痛みと緩和のジャーナル

抽象的な

Randomized Controlled Trial versus Real-World Study in Postherpetic Neuralgia

Nalamachu S* and Bucior I

Background: Potential flaws in the design of randomized controlled trials (RCTs) and their low generalizability to clinical practice are being increasingly discussed. As some recent RCTs in neuropathic pain, including postherpetic neuralgia (PHN), demonstrated moderate or no treatment effect, better understanding of factors that may improve trial design, effectiveness, and data interpretation is needed. Objective: To compare RCTs and a real-world study of gastroretentive gabapentin (G-GR) in PHN Methods: Data from two RCTs (Phase 3; n=359) and one real-world study (Phase 4; n=197) of patients with PHN who received G-GR 1800 mg once-daily. The Visual Analog Scale (VAS) and Brief Pain Inventory (BPI) were completed at baseline and the end of study. Patients’ Global Impression of Change (PGIC) was completed at the end of study. Results: Main differences in patient characteristics included higher baseline pain intensity on the VAS and BPI and no use of concomitant neuropathic pain medication in Phase 3. Reductions from baseline in the VAS (p=0.0201) and BPI pain scores (all p<0.05) were significantly greater in Phase 3 compared with Phase 4. In contrast, more patients reported “Very Much” or “Much” improvement on the PGIC in Phase 4 (p=0.0446). Similar proportion of patients experienced ≥1 AE (Phase 3, 54.6%; Phase 4, 50.8%), and AE incidence decreased rapidly to steady low levels after the 2-week titration. More patients discontinued treatment due to AEs during titration in Phase 4 (12.2% vs. 3.1%). Conclusion: To support evidence relevant to clinical practice in PHN and other neuropathic pain syndromes, real-world studies should be a standard complement to RCTs. Based on the RCT vs. real-world study comparison, management of AEs during titration seems important for achieving optimal treatment in clinical practice. For better trial design, measures of overall improvement (e.g., PGIC) should be considered as co-primary efficacy endpoints, along with pain intensity.