Clinical equipoise as inclusion criterion to control for confounding in observational studies

This study investigates whether higher levels of expert disagreement, as a proxy for clinical equipoise, are associated with improved baseline comparability between treatment groups in patients with proximal humerus fractures. Additionally, it aimed to assess how progressively stricter inclusion criteria-based on this disagreement-affect the distribution of baseline characteristics between the treatment groups.

We used data from the LADON Humerus study, a multicentre, prospective cohort including patients treated operatively or non-operatively in five hospitals in the Netherlands and Switzerland. An international expert panel of trauma surgeons assessed anonymized cases, blinded to the actual treatment, and each expert gave a treatment recommendation. Disagreement between the treatment given and the expert recommendations was categorized into four levels (A: complete disagreement, B: partial disagreement, C: partial agreement, D: complete agreement). Standardized differences (StDiff) for age, sex, ASA score, and AO classification were used to assess comparability between treatment groups across disagreement levels.

A total of 351 patients were included in the analysis. Comparability between treatment groups improved as the level of disagreement increased. At complete disagreement (Level A), the groups were well balanced with respect to age, sex, and ASA score (StDiff ≤ 0.1). For AO classification, group comparability improved but remained insufficiently balanced at the highest level of disagreement. Stricter inclusion criteria resulted in improved balance at the cost of reduced sample size.

Using expert panel disagreement as inclusion criterion can enhance group comparability in observational research. This approach may reduce the potential for confounding when RCTs are not possible.