Definition and Prioritization of Data Elements for Cohort Studies and Clinical Trials on Patients with Unruptured Intracranial Aneurysms: Proposal of a Multidisciplinary Research Group

  • Katharina A. M. HackenbergEmail author
  • Ale Algra
  • Rustam Al-Shahi Salman
  • Juhana Frösen
  • David Hasan
  • Seppo Juvela
  • David Langer
  • Philip Meyers
  • Akio Morita
  • Gabriel Rinkel
  • Nima Etminan
  • the Unruptured Aneurysms and SAH CDE Project Investigators
Special Article



Variability in usage and definition of data characteristics in previous cohort studies on unruptured intracranial aneurysms (UIA) complicated pooling and proper interpretation of these data. The aim of the National Institute of Health/National Institute of Neurological Disorders and Stroke UIA and Subarachnoid Hemorrhage (SAH) Common Data Elements (CDE) Project was to provide a common structure for data collection in future research on UIA and SAH.


This paper describes the development and summarization of the recommendations of the working groups (WGs) on UIAs, which consisted of an international and multidisciplinary panel of cerebrovascular specialists on research and treatment of UIAs. Consensus recommendations were developed by review of previously published CDEs for other neurological diseases and the literature on UIAs. Recommendations for CDEs were classified by priority into ‘Core,’ ‘Supplemental—Highly Recommended,’ ‘Supplemental,’ and ‘Exploratory.’


Ninety-one CDEs were compiled; 69 were newly created and 22 were existing CDEs. The CDEs were assigned to eight subcategories and were classified as Core (8), Supplemental—Highly Recommended (23), Supplemental (25), and Exploratory (35) elements. Additionally, the WG developed and agreed on a classification for aneurysm morphology.


The proposed CDEs have been distilled from a broad pool of characteristics, measures, or outcomes. The usage of these CDEs will facilitate pooling of data from cohort studies or clinical trials on patients with UIAs.


Common data elements Unruptured intracranial aneurysms Risk factors Morphology Data standardization 



The views expressed here are those of the authors and do not represent those of the National Institutes of Health (NIH), the National Institute of Neurological Disorders and Stroke (NINDS), or the US Government. Logistical support for this project was provided in part through NIH Contract HHSN271201200034C, the Intramural Research Program of the NIH, NLM, The Neurocritical Care Society, and the CHI Baylor St Luke’s Medical Center in Houston, TX. The development of the NINDS SAH CDEs was made possible thanks to the great investment of time and effort of WG members and the members of the NINDS CDE Project and NLM CDE project teams participating from 2015–2017.

Authors’ Contributions

KAMH, NE, and GR contributed to protocol development, and manuscript writing/editing; AA, RA-SS, JF, DH, SJ, DL, PM, and AM contributed to manuscript writing/editing. The corresponding author confirms that authorship requirements have been met, the final manuscript was approved by ALL authors, and that this manuscript has not been published elsewhere and is not under consideration by another journal. The UIA and SAH CDEs project adhered to ethical guidelines.

Compliance with Ethical Standards

Source of support


Conflict of interest

All authors have no conflicts of interest.

Ethical approval/informed consent

This article does not contain any studies with human participants or animals performed by any of the authors.

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 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, MPHMayo Clinic, Rochester, MN, co-Chair; Akio Morita, MD, PhDNippon 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, MDHenry 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, MDUniversity of Illinois at Chicago, Chicago, IL, co-Chair; Airton Leonardo de Oliveira Manoel, MD, PhDUniversity 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, MDUniversity 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, FACRUniversity of Iowa, Carver College of Medicine, Iowa City, IA, co-Chair; Nima Etminan, MD University Hospital Mannheim, Mannheim, Germany, co-Chair; Katharina A. M. 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, PhDUniversity of Iowa, Iowa City, IA, co-Chair (Superuser); George K. C. Wong, MDChinese 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, MDUniversity Hospital Mannheim, Mannheim, Germany, co-Chair; Gabriel Rinkel, MDUniversity Medical Center, Utrecht, The Netherlands, co-Chair; Katharina A. M.  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, FEBNSUniversity of Zurich, Zurich, Switzerland, co-Chair (Superuser); Mervyn D.I. Vergouwen, MD, PhDUniversity 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.


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.


  1. 1.
    Vlak MH, Rinkel GJ, Greebe P, Algra A. Risk of rupture of an intracranial aneurysm based on patient characteristics: a case–control study. Stroke. 2013;44(5):1256–9.CrossRefGoogle Scholar
  2. 2.
    Nieuwkamp DJ, Setz LE, Algra A, Linn FH, de Rooij NK, Rinkel GJ. Changes in case fatality of aneurysmal subarachnoid haemorrhage over time, according to age, sex, and region: a meta-analysis. Lancet Neurol. 2009;8(7):635–42.CrossRefGoogle Scholar
  3. 3.
    Lovelock CE, Rinkel GJ, Rothwell PM. Time trends in outcome of subarachnoid hemorrhage: population-based study and systematic review. Neurology. 2010;74(19):1494–501.CrossRefGoogle Scholar
  4. 4.
    Feigin VL, Rinkel GJ, Lawes CM, Algra A, Bennett DA, van Gijn J, et al. Risk factors for subarachnoid hemorrhage: an updated systematic review of epidemiological studies. Stroke. 2005;36(12):2773–80.CrossRefGoogle Scholar
  5. 5.
    Greving JP, Wermer MJ, Brown RD Jr., Morita A, Juvela S, Yonekura M, et al. Development of the PHASES score for prediction of risk of rupture of intracranial aneurysms: a pooled analysis of six prospective cohort studies. Lancet Neurol. 2014;13(1):59–66.CrossRefGoogle Scholar
  6. 6.
    Backes D, Rinkel GJE, Greving JP, Velthuis BK, Murayama Y, Takao H, et al. ELAPSS score for prediction of risk of growth of unruptured intracranial aneurysms. Neurology. 2017;88(17):1600–6.CrossRefGoogle Scholar
  7. 7.
    Damani R, Mayer S, Dhar R, Martin RH, Nyquist P, Olson DM, et al. Common data element for unruptured intracranial aneurysm and subarachnoid hemorrhage: recommendations from assessments and clinical examination workgroup/subcommittee. Neurocrit Care. 2019. Scholar
  8. 8.
    Sonobe M, Yamazaki T, Yonekura M, Kikuchi H. Small unruptured intracranial aneurysm verification study: SUAVe study, Japan. Stroke. 2010;41(9):1969–77.CrossRefGoogle Scholar
  9. 9.
    Juvela S, Poussa K, Lehto H, Porras M. Natural history of unruptured intracranial aneurysms: a long-term follow-up study. Stroke. 2013;44(9):2414–21.CrossRefGoogle Scholar
  10. 10.
    Lindgren AE, Raisanen S, Bjorkman J, Tattari H, Huttunen J, Huttunen T, et al. De novo aneurysm formation in carriers of saccular intracranial aneurysm disease in eastern Finland. Stroke. 2016;47(5):1213–8.CrossRefGoogle Scholar
  11. 11.
    Vlak MH, Rinkel GJ, Greebe P, Algra A. Independent risk factors for intracranial aneurysms and their joint effect: a case-control study. Stroke. 2013;44(4):984–7.CrossRefGoogle Scholar
  12. 12.
    Wermer MJ, van der Schaaf IC, Velthuis BK, Algra A, Buskens E, Rinkel GJ. Follow-up screening after subarachnoid haemorrhage: frequency and determinants of new aneurysms and enlargement of existing aneurysms. Brain. 2005;128(Pt 10):2421–9.CrossRefGoogle Scholar
  13. 13.
    Etminan N, Beseoglu K, Steiger HJ, Hanggi D. The impact of hypertension and nicotine on the size of ruptured intracranial aneurysms. J Neurol Neurosurg Psychiatry. 2011;82(1):4–7.CrossRefGoogle Scholar
  14. 14.
    Vlak MH, Algra A, Brandenburg R, Rinkel GJ. Prevalence of unruptured intracranial aneurysms, with emphasis on sex, age, comorbidity, country, and time period: a systematic review and meta-analysis. Lancet Neurol. 2011;10(7):626–36.CrossRefGoogle Scholar
  15. 15.
    Juvela S, Poussa K, Porras M. Factors affecting formation and growth of intracranial aneurysms: a long-term follow-up study. Stroke. 2001;32(2):485–91.CrossRefGoogle Scholar
  16. 16.
    Korja M, Lehto H, Juvela S. Lifelong rupture risk of intracranial aneurysms depends on risk factors: a prospective Finnish cohort study. Stroke. 2014;45(7):1958–63.CrossRefGoogle Scholar
  17. 17.
    Igase M, Igase K, Kohara K, Yamashita S, Fujisawa M, Katagi R, et al. Visit-to-visit variability in systolic blood pressure is a novel risk factor for the growth of intracranial aneurysms. Cerebrovasc Dis. 2013;36(5–6):401–6.CrossRefGoogle Scholar
  18. 18.
    Juvela S, Korja M. Intracranial aneurysm parameters for predicting a future subarachnoid hemorrhage: a long-term follow-up study. Neurosurgery. 2017;81(3):432–40.CrossRefGoogle Scholar
  19. 19.
    Wiebers DO, Whisnant JP, Huston J III, Meissner I, Brown RD Jr, Piepgras DG, et al. Unruptured intracranial aneurysms: natural history, clinical outcome, and risks of surgical and endovascular treatment. Lancet. 2003;362(9378):103–10.CrossRefGoogle Scholar
  20. 20.
    Morita A, Kirino T, Hashi K, Aoki N, Fukuhara S, Hashimoto N, et al. The natural course of unruptured cerebral aneurysms in a Japanese cohort. N Engl J Med. 2012;366(26):2474–82.CrossRefGoogle Scholar
  21. 21.
    Schneiders JJ, Marquering HA, van Ooij P, van den Berg R, Nederveen AJ, Verbaan D, et al. Additional value of intra-aneurysmal hemodynamics in discriminating ruptured versus unruptured intracranial aneurysms. AJNR Am J Neuroradiol. 2015;36(10):1920–6.CrossRefGoogle Scholar
  22. 22.
    Backes D, Rinkel GJ, Laban KG, Algra A, Vergouwen MD. Patient- and aneurysm-specific risk factors for intracranial aneurysm growth: a systematic review and meta-analysis. Stroke. 2016;47(4):951–7.CrossRefGoogle Scholar
  23. 23.
    Murayama Y, Takao H, Ishibashi T, Saguchi T, Ebara M, Yuki I, et al. Risk analysis of unruptured intracranial aneurysms: prospective 10-year cohort study. Stroke. 2016;47(2):365–71.CrossRefGoogle Scholar
  24. 24.
    Ishibashi T, Murayama Y, Urashima M, Saguchi T, Ebara M, Arakawa H, et al. Unruptured intracranial aneurysms: incidence of rupture and risk factors. Stroke. 2009;40(1):313–6.CrossRefGoogle Scholar
  25. 25.
    Matsubara S, Hadeishi H, Suzuki A, Yasui N, Nishimura H. Incidence and risk factors for the growth of unruptured cerebral aneurysms: observation using serial computerized tomography angiography. J Neurosurg. 2004;101(6):908–14.CrossRefGoogle Scholar
  26. 26.
    Miyazawa N, Akiyama I, Yamagata Z. Risk factors for growth of unruptured intracranial aneurysms: follow-up study by serial 0.5-T magnetic resonance angiography. Neurosurgery. 2006;58(6):1047–53 (discussion -53).CrossRefGoogle Scholar
  27. 27.
    Jing L, Fan J, Wang Y, Li H, Wang S, Yang X, et al. Morphologic and hemodynamic analysis in the patients with multiple intracranial aneurysms: ruptured versus unruptured. PLoS ONE. 2015;10(7):e0132494.CrossRefGoogle Scholar
  28. 28.
    Kashiwazaki D, Kuroda S. Size ratio can highly predict rupture risk in intracranial small (< 5 mm) aneurysms. Stroke. 2013;44(8):2169–73.CrossRefGoogle Scholar
  29. 29.
    Burns JD, Huston J III, Layton KF, Piepgras DG, Brown RD Jr. Intracranial aneurysm enlargement on serial magnetic resonance angiography: frequency and risk factors. Stroke. 2009;40(2):406–11.CrossRefGoogle Scholar
  30. 30.
    Bor AS, Tiel Groenestege AT, terBrugge KG, Agid R, Velthuis BK, Rinkel GJ, et al. Clinical, radiological, and flow-related risk factors for growth of untreated, unruptured intracranial aneurysms. Stroke. 2015;46(1):42–8.CrossRefGoogle Scholar
  31. 31.
    de Rooij NK, Velthuis BK, Algra A, Rinkel GJ. Configuration of the circle of Willis, direction of flow, and shape of the aneurysm as risk factors for rupture of intracranial aneurysms. J Neurol. 2009;256(1):45–50.CrossRefGoogle Scholar
  32. 32.
    Lindgren AE, Koivisto T, Bjorkman J, von Und Zu Fraunberg M, Helin K, Jaaskelainen JE, et al. Irregular shape of intracranial aneurysm indicates rupture risk irrespective of size in a population-based cohort. Stroke. 2016;47(5):1219–26.CrossRefGoogle Scholar
  33. 33.
    Backes D, Vergouwen MD, Velthuis BK, van der Schaaf IC, Bor AS, Algra A, et al. Difference in aneurysm characteristics between ruptured and unruptured aneurysms in patients with multiple intracranial aneurysms. Stroke. 2014;45(5):1299–303.CrossRefGoogle Scholar

Copyright information

© Neurocritical Care Society 2019

Authors and Affiliations

  • Katharina A. M. Hackenberg
    • 1
    Email author
  • Ale Algra
    • 2
  • Rustam Al-Shahi Salman
    • 3
  • Juhana Frösen
    • 4
  • David Hasan
    • 5
  • Seppo Juvela
    • 6
  • David Langer
    • 7
  • Philip Meyers
    • 8
  • Akio Morita
    • 9
  • Gabriel Rinkel
    • 10
  • Nima Etminan
    • 1
  • the Unruptured Aneurysms and SAH CDE Project Investigators
  1. 1.Department of Neurosurgery, University Hospital MannheimUniversity of HeidelbergMannheimGermany
  2. 2.Brain Center Rudolph Magnus, Department of Neurology and Neurosurgery, and the Julius Center for Health Sciences and Primary CareUniversity Medical Center UtrechtUtrechtThe Netherlands
  3. 3.Centre for Clinical Brain SciencesUniversity of EdinburghEdinburghUK
  4. 4.Department of NeurosurgeryKuopio University HospitalKuopioFinland
  5. 5.Department of NeurosurgeryUniversity of Iowa Carver College of MedicineIowa CityUSA
  6. 6.Department of Clinical NeurosciencesUniversity of HelsinkiHelsinkiFinland
  7. 7.Department of Neurosurgery, Hofstra Northwell School of Medicine, and Northwell HealthLenox-Hill HospitalNew YorkUSA
  8. 8.Departments of Neurosurgery and RadiologyColumbia University Medical CenterNew YorkUSA
  9. 9.Department of Neurological SurgeryNippon Medical SchoolBunkyo-ku, TokyoJapan
  10. 10.Brain Center Rudolf Magnus, Department of Neurology and Neurosurgery and Center of Excellence for Rehabilitation MedicineUniversity Medical Center UtrechtUtrechtThe Netherlands

Personalised recommendations