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).
Insert Figure 1 here.
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.
Insert Table 1 here.
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.
Insert Figure 2 here.
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.