# The information in diagnostic tests: registered protocol **Record version:** 1.3.1 | **Registry:** ConductScience | **Registration ID:** CSR-DI-2026-001 **Registered with ConductScience:** August 16, 2026 **Published online:** September 13, 2026 **DOI registered:** September 13, 2026 **DOI:** https://doi.org/10.55157/csr.di.2026.001 https://conductscience.org/systematic-reviews/diagnostic-information ## Study overview Methodological evidence map and secondary synthesis of diagnostic accuracy reviews. Analysis completed; manuscript version 1.11.0 released on September 8, 2026. The complete analysis and manuscript release are documented by September 8, 2026. The exact review completion date is not separately recorded. ## Authors and correspondence Shuhan He (A1, A2, A3, A4); Joshua W. Joseph (A1); David M. Liebovitz (A5); Cory Rohlfsen (A6); Brian W. Locke (A7); Allison Goff (A4); Pedram Safari (A4); Christopher Kabrhel (A8, A3); Amal Mohamed (A1); Ali S. Raja (A9); Joshua N. Goldstein (A9). - A1: Division of AI, Department of Emergency Medicine, Mass General Brigham, Boston, Massachusetts, USA - A2: Laboratory of Computer Science, Massachusetts General Hospital, Boston, Massachusetts, USA - A3: Harvard Medical School, Boston, Massachusetts, USA - A4: Master of Science in Data Analytics, Health Sciences, Mass General Brigham University, Boston, Massachusetts, USA - A5: Departments of Medicine and Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA - A6: Department of Internal Medicine, University of Nebraska Medical Center, Omaha, Nebraska, USA - A7: Department of Pulmonary and Critical Care, Intermountain Medical Center, Murray, Utah, USA - A8: Department of Emergency Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA - A9: Department of Emergency Medicine, Mass General Brigham, Boston, Massachusetts, USA - Shuhan He: - Joshua W. Joseph: - David M. Liebovitz: - Cory Rohlfsen: - Brian W. Locke: - Allison Goff: - Pedram Safari: - Christopher Kabrhel: - Amal Mohamed: - Ali S. Raja: - Joshua N. Goldstein: Corresponding author: Shuhan He, she8@mgb.org. Shuhan He conceived the study, assembled the structured review data, specified and performed the analyses, interpreted the findings, created the figures and drafted the article. The other named authors contributed to interpretation and critically revised the manuscript. Shuhan He is the guarantor. OpenAI Codex assisted retrieval, code and language editing under author review. ## Research question Across reproducibly accessible diagnostic accuracy reviews, how much uncertainty about a binary target condition is a test or threshold expected to resolve at a stated starting probability, and how does this information relate to conventional test-performance measures? ## Rationale Diagnostic testing changes what is known about a target condition. Sensitivity and specificity describe test performance; likelihood ratios and post-test probabilities describe an observed result. Mutual information expresses the expected reduction in uncertainty before either result is known. Earlier studies established diagnostic applications of this measure. This study assembles a broad empirical reference scale from accessible diagnostic-review data so readers can interpret a diagnostic profile at a stated starting probability and compare its information with conventional accuracy measures. Information describes learning about a binary target. Clinical value also depends on consequences, available actions, and patient preferences. ## Objectives - Build an empirical reference distribution of expected diagnostic information from source-defined tests and thresholds. - Compare uncertainty resolved at 5%, 20%, and 50% starting disease probability and across a 1%-50% grid. - Examine agreement and differences between diagnostic information and Youden's J using source-comparable examples. - Distinguish expected information before testing from the probability update and uncertainty change after each result. ## Outcomes - Distribution of 100 x I(D;T)/H(D) at 5%, 20%, and 50% starting probabilities, with corresponding information in bits; each pooled estimate has equal weight. - Information profiles from 1% to 50% in one-percentage-point steps. - Spearman correlations with Youden's J and descriptive near-tie comparisons. - CEA information crossings and Ottawa ankle rule result branches. - Sensitivity to zero-cell correction and the regularized direct-binomial estimator. ## Eligibility ### Include - Diagnostic-review data with explicit study identifiers, source links, and non-negative integer TP, FP, FN, TN counts. - Groups with at least five unique study identifiers, one result per identifier, and at least three studies with both disease states represented. - Aggregate sensitivity plus specificity at least one in the source-defined orientation, with one canonical representation after exact row-signature deduplication. - Historical Cochrane groups linked to review-author-reported pooled findings; modern Cochrane main analyses; at most one canonical main table per OSF, Zenodo, or PMC review under the recorded priority rules. ### Exclude - Too few studies, repeated identifiers within a group, too few studies representing both disease states, or below-chance performance in the original orientation. - Counts reconstructed from rounded accuracy measures, pooled-only or consequence tables, and unsupported narrative transcription. - Duplicate representations and alternatives not selected by source-specific primary designation; preserve their status in the audit record. Secondary methodological synthesis of diagnostic accuracy reviews with accessible study-level cross-classification data; original designs are inherited from each source review. ## Search strategy No common date window: historical Cochrane is a fixed 2018 release; PMC uses 2020-2026 publication years; other sources use recorded inventories or queries. Source-specific limits govern inclusion. Search terms were English. The recorded API queries contain no language filter; eligibility depended on accessible structured study-level tables. No translation workflow was used in the recorded computational extraction. Public OSF, Zenodo, Figshare, Dryad, and SRDR deposits were examined for reusable diagnostic-review data. Dryad and SRDR contributed no primary pooled estimates. This accessible evidence sample is not an exhaustive search of unpublished studies or all diagnostic medicine. Searches are reproducible from the recorded queries, fixed inventories, dates and checksums. The Cochrane benchmark and two modern review packages were used for source-format validation. No separate search-validation exercise against an independent seed set is documented. The recorded acquisition used public repository files, published review packages and machine-readable PMC tables. No author-supplied private dataset or author-contact campaign is documented in this evidence base. This is a fixed evidence map. The registered analysis uses the dated inventories below; no rolling search update is part of this version. Any later update will be recorded as an amendment. ## Searches and source inventories The seven frozen inventories contain 3,979 discovery records. The primary analysis includes 210 reviews. Public discovery CSVs retain identifiers, titles, source links and recorded source terms; abstracts and raw documents are omitted. Their hashes are distinct from the original inventory hashes. ### Fixed historical and modern Cochrane sources Cochrane reference dataset and published review packages | 65 inventory records | August 16, 2026 ```text Retrieve CL145_open_set_20181101.zip from https://zenodo.org/records/1303259 (SHA-256 f921cf6f1a9236c86f89e7c646497639f45e8ff8fcf56008c1b27422829fec4f), and the already-held published packages for CD014911 and CD015089. Parse available study-level 2x2 tables with scripts/cochrane_dta_atlas.py at the pinned commit. This is fixed-corpus acquisition, not a new exhaustive Cochrane search. ``` 63 historical reviews and two selected modern reviews. The count and checksum identify the normalized corpus manifest. Acquisition and analysis are documented by 16 August 2026; the first download date of already-held packages is not recorded. [Download discovery index: Fixed historical and modern Cochrane sources (CSV)](https://conductscience.org/review-pilots/diagnostic-information/support/cochrane-discovery-1.0.0.csv) Public CSV SHA-256: `6dd1298f261c8015aad7f308f9fa3a5dfa7ef7485423e7a18dcf6c7d3d321d78` Original inventory SHA-256: `1a17f47b78c0e2ba7c2f326111e18d2a387d04780b2a36e7b7fe54a874f51321` ### OSF public deposits Frozen OSF metadata inventory and public-file inspection | 1,152 inventory records | August 17, 2026 ```text Run each recorded query separately: "diagnostic test accuracy" "diagnostic accuracy" "sensitivity and specificity" sensitivity specificity meta-analysis "true positive" "false positive" "2x2" diagnostic ``` The count and checksum identify the saved discovery inventory. Eligible evidence consists of publicly retrievable structured diagnostic-review data. [Download discovery index: OSF public deposits (CSV)](https://conductscience.org/review-pilots/diagnostic-information/support/osf-discovery-1.0.0.csv) Public CSV SHA-256: `c39cd11ee847db53b5f659aafc716af057b3ef71374d220cb4bafe8dc300406d` Original inventory SHA-256: `1f46eedb7af4d6d0724d55156ba98ebb92572f3b0c4378e521400d2cd634ec44` ### Zenodo public deposits Zenodo public metadata API | 799 inventory records | August 17, 2026 ```text Run each recorded query separately: "diagnostic test accuracy" "diagnostic accuracy" AND "systematic review" "diagnostic accuracy" AND "meta-analysis" "test accuracy" AND "meta-analysis" "sensitivity and specificity" AND "meta-analysis" "true positive" AND "false positive" AND "meta-analysis" "2x2" AND diagnostic AND "meta-analysis" ``` The count and checksum identify the saved discovery inventory. Eligible evidence consists of publicly retrievable structured diagnostic-review data. [Download discovery index: Zenodo public deposits (CSV)](https://conductscience.org/review-pilots/diagnostic-information/support/zenodo-discovery-1.0.0.csv) Public CSV SHA-256: `0d2f5cf21d79fd5fda118ca495b684058dfc7f416bdaac3584768ed8db49447a` Original inventory SHA-256: `0fa8e301ef599db6657089e96ef341e816f790e444a2c5fe28da202d4e61a44c` ### Figshare public deposits Figshare public metadata API | 262 inventory records | August 17, 2026 ```text Run each recorded query separately: "diagnostic test accuracy" "diagnostic accuracy" AND "systematic review" "diagnostic accuracy" AND "meta-analysis" "test accuracy" AND "meta-analysis" "sensitivity and specificity" AND "meta-analysis" "true positive" AND "false positive" AND "meta-analysis" "2x2" AND diagnostic AND "meta-analysis" ``` The count and checksum identify the saved discovery inventory. Eligible evidence consists of publicly retrievable structured diagnostic-review data. [Download discovery index: Figshare public deposits (CSV)](https://conductscience.org/review-pilots/diagnostic-information/support/figshare-discovery-1.0.0.csv) Public CSV SHA-256: `4189c39b0661362183e0bec516143b7a9c39b590ff622cc9bd2a986bfe39dbcc` Original inventory SHA-256: `b38dfd72097e51a97cc52f0d679097e3897e29249ad7a7cf11c50a14bb0efb4f` ### Dryad public deposits Dryad public metadata API | 11 inventory records | August 17, 2026 ```text Run each recorded query separately: "diagnostic test accuracy" "diagnostic accuracy" AND "systematic review" "diagnostic accuracy" AND "meta-analysis" "test accuracy" AND "meta-analysis" "sensitivity and specificity" AND "meta-analysis" "true positive" AND "false positive" AND "meta-analysis" "2x2" AND diagnostic AND "meta-analysis" ``` The count and checksum identify the saved discovery inventory. Eligible evidence consists of publicly retrievable structured diagnostic-review data. [Download discovery index: Dryad public deposits (CSV)](https://conductscience.org/review-pilots/diagnostic-information/support/dryad-discovery-1.0.0.csv) Public CSV SHA-256: `ab19fa797afc79a6cf998ee86207075fa6aa035d254934557a9df164d0572888` Original inventory SHA-256: `e2e5e7913d05a578b36fbaaca5f107bf5d2bb1d0b8905ad2953c43e4e1a5d52f` ### SRDR+ public deposits DataCite SRDR metadata and fixed public SRDR inventory | 172 inventory records | August 17, 2026 ```text publisher:"Systematic Review Data Repository"; retain the fixed inventory of 172 projects and apply the source-specific discovery and diagnostic-candidate rules in scripts/open_repository_dta.py. ``` The count and checksum identify the saved discovery inventory. Eligible evidence consists of publicly retrievable structured diagnostic-review data. [Download discovery index: SRDR+ public deposits (CSV)](https://conductscience.org/review-pilots/diagnostic-information/support/srdr-discovery-1.0.0.csv) Public CSV SHA-256: `31b6d35de9b9b2bf14e1328e82f9788e24122883586cf5128a874971415b9002` Original inventory SHA-256: `0576f936db6c27b7cde5147f346289b08c399d7ef90e5f96902a066c669ff88a` ### PubMed Central open-access review tables NCBI E-Utilities and PMC JATS XML | 1,518 inventory records | August 17, 2026 ```text (("diagnostic test accuracy"[Title/Abstract]) OR ("diagnostic accuracy"[Title/Abstract])) AND ("2x2"[All Fields] OR "2 x 2"[All Fields] OR ("true positive"[All Fields] AND "false positive"[All Fields] AND "false negative"[All Fields] AND "true negative"[All Fields])) AND (systematic review[Title/Abstract] OR meta-analysis[Title/Abstract]) AND open access[filter] AND 2020:2026[Publication Date] NOT protocol[Title] ``` The fixed query returned 1,518 articles on 2026-08-17; all were retrieved. Only explicit identifiers and integer TP, FP, FN, TN columns were normalized. Count and checksum identify articles.csv. [Download discovery index: PubMed Central open-access review tables (CSV)](https://conductscience.org/review-pilots/diagnostic-information/support/pmc-discovery-1.0.0.csv) Public CSV SHA-256: `fbf8c2be9e4690b934bc467cd271f3b8fcdbd6e4513e94ce02a1029c3ed47558` Original inventory SHA-256: `c0dbf4a9a700ef837e76b1f8551a1cb09c237d93a1ce1c8b9465ff731b81f8f3` ## Deduplication Retain source identifiers and compare exact normalized count-row signatures. Keep one result per identifier within a group; repeated identifiers make that group ineligible. The same study may contribute to different diagnostic profiles, so study-result appearances are not unique studies. ## Screening and table selection Shuhan He directed the computational selection and author audit. Fixed source priorities resolved representations; ambiguous groups were excluded or retained outside the primary sample. Source identities and metadata remained visible. The recorded workflow used one screener; no inter-reviewer agreement statistic was reported. Inspect structured review deposits and machine-readable PMC tables for explicit study-level counts. Preserve article, table, file and review identifiers and exclusion reasons. Selection used the single author-directed workflow described above. Codex assisted retrieval, parsing and code drafting. Selection used deterministic rules with author oversight. ## Data extraction and validation Parse explicit study identifiers and integer TP, FP, FN, TN cells while retaining source location, orientation and checksums. Do not reconstruct counts from rounded accuracy metrics. Apply canonical workbook/table rules. Shuhan He directed extraction and rechecked 50 table decisions and 1,640 extracted cells; the recorded audit found no acceptance or transcription errors. This was an author audit within the same workflow, with source identities retained. ## Missing data Groups require explicit study identifiers and integer 2x2 counts. Unavailable counts are not imputed or reconstructed from rounded accuracy measures. Missing threshold, setting, population and reference-standard descriptors remain missing and limit contextual comparisons. ## Risk of bias Interpret the estimates in the context of source-reported risk of bias and clinical setting. The atlas did not undertake a uniform study-level QUADAS-2 assessment; source reporting varies. ## Statistical synthesis Pool each eligible source-defined test or threshold separately with bivariate random-effects REML on sensitivity/specificity logits, adding 0.5 to all four cells in every study. Back-transform the fitted mean logits. Compute entropy, mutual information and percentage uncertainty resolved at the specified starting probabilities. Give each pooled estimate equal reference-distribution weight. Report pooled-mean intervals and plug-in predictive ranges conditional on fitted heterogeneity. Bootstrap reference medians over pooled estimates with 2,000 percentile replicates and a fixed seed; this does not propagate within-estimate uncertainty. Repeat analyses with correction only in zero-containing studies and with the regularized direct-binomial estimator. Treat within-review contrasts and CEA crossings as descriptive; no paired superiority inference or clinical utility ranking is supported. Distinguish signed entropy change, posterior-to-prior KL divergence, log2 likelihood ratio, and expected mutual information. The completed analysis contains 444 converged eligible bivariate fits. The primary reference scale retains 273 pooled estimates from 210 reviews and 4,104 study-result appearances. At a 20% starting probability, the median estimate removes 29.2% of starting uncertainty (0.211 of 0.722 bits). Shuhan He specified and performed the analyses. The workflow retained source identities and used deterministic scripts, numerical tests, source-summary comparisons and estimator sensitivity checks. No independent blinded second synthesis is documented. ## Publication bias No formal publication-bias analysis is part of this methodological reference scale. The distribution describes reproducibly accessible reviews across different tests and conditions; it is not a pooled estimate of one clinical effect. ## Certainty and interpretation Report source fidelity, numerical diagnostics, estimator sensitivity, model-based uncertainty and sample limitations. This methodological reference scale does not assign GRADE ratings to clinical effects or recommendations. ## Software and reproducibility The archived release environment is CPython 3.13.12 on Windows x86-64, NumPy 2.4.4, pandas 3.0.2, SciPy 1.17.1 and Matplotlib 3.10.8. The downloadable code package includes the complete pinned requirements and original script versions. [Open the complete ConductScience Data release](https://conductscience.org/data/records/diagnostic-information) [Download the frozen data and analysis archive](https://conductscience.org/data/records/diagnostic-information/1.13.3/diagnostic-information-data-1.13.3.zip) Dataset DOI: . Crossref registered this DOI on September 14, 2026 local time (September 15, 2026 at 1:59 AM UTC), after the data release was published on September 14, 2026. Release 1.13.3 is fixed to source tag v1.13.3 at commit `83af3c4c1dfd1d05c1eeb26be49f9bcd54eb6df0`. Archive SHA-256: `fec4f2c210c0b88e17b20833da89ccaff01b07ff008b2f04a2334e1f6a6f737c`. ## Data and code access Download the complete derived data, source identifiers, selection records, results and analysis code from the ConductScience Data release below. Restricted original Cochrane packages and full article texts are excluded and remain available only from their source publishers. Every included file is fixed by byte count and SHA-256 in the release manifest. [View the ConductScience Data record](https://conductscience.org/data/records/diagnostic-information) [Cite the dataset](https://doi.org/10.55157/csd.di.2026.001) [Download release 1.13.3 (ZIP)](https://conductscience.org/data/records/diagnostic-information/1.13.3/diagnostic-information-data-1.13.3.zip) [Inspect the file manifest](https://conductscience.org/data/records/diagnostic-information/1.13.3/MANIFEST.json) The historical Cochrane DTA Reference Dataset is available at under CC BY-NC 4.0. Other source data retain their original terms. The protocol's CC BY 4.0 license applies to protocol text; it does not relicense third-party data or code. ### Downloads - [Fixed historical and modern Cochrane sources (CSV)](https://conductscience.org/review-pilots/diagnostic-information/support/cochrane-discovery-1.0.0.csv); version 1.0.0; 65 discovery records. - [OSF public deposits (CSV)](https://conductscience.org/review-pilots/diagnostic-information/support/osf-discovery-1.0.0.csv); version 1.0.0; 1,152 discovery records. - [Zenodo public deposits (CSV)](https://conductscience.org/review-pilots/diagnostic-information/support/zenodo-discovery-1.0.0.csv); version 1.0.0; 799 discovery records. - [Figshare public deposits (CSV)](https://conductscience.org/review-pilots/diagnostic-information/support/figshare-discovery-1.0.0.csv); version 1.0.0; 262 discovery records. - [Dryad public deposits (CSV)](https://conductscience.org/review-pilots/diagnostic-information/support/dryad-discovery-1.0.0.csv); version 1.0.0; 11 discovery records. - [SRDR+ public deposits (CSV)](https://conductscience.org/review-pilots/diagnostic-information/support/srdr-discovery-1.0.0.csv); version 1.0.0; 172 discovery records. - [PubMed Central open-access review tables (CSV)](https://conductscience.org/review-pilots/diagnostic-information/support/pmc-discovery-1.0.0.csv); version 1.0.0; 1,518 discovery records. - [Dataset DOI](https://doi.org/10.55157/csd.di.2026.001); version 1.13.3; registered by Crossref. - [Complete data and analysis archive (ZIP)](https://conductscience.org/data/records/diagnostic-information/1.13.3/diagnostic-information-data-1.13.3.zip); version 1.13.3; SHA-256 fec4f2c210c0b88e17b20833da89ccaff01b07ff008b2f04a2334e1f6a6f737c. - [Protocol (JSON)](https://conductscience.org/review-pilots/diagnostic-information/protocol.json); record version 1.3.1. - [Protocol text (Markdown)](https://conductscience.org/review-pilots/diagnostic-information/protocol.md); record version 1.3.1. - [Registration, date and source metadata (JSON)](https://conductscience.org/review-pilots/diagnostic-information/source-evidence.json); metadata version 2.1.1. ## Funding and declarations National Academy of Medicine, Agreement 2026A008797. The manuscript states that the funder had no role in design, acquisition, analysis, interpretation, writing, or submission. The authors declare support from the National Academy of Medicine for the submitted work (Agreement No. 2026A008797); no other competing interests are declared. ## Registration and version history The study was registered internally with ConductScience on 16 August 2026. The public protocol record and its DOI were established on 13 September 2026. The protocol has a versioned amendment history: source-priority rules developed during staged audits were fixed before the final reference analysis. This version documents the completed methods and distinguishes the original internal registration from subsequent amendments and public posting. - August 16, 2026: Internal study registration with ConductScience; subsequent method amendments retain their own history. - September 8, 2026: Manuscript version 1.11.0 records the completed analysis. - September 13, 2026: Public protocol record posted and DOI created by Crossref. - September 13, 2026: Protocol version 1.2.0 clarifies date meanings and adds the documented methods and support files. - September 13, 2026: Protocol version 1.2.1 improves navigation, formatting and file access, and labels the registration and publication dates. Scientific methods and supporting files are unchanged. - September 14, 2026: Protocol presentation 1.3.0 links the unchanged registered protocol to the complete ConductScience Data release version 1.13.3. The dataset DOI is recorded only after Crossref verification. - September 14, 2026: Crossref created dataset DOI 10.55157/csd.di.2026.001 on September 14 in the publisher's local time zone (01:59:05 UTC on September 15) for the ConductScience Data release published on September 14. The protocol remains registered August 16 and published September 13. [Previous protocol version 1.3.0 (JSON)](https://conductscience.org/review-pilots/diagnostic-information/versions/1.3.0/protocol.json) The DOI identifies this protocol record. Protocol 1.3.1 SHA-256 (canonical sorted-key JSON): `66dcc5b45b9e2b344950c30d375f329fffebbeb2fde7f72a42565e70fa78c2d2` ## Documented milestones - Pilot search started: August 15, 2026 - Formal search started: August 16, 2026 - Screening started: August 16, 2026 - Extraction started: August 16, 2026 - Synthesis started: August 16, 2026 ## Cite this record He S, Joseph JW, Liebovitz DM, et al. The information in diagnostic tests: registered protocol. ConductScience; 2026. Version 1.3.1. CSR-DI-2026-001. Registered with ConductScience: August 16, 2026. Published online: September 13, 2026. [Registration, date and source metadata (JSON)](https://conductscience.org/review-pilots/diagnostic-information/source-evidence.json)