CSRC Spearheads Creation of First National Pediatric Cardiac Screening Database

FDA, industry, and patient advocacy groups join effort to advance effective cardiac screening

Durham, NC, October 15, 2020 – The Cardiac Safety Research Consortium (CSRC) announces the establishment of a first-in-kind national database of pediatric cardiac screening information aimed at advancing the ability to discover potentially dangerous pediatric cardiac conditions and preventing sudden cardiac arrest or death in young people (SCDY). This database is being developed through a multidisciplinary partnership formed by the CSRC with support from the U.S. Food and Drug Administration (FDA) with the goal of identifying and overcoming barriers to effective pediatric cardiac screening.

“For the first time, we will have access to high-quality pediatric data on a scale that will allow us to further research a wide array of cardiac issues facing children – from sudden cardiac arrest to cardiac side effects of drugs to the cardiac effects of having had a COVID-19 infection,” explained the project’s principal investigator, Salim F. Idriss, MD, PhD, executive co-director of the Duke Pediatric and Adult Congenital Heart Center and director of pediatric electrophysiology at Duke University Medical Center. “Establishing a scalable, reliable national warehouse of pediatric cardiac screening data, including metrics such as data completeness, ECG interpretability, and assessment of long and short-term follow up, is the key to improved cardiac care in this population.”

“CSRC’s mission is to drive collaboration among public health, academia, government and industry experts to address complex cardiac safety issues,” said Jonathan Seltzer, MD, MBA, FACC, executive director of the CSRC. “This database is a prime example of how collaboration can fast-forward research for a pressing public health problem.”

Ten community screening organizations from across the country have been recruited to date as partners to help establish the national data warehouse. The organizations were recruited through national project partner, Parent Heart Watch, whose prevention-driven initiatives include cultivating local champions who create community programs focused on the prevention of SCDY. Parent Heart Watch anticipates actionable outcomes from this collaboration, in particular, converting research into strategies that affect systemic change in pediatric primary care protocol. “At the heart of our movement is the knowledge that sudden cardiac death can be prevented,” explained Martha Lopez-Anderson, executive director. “This project fully aligns with our mission to ultimately empower medical practitioners and families to recognize warning signs and risk factors before tragedy strikes—it’s truly a life-saving initiative.”

In addition to Parent Heart Watch, current partners include:

  • Community screening organizations including: Championship Hearts Foundation (Texas), Cody Stephens Go Big or Go Home Memorial Foundation (Texas), Saving Hearts Foundation (California), Eric Paredes Save A Life Foundation (California), Screening America (South Dakota), Heart Screen New York (New York), Peyton Walker Foundation (Pennsylvania), Hearts for Athletes (Alabama), Thomas Smith Memorial Foundation (Michigan), Play for Jake Foundation (Indiana)
  • Academic leaders from Children’s Hospital of Philadelphia, Lurie Children’s Hospital, Cleveland Clinic Lerner College of Medicine, and Baylor College of Medicine
  • Industry partners including: AMPS LLC (Analyzing Medical Parameters for Solutions), AstraZeneca, Cardiac Insight Inc., Eli Lily, ERT, and IQVIA

The study is ongoing, and anyone interested in supporting the initiative is encouraged to contact CSRC about how to get involved. “Partnership is essential to this effort, and we welcome others who are interested in lending their support – financial or otherwise – to the study,” Dr. Idriss added.

About Cardiac Safety Research Consortium

The Cardiac Safety Research Consortium (CSRC) provides leadership and guidance for regulators, public and private clinical researchers, and industry through an open, interactive forum to collectively address cardiovascular related issues in clinical trials for both new and existing products. The organization offers unique resources and a collaborative structure that allows for valuable contributions to scientific study design, data analysis and interpretation, and dissemination to the public. CSRC’s non-competitive environment allows for experts to engage in a rigorous, transparent process to define an optimal path forward in the advancement of cardiac safety research, knowledge, and excellence. The impact of CSRC and the thought leadership of its members on key cardiac safety research issues has a proven track record of benefiting the global scientific and regulatory community. For more information about CSRC, visit their website or email info@cardiac-safety.org.

Restricted mean survival time for the analysis of cardiovascular outcome trials assessing non-inferiority: Case studies from antihyperglycemic drug development

Read the paper here: Restricted mean survival time for the analysis of cardiovascular outcome trials assessing non-inferiority: Case studies from antihyperglycemic drug development

Manner, D. H., Battioui, C., et al. Restricted mean survival time for the analysis of cardiovascular outcome trials assessing non-inferiority: Case studies from antihyperglycemic drug development. Am Heart J 2019; 215: 178-86

Practical Approaches to Generating Clinical Evidence for the Treatment of Cardiogenic Shock

Practical Approaches to Generating Clinical Evidence for the Treatment of Cardiogenic Shock

FDA White Oak Campus
10903 New Hampshire Avenue
Silver Spring, MD
July 24, 2019

8:00 – 8:15 Introduction and Purpose of Think Tank
Mitchell Krucoff, MD (Duke)

8:15 – 8:30 Summary of CSRC Shock I
Marc Samsky, MD (Duke)

8:30 – 9:10 Session 1: Plenary Session: Unmet needs in treating cardiogenic shock
Moderators: Mitchell Krucoff, MD (Duke)

9:10 – 10:30 Session 2: Definitions of Cardiogenic Shock
Moderator: David Morrow, MD MPH (Brigham and Women’s Hospital) and Eric Chen, MS (Abbott Vascular)

9:30 – 10:30 Discussion
Lead Discussant: Ian Gilchrist, MD (Penn State)

10:30 – 10:45 Break

10:45 – 12:15 Session 3: Systems-based care for patients with cardiogenic shock: Organized Shock Teams and Centers of Excellence
Moderator: Joaquin Cigarroa, MD (Oregon Health and Sciences)

10:55 – 12:15 Discussion
Lead Discussant: Alex Truesdell, MD (INOVA)

12:15 – 12:45 Break/Lunch

12:45 – 2:15 Session 4: What is the best approach to generating evidence? Registries, trials, both?
Moderator: Alastair Proudfoot, MD, PhD (St. Barts, London) and Ron Waksman, MD (MedStar)

1:15 – 2:15 Discussion

2:15 – 2:25 Break

2:25 – 3:15 Open session for discussion and concluding thoughts: Where do we go from here?
Moderator: Sunil Rao, MD (Duke) and Fernando Aguel, MSE (FDA)

3:15 – 3:30 Summary and Adjourn

CiPA Update December 2018

Dear CiPA Community,
Welcome to the CiPA Quarterly Update!

We are happy to share news from the recent ICH face-to-face meeting held in November 2018. The ICH S7B/E14 Q&A concept paper and work plan have been approved! The ICH Assembly endorsed the establishment of an Implementation Working Group (IWG) to begin the process of developing a Q&A document. This IWG will build on work done by the former E14/S7B Discussion Group (DG) including work on the CiPA initiative.

The purpose of the IWG will be to provide guidance around the proposed nonclinical assays (in vitro, in silico, and in vivo). The current plan calls for a two-staged Q&A approach starting with S7B and then E14 guidance with the goal to have this be a more efficient process. Read more online including the concept paper and work plan:

E14/S7B Questions & Answers: Clinical and non-Clinical Evaluation of QT/QTc Interval Prolongation and Proarrhythmic Potential

Concept Paper

Work Plan

Recent Publications:

  • Vicente J, Zusterzeel R, Johannesen L, Ochoa-Jimenez R, Mason JW, Sanabria C, Kemp S, Sager PT, Patel V, Matta MK, Liu J, Florian J, Garnett C, Stockbridge N, Strauss DG. (2018.) Assessment of Multi-Ion Channel Block in a Phase-1 Randomized Study Design: Results of the CiPA Phase 1 ECG Biomarker Validation Study. Clin Pharmacol Ther. 2018 Nov 17. doi: 10.1002/cpt.1303.
  • Li Z., Ridder B. J., Han X., Wu W. W., Sheng J., Tran P. N., Wu M., Randolph A., Johnstone R. H., Mirams G. R., Kuryshev Y., Kramer J., Wu C., Crumb W. J., Strauss,
    D. G. (2018). Assessment of an In Silico Mechanistic Model for Proarrhythmia Risk Prediction Under the CiPA Initiative. Clinical Pharmacology and Therapuetics. Available online August 27, 2018. doi:10.1002/cpt.1184
  • Blinova K., Dang Q., Millard D., Smith G., Pierson J., Liang G., Brock M., Lu H.R., Kraushaar U., Zeng H., Shi H., Zhang X., Sawada K., Osada T., Kanda Y., Sekino Y., Pang L., Feaster T.K., Kettenhofen R., Stockbridge N., Strauss D.G., Gintant G. (2018). (2018). International Multisite Study of Human Induced Pluripotent Stem Cell Derived Cardiomyocytes for Drug Proarrhythmic Potential Assessment. Cell Reports. Available online September 25, 2018. https://doi.org/10.1016/j.celrep.2018.08.079.

If you’re interested in finding past Quarterly Updates, they are available online.

Regards,


____________________________
Jennifer Pierson, MPH
Senior Scientific Program Manager
Health and Environmental Sciences Institute (HESI)
jpierson@hesiglobal.org

CSRC Think Tank: Defining the Clinical and Regulatory Landscape for Cardiogenic Shock

September 7, 2018

8:00am – 8:15am Introduction and Purpose of Think Tank Mitchell Krucoff, MD (Duke)

  • Introduction to CSRC
  • Anatomy of a Think Tank

8:15am – 8:45am Session I: Overview of shock

Session I Objectives:

8:45am – 9:00am BREAK

9:00am – 10:30am Session II: Defining unmet needs, clinical study barriers, and targets for drug and device therapy for shock: Part I Moderator: Joseph Rogers, MD (Duke)

Session II Objectives:

  • Define a population of intended use for drug and device therapies in cardiogenic shock.
  • Discuss and identify comparator cohorts for cardiogenic shock trials.
  • Discuss and identify primary and secondary outcomes for cardiogenic shock trials.

9:00am – 9:10am Cohorts to study: defining a “population of intended use”

9:10am – 9:20am Comparators for drug and device trials in shock patients

  • Clinical/best practice perspective Judith Hochman, MD (NYU Langone)

9:20am – 9:30am Outcome endpoints: mortality plus?

9:30am – 9:40am FDA Perspective Ileana Pina, MD
9:40am – 9:50am Health Canada Perspective Roy Masters, MD
9:50am – 10:30am Discussion

  • Lead Discussant: Ron Waksman, MD (Medstar Health)

10:30am – 10:45am BREAK

10:45am -12:15pm Session III: Defining unmet needs, clinical study barriers, and targets for drug and device therapy for shock: Part II | Moderator: David Morrow, MD MPH (Harvard)

Session III Objectives:

  • Discuss enrollment of patients who may not be capable of providing informed consent.
  • Discuss and identify novel evidence structures for future shock trials.
  • Discuss and identify novel statistical approaches for trials of shock therapies.

10:45am – 10:55am Informed consent

  • Clinical/best practice perspective Timothy Henry, MD (Cedars-Sinai)

10:55am – 11:05am Avenues for real world evidence, pragmatic trials, or novel infrastructure for shock trials

  • Clinical/best practice perspective Holger Thiele, MD (University of Leipzig)

11:05am – 11:15am Novel statistical approaches for shock studies

11:15am – 11:20am Improving Patient Outcomes in Cardiogenic Shock as a core mission of clinical development programs Seth Bilazarian, MD (Abiomed)

11:20am-11:30am FDA Perspective John Sapirstein, MD

11:30am – 12:10pm Discussion

  • Lead Discussant: Roseann White, MA (Duke)

12:10pm – 1:00pm LUNCH

1:00pm – 2:00pm Session IV: Future directions for device and drug development in shock. Moderator: Sunil Rao, MD (Duke)

Session IV Objectives:

  • Identify global collaborators for trials of shock therapies.
  • Discuss trial designs incorporating both drug and device therapies for patients with cardiogenic shock.
  • Discuss and define “-ARC” definitions of shock (SHARC).

1:00pm – 1:10pm Global collaboration: is it possible? Is it desirable? Clinical/best practice perspective William Abraham, MD (Ohio State)

1:10pm – 1:20pm Factorial device and drug study designs

  • Clinical/best practice perspective Roxana Mehran, MD (Mount Sinai)

1:20pm – 1:30pm Definitions: Shock-ARC (SHARC)

  • Clinical/best practice perspective George Dangas, MD (Mount Sinai)

1:30pm-1:40pm FDA Perspective Fortunato Senatore, MD, PhD
1:40pm – 2:30pm Discussion
2:30pm – Closing Remarks

Scientific Programs Committee Chair Attends CEC Summit

CSRC Executive Committee member and Scientific Programs Committee Chair Jonathan Seltzer, MD, MBA, MA, attended the inaugural 2018 CEC Summit on September 26-27, 2018. This event, cohosted by the Duke Clinical Research Institute and Stanford Center for Clinical Research, brought together thought leaders from academia, industry, and government to establish consistent standards globally for clinical events classification (CEC) and adjudication in clinical trials.

“This meeting was special as it examined both the scientific justification for endpoint adjudication as well as operational best practices. It is likely that future meetings with this group will deliver innovative solutions to issues whereby adjudication strategies can be more broadly applied, but in an intelligent, cost-effective manner,” said Seltzer, who also serves as the president and CEO of ACI Clinical.

Event panelists and speakers represented various organizations including the U.S. Food and Drug Administration (FDA), Harvard University, Cleveland Clinic, George Clinical, the Cardiovascular Research Foundation, Cardialysis, and more.

Hear what others had to say about the event in this recap.

CiPA Update October 2018


Dear CiPA Community,
Welcome to the CiPA Quarterly Update!

Recent publications from the CiPA workstreams are listed below. Visit the CiPA website to see all publications: http://cipaproject.org/publications/:

  • Strauss D.G., Gintant G, Li Z, Wu W, Blinova K, Vicente J, Turner J.R., Sager P.T. (2018). Comprehensive In Vitro Proarrhythmia Assay (CiPA) Update from a Cardiac Safety Research Consortium / Health and Environmental Sciences Institute / FDA Meeting. Therapeutic Innovation & Regulatory Science. First Published August 29, 2018. doi.org/10.1177/2168479018795117
  • Li Z., Ridder B. J., Han X., Wu W. W., Sheng J., Tran P. N., Wu M., Randolph A., Johnstone R. H., Mirams G. R., Kuryshev Y., Kramer J., Wu C., Crumb W. J., Strauss, D. G. (2018). Assessment of an In Silico Mechanistic Model for Proarrhythmia Risk Prediction Under the CiPA Initiative. Clinical Pharmacology and Therapuetics. Available online August 27, 2018. doi:10.1002/cpt.1184
  • Blinova K., Dang Q., Millard D., Smith G., Pierson J., Liang G., Brock M., Lu H.R., Kraushaar U., Zeng H., Shi H., Zhang X., Sawada K., Osada T., Kanda Y., Sekino Y., Pang L., Feaster T.K., Kettenhofen R., Stockbridge N., Strauss D.G., Gintant G. (2018). (2018). International Multisite Study of Human Induced Pluripotent Stem Cell Derived Cardiomyocytes for Drug Proarrhythmic Potential Assessment. Cell Reports. Available online September 25, 2018. https://doi.org/10.1016/j.celrep.2018.08.079.

Open Data Formatting:
A subteam including volunteers from industry and FDA is currently working on an open data format specification for manual and automated patch clamp data. The open format will be manufacturer independent and will meet CiPA in vitro and in silico needs. The format will be also eCTD compliant.

Best Practices Papers:
The CiPA Work Streams continue to make progress on additional manuscripts including one from each group that will detail some of the discussions and recommendations that came out of the recent May 2018 CiPA Meeting. These publications will cover topics such as quality standards necessary for regulatory submissions to best practices and recommendations. The hope is to help provide some further clarity around expectations around the differences in early drug development screening tools and data that will be submitted as part of a regulatory submission package.

If you’re interested in finding past Quarterly Updates, they are available online: http://cipaproject.org/latest-news/.

Jennifer Pierson, MPH
Senior Scientific Program Manager
Health and Environmental Sciences Institute (HESI) jpierson@hesiglobal.org

Over the Edge for Cardiac Safety

October 4, 2018

Salim Idriss, MD, PhD, principal investigator for CSRC’s Sudden Cardiac Death in the Young initiative, is going Over the Edge for cardiac safety. What does this mean? Dr. Idriss is participating in the 2018 Over the Edge fundraiser on behalf of sudden cardiac death in the young initiatives. On Saturday, October 13, Dr. Idriss and Clare Matti, assistant director of Regulatory Services at the Duke Clinical Research Institute, will rappel 17 stories down the side of the historic 21c Museum Hotel in downtown Durham.

This event, sponsored by Duke Children’s Hospital, helps support patient care, medical research, and physician training at Duke Children’s.

Through your 100% tax-deductible donation, you can help support efforts to end sudden cardiac death in the young. Hear what Dr. Idriss has to say about the event.

DONATE HERE.

CSRC forms partnership with ACCP

August 1, 2018

In July 2018, the American College of Clinical Pharmacology (ACCP) and Cardiac Safety Research Consortim announced the signing of a collaborative Memorandum of Understanding (MOA). CSRC and ACCP will work together to develop, plan and conduct various educational events and programs. The partnership will also develop and produce research and policy statements/position papers relevant to the fields of clinical pharmacology and the cardiac and vascular safety of medical products.

Two collaborative activities defined in the agreement are already underway. First, a group of coauthors from both organizations is preparing a joint position paper on the use of the heart rate-corrected J-Tpeak interval as seen on the human electrocardiogram for purposes of evaluating a new drug’s potential to induce Torsade de Pointes, a rare polymorphic ventricular arrhythmia that typically occurs in self-limiting bursts and can lead to symptoms of dizziness, palpitations, syncope, and seizures. Torsade de Pointes can occasionally progress to ventricular fibrillation and sudden cardiac death.

Second, a CSRC/ACCP sponsored symposium will be held September 25th at the 2018 ACCP Annual Meeting in Bethesda, MD. At the symposium, titled “The Challenging World of Cardiac Evaluation & Utilization of Concentration-QT Analyses of Phase I Data to Waive the Thorough QT/QTc Study Requirement,” Chairs and Faculty Speakers will present industry, academia and regulatory agency viewpoints. ACCP will provide CME & CPE credits for the course.

CSRC and ACCP look forward to the continued opportunities that will arise from this new collaboration. If you are interested in becoming involved in these activities, please contact us at info@cardiac-safety.org.