Interpreting heterogeneity and effect size in meta-analysis of Suzetrigine for acute pain
Abstract
Dear Editor, We read with interest the systematic review and meta-analysis by Bansal et al.[1] evaluating Suzetrigine, a selective NaV1.8 inhibitor, for acute postoperative pain. The authors should be commended for synthesizing emerging phase 2 and phase 3 data on this promising non-opioid analgesic. However, certain methodological considerations warrant further discussion to aid clinical interpretation. First, the primary efficacy outcomes demonstrated extremely high statistical heterogeneity [I² ≈ 99–100% for both sum of pain intensity difference over 48 h (SPID48) and over 24 h (SPID24)].[1] While the use of a random-effects model is appropriate, such levels of inconsistency substantially limit the interpretability of pooled estimates. Contemporary methodological guidance emphasizes that when heterogeneity approaches this magnitude, exploration through subgroup or sensitivity analyses becomes essential rather than relying solely on summary effects.[2] Given that the included trials represent two distinct surgical pain models, bunionectomy and abdominoplasty, procedure-specific subgroup analyses could have clarified whether treatment effects differ across nociceptive contexts. Second, in phase 2 trials evaluating multiple dosing regimens, only the highest-dose Suzetrigine arms were selectively incorporated into pooled analyses.[1] This approach risks dose-selection bias and potential inflation of effect size estimates. Current recommendations for evidence synthesis support…
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