Biospecimens and Molecular and Cellular Biomarkers in Aneurysmal Subarachnoid Hemorrhage Studies: Common Data Elements and Standard Reporting Recommendations

Abstract

Introduction

Development of clinical biomarkers to guide therapy is an important unmet need in aneurysmal subarachnoid hemorrhage (SAH). A wide spectrum of plausible biomarkers has been reported for SAH, but none have been validated due to significant variabilities in study design, methodology, laboratory techniques, and outcome endpoints.

Methods

A systematic review of SAH biomarkers was performed per the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The panel’s recommendations focused on harmonization of (1) target cellular and molecular biomarkers for future investigation in SAH, (2) standardization of best-practice procedures in biospecimen and biomarker studies, and (3) experimental method reporting requirements to facilitate meta-analyses and future validation of putative biomarkers.

Results

No cellular or molecular biomarker has been validated for inclusion as “core” recommendation. Fifty-four studies met inclusion criteria and generated 33 supplemental and emerging biomarker targets. Core recommendations include best-practice protocols for biospecimen collection and handling as well as standardized reporting guidelines to capture the heterogeneity and variabilities in experimental methodologies and biomarker analyses platforms.

Conclusion

Significant variabilities in study design, methodology, laboratory techniques, and outcome endpoints exist in SAH biomarker studies and present significant barriers toward validation and translation of putative biomarkers to clinical use. Adaptation of common data elements, recommended biospecimen protocols, and reporting guidelines will reduce heterogeneity and facilitate future meta-analyses and development of validated clinical biomarkers in SAH.

Appendix: SAH WORKING GROUP MEMBERS

Steering Committee

Jose I Suarez, MD, FNCS, FANA, Johns Hopkins University School of Medicine, Baltimore, MD, co - Chair

R Loch Macdonald, MD, PhD, University of Toronto, Toronto, ON, Canada, co - Chair

Sepideh Amin-Hanjani, MD—University of Illinois at Chicago, Chicago, IL

Robert D. Brown, Jr., MD, MPH—Mayo Clinic, Rochester, MN

Airton Leonardo de Oliveira Manoel, MD, PhD—University of Toronto, Toronto, Ontario, Canada

Colin P Derdeyn, MD, FACR—University of Iowa, Carver College of Medicine, Iowa City, IA

Nima Etminan, MD—University Hospital Mannheim, Mannheim, Germany

Emanuela Keller, MD—University of Zurich, Zurich, Switzerland

Peter D. LeRoux, MD, FACS—Main Line Health, Wynnewood, PA

Stephan Mayer, MD—Henry Ford Hospital, Detroit, MI

Akio Morita, MD, PhD—Nippon Medical School, Tokyo, Japan

Gabriel Rinkel, MD—University Medical Center, Utrecht, The Netherlands

Daniel Rufennacht, MD—Klinik Hirslanden, Zurich, Switzerland

Martin N. Stienen, MD, FEBNS—University of Zurich, Zurich, Switzerland

James Torner, MSc, PhD—University of Iowa, Iowa City, IA

Mervyn D.I. Vergouwen, MD, PhD—University Medical Center, Utrecht, The Netherlands

George K. C. Wong, MD—Chinese University of Hong Kong, Shatin, Hong Kong

Subject Characteristics Working Group

Robert D. Brown, Jr., MD, MPH—Mayo Clinic, Rochester, MN, co-Chair

Akio Morita, MD, PhD—Nippon Medical School, Tokyo, Japan, co-Chair

Philippe Bijlenga, MD, PhD, Geneva University Hospital, Geneva, Switzerland (Superuser)

Nerissa Ko, MD; Cameron G McDougall, MD; J Mocco, MS, MD; Yuuichi Murayama, MD; Marieke J H Werner, MD, PhD

Assessments and Examinations Working Group

Stephan Mayer, MD—Henry Ford Hospital, Detroit, MI, co-Chair

Jose I Suarez, MD, FNCS, FANA, The Johns Hopkins University School of Medicine, Baltimore, MD, co-Chair

Rahul Damani, MD, MPH, Baylor College of Medicine, Houston, TX (Superuser)

Joseph Broderick, MD; Raj Dhar, MD, FRCPC; Edward C Jauch, MD, MS, FACEP, FAHA; Peter J Kirkpatrick; Renee H Martin, PhD; J Mocco, MS, MD; Susanne Muehlschlegel, MD, MPH; Tatsushi Mutoh, MD, DVM, PhD; Paul Nyquist, MD, MPH; Daiwai Olson, RN, PhD; Jorge H Mejia-Mantilla, MD, MSc.

Hospital Course and Acute Therapies Working Group

Sepideh Amin-Hanjani, MD—University of Illinois at Chicago, Chicago, IL, co-Chair

Airton Leonardo de Oliveira Manoel, MD, PhD—University of Toronto, Toronto, Ontario, Canada, co-Chair (Superuser)

Mathieu van der Jagt, MD, PhD, Erasmus Medical Center, Rotterdam, The Netherlands (Superuser)

Nicholas Bambakidis, MD; Gretchen Brophy, PharmD, BCPS, FCCP, FCCM, FNCS; Ketan Bulsara, MD; Jan Claassen, MD, PhD; E Sander Connolly, MD, FACS; S Alan Hoffer, MD; Brian L Hoh, MD, FACS; Robert G Holloway, MD, MPH; Adam Kelly, MD; Stephan Mayer, MD; Peter Nakaji, MD; Alejandro Rabinstein, MD; Jose I Suarez, MD, FNCS, FANA; Peter Vajkoczy, MD; Mervyn D. I. Vergouwen, MD, PhD; Henry Woo, MD; Gregory J Zipfel, MD.

Biospecimens and Biomarkers Working Group

Emanuela Keller, MD—University of Zurich, Zurich, Switzerland, co-Chair (Superuser)

R Loch Macdonald, MD, PhD, University of Toronto, Toronto, ON, Canada, co-Chair

Sherry H-Y Chou, MD, MMSc (Superuser); Sylvain Doré, PhD, FAHA; Aaron S Dumont, MD; Murat Gunel, MD, FACS, FAHA; Hidetoshi Kasuya, MD; Alexander Roederer, PhD; Ynte Ruigrok, MD; Paul M Vespa, MD, FCCM, FAAN, FANA, FNCS; Asita Simone Sarrafzadeh-Khorrasani, PhD.

Imaging Working Group

Colin P Derdeyn, MD, FACR—University of Iowa, Carver College of Medicine, Iowa City, IA, co-Chair

Nima Etminan, MD University Hospital Mannheim, Mannheim, Germany, co-Chair

Katharina Hackenberg, MD, University Hospital Mannheim, Mannheim, Germany (Superuser)

John Huston, III, MD; Timo Krings, MD, PhD, FRCPC; Giuseppe Lanzino, MD; Philip M Meyers, MD, FACR, FSIR, FAHA; Gabriel Rinkel, MD; Daniel Rufennacht, MD; Max Wintermark, MD.

Long-Term Therapies Working Group

James Torner, MSc, PhD—University of Iowa, Iowa City, IA, co-Chair (Superuser)

George K. C. Wong, MD—Chinese University of Hong Kong, Shatin, Hong Kong, co-Chair (Superuser)

Joseph Broderick, MD; Janis Daly, PhD, MS; Christopher Ogilvy, MD; Denise H Rhoney, PharmD, FCCP, FCCM, FNCS; YB Roos, PhD; Adnan Siddiqui, MD, PhD, FAHA.

Unruptured Intracranial Aneurysms Working Group

Nima Etminan, MD—University Hospital Mannheim, Mannheim, Germany, co-Chair

Gabriel Rinkel, MD—University Medical Center, Utrecht, The Netherlands, co-Chair

Katharina Hackenberg, MD, University Hospital Mannheim, Mannheim, Germany (Superuser)

Ale Algra, MD, FAHA; Juhanna Frösen, MD; David Hasan, MD; Seppo Juvela, MD, PhD; David J Langer, MD; Philip M Meyers, MD, FACR, FSIR, FAHA; Akio Morita, MD, PhD; Rustam Al-Shahi Salman, MA, PhD, FRCP.

Outcomes and Endpoints Working Group

Martin N. Stienen, MD, FEBNS—University of Zurich, Zurich, Switzerland, co-Chair (Superuser).

Mervyn D.I. Vergouwen, MD, PhD—University Medical Center, Utrecht, The Netherlands, co-Chair.

Daniel Hanggi, MD; R Loch Macdonald, MD, PhD; Tom Schweizer, PhD; Johanna Visser-Meily, MD, PhD.

National Library of Medicine CDE Team

Liz Amos, MLIS, National Information Center on Health Services Research and Health Care Technology, National Library of Medicine.

Christophe Ludet, MS, National Library of Medicine, Bethesda, MD.

NINDS CDE Team

Claudia Moy, PhD, NINDS, Bethesda, MD

Joanne Odenkirchen, MPH, NINDS, Bethesda, MD

Sherita Ala’i, MS, The Emmes Corporation, Rockville, MD

Joy Esterlitz, MS, The Emmes Corporation, Rockville, MD

Kristen Joseph, MA, The Emmes Corporation, Rockville, MD

Muniza Sheikh, MS, MBA, The Emmes Corporation, Rockville, MD