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To the Editor, We thank Dr. Staal et al. for their interest in our review article on complex regional pain syndrome (CRPS) and for bringing to our attention a trial that had escaped the literature search. We have read the three trials discussed by Staal et al. and would like to present readers with a more cautious interpretation. First, in Barnhoon et al.’s study, an intention-to-treat analysis clearly showed no benefit associated with pain exposure physical therapy (PEPT) compared with conventional treatment. Staal et al. argue that more ‘‘nuanced’’ (i.e., positive) findings could be derived from a per protocol analysis. We respectfully disagree as the scientific gold standard remains intentionto-treat and not per protocol analysis. In fact, introducing the latter confers inherent bias (rather than ‘‘nuance’’), particularly as the authors might not have conducted a per protocol analysis had the intention-to-treat analysis revealed a treatment effect. For example, in Barnhoon et al.’s secondary analysis of the healthcare costs incurred during the first nine months of treatment, the intention-totreat analysis revealed that conventional treatment was 64% more expensive than PEPT. This led the authors to immediately conclude that cost differences favour PEPT without resorting to the ‘‘nuanced’’ per protocol analysis to confirm or disprove these findings. Second, den Hollander et al. have indeed reported that, compared with conventional treatment, exposure in vivo resulted in decreased self-reported disability, pain intensity, pain catastrophizing, perceived harmfulness of activities, and increased health-related quality of life. However, den Hollander et al. specifically recruited subjects with documented pain-related fear, whereas Barnhoon et al. did not triage for such a subset of patients. Despite this important distinction, Staal et al. draw a parallel between the two trials because they ‘‘share the theory of exposure to pain and stimulated use of the affected limb’’. Such an argument is flawed—it would be akin to stating that, since root canal therapy is indicated for dental cavities complicated by abscesses, it should also be performed for all cavities. In summary, based on our reading of the literature, we respectfully disagree with the assertion that PEPT ‘‘deserves a place in the treatment of CRPS’’. We concede that the current evidence supports its role in patients with pain-related fear. However, the available trials do not (yet) support its use in other subsets of CRPS patients. Nonetheless, they highlight the need for further randomized investigation with proper intention-to-treat analysis.

In reply: Pain exposure physical therapy in complex regional pain syndrome: promising enough to warrant further investigation