OBJECTIVES: Managing high-cost and highly toxic orphan and ultra-orphan drugs of precision medicine presents medication therapy management (MTM) problems for payers and their pharmacy benefit management and specialty pharmacy vendors who increasingly leverage volume throughput to lower cost. The rapid expansion of this drug class, fragmentation between pharmacy and medical benefit, and increasing use of pathways-based disease management add urgency to finding a solution to these problems. Patient-reported outcomes (PROs) may be the most direct and accurate assessment of disease and treatment impact. We report on an MTM pilot program using a PRO-based intervention algorithm. METHODS: OncoSource Rx (OSRx), a wholly owned specialty pharmacy of Cardinal Health, conducted a 1-month pilot study of a novel PRO-based MTM solution in conjunction with a regional Mid-Atlantic insurer. Patient-risk stratification by diagnosis and drug resulted in a scripted pharmacy technician phone call triage. All patients were contacted at initial fill of a specialty pharmacy prescription and periodically thereafter based on their risk profile. Patient queries were designed to identify barriers to medication possession. RESULTS: From CONCLUSIONS: PROs are believed to be a critical component of patient centered care. Incorporating PROs into daily practice is being actively studied. This pilot affirms that direct patient engagement via PRO can successfully overcome barriers to initiation of and adherence to prescribed treatment distributed by a specialty pharmacy.