STROBE-ME (STROBE Extension for Molecular Epidemiology)

What it is

— STROBE-ME (STrengthening the Reporting of OBservational studies in Epidemiology — Molecular Epidemiology) is a reporting checklist that extends the parent STROBE statement to observational studies that measure biomarkers in biological specimens (genetic, epigenetic, protein, metabolite, adduct, exposure, or effect markers). It does not replace STROBE; it adds nine biomarker-specific items and amends eight existing STROBE items so that the laboratory and biospecimen layer of a molecular-epidemiology study is reported as transparently as the design and analysis layers. STROBE-ME was published by Gallo, Egger, Vineis and colleagues in 2011, released simultaneously across seven journals (the open-access canonical version is PLoS Medicine 8(10):e1001117), and is hosted and maintained as a STROBE extension within the EQUATOR Network. Its purpose is to make the provenance, measurement, and quality control of every biomarker auditable, so that a reader can judge whether a reported exposure–outcome or biomarker–outcome association is real or an artifact of assay error, batch effects, specimen degradation, or differential measurement.

When to use

— Apply STROBE-ME when reporting an observational study (cohort, case-control, or nested case-control, including biobank- and registry-linked designs) in which a biomarker measured from a biological sample is a study variable — as exposure, effect, susceptibility, intermediate, or outcome marker. It is the appropriate checklist for a peer-reviewed molecular-epidemiology manuscript and for the molecular-epidemiology components of a biomarker-qualification or exposure-assessment package submitted to a regulator. Decision rule for choosing the right family member: use the parent STROBE for an observational study with no biospecimen measurement; use STROBE-ME when a biomarker is measured and the study is general molecular epidemiology; use STROME-ID (a separate extension, slug `strome-id`) for molecular epidemiology of infectious diseases where pathogen typing and transmission inference dominate; and use STREGA / STROBE-MR for the gene-association and Mendelian-randomization questions those extensions were written for. If your study uses routinely collected administrative claims or EHR data with no biospecimen assay, STROBE-ME is the wrong checklist — use RECORD (or RECORD-PE for pharmacoepidemiology on routinely collected data), or HARPER/the ENCePP checklist for a non-interventional study protocol.

What it requires

— STROBE-ME enforces reporting of the biospecimen-and-assay chain that the parent STROBE leaves implicit. The substantive added/amended domains are: (1) biomarker rationale and choice — why this marker, what biological construct it stands for, and whether it is a marker of exposure, effect, or susceptibility; (2) biospecimen collection, transport, processing, and storage — sample type, time and conditions of collection, freeze–thaw history, storage duration and temperature, and any pre-analytical handling that could degrade the analyte; (3) laboratory methods — the assay/platform, analytic protocol, batch design and randomization of samples across batches, and blinding of laboratory personnel to case/control or outcome status; (4) validity, reliability, and reproducibility of the biomarker — limits of detection/quantification, coefficients of variation, intra-/inter-assay reproducibility, and use of internal/external quality-control samples; (5) measurement error and its handling — reporting how below-limit-of-detection values, missing assays, and classical or differential measurement error are treated, and any validation substudy or external adjustment used to correct attenuation; (6) population stratification when genetic markers are used; and (7) ethics of stored specimens — consent for storage and future use, biobank governance, and return of incidental/individual findings. The parent STROBE items it amends are framed so that, for a biomarker variable, "measurement" (item 8), "bias" (item 9), and "limitations" (item 19) are all answered in terms of assay validity, not just design.

When NOT to use — limitations and common misapplications

— STROBE-ME is a reporting checklist, not a risk-of-bias instrument, not a quality score, and not a substitute for design validity. Concrete failure modes: (1) Wrong extension for the design — using STROBE-ME for a study with no biomarker (use parent STROBE), for an infectious-disease molecular study (use STROME-ID), or for a routinely-collected-data pharmacoepidemiology study (use RECORD/RECORD-PE) — and, conversely, citing plain STROBE for a biomarker study, which omits the entire laboratory-reporting layer. (2) Checklist-as-theater — ticking the biomarker items while leaving batch design, blinding, limit-of-detection handling, or storage history vague defeats the purpose; the value is the specificity, not the page count. (3) Mistaking reporting for validity — a fully STROBE-ME-compliant paper can still describe a study crippled by batch confounding, reverse causation (the biomarker measured after disease onset), or selection into the biobank; completing the checklist does not make an observational biomarker association causal or unconfounded. (4) Treating it as a substitute for STROBE — STROBE-ME is an extension; the parent items still apply. (5) Ignoring measurement-error correction — reporting a single biomarker value without CVs, reliability, or attenuation correction invites regression dilution that no amount of confounding adjustment fixes.

How it maps to this catalog

— STROBE-ME's biomarker layer maps to a focused set of concepts in this repo; the overlap with generic pharmacoepidemiology design machinery is deliberately thin, because STROBE-ME governs assay and specimen reporting rather than confounding control: - The study object: biomarker-defined-cohort-rwe is the design STROBE-ME most directly governs; cohort-prospective, cohort-retrospective, and case-control (and nested-case-control) are the parent designs whose biomarker variables it reports. - Assay validity and measurement (items 3–5 above): algorithm-validation supplies the validity/reliability and sensitivity/specificity discipline that STROBE-ME demands of a biomarker assay (the analogue of phenotype-algorithm validation); misclassification-bias-correction-rwe and external-adjustment-validation-substudy-bias-correction-rwe implement the measurement-error correction and validation-substudy adjustment the checklist asks authors to report; negative-control-exposures-rwe operationalizes the residual-confounding/quality-control checks that detect batch or measurement artifacts. - Generalizability of a biobank sample: generalizability-transportability-external-validity-rwe addresses the selection-into-biobank limitation STROBE-ME asks authors to acknowledge. These are the lens STROBE-ME pre-specifies for a biomarker study — not a claim that hdPS, time-zero alignment, or active-comparator design are STROBE-ME items.

Applied note (biobank-/registry-linked RWE)

A molecular-epidemiology study that links a biobank to a disease registry or claims data should, under STROBE-ME, report the full pre-analytical history of each specimen, randomize samples across assay batches and blind the laboratory to case status, quantify assay reliability with QC samples and CVs, state how below-LOD and missing biomarker values are handled, and — where a single measurement stands in for a long-term construct — report a validation substudy or external adjustment for measurement error. For the non-biomarker parts of such a linked study (administrative exposure or outcome definitions, attrition, confounding), the routinely-collected-data reporting items live in RECORD/RECORD-PE, not STROBE-ME.