1. Assessment of Harm based on our best available evidences The EBM workshop A.A.Haghdoost, MD; PhD of Epidemiology Ahaghdoost@kmu.ac.ir

2. EBM workshop: Assessment of Harm Dr. A.A.Haghdoost Why should we assess Harm  To choose the best treatment strategy  To address to public questions and mass media “Do oral contraceptives cause breast cancer?” “Do calcium antagonists increase the risk of death or cancer?”

3. EBM workshop: Assessment of Harm Dr. A.A.Haghdoost Main steps  Systematic search  Check the validity of findings  Evaluate the importance of findings  Assess if the results are applicable to our setting

4. EBM workshop: Assessment of Harm Dr. A.A.Haghdoost Concerns Are the results of published harm/aetiology study valid? People listen to mass media much more than expert

5. EBM workshop: Assessment of Harm Dr. A.A.Haghdoost Main question? 1. 1.Were there clearly defined groups of patients, similar in all important ways other than exposure to the treatment or other cause  Clinical trials  Cohorts  Case-controls  Case reports phocomelia in children born to women who took thalidomide Continued in next page

6. EBM workshop: Assessment of Harm Dr. A.A.Haghdoost Main question? WeaknessesStrengthsAssessment Starting Point Design feasibility, generalizabilityinternal validity adverse event status exposure status RCT susceptible to threats to internal validity feasible when randomization of exposure not possible adverse event status exposure status Cohort susceptible to threats to internal validity overcomes temporal delays, may only require small sample size exposure status adverse event status Case- Control

7. EBM workshop: Assessment of Harm Dr. A.A.Haghdoost 2. 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?)  More attention to positive group  Hawthorn effect Continued in next page Main question?

8. EBM workshop: Assessment of Harm Dr. A.A.Haghdoost 3. Was the follow-up of the study patients sufficiently long (for the outcome to occur and complete)?  Long enough to present the adverse effect  Long follow up usually increases the number of censured records Continued in next page Main question?

9. EBM workshop: Assessment of Harm Dr. A.A.Haghdoost 4. Do the results of the harm study fulfill 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? Main question?

10. EBM workshop: Assessment of Harm Dr. A.A.Haghdoost Are the valid results of the harm study important? What is the magnitude and precision of the association between the exposure and outcome?  OR, RR  NNH (Number Needed for Harm)  PAF (Population attributable Fraction)  Cost-benefits

11. EBM workshop: Assessment of Harm Dr. A.A.Haghdoost Can be applied on our setting 1. 1.Is our patient so different from those included in the study that its results don’t apply? 2. 2. What is our patient’s risk of the adverse event? What is our patient’s potential benefit from the therapy? 3. 3.What are our patient’s preferences, concerns and expectations from this treatment? 4. 4.What alternative treatments are available?