Welcome to the 10 th Annual Meeting of ISMPP! Leading Through Collaboration

Transcription

1 Welcome to the 10 th Annual Meeting of ISMPP! Leading Through Collaboration 1

2 The PARTNER Publications Office (PPO)

3 Why PPO?

4 Obstacles to publication Access to data Availability of resources Time management

5 What is the PPO?

6 Mission Statement The PARTNER Publications Office exists to facilitate, expedite, coordinate, and execute an aggressive academic publications process such that PARTNER investigators will have an opportunity to participate as primary and co-authors on creative manuscripts (and abstracts) utilizing data and observations from the PARTNER clinical trials.

7 PARTNER Study Design Symptomatic Severe Aortic Stenosis ASSESSMENT: High-Risk AVR Candidate 3,105 Total Patients Screened N = 699 High Risk Total = 1,057 patients 2 Parallel Trials: Individually Powered Inoperable N = 358 Yes ASSESSMENT: Transfemoral Access No ASSESSMENT: Transfemoral Access Transfemoral (TF) Transapical (TA) Yes No 1:1 Randomization 1:1 Randomization 1:1 Randomization Not In Study N = 244 N = 248 N = 104 N = 103 N = 179 N = 179 TF TAVR VS AVR TA TAVR VS AVR TF TAVR VS Standard Therapy Primary Endpoint: All-Cause Mortality at 1 yr (Non-inferiority) Primary Endpoint: All-Cause Mortality Over Length of Trial (Superiority) Co-Primary Endpoint: Composite of All-Cause Mortality and Repeat Hospitalization (Superiority)

8 Continued Access Symptomatic Severe Aortic Stenosis ASSESSMENT: High-Risk AVR Candidate Same Inclusion/Exclusion Criteria as PMA Trial PARTNER NRCA n=2014 Transfemoral n=1041 Transapical n=953

9 The PARTNER II Trial Study Design Symptomatic Severe Aortic Stenosis ASSESSMENT by Heart Valve Team n = 2000 Randomized Patients Operable (STS 4) Two Parallel Randomized Trials +6 Nested Registries Inoperable n = 560 Randomized Patients Yes ASSESSMENT: Transfemoral Access No ASSESSMENT: Transfemoral Access Transfemoral (TF) Transapical (TA) / TransAortic (TAo) Yes 1:1 Randomization 1:1 Randomization 1:1 Randomization 6 Nested Registries Sample Size TF TAVR SAPIEN XT VS Surgical AVR TAVR: TA / TAo SAPIEN XT Primary Endpoint: All-Cause Mortality + Disabling Stroke at Two Years (Non-inferiority) VS Surgical AVR TF TAVR SAPIEN XT VS TF TAVR SAPIEN Primary Endpoint: All-Cause Mortality + Disabling Stroke + Repeat Hospitalization at One Year (Non-inferiority) NR1 (Transapical) 100 NR2 (Small Vessel) 100 NR3 (ViV) 100 NR4 (TAo) 100 NR5 (29 mm TF) 50 NR6 (29 mm TA) 50

10 Who is the PPO?

11 PPO Setting a Bar CRF / Columbia Cleveland Clinic Martin B. Leon, MD E. Murat Tuzcu, MD Ajay Kirtane, MD Lars Svensson, MD, PhD Susheel Kodali, MD Eugene Blackstone, MD Mat Williams, MD Becky Hahn, MD Philippe Genereux, MD Phil Green, MD Darshan Doshi, MD Ke (Steven) Xu, PhD Maria Alu Columbia University / CRF Cleveland Clinic Foundation Samir Kapadia, MD Ashley Lowry, MS Jeevanitham Rajeswaran, PhD Gina Ventre MedStar Health

12 Publications Committee Executive Committee Craig Smith, MD (Columbia) Jeffrey W. Moses, MD (Columbia) Mike Mack, MD (Dallas) John Webb, MD (St. Paul s/university of BC) D. Craig Miller, MD (Stanford) Other Participants Neil J. Weissman, MD (Medstar/Washington Hospital Center) David J. Cohen, MD (St. Luke s Mid-America Heart Institute) Pam Douglas, MD (Duke) Vinod Thourani, MD (Emory) Nirat Beohar, MD (Mount Sinai Medical Center - Miami) Raj Makkar, MD (Cedars-Sinai) Larry Wood (Edwards) Scott Beggins (Edwards) Wilson Y. Szeto (U Penn) Rakesh Suri (Mayo Clinic) Chet Rihal (Mayo Clinic) John Petersen II (Swedish Medical Center) Ron Waksman (Medstar Washington Hospital Center) Vasilis Babaliaros, MD (Emory University School of Medicine) Howard C. Herrmann, MD (University of Pennsylvania) Dean Kereiakes, MD (The Christ Hospital) Jonathan Leipsic, MD (St. Paul s Hospital, Vancouver)

13 How does the PPO work?

14 The Process Proposal Submission Investigators submit a proposal PPO staff gives initial review Publications Committee Review On twice monthly calls, Publications Committee reviews new proposals and assign writing group and statistician. Analysis Plan Conference Call Statistician and Writing group have a kickoff call to discuss the analysis plan for each approved proposal

15 The Process Analysis Statistician implements SAP. Additional queries handled with direct communication between stats team, PPO staff, and First author. Draft #1 Draft #1 reviewed internally, then circulated to co-authors for discussion via teleconference and/or . Subsequent drafts and revisions Submission

16 PPO Current Status Academic Output: Papers published (includes accepted/in press): 32 Papers currently under review at journals: 12 Abstracts Presented in 2012: 13 Abstracts Presented in 2013: (so far): 10 Abstracts presented 3 Abstracts to be presented this spring 2 Abstracts under review

17 Removing obstacles to publication Access to data Any PARTNER investigator can submit a proposal and receive data Availability of resources Statistical support Editorial support Fellow Advice and input from more experienced author-investigators Time management Administrative support, enforced deadlines, writing group, regularly scheduled conference calls, constant communication

18 Industry/Academic Collaboration A New Paradigm? Brian R. Lindman, MD, MSCI Assistant Professor of Medicine Cardiovascular Division Washington University School of Medicine, St. Louis, MO International Society for Medical Publication Professionals Leading Through Collaboration April 9, 2014

19 Disclosures Grant funding American Heart Association NIH (KL2 and K23) Gilead Sciences Research Scholars Award Barnes-Jewish Hospital Foundation Consulting Gerson Lehman Group Research Industry support Roche and BG-Medicine (biomarker assays)

20 Left Ventricle

21 Aortic Stenosis

22 Mild AS Moderate AS Severe, Asymptomatic AS Severe, Symptomatic AS Severe, Decompensated AS

23 Mild AS Moderate AS Severe, Asymptomatic AS Severe, Symptomatic AS Severe, Decompensated AS AVR Aortic valve replacement

24 Symptomatic Aortic Stenosis Schwarz, F. et al. Circulation 1982.

25 Unmet Clinical Need Approximately 1/3 of patients with severe symptomatic aortic stenosis are not treated with aortic valve replacement due to: Advanced age Co-morbidities Left ventricular dysfunction

26 Transcatheter aortic valve replacement

27 Published June 2011

28 All-Cause Mortality PARTNER I Trial, High-risk cohort, overall population (intention-to-treat cohort)

29 PARTNER Publications Office An Investigator s Experience 1. Does diabetes alter the clinical outcome after surgical vs. transcatheter aortic valve replacement? Industry would be interested in the answer 2. Is regression of severe left ventricular hypertrophy associated with improved clinical outcomes after aortic valve replacement? Industry not so interested in the answer

30 Diabetes Paper Submitted an initial proposal (got stuck ) Submitted revised proposal approval Detailed analysis plan Back-and-forth with statistician over results Reviewed findings on call with writing group Drafted manuscript Initial review and revision (couple co-authors) Manuscript to all authors debate Revisions and submission (no industry approval )

31 All-Cause Mortality PARTNER I Trial, Diabetics

32 JACC March 25, 2014

33 Left Ventricular Hypertrophy Paper Invited to join an approved idea Worked with 1-2 others to develop a plan for 2-3 papers on the topic of LVH (coordinated papers) Helped develop detailed analysis plans and took lead on 1 paper (committee reviewed) Back-and-forth with statistician over results Reviewed findings on call with writing group Drafted manuscript Initial review and revision (couple co-authors) Manuscript to all authors debate Revisions and submission (no industry approval )

34 Repeat Hospitalizations Patients with severe LVH treated with TAVR

35 Early Regression of Severe Left Ventricular Hypertrophy after Transcatheter Aortic Valve Replacement is Associated with Decreased Hospitalizations Brian R. Lindman, William J. Stewart, Philippe Pibarot, Rebecca T. Hahn, Catherine M. Otto, Ke Xu, Richard B. Devereux, Neil J. Weissman, Maurice Enriquez-Sarano, Wilson Y. Szeto, Raj Makkar, D. Craig Miller, Stamatios Lerakis, Samir Kapadia, Bruce Bowers, Kevin L. Greason, Thomas C. McAndrew, Yang Lei, Martin B. Leon, Pamela S. Douglas JACC: Cardiovascular Interventions 2014 (in press).

36 PPO Opportunities from an Investigator Perspective Explore questions about the procedure, complications, secondary outcomes Compare procedures (transcatheter vs. surgical) in sub-groups Diabetes paper Pathophysiology questions that can leverage a large database with careful phenotyping and adjudicated clinical outcomes LVH paper Not so interesting to industry, but can make an important impact on the field

37 Thank You

38 Maria Alu Cardiology Publications Manager Columbia University Medical Center Brian Lindman, MD, MSCI, Washington University School of Medicine, Cardiovascular Division St. Louis, MO Neil J. Weissman, MD, FACC, FASE Director, Cardiovascular Core Labs; President, MedStar Health Research Institute; Professor of Medicine, Georgetown University 38

39 Welcome to the 10 th Annual Meeting of ISMPP! Leading Through Collaboration 39