Clinical utility and harm potential of direct-to-consumer laboratory test panels: a cross-sectional content analysis across commercial providers in the United States and Europe

Objectives No study has systematically assessed the clinical appropriateness of tests in commercial direct-to-consumer (DTC) laboratory panels. We classified tests from major DTC platforms against screening guidelines and mapped the European regulatory landscape. Methods Cross-sectional content analysis of 76 wellness panels (≥10 biomarkers) offered through the direct access testing (DAT) model from 12 platforms across seven countries (April 2026). Tests were standardized to Logical Observation Identifiers Names and Codes (LOINC) and classified into four tiers: beneficial (Tier 1), context-dependent (Tier 2), low-value waste (Tier 3), and cascade-driving harm (Tier 4 – false positives triggering biopsies, surgery, or imaging). Two blinded coders classified tests (Cohen’s κ=0.71, linear weighted, below pre-specified κ≥0.80; 100 % agreement on Tier 4). Results Of 191 unique tests across 2,829 test-instances, 58.1 % (95 % confidence interval [CI] 51.0–64.9 %) were Tier 3 or 4. Nine tests (4.7 %), predominantly tumor markers, were Tier 4 cascade drivers. Tier 3 + 4 proportions varied across platforms (χ 2 =242.33, degrees of freedom [df]=11, p<0.001), from 2.8 % to 37.9 %. The largest panel generated 9.8 expected false positives per healthy consumer. The same multinational corporation operated under mandatory prescription in one EU country and unrestricted DTC access in another. Conclusions Over half of tests in commercial DAT wellness panels lack screening evidence, and a subset – predominantly tumor markers – functions as documented cascade drivers in healthy individuals. The four-tier framework distinguishing waste from harm offers a tool for regulatory evaluation of DTC panel composition.