Were treatments/exposures and clinical outcomes measured in the same ways in both groups? (Was the assessment of outcomes either objective or blinded to exposure?)
The application of explicit criteria for the outcomes of interest, a discussion of how they were applied and evidence that they were applied without knowledge of which group the patient was in is important. Blinding is crucial if any judgment is required to assess the outcome (in RCTs and cohorts studies) or the exposure (in case control studies). For example, an unblinded investigator may search more aggressively for outcomes in people with exposure to the putative agent. Similarly, people with the adverse outcome may be more likely to have brooded about their situation and may have greater incentive to recall possible exposure. Therefore we would want patients and interviewers to be blind to the study hypothesis.
In the RCT that we retrieved, the outcome was death and was the same for both groups.
- Were there clearly defined groups of patients, similar in all important ways other than exposure to the treatment or other cause?
- Were treatments/exposures and clinical outcomes measured in the same ways in both groups? (Was the assessment of outcomes either objective or blinded to exposure?)
- Was the follow-up of the study patients sufficiently long (for the outcome to occur and complete)?
Do the results of the harm study fulfil some of the diagnostic tests for causation?
- Is it clear that the exposure preceded the onset of the outcome?
- Is there a dose-response gradient?
- Is there any positive evidence from a 'dechallenge-rechallenge' study?
- Is the association consistent from study to study?
- Does the association make biological sense?