2. Responses to ROBINS‐I signalling questions and 'Risk of bias' judgements for Langan 2005.

Question	Signalling question response	Description
Bias due to confounding
1.1 Is there potential for confounding of the effect of intervention in this study?	Y	Aim of the study was to explore variables that may influence the factors associated with SUDEP. The 'intervention' of interest to us is 1 of those variables, so confounding is inevitable
1.2. If Y or PY to 1.1 Was the analysis based on splitting participants’ follow up time according to intervention received?	NA	Case‐control study, cases and controls were retrospectively examined over the same period of time
1.4. Did the authors use an appropriate analysis method that adjusted for all the critically important confounding domains?	PY	Multivariable logistic regression, but variables that were not significant in the model are not reported in the results
1.5. If Y or PY to 1.4: Were confounding domains that were adjusted for measured validly and reliably by the variables available in this study?	PY	Variables taken from a Medical Research Council (MRC) database/coroners' records/interviews with bereaved families. Probably fairly accurate
1.6. Did the authors control for any post‐ intervention variables that could have been affected by the intervention?	PN	Intervention is given over a period of time, and variables are also measured over a period of time with probable overlap
1.7. Did the authors use an appropriate analysis method that controlled for all the important confounding domains and for time‐varying confounding?	NA	Case‐control study, cases and controls were examined over the same period of time
'Risk of bias' judgement	Moderate	The objective of the study means that confounding is inevitable; however from the limited information available, it seems that an appropriate adjusted analysis was performed
Bias in selection of participants into the study
2.1. Was selection of participants into the study (or into the analysis) based on participant characteristics observed after the start of intervention?	N	Case‐control study, therefore selection was based on outcome (SUDEP or no SUDEP), not based on any participants characteristics and not related to the intervention
2.4 Do start of follow‐up and start of intervention coincide for most participants?	PN	Cases and controls are examined over a fixed period and it is not stated when any interventions were started for the cases and controls, unlikely that interventions were started at the beginning of the time period of interest for most participants
2.5 If N or PN to 2.4 Were adjustment techniques used that are likely to correct for the presence of selection biases?	PN	Controls were randomly sampled from a national database so unlikely that any selection bias was presented, therefore adjustment techniques probably not required
'Risk of bias' judgement	Low	Random sample of controls used and no evidence of any selection bias
Bias in classification of interventions
3.1 Were intervention groups clearly defined?	Y	Clear whether a participant had any of the listed supervision, but data for the controls missing
3.2 Was the information used to define intervention groups recorded at the start of the intervention?	PY	For controls, likely recorded at the time of intervention (continuous intervention over a period of time). For cases, this information may have been recorded following the outcome and information provided by a relative rather than the case (deceased)
3.3 Could classification of intervention status have been affected by knowledge of the outcome or risk of the outcome?	PN	For controls, likely recorded at the time of intervention (continuous intervention over a period of time). For cases, this information may have been recorded following the outcome and information provided by a relative rather than the case (deceased)
'Risk of bias' judgement	Moderate	For cases, it is possible that intervention status was recorded after outcome, which could be a source of bias
Bias due to deviations from intended interventions (aim for this study is to assess the effect of starting and adhering to intervention)
4.3. Were important co‐interventions balanced across intervention groups?	N	Number of AEDs and current use of carbamazepine not balanced across cases and controls
4.4. Was the intervention implemented successfully for most participants?	NI	No information given but possible that intervention could be disrupted (e.g. person supervised leaves the room) or devices fail
4.5. Did study participants adhere to the assigned intervention regimen?	NI	No information given regarding adherence to the interventions
4.6. If N or PN to 4.3, 4.4 or 4.5 Was an appropriate analysis used to estimate the effect of starting and adhering to the intervention?	N	Adherence to the intervention is not mentioned or taken account of in analysis
'Risk of bias' judgement	Moderate	Intervention of interest to us was not intended to be the only 'intervention' in the study. No information is given regarding adherence to the intervention, and co‐interventions may have been present
Bias due to missing data
5.1 Were outcome data available for all, or nearly all, participants?	Y	Participants selected based on outcome status (case‐control study)
5.2 Were participants excluded due to missing data on intervention status?	Y	A lot of missing data for the controls for intervention status
5.3 Were participants excluded due to missing data on other variables needed for the analysis?	Y	Data also missing for controls for other variables
5.4 If PN/N to 5.1, or Y/PY to 5.2 or 5.3: Are the proportion of participants and reasons for missing data similar across cases and controls?	N	A lot of missing data for controls, mostly complete for cases
5.5 If PN/N to 5.1, or Y/PY to 5.2 or 5.3: Is there evidence that results were robust to the presence of missing data?	N	Participants and variables with missing data excluded from analysis
'Risk of bias' judgement	Serious	A large proportion of missing data for outcome status and an imbalance of missing data across cases and controls
Bias in measurement of outcomes
6.1 Could the outcome measure have been influenced by knowledge of the intervention received?	N	Cases were those who had experienced SUDEP, controls had not experienced SUDEP
6.2 Were outcome assessors aware of the intervention received by study participants?	N	By design, cases and controls established first and then variable information including intervention status extracted afterwards
6.3 Were the methods of outcome assessment comparable across intervention groups?	N	By design, cases and controls established first and then variable information including intervention status extracted afterwards
6.4 Were any systematic errors in measurement of the outcome related to intervention received?	N	Cases were those who had experienced SUDEP, controls had not experienced SUDEP, therefore very unlikely that any errors related to measurement of the outcome occurred
'Risk of bias' judgement	Low	Objective outcome measurement established before intervention status
Bias in selection of the reported result
Is the reported effect estimate likely to be selected, on the basis of the results, from...
7.1 ...multiple outcome measurements within the outcome domain?	N	A single and clearly defined outcome, SUDEP or no SUDEP.
7.2 ...multiple analyses of the intervention‐outcome relationship?	PN	Multivariable analysis performed, unclear exactly how many variables were included in the model and whether results would have been different for the intervention‐outcome relationship if other non‐significant variables had been retained in the model
7.3 ...different subgroups?	N	No subgroups reported
'Risk of bias' judgement	Moderate	Results for 1 multivariable model reported, unclear if results would have been different for other multivariable models

Abbreviations: Y: yes; PY: probably yes; PN: probably no; N: no; NI: no information

AEDs: antiepileptic drugs
 SUDEP: Sudden Unexpected Death in Epilepsy