Added value and cascade effects of inflammatory marker tests in UK primary care: a cohort study from the Clinical Practice Research Datalink

BACKGROUND: Inflammatory markers (C-reactive protein, erythrocyte sedimentation rate, and plasma viscosity) are commonly used in primary care. Though established for specific diagnostic purposes, there is uncertainty around their utility as a non-specific marker to rule out underlying disease in primary care. AIM: To identify the value of inflammatory marker testing in primary care as a rule-out test, and measure the cascade effects of testing in terms of further blood tests, GP appointments, and referrals. DESIGN AND SETTING: Cohort study of 160 000 patients with inflammatory marker testing in 2014, and 40 000 untested age, sex, and practice-matched controls, using UK primary care data from the Clinical Practice Research Datalink. METHOD: The primary outcome was incidence of relevant disease, including infections, autoimmune conditions, and cancers, among those with raised versus normal inflammatory markers and untested controls. Process outcomes included rates of GP consultations, blood tests, and referrals in the 6 months after testing. RESULTS: The overall incidence of disease following a raised inflammatory marker was 15%: 6.3% infections, 5.6% autoimmune conditions, 3.7% cancers. Inflammatory markers had an overall sensitivity of <50% for the primary outcome, any relevant disease (defined as any infections, autoimmune conditions, or cancers). For 1000 inflammatory marker tests performed, the authors would anticipate 236 false-positives, resulting in an additional 710 GP appointments, 229 phlebotomy appointments, and 24 referrals in the following 6 months. CONCLUSION: Inflammatory markers have poor sensitivity and should not be used as a rule-out test. False-positive results are common and lead to increased rates of follow-on GP consultations, tests, and referrals.