A Randomized Hybrid-Effectiveness Trial Comparing Pharmacogenomics (PGx) to Standard Care: The PGx Applied to Chronic Pain Treatment in Primary Care (PGx-ACT) Trial.

This trial aimed to identify the effects of providing pharmacogenomic (PGx) results and recommendations for patients with chronic pain treated in primary care practices compared to standard care. An open-label, prospective, largely virtual, type-2 hybrid effectiveness trial randomized participants to PGx or standard care arms. Adults with pain ≥ 3 months who were treated with tramadol, codeine, or hydrocodone enrolled. Alternative analgesics were recommended for CYP2D6 intermediate or poor metabolizers (IM/PMs). Prescribing decisions were at providers' discretion. The trial randomized 253 participants. A modified intent-to-treat primary analysis assessed change in pain intensity over 3 months among IM/PMs (PGx: 49; Standard care: 57). The PGx and standard care arms showed no difference in pain intensity change (-0.10 ± 0.63 vs. -0.21 ± 0.75 standard deviation; p = 0.74) or PGx-aligned care (69% vs. 63%; standardized difference [SD] = 0.13). In IM/PMs, secondary analyses of pain intensity change suggested improvements with PGx-aligned (n = 70; -0.21 ± 0.70) vs. unaligned care (n = 36; -0.06 ± 0.69) (SD = -0.22), with this difference increasing when examining IM/PMs with an analgesic change (aligned: n = 31, -0.28 ± 0.76; unaligned: n = 36, -0.06 ± 0.69; SD = -0.31). This approach to PGx implementation for chronic pain was not associated with different prescribing (i.e., similar proportions of PGx-aligned care) or clinical outcomes. Secondary analyses suggest that prescribing aligned with PGx recommendations showed a small improvement in pain intensity. However, the proportion of patients with a clinically meaningful improvement (≥ 30%) in pain intensity was similar. Future efforts should identify effective implementation methods.