- Were there clearly defined groups of patients, similar in all important ways other than exposure to the treatment?
- Were treatment exposures and clinical outcomes measured in the same way in both groups?
- Was the follow-up of study patients complete and long enough?
- Do the results satisfy some “diagnostic tests for causation”?
- Is it clear that the exposure preceded the onset of the outcome?
- Is there a dose-response gradient?
- Is there positive evidence from a “dechallenge – rechallenge” study?
- Is the association consistent from study to study?
- Does the association make biological sense?
Reference: Evidence-based Medicine – Sackett, Richardson, Rosenberg and Haynes.