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American Journal of Clinical Dermatology
https://doi.org/10.1007/s40257-022-00733-9
ORIGINAL RESEARCH ARTICLE
A Patient‑Centered Perspective ofMolluscum Contagiosum
asReported byB‑SIMPLE4 Clinical Trial Patients andCaregivers: Global
Impression ofChange andExit Interview Substudy Results
JohnCalebBrowning1 · MartinaCartwright2 · IraThorlaJr3 · SusanA.Martin4 ·
OyebimpeOlayinka‑Amao5 · TomokoMaeda‑Chubachi2
Accepted: 27 September 2022
© The Author(s) 2022
Abstract
Background Molluscum contagiosum is often characterized by persistent lesions and bothersome symptomology. What
patients with molluscum contagiosum and/or caregivers consider to be meaningful measures of therapeutic success is
unknown.
Objective We aimed to collect patient experience data and assess Global Impression of Change from patients and/or caregiv-
ers participating in a large phase III molluscum contagiosum interventional trial.
Methods The Berdazimer Sodium In Molluscum Patients with LEsions (B-SIMPLE4) phase III study enrolled 891 patients
with molluscum contagiosum. Patients were randomly assigned to berdazimer gel, 10.3% or vehicle gel applied once daily
for 12 weeks. Assessments of participant and investigator perceptions of complete lesion clearance were collected at weeks
12 and 24 along with Global Impression of Change scores from 1 (very much improved) to 7 (very much worse). A subset
of 30 B-SIMPLE4 patients participated in the patient/caregiver experience exit interview to evaluate bothersome signs and
symptoms.
Results At week 12, amongparticipants with a ≥75% molluscum contagiosum lesion count reduction from baseline (as
assessed by investigators), 99% (373/376) reported improvement. Perceptions of complete clearance at week 12 were nearly
40% for both participant-reported and investigator-reported Global Impression of Changein berdazimer group vs 20% in
the vehicle group: 82% (322/392) of participants in the berdazimer group and 60% (237/394) in the vehicle group reported
their molluscum contagiosum lesions were either very much improved or much improved at week 12. Similarly, investigators
scored 80% (314/393) of berdazimer and 54% (215/396) of vehicle participants as very much improved or much improved.
From the exit interview, the mean duration of participant-reported molluscum contagiosum was nearly2years. The most fre-
quently reported molluscum contagiosum-related signs and symptoms were itch (n=20), scarring (n=18), and pain (n=13).
Visibility and contagiousness of molluscum contagiosum were the most bothersome aspects to participants. The most fre-
quently reported psychosocial impacts were self-consciousness (n=15) and embarrassment (n=14). Lesion clearance was
an expectation of 28/30 study participants. Overall, 26/30 reported being very satisfied (n=18) or satisfied (n=8) with the
changes in their disease over the duration of the trial; 23/30 stated that the change in lesion count was meaningful. A mean
reduction of 18 lesions (76% decrease) from the baseline lesion count was reported by participants (n = 28). Although 22
of 28 had less than complete lesion clearance, 17 of 22 reported that the reduction in the number of lesions was meaningful.
Conclusions Molluscum contagiosum lesion reductions, with or without complete clearance, may be considered a therapeutic
“success” by the patient/caregiver.
Clinical Trial Registration NCT04535531 (registered 2 September, 2020).
* Tomoko Maeda-Chubachi
tmaeda-chubachi@novan.com
Extended author information available on the last page of the article
J.C.Browning et al.
Key Points
The most bothersome aspects for patients/caregivers are
molluscum contagiosum lesion visibility and contagious-
ness.
Lesion count reductions are meaningful to patients/car-
egivers, even when complete clearance is not achieved.
1 Introduction
Molluscum contagiosum (MC), a common, highly conta-
gious viral skin infection caused by the molluscipoxvirus
[1], replicates only in human skin cells and has the unique
ability to produce proteins that enable the virus to evade the
host’s immune surveillance system [2, 3]. Molluscum conta-
giosum manifests as clusters of small raised firm bumps on
infected skin and is especially common in younger children
[4, 5]. Molluscum contagiosum lesions may be widespread,
affecting sensitive body areas, causing pain, irritation, and
redness, and if scratched, autoinoculation and heightened
communicability [1]. Molluscum contagiosum infections
may clear without treatment yet can persist for months or
years [6]. Indeed, prolonged duration and visibility of MC
lesions coupled with the potential to spread the virus can
create psychosocial distress and anxiety [5] for both the
patient and caregiver.
Currently, there is lack of consensus regarding treatment
approaches to MC [7] and there is no US Food and Drug
Administration (FDA)-approved prescription medication.
Therefore, many healthcare providers take a watch-and-wait
strategy with an estimated 74% of patients with MC left
untreated [8]. It is unknown what impact the lack of a MC
therapeutic intervention has on patient/caregiver physical
and/or psychosocial well-being.
Berdazimer gel, 10.3% (SB206) is a novel, topical, nitric
oxide-releasing agent under investigation as a first-in-class
therapy for the treatment of MC [9–12]. The Berdazimer
Sodium In Molluscum Patients with Lesions (B-SIMPLE4)
pivotal phase III trial of berdazimer gel, 10.3% (Clinical-
Trials.gov identifier: NCT04535531) enrolled the largest-
ever cohort of patients with MC in a clinical trial (N = 891)
with the results showing favorable efficacy and tolerability
[9–12].
Capturing the patient experience and integrating the
patient voice in dermatologic clinical trials have been
a collaborative effort led by the FDA, patient advocacy
groups, and the pharmaceutical industry [13]. Therefore, to
better understand patients’ and caregivers’ experiences with
the MC disease state and MC therapeutic strategies, patient-
experience data (PED), including participant-reported and
investigator-reported perception of complete clearance
and participant-reported and investigator-reported Global
Impression of Change (GIC), were collected in B-SIMPLE4.
In addition, a qualitative exit interview was conducted with a
subset of B-SIMPLE4 patients and caregivers. The objective
of the exit interview was to gather input from patients and
caregivers on the most bothersome signs and symptoms of
MC, the psychosocial aspects of MC, expectations regard-
ing clinical trial participation, and the meaningfulness of
changes in MC lesion count and location, with special atten-
tion given to the impact of a reduced lesion count in the
absence of complete clearance.
2 Methods
2.1 PED Assessments andPopulation
Briefly, B-SIMPLE4 was a multicenter, double-blind, vehi-
cle-controlled, parallel-group (1:1) randomized clinical trial
of the efficacy and safety of berdazimer gel, 10.3% applied
topically once daily for 12 weeks [9]. The study methodol-
ogy, eligibility criteria, patient disposition, and efficacy and
safety results for B-SIMPLE4 have been published [9]. For
the PED, B-SIMPLE4 included participant and investigator
perceptions of MC lesion clearance at baseline and weeks
12 and 24. These assessments were based on participants’
(including patients and caregivers) and investigators’ percep-
tion of lesion clearance rather than a formal lesion count. For
the GIC ratings, participants and investigators reported their
overall impression of change from baseline in the patient’s
overall MC condition at weeks 12 and 24 on a scale from 1
(very much improved) to 7 (very much worse) using a non-
validated scale.
2.2 Exit Interview Study Design andPopulation
For the qualitative exit interview, all English-speaking
B-SIMPLE4 participants at select sites who had less than
complete MC lesion clearance from baseline to their week12
visit as determined by the investigator were eligible for qual-
itative exit interviews. The goal was to engage ~30 partici-
pants (balanced between berdazimer gel, 10.3% and placebo
groups), including ~20 participants with lesion count reduc-
tions that ranged from 75 to <100% and approximately three
Patient/Caregiver Experiences with Molluscum Contagiosum
to four participants with reductions in each of the following
ranges: from 50 to <75%, 25 to <50%, and 0 to <25%.
The 60-min qualitative interviews of participants (patients
or caregivers were interviewed, depending on patient age)
were conducted using an interview guide by one of two RTI
Health Solutions staff members via telephone 2–4 weeks
after their week 12 visit.
2.3 Analyses
2.3.1 PED Analyses
For the PED from B-SIMPLE4, the participant-reported and
investigator-reported perceptions of complete lesion clear-
ance and participant-reported and investigator-reported GIC
were summarized descriptively.
2.3.2 Exit Interview Analyses
For the exit interview, each semi-structured interview began
with a brief overview of the interview process and a few
general questions intended to prompt participants to discuss
symptoms and impacts of MC. Additionally, patients were
asked specifically what their treatment expectations were
before entering the clinical trial and what their experiences
were during the trial. Caregivers were asked specifically
what their treatment expectations were before entering the
clinical trial and what their child’s experiences were dur-
ing the trial. Finally, interview participants were queried
about various treatment benefits and outcomes, including
any improvements observed, and the importance and mean-
ingfulness of those improvements.
Exit interview data were systematically collected from
study participants as field notes captured in Microsoft Excel
(Microsoft Corporation, Redmond, WA, USA) and audio
files. After interviews concluded, all audio files were tran-
scribed verbatim and prepared for qualitative analysis.
The qualitative analysis of exit interviews was facili-
tated by a coding software (ATLAS.ti 9; Atlas.ti Scientific
Software Development GmbH, Berlin, Germany), using a
coding framework that was developed and adapted as the
analysis progressed and emerging themes were incorporated.
Interview results were analyzed using a thematic analysis
approach [14]. Using the transcripts and interviewer field
notes, dominant trends in each interview were identified
and compared across interviews [15] to describe themes
and the relative importance of concepts described by inter-
view participants. This analytical process generated themes
or patterns in the way interview participants described their
observations and experiences.
3 Results
3.1 B‑SIMPLE4 PED
3.1.1 Participant‑Reported andInvestigator‑Reported
Perception ofLesion Clearance
Among all B-SIMPLE4 participants who completed the par-
ticipant-reported assessment of lesion clearance, complete
clearance was reported by 37% (145/391) of the berdazimer
group at week12 and 60% (226/374) at week 24 compared
with 20% (79/390) of the vehicle group at week 12 and 46%
(174/378) at week 24 (Fig.1A). This trend was also con-
sistent with investigators’ perception of complete clearance,
which was reported for 37% (147/393) of the berdazimer
group at week 12 and 61% (230/378) at week 24 compared
with 22% (89/396) of the vehicle group at week 12 and 47%
(177/379) at week 24 (Fig.1B).
3.1.2 Participant‑Reported andInvestigator‑Reported GIC
At week 12 of B-SIMPLE4, 82% (322/392) of participants
in the berdazimer group and 60% (237/394) in the vehicle
group reported their MC lesions were either very much
improved or much improved on the GIC, for a difference
between groups of 22 percentage points (Fig.2A). The
35 and 25% of vehicle patients who reported their lesions
were very much improved or much improved at week 12,
respectively, may reflect the typically self-limiting nature
of MC. However, at week 24, there continued to be a dif-
ference between groups (12 percentage points) with more
berdazimer (84% [313/374]) than vehicle (71% [270/378])
participants reporting their lesions were either very much
improved or much improved (Fig.2A). Results for the inves-
tigator-reported GIC were similar (Fig.2B). For participants
with a ≥75% reduction in MC lesion count from baseline at
week 12, almost all felt improvement regardless of treatment
assignment (Table1).
3.2 Exit Interviews
3.2.1 Baseline Demographic andClinical Characteristics
Qualitative interviews were conducted with 30 English-
speaking participants (two patients and 28 caregivers) from
16 US clinical trial sites. Baseline demographic and clinical
characteristics are presented in Table2. Most participants
J.C.Browning et al.
Fig. 1 Participant (a)and investigator (b)perceptions of complete lesion clearance
Patient/Caregiver Experiences with Molluscum Contagiosum
lived in the Southern region of the USA, and all participants
were white.
The mean duration of MC at baseline (as reported by
participants) was 20.2 months. The mean number of lesions
estimated by participants at the time of B-SIMPLE4 study
entry was21.7. The recruitment target for different ranges
of lesion reduction at week12 was generally met (Fig.3).
Participants were also balanced by treatment group, with
15 from the berdazimer gel, 10.3% group, and 15 from the
vehicle group interviewed.
Fig. 2 Global Impression of Change over time. a Participant-reported Global Impression of Change and b investigator-reported Global Impres-
sion of Change
J.C.Browning et al.
3.2.2 Signs andSymptoms ofMC
Participants described their MC lesions as bumps, spots,
rashes, and warts. Caregivers frequently reported use of
the term “bumps” by their child to describe lesions. Par-
ticipants also reported various attributes of MC lesions
including location, size, number, contagiousness, and
visibility.
The most frequently reported MC-related signs and
symptoms were itch, scarring, and pain (Table3). Addi-
tionally, some participants spontaneously reported the
terms pustules or inflammation, sores or blisters, and
bleeding when describing their MC lesions. Participants
could distinguish between MC-related signs and symptoms
and adverse events associated with study medication.
The two patient participants indicated visibility and
contagiousness as the most bothersome aspects of MC
(Table3). Similarly, caregivers most frequently reported
visibility and contagiousness as the most bothersome
aspect of their child’s MC. Of note, two caregivers
reported that nothing about their child’s MC bothered
them.
3.2.3 Impacts ofMC
The most frequently reported impacts of MC were psycho-
social, including self-consciousness, embarrassment, and
worrying about others noticing or commenting on lesions
(Table4). Other impacts reported by ≥20% of participants
included having to avoid certain clothing and physical activ-
ity limitations. One participant each reported impact on
mood (annoying), social relationships, work, interpersonal
relationships, and sleep. Caregiver impacts of MC focused
on the time required to apply the study medicine and the
time and effort needed to clean household surfaces to pre-
vent viral spread.
3.2.4 Clinical Trial Participation Expectations
The two patients and 26 of 28 caregivers reported that
lesion clearance was an expectation of study participation
before enrolling in B-SIMPLE4. Additionally, two caregiv-
ers reported an expectation of preventing MC recurrence.
Other reasons caregivers provided for deciding to enroll their
children in B-SIMPLE4 were trying something new in hopes
of treating their child’s MC and the possibility of a quicker
resolution of their child’s MC.
3.2.5 Improvements During theCourse oftheClinical Trial
The most frequently reported improvement was a reduction
in lesion number, reported by 28 of 30 participants (two
patients and 26 caregivers [93%]). Although participants
Table 1 Participant-reported Global Impression of Change by lesion reductionat week 12
MC molluscum contagiosum
Efficacy Vehicle once daily (N = 447) Berdazimer gel, 10.3% once daily (N = 444) Total (N=891)
Improvement
(n=331)
No improvement
(n=63)
Improvement
(n = 371)
No improvement
(n = 21)
Improvement
(n=702)
No improvement (n=84)
Patients with ≥75%
reduction from baseline
in MC lesion count
141 0 232 3 373 3
Patients with ≥90%
reduction from baseline
in MC lesion count
106 0 189 1 295 1
Patient/Caregiver Experiences with Molluscum Contagiosum
Table 2 Participant characteristics reported at the time of the interview
MC molluscum contagiosum, NAnot applicable
a Participant was in grade school at the time of the interview
Characteristic Patients (n=2) Caregivers (n=28) Total (N=30)
Sex, n (%)
Male 1 (50) 2 (7.1) 3 (10)
Female 1 (50) 26 (92.8) 27 (90)
Age, years
Mean (range) 30 (12–48) 36.9 (27–59) 36.4 (12–59)
Age of caregiver’s child, years
Mean (range) NA 5.6 (2–11) 5.6 (2–11)
Self-reported duration of MC at study entry, months
Mean (range) 90 (36–144) 15.2 (1–48) 20.2 (1–144)
Estimated number of lesions at study entry
Mean (range) 14.5 (9–20) 22.2 (5–67) 21.7 (5–67)
Region, n (%)
Northeast 0 1 (4) 1 (3)
South 1 (50) 18 (64) 19 (63)
Midwest 0 3 (11) 3 (10)
West 1 (50) 6 (21) 7 (23)
Race, n (%)
White 2 (100) 28 (100) 30 (100)
Education, n (%)
High school or less 1 (50) a 0 1 (3.3)
Some college 1 (50) 9 (32.1) 10 (33.3)
College 0 (0) 11 (39.3) 11 (36.7)
Post college 0 (0) 8 (28.6) 7 (23)
Employment status, n (%)
Not applicable 1 (50) 0 1 (3.3)
Part time 1 (50) 5 (17.9) 6 (20)
Full time 0 (0) 15 (53.6) 15 (50)
Unemployed 0 (0) 8 (28.6) 8 (26.7)
were selected based on less than complete lesion clear-
ance as assessed by the investigator, six (20%) participants
reported complete clearance at the time of the interview. The
two caregivers who did not report lesion count improvement
reported no change in lesion count (n=1; 3%) or an increase
in lesion count (n=1; 3%). Other reported improvements
were a shorter duration of healing (n=4; 13%), a reduction
in lesion size (n=4; 13%), and less inflammation (n=2;
7%). Improvements in spreading, redness, itch, and swelling
were each reported by one caregiver.
3.2.6 Improvement inMost Bothersome Symptom
andImpact
Of the 24 participants who reported a most bothersome
sign or symptom, 21 (88%) stated that the sign or symptom
had improved during the study. Of the 22 participants who
reported a most bothersome impact, 19 (86%) reported that
the impact had improved during the study.
3.2.7 Change inLesion Number
For the 28 participants who reported a reduction in lesions,
the average was 18 fewer lesions, which represented a 76%
decrease from the baseline lesion count (Table5). Of these
28 participants, 22 (79%) reported that the decrease rep-
resented “many less” lesions and 6(21%) reported “less”
lesions at study end, compared with the baseline lesion
count.
J.C.Browning et al.
3.2.8 Meaningfulness ofChange inLesion Count
andLesion Location
Of 30 participants, 23 (77%) reported a meaningful change
in lesion count since study initiation, and 25 (83%) reported
a change in lesion location during the study. Of these 25par-
ticipants, 14 (56%) reported the change in lesion location
had not been as important or as meaningful as the reduction
in lesion number, whereas 11 (44%) reported the change
Fig. 3 Participant-reported reduction in lesion count at the time of the
interview. One participant in the 0–24% category reported an over-
all increase in lesion count. Participants were selected for interviews
based on the investigator-determined reduction in lesion count, these
numbers represent the participant-reported reduction in lesion count
Table 3 Signs, symptoms, and characteristics of molluscum contagiosum reported by participants
a Symptom not probed during interview but spontaneously reported by participants
Reported sign, symptom, or characteristic Patients (n=2)
n
Caregivers (n=28)
n
Total (N=30)
n (%)
Raised skin (bump, spot, wart) 2 28 30 (100.0)
Location 2 28 30 (100.0)
Number 2 27 29 (96.7)
Size 1 27 28 (93.3)
Contagiousness 1 20 21 (70.0)
Itch 1 19 20 (66.7)
Visibility 1 19 20 (66.7)
Scarring 1 17 18 (60.0)
Pain 1 12 13 (43.3)
Pustules or inflamed a 1 12 13 (43.3)
Sore or blister a 1 6 7 (23.3)
Bleeding a 0 1 1 (3.3)
Looks infected a 0 2 2 (6.7)
Patient/Caregiver Experiences with Molluscum Contagiosum
in lesion location had been meaningful because of reduced
visibility and less irritation or discomfort.
3.2.9 Level ofSatisfaction withAny Changes Since Study
Initiation
Overall, 26 of 30 participants reported being very satisfied
(n=18; 60%) or satisfied (n=8; 27%) with any MC lesion
changes since study initiation (range of percent improvement
in lesion count from baseline as reported by participants at
the time of the interview: 23–100%). Of the remaining four
participants, three (10%) reported being neither satisfied
nor dissatisfied, and one(3%) reported being dissatisfied.
Twenty-one caregivers provided a satisfaction rating from
their child’s perspective: 17(57%) said their child was “very
satisfied” (n=12; 40%) or “satisfied” (n=5; 17%), and four
said their child was “neither satisfied nor dissatisfied” (n =
2; 7%) or “dissatisfied” (n = 2; 7%).
3.2.10 Changes inLesion Count andLocation
inParticipants withLess Than Complete Clearance
Of the 28 participants who reported a lesion count reduction,
22 (79%) reported less than complete clearance. For these
22 participants, the mean lesion count reduction was 14,
representing a mean percentage decrease from baseline of
70%. When probed, these participants described the change
as “many less” (n=16; 73%) or “less” (n=6; 27%) lesions
compared with baseline. Of these 22 participants, 17 (77%)
reported that the reduction in lesion number was meaning-
ful and 11 (50%) reported that the change in lesion location
was meaningful. Consistent with GIC results captured in
the full B-SIMPLE4 sample, most of these participants (n
= 19; 86%) reported being “very satisfied” (n = 13; 68%)
or “satisfied” (n = 6; 32%) with MC lesion changes during
the clinical trial. Patient and caregiver quotes grouped by
interview topics are shown in Table6.
4 Discussion
Patient experiences are becoming increasingly important
in the understanding of skin disease burden and unmet
therapeutic needs [13]. Indeed, patients’ views of their
symptoms and how symptoms may affect their daily lives
are instrumental in treatment decisions in dermatology
[13]. Although healthcare providers may be aware of the
bothersome symptomology of dermatologic diseases, the
impact on patient and/or caregiver quality of life is not
well understood. Patient-centric assessments can measure
Table 4 Impacts of molluscum contagiosum reported by participants
a Impact not probed during the interview but spontaneously reported by participants
Impact Patients (n=2)
n
Caregivers (n=28)
n
Total (N=30)
n (%)
Self-consciousness 1 14 15 (50.0)
Embarrassment 2 12 14 (46.7)
Worry about others noticing or commenting 2 8 10 (33.3)
Avoiding certain clothing (e.g.,shorts or bathing suits) 2 6 8 (26.7)
Physical activities 1 5 6 (20.0)
Worry about contagiousness 1 1 2 (6.7)
Teased or treated meanly 1 2 3 (10.0)
Bath time 1 1 2 (6.7)
Daily activities – 2 2 (6.7)
Sleep a – 1 1 (3.3)
Interpersonal or social relationships a 1 1 2 (6.7)
Wor k a 1 – 1 (3.3)
Table 5 Participant-reported change in lesion count since study ini-
tiation
NAnot applicable
a Participant reported 30 additional lesions
Lesions Increased
(n=1)
No change
(n=1)
Decreased
(n=28)
Count
Mean (range) 30 a (NA) 0 (NA) 18 (1-67)
Percentage
Mean (range) 150% (NA) 0% (NA) 76% (11–100%)
J.C.Browning et al.
what is important to patients and generate information
on patient perceptions regarding the clinical benefit of an
experimental medication that goes beyond overt physical
changes in severity or lesion count as evaluated by a clini-
cal investigator [13].
Molluscum contagiosum, although one of the most
common skin diseases affecting children, has not been
widely investigated in clinical trials or through qualita-
tive research. The B-SIMPLE4 trial provided the oppor-
tunity to query study patients and/or their caregivers on
the impact of MC and a topical clinical intervention. Find-
ings from the exit interviews revealed that lesion location,
number, and size, as well as pain, scarring, itching, vis-
ibility, and contagiousness, were of concern to patients and
caregivers, with visibility and contagiousness being the
most bothersome. The most common psychosocial con-
cerns were self-consciousness, embarrassment, and worry
about others noticing or commenting on MC lesions.
In the absence of either FDA-approved medications
or standard-of-care guidelines for MC, many clinicians
adopt a watch-and-wait strategy. Many of the exit inter-
view participants reported being motivated to participate
in B-SIMPLE4 because of a desire to try an investigational
topical treatment that might result in partial or complete
lesion clearance. Availability of new treatment options
will likely be welcomed by clinicians and patients [16, 17].
Indeed, participants who experienced partial or com-
plete MC lesion clearance were satisfied with their clini-
cal trial participation. Additionally, participants with
less than complete clearance reported that the change in
lesion count since study initiation was meaningful. These
results highlight the importance of lesion count reductions
to patients with MC and caregivers, even when complete
clearance is not achieved. The PED indicated that nearly
40% of B-SIMPLE4 participants who received berda-
zimer gel, 10.3% perceived complete clearance by week
12, indicating that some may have perceived lesion reso-
lution at week 12 as complete clearance even when the
complete clearance rate was 34% based on investigator
lesion counts in the primary study [9]. In addition, some
patients who participated in the exit interview may have
achieved complete clearance at the time of the interview,
which occurred 2–4 weeks after the week 12 visit. Despite
actual lesion counts, most participants reported their MC
was much or very much improved by week 12. The nearly
identical scores between participant-reported GIC and
investigator-reported GIC were notable.
4.1 Limitations
Because the B-SIMPLE4 study was designed to fulfill
regulatory requirements for marketing authorization, the
exit interviews conducted as a substudy may not be an opti-
mal setting to fully capture experiences of a wide range of
patients with MC. All exit interview patients were white
as the majority of B-SIMPLE4 patients were white [9];
therefore, results may not be generalizable to the general
population of patients with MC. In addition, most exit inter-
view participants were caregivers, and therefore the patient
experience was primarily reported by caregivers. In addition,
the sample size was small (n = 30), though reasonable for a
qualitative design. Despite these limitations, the study pro-
vided valuable qualitative data on both patient and caregiver
experiences with MC treatment. The research methodology
and analysis were guided by established qualitative research
practices and followed FDA guidance [18–20]. To expand
upon study findings and further confirm these results, addi-
tional qualitative research is needed in a more diverse group
of patients with MC and their caregivers. Additionally, qual-
itative interviews should be conducted in patients less than
11 years of age who are able to self-report on their experi-
ences with MC so that information can be gathered directly
from the patient perspective. Finally, although B-SIMPLE4
included two PED assessments, development of a fit-for-pur-
pose patient-reported outcome measure for patients with MC
may be a worthy endeavor that would allow for the compari-
son of patient-reported outcomes between treatment groups
in future, randomized controlled intervention trials.
5 Conclusions
The PED and exit interviews revealed important factors
motivating MC patients/caregivers to participate in clinical
trials that might result in complete, partial, or accelerated
MC lesion clearance. The underlying drivers appear to be
related to the desire to mitigate both physical and psycho-
social MC symptomology. Although statistical success of a
clinical trial in patients with MC is typically measured by
complete lesion clearance, patients/caregivers may be sat-
isfied with partial clearance. Indeed, the PED results and
interviews reveal the importance of a reduction in MC lesion
count, with or without complete clearance, which highlights
the need to involve patients/caregivers in defining therapeu-
tic “success.”
Patient/Caregiver Experiences with Molluscum Contagiosum
Table 6 Select quotes grouped by interview topic
Description of molluscum contagiosum
“He’d just say that he has little bumps that are his boo-boos, on his leg or on his arm. I would say it’s like little warts all over your skin, and some
areas have more than others, but then they also turn into big sores and pustules.”
“He just calls them his bumps. It’s kind of warts.”
Signs, symptoms, and characteristics
Itch
“They’re itchy and quite bothersome.”
Pain
“They also turn into big sores and pustules, and they’re very painful when they get to that point.”
Scarring
“Yes, we have scarring. They pretty much look like chickenpox scars, which are like a lighter-skin, circular scar.”
Location
“Before the study he had some all over his eyebrows and around his eyes, and he had them on…a couple near his hands in the study, and then on
his legs. He had a lot on his legs, lower extremities.”
Size
“Most of them were little. Some of them were medium and then some of them were big and huge.”
Number
“There was probably at least 10 on his face, probably at least 10 more on his legs. I mean, I’d say a good 20 lesions on his body at least.”
“Yes. I think on our first visit I counted 67 bumps.”
Contagiousness
“I personally feel like the contagiousness of it is the most alarming part of it for me. Realizing how contagious they are and I’m giving my kid a
hug, consoling my kid. It’s frustrating because you can’t really do much about that.”
“It was primarily because he has a sister. They are 20 months apart and they used to bathe together all the time. That was a big thing because
they had to stop taking a bath together. And they really enjoyed bathing together and playing in the tub.”
“It definitely spread. It was spread through contact. Her largest molluscum were on her left shoulder and upper arms. And they continued to
spread to up her arm and started to form on her chin and jaw line on that side.”
Visibility and contagiousness as bothersome aspects of MC
“The fact that they turn into these sores, and they leave scars. That’s the most bothersome, because every time a molluscum, I guess, bump
turned into a sore or turned into a pustule it would leave somewhat of a scar, and it wouldn’t go away quickly.”
“I didn’t like it being on her face, because she is in school, and I’m a schoolteacher, and I know how mean kids are. And so, I didn’t want people
making fun of her either. And I didn’t want it to keep spreading and not … the spreading them, the contagiousness.”
“I feel bad because there was nothing we could do and I know it was bothersome to her, so it always bothered me that it felt like we were doing
nothing to make it better. And then just the added complication of trying to remember to not have the kids together, make sure her towels go in
the wash after use, and nobody else is using the towels that come from her and trying to stop it from spreading. It took a lot of effort. And then
in the end it happened anyway.”
“Yes, we avoided going to the lake right before the clinical study, because we were worried they would get infected from the water.”
“I wasn’t worried about them being contagious, but my younger brother got molluscum from me. So I would say they were contagious, because
he got them.”
“The one on the chin I didn’t like because others could see them but the rest of them I didn’t like them because I didn’t like them on my skin.”
“The visibility, the location. Just she didn’t like people talking about it.”
Self-consciousness/embarrassment/worry
“It definitely made her more self-conscious.”
“She would tell me that kids would point it out at school and point at it and laugh and say that they didn’t want to play with her:
“He would just make comments like, ‘I hate them so bad; they look so gross, I don’t want people to see them, I wish they would just go away,”
things like that. And then when we’d go swimming, he’d be like, ‘I don’t want to take off my shirt.’ Just things like that.”
“But other than the looks and where it was, and her self-esteem; thinking people are looking at her or talking about her.”
“Only the one on my chin [I was embarrassed]. Every time we went out into public.”
J.C.Browning et al.
Table 6 (continued)
Clothing choices
“Yeah, I’ve had to put him in pants before when his sores were bad instead of shorts.”
“We did avoid wearing certain … any clothes that had direct contact, like hard pressure on there because it was rough and they’d become
uncomfortable to her because she’d rub them raw if she didn’t have a band-aid.”
“Probably would be having to dress differently. That’s unfortunate … well, I mentioned living in [name deleted] and being in the heat of humid-
ity, this is uncomfortable and then you get hot and sweaty and then things start to itch and then guess what? Now you have more itching and
you’re trying to keep them covered you’re trying not to expose anyone else but you’re also sweating and dying and it’s not comfortable. It’s not
fun. People are looking at you, like you’re weird too because it’s 110 degrees outside and you’re wearing a long sleeve shirt.”
Physical activities
“There was one time where he didn’t get to go kind of swim with friends because of the sores, because I didn’t want them to spread.”
“She plays softball. Running sometimes would … the way that her pants would rub against them because they are up on the top of her thighs.
That would be bothersome so it would make her not want to run because that hurt.”
Being teased/treated meanly
“I think there was a little bit of bullying at school around it.”
Clinical trial expectations
“I really wanted to see if there was something that would work on it, and his molluscum bumps, because we had gotten a bunch of different
ointments and I just didn’t feel like they were … I felt like they were hurting him, because he didn’t like them, he noticed them. I felt like they
didn’t work very well, so I just was open to try something else.”
“I was thrilled that they had some kind of way to treat her because I’ve never been given an option before.”
“She had very large molluscum compared to the size that our son had and they seemed to be spreading at that point. So, I was very much hoping
to find a resolution because had tried many of the home remedy types of solutions with my son and my daughter and they were not working so
I was extremely excited to find a study to hopefully help her stop the spread. Especially since they were on her face at that point.”
“I was hopeful that she would be one of the kids in the study that receives the medication and that it actually helped to clear up the molluscum
after we’d been going through it for a year.”
“I was hopeful that they would put something on her bumps and that they would magically go away. That they would disappear and that we
would be molluscum free.”
“Because he wanted them to go away, and we’d already tried something and didn’t work completely. It left him with some scarring, so we
thought we could find something else that would maybe work better without the scarring.”
“Because it was bothering her quite a bit, it was pretty itchy, it would burn, and she complained about it a lot.”
Improvements during the clinical trial
“It seemed like it improved when I say that the bumps decreased and disappeared quicker than our previous medicine we were using. There was
less of an inflamed time for each bump. Well, I guess the pustule inflammation time was smaller.”
“It has lessened because the size of the molluscums shrank pretty quickly, so the smaller that they became, the less areas she had that were
irritated, so the less itching she did.”
“They’re almost all gone. Visually you can’t really see them, you can still feel where they were but for the most part it’s not noticeable at all.”
“I have noticed some like where he’s cleared up in some places like in his neck area, a lot of those have went away. It’s just mostly now confined
to just, like I said, his upper torso and his belly area. He has had some that popped up on his arms and those have went away. Some on his
knees and went away.”
“The ones on her face went away, so I’m happy.”
“Yes, since most of his bumps are gone, or pretty much all are gone that we don’t really have a concern of it spreading more on him since there’s
none on there.”
“They actually did clear up. I think she only has one small area left, one small lesion left. So they almost completely cleared up.”
“I want to say yes, that they went away faster, because they would go away within 4weeks of treatment as opposed to months of them, letting
them go away on their own. So, yes, they got treated faster.”
“Yeah, she doesn’t itch as much, at least not in those areas anymore. She’s not complaining about the bumps, the itching, the burning and so,
yeah, that’s pretty much it.”
Improvement in most bothersome sign or symptom
“She doesn’t complain of itching at all anymore.”
Improvement in most bothersome impact
“I felt much better just finding that there was something that we could do and that it worked for him. As a parent you kind of want to be able to
fix things.”
“I teach Pilates. I’m in fitness. So I want to wear a tank top, I want people to see that Pilates does wonderful things for my triceps but if I’ve got
a low hanging armhole in my tank top, that could be an area where I’m going to have some spots. Well, I can wear that cute little tank top now
because I’m not worried about having all those spots.”
Patient/Caregiver Experiences with Molluscum Contagiosum
Acknowledgements The authors are grateful to the patients and car-
egivers who gave the gift of clinical research participation. In addi-
tion, we thank the following B-SIMPLE4 investigators for recruit-
ing patients for the exit interview: Michael P. Husseman, MD, Wee
Care Pediatrics—Layton, Layton, UT, USA; Jane C. Gibson, MD,
Qualmedica Research, LLC, Bowling Green, KY, USA; Cindy E.
Owen, MD, DC Research, Louisville, KY, USA; David Brougher,
MD, Qualmedica Research, LLC, Evansville, IN, USA; Joseph A.
Ley, MD, Holston Medical Group, Kingsport, TN, USA; Jennifer
Martin, MD, Qualmedica Research, LLC, Owensboro, KY, USA,
Navid Ezra, MD, Clinical Trials Research Institute, Thousand Oaks,
CA, USA; Edward Primka, Dermatology Associates of Knoxville,
Knoxville, TN, USA; Richard Ohnmacht, MD, Omega Medical
Research, Warwick, RI, USA; Mary Christian-Reed, MD, DelRicht
Research, Tulsa, OK, USA; Sarah Jackson, MD, DelRicht Research,
New Orleans, LA, USA; Matthew Miller, MD, Palmetto Clinical
Trial Services, LLC, Greenville, SC, USA; Douglass Forsha, MD,
Jordan Valley Dermatology Center, West Jordan, UT, USA; and Joel
Cohen, MD, AboutSkin Research, LLC, Greenwood Village, CO,
USA.
Table 6 (continued)
“I feel like that the bumps went away and I didn’t notice the scars. I didn’t even notice where they were as much as I did before with the other
ones. So there was less scarring, there was less noticeable marks when they went away.”
“I mean, like I said, we didn’t have too many before. We just had a few because of the facial ones, and like I said, the swimming thing. I feel like
there were less impacts while we were on the study because of the medicine we were taking. I felt like it was helping.”
“Yeah. She’s pretty much back to her normal self, so I don’t really have to worry about anything [worrying about the contagiousness of it, about
it spreading, dressing her a certain way] anymore.”
Change in number of lesions
“I would say many less than at the beginning of the study. Sheer numbers. She had so many the first time we went that we were flipping her from
back to belly counting all of them on her legs. And the last visit we went, we were having a hard time figuring out if there were even any that
were actually still active. So, it just, like you’re saying, from 10 to 1 small one left.”
Meaningfulness of change
“The most important improvement is the resolution of the spots with a lack of scarring.”
“If I had 1 small one left yeah that’d be fine. Two small ones. Yeah, that’d be fine too.”
“It’s been the same location since the beginning. I’ve always had them in that area so I would say the location doesn’t matter to me as much as
the number of them.”
“Yes. That’s exactly what I wanted. I just wanted to be done with the bumps all over her. They just kept getting worse and worse and immedi-
ately it just started clearing up and she’s happy they’re gone and I’m happy because I don’t have to worry about them spreading to everybody
else. And that’s it.”
“Yeah, extremely important. That way we’re not having to watch our daughter suffering through pain, and just constant itching, and we don’t
have to worry about her spreading it to other people either.”
“I think the change in the number would be more significant to me. If they … if we treated some and then some others popped up, I wouldn’t see
the study drug being a failure.”
“At least half. Just because it would, I guess, an overall improvement, I think. Any improvement I guess is good, but that would be a great
improvement.”
Level of satisfaction
“Very satisfied. Because we did see so much improvement with her not just in the physical aspect of it, but the emotional aspect of it too, I guess
you could say. And just being able to see her go back to the way she was before everything.”
“I’m very satisfied because the visibility and potential scarring was my number one concern, and that concern is now eliminated because the
molluscum are gone.”
“Very satisfied. Because I went into this just thinking that they would … it would take a while to do anything, any kind of changes and within
that first month, so they started disappearing real fast. I didn’t expect it to happen this fast.”
“Very satisfied. Because we went from 25 to 30 molluscum bumps, down to practically zero. And so her legs look better, it’s something she
won’t be self-conscious about, and it’s an irritant that we don’t have to deal with, at least for the time being.”
“I was very satisfied after I saw a change after taking the medication. After starting the medication, it was nice to see that change of them going
away, even though sometimes she’d wake up and have more, and then other times wake up and have less. But the fact that they’ve gone down
so many, going from so many to so little, I’m very satisfied.”
“I would say satisfied. I think that learning a lot about what this was and kind of how these processes work. I’m hopeful that this is the beginning
of the end for them because everyone has said about a year. It’s been about a year.”
“I would say neither satisfied nor dissatisfied. I’m just kind of indifferent to the results. I didn’t like…I mean I knew it was a study, it may or may
not … there may or may not be results and I’m not sure that they’re less significant results, so it doesn’t bother me and I’m not thrilled with it
either.”
“Probably neither one [satisfied or dissatisfied]. Just because he’s got so much more and didn’t get rid of many.”
“I would probably say dissatisfied. Like I said, it became an ethical quandary for me of just being like, have I done something wrong in … what’s
the bigger picture here and trying to outweigh the balance [of treatment and discomfort].”
J.C.Browning et al.
Declarations
Funding Novan, Inc. funded B-SIMPLE4, the qualitative analyses of
the exit interviews, and manuscript development.
Conflict of interest John Caleb Browning and Ira Thorla Jr were study
investigators and are compensated (i.e., honoraria, personal fees) advi-
sors to Novan, Inc. Martina Cartwright and Tomoko Maeda-Chubachi
are employees of and stockholders in Novan, Inc. Oyebimpe Olayinka-
Amao and Susan A. Martin are employees of RTI Health Solutions,
which received funding to conduct the qualitative research and manu-
script development. Martina Cartwright was employed by Cassiopea
Inc. at the time the study was conducted.
Ethics approval The interviews were included as part of the B-SIM-
PLE4 clinical trial. Study approval was obtained from relevant ethics
committees and institutional review boards for all 55 B-SIMPLE4 US
clinical trial sites that participated in B-SIMPLE4, and the protocol was
reviewed by the FDA. The study was conducted in accordance with the
Declaration of Helsinki.
Consent to participate/publish Study approval was obtained from
relevant ethics committees and institutional review boards for all 55
B-SIMPLE4 US clinical trial sites that participated in B-SIMPLE4,
and the protocol was reviewed by the FDA. The study was conducted
in accordance with the Declaration of Helsinki. Patients/caregivers
voluntarily provided written informed consent/assent before screen-
ing procedures for B-SIMPLE4 were initiated. Verbal consent/assent
for the interviews were confirmed before each telephone interview.
Availability of data and material Data will not be shared.
Code availability Not applicable.
Author contributions TMC, SAM, and OO-A contributed to the exit
interview study conception and design. Data collection and analysis
were performed by SAM and OO-A. The first draft of the manuscript
was written by OO-A, and all authors commented on previous versions
of the manuscript. All authors read and approved the final manuscript.
Open Access This article is licensed under a Creative Commons Attri-
bution-NonCommercial 4.0 International License, which permits any
non-commercial use, sharing, adaptation, distribution and reproduction
in any medium or format, as long as you give appropriate credit to the
original author(s) and the source, provide a link to the Creative Com-
mons licence, and indicate if changes were made. The images or other
third party material in this article are included in the article's Creative
Commons licence, unless indicated otherwise in a credit line to the
material. If material is not included in the article's Creative Commons
licence and your intended use is not permitted by statutory regula-
tion or exceeds the permitted use, you will need to obtain permission
directly from the copyright holder. To view a copy of this licence, visit
http:// creat iveco mmons. org/ licen ses/ by- nc/4. 0/.
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Authors and Aliations
JohnCalebBrowning1 · MartinaCartwright2 · IraThorlaJr3 · SusanA.Martin4 ·
OyebimpeOlayinka‑Amao5 · TomokoMaeda‑Chubachi2
1 Department ofDermatology, University ofTexas Health
Science Center, SanAntonio, TX, USA
2 Medical Affairs, Novan, Inc., 4020 Stirrup Creek Drive,
Suite 110, Durham, NC27703, USA
3 Dermatology, DelRicht Research, BatonRouge, LA, USA
4 Patient-Centered Outcomes Assessment, RTI Health
Solutions, AnnArbor, MI, USA
5 Patient-Centered Outcomes Assessment, RTI Health
Solutions, Durham, NC, USA
