Table 5 Summary of recommendations for investigating clinical heterogeneity in systematic reviews
Recommendation Category | Recommendation Description |
|---|---|
A-priori planning | 1. All plans for investigating clinical heterogeneity should be made explicit, a-priori (e.g., in the protocol for the systematic review). |
Clinical expertise | 2. The review/investigative team should include clinical experts or state a plan for consulting clinical experts during the review protocol development and implementation (e.g., when choosing clinical covariates and when interpreting the findings). |
Covariate rationale | 3. Clinical covariates should be chosen that have a clearly stated rationale for their importance (e.g., a pathophysiological argument, reference to the results of a previous trial). |
Thinking through covariate categories | 4. Review teams should think through the following categories to determine if related covariates might logically influence the treatment effect in their particular review: participant level, intervention level, outcome level, research setting, or others unique to their research question. |
Covariate hierarchy | 5. A logical hierarchy of clinical covariates should be formed and investigated only if there is sufficient rationale and a sufficient number of trials available (10 trials per covariate). |
Post hoc covariate identification | 6. State any plans to include additional covariates after looking at the data (post hoc) from included studies (e.g., forest plots, radial plots) and how they plan to do this. |
Statistical methods | 7. Describe a-priori the statistical methods proposed to investigate identified covariates. Refer to accepted texts or published papers in the area to be sure to implement these methods in a valid manner. Include an individual with experience in conducting these analyses.1 |
Data sources | 8. Aggregate patient data: Reasonable for investigating trial level covariates |
9. Individual patient data: Consider when investigating participant level covariates (otherwise results are subject to ecologic bias) | |
Interpretation | 10. A. Protocol: Describe how the results of any findings are going to be interpreted and used in the overall synthesis of evidence. B. Review: Consider the observational nature of these investigations; consider confounds and important potential biases; consider magnitude of the effect, confidence intervals and directionality of the effect. |