Evidence-based Medicine Toolkit

44 Evidence-based Medicine Toolkit• Is there a dose–response gradient? If the exposure was causingthe outcome, you might expect to see increased harmful effectsas a result of increased exposure: a dose–response effect.• Is there evidence from a ‘dechallenge–rechallenge’ study? Doesthe adverse effect decrease when the treatment is withdrawn(‘dechallenge’) and worsen or reappear when the treatment isrestarted (‘rechallenge’)?• Is the association consistent from study to study? Try findingother studies, or, ideally, a systematic review of the question.• Does the association make biological sense? If it does, a causalassociation is more likely.Are the results important?This means looking at the risk or odds of the adverse effect with(as opposed to without) exposure to the treatment; the higher therisk or odds, the stronger the association and the more we shouldbe impressed by it. We can use the single table to determine if thevalid results of the study are important.ExposureAdverse outcomePresent(case)Absent(control)TotalsYes (cohort) a b a+bNo (cohort) c d b+dTotals a+c b+dIn a cohort study: Relative risk = (a/[a+b])(c/[c+d])In a case–control study Odds ratio = a × db × cTo calculate NNH for any OR and PEER [PEER (OR – 1)] + 1PEER (OR – 1)(1 – PEER)A cohort study compares the risk of an adverse event amongstpatients who received the exposure of interest with the risk in asimilar group who did not receive it. Therefore, we are able tocalculate a relative risk (or risk ratio). In case–control studies, we