Treatment Effect Heterogeneity in Cardiovascular Medicine

Treatment Effect Heterogeneity in Cardiovascular Medicine - Andrew Foy, MD (wistia.com)

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Learning objectives:

1. Define treatment effect heterogeneity (HTE)

2. Understand the theoretical framework of HTE and the individual domains that contribute to it

3. Appreciate how HTE is scale dependent

4. Know how HTE is traditionally assessed in clinical trials (single variable subgroup analysis) and be able to contrast it with emerging methods of HTE assessment (risk modeling and effect modeling)

5. Recognize important limitations of subgroup analysis

6. Understand limitations of RCTs that limit confidence in the external validity of their results (Efficacy-Effectiveness Gap)

7. Explore mechanisms of HTE through review of cases in CV medicine

Tips for applying RCT results to patient care:

1. When you know your patient would not be included in RCT, proceed cautiously (if at all)

   1. Advanced age, frailty, complex multimorbidity or meets explicit exclusion criteria for trial

2. When you are unsure if your patient would be included, proceed cautiously (reduce TE by half and double harms & think, “Does this still seem like an attractive option?”

3. When you are confident your patient would be included in RCT, attempt to replicate RCT procedures (i.e., dose initiation, up-titration schedule, safety monitoring, etc.)

   1. If you cannot, proceed cautiously

4. Pay attention to entry conditions

5. Appreciate that certain patients are not included in RCTs because investigators know they WILL NOT be able to show benefit – so why would you try it on them?