Positively Framed Risk Information in Patient Information Leaflets Reduces Side Effect Reporting: A Double-Blind Randomized Controlled Trial

Many medication side effects are the result of a psychologically mediated "nocebo effect," triggered by negative expectations.This study investigated if changing how side effect information is framed in patient information leaflets (PILs) reduces symptom reporting.A total of 203 healthy volunteers aged 18 or over were recruited from December 1, 2015 to December 5, 2016 into a double-blind randomized controlled trial carried out at the Clinical Research Facility at King's College Hospital. King's Clinical Trial Unit randomized participants (stratified by gender) to receive a PIL for "a well-known tablet available without prescription" that used standard side effect risk information (e.g., "Common, 1 in 10 people will be affected") or positively framed wording (e.g., "Uncommon, 90% of people will not be affected"). After reading their PIL, participants took the tablet (a placebo) and completed symptom reports 1 hr later. The main outcomes included the number of participants who attributed symptoms to the tablet, and the number and severity of attributed symptoms.A total of 101 participants were assigned the standard PIL and 102 the positive framed PIL. Significantly more standard PIL participants attributed symptoms to the tablet (n = 55, 54.5%) compared to positively framed PIL participants (n = 40, 39.2%), odds ratio (OR) = 0.66, 95% CI: 0.46-0.93. Positive framing did not significantly reduce the total number (p = .148) or severity (p = .149) of symptoms attributed to the tablet.Positive framing reduced the likelihood of participants attributing nocebo-induced side effects to the tablet. Work is needed to assess the effectiveness in a patient population.ISRCTN47470030.