Table 1 ROB-NRSE tool

1

1.1

Is there potential for confounding of the effect of exposure in this study?

If N/PN to 1.1: the study can be considered to be at low risk of bias due to confounding and no further signaling questions need be considered.

If Y/PY to 1.1, answer 1.2 and 1.3 to determine whether there is a need to assess time-varying confounding:

1.2

Was the analysis based on splitting follow up time according to exposure received?

If N or PN to 1.2, answer questions 1.4 to 1.6, which relate to baseline confounding

If Y or PY to 1.2, go to question 1.3

1.3

Were exposure discontinuations or switches likely to be related to factors that are prognostic for the outcome?

If N or PN to 1.3, answer questions 1.4 to 1.6, which relate to baseline confounding

If Y/PY, answer questions relating to both baseline and time-varying confounding (1.7 and 1.8)

1.4

Did the authors use an appropriate analysis method that adjusted for all the important confounding areas?

1.5

If Y/PY to 1.4: Were confounding areas that were adjusted for measured validly and reliably by the variables available in this study?

1.6

Did the authors avoid adjusting for post-exposure variables?

1.7

Did the authors use an appropriate analysis method that adjusted for all the critically important confounding areas and for time-varying confounding?

1.8

If Y or PY to 1.7: Were confounding areas that were adjusted for measured validly and reliably by the variables available in this study?

Risk of bias judgement

Optional: What is the predicted direction of bias due to confounding?

2.

2.1

Was selection of participants into the study (or into the analysis) based on variables measured after the start of the exposure?

If N/PN to 2.1: go to 2.4

2.2

If Y/PY to 2.1: Were the post-exposure variables that influenced selection associated with exposure?

2.3

If Y/PY to 2.2: Were the post-exposure variables that influenced eligibility selection influenced by the outcome or a cause of the outcome?

2.4

Do start of follow-up and start of intervention coincide for most participants?

2.5

If Y/PY to 2.2 and 2.3, or N/PN to 2.4: Were adjustment techniques used that are likely to correct for the presence of selection biases?

Risk of bias judgement

Optional: What is the predicted direction of bias due to selection of participants into the study?

3.

3.1

Is exposure status well defined?

3.2

Did entry into the study begin with start of the exposure?

3.3

Was information used to define exposure status recorded prior to outcome assessment?

3.4

Could classification of exposure status have been affected by knowledge of the outcome or risk of the outcome?

3.5

Were exposure assessment methods robust (including methods used to input data)?

Risk of bias judgement

Optional: What is the predicted direction of bias due to measurement of outcomes or exposures?

4.

4.1

Is there concern that changes in exposure status occurred among participants?

If your aim for this study is to assess the effect of initiating and adhering to an exposure (as in a per-protocol analysis), answer questions 4.2 and 4.3, otherwise continue to 4.4 if Y or PY to 4.1.

4.2

Did many participants switch to other exposures?

4.3

Were the critical co-exposures balanced across exposure groups?

4.4

If Y/PY to 4.1, or Y/PY to 4.2, or 4.3: Were adjustment techniques used that are likely to correct for these issues?

Risk of bias judgement

Optional: What is the predicted direction of bias due to departures from the intended exposures?

5.

5.1

Were there missing outcome data?

5.2

Were participants excluded due to missing data on exposure status?

5.3

Were participants excluded due to missing data on other variables needed for the analysis?

5.4

If Y/PY to 5.1, 5.2 or 5.3: Are the proportion of participants and reasons for missing data similar across exposures?

5.5

If Y/PY to 5.1, 5.2 or 5.3: Were appropriate statistical methods used to account for missing data?

Risk of bias judgement

Optional: What is the predicted direction of bias due to missing data?

6.

6.1

Could the outcome measure have been influenced by knowledge of the exposure received?

6.2

Was the outcome measure sensitive?

6.3

Were outcome assessors unaware of the exposure received by study participants?

6.4

Were the methods of outcome assessment comparable across exposure groups?

6.5

Were any systematic errors in measurement of the outcome unrelated to exposure received?

Risk of bias judgement

Optional: What is the predicted direction of bias due to measurement of outcomes?

7

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?

7.2

…multiple analyses of the exposure-outcome relationship?

7.3

…different subgroups?

Risk of bias judgement

Optional: What is the predicted direction of bias due to selection of the reported result?

Overall risk of bias

Risk of bias judgement

Optional: What is the overall predicted direction of bias for this outcome?