title: "It is not guaranteed that you will benefit": True but misleading?
abstract: BACKGROUND
  Participants of early-phase intervention trials for serious conditions provide high estimates of likelihood of benefit, even when informed consent forms do not promise such benefits. However, some technically correct, negatively stated benefits statements—such as "it is not guaranteed that you will benefit"—could play a role in raising expectations of benefit because in ordinary English usage such statements denote a likely but not a certain-to-occur event.
  
  
  METHODS
  An experimental online survey of 584 English-speaking adults recruited online. They were randomized to receive one of two benefit statements ("not guaranteed" vs "some but very small chance"), using a hypothetical scenario of an early-phase clinical trial testing an intervention to treat amyotrophic lateral sclerosis. We assessed respondents' willingness to consider participating in the amyotrophic lateral sclerosis trial, their estimates of likelihood of benefit, and their explanations for those estimates.
  
  
  RESULTS
  The two arms did not differ in willingness to consider participation in the amyotrophic lateral sclerosis trial. Those receiving "not guaranteed" benefit statement had higher estimates of benefit than those receiving "some but very small chance" statement (35.7% (standard deviation 20.2) vs 28.3% (standard deviation 22.0), p < 0.0001). A total of 43% of all respondents chose expressions of positive sentiment (hope and need to stay positive) as explanations of their estimates; these respondents' estimates of benefit were higher than others but similar between the two arms. The effect of benefit statements was greatest among those who chose "Those are just the facts" as the explanation for their estimate (31.0% (standard deviation 22.4%) in "not guaranteed" arm vs 18.9% (standard deviation 21.0%) in comparison arm, p = 0.008).
  
  
  CONCLUSIONS
  The use of "not guaranteed" language in benefit statements, when compared to "small but very small chance" language, appeared to increase the perception of likelihood of benefit of entering an early-phase trial, especially among those who view their estimates of benefits as "facts." Such "no guarantee" benefit statements may be misleading and should not be used in informed consent forms.
authors.affiliation: Department of Bioethics, National Institutes of Health, Bethesda, MD, USA Department of Psychiatry, University of Michigan, Ann Arbor, MI, USA scott.kim@nih.gov.
authors.forename: Scott Y H
authors.initials: SY
authors.lastname: Kim
authors.affiliation: Center for Human Experimental Therapeutics, University of Rochester, Rochester, NY, USA.
authors.forename: Renee
authors.initials: R
authors.lastname: Wilson
authors.affiliation: Center for Bioethics and Social Sciences in Medicine and Department of Medical Education, University of Michigan, Ann Arbor, MI, USA.
authors.forename: Raymond
authors.initials: R
authors.lastname: De Vries
authors.affiliation: Department of Biostatistics, University of Michigan, Ann Arbor, MI, USA.
authors.forename: H Myra
authors.initials: HM
authors.lastname: Kim
authors.affiliation: Department of Neurology, University of Rochester, Rochester, NY, USA.
authors.forename: Robert G
authors.initials: RG
authors.lastname: Holloway
authors.affiliation: Departments of Environmental Medicine and Public Health Sciences, Clinical and Translational Science Institute, University of Rochester, Rochester, NY, USA.
authors.forename: Karl
authors.initials: K
authors.lastname: Kieburtz
mesh_terms: D000328:Adult; D002986:Clinical Trials as Topic; D005260:Female; D006801:Humans; D007258:Informed Consent; D008297:Male; D010358:Patient Participation / Q000523:psychology*; D018570:Risk Assessment; D011795:Surveys and Questionnaires; D055815:Young Adult
keywords: Informed consent; benefit statements; early-phase trials; research ethics