Methods

The study was conducted at two German universities and the Institutional Review Board of both sites approved the study (reference numbers 2020_236 and 2021-JGU-psychEK-001). The study was conducted in accordance with ethical standards as laid down in the 1964 Declaration of Helsinki and its later amendments. All participants gave informed consent. The study was pre-registered on AsPredicted.org: https://aspredicted.org/9F8_BZ5.

Participants

Participants were recruited via email lists, public postings, newspaper announcements, and social media. The inclusion criteria were: diagnosed allergic rhinitis; at least 18 years old; and sufficient German language skills. As with previous studies 21-23, exclusion criteria were: pregnancy; diabetes; any mental or neurological illness; and lactose intolerance (since the placebo tablets contained lactose). Of note, we did not apply any restrictions regarding the intake of participants’ normal medication (if there was any), but participants were asked not to change their medication (or dosages) for the duration of the study.
We recruited participants during the pollen season, with the first participant being enrolled in late April and the last participant being enrolled in mid-August. In this period, we aimed to reach a sample size of 90 participants to be able to uncover medium effects of OLP (f= .30; α = .05; 1-β = .80). A total of 123 people expressed interest in the study, of whom 96 persons completed a feedback form and were screened for eligibility. Of these, 74 people were randomized to OLP+TAU (subsequently referred to as “OLP”) or TAU. A total of 72 people completed the study at follow-up, as detailed in the CONSORT diagram (see Figure 1).
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In the entire sample, the mean age was 32.4 years (SD = 13.0) and 73.0% of the participants were female (27.0% male). All other sociodemographic data and information on medication use is presented for the two treatment groups separately in Table 1. There were no significant baseline differences between the groups.
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Procedure

If participants were included in the study, the experimenter randomized participants to OLP vs. TAU (see Figure 2). Accordingly, participants were sent a concealed envelope with either placebo tablets for those randomized to OLP or “smarties” (i.e., color-varied sugar-coated chocolate confectionery) for those randomized to TAU in a small glass container (see supplement) and were asked not to open the envelope before the first study visit a few days later (T1). Due to the COVID-19 pandemic, the study visit took place online, using the video platform www.arztkonsultation.de, which is widely used in Germany because of its strict data safety policy. In the virtual encounter, we aimed to ensure a warm and competent clinical encounter through both verbal and non-verbal elements 25,26.
In the first study visit, the provider explained the administration of OLP to the participants. In so doing, we closely adhered to previous studies administering OLP 9,11,15,17,19,21,22,27,28. Using the survey platform www.soscisurvey.de, participants were subsequently asked to complete questionnaires regarding their expectancies and hopes for placebo treatment as well as the extent to which they felt informed about placebos. Furthermore, participants completed questionnaires assessing their current allergic symptoms and the degree of impairment caused by allergic symptoms. After completing the questionnaires, participants were asked to open the envelope with the placebo tablets or smarties. At this point, participants were informed about their treatment group allocation, and potential ensuing questions were discussed. Finally, an appointment was made for the follow-up visit 14 days later (T2). Of note, unlike a previous study on the remote provision of OLP 23, we decided to send participants the placebo tablets or smarties prior to the first appointment, since the previous study discussed the delay between the explanation of OLP and participants’ reception of placebo tablets a few days later as a potential reason for the failure of OLP as patients may have been no longer aware of the potential benefits of placebos when starting to take them.
At T2, the provider asked participants to complete the follow-up questionnaires for their allergic symptoms. Afterwards, the provider asked participants how they experienced taking the placebo and whether they noticed any beneficial or adverse effects. Participants from the TAU group were offered the possibility of taking placebos after the second appointment (“switch-over”). Of 38 participants from the TAU group, 22 persons decided to receive the placebos subsequently. In terms of the intake of placebos, participants from the TAU group received the same information as participants from the OLP group at T1. Participants from the TAU group who wanted to receive placebos were invited for a third virtual appointment (T3), ~17 days later due to the delay of the postal service delivering the placebos. At T3, participants completed the symptom questionnaires again and the provider asked for beneficial and adverse effects of the placebos, as described above.
At each site, the appointments were conducted by a female psychology Master’s student, based on a structured interview guide following the procedure of a previous study 23. The background visible in the online interview was kept constant across all interviews and study sites in the form of a clean white wall.
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Measures

Allergic Symptoms

The primary outcome of the present study was self-reported symptoms of allergic rhinitis. To this end, we applied two previously used measures. First, we used the Combined Symptom Medication Score (CSMS). This 6-item scale assesses symptoms of allergic rhinitis in the past 2 weeks, related to the nose (four items) and the eyes (two items). Each item (reflecting a particular symptom) is rated on a 4-point Likert scale, indicating the severity of symptoms (from 0 = “no symptoms” to 3 = “severe symptoms”). Of note, the CSMS can also be used to compute a medication score; however, as participants in the current study were required not to change their medication during the study period (resulting in a constant that would have been added to the symptom score), the medication score was not used and participants rated only the symptom-related items. At T1, Cronbach’s alpha of the CSMS was α = .70; at T2 it was α = .82; and at T3 it was α = .87.
In addition, we used the 30-item questionnaire developed by Schäfer et al. 21,22 that, unlike the CSMS, assesses not only eye-related and nose-related symptoms, but also focuses on additional symptoms that people with allergic rhinitis typically experience in the pollen season, such as skin irritations, problems with breathing, and more general symptoms such as tiredness. In contrast to the CSMS, the allergy questionnaire by Schäfer et al. does not assess theseverity of allergic symptoms, but the frequency of their occurrence, ranging from 1 (“never”) to 7 (“always”). Like the CSMS, it also refers to the experience of allergic symptoms in the past 2 weeks. At T1, Cronbach’s alpha of that scale was α = .92; at T2 it was α = .93; and at T3 it was α = .92. The intercorrelation of the CSMS with the symptom frequency scale by Schäfer et al. was r = .621 (p < .001) at T1, r = .765 (p < .001) at T2, and r = .864 (p < .001) at T3.