Prioritization and Timing of Outcomes and Endpoints After Aneurysmal Subarachnoid Hemorrhage in Clinical Trials and Observational Studies: Proposal of a Multidisciplinary Research Group

Abstract

Introduction

In studies on aneurysmal subarachnoid hemorrhage (SAH), substantial variability exists in the use and timing of outcomes and endpoints, which complicates interpretation and comparison of results between studies. The aim of the National Institute of Health/National Institute of Neurological Disorders and Stroke/National Library of Medicine Unruptured Intracranial Aneurysm (UIA) and SAH common data elements (CDE) Project was to provide a common structure for future UIA and SAH research.

Methods

This article summarizes the recommendations of the UIA and SAH CDE Outcomes and Endpoints subgroup, which consisted of an international and multidisciplinary ad hoc panel of experts in clinical outcomes after SAH. Consensus recommendations were developed by review of previously published CDEs for other neurological diseases and the SAH literature. Recommendations for CDEs were classified by priority into “Core,” “Supplemental—Highly Recommended,” “Supplemental,” and “Exploratory.”

Results

The subgroup identified over 50 outcomes measures and template case report forms (CRFs) to be included as part of the UIA and SAH CDE recommendations. None was classified as “Core”. The modified Rankin Scale score and Montreal Cognitive Assessment were considered the preferred outcomes and classified as Supplemental—Highly Recommended. Death, Glasgow Outcome Scale score, and Glasgow Outcome Scale-extended were classified as Supplemental. All other outcome measures were categorized as “Exploratory”. We propose outcome assessment at 3 months and at 12 months for studies interested in long-term outcomes. We give recommendations for standardized dichotomization.

Conclusion

The recommended outcome measures and CRFs have been distilled from a broad pool of potentially useful CDEs, scales, instruments, and endpoints. The adherence to these recommendations will facilitate the comparison of results across studies and meta-analyses of individual patient data.

Appendix: UIA and 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 Rüfenacht, 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 Chou, MD, MMSc; 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 Rüfenacht, 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 Hänggi, 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