Was the follow-up of the study patients sufficiently long (for the outcome to occur and complete)?
If follow-up is short, it may be that too few study patients will have the outcome of interest, thus providing little information of use to a patient. For example, if investigators were looking at the association between cancer and a particular agent and the follow-up time was 1 month, this would be too short for the investigators to see a clinically important effect.
The more people who are unavailable for follow-up, the less accurate the estimate of the risk of the outcome is. Losses may occur because patients are too ill (or too well) to be followed or may have died, and the failure to document these losses threatens the validity of the study.
The RCT that we found was stopped early because an increased risk of death was noted.
- 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?