Initial searches generated 998 records. After the removal of duplicates and the first screening of titles and abstracts, 112 records were left for retrieval. Twelve corresponding authors were contacted to identify missing full texts. Fifty-four records were then assessed for eligibility. One author group was still waiting for publication of their study which could therefore not be included. One record had to be excluded subsequently as the same patient cohort was analyzed in two publications by the same research team but published by different primary authors. The preliminary figure of 22 records identified in 2020 through electronic database searches was enlarged by two records identified through reference searches of corresponding literature and two additional records identified through updated electronic database searches in April 2024. The final synthesis and meta-analysis therefore consists of 26 records. The selection process is visualized in more detail in the PRISMA Flowchart (Fig. 1) [24].

PRISMA Flowchart (2020 version) [24]

The 26 included studies were published between 1999 and 2024. Between the year 1999 and 2011 only nine studies were identified [26,27,28,29,30,31,32,33,34] but there was an 88.9% increase in publications over the next 12 years, with 17 studies published [35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50,51] (Fig. 2and Table 1).

Years of publication. Bar diagram illustrating the total number of publications per year over the review period from 1999 until 2024. The diagram shows an increase of 88.9% when comparing the first with the second decade

Of the 26 included studies, the majority (76.9%, n = 20) were quantitative studies. A smaller number were mixed methods (n = 2), or qualitative (n = 4) studies. Of the qualitative studies, two utilized grounded theory [31, 45], one was narrative research [41] and another a longitudinal qualitative study with a grounded theory approach [51].

Of the two mixed methods studies one used a convergent design [33] while the other utilized a sequential explanatory design [34].

Among the quantitative studies were three descriptive cross-sectional studies, five analytical cross-sectional studies, five surveys and seven non-randomized cohort studies (Fig. 3A).

Most studies (42.3%, n = 11) employed a retrospective medical file review and 38.5% personal interviews, while 34.6% chose questionnaires.

Overall the qualitative and mixed methods studies had higher quality scores than the quantitative studies. Only a third (38.5%, n = 10) of the studies had a high quality score of 100% and eight studies (30.7%) had a quality score of 80%. Five studies (19.2%) were assessed with a quality of 60% and three studies (11.5%) were assessed with a quality of 40% (Fig. 3B). All four qualitative studies [31, 41, 45, 51] received a quality score of 100% and the two mixed methods approaches [33, 34] 80% and 100% respectively (Fig. 3C). In 30% of the quantitative studies quality score was impacted by the lack of acknowledgement of confounders or inclusion and exclusion criteria leading to a 20% reduction in the quality assessment score.

Association of study design and MMAT Score. A: 77% were quantitative studies, 15.4% qualitative studies and 7.7% were mixed methods study designs. B: The Mixed Methods Appraisal Tool for the assessment of study quality in its 2018 version was applied. For better visualization, a scoring system ranging from 0 to 100% was applied to all included records. C: One-way ANOVA was performed in GraphPad Prism 8. Symbols representing means and error bars SD

The studies were undertaken in 23 different countries, with most occurring in the United States of America (USA) (n = 9) [26, 28, 29, 32, 34, 46, 48,49,50] or Germany (n = 5) [27, 31, 33, 37, 43]. A smaller number took place in Switzerland (n = 3) [30, 36, 47] or the United Kingdom (n = 3) [27, 38, 40]. Other studies included participants from Italy [27, 44], Belgium [27, 51] and the Netherlands [39, 45], respectively. Seventeen additional countries were included largely as part of Borasio et al. [27] 2021 international survey involving participants from 14 countries (Fig. 4).

Distribution of participating countries. World map indicating the location of origin for the included records. The circle size represents a number of publications in the respective country and shows the focus of research in countries of the global north. © OpenStreetMap

The cohort size varied from n = 15 [31] to n = 1014 participants [28]. In 15 studies (57.7%) only the ALS patient was interviewed [26, 30, 32, 37, 39, 40, 42,43,44,45,46,47,48,49,50]. In one study (3.8%) only health care professionals were interviewed [27] and in four publications (15.4%) the respective caregiver [28, 29, 33, 41]. In five publications (19.2%) data was analyzed from patients and caregivers [34,35,36, 38, 51] and in one case (3.8%) from patients and health care professionals [31]. In four cases the study cohort consisted of an equal number of patients and caregivers [34,35,36, 51] and in one case of patients and neurologists [31]. The sex of the participants was documented in 19 studies (73.1%), and they were either classified as male (57%) or female (43%). Any information on gender was not included in the analyzed studies. Religion and spirituality of the patients were documented in five studies (19.2%) [27, 33, 36, 38, 50].

Eleven out of 26 included studies (42.3%) contained information regarding ACP discussions with ALS patients. In seven additional publications it was unclear whether the signing of AD documents was preceded by ACP conversations. Six studies (23.1%) contained numeral data on the number of patients in the cohorts, that had ACP communication with their health care professional. Two hundred forty-nine out of 341 patients in the respective cohorts (73%) were documented to have had structured conversations about end of life wishes and care goals.

Advance care planning was mostly addressed by the physician (in 63.6% of studies) rather than by the ALS patients themselves. Three German publications stated the topic of ACP being risen by the physician first while only one German study found the patient to seek exchange regarding this subject first.

Eight out of 26 publications (30.8%) stated the time after diagnosis when ACP was first initiated with the patient. In six out of these eight reports (75%) it was initiated early after diagnosis. Three publications (37.5% out of eight publications) specified this to be at the first visit after diagnosis [32, 46, 47], which was the first consultation with a palliative care (PC) specialist, a hospital admission or a consultation with another health care professional. In one report, ACP was incorporated in the conveying of the diagnosis [27]. In two out of eight publications (25%) ACP was postponed until symptoms occurred, or the patients’ physical condition worsened.

Nineteen studies (73.1%) detailed patients’ preferences regarding AD. The fraction of ALS patients that had signed orders regarding care or treatment preferences ranged from 9.1% (2/22 patients) [30] to 90.5% (19/21 patients) [45] with a median of 60.4% (1,629/ 2,696 patients). Figure 6A visualizes this heterogeneity with I2 = 98%. At the same time, the plot shows that the smaller cohort sizes contribute equally to the AD results within the group of ALS patients as the weighted proportions are all within a similar range.

Healthcare proxies and signed Power of Attorney forms were described in five reports. 25.2% of patients (175/ 695 patients) in these studies had a healthcare proxy, and 20.8% (145/ 697 patients) had signed Power of Attorney forms.

Patients’ preferences for IV therapy were documented in two studies, with 6.2% of the patients in favour of (2/32 patients with AD [