title: Impact of individual clinical outcomes on trial participants' perspectives on enrollment in emergency research without consent.
abstract: BACKGROUND
  Evidence suggests that patients are generally accepting of their enrollment in trials for emergency care conducted under exception from informed consent. It is unknown whether individuals with more severe initial injuries or worse clinical outcomes have different perspectives. Determining whether these differences exist may help to structure post-enrollment interactions.
  
  
  METHODS
  Primary clinical data from the Progesterone for the Treatment of Traumatic Brain Injury trial were matched to interview data from the Patients' Experiences in Emergency Research-Progesterone for the Treatment of Traumatic Brain Injury study. Answers to three key questions from Patients' Experiences in Emergency Research-Progesterone for the Treatment of Traumatic Brain Injury study were analyzed in the context of enrolled patients' initial injury severity (initial Glasgow Coma Scale and Injury Severity Score) and principal clinical outcomes (Extended Glasgow Outcome Scale and Extended Glasgow Outcome Scale relative to initial injury severity). The three key questions from Patients' Experiences in Emergency Research-Progesterone for the Treatment of Traumatic Brain Injury study addressed participants' general attitude toward inclusion in the Progesterone for the Treatment of Traumatic Brain Injury trial (general trial inclusion), their specific attitude toward being included in Progesterone for the Treatment of Traumatic Brain Injury trial under the exception from informed consent (personal exception from informed consent enrollment), and their attitude toward the use of exception from informed consent in the Progesterone for the Treatment of Traumatic Brain Injury trial in general (general exception from informed consent enrollment). Qualitative analysis of interview transcripts was performed to provide contextualization and to determine the extent to which respondents framed their attitudes in terms of clinical experience.
  
  
  RESULTS
  Clinical data from Progesterone for the Treatment of Traumatic Brain Injury trial were available for all 74 patients represented in the Patients' Experiences in Emergency Research-Progesterone for the Treatment of Traumatic Brain Injury study (including 46 patients for whom the surrogate was interviewed due to the patient's cognitive status or death). No significant difference was observed regarding acceptance of general trial inclusion or acceptance of general exception from informed consent enrollment between participants with favorable neurological outcomes and those with unfavorable outcomes relative to initial injury. Agreement with personal enrollment in Progesterone for the Treatment of Traumatic Brain Injury trial under exception from informed consent, however, was significantly higher among participants with favorable outcomes compared to those with unfavorable outcomes (89% vs 59%, p = 0.003). There was also a statistically significant relationship between more severe initial injury and increased acceptance of personal exception from informed consent enrollment ( p = 0.040) or general exception from informed consent use ( p = 0.034) in Progesterone for the Treatment of Traumatic Brain Injury trial. Many individuals referenced personal experience as a basis for their attitudes, but these references were not used to support negative views.
  
  
  CONCLUSIONS
  Patients and surrogates of patients with unfavorable clinical outcomes were somewhat less accepting of their own inclusion in the Progesterone for the Treatment of Traumatic Brain Injury trial under exception from informed consent than were patients or surrogates of patients with favorable clinical outcomes. These findings suggest a need to identify optimal strategies for communicating with patients and their surrogates regarding exception from informed consent enrollment when clinical outcomes are poor.
authors.affiliation: 1 Department of Internal Medicine, Hospital of the University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Louisa W
authors.initials: LW
authors.lastname: Whitesides
authors.affiliation: 2 Department of Emergency Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Jill M
authors.initials: JM
authors.lastname: Baren
authors.affiliation: 3 Hennepin County Medical Center, Department of Emergency Medicine, School of Medicine, University of Minnesota, Minneapolis, MN, USA.
authors.forename: Michelle H
authors.initials: MH
authors.lastname: Biros
authors.affiliation: 4 Department of Emergency Medicine, Harbor-UCLA Medical Center, Torrance, CA, USA.
authors.forename: Ross J
authors.initials: RJ
authors.lastname: Fleischman
authors.affiliation: 5 Department of Emergency Medicine, School of Medicine, University of California San Francisco, San Francisco, CA, USA.
authors.forename: Prasanthi R
authors.initials: PR
authors.lastname: Govindarajan
authors.affiliation: 6 Department of Emergency Medicine, University of Texas Medical School at Houston, Houston, TX, USA.
authors.forename: Elizabeth B
authors.initials: EB
authors.lastname: Jones
authors.affiliation: 7 Department of Emergency Medicine, College of Medicine, University of Cincinnati, Cincinnati, OH, USA.
authors.forename: Arthur M
authors.initials: AM
authors.lastname: Pancioli
authors.affiliation: 8 Department of Hematology and Oncology, School of Medicine, Emory University, Atlanta, GA, USA.
authors.forename: Rebecca D
authors.initials: RD
authors.lastname: Pentz
authors.affiliation: 9 School of Medicine, Emory University, Atlanta, GA, USA.
authors.forename: Victoria M
authors.initials: VM
authors.lastname: Scicluna
authors.affiliation: 10 Department of Emergency Medicine, School of Medicine, Emory University, Atlanta, GA, USA.
authors.forename: David W
authors.initials: DW
authors.lastname: Wright
authors.affiliation: 11 Division of Cardiology, Department of Medicine, School of Medicine, Emory University, Atlanta, GA, USA.|12 Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA, USA.
authors.forename: Neal W
authors.initials: NW
authors.lastname: Dickert
mesh_terms: D001294:Attitude to Health; D035843:Biomedical Research; D000070642:Brain Injuries, Traumatic / Q000188:drug therapy*; D017326:Clinical Trials, Phase III as Topic; D004630:Emergencies; D015600:Glasgow Coma Scale; D023261:Glasgow Outcome Scale; D006801:Humans; D007258:Informed Consent; D015601:Injury Severity Score; D015337:Multicenter Studies as Topic; D011374:Progesterone / Q000627:therapeutic use*; D011372:Progestins / Q000627:therapeutic use*; D019727:Proxy; D016032:Randomized Controlled Trials as Topic; D016896:Treatment Outcome
chemical_list: D011372:Progestins; D011374:Progesterone
keywords: Research ethics; acute care research; bioethics; emergency research; informed consent; traumatic brain injury