The effect of Eye Movement Desensitization and Reprocessing (EMDR) on Illness Anxiety Disorder (IAD): two multiple baseline n-of-1 trials across seven participants each.

Mental imagery is a transdiagnostic feature that has been increasingly
recognized as playing an important role in relation to autobiographical memory
and psychopathology. After trauma, involuntary (intrusive) mental images and
memories can make it difficult to recall positive memories, thus creating an
automatic bias toward more negative information. Compared to verbal processing,
the imagery-based route of processing emotional stimuli causes a stronger, but
a negative affective response. Although empirical evidence is still scarce,
these specific mechanisms also seem to be at work in patients with an illness
anxiety disorder (IAD). The prospective and vivid intrusive images found in IAD
cause patients great distress. These intrusive images increase somatic
awareness which, as an emotion regulatory response, leads to typical IAD
avoidance and reassurance-seeking behaviours. This suggests that the intrusive
images found in IAD may be a promising novel target in treatment methods. With
the aim to improve current treatments for IAD, the present study explores the
effectiveness of Eye Movement Desensitization and Reprocessing (EMDR) in
patients with IAD. EMDR treatment for IAD first targets the memories of past
(traumatic) events before targeting future intrusive images of expected
catastrophes. Although in general EMDR treatment starts by treating traumatic
experiences related to the illness, it has been proposed (Bellecci-St. Romain,
2013; Engelhard et al., 2011) that it is not necessary to target the past
events at all because the future catastrophe image has in it all the
anxiety-provoking elements of the past event. The hypotheses tested in this
multiple baseline design across two times seven participants, are 1) is EMDR
treatment focusing on images of traumatic past events effective in reducing IAD
symptoms 2) is EMDR treatment focusing on images of future catastrophes
effective in reducing IAD symptoms and 3) comparing these interventions; is
targeting only the images of future catastrophes with EMDR treatment just as
effective as targeting images of historic events.

Primary Objective study 1: The primary objective of study 1 is to explore the
effectiveness of EMDR treatment targeting images of historic traumatic events
in reducing the daily rated illness anxiety symptoms of patients with IAD.

Primary Objective study 2: The primary objective of study 2 is to explore the
effectiveness of EMDR treatment targeting images of future catastrophes in
reducing the daily rated illness anxiety symptoms for patients with IAD.

Secondary Objective: The secondary objective of the combined studies is to
explore the differences in effectiveness and efficiency of EMDR treatment
targeting images of historic traumatic events versus targeting images of future
catastrophes, in reducing the daily rated illness anxiety symptoms for patients
with IAD.

SCED Design: multiple baseline across seven participants.

The present study consists of two studies each of which consists of 7 N-of-1
studies. N-of1 studies or single case experimental design (SCED) studies are
suitable for conducting scientifically relevant research in a clinical setting.
With this design, the effectiveness of the applied intervention in one person
can be scientifically investigated. This is made possible by collecting data
daily and throughout the study and using all these data points to test the
research question within the subject (*within subject*). Of the SCEDs the
multiple baseline design (MBD) is recommended because of its high internal and
external validity (Kratochwill et al., 2010; Shadish & Sullivan, 2011). Due to
the large number of measurements within a person in the different phases
(baseline, treatment, post-test, and follow-up phase) and by randomizing the
length of the baseline, internal validity is guaranteed. Preferentially is a
concurrent design in which all participants start at the same time with their
baseline. This minimizes the influence and therefore threats to intern validity
of any concurring events, for example, news reports on the COVID-19 pandemic.
To preclude patients from waiting several months we decided to use a partly
concurrent design by letting 2 (or 3) patients start at the same time, making
it a partly concurrent MBD. The changes within a person are assessed visually
(by eye) as well as statistically tested using all data points. In this way, it
can be determined within the individual whether the intervention offered
actually makes a difference.

The design of the present study meets the criteria for a partly concurrent MBD
study, based on which scientifically substantiated statements can be made about
the effect the treatment has on this individual. By repeating this set-up in 7
participants, i.e., performing 7 N-of-1 studies, a meta-analysis can be
performed on these 7 studies and a statement can be made about the 7 N-of-1
studies together. The outcomes (effect sizes) of this statistical analysis
allow comparison with randomized and controlled trials and existing
meta-analyses.

We repeat the above design with two variants of the intervention (EMDR). One
focuses on images related to past events (MBD1). The other on images of future
catastrophes (MBD2). The study, therefore, concerns 2 x 7 N-of-1 studies. In
which we can compare the results of the meta-analyses on each of the 7 N-of-1
studies and thus answer our third research question.

The 7 participants in either MBD1 or MBD2 will be randomly assigned to Baseline
length and starting day; 2 participants to Baseline length 1 (10, 11, 12, 13,
or 14 observations), 2 participants to Baseline length 2 (15, 16, 17, 18, or 19
observations), and 2 participants to Baseline lengths 3 (20, 21, 22, 23, or 24
observations) and 1 last participant to either baseline length 1, 2 or 3. For
each of the time series, the start of the intervention will be randomly chosen.

MBD1 - targeting images of historic traumatic events
Time series 1:
Baseline 1: at least 10 observations, Treatment 1: 49 observations, Baseline 2:
10 observations, Follow up: 10 observations
Time series 2:
Baseline 1: at least 15 observations, Treatment 1:49 observations, Baseline 2:
10 observations, Follow up: 10 observations
Time series 3:
Baseline 1: at least 20 observations, Treatment 1: 49 observations, Baseline 2:
10 observations, Follow up: 10 observations

MDB2 - targeting images of future catastrophes
Time series1:
Baseline 1: at least 10 observations, Treatment 2: 49 observations, Baseline 2:
10 observations, Follow up: 10 observations
Time series 2:
Baseline 1: at least 15 observations, Treatment 2: 49 observations, Baseline 2:
10 observations, Follow up: 10 observations
Time series 3:
Baseline 1: at least 20 observations, Treatment 2: 49 observations, Baseline 2:
10 observations, Follow up: 10 observations

Within the limitations of our practice, the replicated multiple baseline n-of-1
trial seems most fit to provide opportunities to enhance care that is both
patient-centred and evidence-based. The results of our study can therefore be
meaningful to our participants' well-being and at the same time contribute and
give direction to further research on this subject, including those with other
designs.

EMDR (Eye Movement and Desensitization Disorder)

The EMDR-treatment has no known adverse effects or risks. The burden associated
with participation in this study lies in daily answering the questions of the
IIAS (1 or 2 minutes a day)