University of Groningen
Management of heavy menstrual bleeding
van den Brink, Marian
DOI:
10.33612/diss.160486947
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Publication date: 2021
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van den Brink, M. (2021). Management of heavy menstrual bleeding: Towards a patient-centred approach. University of Groningen. https://doi.org/10.33612/diss.160486947
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Women’s preferences for the levonorgestrel
intrauterine system versus endometrial
ablation for heavy menstrual bleeding
Marian J van den Brink, Pleun Beelen,
Malou C Herman, Nathalie JJ Claassen,
Marlies Y Bongers, Peggy M Geomini,
Jan Willem van der Steeg, Lotte van
den Wijngaard, Madelon van Wely
Eur J Obstet Gynecol Reprod Biol.
2018;228:143-147
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OObbjjeeccttiivveess
Women’s preferences for treatment of heavy menstrual bleeding (HMB) are important in clinical decision-making. Our aim was to investigate whether women with HMB have a preference for treatment characteristics of the levonorgestrel intrauterine system (LNG-IUS) or endometrial ablation and to assess the relative importance of these characteristics.
SSttuuddyy DDeessiiggnn
A discrete choice experiment was performed in general practices and gynaecology outpatient clinics in the Netherlands. Women with HMB were asked to choose between hypothetical profiles containing characteristics of LNG-IUS or endometrial ablation. Characteristics included procedure performed by gynaecologist or general practitioner; reversibility of the procedure; probability of dysmenorrhea; probability of irregular bleeding; additional use of contraception; Need to repeat the procedure after five years; and treatment containing hormones. Data were analysed using panel mixed logit models. The main outcome measures were the relative importance of the characteristics and willingness to make trade-offs.
RReessuullttss
165 women completed the questionnaire; 36 (22%) patients were recruited from general practices and 129 (78%) patients were recruited from gynaecology outpatient clinics. The characteristic found most important was whether a treatment contains hormones. Women preferred a treatment without hormones, a treatment with the least side effects, and no need for a repeat procedure or additional contraception. Women completing the questionnaire at the gynaecology outpatient clinic differed from women in primary care in their preference for a definitive treatment to be performed by a gynaecologist. CCoonncclluussiioonnss
Whether or not a treatment contains hormones was the most important characteristic influencing patient treatment choice for HMB. Participants preferred characteristics that were mostly related to endometrial ablation, but were willing to trade off between characteristics.
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Heavy menstrual bleeding (HMB) is an important health issue among women of reproductive age. Every year one in 20 women consults their general practitioner (GP) about HMB. HMB is one of the most common reasons to consult a gynaecologist.1-3Both the Dutch College of General Practitioners’ practice guideline on vaginal bleeding and the Dutch and international gynaecological guidelines on menorrhagia recommend the use of the LNG-IUS as one of the first therapeutic options for HMB.4-6 Endometrial ablation is another frequently used, minimally invasive treatment option for HMB. Both treatments are effective in decreasing blood loss, but there is insufficient evidence to suggest a significant difference in blood loss reduction between the two treatment options.1,7-10 Consequently, current treatment choice is based on patient preferences. The LNG-IUS can be placed by the GP, but has considerable discontinuation rates due to side effects such as irregular bleeding (spotting).1,7The contraceptive effect of the LNG-IUS can be beneficial but only lasts five years, after which the LNG-LNG-IUS has to be replaced. On the other hand, endometrial ablation is an irreversible treatment option, performed by a gynaecologist. It does not provide any contraception and has higher rates of dysmenorrhea.11In order to make a well-informed decision, women need to be aware of the characteristics of the above-mentioned treatments. Moreover, Kennedy et al. showed that providing women with information alone did not affect treatment choices, but clarifying values and eliciting preferences did have a significant effect on women's treatment choice.12 Understanding patients’ considerations in decision making can contribute to improvement in treatment counselling and shared decision making, and can lead to higher patient satisfaction rates.
Few studies on patient preferences regarding treatment with the LNG-IUS or endometrial ablation have been performed.13-15 It is unknown which treatment is preferred and which characteristics of these treatments are important in patient treatment choice. In this discrete choice experiment (DCE), we investigated whether women with HMB have a preference for the treatment characteristics of the LNG-IUS or of endometrial ablation and assessed the importance they place on these characteristics.
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SSeettttiinngg aanndd PPaarrttiicciippaannttss
Women with HMB, without an indication for an organic cause and where treatment with oral medication failed or was not preferred, were informed about the study. Women were recruited in general practices in different regions of the Netherlands and in two gynaecology outpatient departments (Maxima Medical Centre, Veldhoven and Jeroen Bosch Hospital, Den Bosch). Women who agreed to participate were asked to complete a questionnaire before a treatment option was chosen. Participation was voluntary.
D
DCCEE:: aattttrriibbuutteess aanndd lleevveellss
A DCE is a survey-based technique used to quantify patients’ preferences. It is based on the premise that every treatment can be described by its characteristics (attributes), and that women can value these attributes upon their levels. The relative importance of the attributes and the trade-offs that respondents make between them can be assessed by offering a series of choice sets with varying levels of the attributes.16 The selection of attributes and levels was based on literature and expert opinion.1,7,11,13,17-26 We interviewed patients with HMB (n=12) and experienced gynaecologists from different hospitals about the attributes they considered important. We discussed the identified attributes and corresponding levels in an experienced and specialised DCE group at the gynaecology department of the Academic Medical Centre, Amsterdam (AMC). Finally, we asked 20 patients with HMB to rank our list of attributes in order of importance and to indicate whether important attributes were missing (see Supplementary Data Table S1).
We selected the following attributes for the DCE (see Table 1): procedure performed by gynaecologist or GP (1), reversibility of the procedure (2), probability of dysmenorrhea (1% vs. 10%) (3), probability of irregular bleeding (0% vs. 15%) (4), need to use additional contraception (5), need to repeat the procedure after five years (6), and treatment containes hormones (7).
TTaabbllee 11.. Attributes with their corresponding levels
AAttttrriibbuuttee LLeevveell
PPrroocceedduurree iiss ppeerrffoorrmmeedd bbyy General Practitioner Gynaecologist PPrroocceedduurree iiss rreevveerrssiibbllee Yes
No PPrroobbaabbiilliittyy ooff ddyyssmmeennoorrrrhheeaa 1% 10% PPrroobbaabbiilliittyy ooff iirrrreegguullaarr bblleeeeddiinngg 0%
15% UUssee ooff aaddddiittiioonnaall ccoonnttrraacceeppttiioonn Yes
No N
Neeeedd ttoo rreeppeeaatt tthhee pprroocceedduurree aafftteerr 55 yyeeaarrss Yes No TThhee ttrreeaattmmeenntt ccoonnttaaiinnss hhoorrmmoonneess Yes
No
D
Deevveellooppmmeenntt ooff tthhee cchhooiiccee sseettss
The combinations of seven attributes, each with two levels (Table 1) were converted into 16 choice sets. Many scenarios can be developed when using seven attributes with two levels each. It is not feasible to put all these options into one questionnaire, so a functional sample of scenarios was generated using an orthogonal design. This creates an optimal balance of the attributes and attribute levels with minimal correlation.27This resulted in 32 scenarios, which were randomly combined into 16 discrete choice sets using Ngene design software (version 1.1.1. Choicemetrics Pty Ltd, Sydney, NSW, Australia) to create the most efficient design. In a series of 16 choice sets, women were asked in an unlabelled design to choose between hypothetical scenarios of a ‘treatment A’ and ‘treatment B’ (Figure 1). Women did not know which attribute level belonged to which treatment. Women had to choose their most preferred option in each choice set, using a forced choice design. The choice sets did not have an ‘opt out’ alternative (for example a ‘no treatment’ option). One dominant choice set was added with the levels of
6
6
SSeettttiinngg aanndd PPaarrttiicciippaannttss
Women with HMB, without an indication for an organic cause and where treatment with oral medication failed or was not preferred, were informed about the study. Women were recruited in general practices in different regions of the Netherlands and in two gynaecology outpatient departments (Maxima Medical Centre, Veldhoven and Jeroen Bosch Hospital, Den Bosch). Women who agreed to participate were asked to complete a questionnaire before a treatment option was chosen. Participation was voluntary.
D
DCCEE:: aattttrriibbuutteess aanndd lleevveellss
A DCE is a survey-based technique used to quantify patients’ preferences. It is based on the premise that every treatment can be described by its characteristics (attributes), and that women can value these attributes upon their levels. The relative importance of the attributes and the trade-offs that respondents make between them can be assessed by offering a series of choice sets with varying levels of the attributes.16 The selection of attributes and levels was based on literature and expert opinion.1,7,11,13,17-26 We interviewed patients with HMB (n=12) and experienced gynaecologists from different hospitals about the attributes they considered important. We discussed the identified attributes and corresponding levels in an experienced and specialised DCE group at the gynaecology department of the Academic Medical Centre, Amsterdam (AMC). Finally, we asked 20 patients with HMB to rank our list of attributes in order of importance and to indicate whether important attributes were missing (see Supplementary Data Table S1).
We selected the following attributes for the DCE (see Table 1): procedure performed by gynaecologist or GP (1), reversibility of the procedure (2), probability of dysmenorrhea (1% vs. 10%) (3), probability of irregular bleeding (0% vs. 15%) (4), need to use additional contraception (5), need to repeat the procedure after five years (6), and treatment containes hormones (7).
TTaabbllee 11.. Attributes with their corresponding levels
AAttttrriibbuuttee LLeevveell
PPrroocceedduurree iiss ppeerrffoorrmmeedd bbyy General Practitioner Gynaecologist PPrroocceedduurree iiss rreevveerrssiibbllee Yes
No PPrroobbaabbiilliittyy ooff ddyyssmmeennoorrrrhheeaa 1% 10% PPrroobbaabbiilliittyy ooff iirrrreegguullaarr bblleeeeddiinngg 0%
15% UUssee ooff aaddddiittiioonnaall ccoonnttrraacceeppttiioonn Yes
No N
Neeeedd ttoo rreeppeeaatt tthhee pprroocceedduurree aafftteerr 55 yyeeaarrss Yes No TThhee ttrreeaattmmeenntt ccoonnttaaiinnss hhoorrmmoonneess Yes
No
D
Deevveellooppmmeenntt ooff tthhee cchhooiiccee sseettss
The combinations of seven attributes, each with two levels (Table 1) were converted into 16 choice sets. Many scenarios can be developed when using seven attributes with two levels each. It is not feasible to put all these options into one questionnaire, so a functional sample of scenarios was generated using an orthogonal design. This creates an optimal balance of the attributes and attribute levels with minimal correlation.27This resulted in 32 scenarios, which were randomly combined into 16 discrete choice sets using Ngene design software (version 1.1.1. Choicemetrics Pty Ltd, Sydney, NSW, Australia) to create the most efficient design. In a series of 16 choice sets, women were asked in an unlabelled design to choose between hypothetical scenarios of a ‘treatment A’ and ‘treatment B’ (Figure 1). Women did not know which attribute level belonged to which treatment. Women had to choose their most preferred option in each choice set, using a forced choice design. The choice sets did not have an ‘opt out’ alternative (for example a ‘no treatment’ option). One dominant choice set was added with the levels of
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each attribute (where possible) completely in favour of one treatment. Women who failed this rationality test were excluded from the analysis.
QQuueessttiioonnnnaaiirree
The questionnaire consisted of general questions regarding patient characteristics, followed by contextual information about the topic, attributes, questionnaire instructions, and the 16 choice sets. The questionnaire was tested prior to the study by a panel of doctors, nurses and women with HMB to assess interpretation.
EEtthhiiccaall ccoonnssiiddeerraattiioonnss
The methodology of this study does not fall within the scope of the Medical Research Involving Human Subjects Act as participants are not subjected to a treatment or to behavioural adjustment. A declaration of no objection was received from the institutional review board of the AMC, Amsterdam.
SSttaattiissttiiccaall aannaallyyssiiss
Recommendations in literature vary about the appropriate sample-size for DCEs.28 Most DCEs have a sample size between 100 and 300. We aimed to include at least 20 patients per attribute. Our aimed sample size of 140 women in total meets Johnson’s rule-of-thumb.29, 30
Data were processed and transferred to STATA SE 11 (StataCorp LP, College Station, TX, USA). For demographic data, we calculated means and standard deviations (SD) for continuous parameters, and numbers and percentage for dichotomous or nominal data. We analysed the data using a mixed logit model for panel data. The output of a mixed logit model includes mean coefficients (β) representing the relative utility of each attribute that is conditional on other attributes and standard deviations of the random coefficients, along with their respective confidence intervals (CIs). We estimated panel mixed logit models with DCE attributes as the sole explanatory variables using STATA mixlogit command.31 The mean coefficient (β) indicated the relative likelihood of choosing a (theoretical) treatment with a given attribute-level combination, while holding all other levels constant. The negative sign of the coefficient reflects a negative effect on utility.
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6
each attribute (where possible) completely in favour of one treatment. Women who failed this rationality test were excluded from the analysis.
QQuueessttiioonnnnaaiirree
The questionnaire consisted of general questions regarding patient characteristics, followed by contextual information about the topic, attributes, questionnaire instructions, and the 16 choice sets. The questionnaire was tested prior to the study by a panel of doctors, nurses and women with HMB to assess interpretation.
EEtthhiiccaall ccoonnssiiddeerraattiioonnss
The methodology of this study does not fall within the scope of the Medical Research Involving Human Subjects Act as participants are not subjected to a treatment or to behavioural adjustment. A declaration of no objection was received from the institutional review board of the AMC, Amsterdam.
SSttaattiissttiiccaall aannaallyyssiiss
Recommendations in literature vary about the appropriate sample-size for DCEs.28 Most DCEs have a sample size between 100 and 300. We aimed to include at least 20 patients per attribute. Our aimed sample size of 140 women in total meets Johnson’s rule-of-thumb.29, 30
Data were processed and transferred to STATA SE 11 (StataCorp LP, College Station, TX, USA). For demographic data, we calculated means and standard deviations (SD) for continuous parameters, and numbers and percentage for dichotomous or nominal data. We analysed the data using a mixed logit model for panel data. The output of a mixed logit model includes mean coefficients (β) representing the relative utility of each attribute that is conditional on other attributes and standard deviations of the random coefficients, along with their respective confidence intervals (CIs). We estimated panel mixed logit models with DCE attributes as the sole explanatory variables using STATA mixlogit command.31 The mean coefficient (β) indicated the relative likelihood of choosing a (theoretical) treatment with a given attribute-level combination, while holding all other levels constant. The negative sign of the coefficient reflects a negative effect on
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TTaabbllee 22.. Baseline characteristics (n=165)
CChhaarraacctteerriissttiicc MMeeaann ((±±SSDD)) oorr nnuummbbeerr ((%%)) AAggee ((yyeeaarrss)) 45 (±5.6)
RReeccrruuiittmmeenntt bbyy:: General Practitioner 36 (22%) Gynaecologist 129 (78%) H
Hiissttoorryy ooff HHMMBB ((mmoonntthhss)) 64 (±88) D
Duurraattiioonn ooff mmeennssttrruuaall bblloooodd lloossss ((ddaayyss)) 7.6 (±4.0) PPrreesseennccee ooff CClloottss ((ddaayyss)) 3.6 (±2.4) D Dyyssmmeennoorrrrhheeaa No dysmenorrhea 42 (25%) Moderate 69 (42%) Severe 54 (33%) PPaarriittyy
Vaginal deliveries 1.8 (±1.1; range: 0-5) Caesarean sections 0.3 (±0.7; range 0-4) PPrreevviioouuss uutteerriinnee ssuurrggeerryy
None 115 (70%)
Myomectomy 6 (4%) Polypectomy 20 (12%)
Other 22 (13%)
Unknown 2 (1%)
PPrreevviioouuss ttrreeaattmmeenntt ffoorr HHMMBB**
None 109 (66%)
Hormonal** 52 (32%)
Of which LNG-IUS 25 (15%) Endometrial ablation 3 (1.8%) Other*** 7 (4.2%)
SD: standard deviation; HMB: heavy menstrual bleeding. *Women could have had multiple treatments. ** Data include oral contraceptives, Etonogestrel implant, levonorgestrel intrauterine
The value of the coefficient indicates the relative importance of the attribute to total relative utility. A statistically significant coefficient indicates that respondents considered that attribute important (p<0.001).
To understand whether recruitment by GP or gynaecologist, age, previous experience with a LNG-IUS or other hormonal treatment, and previous uterine surgery influenced attributed preferences, we also estimated models that allowed these factors to interact with the treatment-related attributes.
The trade-offs that respondents are willing to make between attributes were estimated by calculating the ratios of the coefficients of two attributes, where we also accounted for preference heterogeneity. As both the constant and the attributes were included as random parameters in the analyses, the trade-offs could not be calculated directly. Importance scores were calculated with a 95% CI to visualise the relative importance of a given attribute by dividing the difference in utility between the highest and lowest level for a single attribute by the sum of the differences of all attributes. A simulation (n = 1000) was used to estimate the trade-offs.
PPaarrttiicciippaannttss
165 patients completed the questionnaire, 36 of which were recruited in general practice while 129 patients were recruited in gynaecology outpatient clinics. All respondents answered the dominant discrete choice set correctly. The respondents had an average age of 45 years and a mean duration of HMB of more than five years. 66% of women had not received previous treatment for HMB; 17% of women had been treated with the LNG-IUS or endometrial ablation (Table 2).
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TTaabbllee 22.. Baseline characteristics (n=165)
CChhaarraacctteerriissttiicc MMeeaann ((±±SSDD)) oorr nnuummbbeerr ((%%)) AAggee ((yyeeaarrss)) 45 (±5.6)
RReeccrruuiittmmeenntt bbyy:: General Practitioner 36 (22%) Gynaecologist 129 (78%) H
Hiissttoorryy ooff HHMMBB ((mmoonntthhss)) 64 (±88) D
Duurraattiioonn ooff mmeennssttrruuaall bblloooodd lloossss ((ddaayyss)) 7.6 (±4.0) PPrreesseennccee ooff CClloottss ((ddaayyss)) 3.6 (±2.4) D Dyyssmmeennoorrrrhheeaa No dysmenorrhea 42 (25%) Moderate 69 (42%) Severe 54 (33%) PPaarriittyy
Vaginal deliveries 1.8 (±1.1; range: 0-5) Caesarean sections 0.3 (±0.7; range 0-4) PPrreevviioouuss uutteerriinnee ssuurrggeerryy
None 115 (70%)
Myomectomy 6 (4%) Polypectomy 20 (12%)
Other 22 (13%)
Unknown 2 (1%)
PPrreevviioouuss ttrreeaattmmeenntt ffoorr HHMMBB**
None 109 (66%)
Hormonal** 52 (32%)
Of which LNG-IUS 25 (15%) Endometrial ablation 3 (1.8%) Other*** 7 (4.2%)
SD: standard deviation; HMB: heavy menstrual bleeding. *Women could have had multiple treatments. ** Data include oral contraceptives, Etonogestrel implant, levonorgestrel intrauterine
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system (LNG-IUS), oral progestogens, or a combination of these therapies. *** Tranexamic acid and/or nonsteroidal anti-inflammatory drugs.
D DCCEE
The results of the panel mixed logit regression model are shown in Table 3. All attributes were found to be important to the respondents (p<0.001).
TTaabbllee 33.. Mixed logit regression analysis (n=165)
AAttttrriibbuutteess MMeeaann ccooeeffffiicciieenntt ((9955%% CCII)) SSDD ((9955%% CCII)) Constant 2.00 (1.77 to 2.24)* 1.48 (0.34 to 2.78)*
Treatment performed by
gynaecologist vs. GP 0.37 (0.21 to 0.54)* 0.68 (0.16 to 1.20)* Reversibility of procedure -0.41 (-0.56 to -0.25)* 0.25 (0.09 to 0.41)*
Probability of dysmenorrhea** -0.09 (-0.10 to -0.08)* 0.05 (-0.11 to 0.21)
Probability of irregular bleeding** -0.04 (-0.05 to -0.03)* 0.06 (-0.04 to 0.16)
Use of additional contraception -0.47 (-0.62 to -0.32)* 0.35 (-0.05 to 0.75)
Need to repeat the procedure
after 5 years -0.62 (-0.76 to -0.47)* 0.95 (0.26 to 1.64)* Treatment contains hormones -1.33 (-1.54 to -1.12)* 1.97 (1.15 to 2.69)*
Number of responses 5232 Log likelihood -874
AIC 1.91
BIC 1.97
GP: general practitioner; SD: standard deviation; CI: confidence interval; AIC: Akaike’s Information Criterion; BIC: Schwarz’s Bayesian Criterion; * P < 0.001 ** Mean coefficient is presented per 1% change in probability. The negative sign of the coefficient reflects a negative effect on utility. A negative sign for probability of dysmenorrhea and irregular bleeding indicates that women prefer a lower probability of this attribute. The positive coefficient for treatment performed by gynaecologist vs GP indicates that women prefer a gynaecologist.
The respondents preferred a treatment that does not contain hormones, does not have to be repeated after five years, eliminates the need for additional contraceptives, is not
6
6
system (LNG-IUS), oral progestogens, or a combination of these therapies. *** Tranexamic acid and/or nonsteroidal anti-inflammatory drugs.
D DCCEE
The results of the panel mixed logit regression model are shown in Table 3. All attributes were found to be important to the respondents (p<0.001).
TTaabbllee 33.. Mixed logit regression analysis (n=165)
AAttttrriibbuutteess MMeeaann ccooeeffffiicciieenntt ((9955%% CCII)) SSDD ((9955%% CCII)) Constant 2.00 (1.77 to 2.24)* 1.48 (0.34 to 2.78)*
Treatment performed by
gynaecologist vs. GP 0.37 (0.21 to 0.54)* 0.68 (0.16 to 1.20)* Reversibility of procedure -0.41 (-0.56 to -0.25)* 0.25 (0.09 to 0.41)*
Probability of dysmenorrhea** -0.09 (-0.10 to -0.08)* 0.05 (-0.11 to 0.21)
Probability of irregular bleeding** -0.04 (-0.05 to -0.03)* 0.06 (-0.04 to 0.16)
Use of additional contraception -0.47 (-0.62 to -0.32)* 0.35 (-0.05 to 0.75)
Need to repeat the procedure
after 5 years -0.62 (-0.76 to -0.47)* 0.95 (0.26 to 1.64)* Treatment contains hormones -1.33 (-1.54 to -1.12)* 1.97 (1.15 to 2.69)*
Number of responses 5232 Log likelihood -874
AIC 1.91
BIC 1.97
GP: general practitioner; SD: standard deviation; CI: confidence interval; AIC: Akaike’s Information Criterion; BIC: Schwarz’s Bayesian Criterion; * P < 0.001 ** Mean coefficient is presented per 1% change in probability. The negative sign of the coefficient reflects a negative effect on utility. A negative sign for probability of dysmenorrhea and irregular bleeding indicates that women prefer a lower probability of this attribute. The positive coefficient for treatment performed by gynaecologist vs GP indicates that women prefer a gynaecologist.
The respondents preferred a treatment that does not contain hormones, does not have to be repeated after five years, eliminates the need for additional contraceptives, is not
reversible, and provides the lowest probability of experiencing dysmenorrhea or irregular bleeding. Overall, respondents preferred being treated by a gynaecologist rather than by a GP. Whether or not a treatment contains hormones was found to be the most important attribute (mean coefficient -1.33; 95% CI -1.54 to -1.12).
The SD for ‘treatment performed by gynaecologist or GP’, ‘reversibility of the procedure’, ‘need to repeat the procedure after five years’ and ‘treatment containing hormones’ was significant. This implies that there was heterogeneity in preference across the participating women for these attributes. Though most women preferred a gynaecologist, some women preferred a GP.
W
Wiilllliinnggnneessss ttoo ttrraaddee bbeettwweeeenn aattttrriibbuutteess
Most respondents were willing to make trade-offs between attributes. For example, irreversibility would be traded off for reversibility in exchange for not requiring additional contraceptives. A treatment without hormones would be traded off for a treatment with hormones in exchange for an absolute 15% (95% CI 6.1 to 23.8) decrease in probability of dysmenorrhea.
EEffffeecctt ooff bbaasseelliinnee ppaarraammeetteerrss
The effect of baseline parameters on the participants’ choices was evaluated in a secondary analysis. The baseline parameter ‘recruiting doctor’ was a significant interaction term. Women who had been recruited by a GP did not have preference for a GP or gynaecologist (β -0.15; 95%CI -0.42 to 0.12), nor did they consider requiring a repeat procedure a significant attribute (β -0.33; 95%CI -0.69 to 0.03). However, these women made similar choices compared to the women recruited by a gynaecologist concerning the remaining characteristics.
Age, previous experience with the LNG-IUS, hormonal treatment or uterine surgery, and severity of dysmenorrhea did not affect the women's choices.
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The results of this DCE suggest that the participating women generally prefer the treatment characteristics related to endometrial ablation: an irreversible treatment without hormones that does not need to be repeated after five years, with a low probability of irregular bleeding. However, women did not express a preference for the need for additional contraception or for the probability of dysmenorrea. The absence of these characteristics represents advantages of the use of the LNG-IUS. Furthermore, most women were willing to trade off their ablation preference for characteristics related to treatment with the LNG-IUS.
Our findings of preference for ablation does not correspond with two previous studies in which most women were found to prefer the LNG-IUS.13, 14 In a study by Leung et al., 200 Chinese women with HMB referred to a university teaching hospital were asked which therapy they preferred when drug therapy failed. The LNG-IUS was preferred by 53.6% of women while endometrial ablation was preferred by 19% of women. Bourdrez et al. studied women’s preferences for endometrial ablation and LNG-IUS as alternatives to hysterectomy in a Dutch hospital. They found that, in cases in which the success rate of alternative treatment was presumed to be 50%, 45% of women would opt for treatment with the LNG-IUS while 30% would opt for endometrial ablation.
The heterogeneity in preference for certain attributes found in our study suggests there are subgroups of women with different preferences. This heterogeneity is often seen in DCEs and is in accordance with a study by Vuorma et al. in which women with menorrhagia referred to gynaecology outpatient clinics were surveyed.15 They found that hysterectomy was favoured as often as conservative treatment (including no treatment). Predictors for hysterectomy preference included a lower education level, higher age, dysmenorrhea, consultations with a gynaecologist and a completed family. In our study, other than recruitment setting, no other patient characteristics influenced the women’s preferences.
SSttrreennggtthhss && lliimmiittaattiioonnss
To our knowledge, this is the first study using a DCE as a valid technique to elicit patient preferences for HMB treatment. We included women from both general practices and
6
6
The results of this DCE suggest that the participating women generally prefer the treatment characteristics related to endometrial ablation: an irreversible treatment without hormones that does not need to be repeated after five years, with a low probability of irregular bleeding. However, women did not express a preference for the need for additional contraception or for the probability of dysmenorrea. The absence of these characteristics represents advantages of the use of the LNG-IUS. Furthermore, most women were willing to trade off their ablation preference for characteristics related to treatment with the LNG-IUS.
Our findings of preference for ablation does not correspond with two previous studies in which most women were found to prefer the LNG-IUS.13, 14 In a study by Leung et al., 200 Chinese women with HMB referred to a university teaching hospital were asked which therapy they preferred when drug therapy failed. The LNG-IUS was preferred by 53.6% of women while endometrial ablation was preferred by 19% of women. Bourdrez et al. studied women’s preferences for endometrial ablation and LNG-IUS as alternatives to hysterectomy in a Dutch hospital. They found that, in cases in which the success rate of alternative treatment was presumed to be 50%, 45% of women would opt for treatment with the LNG-IUS while 30% would opt for endometrial ablation.
The heterogeneity in preference for certain attributes found in our study suggests there are subgroups of women with different preferences. This heterogeneity is often seen in DCEs and is in accordance with a study by Vuorma et al. in which women with menorrhagia referred to gynaecology outpatient clinics were surveyed.15 They found that hysterectomy was favoured as often as conservative treatment (including no treatment). Predictors for hysterectomy preference included a lower education level, higher age, dysmenorrhea, consultations with a gynaecologist and a completed family. In our study, other than recruitment setting, no other patient characteristics influenced the women’s preferences.
SSttrreennggtthhss && lliimmiittaattiioonnss
To our knowledge, this is the first study using a DCE as a valid technique to elicit patient preferences for HMB treatment. We included women from both general practices and
gynaecology outpatient clinics and assessed differences in preferences between those two patient groups.
Our study may have several limitations, the first being its sample size. Although we succeeded in including more than 20 patients per attribute, the percentage of patients recruited in primary care was relatively small (22%). Our sample size was adequate for the main analysis. Caution must however be taken when drawing conclusions from the subgroup of primary care respondents and from the interaction effect of baseline characteristics.
The values for the attribute-levels used in this study are mean probabilities based on available literature. However, there is a wide range of reported values of dysmenorrhea and irregular bleeding attributes in literature, and the effect of each attribute depends on the chosen difference of the levels.
The amount of blood loss following treatment was identified as an important attribute in our expert group, but was not included in our questionnaire as there is insufficient evidence supporting a difference in blood loss between treatment groups.1 Our aim was to gain more insight into the preferences for side effects and burden of both procedures, assuming the effectiveness of both treatment options is comparable. It is unknown to what extent the importance scores of the other attributes would have been affected if this attribute was added to our DCE with a constant level across all choice sets or with theoretically different levels of blood loss reduction.
IImmpplliiccaattiioonnss ffoorr cclliinniiccaall pprraaccttiiccee
The attribute with the most influence on the women’s decisions appeared to be a treatment without hormones. Possible reasons that women avoid a hormone-containing treatment may be due to (expected) negative side effects or an insufficient knowledge about the systemic effects of the LNG-IUS compared to oral contraceptives. Another notable finding is that an irreversible option was preferred, which professionals consider a disadvantage of ablation. After endometrial ablation the uterine cavity is often inaccessible for less invasive reinterventions such as the LNG-IUS. A possible reason for this preference might be that most women referred to a gynaecologist want a definitive solution for their bleeding problem and expect to find this in an irreversible treatment. Before patients make a treatment choice, professionals should inform patients about
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the possible hormone-related side effects of the LNG-IUS and clearly explain that an irreversible treatment does not necessarily mean ‘more effective’.
The treatment preferences of women in primary care seem to differ from those of women referred to the gynaecologist. Previous studies have shown that severe symptoms and gynaecological consultations were associated with a preference for surgical treatment.15,32 It is possible that women recruited by a gynaecologist had more severe complaints or a pre-determined preference for ablation, as it is expected that GPs are more likely to refer patients that are dissatisfied with conservative treatment options. Women in primary care may have other desires and expectations regarding a treatment. Our findings on treatment preferences need to be confirmed in future studies in both primary and secondary care.
Although women differ in their individual treatment preference, all treatment characteristics tested in our DCE were found to be important to the respondents. Further research in other countries will give insight to whether these preferences are culture-related. This knowledge may be used in the development of decision aids to elicit a woman’s individual values and preferences and in counselling women in choosing a desirable treatment for HMB.
6
6
the possible hormone-related side effects of the LNG-IUS and clearly explain that an irreversible treatment does not necessarily mean ‘more effective’.
The treatment preferences of women in primary care seem to differ from those of women referred to the gynaecologist. Previous studies have shown that severe symptoms and gynaecological consultations were associated with a preference for surgical treatment.15,32 It is possible that women recruited by a gynaecologist had more severe complaints or a pre-determined preference for ablation, as it is expected that GPs are more likely to refer patients that are dissatisfied with conservative treatment options. Women in primary care may have other desires and expectations regarding a treatment. Our findings on treatment preferences need to be confirmed in future studies in both primary and secondary care.
Although women differ in their individual treatment preference, all treatment characteristics tested in our DCE were found to be important to the respondents. Further research in other countries will give insight to whether these preferences are culture-related. This knowledge may be used in the development of decision aids to elicit a woman’s individual values and preferences and in counselling women in choosing a desirable treatment for HMB.
1. Lethaby A, Hussain M, Rishworth JR, Rees MC. Progesterone or progestogen-releasing intrauterine systems for heavy menstrual bleeding. Cochrane Database Syst Rev. 2015 Apr 30;4:CD002126.
2. Shapley M, Jordan K, Croft PR. An epidemiological survey of symptoms of menstrual loss in the community. Br J Gen Pract. 2004 May;54(502):359-63.
3. Palep-Singh M, Prentice A. Epidemiology of abnormal uterine bleeding. Best Pract Res
Clin Obstet Gynaecol. 2007 Dec;21(6):887-90.
4. de Vries CJ, Meijer LJ, Janssen CA, Burgers JS, Opstelten W. [Dutch College of General Practitioners' practice guideline on 'Vaginal bleeding']. Ned Tijdschr Geneeskd. 2015;159(0):A8534.
5. National Collaborating Centre for Women's and Children's Health (UK). Clinical guideline Heavy menstrual bleeding - National Institute for Health and Clinical Excellence (NICE). London (UK): RCOG Press; 2018 Mar. Available at:
https://www.nice.org.uk/guidance/ng88.
6. NVOG. Guideline Hevig menstrueel bloedverlies (HMB) [In Dutch]. Nederlandse Vereniging voor Obstetrie en Gynaecologie. 2013.
7. Gupta J, Kai J, Middleton L, Pattison H, Gray R, Daniels J, et al. Levonorgestrel intrauterine system versus medical therapy for menorrhagia. N Engl J Med. 2013 Jan 10;368(2):128-37.
8. Bongers MY. Second-generation endometrial ablation treatment: Novasure. Best Pract
Res Clin Obstet Gynaecol. 2007 Dec;21(6):989-94.
9. Clark TJ, Samuel N, Malick S, Middleton LJ, Daniels J, Gupta JK. Bipolar radiofrequency compared with thermal balloon endometrial ablation in the office: a randomized controlled trial. Obstet Gynecol. 2011 Jan;117(1):109-18.
10. Herman MC, Penninx JP, Mol BW, Bongers MY. Ten-year follow-up of a randomised controlled trial comparing bipolar endometrial ablation with balloon ablation for heavy menstrual bleeding. BJOG. 2013 Jul;120(8):966-70.
11. Daniels JP. The long-term outcomes of endometrial ablation in the treatment of heavy menstrual bleeding. Curr Opin Obstet Gynecol. 2013 Aug;25(4):320-6.
12. Kennedy AD, Sculpher MJ, Coulter A, Dwyer N, Rees M, Abrams KR, et al. Effects of decision aids for menorrhagia on treatment choices, health outcomes, and costs: a randomized controlled trial. JAMA. 2002 Dec 4;288(21):2701-8.
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13. Bourdrez P, Bongers MY, Mol BW. Treatment of dysfunctional uterine bleeding: patient preferences for endometrial ablation, a levonorgestrel-releasing intrauterine device, or hysterectomy. Fertil Steril. 2004 Jul;82(1):160,6, quiz 265.
14. Leung PL, Ng PS, Tam WH, Yuen PM. Preference on the treatments for menorrhagia in Hong Kong chinese women. Gynecol Obstet Invest. 2005;59(2):97-101.
15. Vuorma S, Teperi J, Hurskainen R, Aalto AM, Rissanen P, Kujansuu E. Correlates of women's preferences for treatment of heavy menstrual bleeding. Patient Educ Couns. 2003 Feb;49(2):125-32.
16. Ryan M, Bate A, Eastmond CJ, Ludbrook A. Use of discrete choice experiments to elicit preferences. Qual Health Care. 2001 Sep;10 Suppl 1:i55-60.
17. Penninx JP, Herman MC, Mol BW, Bongers MY. Five-year follow-up after comparing bipolar endometrial ablation with hydrothermablation for menorrhagia. Obstet Gynecol. 2011 Dec;118(6):1287-92.
18. Abbott JA, Garry R. The surgical management of menorrhagia. Hum Reprod Update. 2002 Jan-Feb;8(1):68-78.
19. Barrington JW, Arunkalaivanan AS, Abdel-Fattah M. Comparison between the levonorgestrel intrauterine system (LNG-IUS) and thermal balloon ablation in the treatment of menorrhagia. Eur J Obstet Gynecol Reprod Biol. 2003 May 1;108(1):72-4. 20. Wheeler TL,2nd, Murphy M, Rogers RG, Gala R, Washington B, Bradley L, et al. Clinical
practice guideline for abnormal uterine bleeding: hysterectomy versus alternative therapy. J Minim Invasive Gynecol. 2012 Jan-Feb;19(1):81-8.
21. Cooper KG, Parkin DE, Garratt AM, Grant AM. A randomised comparison of medical and hysteroscopic management in women consulting a gynaecologist for treatment of heavy menstrual loss. Br J Obstet Gynaecol. 1997 Dec;104(12):1360-6.
22. Cox M, Tripp J, Blacksell S. Clinical performance of the levonorgestrel intrauterine system in routine use by the UK Family Planning and Reproductive Health Research Network: 5-year report. J Fam Plann Reprod Health Care. 2002 Apr;28(2):73-7.
23. Ewies AA. Levonorgestrel-releasing intrauterine system--the discontinuing story. Gynecol
Endocrinol. 2009 Oct;25(10):668-73.
24. Hurskainen R, Teperi J, Rissanen P, Aalto AM, Grenman S, Kivela A, et al. Clinical outcomes and costs with the levonorgestrel-releasing intrauterine system or hysterectomy for treatment of menorrhagia: randomized trial 5-year follow-up. JAMA. 2004 Mar 24;291(12):1456-63.
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25. Bongers MY, Bourdrez P, Mol BW, Heintz AP, Brolmann HA. Randomised controlled trial of bipolar radio-frequency endometrial ablation and balloon endometrial ablation. BJOG. 2004 Oct;111(10):1095-102.
26. Kleijn JH, Engels R, Bourdrez P, Mol BW, Bongers MY. Five-year follow up of a randomised controlled trial comparing NovaSure and ThermaChoice endometrial ablation. BJOG. 2008 Jan;115(2):193-8.
27. Louviere JJ, Hensher DA, Swait JD, editors. Stated choice methods: Analysis and applications. Cambridge, United Kingdom: Cambridge University Press; 2000.
28. Bridges JF, Hauber AB, Marshall D, Lloyd A, Prosser LA, Regier DA, et al. Conjoint analysis applications in health--a checklist: a report of the ISPOR Good Research Practices for Conjoint Analysis Task Force. Value Health. 2011 Jun;14(4):403-13.
29. Marshall D, Bridges JF, Hauber B, Cameron R, Donnalley L, Fyie K, et al. Conjoint Analysis Applications in Health - How are Studies being Designed and Reported?: An Update on Current Practice in the Published Literature between 2005 and 2008. Patient. 2010 Dec 1;3(4):249-56.
30. Orme B. Chapter 7: Sample Size Issues. In: Getting Started with Conjoint Analysis: Strategies for Product Design and Pricing Research. Second ed. Madison, Wis.: Research Publishers LLC; 2010.
31. Hole A. Stata module to fit mixed logit models by using maximum simulated likelihood. Statistical Software Components from Boston College Department of Economics. 2007. 32. Coulter A, Peto V, Doll H. Patients' preferences and general practitioners' decisions in the
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TTaabbllee SS11.. Development of DCE attributes
LLiisstt ooff ppoossssiibbllee aattttrriibbuutteess**
(Ir)reversibility of procedure Treatment contains hormones Probability of side effects, e.g.:
Dysmenorrhea, abdominal pain, pelvic pain Irregular or persistent menstrual blood loss Spotting
Acne
Vaginal discharge Headache
Painful or sensitive breasts Need for additional contraception
Need to repeat the procedure after five years
Health professional performing the procedure: general practitioner / gynaecologist Insertion of body foreign material
Anaesthesia during procedure
Possible reinterventions if treatment is unsuccessful
Amount of pain during procedure: Visual Analogue Scale (VAS) Costs of the procedure
Probability of amenorrhea
Probability of persistent heavy menstrual bleeding Short or no hospital admission
No complaints anymore after the procedure Uterus-saving procedure
Quick recovery from procedure / resumption of work Possible risks of the procedure
6
6
TTaabbllee SS11.. Development of DCE attributes
LLiisstt ooff ppoossssiibbllee aattttrriibbuutteess**
(Ir)reversibility of procedure Treatment contains hormones Probability of side effects, e.g.:
Dysmenorrhea, abdominal pain, pelvic pain Irregular or persistent menstrual blood loss Spotting
Acne
Vaginal discharge Headache
Painful or sensitive breasts Need for additional contraception
Need to repeat the procedure after five years
Health professional performing the procedure: general practitioner / gynaecologist Insertion of body foreign material
Anaesthesia during procedure
Possible reinterventions if treatment is unsuccessful
Amount of pain during procedure: Visual Analogue Scale (VAS) Costs of the procedure
Probability of amenorrhea
Probability of persistent heavy menstrual bleeding Short or no hospital admission
No complaints anymore after the procedure Uterus-saving procedure
Quick recovery from procedure / resumption of work Possible risks of the procedure
* In random order. Sources: literature search, interviews with gynaecologists, discussion in DCE expert group. DCE: Discrete Choice Experiment.
RReelleevvaanntt aattttrriibbuutteess ddeerriivveedd ffrroomm ppaattiieenntt iinntteerrvviieewwss ((nn==1122 ppaattiieennttss)) No vaginal blood loss
Previous experience with the LNG-IUS No invasive treatment
No need for a reintervention / repeat surgery Experience of friends with treatment options Pain during the procedure
Child-wish
Afraid to feel the LNG-IUS after insertion Fear of anaesthesia
No dysmenorrhea
Additional contraceptive effect Body foreign material
No hormones
LNG-IUS: levonorgestrel intrauterine system
PPaattiieenntt rraannkkiinngg ooff aattttrriibbuutteess -- ttoopp 1100 1. Probability of irregular bleeding 2. Pain during the procedure* 3. Probability of dysmenorrhea 4. Anaesthesia during the procedure* 5. Quick recovery from the procedure* 6. Treatment contains hormones 7. Procedure is reversible
8. Need to use additional contraception 9. Health professional performing the procedure 10. 10. Need to repeat the procedure after 5 years
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All respondents (n=20) indicated the above mentioned attributes as important, they did not miss an important attribute.
* Attributes excluded from the DCE, with reasons:
Pain during the procedure: no data is available of a significant difference in pain score between the LNG-IUD and endometrial ablation in the literature. Furthermore, a pain score is difficult to imagine and understand for patients and therefore less reliable to include in the DCE.
Anaesthesia during the procedure: (too) many possibilities for anaesthesia, and consequent attribute levels, for both treatments:
o Endometrial ablation: local anaesthesia (paracervical block) – spinal anaesthesia - general anaesthesia
o LNG-IUS: no anaesthesia – local anaesthesia – general anaesthesia
There is a contradiction in the patient desire for little to no pain and no anaesthesia. Ideally, if you include the attribute ‘anaesthesia’, you would also want to include the attribute ‘pain’, to investigate willingness to make trade-offs between these two attributes.
Quick recovery from the procedure: In contrast to a hysterectomy, there is a quick recovery after both the LNG-IUD insertion and endometrial ablation, with no relevant difference between the two treatments.
D
DCCEE –– SSeelleecctteedd aattttrriibbuutteess
1. Probability of irregular bleeding 2. Probability of dysmenorrhea 3. Treatment contains hormones 4. Procedure is reversible
5. Need to use additional contraception 6. Health professional performing the procedure
6
6
All respondents (n=20) indicated the above mentioned attributes as important, they did not miss an important attribute.
* Attributes excluded from the DCE, with reasons:
Pain during the procedure: no data is available of a significant difference in pain score between the LNG-IUD and endometrial ablation in the literature. Furthermore, a pain score is difficult to imagine and understand for patients and therefore less reliable to include in the DCE.
Anaesthesia during the procedure: (too) many possibilities for anaesthesia, and consequent attribute levels, for both treatments:
o Endometrial ablation: local anaesthesia (paracervical block) – spinal anaesthesia - general anaesthesia
o LNG-IUS: no anaesthesia – local anaesthesia – general anaesthesia
There is a contradiction in the patient desire for little to no pain and no anaesthesia. Ideally, if you include the attribute ‘anaesthesia’, you would also want to include the attribute ‘pain’, to investigate willingness to make trade-offs between these two attributes.
Quick recovery from the procedure: In contrast to a hysterectomy, there is a quick recovery after both the LNG-IUD insertion and endometrial ablation, with no relevant difference between the two treatments.
D
DCCEE –– SSeelleecctteedd aattttrriibbuutteess
1. Probability of irregular bleeding 2. Probability of dysmenorrhea 3. Treatment contains hormones 4. Procedure is reversible
5. Need to use additional contraception 6. Health professional performing the procedure
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