessary for HDE approval and the usual PMA approval.

A. Does an HDE study have a formal hypothesis?

B. Does an HDE study have a formal power analysis and a calculated sample size?

c. How does an HDE study pass?

D. How does an HDE study fail?

E. Does an HDE approval require a formal post market study?

2. Do you expect all approvals for pediatric devices to be for HDE designations?

3. The current generation of adult VADs are beginning to have lower limits of acceptable body surface areas. As the FDA is evaluating the entire field, are you willing to consider approval of adult devices for larger pediatric patients?

4. Should pediatric approval studies be stratified based on age or BSA? Should study design explicitly allow for the fact that a pediatric device may perform well in a teen ager but not well in a neonate?

5. Describe the annual need for pediatric devices.

6. In establishing primary and secondary endpoints, how important is survival post transplant and/or post recovery?

7. Does the concept of "destination therapy" have any relevance in pediatric patients?

8. How does the FDA evaluate morbidity data in VAD trials?

9. Given the uncertain outcome after CNS injury in children, and the long latency of these injuries, is post-marketing surveillance ever linked to trial design? If so, how would that link be accomplished?

10. For the Berlin Heart study, ECMO was an acceptable comparator group. If the EXCOR is approved, will this still be true?

11. Given the difficulty in defining and recruiting an ECMO control group (with respect to diagnosis, support equipment and protocols, and numbers of patients) would FDA consider conducting an ECMO trial based on objective performance criteria?

12. Can “probable benefit” be addressed by proving through the PumpKIN VAD clinical study that the patients who are treated using PumpKIN VADs meet or exceed survival to discharge of either a control group of similar patients treated without VADs or historical controls?

13. Can the safety of the experimental devices be assessed by comparing rates and types of adverse events in study patients with rates and types of adverse events in non-study patients with similar etiologies? Should the comparator group be historical controls or a control group?

14. What are appropriate options for assessing neurocognitive outcomes in the PumpKIN trials?

15. Are quality of life assessments required for these types of trials? If so, what are appropriate options for assessing quality of life outcomes in the trials?

The 2011 PumpKIN Contractors’ Meeting was adjourned at 2:30 pm.