"It is not guaranteed that you will benefit": True but misleading?

Clin Trials. 2015 Aug;12(4):424-9. doi: 10.1177/1740774515585120. Epub 2015 May 11.


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).

Conclusion: 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.

Keywords: Informed consent; benefit statements; early-phase trials; research ethics.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural

MeSH terms

  • Adult
  • Clinical Trials as Topic
  • Female
  • Humans
  • Informed Consent*
  • Male
  • Patient Participation / psychology*
  • Risk Assessment
  • Surveys and Questionnaires
  • Young Adult