Associations between pharmaceutical industry interactions with physicians and chronic nonmalignant pain management prescribing practices: a systematic review

Chronic nonmalignant pain (CNMP) is commonly treated with opioids and other analgesics, yet prescribing carries risks and substantial costs. Promotional and financial interactions between clinicians and the pharmaceutical industry may influence analgesic prescribing, but CNMP-relevant evidence has not been systematically synthesized. We searched MEDLINE, EMBASE, CINAHL, PsycINFO, and Web of Science from inception to February 2025 (no language restrictions). We included observational studies assessing associations between pharmaceutical industry interactions and analgesic prescribing outcomes relevant to CNMP. Two reviewers independently screened studies, extracted data, assessed risk of bias using ROBINS‑I, and appraised certainty using GRADE. We synthesized findings using SWiM vote counting by direction of effect, and undertook random‑effects meta‑analysis when exposure and outcome definitions were sufficiently similar. Ten U.S. observational studies met inclusion criteria. Across 44 outcome contrasts, 38 (86%) were directed towards higher prescribing or higher opioid‑related expenditure among clinicians receiving payments/interactions; 6 contrasts evaluating marketing‑restriction policies were directed towards reduced prescribing. Because prescribing‑volume metrics were heterogeneous (e.g., prescriptions vs. days supplied), we did not pool volume outcomes. For expenditure, meta‑analysis of two studies showed that receipt of opioid‑related payments was associated with higher opioid‑related prescribing expenditure (pooled +$4,785 per physician‑year; 95% CI $2,162 to $7,408; I² = 93.5%). Under ROBINS‑I, studies were at low to moderate overall risk of bias, with residual confounding a key concern. GRADE certainty was moderate for prescribing expenditure and prescribing volume and low for dosage intensity. In U.S. real-world prescribing datasets, pharmaceutical industry interactions were consistently associated with higher analgesic prescribing and higher opioid-related expenditures, with repeated evidence of dose–response patterns. Evidence from institutional restriction policies suggests prescribing may be modifiable when promotional access is constrained. However, the evidence is observational and largely does not identify CNMP patients explicitly; residual confounding and indirectness should be considered when interpreting magnitude. PROSPERO CRD42024627184.