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Abstract

Most clinical trials of treatment efficacy evaluate benefits and harms separately. Investigators generally rate the primary outcome of a trial with a binary outcome measure and consider harms separately as adverse events. This approach fails to recognize finer gradations of patient response, correlations between benefits and harms, and the overall effects on individual patients. For example, in status epilepticus trials, efficacy is often defined as the absence of clinically apparent seizures with recovery of consciousness. Such an efficacy outcome fails to recognize that some causes of status epilepticus, such as subarachnoid hemorrhage or stroke, may not be accompanied by return of consciousness, and the need to intubate a patient may be classified as treatment failure even if status was successfully terminated. The Desirability of Outcome Ranking (DOOR) method uses a different approach. The DOOR method involves comparing the experiences of trial participants in different treatment arms by the desirability of the overall patient outcome. Using status epilepticus treatment as an example, a patient who experiences successful termination of status epilepticus but with major side effects would have a less desirable outcome than a patient with treatment success and minor side effects, who in turn would have a less desirable outcome than a patient with treatment success but no side effects. This is a patient-centered approach because it considers treatment efficacy in the context of the costs borne by the patient, for example, toxicity in achieving efficacy. Thus, DOOR considers both the benefits and harms to individual patients in assessing the outcome of a clinical trial. In this article, we present the rationale for the use of DOOR, the issues involved in the development of and statistical analyses of an ordinal outcome, and an example of the potential application of the DOOR method to a clinical trial of convulsive status epilepticus.

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Information & Authors

Information

Published In

Neurology®
Volume 101Number 16October 17, 2023
Pages: e1633-e1639
PubMed: 37580166

Publication History

Received: July 5, 2022
Accepted: June 7, 2023
Published online: August 14, 2023
Published in print: October 17, 2023

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Disclosure

The authors report no relevant disclosures. Go to Neurology.org/N for full disclosures.

Study Funding

The authors report no targeted funding.

Authors

Affiliations & Disclosures

James M. Chamberlain, MD https://orcid.org/0000-0003-0543-1814
From the Division of Emergency Medicine (J.M.C.), Children's National Hospital; Departments of Pediatrics and Emergency Medicine (J.M.C.), George Washington University, Washington, DC; Department of Neurology (J.K.), University of Virginia, Charlottesville; Department of Emergency Medicine (R.S.S.), University of Michigan, Ann Arbor; Medical University of South Carolina (J.J.E.), Charleston; Harvard Medical School (E.S.R.); Massachusetts General Hospital (E.S.R.), Boston; Ken and Ruth Davee Department of Neurology (T.P.B.), Northwestern University Feinberg School of Medicine, Chicago, IL; Albert Einstein College of Medicine and Montefiore Medical Center (S.S.); Department of Emergency Medicine (S.Z.), Downstate Medical Center, New York, NY; and Milken Institute School of Public Health (S.R.E.), George Washington University, Washington, DC.
Disclosure
Scientific Advisory Boards:
1.
None
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
None
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
Fleisher and Ludwig's Textbook of Pediatric Emergency Medicine 8th edition, Wolters Kluwer, 2021
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NINDS, 1U01NS088034-01, Co-PI, 10/01/2014-02/28/2021 NICHD, 1R01HD087363-01A1, Co-I, 04/01/2016-03/31/2021 AHRQ, 1R01HS024953-01, Co-I, 09/30/2016-07/31/2021 NIMHD, R03 MD011654, Co-I, 09/01/2017-08/31/2019NIH, FP2819, Co-I, 9/1/2018–8/31/2020NIH, 1R21NS109669-01A1, Co-I, 7/1/2019–6/30/2021NIH, MCW-20190806, Site PI, 12/1/2018–11/30/2023 NIH, R01 HD 101528-01, Site PI, 07/01/2020-06/30/2025
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
None
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
From the Division of Emergency Medicine (J.M.C.), Children's National Hospital; Departments of Pediatrics and Emergency Medicine (J.M.C.), George Washington University, Washington, DC; Department of Neurology (J.K.), University of Virginia, Charlottesville; Department of Emergency Medicine (R.S.S.), University of Michigan, Ann Arbor; Medical University of South Carolina (J.J.E.), Charleston; Harvard Medical School (E.S.R.); Massachusetts General Hospital (E.S.R.), Boston; Ken and Ruth Davee Department of Neurology (T.P.B.), Northwestern University Feinberg School of Medicine, Chicago, IL; Albert Einstein College of Medicine and Montefiore Medical Center (S.S.); Department of Emergency Medicine (S.Z.), Downstate Medical Center, New York, NY; and Milken Institute School of Public Health (S.R.E.), George Washington University, Washington, DC.
Disclosure
Scientific Advisory Boards:
1.
Marinus Pharmaceutical. A double-blind, randomized, placebo-controlled study to evaluate the efficacy and safetyof intravenous ganaxolone in status epilepticus.
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
None
Editorial Boards:
1.
Experimental Neurology, Editorial Board, 2013-Annals of Neurology, Editorial Board 2016-2019
Patents:
1.
GABA A receptor antibody anti gamma2 and antidelta
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
2000-2021 NIH-NINDS, RO1 NS040337
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
None
Stock/stock Options/board of Directors Compensation:
1.
Royalties on GABA A receptro antibodies
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
Royalties on anti GABA A receptor antibodies
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Robert S. Silbergleit, MD https://orcid.org/0000-0003-4101-2430
From the Division of Emergency Medicine (J.M.C.), Children's National Hospital; Departments of Pediatrics and Emergency Medicine (J.M.C.), George Washington University, Washington, DC; Department of Neurology (J.K.), University of Virginia, Charlottesville; Department of Emergency Medicine (R.S.S.), University of Michigan, Ann Arbor; Medical University of South Carolina (J.J.E.), Charleston; Harvard Medical School (E.S.R.); Massachusetts General Hospital (E.S.R.), Boston; Ken and Ruth Davee Department of Neurology (T.P.B.), Northwestern University Feinberg School of Medicine, Chicago, IL; Albert Einstein College of Medicine and Montefiore Medical Center (S.S.); Department of Emergency Medicine (S.Z.), Downstate Medical Center, New York, NY; and Milken Institute School of Public Health (S.R.E.), George Washington University, Washington, DC.
Disclosure
Scientific Advisory Boards:
1.
None
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
(1) London-Innsbruck Colloquium on Status Epilepticus and Acute Seizures, funding for travel to speak
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
(1) 3D Communications LLC, (2) Marinus Pharmaceuticals,
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
(1) NIH, UG3HL145269, MPI, 2019-2024(2) NIH, U01NS099046, Co-I, 2018-2023(3) NIH, U24NS100659, MPI, 2017-2028(4) NIH, U01NS095926, Co-I, 2017-2022(5) NIH, R01NS099653, Co-I, 2017-2021(6) NIH, U01NS088034, MPI, 2014-2019(7) NIH, R25NS088248, Co-I, 2014-2019(8) NIH, UG3HL159134, Co-I, 2021-2028
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
(1) AHA, 19SFRN34760762, Project PI, 2019-2023
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Jordan J. Elm, PhD
From the Division of Emergency Medicine (J.M.C.), Children's National Hospital; Departments of Pediatrics and Emergency Medicine (J.M.C.), George Washington University, Washington, DC; Department of Neurology (J.K.), University of Virginia, Charlottesville; Department of Emergency Medicine (R.S.S.), University of Michigan, Ann Arbor; Medical University of South Carolina (J.J.E.), Charleston; Harvard Medical School (E.S.R.); Massachusetts General Hospital (E.S.R.), Boston; Ken and Ruth Davee Department of Neurology (T.P.B.), Northwestern University Feinberg School of Medicine, Chicago, IL; Albert Einstein College of Medicine and Montefiore Medical Center (S.S.); Department of Emergency Medicine (S.Z.), Downstate Medical Center, New York, NY; and Milken Institute School of Public Health (S.R.E.), George Washington University, Washington, DC.
Disclosure
Scientific Advisory Boards:
1.
None
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
None
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
Grants from National Institutes of Health.
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
None
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
From the Division of Emergency Medicine (J.M.C.), Children's National Hospital; Departments of Pediatrics and Emergency Medicine (J.M.C.), George Washington University, Washington, DC; Department of Neurology (J.K.), University of Virginia, Charlottesville; Department of Emergency Medicine (R.S.S.), University of Michigan, Ann Arbor; Medical University of South Carolina (J.J.E.), Charleston; Harvard Medical School (E.S.R.); Massachusetts General Hospital (E.S.R.), Boston; Ken and Ruth Davee Department of Neurology (T.P.B.), Northwestern University Feinberg School of Medicine, Chicago, IL; Albert Einstein College of Medicine and Montefiore Medical Center (S.S.); Department of Emergency Medicine (S.Z.), Downstate Medical Center, New York, NY; and Milken Institute School of Public Health (S.R.E.), George Washington University, Washington, DC.
Disclosure
Scientific Advisory Boards:
1.
None
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
None
Editorial Boards:
1.
NONE
Patents:
1.
(1) System and Method for Electrical Impedance Spectroscopy.” United States Patent 9,820,669, Date of patent Nov. 21, 2017 (2) System and Method for Detecting Treatment Outcomes for Neurological Disorders Based on Functional Connectivity Parameters.” Patent Cooperation Treaty (PCT) International Application 125141.03491, filed Sept. 14, 2020
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
(1) Continuous EEG Monitoring 10% of effort
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
(1) 09/20–08/25 ELECTRO-BOOST: Electroencephalography Measures Cerebral Trauma Recovery and Oxygenation NINDS 1R01NS117904(PI) (2) 09/20-08/25 Learning to Predict Delayed Cerebral Ischemia with Novel Continuous Cerebral Arterial State Index NINDS 1R01NS113541 (Co-I) (3) 06/19-05/21 A New Brain Medical Record for Precision Management of TBI US Army W81XWH-18-DMRDP-PTCRA (Co-PI) (4) 04/18-03/23 Real-Time Prediction of Delayed Cerebral Ischemia after Subarachnoid Hemorrhage NIH/NINDS 1K23NS105950 (PI) (5) 09/16-08/21 The Epilepsy Bioinformatics Study for Antiepileptogenic Therapy (EpiBios4Rx) NIH/NINDS U54NS100064 (Co-I) (6) 7/16-7/20 Development and Validation of Spreading Depolarization Monitoring for TBI Management DoD/BAA W81XWH-BAA-15-1 (Co-I) (6) 07/17 - 05/22 NHLBI/NINDS The MASS-SIREN Group 5U24NS100651-04 (Co-I) (7) 09/14-02/20 Established Status Epilepticus Treatment Trial NINDS 1U01NS088034 (Co-I)
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
Andrew David Heitman Foundation
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
From the Division of Emergency Medicine (J.M.C.), Children's National Hospital; Departments of Pediatrics and Emergency Medicine (J.M.C.), George Washington University, Washington, DC; Department of Neurology (J.K.), University of Virginia, Charlottesville; Department of Emergency Medicine (R.S.S.), University of Michigan, Ann Arbor; Medical University of South Carolina (J.J.E.), Charleston; Harvard Medical School (E.S.R.); Massachusetts General Hospital (E.S.R.), Boston; Ken and Ruth Davee Department of Neurology (T.P.B.), Northwestern University Feinberg School of Medicine, Chicago, IL; Albert Einstein College of Medicine and Montefiore Medical Center (S.S.); Department of Emergency Medicine (S.Z.), Downstate Medical Center, New York, NY; and Milken Institute School of Public Health (S.R.E.), George Washington University, Washington, DC.
Disclosure
Scientific Advisory Boards:
1.
(1) SAGE Corporation, DSMB chair(2) Marinus Pharmaceuticals, DSMB chair
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
None
Editorial Boards:
1.
(1) Critical Care Medicine, associate editor, 2016 - 2020; senior editor, 2021 - (2) Annals of Intensive Care, editorial board member, 2010 -(3) Current Opinion in Critical Care, editorial board member, 2019
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
Ceribell Corporation
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NINDS 1U01NS088034-01, Status Epilepticus Treatment Trial (ESETT), executive committee, 2013 -NIH 1DP2HD101400 (NIH Director's New Innovator Award) A Connectome-Based Clinical Trial Platform to Promote Early Recovery of Consciousness after Traumatic Coma (Brian L Edlow MD, PI) Role: Independent Medical MonitorUG3HL145269, U24HL145272, U24NS100659, U24NS100655 Influence of Cooling Duration on Efficacy in Cardiac Arrest Patients (ICECAP), Strategies to Innovate Emergency Care Clinical Trials Network (SIREN) (William Meurer, Romer Geocadin, Robert Silbergleit, national PIs; Peter Pruitt, local PI)Role: Co-principal Investigator
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
None
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
Ceribell Corporation 2017 - 2019
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Shlomo Shinnar, MD, PhD
From the Division of Emergency Medicine (J.M.C.), Children's National Hospital; Departments of Pediatrics and Emergency Medicine (J.M.C.), George Washington University, Washington, DC; Department of Neurology (J.K.), University of Virginia, Charlottesville; Department of Emergency Medicine (R.S.S.), University of Michigan, Ann Arbor; Medical University of South Carolina (J.J.E.), Charleston; Harvard Medical School (E.S.R.); Massachusetts General Hospital (E.S.R.), Boston; Ken and Ruth Davee Department of Neurology (T.P.B.), Northwestern University Feinberg School of Medicine, Chicago, IL; Albert Einstein College of Medicine and Montefiore Medical Center (S.S.); Department of Emergency Medicine (S.Z.), Downstate Medical Center, New York, NY; and Milken Institute School of Public Health (S.R.E.), George Washington University, Washington, DC.
Disclosure
Scientific Advisory Boards:
1.
Eisai - DSMB memberUCB - DSMB member
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
None
Editorial Boards:
1.
Pediatric Neurology - editorial board member 1995-present
Patents:
1.
NONE
Publishing Royalties:
1.
Febrile Seizures: New Concepts and Consequences, Second Edition Baram TZ, Shinnar S and Stafstrom CE Editors, AcdemicPress 2023
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NIH/NINDS R37 NS43209 2003-2022 (PI)NIH/NINDS 1U10NS088034 2014-2019 Co-InvestigatorNIH/NINDS R01NS094257 2016-2021 Co-InvestigatorNIH/NINDS 1R21 NS09669 2019-2021 Consultant
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
None
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Shahriar Zetabchi, MD
From the Division of Emergency Medicine (J.M.C.), Children's National Hospital; Departments of Pediatrics and Emergency Medicine (J.M.C.), George Washington University, Washington, DC; Department of Neurology (J.K.), University of Virginia, Charlottesville; Department of Emergency Medicine (R.S.S.), University of Michigan, Ann Arbor; Medical University of South Carolina (J.J.E.), Charleston; Harvard Medical School (E.S.R.); Massachusetts General Hospital (E.S.R.), Boston; Ken and Ruth Davee Department of Neurology (T.P.B.), Northwestern University Feinberg School of Medicine, Chicago, IL; Albert Einstein College of Medicine and Montefiore Medical Center (S.S.); Department of Emergency Medicine (S.Z.), Downstate Medical Center, New York, NY; and Milken Institute School of Public Health (S.R.E.), George Washington University, Washington, DC.
Disclosure
Scientific Advisory Boards:
1.
None
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
None
Editorial Boards:
1.
1. Associate editor and editorial board member, Academic Emergency Medicine journal, 2. Editor-in-Chief, TheNNT.com website (open access evidence-based medicine resource)
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
None
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Scott R. Evans, PhD
From the Division of Emergency Medicine (J.M.C.), Children's National Hospital; Departments of Pediatrics and Emergency Medicine (J.M.C.), George Washington University, Washington, DC; Department of Neurology (J.K.), University of Virginia, Charlottesville; Department of Emergency Medicine (R.S.S.), University of Michigan, Ann Arbor; Medical University of South Carolina (J.J.E.), Charleston; Harvard Medical School (E.S.R.); Massachusetts General Hospital (E.S.R.), Boston; Ken and Ruth Davee Department of Neurology (T.P.B.), Northwestern University Feinberg School of Medicine, Chicago, IL; Albert Einstein College of Medicine and Montefiore Medical Center (S.S.); Department of Emergency Medicine (S.Z.), Downstate Medical Center, New York, NY; and Milken Institute School of Public Health (S.R.E.), George Washington University, Washington, DC.
Disclosure
Scientific Advisory Boards:
1.
FDA, NIH, Frontier Science Foundation, Analgesic Anesthetic and Addiction Clinical Trial Translations Innovations Opportunities and Networks(ACTTION), Pfizer, Roche, AstraZeneca, Vir, GSK, Genentech, Johnson&Johnson, International Drug Development Institute, Breast International Group, University of Pennsylvania, Duke University, Wake Forest University, Akouous, Apellis, Teva, DayOneBio, Rakuten, Abbvie, Nuvelution, Clover, FHI Clinical, Lung Biotech, SAB Biopharm, Candel, Takeda, Rakuten, Eli Lilly, Novartis
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
International Chinese Statistical Association
Editorial Boards:
1.
STATISTICAL COMMUNICATIONS IN INFECTIOUS DISEASES,EDITOR-IN-CHEIF, (FROM 2016)Statistics in Biopharmaceutical Research, advisory editor (2019-present).
Patents:
1.
NONE
Publishing Royalties:
1.
Evans SR and Ting, N. Fundamental Concepts for NewClinical Trialists. ISBN 9781420090871 - CAT# C9087.Chapman & Hall/CRC Biostatistics Series. 2015.
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
National Institute of Health (NIH) grants including theNational Institute of Allergy and Infectious Diseases(NIAID) of the NIH (award number UM1AI104681) and NCI.
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
None
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE

Notes

Correspondence Dr. Chamberlain [email protected]
Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
Submitted and externally peer reviewed. The handling editor was Associate Editor Barbara Jobst, MD, PhD, FAAN.

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