PROSPERO

What it is

PROSPERO is the International Prospective Register of Systematic Reviews, an open-access registry created in 2011 and maintained by the Centre for Reviews and Dissemination (CRD), University of York, with early support from the UK National Institute for Health Research. It is a prospective protocol registry, not a reporting checklist and not a critical-appraisal instrument. Authors deposit the key methodological intentions of a planned systematic review — the question, eligibility criteria, search strategy, outcomes, risk-of-bias plan, and synthesis plan — before they begin formal screening and data extraction, and receive a permanent registration number and time-stamped public record. Its purpose is to make the review's a-priori plan discoverable and citable so that the published review can be checked against what was promised, reducing unplanned outcome switching, selective reporting, and unintended duplication of effort. Scope is restricted to systematic reviews with a health-related outcome (interventions, diagnosis, prognosis, etiology, screening) where the protocol has not yet progressed past the data extraction stage; reviews already completed cannot be registered. PROSPERO is part of the broader transparency ecosystem alongside the EQUATOR reporting guidelines (PRISMA family), but registration and reporting are distinct acts.

When to use

Register on PROSPERO before screening/extraction whenever you are conducting a systematic review or meta-analysis of human health-related studies — including reviews of randomized trials, reviews of non-randomized/observational (real-world) studies, network meta-analyses, and diagnostic-test-accuracy reviews. Registration is expected by most peer-reviewed journals, is a PRISMA 2020 reporting item (the published review must state the registry and ID), and strengthens HTA/payer evidence dossiers and FDA/EMA submissions that lean on a systematic review of the comparative evidence. Decision rule for which registry: if the deliverable is a systematic review/meta-analysis of human studies, use PROSPERO. If the deliverable is a primary non-interventional/pharmacoepidemiologic study (cohort, case-control, target-trial emulation, or a regulatory post-authorization safety study/PASS on claims, EHR, or registry data), PROSPERO is the wrong registry — register the study in the EU PAS Register / HMA-EMA Catalogue of RWD studies (or ClinicalTrials.gov where appropriate). If the deliverable is an interventional clinical trial, use ClinicalTrials.gov / EudraCT-CTIS. PROSPERO registers the review of such studies, never the primary studies themselves.

What it requires

PROSPERO is a structured registration record, not a checklist scored for completeness; the substantive fields it enforces are the pre-specified methodological commitments of the planned review: (1) review question and PICO/eligibility — population, interventions/exposures, comparators, outcomes, and study designs to be included; (2) the information sources and search strategy (databases, dates, planned search terms); (3) the primary and secondary outcomes, stated a priori so that later outcome switching is detectable; (4) the planned risk-of-bias / quality-assessment tool (e.g., RoB 2, ROBINS-I, AMSTAR-2 for umbrella reviews) and how certainty will be graded (e.g., GRADE); (5) the data-extraction and synthesis plan (qualitative synthesis, meta-analysis model, planned subgroup/sensitivity analyses, handling of heterogeneity); (6) administrative items — anticipated/actual start and completion dates, the review team and roles, funding sources, and conflicts of interest. For reviews of real-world data, the strongest records also pre-specify how the underlying studies' data-fitness and design features (phenotype/ algorithm validity, time-zero alignment, confounding control, attrition) will be appraised and synthesized — but these are appraisal criteria applied to the included studies, not fields PROSPERO imposes on a primary analysis.

When NOT to use — limitations and common misapplications

- It is not a reporting guideline. A PROSPERO record does not substitute for PRISMA-P (protocol reporting) or PRISMA 2020 (final-review reporting); a complete registration with a poorly reported manuscript still fails peer review. - It is not a risk-of-bias or quality instrument. Registering a review says nothing about its methodological quality — that is the job of AMSTAR-2 (appraising the SR) and ROBINS-I / RoB 2 (appraising the included studies). Treating the PROSPERO ID as a quality signal is a category error. - Registration is not adherence. Discrepancies between the registered plan and the published review (outcome switching, added/dropped analyses) are well documented; the value of registration is realized only when reviewers and editors check the record against the paper. Registration-as-theater — a record filed and ignored — provides no protection. - Wrong registry for primary RWE. Using PROSPERO to register a primary pharmacoepidemiology study, target-trial emulation, or a PASS is a scope error; those belong in the EU PAS Register / HMA-EMA RWD Catalogue. PROSPERO will not accept primary studies, only reviews of them. - Too late to register. A review that has already passed the data-extraction stage is not eligible for prospective registration, and back-filling a record after results are known defeats the purpose.

How it maps to this catalog

PROSPERO governs the systematic-review layer, so its natural neighbors are the SR/MA guideline family, not the primary-RWE design concepts. The protocol-reporting requirements it presupposes are implemented by prisma-p; the final-review reporting (which must cite the PROSPERO ID) by prisma-2020; network meta-analyses by prisma-nma and diagnostic-accuracy reviews by prisma-dta; the search-reporting field by prisma-s. The risk-of-bias / certainty plan that PROSPERO asks you to pre-specify is operationalized by robins-i (non-randomized studies of interventions), amstar-2 (critical appraisal of the systematic review itself), and grade (certainty of evidence). When the included studies are real-world database analyses, the appraisal you pre-register draws on the primary-data concepts — e.g., claims-analysis for the data substrate, and the design quality of any target-trial-emulation included in the review. Applied note for claims/EHR/registry RWE: a systematic review or meta-analysis of observational drug-safety or comparative- effectiveness studies built on claims/EHR data should register in PROSPERO and, in the registered protocol, commit to ROBINS-I for the included studies and GRADE for certainty — but the primary database studies being synthesized are themselves registered in the EU PAS Register, not PROSPERO.