title: Placebo-controlled clinical trials: how trial documents justify the use of randomisation and placebo.
abstract: BACKGROUND
  Randomised clinical trials (RCTs) involve procedures such as randomisation, blinding, and placebo use, which are not part of standard medical care. Patients asked to participate in RCTs often experience difficulties in understanding the meaning of these and their justification.
  
  
  METHODS
  We reviewed RCT protocols, statements of the principal investigator (PI), and participant-information materials, as submitted for opinion to a research ethics committee. We evaluated how the justification for the use of placebo was described in these documents and how the participants had been informed about randomisation, placebo use, and the possible risks of receiving placebo.
  
  
  RESULTS
  In total, 52 RCTs were identified. Eighteen of the study protocols (35%) provided some rationale for the use of placebo. In 15 (29%) of the statements, the PI had provided justification for its use. Possible risks related to placebo use were described in nine (17%) of the statements. An explanation as to why placebo was necessary featured in only 12 (23%) of the sets of participant-information materials, and only six (12%) of the documents discussed the possible risks associated with placebo.
  
  
  CONCLUSIONS
  The justification of placebo control was inadequately described in the RCT study protocols, by principal or national co-ordinating investigators, and in participant-information documents. Furthermore, possible health-related risks associated with the use of placebo were poorly explained in the participant-information documents. Ethics committes and study participants need to be better informed of the rationale for the use of placebo, along with the associated risks.
authors.affiliation: Science Service Center, Kuopio University Hospital, P,O, Box 100, Kuopio 70029 KYS, Finland. tapani.keranen@thl.fi.
authors.forename: Tapani
authors.initials: T
authors.lastname: Keränen
authors.forename: Arja
authors.initials: A
authors.lastname: Halkoaho
authors.forename: Emmi
authors.initials: E
authors.lastname: Itkonen
authors.forename: Anna-Maija
authors.initials: AM
authors.lastname: Pietilä
mesh_terms: D003142:Communication; D032882:Comprehension; D003657:Decision Making; D004282:Documentation; D026724:Ethical Review; D028744:Ethics Committees, Research; D006801:Humans; D007258:Informed Consent / Q000941:ethics; D009042:Motivation; D018579:Patient Selection; D015990:Placebo Effect; D016032:Randomized Controlled Trials as Topic / Q000941:ethics*; D012107:Research Design; D035842:Research Subjects; D012306:Risk; D012941:Social Responsibility; D055990:Therapeutic Misconception