The research presented in this critical analysis demonstrated the importance of environmental risk factors on health including inadequate WASH. It also underlined the importance of selected issues in risk factor-attributable disease burden assessments, some of which are specific to inadequate WASH. Data gaps and needs for future research were identified. For most environmental risks, data on exposures and exposure-response relationships are still scarce (5). To fill these data gaps, research on environmental risks encompassing all steps of risk-factor attributable disease burden assessment, including identification and mapping of exposures and quantification of exposure-response relationships, should be conducted (5). Comparative risk assessment methods using theoretical minimum risk exposure distributions should ultimately replace alternative approaches for estimating risk factor-attributable disease burden that are based on lower quality data or more assumptions. More disaggregated exposure, exposure-response and disease data would allow WASH-attributable disease burden estimation for population subgroups of interest such as different socio-economic groups. Issues of comparative risk assessment methods include the appropriate use of adjusted relative risks for estimation of the PAF, the portability of the exposure-response relationship from various source populations to a target population with different underlying conditions and the choice of the most appropriate counterfactual. Recently a few large, well-funded and well-conducted trials that yielded high implementation and compliance showed minimal health impacts from improving WASH (84–86). These trials provided or promoted basic WASH and only targeted households with pregnant women (84–86). Research has shown that much of the health impact from adequate WASH and especially from adequate sanitation is actually from community-level effects, i.e., whether a household is using safe sanitation impacts the health in neighbouring households (75,78–81). Even high coverage with basic sanitation services, as opposed to safely managed sanitation, might however not sufficiently reduce faecal contamination in a community (88). A consensus statement of researchers hypothesized that basic WASH services as implemented in these trials were unlikely to lead to health benefits and that higher level services covering the entire communities were needed (138). The research presented here contributed to this discussion by indicating that community faecal contamination needed to be reduced substantially before health impacts could be observed in intervention studies (section 2.11 (74)). Risk factor-attributable, including WASH-attributable, burden of disease assessments usually rely on intervention studies whose results are pooled for establishing the exposure-response relationship. WASH interventions show great heterogeneity and apply different technologies and levels of services, provide infrastructure or promote certain behaviours. Accordingly, the presented research has shown that much of the observed difference in health impact is due to the type of intervention (sections 2.3 (41) and 2.9 (52)). Furthermore, health impact will likely depend on whether the intervention is tailored to the prevailing exposure routes of the local context (138). A truly theoretical minimum risk exposure level in WASH-attributable disease burden assessments which might be approximated by all the population using safely managed WASH services would represent more comprehensively the amount of the disease burden that could be reduced through adequate WASH. Additionally, this would be in line with the targets of SDG 6 (94). For this, more radical or “transformative” (138) WASH interventions are needed that remove or substantially reduce faecal contamination in a community. Such interventions need to supply whole communities with water and sanitation network connections that provide continuous piped water free from contamination and safe sanitation and effective promotion of comprehensive hygiene behaviours. Such transitions from limited or basic WASH to safely managed WASH services have usually happened over decades in high-income countries and were accompanied with large though deferred population health improvements (138–141). As discussed above even safely managed WASH services might constitute risks to health which was shown through studies on Water Safety Plans (107,108). Depending on the local context, even more comprehensive WASH interventions might be needed, such as those also including reduced contact with animal faeces (142–144). An additional limitation of relying on household interventions for WASH-attributable burden of disease assessments includes likely bias from lack of blinding in studies with self-reported health outcomes. The presented research adjusted for this bias based on prior evidence which resulted in non-significant health impact from certain point-of- use drinking water treatments and from hygiene promotion (sections 2.3 (41) and 2.9 (52)). This is in line with previous research (95,103). Alternative approaches are available that could be directly integrated in intervention design and implementation such as the use of negative control outcomes or attention control groups (145). Negative control outcomes are those outcomes that are not plausibly related to the intervention of interest, such as the prevalence of bruising or scrapes following a WASH intervention (146). In an attention control group an intervention that mimics the non- specific or theoretically inactive elements of the main intervention, such as intensity of contact, is implemented (68,69). The anticipated outcome of the attention control intervention needs to be independent from the outcome of the main intervention (68,69). An attention control group was used in the research presented here to reduce bias from lack of blinding and study drop-out (section 2.7 (65,67)). To further improve WASH interventions and their usability for disease burden analysis, research on intervention implementation, intervention quality, intermediate outcomes, determinants of intervention effectiveness and the relation between access and actual use of services would be useful (12). Regarding the many limitations of intervention studies to derive the exposure-response relationships for disease burden estimation, the role of other study designs should be explored. One example are pre-existing, non-randomized interventions (147,148) which often happen in large and representative populations. Another example is the use of data from country-representative household surveys such as Multiple Indicator Cluster Surveys (MICS) and Demographic and Health Surveys (DHS) (149), potentially using matching methods for generating “intervention” and “control” groups (97). Using results of alternative study designs (27) might be an important step to increase data availability for example for the provision of higher level services and for settings such as high-income countries. Future WASH-attributable burden of disease assessments might benefit from combined exposure scenarios of water, sanitation and hygiene because there are likely important linkages and interactions between the different WASH exposure categories. Such combined scenarios were already used in previous burden of disease assessments (31). This would also solve the discussed issue of using Equation 2 for combining different PAFs for a cluster of risk factors. Future assessments might also calculate the disease burden from several counterfactual scenarios, e.g. different definitions of the theoretical minimum risk but also plausible and feasible minimum risk exposure levels. 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