Participants

58 students (mean age 22.9 ± 2.0 years, 50 females) took part in the study and provided written informed consent (see Flow chart, Fig. 1). The study was approved by the ethical board of the German Psychological Society (Deutsche Gesellschaft für Psychologie, DGPs) and registered at the German clinical trials register (DRKS00013621, registered on 30/01/2018). The authors assert that all procedures contributing to this work comply with the ethical standards of the relevant national and institutional committees on human experimentation and with the Helsinki Declaration of 1975, as revised in 2008.

Figure 1 Flow diagram of patient’s enrollment. Full size image

Participants were recruited via flyers at the local university and social media. Inclusion criteria were age (18–60 years), being a student at a university, and having an exam at the end of the semester. Exclusion criteria included pregnancy, diabetes and any psychiatric or neurological diseases. Participants’ characteristics are shown in Table 1.

Table 1 Demographic and baseline characteristics of participants. Full size table

Study design

58 students were allocated to a two week randomized controlled trial comparing open-label placebo to no-treatment controls. For both groups participant-provider interaction and amount of contact time was held similar. After two weeks (before taking the exam) we tested whether test anxiety and self-management abilities had changed.

Sample size was based on previous research18. Considering an alpha error probability of 0.05 and an estimated effect size of d = 0.8, we calculated 26 participants per cell as necessary for a desired power of 0.80.

Procedure

During the first visit all participants were briefed in the same way (as described in14). They were explained that placebos are inactive substances and that they contain no medications, but placebo effects may still be powerful. They were told that the body may automatically respond to taking placebo pills, like Pavlov’s dogs that salivated when they heard the bell. A positive attitude may be helpful for the placebo effect, but is not necessary. Last, they were told that those participants who were in the placebo group needed to take the placebos faithfully8. These four statements are identical to the instruction used in previous studies on open-label placebos8,9,13.

Subsequently to this information participants completed questionnaires in order to assess test anxiety (German Test Anxiety Inventory, PAF19), quality of life (SF-3620), and self-management abilities (FERUS21). The PAF is a multi-faceted measure of test anxiety and has been used to detect anxiety levels in secondary schools and college students. It consists of 20 items and 4 subscales (worry, emotionality, interference, lack of confidence). The SF-36 assesses quality of life in patients and healthy individuals. It addresses different health concepts and asks, for example, for limitations in physical or social activites because of health or emotional problems, bodily pain, psychological distress and well-being, and general health perceptions. Self-management abilities were measured using the FERUS, which provides a global score for self-management skills and two additional measures (resource change motivation and perceived social support). The global score for self-management skills consists out of five scales (coping, self-efficacy, introspection, hope, and self verbalization).In addition, we asked all participants for the average grade of their previous exams.

Then an opaque envelope was opened, revealing the participant’s randomized assignment. Participants randomized to the OLP group were given a white tube, labeled with the logo of the local university and marked with: “Placebo pills (28), take one in the morning and one before night, for 14 days”. Placebo pills contained sugar, wheat- and cornstarch, and glucose syrup (identical to14). The pills were white, round, and the size was about 4 mm. Participants were instructed to swallow the pills, not to chew or suck them. Participants in the control group received no pills at all, but were reminded of the importance of the control group. After two weeks, on the days before taking the final exam, we invited the participants for a second visit, in which we again assessed test anxiety, self-management abilities, and quality of life. The research assistant was blind to the group assignments of the participants. Finally, participants of the control group were asked about possible feelings of disappointment to be assigned to the control group.

Last, we contacted all subjects after their exam and asked them about their examination grade.

Statistical analysis

The main outcomes were changes from pre to post in test anxiety (PAF) and self-management-skills (FERUS). A further outcome was quality of life (SF-36). Outcomes were measured at baseline and after two weeks (before the exam). Baseline data were examined for differences between groups using independent t-tests.

We computed separate analyses of variance (ANOVA, two factors: time and group) to test differences for these outcomes. Significant changes in test anxiety, self-management abilities, and quality of life were then further analyzed using paired sample t-tests. Cohen’s d was used to assess the power of effects.

The health survey for measuring quality of life (SF-36) results in a physical and a mental sum score. The first one refers to quality of life with respect to the body state, whereas the last one reports mental or emotional quality of life. We calculated separate ANOVAs based on these measures.

Furthermore, we calculated correlations (Pearson) in order to exam whether a possible improvement in test anxiety is accompanied with changes in self-management skills or quality of life.

Last, we computed Pearson’s correlations in order to investigate possible relationships between improvements in test anxiety or self-management skills, respectively, with the performance in the final exam.

We used the SPSS software package for all statistical analysis (IBM Corp., Armonk, NY, USA). P values of < 0.05 were considered as significant.