contains a justification of the criteria presented to support causality). In this summary of evidence, we have focused on randomised controlled trials and prospective observational studies, along with supporting evidence, like dose–response relationships and biologically plausible mechanisms.Table 1Descriptive cataloguing of the epidemiological evidence used to assess whether each risk-outcome paper meets the causal criteria for inclusion in the Global Burden of Disease Study 2016 by risk levelRiskOutcomeRCTs (n)RCTs with significant effect in the opposite direction (%)RCTs with null findings (%)Prospective observational studies (n)*Prospective observational studies with significant association in the opposite direction (%)Case-control studies assessing the risk- outcome pair relationship (n)†Case-control studies that show significant association in the opposite direction (%)Lower limit of RR >1·5Dose–response relationshipBiological plausibility‡Analogy§2Unsafe water, sanitation, and handwashing3Unsafe water source– chlorination or solar (point of use treatment)Diarrhoeal diseases2404260····Yes··YesNo3Unsafe water source–pipedDiarrhoeal diseases100911····Yes··YesNo3Unsafe water source–filterDiarrhoeal diseases1104520····Yes··YesNo3Unsafe water source– improved waterDiarrhoeal diseases0····50····Yes··YesNo3Unsafe sanitation– pipedDiarrhoeal diseases0····70····Yes··YesNo3Unsafe sanitation– improved sanitationDiarrhoeal diseases0····90····Yes··YesNo3No access to handwashing facilityDiarrhoeal diseases190420······No··YesNo3No access to handwashing facilityLower respiratory infections8050110····No··YesNo2Air pollution3Ambient particulate matter pollutionLower respiratory infections0····190····NoYesYesNo3Ambient particulate matter pollutionTracheal, bronchus, and lung cancer0····270····NoYesYesYes3Ambient particulate matter pollutionIschaemic heart disease0····160····NoYesYesYes3Ambient particulate matter pollutionIschaemic stroke0····250····NoYesYesYes3Ambient particulate matter pollutionHaemorrhagic stroke0····250····NoYesYesYes3Ambient particulate matter pollutionChronic obstructive pulmonary disease0····120····NoYesYesYes3Household air pollution from solid fuelsLower respiratory infections0····0··90NoYesYesNo3Household air
