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\begin{document}

\title{Treatment preferences for medication or surgery in patients with deep
endometriosis and bowel involvement -- A Discrete Choice Experiment}



\author[1]{Jeroen Metzemaekers}%
\author[1]{M. Elske  Akker-van Marle }%
\author[2]{Jonathan Sampat }%
\author[3]{Mathilde J.G.H.  Smeets}%
\author[3]{James English}%
\author[2]{Elke Thijs}%
\author[2]{Jacques W.M. Maas}%
\author[1]{Frank Willem Jansen}%
\author[2]{Brigitte Essers}%
\affil[1]{LUMC}%
\affil[2]{Maastricht UMC+}%
\affil[3]{Medisch Centrum Haaglanden}%


\vspace{-1em}



  
  \date{May 18, 2024}


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\selectlanguage{english}
\begin{abstract}
Objective To study the preferences and risk tolerance of women suffering
from deep endometriosis (DE) with bowel involvement when they have to
choose between conservative or surgical. Design Labelled Discrete Choice
Experiment (DCE). Setting Dutch academic and non-academic hospitals and
online recruitment. Population or Sample A total of 169 patients
diagnosed with DE of the bowel. Methods Baseline characteristics and the
fear for surgery were collected. Women were asked to rank attributes and
choose between hypothetical conservative (medication) or surgical
treatment in different choice sets (scenarios). Each choice set offered
different levels of all treatment attributes. Data were analysed by
using multinomial logistic regression. Main Outcome Measures The
following attributes; effect/or risk on pain, fatigue, pregnancy,
endometriosis lesions, mood swings, osteoporosis, temporary stoma and
permanent intestinal symptoms were used in this DCE. Results In the
ranking osteoporosis is the least important attribute, while in the DCE,
a lower chance of osteoporosis is one of the most important drivers when
choosing a conservative treatment. Women with previous surgery show less
fear for surgery compared to women without surgery. The low anterior
resection syndrome is almost equally important for patients as the
chance of pain reduction. Pain reduction has higher importance than
improving fertility chances even in women with a future child wish.
Conclusions The risk of suffering from LARS as a result of treatment is
almost equally important as the reduction of pain symptoms. Women with
previous surgery experience less fear for surgery compared to women
without a surgical history.%
\end{abstract}%



\sloppy


\textbf{T} \textbf{reatment preferences for medication or surgery in
patients with deep endometriosis and bowel involvement -- A Discrete
Choice Experiment}

\textbf{Running title:} Discrete Choice Experiment in deep endometriosis

Jeroen Metzemaekers M.D.\selectlanguage{greek}\textsuperscript{aϮ}/ \selectlanguage{english}M. Elske van den Akker-van
Marle Ph.D.\selectlanguage{greek}\textsuperscript{bϮ}, \selectlanguage{english}Jonathan Sampat
M.D.\textsuperscript{c}, Mathilde J.G.H. Smeets M.D.\textsuperscript{d},
James English M.D., MRCOG.\textsuperscript{d} Elke Thijs
M.D.\textsuperscript{c}, Jacques W.M. Maas M.D.,
Ph.D.\textsuperscript{c} , Frank Willem Jansen M.D.,
Ph.D.\textsuperscript{a,e,*}, Brigitte Essers Ph.D.\textsuperscript{f}

\textsuperscript{a}Department of Gynaecology, Leiden University Medical
Centre, Leiden, the Netherlands

\textsuperscript{b}Department of Biomedical Data Sciences, Section
Medical Decision Making, Leiden University Medical Centre, Leiden, the
Netherlands

\textsuperscript{c}Department of Gynaecology, Maastricht University
Medical Centre+, Maastricht, the Netherlands

\textsuperscript{d}Department of Gynaecology, Haaglanden Medisch
Centrum, Den Haag, the Netherlands

\textsuperscript{e}Department of Biomechanical Engineering, Delft
University of Technology, Delft, the Netherlands

\textsuperscript{f}Clinical Epidemiology and Medical Technology
Assessment, Maastricht University Medical Centre+, Maastricht, the
Netherlands

\selectlanguage{greek}Ϯ\selectlanguage{english}\textbf{Shared first authorship}

\textbf{*Corresponding author contact information:}

Professor F.W. Jansen, MD, PhD Department of Gynaecology, minimally
invasive surgery Leiden University Medical Center PO Box 9600, 2300 RC
Leiden, the Netherlands E-mail: f.w.jansen@lumc.nl

\textbf{Abstract}

\textbf{Objective}

To study the preferences and risk tolerance of women suffering from deep
endometriosis (DE) with bowel involvement when they have to choose
between conservative or surgical.

\textbf{Design}

Labelled Discrete Choice Experiment (DCE).

\textbf{Setting}

Dutch academic and non-academic hospitals and online recruitment.

\textbf{Population or Sample} A total of 169 patients diagnosed with DE
of the bowel.

\textbf{Methods}

Baseline characteristics and the fear for surgery were collected. Women
were asked to rank attributes and choose between hypothetical
conservative (medication) or surgical treatment in different choice sets
(scenarios). Each choice set offered different levels of all treatment
attributes. Data were analysed by using multinomial logistic regression.

\textbf{Main Outcome Measures}

The following attributes; effect/or risk on pain, fatigue, pregnancy,
endometriosis lesions, mood swings, osteoporosis, temporary stoma and
permanent intestinal symptoms were used in this DCE.

\textbf{Results}

In the ranking osteoporosis is the least important attribute, while in
the DCE, a lower chance of osteoporosis is one of the most important
drivers when choosing a conservative treatment. Women with previous
surgery show less fear for surgery compared to women without surgery.
The low anterior resection syndrome is almost equally important for
patients as the chance of pain reduction. Pain reduction has higher
importance than improving fertility chances even in women with a future
child wish.

\textbf{Conclusions}

The risk of suffering from LARS as a result of treatment is almost
equally important as the reduction of pain symptoms. Women with previous
surgery experience less fear for surgery compared to women without a
surgical history.

\textbf{Funding}

The author(s) received no financial support for the research,
authorship, and/or publication of this article.

\textbf{Key words:}

Endometriosis, Discrete Choice Experiment, surgery, decision making,
Deep Endometriosis

\textbf{Tweetable abstract:} First discrete choice experiment in
patients with deep endometriosis

\textbf{Introduction}

Patient centeredness, which is guided by patients' values, needs and
preferences is an important quality dimension in modern healthcare (1).
This approach is especially relevant in patients suffering from
endometriosis, since endometriosis affects all facets of life (work,
mood, quality of life, relationships, sexuality) (2). Even though
endometriosis is a benign disease, it can cause significant decrease in
the quality of life (QoL), social participation (e.g. loss of
productivity) and sexual health (3) (4). Therefore, it is extremely
important to realise that effective treatment goes beyond a purely
somatic approach and should be patient centered.

Endometriosis is a disease in which endometrium-like tissue grows
outside the uterus inducing chronic inflammation and adhesion formation
(5). Numerous treatment options are available for endometriosis, but
there are two main strategies: conservative treatment (analgesics and/or
hormones) and surgical treatment. However, none of these options offer a
complete curation, making endometriosis a chronic condition. Therefore,
the main goal of these treatments is not to cure but to reduce pain,
prevent further organ damage (e.g. ureteric obstruction), increase QoL
and (potentially) increase the chance of pregnancy (6). Available data
suggest that both conservative and surgical treatment are effective in
reducing pain (7). The improvement of fertility chances with surgical
treatment options remains uncertain, due to inconclusive study results
on this topic (8). Although most of the treatment options are proven to
be effective in reducing pain, they unfortunately do not come without
consequences. On the one hand conservative treatments may have potential
harmful side effects (e.g. depressive mood, weight gain, osteoporosis,
menopause, decreased libido, headaches) which may cause treatment
failure. Other reasons for treatment failure include therapy
noncompliance or contraindications (deep venous thrombosis, other
cardiovascular disease, hormone-sensitive tumours, active wish to
conceive etc.) (7). On the other hand, surgical treatment options have
the possible risks of severe complications and recurrence of disease. DE
surgery is associated with significant complication rates up to 14\%
(9), which include bowel injury, anastomosis leakage, temporary or
permanent stoma placement, urinary tract injury, formation of recto and
or vesicovaginal fistulas (10). Making a careful and well-considered
choice in endometriosis treatment options is especially relevant for
deep endometriosis (DE), since these patients have to deal with complex
treatment trade-offs.

In patient centered health care, decisions about treatment options are
preferably made in consultation between the physician and the patient
(11). Therefore, gynaecologists need to inform patients optimally by
providing extensive information on the pros and cons of each treatment
and by supporting the decision making process. This can only be achieved
when gynaecologists are trained in guiding shared decision making (SDM)
and understand which risks and benefits may be important to patients.
Unfortunately, limited research has been performed to study the value
and preferences in women with DE, which makes optimal counselling
challenging. In addition, there is no conclusive evidence to advise
patients for a particular treatment that is clearly superior. This makes
preference sensitive care the most suitable form to use (12). In
preference sensitive care, it remains important to make a
well-considered choice that includes the patient's wishes, priorities,
risks and benefits. Especially for women suffering from endometriosis,
the decision making process can be difficult and complex, since it is
not only a matter of choosing pills or surgery. Their choice is also
highly dependent on the different phases of life (school going,
career/work, wish to conceive or not), and some choices can have
lifelong consequences (hysterectomy, low anterior resection etc.).
Therefore, optimal counselling is mandatory to assist these women in
their decision making.

A technique to gain insight in treatment preferences is a so-called
discrete choice experiment (DCE). This DCE technique assumes that
patients value different characteristics of a treatment, (e.g. pain
reduction, pregnancy chance, risk of complications) which will determine
their preference. When presenting different choices, patients will
usually choose the option that is most beneficial (13, 14).

This study aims to investigate patients' preferences in DE treatment
options for conservative or surgical treatment options and which
characteristics are relevant in their treatment choice. To achieve this,
we performed a labeled discrete choice experiment.

\textbf{Methods}

\textbf{Study design}

A discrete choice experiment (DCE) was used to gain insight in treatment
preferences of women with DE and bowel involvement when they have to
choose between conservative or surgical treatment. This DCE technique
assumes that patients value different characteristics of a treatment,
(e.g. pain reduction, pregnancy chance, risk of complications) which
will determine their preference. When presenting different choices,
patients will usually choose the option that is most beneficial (13,
14).

\textbf{Participant recruitment}

Inclusion took place between January 2019 and October 2020 in six Dutch
academic hospitals (23.7\% of the patients) and eight non-academic
hospitals (46.7\%) and also by the Dutch and Belgian endometriosis
foundation (29.6\%). Women who were interested could visit the website
(www.endokeuze.com) for information about the study. It was especially
noted that only women with DE and bowel involvement could participate in
this study. Women willing to participate had to pass three inclusion
questions, which are commonly used and accepted in endometriosis
questionnaire studies (15) (16) (17). For this DCE only women with
surgically or radiologically (ultrasound and/or MRI) diagnosed DE with
bowel involvement, prior to a treatment decision and currently not in
any fertility treatment trajectory could participate. Women could not
see which answer would in- or exclude them. The first question was:
``\emph{Do you have deep endometriosis with bowel involvement, which is
diagnosed by a doctor by ultrasound, MRI or surgery?''} Patients who
answered this with `yes' received a second question; ``\emph{Are you
prior to a treatment choice with medication or surgery?''} Patients who
answered this with `yes' received a final question; ``\emph{Are you
currently in a trajectory to become pregnant (e.g. hormonal treatment
for ovulation induction, IVF)?''} Patients who answered these questions
with `no' were included in the study prior to a digital informed consent
form. Patients who did not meet the inclusion criteria, were
acknowledged for their interest in the study, but could not further
participate. Further exclusion criteria were low health literacy, this
was tested with three questions (18).

Further exclusion criteria were low health literacy, this was tested
with three questions (18). We excluded patients who indicated to always
have difficulties with understanding medical information about their
disease and treatment, always need help with reading information about
their disease and treatment and have no confidence at all in filling in
medical forms. Furthermore, patients with no informed consent, patients
who did not complete the 10 DCE questions, patients who completed the
whole survey in [?] 10 minutes time (this `too fast' threshold was set
after the pilot) and patients who gave the same answer on all questions
in the first section of the survey and DCE, were excluded. A total of
641 patients started the survey (Supplementary table S1), 141 patients
were excluded at inclusion question one (no DE with bowel involvement),
152 patients were excluded at inclusion question two (not prior to a
treatment decision), 53 patients were excluded at inclusion question
three (patients in fertility treatment). A total of 91 patients who met
the inclusion criteria but stopped after reading the information were
also excluded, five patients with no informed consent were excluded. One
patient who filled in the same answer at all questions (survey fatigue),
24 patients who did not complete the DCE task, three patients with poor
health literacy were excluded. One patient indicated to always have
difficulties with understanding medical information about her disease
and treatment, one patient always needed help with reading information
about her disease and treatment and one patient who had no confidence at
all in filling in medical forms. Furthermore, two patients were excluded
who completed the DCE within 10 minutes. This resulted in 169 patients
who met all inclusion criteria (26.4\% of the initial amount of patients
who started the survey).

\textbf{Data collection}

For hosting the internet survey and data collection, we used Sawtooth
Software's (Orem, UT) SSI Web. As recommended by earlier studies, the
identification and selection of the final attributes and levels was
based on literature review, qualitative research and an expert panel
(19) (20) (21). The four stages as described by Heller et al were
applied although we slightly customized these as seen in Figure 1, which
means that we used several data sources in stage 1. To find out which
attributes were important for DE patients, we firstly (Stage 1)
collected data by performing a literature- and qualitative study. We
performed a survey among 28 patients, one focus group with eight
patients prior to their decision making (22) and a focus group with 10
gynaecologists with expertise on deep endometriosis. The results
combined from stage 1 resulted in 158 attributes.

The second step (Stage 2) in attribute development is data reduction.
This was achieved by frequency and rank order by the researchers (JeM
and JS) combined with thematic analysis (grouping attributes with more
or less the same theme), which resulted in 28 attributes. In the third
and fourth stage, concerning respectively removing inappropriate
attributes and wording of attributes, we selected attributes which
comply with the research question, are relevant for the DE population,
and are intelligible for all patients (23). The last process of
attribute selection was performed in collaboration with all members of
the research group, which resulted in eight final attributes (Table 1).

The first part of the survey included questions about baseline
characteristics (i.e. age, educational level, medication use, medical
history and pain symptoms), surgical fear measured with the validated
Dutch surgical fear questionnaire (SFQ) (24) and three health literacy
screening questions. We included the short surgical fear questionnaire,
while we hypothesized that the fear for surgery could influence the
results of the DCE. Women with surgical fear could have a tendency
towards choosing the conservative treatment compared to women with less
surgical fear. The surgical fear has a subscale sum score for short -and
long term fear that ranges from 0 (no fear) to 40 (very afraid), the
total sum score ranges from 0 (no fear) to 80 (very afraid). Pain was
recorded on a numeric rating scale, patients rated their pain intensity
(0 = no pain and 10 = maximum pain, or inapplicable option). The pain
intensity score was obtained for menstrual cycle and non-cycle related
pain, on the dimensions of dysmenorrhea, pelvic pain, dyspareunia,
dysuria and dyschezia.

Part two of this survey included information about the DCE
(Supplementary table S2 includes the attributes explanation). Prior to
the DCE, we asked the women to rank the eight attributes from most
important (1) to least important (8) when making a treatment decision.
In the ranking we did not distinguish between conservative or surgical
treatment. To get familiar with the concept of a DCE, a simple DCE
question for choosing a phone. Subsequently, the actual DCE was
presented with 10 choice sets. Each choice set consisted of two
hypothetical treatment options labeled as pharmaceutical (conservative)
and surgical treatment. The reason for choosing a labeled DCE is that
both conservative and surgical treatment have a number of specific
attributes and levels that are not generic for both treatments. The
women were asked to choose their preferred treatment of choice for each
of the 10 choice sets (Figure 2). The conservative treatment option
included specific attributes like side effects of hormonal treatment:
depressive feelings and the chance of developing osteoporosis. The
surgical option included treatment specific risks like, the chance of
getting a temporary stoma and the chance of permanent intestinal
symptoms (LARS) ( Table 1).

\textbf{Data analysis}

Ngene software (version 1.2.1) was used to construct a fractional
factorial efficient design based on the selected attributes and their
levels. In the design, one constraint was taken into account in order to
avoid implausible combinations (if surgery removes the endometriosis as
much as possible without major bowel surgery, then the chance of
permanent intestinal symptoms can only be 10\%). Thirty choice sets were
created with each choice set consisting of two treatment options, that
is conservative and surgical treatment. In order to reduce the burden
for the patient, the thirty choice sets were blocked into three versions
of 10 choice sets.

To assess if the DCE, levels, attributes, explanation text and baseline
questions were understood, we performed a pilot test with a group of
pre-surgical patients. Small adjustments were made, mainly in the
information text of the attributes and levels. After the DCE was online
and open for inclusion, an interim analysis was performed to test our
expected direction of effect. The results were in line with our
expectations; therefore no adjustments were made. For the whole design
of this DCE we followed the checklist of the ISPOR Conjoint Analysis
Experimental Design Good Research Practices Task Force (25).

For internal consistency, we included one fixed task, with one dominant
option (conservative treatment option) which is more favorable (higher
chance of pain reduction and little side effects, compared to a surgical
option with maximum side effects and little to no beneficial effects).
However, it should be noted that this is not automatically and
unambiguously always the `best' treatment because some women can have a
strong preference for a conservative treatment or surgery regardless of
the specific levels of the attributes.

Optimal sample size calculation for estimating for non-linear discrete
choice models is complicated as it depends on the true values of the
unknown parameters estimated in the DCE (26). Given the lack of a
definite method for calculating a sample size, we based our sample size
on a literature review (27). Marshall et al. described that most studies
published between 2005-2008 had a sample size of 100-300 respondents. We
aimed for 300 respondents because we also wanted to study subgroups.

\textbf{Statistical analysis}

IBM SPSS version 25.0 for Windows was used for our analysis and we used
the Shapiro--Wilk test to evaluate the distribution of the data. Data
are presented as mean \selectlanguage{ngerman}± standard deviation (SD) or median (with
interquartile range) for normally distributed or skewed data,
respectively (baseline characteristics like age, time till diagnose
etc.). We used Student's~t-test for normally distributed data (surgical
fear questionnaire). For the ranking exercise we calculated the mean and
standard deviation, and ranked form low (ranked most important) to high
(least important). We considered a 2-tailed p-value of \textless{} 0.05
as statistically significant.

For the DCE analysis we used Nlogit software version 6. Data were
analyzed using a multinomial regression model. This model has the
following regression equation

\selectlanguage{greek}\emph{V(conservative treatment/surgery treatment) =β0+ β1*chance of pain
reduction\_med + β2* chance of fatigue + β3* chance of pregnancy +
β4*presence of endometriosis\_med+ β5 *chance on depressed mood\_med +
β6 * chance on osteoporosis\_med+ β7*chance of pain reduction\_surg +
β8* presence of endometriosis\_surg + β9* chance on temporary
stoma\_surg + β10* permanent intestinal symptoms\_surg + β2* chance of
fatigue + β3* chance of pregnancy + ε}

\selectlanguage{english}V represents the relative utility that a respondent derives from
choosing conservative treatment or surgery. \selectlanguage{greek}β\selectlanguage{english}\textsubscript{0} is the
alternative specific constant, reflecting a preference for the label
irrespective of the levels of the attributes

\selectlanguage{greek}β\selectlanguage{english}1- \selectlanguage{greek}β\selectlanguage{english}10 are the alternative specific coefficients of each attribute with
the exception of \selectlanguage{greek}β\selectlanguage{english}2 chance of fatigue and \selectlanguage{greek}β\selectlanguage{english}3 chance of pregnancy. The
levels of these attributes were generic across the treatments.

A priori, we expected that patients prefer a higher chance of pain
reduction (positive coefficient), lower levels of fatigue (positive
coefficient for decreasing fatigue, negative for increasing fatigue),
higher pregnancy chance, reduction of endometriosis nodules/spots, low
chance of getting a depressed mood, osteoporosis, temporary stoma and
permanent intestinal symptoms.

\selectlanguage{greek}ε \selectlanguage{english}is an unobserved component of the utility function or error term. Pain
reduction, chance on depressed mood, chance on osteoporosis, chance on
temporary stoma and permanent intestinal symptoms were included as
continuous variables while for fatigue, chance on pregnancy and presence
of endometriosis dummy coding was used. In addition, we performed
subgroup analysis with women with or without a future child wish.
Relative importance was calculated by multiplying the coefficient of an
attribute with the range used for the attribute levels or using the
difference in coefficients between the best and worst level of the same
attribute (in case of dummy coding). Subsequently, the resulting
part-worth utility of each attribute was divided by the sum of all
part-worth utilities which gives the relative importance per attribute
(28). A significance level of 5\% was chosen to determine statistically
significant coefficients.

\textbf{Results}

Table 2 shows the baseline characteristics of all participants. The mean
age was 36.2 years. The median time to diagnosis was reported to be 9
years. The majority had a paid job (86.4\%) and was currently in a
relationship (82.8\%). Looking at the obstetric history, 51.5\% of the
women had never been pregnant, and 34.9\% of the participants had a
future child wish. The total spontaneous conception percentage was
76.9\% (133/173). The majority of participants rarely had difficulty
with written medical information (39.6\%), did not need help with
reading medical information (55.0\%) and had extreme trust in filling in
medical forms (58.6\%). Hormonal medication for the endometriosis was
used in 72.8\% and 71.0\% used painkillers. Looking at the surgical
history, 69.2\% had previous abdominal surgery with a total complication
rate of 33\% (ever experienced a surgical complication, ranging from
cystitis to anastomosis leakage). Regarding the surgical fear, the mean
(SD) score for the short-term consequences was 15.5 (\selectlanguage{ngerman}±8.9) and for the
long-term consequences this was 18.1 (±10.0). The mean total score was
33.6 (±16.6).

\textbf{Pain}

Dysmenorrhea was reported with a mean (SD) numeric rating scale for pain
of 7.9(±1.5), and cycle related pelvic pain of 7.7(±1.7), dyschezia
7.1(±2.6), dyspareunia 6.1(±2.8) and dysuria 4.4(±3.2) (Table 3).
Non-cycle related pain was reported for pelvic pain with a mean (SD)
numeric rating scale for pain of 5.5(±2.3), dyschezia 5.0(±2.8),
dyspareunia 5.0(±2.7), and dysuria 3.1(±2.8).

\textbf{Subgroup analysis regarding surgical fear}

Surgical fear was assessed for patients with or without a future child
wish and patients with or without previous surgery. The surgical fear
was significant lower in the group of women with previous surgery (30.9
vs. 39.8, p=0.01), no significant difference in surgical fear was seen
between the group of patients with and without a future child wish (34.7
vs. 30.9, p=0.17)

\textbf{Ranking of attributes prior the DCE}

Reducing pain (1) was ranked most important followed by no permanent
intestinal symptoms (LARS) (2), decrease of fatigue (3), reduction of
endometriosis (4), no temporary stoma (5), stable mood (6), increase of
pregnancy chances (7) and no osteoporosis (7) ranked equally important
on the last place (Table 4). For the subgroup of women with a future
child wish, the ranking was as followed: reducing pain (1), increase of
pregnancy chances (2), no permanent intestinal symptoms (3), reduction
of endometriosis (4), decrease of fatigue (4), no temporary stoma (5),
stable mood (6) and no osteoporosis (7).

\textbf{Attributes coefficients and relative importance}

Table 5 shows the main results of the DCE which includes the
coefficients and relative importance in the main model and the subgroup
of women with/without a future child wish.

\textbf{Main model}

When making a choice for conservative treatment a lower chance of
osteoporosis, an improvement in fatigue symptoms, a higher chance of
reducing pain, a higher chance of pregnancy and a reduction of
endometriosis lesions all had a significant impact while the chance of a
depressed mood did not show a significant effect. The three most
important drivers for a conservative treatment were lower chance of
osteoporosis (33\%), improvement of fatigue (25\%) and a higher chance
of reducing pain (24\%), accounting for 82\% of the relative importance
results. The improvement of fertility (9.4\%) and the reduction of
endometriosis lesions (8.5\%) showed low relative importance.

When making a choice for surgery, a lower chance of permanent intestinal
symptoms, reducing pain, improving fatigue symptoms, improving
fertility, a lower chance of getting a temporary stoma all have a
significant effect with the exception of the attribute reducing
endometriosis nodules/spots. A lower chance of permanent intestinal
symptoms (38\%), reducing pain (25\%) and improvement of fatigue (22\%)
are the most important drivers for the surgical treatment, accounting
for 85\% of the relative importance results.

\textbf{Subgroup analysis in women with a future child wish}

In the subgroup model, it is shown that improving fatigue symptoms
(34\%) together with reducing pain (28\%) and improving fertility (24\%)
are the three most important attributes when making a choice for
conservative treatment (86\% of the relative importance). Reducing
endometriosis (14\%) shows a low relative importance. Lower chance on
osteoporosis and impact on mood did not show a significant effect.

The subgroup model also shows that the chance of permanent intestinal
symptoms (35\%), reducing pain (21\%) and improving fatigue symptoms
(19\%) are the most important attributes when making a choice for
surgery (75\% of the relative importance). Improving fertility (14\%)
and the chance of getting a temporary stoma (10\%) have low relative
importance. Reducing endometriosis nodules/spots do not show a
significant effect.

\textbf{Discussion}

\textbf{Main findings}

Translating the main findings of this DCE with women suffering from DE
and bowel involvement towards the clinical setting we can conclude that
1) In the general ranking, osteoporosis is ranked as least important
attribute, while in the DCE, a lower chance of osteoporosis is one of
the most important drivers for making a choice in the conservative
treatment. 2) Osteoporosis, fatigue symptoms, pain symptoms, pregnancy
rates and the presence of endometriosis nodules all have a significant
impact on the preference for conservative treatment. The three most
important drivers for conservative treatment are lower chance of
developing osteoporosis (gonadotropin-releasing hormone (GnRH)
analogues), higher chance of improving fatigue symptoms and higher
chance of reducing pain symptoms. For surgery, the attributes with a
significant impact are getting intestinal symptoms (LARS), pain
symptoms, fatigue symptoms, pregnancy rates and getting a temporary
stoma. The three most important drivers for surgery are lower chance of
getting bowel symptoms (LARS), higher chance of reducing pain symptoms
and higher chance of improving fatigue symptoms. 3) The chance of
getting a temporary stoma plays a less important role in the context of
this study compared to pain reduction and the risk of LARS. 4) Women
with a future child wish put pain reduction above possible improvement
of fertility chances. 5) Women with previous surgery have significant
lower fear for surgery compared to women without a surgical history (DE
surgery).

Comparing the results of the direct ranking method and those of the
relative importance of the DCE shows discrepancy between both methods.
In particular the attribute chance of osteoporosis is considered least
important in the ranking exercise while one of the most important
attributes when choosing conservative treatment in the DCE. However, as
described by Louviere and Islam (29), explicit context like in this case
information about the type of treatment, the description of the
attributes and the associated levels might explain the difference
between the methods. For the ranking exercise, no levels were provided
and thus, in contrast with the discrete choice experiment, a trade-off
between levels of different attributes when making a choice for
conservative treatment or surgery was not required. We believe that the
DCE in this study provides more detailed and reliable outcomes, but also
requires more intellectual effort from the participants and therefore
more challenging to make. Solely ranking attributes is easy, but it
should be kept in mind that no considerations about the levels are taken
into account.

The risk of permanent intestinal symptoms being almost equally important
as pain reduction is an important finding, since the debate about
radical DE bowel surgery (resection) versus conservative surgery
(shaving/discoid) is ongoing and still undecided. Believers of radical
surgery have an approach (radical as possible) almost similar to
oncological surgical approaches (30) (31) and aim to reduce pain,
prevent recurrence and perhaps even cure women with DE. The potential
price they have to pay for this approach is theoretically more severe
complications and the risk of permanent intestinal symptoms (LARS) (32).
Surgeons who believe in a more reluctant approach aim to reduce pain
symptoms and accept possible recurrence/incomplete removal of
endometriosis, but try to reduce severe complications and prevent
possible permanent bowel symptoms (LARS) (33) (34) (35). However,
regarding the good results from the more reluctant surgical approach
from Donnez it has to be noted that these patients were treated with
progesterone afterwards and only followed up for one year. Long term
effects and patients without progesterone should be studied as well to
support the more reluctant surgical DE approach.

\textbf{Strengths and limitations}

The main strength of this study is the extensive preparation
(qualitative study) in order to correctly identify the attributes of
importance. Identifying the attributes is seen as the key aspect of the
design of a DCE. Attributes should be relevant to the target population,
should be relevant to the decision making context and the research
question and the attributes should be defined in a way that is
intelligible for patients. Without extensive work in defining the
attributes, a DCE will not provide valid preferences, while important
attributes could be missed that would have been paramount in making a
treatment choice. With our qualitative, quantitative and literature
search we believe that we used all possible information sources for an
optimal selection of relevant attributes, and therefore increased the
chance of valid preferences.

The second strength of this study is the strict selection of appropriate
patients (26.3\%) who were suitable for our DCE and would comply to our
research question. Completing a DCE is a complex task and requires
concentration and a certain level of intellect. With the three inclusion
questions we aimed to select only patients with DE and bowel
endometriosis, were not in actual fertility treatment and prior to a
treatment decision. Furthermore, we excluded patients with poor health
literacy, patients who filled in the DCE unreasonable quickly, patients
who showed signs of being survey fatigue by filling in the same answer
on almost all questions and finally we excluded patients who did not
complete the DCE part of the survey. This way we aimed to select
patients without linguistic bias, were focused, and took the time to
fill in this DCE.

This study has two main limitations. The first limitation is the method
of recruitment. The vast majority of patients (70.4\%) were recruited by
their gynaecologist and 29.6\% through advertisement via the Dutch and
Belgian endometriosis foundation. Ideally we only included patients via
their gynaecologist who also confirmed the deep endometriosis with bowel
involvement, but because deep endometriosis is less prevalent (\selectlanguage{english}[?] 1/10 of
the general endometriosis population), we anticipated on the fact that
recruitment would not be sufficient if we only included patients through
their treating gynaecologists. We specifically choose advertising via
official endometriosis organisations to reduce the potential bias
recruiting patients without endometriosis, although there was no actual
benefit in completing this DCE (no financial fee). To reduce the
potential bias of patients without deep endometriosis we included three
inclusion questions, whereby it was not clear for the participant which
question would in or exclude the participant. This method of inclusion
had been used more often, also in endometriosis research (15) (16) (17).

The second limitation could be the sample size. Prior to the start of
the DCE we aimed to include 300 inclusions. We did not reach that amount
of inclusions because recruitment took more time as previously
anticipated. We took several steps to increase the number of
participants like advertisement through the Dutch and Belgian
endometriosis population. Finally, we were able to include 169 patients.
Lancsar (26) states that based on empirical experience per questionnaire
version rarely more than 20 respondents are needed although that number
has to increase when performing extensive subgroup analyses. Given that
we used three blocks (questionnaire versions) and performed one subgroup
analysis, we calculated that our sample size of 169 was sufficient for
reliable analysis.

\textbf{Interpretation}

From the findings in our study we can conclude that pain reduction
should not be the only motivation for surgery at all costs. This new
insight in patients' considerations could help in the shared decision
making process and should be considered as an important factor in the
final treatment decision. Pain can negatively impact the quality of
life, but the chance on LARS in more radical surgery due to bowel
resection (faecal incontinence or urgency, frequent or fragmented bowel
movements, emptying difficulties) is also debilitating and has major
impact on the quality of life (36). Therefore DE patients with an
indication for bowel resection should be counselled for the possible
benefits and potential risk of developing permanent intestinal symptoms
(LARS). Consequently, a multidisciplinary approach with SDM should
enable a patient to make a well informed choice that is based on
patients' preferences and clinical judgement of their treating physician
(gynaecologist/surgeon) to ensure treatment satisfaction and improved
quality of life after the treatment and recovery process.

Regarding surgical fear, women with previous surgery have significant
lower surgical fear compared to women without a surgical history. This
is also an important finding which could be useful in the shared
decision making process. The physician should be aware that women
without surgery might have more fear towards surgery, which could
influence their decision. This is in line with the findings of patients
undergoing cataract surgery, they found lower surgical fear in the group
who underwent the second surgery (37).

However, this information could also mean that women with previous
surgery and less fear have a tendency to choose surgery more easily and
pay less attention to the possible complications or long term side
effects (LARS). The clinician should be aware of both possibility's when
counseling women (with and without a surgical history) in the SDM
process.

\textbf{Conclusion}

The aim of the present study was to gain insight in preferences for a
conservative or surgical treatment approach of patients suffering from
DE. This is the first DCE on treatment preferences from a nationally
representative cohort of patients with deep endometriosis. These
findings make several contributions to the current literature in DE. The
risk of permanent intestinal symptoms (from the treatment) is almost
equally important for patients as the chance of reduction in pain
symptoms. The results of this study can be used in the decision-making
process between doctor and patient, where it is important that symptoms
arising from the endometriosis are treated such as pain reduction and
improvement of fatigue. However, it is also important to pay attention,
when choosing a treatment to consider the short and long term risks. In
which the risk of getting LARS during surgery needs attention, as well
as a long term risk such as osteoporosis when choosing certain
conservative treatment (GnRH analogues). Women with previous surgery
showed less surgical anxiety, this information could help to inform
anxious women without a surgical history, but who need surgery in their
decision process. The current results can be used to assist SDM, e.g. by
developing a decision aid aimed at providing relevant information and
assisting patients in difficult treatment choices in DE care. Further
studies regarding the role of decision making in non-DE would be
worthwhile.

\textbf{Disclosure of interest}

None declared.

\textbf{Contribution to authorship}

Je.M. and J.S. conducted the qualitative research, the DCE was designed
by all researchers, Je.M. and E.T. were responsible for collecting data,
B.E. and JeM performed the analyses. Je.M., J.M., F.J., E.A., and B.E.
took the lead in writing the manuscript. All authors were responsible
for interpreting the data and final review of the manuscript. All
authors approved the final manuscript.

\textbf{Details of ethics approval}

The Medical Ethical Committee of the two executive centers Leiden
University Medical Centre (P18.142) and Maxima Medisch Centrum (N18.088)
approved the study protocol and procedure (online recruitment).

\textbf{Funding:} The author(s) received no financial support for the
research, authorship, and/or publication of this article.

\textbf{Acknowledgements}

First of all we would like to thank all participating women for
their~time and effort in this study. Furthermore, we would like to thank
the Dutch and Belgian endometriosis foundation for their support in
recruiting women for this study. And finally we would like to thank the
following participating centers: UMC Groningen (dr. Ellen Klinkert),
Medisch Spectrum Twente (drs. Laurens van Boven), Catharina Ziekenhuis
(Prof. dr. Dick Schoot), Isala clinic (dr. Joke Schutte), Rijnstate
hospital (Prof. dr. Annemiek Nap), VUmc (Prof. dr. Velja Mijatovic),
MUMC (dr. Lennie van Hanegem), Bravis hospital (dr. Marja Noordam),
Radboud UMC (dr. Bertho Nieboer), OLVG (dr. Paul van Kesteren), Erasmus
MC (dr. Anneke Steensma).

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