Composition Vendor Newgen KnowledgeWorks (P) Ltd. PLoS Med plos plosmed PLOS Medicine 1549-1277 1549-1676 Public Library of Science San Francisco, CA USA 10.1371/journal.pmed.1004522 PMEDICINE-D-24-04457 Research Article Medicine and health sciencesEuthanasia Medicine and health sciencesMental health and psychiatryDementia Medicine and health sciencesNeurologyDementia Medicine and health sciencesHealth carePalliative care Biology and life sciencesNeuroscienceCognitive scienceCognitive psychologyLanguage Biology and life sciencesPsychologyCognitive psychologyLanguage Social sciencesPsychologyCognitive psychologyLanguage Medicine and health sciencesHealth careHealth care facilitiesNursing homes Medicine and health sciencesEpidemiologyMedical risk factors People and placesPopulation groupingsAge groups Medicine and health sciencesHealth careHealth care providersPhysicians People and placesPopulation groupingsProfessionsMedical personnelPhysicians Trends in assisted dying among patients with psychiatric disorders and dementia in Belgium: A health registry study Assisted dying among patients with psychiatric disorders and dementia in Belgium https://orcid.org/0000-0002-9292-917X Wels Jacques Conceptualization Data curation Formal analysis Investigation Methodology Resources Software Supervision Validation Visualization Writing – original draft 1 2 * Hamarat Natasia Conceptualization Project administration Validation Writing – review & editing 2 3 University College London, Unit for Lifelong Health and Ageing (LHA), London, United Kingdom Université libre de Bruxelles, Health & Society Research Unit, Brussels, Belgium Université libre de Bruxelles, Centre de droit public et social, Brussels, Belgium Brayne Carol Academic Editor University of Cambridge, UNITED KINGDOM OF GREAT BRITAIN AND NORTHERN IRELAND * E-mail: w.jacques@ucl.ac.uk

I have read the journal’s policy and the authors of this manuscript have the following competing interests: NH is a member of the Federal Commission for the Control and Evaluation of Euthanasia (FCCEE); JW is a member of the user committee of the Belgian Health Data Agency (HDA). Neither the FCCEE nor the HAD were involved in the research protocol, writing or publication of the study.

 19112025 112025 22 11 e1004522 29122024 29102025 2025 Wels, Hamarat This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Background

Assisted dying and euthanasia (ADE) for patients with psychiatric disorders or dementia have increased in jurisdictions where the practice is legal. In this study, we examine trends in euthanasia cases involving patients with these conditions in Belgium, where the law makes a distinction based on whether a patient’s death is not expected in the foreseeable future (>12 months)—a common situation in cases of dementia or psychiatric disorders.

 Methods and findings

We use data on all cases of euthanasia reported to the Federal Commission for the Control and Evaluation of Euthanasia from 2002 (when the legislation was introduced) to 2023 (N = 33,592). Psychiatric disorders and dementia represent 1.27% and 0.92% of all cases, respectively. Using time-series zero-inflated negative binomial regression, we model trends by first examining interactions between euthanasia reasons and year, then extending to three-way interactions with patients’ characteristics. The model calculates change in count and is replicated with an offset to account for demographic changes and generate rates. Our results show that euthanasia for psychiatric disorders and dementia showed distinct trends over time. Although slightly increasing, euthanasia for psychiatric disorders followed trends similar to the other types of euthanasia (count = 1.00 [95%CI: 0.98; 1.03]—rate = 1.02 [95%CI: 0.99; 1.04]), while euthanasia cases for dementia increased faster than other types of euthanasia (count = 1.03 [95%CI: 1.00; 1.06]—rate = 1.04 [95%CI: 1.01;1.07]). Trends in euthanasia for dementia and psychiatric disorders coincide with demographic changes. While euthanasia rates for psychiatric disorders were initially higher among women, the rate among men has been increasing over time. Regional trends show higher overall euthanasia rates in the Dutch-speaking population, but with faster increases in the French-speaking population. A key limitation of this study is the lack of information on patients’ socio-economic profiles.

 Conclusions

In Belgium, between 2002 and 2023, there are distinct trends for euthanasia for non-terminal illnesses. Euthanasia for psychiatric disorders followed similar trends as euthanasia for terminal illnesses, whereas euthanasia cases involving cognitive conditions increased at a faster rate. Furthermore, there were gender and regional differences, which diminished over time.

 Author summary Why was this study done?

Assisted dying and euthanasia (ADE) for people with psychiatric disorders or dementia often raise ethical concerns, especially in countries considering legalisation.

We studied how often euthanasia is performed for these conditions in Belgium, where it has been legal since 2002.

 What did the researchers do and find?

We analysed all reported euthanasia cases in Belgium from 2002 to 2023, focussing on those involving psychiatric disorders or dementia.

These cases made up a small portion of all euthanasia cases—less than 2.5% combined. We found that euthanasia for psychiatric disorders has increased at a similar rate to all euthanasia cases, whereas cases of euthanasia for dementia have increased slightly more. There were gender and regional differences in these trends

 What do these findings mean?

Increase of cases of euthanasia for psychiatric disorders have increased in line with the total increase in cases for all other reasons while cases for dementia have increased more than other cases.

A major limitation of the study is the lack of data on patients’ socio-economic status.

In this registry study, Jacques Wels and Natasia Hamarat use data on all cases of euthanasia in Belgium between 2002-2023 to assess trends in assisted dying for patients with psychiatric disorders and dementia.

 http://dx.doi.org/10.13039/501100002661 Fonds De La Recherche Scientifique - FNRS MIS 40021242 https://orcid.org/0000-0002-9292-917X WelsJacques http://dx.doi.org/10.13039/501100002661 Fonds De La Recherche Scientifique - FNRS CQ 40010931 https://orcid.org/0000-0002-9292-917X WelsJacques http://dx.doi.org/10.13039/100014013 UK Research and Innovation UKRI1426 https://orcid.org/0000-0002-9292-917X WelsJacques JW reports funding from the Belgian National Scientific Fund (FNRS, https://www.frs-fnrs.be/en/) (Incentive Grant for Scientific Research (MIS), Grant 40021242; Research Associate (CQ) funding, Grant 40010931) and the UK Research and Innovation (UKRI, https://www.ukri.org) (Guarantee funding for Horizon Europe ERC grant, UHealth – Grant UKRI1426). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Data Availability Access can be granted upon request to the Federal Commission for the Control and Evaluation of Euthanasia (FCCEE): https://consultativebodies.health.belgium.be/en/advisory-and-consultative-bodies/federal-commission-control-and-evaluation-euthanasia. PLOS Publication Stage vor-update-to-uncorrected-proof Publication Update 2025-11-25 Background

A central point of contention in the debate surrounding the implementation or expansion of assisted dying and euthanasia (ADE) regulations concerns the permissibility of such practices for individuals with non-terminal illnesses. The discourse primarily focuses on two categories of conditions where death is not expected in the foreseeable future: dementia and other degenerative disorders, and severe psychiatric illnesses.

Empirical research on ADE using data is sparse [1], and much of the scientific literature—often consisting of opinion pieces [2,3]—relies on ethical debates [4]. When data are mobilised, they are often examined at a very descriptive level, focussing on ADE trends while overlooking changes in population structures [4,5]. We have recently demonstrated that failing to account for population change when analysing annual ADE cases can lead to trends that are overstated due to demographic shifts. For example, population ageing contributes to increased number of cases, as euthanasia rates are higher among older age groups [4].

The observed increase in cases fuel concerns about a gradual expansion of eligibility criteria, particularly leading to concerns regarding vulnerable patients [5–9]. These concerns are used as an argument against implementing ADE for non-terminal illness in other jurisdictions and as an argument in favour of introducing stricter safeguards [8–13].

The idea that eligibility criteria in ADE regulations are gradually expanded, or that vulnerable populations are at greater risk is not substantiated by empirical studies [14–16]. This does not mean that sub-groups differences in ADE do not exist and that trends are not evolving over time. Many studies have focussed on gender and regional discrepancies. For instance, it was shown that female patients are notably overrepresented in psychiatric cases, although these comprise a small fraction of total cases [17,18]. Gender disparities have been noted in the context of Belgian euthanasia data, which shows a relatively balanced distribution with females representing 49.6% of euthanasia cases in 2020 [19] and data on euthanasia as the ratio on all deaths by gender show similar rates among genders [20]. Regional differences have also been documented. For example, in the Netherlands, unexplained geographical variations in euthanasia incidence were observed across provinces. Factors such as age, church attendance, political orientation, income, self-perceived health, and availability of voluntary workers have been associated with these differences, yet a significant portion of the variation remains unexplained [21]. In Belgium, official statistics reveal higher propensities for euthanasia in the Flemish region [22], with most research predominantly focussed on Flanders [23,24].

Using administrative data on all euthanasia cases reported to the Belgian Federal Commission for the Control and Evaluation of Euthanasia (FCCEE) between 2002 and 2023, this study examines trends in the practice of euthanasia by addressing two research questions: (R.Q.1) How do trends in euthanasia cases involving psychiatric conditions and cognitive disorders compare with those for other reasons, such as terminal illness, and how does this comparison change when demographic composition is taken into account?; (R.Q.2) Are distinct patterns observable across population sub-groups, such as gender and region?

 Data and methods Ethics statement

The data used in this study are fully anonymized and encompass all reported euthanasia cases since 2002. the Belgian FCCEE granted ethical approval on May 14, 2024. To obtain approval, we submitted a detailed research proposal to the FCCEE outlining the study objectives, methodology, and data protection measures. The Commission reviewed and approved the project, authorising access to anonymized data. This is done in full compliance with the 2002 Belgian law governing euthanasia and data protection. Consent to participate was waived by the FCCEE in accordance with Belgian regulations.

 Data

We use data routinely collected by the FCCEE, derived from individual reports submitted by euthanasia practitioners. These reports are fully anonymized and encompass all reported euthanasia cases since 2002, including information on the reasons for euthanasia, as well as the patients’ gender, age group, and language. The dataset includes 33,647 cases, representing all reported euthanasia cases in Belgium between 2002 and 2023. Since the euthanasia law was implemented in mid-2002, we exclude data from 2002 in our empirical models because the law was implemented in mid-2002 leading to low cases (N = 24). Additionally, 43 cases were removed due to incomplete information. No imputations were made to address the missing data, given the small proportion (0.1% of the total) and limited available information. The final sample includes 33,623 cases. Among these, 427 cases were justified by psychiatric disorders and 310 cases by dementia, i.e., respectively, 1.27% and 0.92% of all cases of euthanasia observed over the period.

The dataset contains aggregated count data stratified by multiple demographic, temporal, and contextual factors. Each row represents a unique combination of attributes, including year, language, gender, age, age group, location, and reason for the case. The primary variable of interest is the count of cases for each combination of factors, with an additional variable providing the total count of cases aggregated by year. The dataset is structured as a rectangular table, with each row corresponding to a unique combination of predictor variables, ensuring that all possible combinations are represented, including those with zero counts.

 Reasons for euthanasia

Under Belgian law, euthanasia is defined as the “act performed by a third party who intentionally ends a person’s life at that person’s request”. Eligible patients must experience “constant and unbearable physical or mental suffering that cannot be alleviated” resulting from a serious and incurable medical condition. The law imposes strict criteria, including the following: (1) the patient must be legally an adult or an emancipated minor, competent, and conscious when making the request; (2) the request must be voluntary, well-considered, repeated, and free from external pressure; (3) the patient must have a serious and incurable medical condition caused by illness or accident with no prospect of improvement; (4) they must be experiencing constant and unbearable physical or mental suffering that cannot be alleviated; (5) the patient must be fully informed about their condition, prognosis, treatment options, and palliative care; (6) the physician must confirm that all criteria are met and consult the treatment team; (7) an independent doctor must be consulted, and in non-terminal cases, also a psychiatrist or relevant specialist, with a 1-month waiting period; (8) the request must be made in writing by the patient; (9) the physician must submit the euthanasia declaration form to the FCCEE within four working days following the procedure, which retrospectively assesses legal compliance and may refer cases to the public prosecutor if necessary [25].

In other words, in cases of euthanasia when death is not expected in the foreseeable future (defined by the FCCEE as a period of 12 months or more)—such as for psychiatric disorders or dementia or cognitive conditions—a reinforced procedure applies. In this case, a second physician (i.e., independent psychiatrist or specialist in the condition prompting the euthanasia) should be consulted, and a mandatory waiting period applies [25]. Euthanasia is typically administered intravenously, but rare cases of supervised self-administration exist (0.3% of all cases in 2022−2023 [26]).

Since 2014, the scope of the law has extended euthanasia access to non-emancipated minors under strict conditions. The minor must demonstrate the capacity for discernment, be suffering from a physical (not psychiatric) condition that is incurable and leads to death in the near term, and receive the explicit consent of their parents or legal representatives. These cases are rare, with five recorded between 2014 and 2023 [26]. Therefore, they are excluded from this study.

The FCCEE identifies 12 medical conditions that may justify euthanasia (post-coded based on specific conditions mentioned by the medical practitioner on the euthanasia certificate) [27]: cancer and tumours, multimorbidity, nervous system diseases, psychiatric disorders, dementia (cognitive disorders), diseases of the respiratory system, diseases of the circulatory system, diseases of the genitourinary system, diseases of the digestive system, haematological disorders, endocrine, nutritional, and metabolic diseases, musculoskeletal and connective tissue diseases. We maintain the FCCEE’s distinction between psychiatric and cognitive disorders due to their differing clinical profiles. For analytical purposes, we group the reasons for euthanasia into three broad categories: (1) psychiatric disorders, (2) dementia and (3) all other justifications, excluding psychiatric disorders and dementia.

It should be noted that cases involving multimorbidity may include dementia or psychiatric disorders. Among patients who received euthanasia with a multimorbidity profile between 2002 and 2023, 11.3% had psychiatric disorders and 4.9% had dementia or memory disorders. However, with an average number of recorded conditions per patient of between 2.5 and 3, these pathologies co-occurred with other illness(es) and these cases were excluded from this study.

For the purposes of this paper, “assisted dying” serves as an umbrella term for assisted dying, assisted suicide and euthanasia. The term “euthanasia” is used when discussing Belgium, in alignment with its statutory language [28].

 Covariates

The dataset includes several key variables for analysis. The year of euthanasia, recorded from 2002 to 2023, is used as a continuous variable (coded 0–22) in main analyses, with a sensitivity check treating it as categorical to address non-linear trends. Age is categorised into eight groups—15–29, 30–39, 40–49, 50–59 (reference), 60–69, 70–79, 80–89, and 90+—to ensure anonymity. Gender, reported by the medical practitioner, is recorded as male or female (reference). To account for regional differences within Belgium’s federal structure, we include language data (Dutch or French, reference) used by the reporting practitioner, as place of residence was inconsistently collected.

Additional variables type of unbearable suffering (physical, reference; mental; or both), basis for euthanasia (advanced request, made beforehand and valid in cases of irreversible coma, or actual request, which must be reaffirmed by the patient at the time of euthanasia, reference), and place of death, categorised as home (reference), hospital, care home, palliative care, or other. We also include a variable on the term of death (expected within a year (reference) or longer), as the Belgian law distinguishes between death expected in the near term and death that is not, which determines whether a standard or reinforced procedure applies (involving the attending physician and two other physicians independent from each other and from the patient, including a psychiatrist or specialist, and a mandatory 1-month delay between the written request and the act). Only patients with non-evolving or very slowly progressive conditions are considered to fall under the latter [25].

 Population offset

We generate population figures based on demographic data retrieved from Federal Agency for National Statistics (Statbel). This data includes information on the total population as of January 1st for each selected year (2002–2023), broken down by age group, sex, and region of residence. We chose to use population figures instead of the number of deaths by sub-group, as done in previous studies [5,21,29,30], because a non-negligible share of euthanasia is performed on patients not expected to die in the foreseeable future, including those with dementia or psychiatric disorders—14.4% of all cases in 2020–2021 [19]. The figures are calculated for each line of euthanasia counts by year, age, gender, and language, and are then used as offset in the model. Demographic data do not include information on language. To tackle this issue, the French-speaking population was calculated as the sum of the population residing in Wallonia and 90% of the population in Brussels and the Dutch-speaking as the sum of the Flanders residents and 10% of the Brussels population, reflecting the Belgian language repartition. This 10% figure is an estimate of the Dutch-speaking population residing in Brussels. In 2001, 8.4% of Brussels residents were born in Flanders, and this proportion has slightly increased over time [31].

 Analyses

The dataset contains 126,720 lines in total, with each line reporting the number of euthanasia cases (including zero counts). These lines represent combinations of population characteristics (gender [2] × language [2] × age group [8] = 32) and euthanasia characteristics (reason [3] × place of death [5] × type of suffering [3] × term of death [2] × basis of euthanasia [2] = 180) across 22 years.

To examine trends in euthanasia case counts across demographic and clinical subgroups, we employed zero-inflated negative binomial (ZINB) regression models [31] using the glmmTMB package in R [32]. Original analyses were made using Poisson Regression modelling. We used ZINB following reviewers’ recommendations. The initial Poisson regression revealed substantial overdispersion—where the variance significantly exceeded the mean—violating the core assumptions of the Poisson model. Specifically, the dispersion ratio was considerably greater than 1 (see S1 File). In contrast, negative binomial models, based on the “nbinom2” parameterisation, substantially reduced overdispersion, indicating improved model fit. This formulation models the variance as a quadratic function of the mean: Var(Y) = μ + μ2/θ, making it well-suited to count data with moderate to high overdispersion.

Because excess zeros in the data due to low cases among the population, we specified a zero-inflated component in the models [33,34]. Specifically, we included age group, gender, and language group as predictors in the zero-inflation formula to account for differential probabilities of observing structural zeros across subpopulations. This approach allowed us to model both the count process and the zero-generating process simultaneously, offering a more nuanced and accurate representation of the data-generating mechanisms. We only report results from the main model in this study.

Our primary count model included a two-way interaction between year (treated as a continuous variable) and reason for euthanasia, controlling for age-groups, gender, and languages. To account for variability in the underlying population at risk across different strata, we estimated two versions of each model: one without an offset term (model 1)—interpretable as modelling expected case counts—and one including a log-offset for the relevant population denominator (model 2), thereby modelling incidence rates.

In Model 1 (without offset), the exponentiated coefficients represent multiplicative changes in the expected number of euthanasia cases (count) associated with a one-unit increase in the predictor variables. For example, if the exponentiated coefficient for year is 1.05, this suggests that each additional year is associated with a 5% increase in the expected euthanasia count, assuming all other variables remain constant. Similarly, categorical predictors (e.g., gender or age groups) compare the expected counts between groups. Importantly, this model treats the outcome purely as a count, without accounting for differences in population size.

In Model 2 (with offset), the exponentiated coefficients instead reflect changes in the rate of euthanasia per unit of the offset variable (i.e., sub-groups population size). Here, a coefficient of 1.05 for year would mean that each additional year corresponds to a 5% increase in the euthanasia rate (number of cases relative to the offset), holding other variables constant. This model is more appropriate when the underlying population size influences the observed counts and to isolate the effects of predictors on the rate rather than the raw count.

Similarity in estimates between the two models would suggest that the sub-groups populations have limited variability across observations, meaning population size does not substantially modify the observed relationships. If the offset variable is highly variable, the coefficients in Model 2 would adjust for these disparities, potentially diverging from Model 1.

To explore how temporal trends in euthanasia case counts might differ across demographic or clinical subgroups, we further estimated extended models incorporating three-way interactions between year, reason for euthanasia, and each covariate of interest controlling only for socio-demographic variables (i.e., gender, region, age-group). For transparency, we calculated 95% confidence intervals (CIs) for each model. Additionally, due to low counts in some sub-categories, the 95% CIs could not be calculated because of convergence issues.

This study is reported as per the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guideline (S1 Checklist).

 Results

Table 1 exhibits the number of euthanasia cases by reason, distinguishing between dementia, psychiatric disorders, and other causes from 2002 to 2023. To ensure anonymity and avoid low counts (<3), the years 2002–2007 (the first 6 years following legalization) are grouped into a single category. Euthanasia cases for dementia or psychiatric disorders are reported 100 times less frequently than for other reasons, such as cancer or comorbidities, while following a similar trend to these more common cases. Over the selected period, psychiatric disorders and dementia represent 1.27% and 0.92% of all cases, respectively, and followed similar trends to the overall number of cases.

10.1371/journal.pmed.1004522.t001Yearly count of reported cases of euthanasia by reason.
Terminal illness Dementia Psychiatric disorders Total
Year Count Percent Count Percent Count Percent
2002–2007 1,908 99.38 6 0.31 6 0.31 1,920
2008 695 98.86 5 0.71 3 0.43 703
2009 804 98.17 6 0.73 9 1.10 819
2010 928 98.10 8 0.85 10 1.06 946
2011 1,099 97.52 14 1.24 14 1.24 1,127
2012 1,384 96.92 14 0.98 30 2.10 1,428
2013 1,760 97.24 13 0.72 37 2.04 1,810
2014 1,866 96.78 18 0.93 44 2.28 1,928
2015 1,959 96.88 20 0.99 43 2.13 2,022
2016 1,988 98.03 11 0.54 29 1.43 2,028
2017 2,273 98.27 14 0.61 26 1.12 2,313
2018 2,303 97.63 22 0.93 34 1.44 2,359
2019 2,608 98.16 26 0.98 23 0.87 2,657
2020 2,401 98.20 23 0.94 21 0.86 2,445
2021 2,647 98.11 27 1.00 24 0.89 2,698
2022 2,898 97.71 42 1.42 26 0.88 2,966
2023 3,334 97.40 41 1.20 48 1.40 3,423
Total 32,855 97.81 310 0.92 427 1.27 33,592
(R.Q.1) How do trends in euthanasia cases involving psychiatric conditions and cognitive disorders compare with those for other reasons, such as terminal illness, and how does this comparison change when demographic composition is taken into account?

We present the exponentialized coefficients, i.e., the counts (without demographic offset) and rates (with demographic offset) and 95%CI in Table 2. The main model includes a two-way multiplicative interaction term between the year cases were reported and reason for euthanasia. Other models use a three-way interaction including, respectively, gender, region, basis for euthanasia (i.e., whether the request was made in advance or not), expected term of death, type of suffering and place of death. The full results are shown in S2–S8 Files.

10.1371/journal.pmed.1004522.t002Relative risks (RR) and Incidence Ratios (IR) of the two-way and three-way interactions.
Count Rate Count Rate
Main model Exp(B) (95% CI) Exp(B) 95%CI Type of suffering (Ref.: physical) Exp(B) (95% CI) Exp(B) 95%CI
Year 1.075 (1.06; 1.091) 1.044 (1.036; 1.053) Year 1.043 (1.032; 1.054) 1.025 (1.014; 1.036)
Dementia 0.028 (0.018; 0.044) 0.024 (0.015; 0.037) Dementia 0.021 (0.005; 0.082) 0.021 (0.005; 0.081)
Psychiatric disorders 0.071 (0.05; 0.102) 0.065 (0.045; 0.095) Psychiatric disorders 0.016 (0.003; 0.08) 0.016 (0.003; 0.079)
Year × Dementia 1.032 (1.003; 1.062) 1.044 (1.014; 1.074) Mental 0.247 (0.189; 0.323) 0.244 (0.187; 0.319)
Year × Psychiatric disorders 1.004 (0.98; 1.029) 1.016 (0.99; 1.042) Both 2.304 (1.939; 2.738) 2.302 (1.936; 2.738)
Gender (ref.: Female) Year × Dementia 0.937 (0.846; 1.037) 0.936 (0.846; 1.036)
Year 1.077 (1.066; 1.089) 1.071 (1.058; 1.084) Year × Psychiatric disorders 0.929 (0.823; 1.047) 0.928 (0.824; 1.046)
Dementia 0.03 (0.016; 0.055) 0.035 (0.019; 0.062) Year × mental 0.897 (0.879; 0.916) 0.898 (0.88; 0.916)
Psychiatric disorders 0.092 (0.058; 0.148) 0.101 (0.064; 0.157) Year × both 1.026 (1.014; 1.038) 1.026 (1.014; 1.038)
Male 1.459 (1.175; 1.812) 1.659 (1.382; 1.992) Dementia × mental 7.706 (1.69; 35) 7.932 (1.75; 35)
Year × Dementia 1.026 (0.987; 1.068) 1.017 (0.979; 1.057) Psychiatric disorders × mental 39.208 (7.318; 210) 40.198 (7.567; 213)
Year × Psychiatric disorders 1.016 (0.984; 1.049) 1.007 (0.976; 1.038) Dementia × both 0.659 (0.139; 3.126) 0.665 (0.141; 3.131)
Year × Male 0.975 (0.962; 0.988) 0.988 (0.976; 1) Psychiatric disorders × both 1.379 (0.242; 7.857) 1.392 (0.246; 7.864)
Dementia × Male 0.588 (0.237; 1.461) 0.679 (0.283; 1.63) Year × Dementia × mental 1.283 (1.149; 1.432) 1.281 (1.148; 1.43)
Psychiatric disorders × Male 0.387 (0.173; 0.867) 0.41 (0.19; 0.884) Year × Psychiatric disorders × mental 1.252 (1.104; 1.42) 1.252 (1.105; 1.419)
Year × Dementia × Male 1.038 (0.98; 1.101) 1.025 (0.97; 1.084) Year × Dementia × both 1.092 (0.976; 1.222) 1.091 (0.976; 1.22)
Year × Psychiatric disorders × Male 1.005 (0.952; 1.06) 0.997 (0.947; 1.05) Year × Psychiatric disorders × both 1.071 (0.942; 1.219) 1.071 (0.943; 1.217)
Region (ref.: FR) Place (ref.: home)
Year 1.098 (1.082; 1.115) 1.092 (1.078; 1.106) Year 1.152 N/C 1.07 (1.058; 1.082)
Dementia 0.014 (0.005; 0.042) 0.014 (0.005; 0.042) Dementia 0.037 N/C 0.026 (0.013; 0.051)
Psychiatric disorders 0.002 (0; 0.011) 0.002 (0; 0.011) Psychiatric disorders 0.093 N/C 0.085 (0.049; 0.15)
NL 5.196 (4.246; 6.358) 3.403 (2.804; 4.129) Hospital 1.452 N/C 1.474 (1.217; 1.787)
year × Dementia 1.068 (1.002; 1.139) 1.068 (1.002; 1.138) Palliative care 0.005 N/C 0.003 (0.002; 0.005)
year × Psychiatric disorders 1.175 (1.059; 1.303) 1.173 (1.058; 1.3) Nursing home 0.121 N/C 0.098 (0.078; 0.125)
year × NL 0.964 (0.952; 0.976) 0.96 (0.949; 0.972) Other 0.053 N/C 0.042 (0.031; 0.059)
Dementia × NL 2.099 (0.641; 6.875) 2.165 (0.662; 7.081) Year × Dementia 1.018 N/C 1.041 (0.996; 1.088)
Psychiatric disorders × NL 51.977 (7.634; 353.8) 50.855 (7.513; 344.2) Year × Psychiatric disorders 1.005 N/C 1.021 (0.982; 1.061)
Year × Dementia × NL 0.967 (0.9; 1.038) 0.963 (0.897; 1.034) Year × Hospital 0.964 N/C 0.962 (0.948; 0.975)
Year × Psychiatric disorders × NL 0.863 (0.775; 0.96) 0.865 (0.777; 0.962) Year × Palliative care 1.144 N/C 1.184 (1.152; 1.218)
Basis (Ref.: not advanced) Year × Nursing home 1.06 N/C 1.061 (1.044; 1.078)
Year 1.134 N/C 1.042 (1.034; 1.051) Year × Other 0.98 N/C 0.994 (0.973; 1.017)
Dementia 0.031 N/C 0.022 (0.014; 0.035) Dementia × Hospital 0.572 N/C 0.591 (0.206; 1.692)
Psychiatric disorders 0.077 N/C 0.069 (0.047; 0.1) Psychiatric disorders × Hospital 0.458 N/C 0.445 (0.182; 1.087)
Advanced 0.047 N/C 0.041 (0.032; 0.054) Dementia × Palliative care 0 N/C 0 N/C
Year × Dementia 1.022 N/C 1.049 (1.018; 1.08) Psychiatric disorders × Palliative care 0 N/C 0 (0; 72038.79)
Year × Psychiatric disorders 0.996 N/C 1.013 (0.988; 1.04) Dementia × Nursing home 2.793 N/C 3.251 (0.96; 11.003)
Year × advanced 0.912 N/C 0.923 (0.905; 0.941) Psychiatric disorders × Nursing home 2.446 N/C 2.401 (0.834; 6.908)
Dementia × advanced 4.104 N/C 5.508 (1.191; 25.4) Dementia × Other 0.703 N/C 0.796 (0.06; 10.59)
Psychiatric disorders × advanced 0 N/C 0.334 N/C Psychiatric disorders × Other 1.057 N/C 0.921 (0.214; 3.967)
Year × Dementia × advanced 0.978 N/C 0.956 (0.855; 1.07) Year × Dementia × Hospital 1.004 N/C 1.005 (0.938; 1.077)
Year × Psychiatric disorders × advanced 0.616 N/C 0.002 N/C Year × Psychiatric disorders × Hospital 0.993 N/C 0.99 (0.93; 1.054)
Term of death Ref.: short-term) Year × Dementia × Palliative care 18,325 N/C 20,316 N/C
Year 1.137 (1.128; 1.145) 1.068 (1.042; 1.094) Year × Psychiatric disorders × Palliative care 3.37 N/C 3.343 (0.556; 20.09)
Dementia 0.018 (0.009; 0.039) 0.016 (0.007; 0.035) Year × Dementia × Nursing home 0.958 N/C 0.96 (0.889; 1.036)
Psychiatric disorders 0.007 (0.002; 0.023) 0.006 (0.002; 0.021) Year × Psychiatric disorders × Nursing home 0.913 N/C 0.915 (0.852; 0.983)
Not short-term 0.073 (0.062; 0.086) 0.068 (0.056; 0.083) Year × Dementia × Other 1.066 N/C 1.059 (0.908; 1.236)
Year × Dementia 0.939 (0.89; 0.992) 0.951 (0.9; 1.005) Year × Psychiatric disorders × Other 1.089 N/C 1.092 (0.997; 1.196)
Year × Psychiatric disorders 0.942 (0.868; 1.023) 0.954 (0.878; 1.037)
Year × Not short-term 1.054 (1.042: 1.067) 1.058 (1.044; 1.072)
Dementia × Not short-term 16.143 (6.4; 40) 16.971 (6.6; 43.1)
Psychiatric disorders × Not short-term 125.2 (36.3; 430.9) 146.462 (41.5; 515)
Year × Dementia × Not short-term 1.056 (0.991; 1.125) 1.053 (0.988; 1.123)
Year × Psychiatric disorders × Not short-term 1.023 (0.939; 1.116) 1.016 (0.931; 1.109)

Note: N/C denotes non-convergence.

The main model investigated the two-way interaction between the reason for euthanasia and time, comparing trends for psychiatric disorders and dementia to “other” reasons, which serve as the reference category. The findings indicate that euthanasia for dementia has shown a modest but significant annual increase relative to “other” reasons. The interaction term between “year” and “dementia” cases is 1.03 in the model without offset (year × dementia, count = 1.03 [95%CI: 1.00; 1.07]) and 1.04 in the model with offset (rate = 1.04 [95%CI: 1.01; 1.07]). This result suggests that euthanasia for dementia-related cases is becoming relatively more common over time compared to “other” reasons. In contrast, the trend for psychiatric disorders remains relatively stable, although a slight increase is observed when the model includes an offset (year × psychiatric disorders, RR = 1.00 [95%CI: 0.98; 1.03]; IR = 1.02 [95%CI: 0.99; 1.04]). This finding highlights that psychiatric disorders have not followed the same increasing trajectory as dementia when compared to “other” reasons.

Fig 1 plots the expected counts and rates of the main model. In the left panel, the predicted counts (without offset) show a curved pattern over time because they reflect both changes in the underlying risk of the event and fluctuations in the population size. In contrast, the right panel shows predicted rates (with offset), which adjust for population size and therefore isolate the trend in the individual risk of the event. The difference between predicted rates with and without adjustment for population composition and change suggests that population change may partially underlie changes observed in euthanasia prevalence. Furthermore, the rate of change is relatively similar when comparing euthanasia for psychiatric disorders to the other types of causes, but the increase is sharper for dementia.

10.1371/journal.pmed.1004522.g001Predicted counts and rates of euthanasia for dementia, psychiatric disorders and other causes by year (2003–2023), negative binomial regression (and 95%CI).

We have replicated the main model using year as a factor variable (i.e., calculating the rates separately for each time points) with no significant difference observed as can be seen in S9 File).

 (R.Q.2) Are distinct patterns observable across population sub-groups?

The three-way model looking at gender revealed notable differences in trends. We observe overall lower prevalence in male in euthanasia for dementia and psychiatric disorders (Dementia × Male, rate: 0.68 [95%CI: 0.28; 1.63]—Psychiatric disorders × Male: 0.41 [95%CI: 0.19; 0.88]). The trend was relatively stable for psychiatric disorders, but the prevalence of euthanasia for dementia among male patients has increased over time (Year * Dementia × Male: 1.02 [95%CI: 0.97; 1.08]).

Regional patterns between the Dutch-speaking region (NL—the Flanders) and the French-speaking region (Wallonia–Brussels) also emerged. Dementia-related euthanasia are more often observed in the Flanders (dementia × NL, rate = 2.16 (95%CI: 0.66; 7.08)), but the rate for psychiatric disorders is particularly high (Psychiatric disorders × NL, rate: 50.85 (95%CI: 7.51; 344.2) indicating that cases of euthanasia for psychiatric disorders and dementia are less often observed in Wallonia and Brussels. However, the rate of change is lower for the Flanders compared to Wallonia–Brussels over the selected period (Year × Dementia × NL, rate: 0.96 [95%CI: 0.90; 1.03] − Year × Psychiatric disorders × NL, rate: 0.865 [95%CI: 0.78; 0.96].

Analyses of the basis of euthanasia (i.e., advanced or not) cause non-convergence issues because of the low count observed for dementia and psychiatric disorder cases. Estimates show a higher rate for dementia with advanced request when looking at the two-way interaction, but this is balanced by below-1 rates for the main term and the three-way interaction. In other words, neither dementia nor psychiatric disorders are associated with advanced request and this has not changed over the selected period.

Mental suffering was higher in cases of euthanasia for dementia and psychiatric disorders compared to non-psychiatric/dementia cases (dementia × mental suffering, rate = 7.93 [95%CI: 1.75; 35]) − Psychiatric disorders × mental suffering, rate = 40.198 [95%CI: 7.57; 213]).

The three-way interaction with the place of death is less easy to interpret given the low count observed of euthanasia for psychiatric disorders and dementia. What can be observed is that euthanasia for both psychiatric and dementia reasons is more prevalent at home than in hospital or palliative care settings. Data indicate a potential increase of euthanasia for dementia and psychiatric disorders in palliative care, but low counts lead to convergence issue and this trend should be taken with caution. Unsurprisingly, euthanasia for dementia is more likely to occur in a nursing home than at home (rate = 3.25 [95%CI: 0.96; 11.00]), but this is also the case of euthanasia for psychiatric disorders (rate = 2.40 [95%CI: 0.83; 6.91]).

To visualise these trends, Fig 2 presents the expected rates of euthanasia by gender, region, basis of request, and expected term of death.

10.1371/journal.pmed.1004522.g002Predicted Incidence Ratios of euthanasia by reason, year and gender, region, basis and term, 2003–2023.

A clear divergence emerges in terms of gender. Euthanasia due to psychiatric disorders has been consistently more prevalent among women since the beginning of the observed period, and the gap with men has slightly widened over time. In contrast, cases involving dementia were initially slightly more common among men, and this disparity has increased over time.

These cases have been more prevalent in the Dutch-speaking community than the French-speaking community, although this regional difference has diminished over time. Furthermore, we observed that most of the increase in psychiatric and dementia-related euthanasia occurred in the French-speaking community.

Euthanasia for psychiatric disorders and dementia based on advance requests has not increased significantly. The rise in cases is largely attributable to actual (non-advance) requests.

 Discussion

Recent debates on the implementation of assisted dying in the United Kingdom and France have highlighted the distinction between euthanasia for terminal- and non-terminal causes, with both these countries considering implementation of euthanasia for terminal illnesses only, excluding patients with psychiatric disorders or degenerative conditions [35,36]. In contrast, Belgium euthanasia law has allowed euthanasia for non-terminal and non-physical illnesses from its inception in 2002, allowing us to compare rates in euthanasia for terminal illnesses, psychiatric disorders, and dementia.

These regulations would de facto exclude patients with psychiatric disorders or degenerative conditions such as dementia who may wish to request ADE. Opponents of such rights often argue that a narrowly defined assisted dying law would inevitably expand to include non-terminal illnesses, resulting in an over increase in cases. The Belgian experience, however, offers contextual insights into these concerns. From the outset, the Belgian law has allowed euthanasia for non-terminal and non-physical illnesses under specific safeguards, enforced by medical practitioners and monitored by the FCCEE.

Our study shows a significant, but still modest, increase in euthanasia for dementia. Furthermore, differences across genders and linguistic regions have declined over time. Trends show gradual implementation, with a steady yearly rate of change for psychiatric conditions and a slightly sharper but still modest increase for dementia. During the first 5 years following the implementation of the regulation, cases of euthanasia for psychiatric disorders and dementia remained infrequent. Differences in access across genders and linguistic regions have narrowed over time. In 2023, psychiatric disorders and dementia accounted for 1.4% and 1.2% of all cases, respectively.

Requests for euthanasia made in advance are rare and mainly associated with non-psychiatric and non-dementia conditions. Euthanasia on patients not expected to die in the foreseeable future have risen more sharply among those with ‘other” conditions groups rather than among those with psychiatric conditions. However, we observe a sharp increase in euthanasia for patients with dementia not expected to die in the foreseeable future. As cases remain low, it is difficult to draw any conclusion on future trends, but euthanasia seems to become more common among patients with dementia, living in care facilities, and not expected to die within a year.

This study has two major limitations.

A first limitation is about the data. Studies focussing on the Belgian context rely on administrative data collected by the FCCEE. The absence of social security identifiers in euthanasia records prevents data linkage with socio-economic information, while a lack of geographic data precludes sub-regional comparisons. The FCCEE acts as a commission controlling individual cases, not as an organism controlling euthanasia as a public policy. Critics of ADE regulations often focus on both the safeguards that should protect individuals and the trends that affect populations and sub-populations. This well-known distinction in public health between populations and individuals [37] reflects in the way data are collected in Belgium and policymakers should consider proactive data planning, including establishing data collection protocols, securing patient consent, ensuring data anonymization, enabling data linkage, and committing to independent research. Furthermore, this study focuses on administrative trends and does not address clinical, psychological, or qualitative dimensions.

A second limitation concerns the methods used to analyse ADE figures. Compared to our previous work where we used a Poisson regression modelling [4], this study uses a zero-inflated binomial model. Count data exhibit excess zeros that are not well accounted for by the Poisson distribution and the binomial model is appropriate when counts are bounded by a known total. We observe no significant differences in trends across both models but the Poisson distribution tends to reduce the trends observed of psychiatric disorders while a relative increase is observed in this study. Analyses on small counts may be sensitive to the model used, and we encourage researchers to compare different models to strengthen their findings.

Concerns have been raised, both in parliamentary debates [38] and within professional medical bodies, that permitting euthanasia in limited cases (e.g., terminal illness) may gradually lead to less justified applications, and whether safeguards are effectively maintained when euthanasia is extended to non-terminal conditions or psychiatric disorders [39]. While we acknowledge that empirical data cannot resolve ethical and normative questions, our findings demonstrate that euthanasia for psychiatric and cognitive conditions, which has been legally permissible in Belgium since 2002, has not substantially increased between 2002 and 2023. These findings can add to the discussion of end-of-life issues and their inherent complexities.

 Supporting information Comparison between Poisson and negative binomial models for the main outcomes.

(DOCX)

 Zero-inflated negative binomial regression of Reason by Year (two-way interaction) and Predicted counts and rates.

(DOCX)

 Zero-inflated negative binomial regression of Reason by Year and Gender (three-way interaction) and Predicted counts and rates.

(DOCX)

 Zero-inflated negative binomial regression of Reason by Year and Region (three-way interaction) and Predicted relative risks and incidence ratios.

(DOCX)

 Zero-inflated negative binomial regression of Reason by Year and basis (three-way interaction) and Predicted counts and rates.

(DOCX)

 Zero-inflated negative binomial regression of Reason by Year and expected term of death (three-way interaction) and Predicted counts and rates.

(DOCX)

 Zero-inflated negative binomial regression of Reason by Year and type of suffering (three-way interaction) and Predicted relative risks and incidence ratios.

(DOCX)

 Zero-inflated negative binomial regression of Reason by Year and place of death (three-way interaction).

(DOCX)

 Zero-inflated negative binomial regression, predicted counts and rates of Reason by Year (factor) (two-way interaction).

(DOCX)

 DOI: 10.1016/j.jclinepi.2007.11.008.

(DOCX)

 Abbreviations ADE

Assisted dying and euthanasia

CIs

confidence intervals

FCCEE

Federal Control and Evaluation Commission on Euthanasia

STROBE

Strengthening the Reporting of Observational Studies in Epidemiology

ZINB

zero-inflated negative binomial

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Health Policy. 2009;90(2–3):181–7. doi: 10.1016/j.healthpol.2008.10.003 19019485 10.1371/journal.pmed.1004522.r001 Decision Letter 0 De Bruijn Suzanne Senior Editor 2025 Suzanne De Bruijn This is an open access article distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Submission Version 0

7 Jan 2025

Dear Dr Wels,

Thank you for submitting your manuscript entitled "Addressing the Slippery Slope Argument: Trends in Euthanasia Among Patients with Psychiatric Disorders and Dementia in Belgium, 2002–2023" for consideration by PLOS Medicine.

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Senior Editor

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 10.1371/journal.pmed.1004522.r002 Decision Letter 1 De Bruijn Suzanne Senior Editor 2025 Suzanne De Bruijn This is an open access article distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Submission Version 1

17 Mar 2025

Dear Dr Wels,

Many thanks for submitting your manuscript "Addressing the Slippery Slope Argument: Trends in Euthanasia Among Patients with Psychiatric Disorders and Dementia in Belgium, 2002–2023" (PMEDICINE-D-24-04457R1) to PLOS Medicine. The paper has been reviewed by subject experts and a statistician; their comments are included below and can also be accessed here: [LINK]

As you will see, the reviewers thought this data is valuable, but they also have several major concerns about the study. After discussing the paper with the editorial team and an academic editor with relevant expertise, I'm pleased to invite you to revise the paper in response to the reviewers' comments. In this revision, we would like you to address all reviewer comments. Specifically, we will require the article to be revised to ensure the language is objective in discussing the data. We also ask you to include the relevant literature cited by the reviewers and we would ask you to discuss circumstances that may have influenced euthanasia cases in this time frame, specifically the court case that occurred during the analysed time frame. Although we won't require it, it may also be beneficial to get input from an ethicist. We plan to send the revised paper to some or all of the original reviewers, and we cannot provide any guarantees at this stage regarding publication.

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Suzanne

Suzanne De Bruijn, PhD

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Comments from the academic editor:

Very interesting set of reviews, all with very legitimate points. I think neutrality of presentation is one clear message coming out of them. The authors should step back and consider their own biases which influence readers, manifest in the language. They should also clearly describe the limitations of this study.

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Comments from the reviewers:

Reviewer #1: "Addressing the Slippery Slope Argument: Trends in Euthanasia Among Patients with Psychiatric Disorders and Dementia in Belgium, 2002-2023" analyzed data on all reported cases of euthanasia in Belgium over about two decades via time-series Poisson regression, to determine whether euthanasia trends for psychiatric disorders and dementia indicate a possible "slippery slope". It was found that while euthanasia rates for psychiatric disorders followed similar trends as for other types of euthanasia, dementia had a slight over-increase only partly explained by demographic change. Nevertheless, it was concluded that there was no evidence of significant misuse of euthanasia regulations allowing for non-terminal psychiatric conditions.

While informative, some issues might be considered:

1. Some additional details could be included in the Introduction, to establish the context. In particular,

a) How is euthanasia administered, and what is the typical waiting time between the initial request(s), approval, and administration?

b) Would withdrawal of care count as euthanasia for terminally-ill patients?

c) Is there any specific definition of terminal illness, in terms of expected remaining lifespan and/or suffering?

2. In the Data subsection, it is stated that "The dataset contains aggregated count data stratified by multiple demographic, temporal, and contextual factors. Each row represents a unique combination of attributes, including year, language, gender, age, age group, location, and reason for the case... The dataset is structured as a rectangular table, with each row corresponding to a unique combination of predictor variables, ensuring that all possible combinations are represented, including those with zero counts". This description might be clarified - does it mean that the dataset has 127 unique combinations of (the 7) attributes?

3. In the Reasons for euthanasia subsesction, it might be clarified as to whether the "multimorbidity" category applies whenever a patient would otherwise fall into two or more of the other categories (possibly including psychiatric disorders/dementia).

4. Further, it may be appropriate to consider the baseline prevalence of the various medical conditions, over the time period.

5. In the Population offset subsection, assumptions for language are stated. They might be further justified by relevant citations or otherwise, if possible.

Reviewer #2: See attached file

Reviewer #3: Summary:

This is a population-based register-analysis of aggregated data to investigate the alleged "slippery slope"-phenomena in euthanasia. Data from 2002, the year of initiating euthanasia in Belgium, to 2023 is used and incidence rates and -ratios are calculated to answer questions around the time trend of euthanasia for different underlaying diagnoses, with a particular focus on dementia and psychiatric illnesses. This type of scientific contribution is sorely needed in the field, the aim is admirable, and the analysis are ambitious but there are some clarifications needed, both in analytic approach and in presentation.

Major comments:

1. To me, the text is not objective, but biased in favour of euthanasia, in the choice of word and phrases, please consider revision. (A read-through by a "critical friend" might help)

2. Please clarify the aim in relation to the "slippery slope". Since euthanasia was allowed from the beginning for non-terminal illnesses, including psychiatric ones, in Belgium it is unclear to me what slippery slope that is investigated in the paper. Is it a question of inferring what the more ethically troublesome parts of euthanasia are, and looking into those diagnoses?

3. I acknowledge your take on statistical significance, it is a standpoint but not mine, in my mind Belgium is not the whole world, and 2002-2023 it not all time, therefore, if we wish to generalize the findings to other times and/or places, we need the statistical significance tests. They describe the uncertainty of the data and contribute important information. Especially if one would like to compare IRRs, to say that one is more pronounced than the other, but both estimates are based on very small numbers I think the CIs are very important indeed.

4. I find the analyses difficult to interpret (I note that the authors do not interpret their estimates in words either very much either). Since I am not a statistician, I suggest to the editor for your paper to go to statistical review, but I think there have to be more work done on the analysis, as this is not the customary way to do either IRR or interactions. I would suggest considering a structure like this:

Table 2: Incidence rates (IR) i.e. number of cases/100 000 person-years, for different subtypes of euthanasia, and the total, per year. Be clear in the heading of the table what is shown, the table (with heading and notes) should be self-explanatory.

Table 3: Incidence rate ratios (IRR). Give the estimate by year (e.g. IRR=1.03, there is 3% increase in the probability to die from euthanasia each year). Then, test the statistical significance of the interaction terms that you choose (e.g. There is a statistically significant interaction between year and reason for euthanasia, p=0.03). Then make dummy variables, perhaps grouping the years into categories (e.g. IRR for each year with dementia as reason: 1.02, IRR for each year with other reason: 1.03). (I do not at all require your paper to follow the above exactly, it is intended as a help to describe how an interaction analysis can be presented, I am sure there are many ways, but you current one does not work).

5. What does the first model, that calculate the "occurrence" (frequency?) of euthanasia, contribute with? Does this model take person-time at risk into account at all? Also, I do not find much value in the graphs unfortunately. What does "predicted" mean? Estimated?

6. Interactions are notoriously easy to preform statistically but hard to interpret, please consider excluding the three-way-interactions, (a hint of this is that you yourself state that it is hard to interpret, follow your gut in this case).

Minor comments:

7. Be clear in the year of study start, is it 2002 or 2003?

8. "Informed consent" on p.5 can't possibly be the correct term for requesting euthansia?

9. There are some missing references, e.g. Statbel and R.

10. The incidence rate is called a "prevalence rate" in the method.

11. Twelve medical conditions that are categorized into 7, that are then categorized again into 3: I am not certain that the description of the 7 categories adds value (Methods, p.8).

I reserve the right to add additional comments, primarily on wording, if the authors choose to submit a revised version of the manuscript.

Reviewer #4: This is a scholarly paper in that it uses sophisticated statistical techniques to provide some detailed analysis of complicated data. However, I think you have undermined the academic standing of the paper by your focus (in the paper's title and in its content) on the slippery slope argument. You could publish your results without any reference to the slippery slope argument, in which case the paper would provide something interesting for the research community to ponder. Unfortunately, the focus on the slippery slope argument means that the whole endeavour is wasted.

For a start, if you are going to use your data to attack or undermine the slippery slope argument, you should start with the best account of that argument that you cane find. Instead, you provide only a cursory definition of the argument. Indeed, right from the start (p. 4) you assert that the argument is "fallacious". If the argument is so obviously fallacious, why bother to say anything further. But the argument is not obviously "fallacious". Indeed, in the best hands, there are two aspects to the argument (it's perhaps better to refer to "arguments" in the plural), an empirical aspect and a logical aspect (see Keown (2018) 'Euthanasia, Ethics and Public Policy' pp. 67-89). You might say that you are obviously only applying your analysis to the empirical argument. But that would leave the other aspects of the argument(s) intact, so you would not have achieved your objective and your conclusions would be wrong. In any case, although empirical data can be relevant to the argument, in the end the argument is a normative one which needs to be addressed at a conceptual level not at a statistical one.

There is a very basic point to be made about how the Belgian law demonstrates a slippery slope. The law was passed in 2002 to allow voluntary active euthanasia. Then, in 2014 the Euthanasia Act was amended to allow euthanasia for minors. In so doing, Belgium slid some way down a slippery slope. Full stop. We don't need any further empirical analysis. The eligibility criteria have been extended in keeping with the slippery slope argument(s). But there are lots of other ways in which this slippage can be demonstrated: the move from serious and incurable disorders to multiple disorders, the stretching of the notion of suffering, the inclusion of physician-assisted suicide, and so on. Keown (2018) discusses all of this in some detail (pp.298-325) in a chapter entitled 'Belgium's lack of effective control'. Proper academic discussion of the issue would surely need to include some mention of Keown (2018), where there are two chapter devoted purely to the experience in Belgium. Moreover, I would also have expected some discussion of the book 'Euthanasia and Assisted Suicide: Lessons from Belgium' edited by Jones, Gastmans and MacKellar and published in 2017. One of the things that these works highlight is the number of cases of euthanasia which are not reported, which would also be relevant to a discussion of the possibility of slippery slopes.

There is another point. Whenever euthanasia or assisted suicide are legalised in a country, the rates of "assisted dying" gradually rise. Those against "assisted dying" point to this increasing prevalence as a sign that it is getting out of control; those in favour argue that one would expect the prevalence to increase and suggest it shows that "assisted dying" is acceptable. But, of course, the numbers don't on their own tell us anything, because we don't know what the normal prevalence should be; and, moreover, there is no way of knowing. What is normal here requires an evaluative decision. We need a completely different type of research to say whether or not the prevalence is (normatively) high or low. The same sort of difficulty faces your research. But in any case, the evidence that there is some sort of slippery slope in Belgium is apparent and is not simply based on opinion.

Any attachments provided with reviews can be seen via the following link: [LINK]

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* Please state in the Methods section whether the study had a prospective protocol or analysis plan. If a prospective analysis plan (from your funding proposal, IRB or other ethics committee submission, study protocol, or other planning document written before analyzing the data) was used in designing the study, please include the relevant document(s) with your revised manuscript as a Supporting Information file to be published alongside your study and cite it in the Methods section. A legend for this file should be included at the end of your manuscript. If no such document exists, please make sure that the Methods section transparently describes when analyses were planned, and when/why any data-driven changes to analyses took place. Changes in the analysis, including those made in response to peer review comments, should be identified as such in the Methods section of the paper, with rationale.

Submitted filename: PLOSONE - review.docx

 10.1371/journal.pmed.1004522.r003 Author response to Decision Letter 2 Submission Version 2

9 May 2025

Submitted filename: Answers.docx

 10.1371/journal.pmed.1004522.r004 Decision Letter 2 De Bruijn Suzanne Senior Editor 2025 Suzanne De Bruijn This is an open access article distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Submission Version 2

30 Jun 2025

Dear Dr Wels,

Many thanks for submitting your manuscript "Trends in Assisted Dying Among Patients with Psychiatric Disorders and Dementia in Belgium" (PMEDICINE-D-24-04457R2) to PLOS Medicine. The paper has been reviewed by subject experts and a statistician; their comments are included below and can also be accessed here: [LINK]

As you will see, the reviewers thought the manuscript has improved but they still have serious concern about bias. After discussing the paper with the editorial team and an academic editor with relevant expertise, we agreed to offer you one more round of revision to address this issue. We plan to send the revised paper to some or all of the original reviewers, and we cannot provide any guarantees at this stage regarding publication.

Specifically we would like you to address the following:

1) Revise the language sentence by sentence. This applies to the whole manuscript, but the Abstract and Discussion in particular.

Specific points:

-remove the causal language on line 36 of the abstract.

-remove line 42-44 of the abstract and re-write this.

2) Please remove any use of the slippery slope argument completely, and instead just focus on the examination of the trends in euthanasia cases. This can be along the lines of “Legislation for ADE was adopted in 2002 in Belgium permitting euthanasia for terminal illness and for non-terminal illnesses such as XYZ. In this study we examined trends in euthanasia cases involving patients psychiatric disorders, dementia and terminal illness from 200X-20XX”

3) Please remove the court case discussion in the introduction, instead it would be fine to state it’s a contentions issue. Court cases could be mentioned in the discussion only.

4) Please shorten your introduction to 750 words.

5) Please trim the discussion, as this is overly long currently.

In addition to these revisions, you will need to complete some formatting changes, which you will receive in a follow up email. A member of our team will be in touch with a set of requests shortly.

When you upload your revision, please include a point-by-point response that addresses all of the reviewer and editorial points, indicating the changes made in the manuscript and either an excerpt of the revised text or the location (eg: page and line number) where each change can be found. Please also be sure to check the general editorial comments at the end of this letter and include these in your point-by-point response. When you resubmit your paper, please include a clean version of the paper as the main article file and a version with changes tracked as a marked-up manuscript. It may also be helpful to check the guidelines for revised papers at http://journals.plos.org/plosmedicine/s/revising-your-manuscript for any that apply to your paper.

We ask that you submit your revision by Jul 21 2025 11:59PM. However, if this deadline is not feasible, please contact me by email, and we can discuss a suitable alternative.

Don't hesitate to contact me directly with any questions (sbruijn@plos.org).

Best regards,

Suzanne

Suzanne De Bruijn, PhD

Associate Editor

PLOS Medicine

sbruijn@plos.org

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Comments from the academic editor:

Please ensure that they text is neutral. I suggest to examine every sentence to consider whether the text is justified, and whether there is any implicit bias still there. Maybe imagine you are someone very much against assisted suicide, and read the manuscript from their perspective.

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Comments from the reviewers:

Reviewer #1: We thank the authors for addressing our previous comments, and the other reviewers for improving the statistical analyses.

Reviewer #2: I sincerely thank the authors for carefully addressing the reviewers' comments. The revisions have significantly improved the clarity and quality of the manuscript.

There still remains minor issues to be addressed:

1. Terminology: Euthanasia vs. Assisted Suicide

The clarification provided in the methods and background sections regarding the exclusive use of "euthanasia" in line with Belgian legal definitions is well explained. However, I recommend adding a brief footnote at the first mention of the term "euthanasia" to inform international readers that in Belgium, this may include rare cases of supervised self-administration that are still legally classified as euthanasia.

Concerning terminologia, i point that assisted dying is commonly used as an umbrella term , including euthanasia and assisted suicide. For this reason, I suggests that authors to use only the term assisted dying and not assisted dying and euthanasia.

2. Interpretation of the Slippery Slope Argument

The revised manuscript commendably distinguishes between the empirical and normative dimensions of the "slippery slope" argument.

Suggestion:

I recommend including an explicit statement in the discussion acknowledging that while the empirical data do not support a slippery slope in numerical terms, ethical concerns about the broadening of eligibility criteria remain valid and deserve further comparative research.

3. Gender and Regional Trends

The authors have appropriately acknowledged data limitations and refrained from speculation regarding gender and regional disparities.

Further Recommendation:

Consider moving part of this discussion into the limitations section, where it may be more visible.

4. Policy and Limitations

The discussion section has been usefully restructured.

Additional Suggestion:

The authors may wish to state more explicitly that while dementia-related euthanasia remains infrequent, the upward trend over time is noteworthy and warrants monitoring.

5. Minor issues

- The shift to a zero-inflated negative binomial model is appropriate and well justified.

- Including 95% confidence intervals greatly improves transparency.

- Some defensive phrasing remains, especially regarding critical literature (e.g., references to the 2017 edited volume). I encourage the authors to maintain a more neutral and academic tone throughout.

Conclusion

Overall, this is a strong and timely study. With a few remaining refinements to language and emphasis, I believe the manuscript will be ready for publication.

Reviewer #3: I acknowledge that the authors have invested into the revision of the manuscript, and improvements has been achieved, however there is still significant issues remaining.

1. Formulations in the text still puts into question the neutrality of the authors in terms of euthanasia as a concept. Would one for example use the phrase "catching up" if cancer incidence of one region were approaching another region with higher incidence? This is not easily fixed with further revisions, since the text is a sign of the problem, rather than the problem itself.

Also, in abstract conclusion is stated "…without evidence of significant misuse…" the misuse, or lack of it, has not been investigated, only time trends. The fact that this is the conclusion after another reviewer pointed out that the conclusions were overreaching is troublesome.

2. There is a lack of scientific integrity shown in the discrepancy between the answer to me regarding 95%CIs: "We have now added 95% confidence intervals (CIs) to the paper, as we agree they contribute valuable information for interpreting the robustness of the results." Vs the text in the manuscript: "the 95% CIs are unnecessary and do not provide meaningful insights." (row 412 in tracked changes version).

In addition, the authors state that they do not wish to extrapolate the findings outside of Belgium. In the second paragraph of the Discussion (rows 569-584) the authors reason around the situation in UK and France, concluding "The Belgian experience, however, addresses this concern." I don't mind this, I fact I think this is why we do research at all: to be able to extrapolate into the unknown, (the etiology of cancer tumours not yet developed e.g.), but the fact the authors don't see that this is what they doing is concerning.

3. I appreciate the decreased focus and usage of the term/concept "slippery slope", however, it is still present (e.g. in the conclusion of the Abstract). This is from the revised abstract: "Assisted dying and euthanasia (ADE) for patients with psychiatric disorders or dementia have increased in countries where the practice is legal. These cases are often cited in arguments against ADE legislation, as they are perceived to contribute to a potential slippery slope in case numbers." The fact that the case numbers increase, or not, does not tell us if that is good (good uptake of new legislation, the opportunity of new treatment reaches all part of the population) or bad (misuse, lax definition of eligible patients), that is an ethical interpretation, not empirical. It is built into the "slippery slope"-argument that an increase is bad, but the increase itself does not carry any value when not coupled with an ethical standpoint. Which is why I would wish the authors really kept only to analyses of the data and conclusion that can be drawn from these.

4. In my first review I asked "What does the first model, that calculate the "occurrence" (frequency?) of euthanasia, contribute with?" this was not answered but the manuscript now states "Importantly, this model treats the outcome purely as a count, without accounting for differences in population size." This would seem to indicate that Model 1 adds no value to the manuscript and should be removed. (Or, an explanation in the manuscript of how the interpretation of model 1 helps the final conclusion is needed)

(This remind me of papers of my own where we started analysis somewhere, moved on in our thinking and did not until late realize that the first attempts were superfluous in the manuscript, even if they were instrumental for our moving forwards in analytical stage)

Any attachments provided with reviews can be seen via the following link: [LINK]

--------------------------------------------------------- ---

General editorial requests:

* Please ensure that the study is reported according to the Strobe guideline and include the completed Strobe checklist as Supporting Information. When completing the checklist, please use section and paragraph numbers, rather than page numbers. Please add the following statement, or similar, to the Methods: "This study is reported as per Strobe guideline (S1 Checklist)."

* For all observational studies, in the manuscript text, please indicate: (1) the specific hypotheses you intended to test, (2) the analytical methods by which you planned to test them, (3) the analyses you actually performed, and (4) when reported analyses differ from those that were planned, transparent explanations for differences that affect the reliability of the study's results. If a reported analysis was performed based on an interesting but unanticipated pattern in the data, please be clear that the analysis was data driven.

* Please state in the Methods section whether the study had a prospective protocol or analysis plan. If a prospective analysis plan (from your funding proposal, IRB or other ethics committee submission, study protocol, or other planning document written before analyzing the data) was used in designing the study, please include the relevant document(s) with your revised manuscript as a Supporting Information file to be published alongside your study and cite it in the Methods section. A legend for this file should be included at the end of your manuscript. If no such document exists, please make sure that the Methods section transparently describes when analyses were planned, and when/why any data-driven changes to analyses took place. Changes in the analysis, including those made in response to peer review comments, should be identified as such in the Methods section of the paper, with rationale.

 10.1371/journal.pmed.1004522.r005 Author response to Decision Letter 3 Submission Version 3

31 Aug 2025

Submitted filename: Reviews-2.docx

 10.1371/journal.pmed.1004522.r006 Decision Letter 3 De Bruijn Suzanne Senior Editor 2025 Suzanne De Bruijn This is an open access article distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Submission Version 3

8 Oct 2025

Dear Dr. Wels,

Thank you very much for re-submitting your manuscript "Trends in Assisted Dying Among Patients with Psychiatric Disorders and Dementia in Belgium" (PMEDICINE-D-24-04457R3) for review by PLOS Medicine.

I have discussed the paper with my colleagues and the academic editor and it was also seen again by 1 reviewer. I am pleased to say that provided the remaining editorial and production issues are dealt with we are planning to accept the paper for publication in the journal. However, please note that we will require you to incorporate the textual suggestions from reviewer #2, as well as the textual suggestions from the editors. Furthermore, there are several editorial issues that need to be addressed, which are listed at the end of this email.

Any accompanying reviewer attachments can be seen via the link below. Please take these into account before resubmitting your manuscript:

[LINK]

***Please note while forming your response, if your article is accepted, you may have the opportunity to make the peer review history publicly available. The record will include editor decision letters (with reviews) and your responses to reviewer comments. If eligible, we will contact you to opt in or out.***

In revising the manuscript for further consideration here, please ensure you address the specific points made by each reviewer and the editors. In your rebuttal letter you should indicate your response to the reviewers' and editors' comments and the changes you have made in the manuscript. Please submit a clean version of the paper as the main article file. A version with changes marked must also be uploaded as a marked up manuscript file.

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In addition to these revisions, you may need to complete some formatting changes, which you will receive in a follow up email. A member of our team will be in touch with a set of requests shortly. If you do not receive a separate email within a few days, please assume that checks have been completed, and no additional changes are required.

We expect to receive your revised manuscript within 1 week. Please email us (plosmedicine@plos.org) if you have any questions or concerns.

We ask every co-author listed on the manuscript to fill in a contributing author statement. If any of the co-authors have not filled in the statement, we will remind them to do so when the paper is revised. If all statements are not completed in a timely fashion this could hold up the re-review process. Should there be a problem getting one of your co-authors to fill in a statement we will be in contact. YOU MUST NOT ADD OR REMOVE AUTHORS UNLESS YOU HAVE ALERTED THE EDITOR HANDLING THE MANUSCRIPT TO THE CHANGE AND THEY SPECIFICALLY HAVE AGREED TO IT.

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To enhance the reproducibility of your results, we recommend that you deposit your laboratory protocols in protocols.io, where a protocol can be assigned its own identifier (DOI) such that it can be cited independently in the future. Additionally, PLOS ONE offers an option to publish peer-reviewed clinical study protocols. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols

Please review your reference list to ensure that it is complete and correct. If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references. Any changes to the reference list should be mentioned in the rebuttal letter that accompanies your revised manuscript.

Please note, when your manuscript is accepted, an uncorrected proof of your manuscript will be published online ahead of the final version, unless you've already opted out via the online submission form. If, for any reason, you do not want an earlier version of your manuscript published online or are unsure if you have already indicated as such, please let the journal staff know immediately at plosmedicine@plos.org.

If you have any questions in the meantime, please contact me or the journal staff on plosmedicine@plos.org.  

We look forward to receiving the revised manuscript by Oct 22 2025 11:59PM.   

Sincerely,

Suzanne De Bruijn, PhD

Associate Editor 

PLOS Medicine

plosmedicine.org

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Requests from Editors:

* Please use the active voice throughout the manuscript.

* Please remove any use of the phrase 'uncontrolled increase'

* Please move the ‘limitations’ section to the discussion.

Specific textual requests:

ABSTRACT

Line 20-24 (background): Please change to:

“Assisted dying and euthanasia (ADE) laws make a distinction between ADE for terminal illnesses and non-terminal illnesses such as psychiatric disorders or dementia. ADE for patients with psychiatric disorders or dementia have increased in countries where the practice is legal. In this study, we examine trends in euthanasia cases involving patients with these conditions in Belgium, between 2002 and 2023.

Line 32-35 (methods and findings). Please change to:

“Although slightly increasing, euthanasia for psychiatric disorders followed trends similar to the other types of euthanasia (count=1.00 [95%CI: 0.98; 1.03] – rate=1.02 [95%CI: 0.99; 1.04]), while euthanasia cases for dementia increased faster than other types of dementia (count= 1.03 [95%CI: 1.00; 1.06] – rate= 1.04 [95%CI: 36 1.01;1.07]).

Line 41: please change ‘discussion’ into ‘Conclusion’.

Line 41- 46 (Conclusion): Please change to:

“In Belgium, between 2002 and 2023, there are distinct trends for euthanasia for non-terminal illnesses. Euthanasia for psychiatric disorders followed similar trends as euthanasia for terminal illnesses, whereas euthanasia cases involving cognitive conditions increased at a faster rate. Furthermore, there were gender and regional differences, which diminished over time.”

BACKGROUND

Line 58-60: change to:

“The discourse primarily focuses on two categories of conditions where death is not expected within 12 months: dementia and other degenerative disorders, and severe psychiatric illnesses.”

Line 65-67: remove ‘actual’ , remove ‘leaving little room for empirical evidence’.

Line 67: remove ‘Similarly’.

Line 71: change ‘demand’ to ‘numbers of cases’

Line 73-76: change to:

“The observed increase in cases fuel concerns about a gradual expansion of eligibility criteria, particularly leading to concerns regarding vulnerable patients. These concerns are used as an argument against implementing ADE for non-terminal illness in other jurisdictions and as an argument in favour of introducing stricter safeguards.”

Line 80-82:change to:

“the idea that eligibility criteria in ADE regulations are gradually expanded, or that vulnerable populations are at greater risk is not substantiated by empirical studies.”

Line 83 remove ‘notably’ before focused.

RESULTS:

Line 258-261: Please change to:

“Over the selected period, psychiatric disorders and dementia represent 1.27% and 0.92% of all cases, respectively, and followed similar trends to the overall number of cases.”

Line 264: Besides psychiatric conditions and cognitive disorders, are there any other non-terminal illnesses reason for euthanasia? If not, please change ‘with those for other reasons’ to ‘with those for terminal illnesses’.

Line 288-293: Change to:

“the difference between predicted rates with and without adjustment for population composition and change suggests that population change may partially underlie changes observed in euthanasia prevalence. Furthermore, we observe that the rate of increase in euthanasia cases is similar for terminal illnesses and psychiatric disorders, but higher for dementia cases.”

Line 311-313: Change to:

‘However, over time the rate of increase is becoming larger in Wallonia-Brussels compared with Flanders, indicating that the observed difference between these two regions is diminishing.’

Line 322-324: what is meant here? ‘other’ reasons involving mental suffering? Or all euthanasia cases for ‘other’ (which sounds unlikely?). Please clarify.

Line 328-329: Please remove this sentence, as there is no statistical significance for these findings.

Line 341-347: change to:

“These cases have been more prevalent in the Dutch-speaking community than the French-speaking community, although this regional difference has diminished over time. Furthermore, we observed that most of the increase in psychiatric and dementia-related euthanasia occurred in the French-speaking community.”

Line 350-353: Please remove this paragraph. Especially the last sentence ‘Overall, much of the increase in euthanasia cases is driven by short-term death expectations, rather than long-term ones.’ as this statement is not directly linked to the goal of the study.

Line 360-363: Please remove these 2 sentences, as it seems overly political, and can be perceived as bias.

Line 367: remove ‘proactively’

Line 370-375: Please reconsider this paragraph. ‘methods used to analyse ADE figures….’ As this seems to criticize other studies, rather than highlighting a limitation of the current study.

DISCUSSION:

Line 385-396: change to:

“Recent debates on the implementation of assisted dying in the united Kingdom and France have highlighted the distinction between euthanasia for terminal- and non-terminal causes, with both these countries considering implementation of euthanasia for terminal-illnesses only, excluding patients with psychiatric disorders or degenerative conditions.

In contrast, Belgium euthanasia law has allowed euthanasia for non-terminal and non-physical illnesses from its inception in 2002, allowing us to compare rates in euthanasia for terminal illnesses, psychiatric disorders, and dementia.

Line 397-: remove ‘dramatic increase’. Suggested text:

“In 2023, psychiatric disorders and dementia accounted for 1.4% and 1.2% of all cases, respectively. We observed a significant, but still modest, increase in euthanasia for dementia. Furthermore, we observed that differences across genders and linguistic regions have narrowed over time.

Line 414-418: Please consider removing this paragraph; without data on changes in quantity/quality of palliative care units, this adds little to the discussion.

Line 419-435; please change the last paragraph to:

“Concerns have been raised, both in parliamentary debates [39] and within professional medical bodies, that permitting euthanasia in limited cases (e.g., terminal illness) may gradually lead to less justified applications, and whether safeguards are effectively maintained when euthanasia is extended to non-terminal conditions or psychiatric disorders [41] . Whilst we acknowledge that empirical data cannot resolve ethical and normative questions, our findings demonstrate that euthanasia for psychiatric and cognitive conditions, which has been legally permissible in Belgium since 2002, has not substantially increased between 2002 and 2023. These findings can add to the discussion of end-of-life issues and their inherent complexities.”

GENERAL EDITORIAL REQUESTS

* Thank you for providing an Author summary. Can you please include this within the main manuscript, directly following the Abstract. In the final bullet point of ‘What Do These Findings Mean?’ Please include the main limitations of the study in non-technical language.

* Please confirm that your title complies with to PLOS Medicine's style. Your title must be nondeclarative and not a question. It should begin with main concept if possible. "Effect of" should be used only if causality can be inferred, i.e., for an RCT. Please place the study design ("A randomized controlled trial," "A retrospective study," "A modelling study," etc.) in the subtitle (ie, after a colon).

* Please confirm that your abstract complies with our requirements, including format (three sections: Background, Methods and Findings, and Conclusions) and providing all the information relevant to this study type https://journals.plos.org/plosmedicine/s/submission-guidelines#loc-abstract

* Please confirm that all numbers presented in the abstract are present and identical to numbers presented in the main manuscript text.

GENERAL

* In the last sentence of the Abstract Methods and Findings section, please describe the main limitation(s) of the study's methodology.

* In the author summary, in the final bullet point of 'What Do These Findings Mean?', please include the main limitations of the study in non-technical language.

* Ensure all supplementary material has titles and legends, specifically the figures in the supplements.

AUTHOR SUMMARY:

* What did the researchers do and find, 2nd bullet point: Please remove. If you prefer, you may add these numbers in bullet point 1.

* What did the researchers do and find, 3rd bullet point: please change to:

"we found that euthanasia for psychiatric disorders has increased at a similar rate to all euthanasia cases, whereas cases of euthanasia for dementia have increased slightly more."

* What did the researchers do and find: Please consider adding a new bullet point including the information: "there were gender and regional differences in these trends.”

* What do these findings mean, 1st bullet point: Please rephrase this. I appreciate that the number of euthanasia cases for these conditions is limited, which should be stated here. However, as dementia cases increased more than ‘all’ cases, the statement ‘not led to disproportionate growth’ is not completely accurate.

* What do these findings mean, 2nd bullet point: please consider removing this.

FUNDING STATEMENT

* Thank you for providing your funding statement. Please also include the URLs for the funders in this statement.

ETHICS AND CONSENT

* Please provide the name(s) of the institutional review board(s) that provided ethical approval.

OBSERVATIONAL, COHORT, CROSS-SECTIONAL, AND CASE CONTROL STUDIES

* Thank you for including the STROBE checklist in your submission. Please also mention this in the methods section of your manuscript, with the suggested text: "This study is reported as per the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guideline (S1 Checklist)."

* Did your study have a prospective protocol or analysis plan? Please state this (either way) early in the Methods section.

a) If a prospective analysis plan (from your funding proposal, IRB or other ethics committee submission, study protocol, or other planning document written before analyzing the data) was used in designing the study, please include the relevant prospectively written document with your revised manuscript as a Supporting Information file to be published alongside your study, and cite it in the Methods section. A legend for this file should be included at the end of your manuscript.

b) If no such document exists, please make sure that the Methods section transparently describes when analyses were planned, and when/why any data-driven changes to analyses took place.

c) In either case, changes in the analysis-- including those made in response to peer review comments-- should be identified as such in the Methods section of the paper, with rationale.

Comments from Reviewers:

Reviewer #2:

see attached document

Any attachments provided with reviews can be seen via the following link:

[LINK]

Submitted filename: Review 3. PLOS one. 2025.docx

 10.1371/journal.pmed.1004522.r007 Author response to Decision Letter 4 Submission Version 4

9 Oct 2025

Submitted filename: Response to reviewers.docx

 10.1371/journal.pmed.1004522.r008 Decision Letter 4 De Bruijn Suzanne Senior Editor 2025 Suzanne De Bruijn This is an open access article distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Submission Version 4

16 Oct 2025

Dear Dr. Wels,

Thank you very much for re-submitting your manuscript "Trends in Assisted Dying Among Patients with Psychiatric Disorders and Dementia in Belgium" (PMEDICINE-D-24-04457R4) for review by PLOS Medicine.

However we have several remaining editorial requests that we would like you to address.

* Please change your title to: "Trends in Assisted Dying Among Patients with Psychiatric Disorders and Dementia in Belgium: a health registry study"

* I noted the limitations are copied to the discussion as requested, but not removed from their original location. Please remove this to ensure the text is not duplicated.

* Author summary: Please move the limitations from 'what did the researchers do and find' to 'what do these findings mean?"

* FUNDING STATEMENT:

Thank you for providing your funding statement. Please also include the URLs for the funders in this statement

* ETHICS STATEMENT: Please also provide an IRB approval number.

* Line 264: could you give a bit more detail about multi-morbidity, given that it's a non-terminal area not covered by the analysis.

* Line 316: there is a typo: please change 'in' to 'is'.

* Line 412: Please edit this paragraph to: "During the first five years following the implementation of the regulation, cases of euthanasia for psychiatric disorders and dementia remained infrequent. Differences in access across genders and linguistic regions have narrowed over time".

Further there were 2 additional comments from the Academic Editor:

-lines 336-368 and 346-348: the units and the way these are representated are likely to be opaque for readers; is there a way to make them more meaningful to interpret? one possibility is events/population/time unit, and not using so many decimal points. This would be simply for clarity.

-Agree with your rebuttal on the comment regarding line 328-329.

***Please note while forming your response, if your article is accepted, you may have the opportunity to make the peer review history publicly available. The record will include editor decision letters (with reviews) and your responses to reviewer comments. If eligible, we will contact you to opt in or out.***

In revising the manuscript for further consideration here, please ensure you address the specific points made by each reviewer and the editors. In your rebuttal letter you should indicate your response to the reviewers' and editors' comments and the changes you have made in the manuscript. Please submit a clean version of the paper as the main article file. A version with changes marked must also be uploaded as a marked up manuscript file.

Please also check the guidelines for revised papers at http://journals.plos.org/plosmedicine/s/revising-your-manuscript for any that apply to your paper. If you haven't already, we ask that you provide a short, non-technical Author Summary of your research to make findings accessible to a wide audience that includes both scientists and non-scientists. The Author Summary should immediately follow the Abstract in your revised manuscript. This text is subject to editorial change and should be distinct from the scientific abstract.

In addition to these revisions, you may need to complete some formatting changes, which you will receive in a follow up email. A member of our team will be in touch with a set of requests shortly. If you do not receive a separate email within a few days, please assume that checks have been completed, and no additional changes are required.

We expect to receive your revised manuscript within 1 day. Please email us (plosmedicine@plos.org) if you have any questions or concerns.

Please note, when your manuscript is accepted, an uncorrected proof of your manuscript will be published online ahead of the final version, unless you've already opted out via the online submission form. If, for any reason, you do not want an earlier version of your manuscript published online or are unsure if you have already indicated as such, please let the journal staff know immediately at plosmedicine@plos.org.

If you have any questions in the meantime, please contact me or the journal staff on plosmedicine@plos.org.  

We look forward to receiving the revised manuscript by Oct 18 2025 11:59PM.   

Sincerely,

Suzanne De Bruijn, PhD

Associate Editor 

PLOS Medicine

plosmedicine.org

 10.1371/journal.pmed.1004522.r009 Decision Letter 5 De Bruijn Suzanne Senior Editor 2025 Suzanne De Bruijn This is an open access article distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Submission Version 5

29 Oct 2025

Dear Dr Wels, 

On behalf of my colleagues and the Academic Editor, Carol Brayne, I am pleased to inform you that we have agreed to publish your manuscript "Trends in Assisted Dying Among Patients with Psychiatric Disorders and Dementia in Belgium: a health registry study" (PMEDICINE-D-24-04457R5) in PLOS Medicine.

As a final request, we would ask you to include some more detail into your ethics statement, regarding how approval from the FCCEE was obtained.

Furthermore, before your manuscript can be formally accepted you will need to complete some formatting changes, which you will receive in a follow up email. Please be aware that it may take several days for you to receive this email; during this time no action is required by you. Once you have received these formatting requests, please note that your manuscript will not be scheduled for publication until you have made the required changes.

In the meantime, please log into Editorial Manager at http://www.editorialmanager.com/pmedicine/, click the "Update My Information" link at the top of the page, and update your user information to ensure an efficient production process. 

PRESS

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We also ask that you take this opportunity to read our Embargo Policy regarding the discussion, promotion and media coverage of work that is yet to be published by PLOS. As your manuscript is not yet published, it is bound by the conditions of our Embargo Policy. Please be aware that this policy is in place both to ensure that any press coverage of your article is fully substantiated and to provide a direct link between such coverage and the published work. For full details of our Embargo Policy, please visit http://www.plos.org/about/media-inquiries/embargo-policy/.

Thank you again for submitting to PLOS Medicine. We look forward to publishing your paper. 

Sincerely, 

Suzanne De Bruijn, PhD 

Associate Editor 

PLOS Medicine