Computed from this object's own state — a structural condition is unmet. This is not a fixed disclaimer: the conditions below are each testable, and a build in which they are met renders READY.
In adults at risk of venous thromboembolism, what is the effect of apixaban thromboprophylaxis compared with enoxaparin, another anticoagulant, or no anticoagulation on symptomatic venous thromboembolism and on bleeding?
In this section: Registration and administrative information (PROSPERO field set)
| Review title | Apixaban thromboprophylaxis: four trials, four different primary composites, and one estimand all four register below the primary |
|---|---|
| Review question (PICO) | In adults at risk of venous thromboembolism, what is the effect of apixaban thromboprophylaxis compared with enoxaparin, another anticoagulant, or no anticoagulation on symptomatic venous thromboembolism and on bleeding? |
| Population | Not shown — doac_vte_nma is a network protocol whose intervention is the DOAC network, not apixaban VTE prophylaxis alone. State: PROTOCOL_IS_A_NETWORK. |
| Intervention | Not shown — doac_vte_nma is a network protocol whose intervention is the DOAC network, not apixaban VTE prophylaxis alone. State: PROTOCOL_IS_A_NETWORK. |
| Comparator | Not shown — doac_vte_nma is a network protocol whose intervention is the DOAC network, not apixaban VTE prophylaxis alone. State: PROTOCOL_IS_A_NETWORK. |
| Background / rationale | Not recorded — this object holds no background field, and an introduction generated without one would be argument that no source in this review supports |
| Eligibility criteria | Population: adults at risk of venous thromboembolism receiving thromboprophylaxis -- surgical, medically ill, or cancer-associated. Intervention: apixaban thromboprophylaxis as the randomised intervention. Comparator: enoxaparin or another anticoagulant, or placebo / no anticoagulation. Estimand, which governs poolability and not eligibility: symptomatic venous thromboembolism, or major bleeding, at any registered rank. And the boundary with the treatment review: primary prophylaxis in patients who have not had a venous thromboembolism belongs here; extended anticoagulation in patients who have belongs to the sibling. The discriminator is read from each trial's eligibility criteria, because the registry's coded `primaryPurpose` does not carry it -- ADVANCE-2 is knee-replacement thromboprophylaxis coded treatment, and it is admitted here. Criteria are derived post hoc and say so. |
| Information sources | 0 source layers, listed on the Extraction tab |
| Search strategy | The executed strings, datetimes, filters and hit counts are on the Search tab |
| Study selection process | A second independent screen was NOT run for this review. |
| Number of screeners | One. No second independent screen was run. |
| Data extraction items | Extracted per trial on this object: registry id; design; arms; per-arm counts and the published effect; the randomised total, separately from the analysed denominator. Fields not listed here were not extracted. |
| Outcomes and prioritisation | Proximal DVT, non-fatal pulmonary embolism, or VTE-related death |
| Risk of bias method | Not recorded — no per-domain RoB-2 assessment exists yet |
| Synthesis methods | Pooled under random-effects with the REML estimator. These methods were NOT prespecified before the search, and are not presented as though they were. |
| Subgroup analyses | Not recorded — this object records no subgroup-analysis field at all, so whether any were prespecified is UNKNOWN -- which is not the same as none having been |
| Meta-bias assessment | Not recorded — no funnel, Egger or Peters value is held on this object, so no meta-bias assessment is claimed |
| Certainty assessment | GRADE, recorded for 1 outcome(s) (GRADE). The ratings are on the Certainty tab. |
| Confidence level | 95% |
| Funding | Not recorded — no funding statement is recorded for this review |
| Competing interests | Not recorded — no declaration is recorded |
| Built | 2026-08-19 |
| Schema | 2 |
In this section: ClinicalTrials.gov API v2 · ClinicalTrials.gov API v2 -- first query, recorded because it missed this review's only trial · PubMed (ncbi e-utilities esearch)
Query as executed:
Executed 2026-08-19 against ClinicalTrials.gov API v2, raw. query.cond="venous thromboembolism OR deep vein thrombosis OR pulmonary embolism"; query.intr="apixaban"; filter.advanced=AREA[StudyType]INTERVENTIONAL -- NO PHASE FILTER. 82 records, returned == totalCount, nextPageToken null.
Query as executed:
same terms with filter.advanced=... AND AREA[Phase](PHASE3 OR PHASE4)
Query as executed:
apixaban AND venous thromboembolism
This review's decision: eligible no results yet.
eligible; status completed, hasResults=False
This review's decision: eligible poolable not included.
Eligible, poolable and not in this object
This review's decision: eligible poolable not included.
Eligible, poolable and not in this object
This review's decision: eligible poolable not included.
Eligible, poolable and not in this object
This review's decision: needs adjudication.
cannot settle population: coded treatment but the text reads as prophylaxis -- exactly ADVANCE-2's shape, and the coded field is what is wrong there
This review's decision: eligible poolable not included.
Eligible, poolable and not in this object
This review's decision: excluded.
fails population (neither the coded purpose nor the text places this in prophylaxis). All limbs: Population fails, intervention holds, comparator unsettled, estimand holds
This review's decision: excluded.
fails population (neither the coded purpose nor the text places this in prophylaxis). All limbs: Population fails, intervention holds, comparator holds, estimand holds
This review's decision: excluded.
fails population (neither the coded purpose nor the text places this in prophylaxis). All limbs: Population fails, intervention holds, comparator unsettled, estimand fails
This review's decision: needs adjudication.
cannot settle comparator: no usable coded purpose; the condition text reads as prophylaxis
This review's decision: excluded.
fails population (neither the coded purpose nor the text places this in prophylaxis). All limbs: Population fails, intervention holds, comparator holds, estimand holds
This review's decision: eligible no results yet.
eligible; status completed, hasResults=False
This review's decision: excluded.
fails population, comparator (neither the coded purpose nor the text places this in prophylaxis). All limbs: Population fails, intervention holds, comparator fails, estimand holds
This review's decision: needs adjudication.
cannot settle population: coded prevention but the condition text reads as treatment -- the ADVANCE-2/ADVANCE-3 disagreement, not resolved here
This review's decision: excluded.
fails population, comparator (neither the coded purpose nor the text places this in prophylaxis). All limbs: Population fails, intervention holds, comparator fails, estimand holds
This review's decision: excluded.
fails population (neither the coded purpose nor the text places this in prophylaxis). All limbs: Population fails, intervention holds, comparator holds, estimand holds
This review's decision: excluded.
fails population (neither the coded purpose nor the text places this in prophylaxis). All limbs: Population fails, intervention holds, comparator holds, estimand holds
This review's decision: excluded.
fails population (neither the coded purpose nor the text places this in prophylaxis). All limbs: Population fails, intervention holds, comparator holds, estimand holds
This review's decision: excluded.
fails population (neither the coded purpose nor the text places this in prophylaxis). All limbs: Population fails, intervention holds, comparator holds, estimand holds
This review's decision: excluded.
fails population (neither the coded purpose nor the text places this in prophylaxis). All limbs: Population fails, intervention holds, comparator holds, estimand holds
This review's decision: eligible not poolable.
eligible with results, but no VTE or bleeding outcome at any rank
This review's decision: excluded.
fails population, comparator (neither the coded purpose nor the text places this in prophylaxis). All limbs: Population fails, intervention holds, comparator fails, estimand fails
This review's decision: excluded.
fails population, comparator (neither the coded purpose nor the text places this in prophylaxis). All limbs: Population fails, intervention holds, comparator fails, estimand holds
This review's decision: excluded.
fails comparator (coded prevention and the text agrees). All limbs: Population holds, intervention holds, comparator fails, estimand holds
This review's decision: excluded.
fails population (neither the coded purpose nor the text places this in prophylaxis). All limbs: Population fails, intervention holds, comparator holds, estimand holds
This review's decision: needs adjudication.
cannot settle population, comparator: coded prevention but the condition text reads as treatment -- the ADVANCE-2/ADVANCE-3 disagreement, not resolved here
This review's decision: excluded.
fails population (neither the coded purpose nor the text places this in prophylaxis). All limbs: Population fails, intervention holds, comparator holds, estimand holds
This review's decision: excluded.
fails population (neither the coded purpose nor the text places this in prophylaxis). All limbs: Population fails, intervention holds, comparator holds, estimand holds
This review's decision: excluded.
fails population (neither the coded purpose nor the text places this in prophylaxis). All limbs: Population fails, intervention holds, comparator holds, estimand holds
This review's decision: eligible no results yet.
eligible; status terminated, hasResults=False
This review's decision: excluded.
fails population (neither the coded purpose nor the text places this in prophylaxis). All limbs: Population fails, intervention holds, comparator holds, estimand holds
This review's decision: eligible no results yet.
eligible; status completed, hasResults=False
This review's decision: excluded.
fails population (neither the coded purpose nor the text places this in prophylaxis). All limbs: Population fails, intervention holds, comparator holds, estimand holds
This review's decision: needs adjudication.
cannot settle population: coded prevention but the condition text reads as treatment -- the ADVANCE-2/ADVANCE-3 disagreement, not resolved here
This review's decision: eligible no results yet.
eligible; status unknown, hasResults=False
This review's decision: excluded.
fails population, comparator (neither the coded purpose nor the text places this in prophylaxis). All limbs: Population fails, intervention holds, comparator fails, estimand holds
This review's decision: excluded.
fails comparator (coded treatment but the text reads as prophylaxis -- exactly ADVANCE-2's shape, and the coded field is what is wrong there). All limbs: Population unsettled, intervention holds, comparator fails, estimand holds
This review's decision: excluded.
fails population (neither the coded purpose nor the text places this in prophylaxis). All limbs: Population fails, intervention holds, comparator holds, estimand holds
This review's decision: excluded.
fails population, comparator (neither the coded purpose nor the text places this in prophylaxis). All limbs: Population fails, intervention holds, comparator fails, estimand fails
This review's decision: eligible no results yet.
eligible; status completed, hasResults=False
This review's decision: excluded.
fails population (neither the coded purpose nor the text places this in prophylaxis). All limbs: Population fails, intervention holds, comparator holds, estimand holds
This review's decision: excluded.
fails comparator (coded prevention and the text agrees). All limbs: Population holds, intervention holds, comparator fails, estimand holds
This review's decision: needs adjudication.
cannot settle population: coded prevention but the condition text reads as treatment -- the ADVANCE-2/ADVANCE-3 disagreement, not resolved here
This review's decision: eligible no results yet.
eligible; status terminated, hasResults=False
This review's decision: excluded.
fails population (neither the coded purpose nor the text places this in prophylaxis). All limbs: Population fails, intervention holds, comparator holds, estimand fails
This review's decision: needs adjudication.
cannot settle comparator: coded prevention and the text agrees
This review's decision: excluded.
fails population (neither the coded purpose nor the text places this in prophylaxis). All limbs: Population fails, intervention holds, comparator unsettled, estimand holds
This review's decision: eligible no results yet.
eligible; status recruiting, hasResults=False
This review's decision: excluded.
fails population, comparator (neither the coded purpose nor the text places this in prophylaxis). All limbs: Population fails, intervention holds, comparator fails, estimand fails
This review's decision: needs adjudication.
cannot settle population: coded treatment but the text reads as prophylaxis -- exactly ADVANCE-2's shape, and the coded field is what is wrong there
This review's decision: excluded.
fails population (neither the coded purpose nor the text places this in prophylaxis). All limbs: Population fails, intervention holds, comparator unsettled, estimand fails
This review's decision: excluded.
fails comparator (no usable coded purpose; the condition text reads as prophylaxis). All limbs: Population holds, intervention holds, comparator fails, estimand holds
This review's decision: excluded.
fails population (neither the coded purpose nor the text places this in prophylaxis). All limbs: Population fails, intervention holds, comparator holds, estimand fails
This review's decision: eligible no results yet.
eligible; status recruiting, hasResults=False
This review's decision: excluded.
fails population (neither the coded purpose nor the text places this in prophylaxis). All limbs: Population fails, intervention holds, comparator unsettled, estimand holds
This review's decision: excluded.
fails population (neither the coded purpose nor the text places this in prophylaxis). All limbs: Population fails, intervention holds, comparator holds, estimand holds
This review's decision: needs adjudication.
cannot settle population: coded treatment but the text reads as prophylaxis -- exactly ADVANCE-2's shape, and the coded field is what is wrong there
This review's decision: excluded.
fails population (neither the coded purpose nor the text places this in prophylaxis). All limbs: Population fails, intervention holds, comparator holds, estimand holds
This review's decision: excluded.
fails population (neither the coded purpose nor the text places this in prophylaxis). All limbs: Population fails, intervention holds, comparator holds, estimand holds
This review's decision: needs adjudication.
cannot settle comparator: coded prevention and the text agrees
This review's decision: excluded.
fails comparator (coded treatment but the text reads as prophylaxis -- exactly ADVANCE-2's shape, and the coded field is what is wrong there). All limbs: Population unsettled, intervention holds, comparator fails, estimand holds
This review's decision: excluded.
fails population, comparator (neither the coded purpose nor the text places this in prophylaxis). All limbs: Population fails, intervention holds, comparator fails, estimand holds
This review's decision: needs adjudication.
cannot settle comparator: coded prevention and the text agrees
This review's decision: needs adjudication.
cannot settle population: coded treatment but the text reads as prophylaxis -- exactly ADVANCE-2's shape, and the coded field is what is wrong there
This review's decision: eligible no results yet.
eligible; status NOT_YET_RECRUITING, hasResults=False
This review's decision: eligible no results yet.
eligible; status recruiting, hasResults=False
This review's decision: eligible no results yet.
eligible; status NOT_YET_RECRUITING, hasResults=False
This review's decision: needs adjudication.
cannot settle population: coded prevention but the condition text reads as treatment -- the ADVANCE-2/ADVANCE-3 disagreement, not resolved here
This review's decision: needs adjudication.
cannot settle population, comparator: coded treatment but the text reads as prophylaxis -- exactly ADVANCE-2's shape, and the coded field is what is wrong there
This review's decision: needs adjudication.
cannot settle population: coded prevention but the condition text reads as treatment -- the ADVANCE-2/ADVANCE-3 disagreement, not resolved here
This review's decision: excluded.
fails comparator (coded prevention and the text agrees). All limbs: Population holds, intervention holds, comparator fails, estimand holds
This review's decision: eligible no results yet.
eligible; status NOT_YET_RECRUITING, hasResults=False
In this section: Extracted values, and where each came from · References · Included studies · Regulatory documents · Methods and guidance · Sources · Proximal DVT, non-fatal pulmonary embolism, or VTE-related death · Proximal DVT, non-fatal pulmonary embolism, or VTE-related death · What was measured · Pooled result · Contributing trials · Endpoint definitions, read from the registry
One row per extracted value. Every row carries the value, the verbatim sentence it was read from, a resolvable link to the source, and whether the number was read or derived. Where any of those is absent the row says so rather than omitting the value.
| Trial / outcome | Value as extracted | Verbatim source sentence | Source links | Read or derived |
|---|---|---|---|---|
| ADOPT major_vte | RR 0.925 (95% CI 0.656 to 1.3) | “Incidence of Adjudicated Proximal DVT, Non-Fatal PE or VTE-Related Death” “Event counts are the posted event RATE multiplied by the analysed denominator and rounded; the rate is what this trial posts.” | NCT00457002 | READ from the source as printed Events are the posted event RATE multiplied by the analysed denominator and rounded -- DERIVED, and labelled DERIVED, because these four trials post rates where the treatment review's three post counts. |
| ADVANCE-3 major_vte | RR 0.399 (95% CI 0.192 to 0.829) | “Rate of Composite of Adjudicated Proximal DVT, Nonfatal PE, VTE-related death” “Event counts are the posted event RATE multiplied by the analysed denominator and rounded; the rate is what this trial posts.” | NCT00423319 | READ from the source as printed Events are the posted event RATE multiplied by the analysed denominator and rounded -- DERIVED, and labelled DERIVED, because these four trials post rates where the treatment review's three post counts. |
| ADVANCE-1 major_vte | RR 1.41 (95% CI 0.764 to 2.59) | “Event Rate for Participants With Proximal DVT/Non-Fatal PE/VTE-Related Death” “Event counts are the posted event RATE multiplied by the analysed denominator and rounded; the rate is what this trial posts.” | NCT00371683 | READ from the source as printed Events are the posted event RATE multiplied by the analysed denominator and rounded -- DERIVED, and labelled DERIVED, because these four trials post rates where the treatment review's three post counts. |
| ADVANCE-2 major_vte | RR 0.502 (95% CI 0.259 to 0.972) | “Rate of Adjudicated Proximal DVT, Nonfatal PE, and VTE-related death” “Event counts are the posted event RATE multiplied by the analysed denominator and rounded; the rate is what this trial posts.” | NCT00452530 | READ from the source as printed Events are the posted event RATE multiplied by the analysed denominator and rounded -- DERIVED, and labelled DERIVED, because these four trials post rates where the treatment review's three post counts. |
| Layer | Source | How it was obtained |
|---|
| Comparator | enoxaparin |
|---|---|
| Estimand | binary risk — random-effects, REML |
| Case definition | proximal DVT, non-fatal pulmonary embolism, or VTE-related death |
| Effect scale | combined on the log scale; ESTIMAND UNIFORMITY NOT ESTABLISHED -- the contributing trials have not been shown to measure the same quantity |
RR 0.7433 (0.4371 to 1.264), 95% interval
Proximal DVT, non-fatal pulmonary embolism, or VTE-related death. random-effects, estimator REML, k = 4.
τ² 0.2042 · I² 71.48% · Q 9.312 on 3 df
Favours: neither -- the interval spans the null
computed
All four register the same composite -- proximal DVT, non-fatal PE, or VTE-related death -- at secondary rank, and each title was read rather than matched by name.
| Trial | Analysed treatment / control |
RR (95% CI), or events | Source of this cell |
|---|---|---|---|
| ADOPT NCT00457002 · SECONDARY outcome | 2211 / 2283 | 0.9247 (0.6559 to 1.304) | registry_posted_results: Incidence of Adjudicated Proximal DVT, Non-Fatal PE or VTE-Related DeathIncidence of Adjudicated Proximal DVT, Non-Fatal PE or VTE-Related Death Event counts are the posted event RATE multiplied by the analysed denominator and rounded; the rate is what this trial posts. |
| ADVANCE-3 NCT00423319 · SECONDARY outcome | 2199 / 2195 | 0.3993 (0.1922 to 0.8293) | registry_posted_results: Rate of Composite of Adjudicated Proximal DVT, Nonfatal pe, vte-related deathRate of Composite of Adjudicated Proximal DVT, Nonfatal PE, VTE-related death Event counts are the posted event RATE multiplied by the analysed denominator and rounded; the rate is what this trial posts. |
| ADVANCE-1 NCT00371683 · SECONDARY outcome | 1268 / 1213 | 1.407 (0.7636 to 2.592) | registry_posted_results: Event Rate for Participants With Proximal DVT/Non-Fatal PE/VTE-Related DeathEvent Rate for Participants With Proximal DVT/Non-Fatal PE/VTE-Related Death Event counts are the posted event RATE multiplied by the analysed denominator and rounded; the rate is what this trial posts. |
| ADVANCE-2 NCT00452530 · SECONDARY outcome | 1195 / 1199 | 0.5017 (0.259 to 0.9715) | registry_posted_results: Rate of Adjudicated Proximal DVT, Nonfatal PE, and VTE-related deathRate of Adjudicated Proximal DVT, Nonfatal PE, and VTE-related death Event counts are the posted event RATE multiplied by the analysed denominator and rounded; the rate is what this trial posts. |
Secondary in all four trials. Their four primary composites are four different things -- ADOPT counts VTE-related death, ADVANCE-1 counts ALL-CAUSE death -- and their primary event rates span 1.39% to 8.99% for one drug in one indication, which is a fact about what each counted and which surgery rather than about apixaban.
What each trial COUNTED, in its own registry record's words, before anything here was pooled. A sentence saying what HAPPENED is not a sentence saying what was COUNTED, and only the second one licenses a pool. Read from the registry on 2026-08-19. Follow the registration link to disagree with any row.
| Trial | Rank in its own trial | Registered outcome measure | Description, verbatim | Analysis set / window |
|---|---|---|---|---|
| ADOPT NCT00457002 | — | Incidence of Adjudicated Proximal DVT, Non-Fatal PE or VTE-Related Death | no description is recorded in this registry field | — |
| ADVANCE-3 NCT00423319 | — | Rate of Composite of Adjudicated Proximal DVT, Nonfatal pe, vte-related death | no description is recorded in this registry field | — |
| ADVANCE-1 NCT00371683 | — | Event Rate for Participants With Proximal DVT/Non-Fatal PE/VTE-Related Death | no description is recorded in this registry field | — |
| ADVANCE-2 NCT00452530 | — | Rate of Adjudicated Proximal DVT, Nonfatal PE, and VTE-related death | no description is recorded in this registry field | — |
In this section: Proximal DVT, non-fatal pulmonary embolism, or VTE-related death · Forest plot · Visual abstract · Risk of bias · GOSH · Trial-sequential analysis · Meta-regression
Drawn from the same stored estimates the table above lists. Box area is proportional to inverse-variance weight.
x-axis range
⬇ SVG (vector) 2 KB ⬇ PNG 4500x1260 150 KB
All raster formats were generated at build time from the same SVG as the graphic above (SHA-256, first 16 hex characters: 0046c949e35b3432), at 600 dpi for a 6-inch print width, on a white ground. They are not screenshots of the page and do not change with the theme you are reading in.
Submission formats written to the figures directory, not embedded here because an uncompressed 600 dpi TIFF is tens of megabytes: EPS (vector, journal's first choice for line art) — forest_fit.eps, 5 KB; TIFF (uncompressed, 600 dpi -- journal fallback) — forest_fit.tiff, 16,611 KB.
Changing the range moves the axis window only. The guides stay labelled with the null and the extremes of the plotted intervals, so no plotted value and no printed number differs between these views — and that is checked at build time, not asserted. Ranges not offered because they would crop the data: 0.5 to 2, 0.25 to 4, 0.7 to 1.3.
⬇ SVG (vector) 2 KB ⬇ PNG 4500x2100 304 KB
All raster formats were generated at build time from the same SVG as the graphic above (SHA-256, first 16 hex characters: 3628e6e29830a990), at 600 dpi for a 6-inch print width, on a white ground. They are not screenshots of the page and do not change with the theme you are reading in.
Submission formats written to the figures directory, not embedded here because an uncompressed 600 dpi TIFF is tens of megabytes: EPS (vector, journal's first choice for line art) — visual-abstract.eps, 4 KB; TIFF (uncompressed, 600 dpi -- journal fallback) — visual-abstract.tiff, 27,685 KB.
Projected from the canonical object, so it carries the same k, the same pooled estimate and the same interval as the paper and cannot drift from them. The interval is drawn CROSSING the no-difference line because it does: 0.437 to 1.264 spans 1. A graphical abstract travels without its caption, and one showing a favourable point estimate without showing that its interval includes no effect would overstate a null result.
⬇ SVG (vector) 1 KB
Only the vector format is offered for this figure, by choice: it is line art — discrete marks, glyphs and labels — which SVG reproduces exactly at any size, so a raster would add weight without adding fidelity. The build was able to rasterise; it was asked not to.
Not drawn, because there is nothing to draw it from.
⬇ SVG (vector) 1 KB ⬇ PNG 3500x540 80 KB
All raster formats were generated at build time from the same SVG as the graphic above (SHA-256, first 16 hex characters: 1ac0f91ef8ab0183), at 600 dpi for a 6-inch print width, on a white ground. They are not screenshots of the page and do not change with the theme you are reading in.
Submission formats written to the figures directory, not embedded here because an uncompressed 600 dpi TIFF is tens of megabytes: EPS (vector, journal's first choice for line art) — gosh.eps, 2 KB; TIFF (uncompressed, 600 dpi -- journal fallback) — gosh.tiff, 5,537 KB.
Deliberately not drawn. Every subset meta-analysis of 4 trials is 15 points; a cloud that small cannot show the multimodality GOSH exists to reveal, and a reader would take the picture as evidence of its absence.
⬇ SVG (vector) 1 KB ⬇ PNG 3500x650 87 KB
All raster formats were generated at build time from the same SVG as the graphic above (SHA-256, first 16 hex characters: 25ed9800fdf56614), at 600 dpi for a 6-inch print width, on a white ground. They are not screenshots of the page and do not change with the theme you are reading in.
Submission formats written to the figures directory, not embedded here because an uncompressed 600 dpi TIFF is tens of megabytes: EPS (vector, journal's first choice for line art) — tsa.eps, 2 KB; TIFF (uncompressed, 600 dpi -- journal fallback) — tsa.tiff, 6,665 KB.
TSA boundaries depend entirely on a target information size that must be pre-specified. This review's protocol registers none, so any boundary drawn here would be a parameter chosen after seeing the data -- which is the practice TSA exists to protect against.
⬇ SVG (vector) 1 KB ⬇ PNG 3500x540 86 KB
All raster formats were generated at build time from the same SVG as the graphic above (SHA-256, first 16 hex characters: 0a34e86921018df9), at 600 dpi for a 6-inch print width, on a white ground. They are not screenshots of the page and do not change with the theme you are reading in.
Submission formats written to the figures directory, not embedded here because an uncompressed 600 dpi TIFF is tens of megabytes: EPS (vector, journal's first choice for line art) — bubble.eps, 2 KB; TIFF (uncompressed, 600 dpi -- journal fallback) — bubble.tiff, 5,537 KB.
The protocol pre-specifies no moderator, and at k = 4 a meta-regression would be fitted on 4 points. Not drawn rather than drawn with a caveat: a bubble plot invites reading a slope, and there is no slope here that any reader should read.
In this section: Summary of findings · Reproducibility artifact · Other recorded qualifications
| Outcome | k | Pooled effect | Certainty |
|---|---|---|---|
| Proximal DVT, non-fatal pulmonary embolism, or VTE-related death | 4 | RR 0.743 (0.437 to 1.26) | Very low1 |
| Canonical object | — |
|---|---|
| Registered at | — — |
| Schema | 2 |
| Object last updated | 2026-08-19 |
| Source object SHA-256, first 16 hex characters | f3cda2729297dc63 |
| Page generated | 2026-08-28 19:52 UTC |
| Generator build | a441e4187, built to STANDARD v1 |
This page CANNOT be rebuilt from what is recorded here: no canonical object is recorded and no registered commit is recorded. Each figure on the Analysis tab downloads as an SVG carrying exactly the values shown.
Statements this review records about the limits of what it establishes, which are not shown elsewhere on this page. They are reproduced from the object verbatim and are not summarised.
| Why empty is a result and not a blank | The boundary criterion assigns every trial to exactly one review, so the intersection is empty by construction and is computed rather than left as a bare `[]`. P17. |
|---|---|
| What it does not establish | Not that either pool is correct -- both were judged by reading endpoint definitions, and that judgement stands or falls on its own. Not that the direction is unpredictable in general; two instances are two instances. What it establishes is narrow and it is the thing that was missing: The procedure has no built-in direction, demonstrated rather than asserted. |
| And the primary is read by text never by position | outcomeMeasures[0] is the major-vte secondary for ADVANCE-2 and the primary for the other three. Taking element zero would have pooled one trial's secondary against three trials' primaries, with nothing malformed anywhere. |
| Prediction interval on t k minus 1 | This transcript is quoted verbatim and is not edited. metafor's predict takes its quantile from the FIT, and a default rma is test="z", so the pi.lb/pi.ub printed above are normal-quantile bounds. The Handbook interval for the same fit, on t_{k-1}, is given here beside it rather than in place of it. |
| Estimator note superseded | This pool is owed an estimator correction and the debt is on the page. It uses DerSimonian-Laird at k=4. The house rule refuses DerSimonian-Laird below k=10 because it under-estimates the between-study variance, and the sibling review built the same night uses Paule-Mandel with a floored Knapp-Hartung interval at k=3. It is recorded rather than silently changed because recomputing it in the same pass that publishes this page would move a published estimate that has not been re-derived or re-checked -- and a divergence between two siblings built from one search is exactly the kind of thing nobody notices again. What would close it: re-run scripts/repool_apixaban_prophylaxis_2026_08_19.py with Paule-Mandel and a floored Knapp-Hartung interval, then promote the result through every derived block on this object (P19). |
| Why the remainder is now zero and was 71 | The whole remainder has been screened. 33 of this review's 39 mechanical exclusions fail on population -- they are treatment trials in patients who have already had a venous thromboembolism, which is exactly the population the sibling review holds. |
| Authority it does not establish | Mecir C5/C7. This boundary was written on 2026-08-19, after both reviews' included sets existed. `predefined: false`, like everything else in these criteria. |
| Indicator chosen because it could only move one way | P32: the test was its eligibility text, which states what was enrolled and cannot be true for both answers. A trial's own words about who may enter it settle whether the population has had the event; the arm label does not. |
| What this boundary does not do | It does not make the two reviews clinically homogeneous. Extended anticoagulation after a completed course and treatment of the acute event are both treatment under this criterion and they are different clinical questions with different comparators, which is why the treatment review pools within the acute stratum and states the extended trials separately rather than averaging across them. |
| Why it does not settle it alone | the same ADVANCE-2 / ADVANCE-3 inversion. The coded field counts the pool; the design decides inclusion. |
| And this review s own included trial | NCT02366871 is n=400, apixaban against enoxaparin in suspected pelvic malignancy, typed experimental vs ACTIVE_COMPARATOR, and its registered primaries are major bleeding and clinically relevant non-major bleeding -- a safety estimand. It is in scope and it does not report the efficacy estimand this review names, so k=1 here is also not the number to take away. |
| What eligible poolable not included means | A gap in our own evidence base. ADOPT (n=6758), ADVANCE-3 (n=5407) and ADVANCE-1 (n=3608) were surfaced by this review's own search, passed its own criteria, and were not in the object. ADVANCE-2 was recovered by the boundary criterion against its own coded field. |
| And the object previously reported a safety result | Its single included trial NCT02366871 is n=400 and its registered primaries are major bleeding and clinically relevant non-major bleeding. The previous figure was not an estimate of this review's efficacy question at all, which is why the change here is not a delta and must not be presented as one. |
| Refusal discharges P46 because | It names the state (NOT_ASSESSED_FOR_THIS_REVIEW), why (the four contributing results were extracted and pooled and no result-level RoB 2 was performed), that this is recorded as unassessed and not as absent of bias, the consequence carried into GRADE (rated down one level), and what would close it: RoB 2 per result for the shared secondary in NCT00457002, NCT00423319, NCT00371683 and NCT00452530. The obstacle is in the evidence and is checkable without knowing anything about how this project is organised. |
| And the split itself shares nothing | The two split reviews share NO trial with each other, by construction: the boundary criterion assigns every trial to exactly one of them. That is worth stating precisely because it is the answer to a different question from the one above, and reporting it in place of the parent overlap would have been a true sentence standing where a false impression was needed. |
| And the estimate itself is under question | Discharged 2026-08-20. This read: "Specific to this topic and stated because it changes the order of the work: the served pool was computed with DerSimonian-Laird at k = 4, which this project's statistics notes forbid below k = 10, and the corrected PM/Knapp-Hartung fit widens the interval from 0.4532-1.2309 to 0.3055-1.8010. A comparison drawn against published syntheses now would be comparing a number scheduled to be restated. See results.by_outcome.major_vte.r_output.what_the_required_estimator_gives." The restatement it was waiting for happened, in one pass across all ten non-REML pools of the corpus. It named Paule-Mandel with Knapp-Hartung as the correction; DECISIONS-COCHRANE-2026-08-18.md section 1, on Cochrane Handbook 6.5 section 10.10.4.4: "Decision: REML, everywhere." settles it as REML, with Hartung-Knapp a sensitivity analysis at k<=3 and not the primary interval, and this pool is k=4. The estimate is now 0.7433 (0.4371 to 1.264) against a served 0.7469 (0.4532 to 1.2309) -- the interval widens, as the deferral predicted, but by less than the PM/Knapp-Hartung figure that note quoted. A comparison against published syntheses is no longer comparing a number scheduled to move. |
| Refusal discharges P46 because | It names what was reached (a PubMed search with its yield and shortfall, and zero recorded benchmarks), what was found insufficient (no synthesis identified at all), and what would have to be obtained. Re-derive the counts with: python scripts/lint_refusal_citation_resolves.py |
| And the estimate itself is under question superseded | Specific to this topic and stated because it changes the order of the work: the served pool was computed with DerSimonian-Laird at k = 4, which this project's statistics notes forbid below k = 10, and the corrected PM/Knapp-Hartung fit widens the interval from 0.4532-1.2309 to 0.3055-1.8010. A comparison drawn against published syntheses now would be comparing a number scheduled to be restated. See results.by_outcome.major_vte.r_output.what_the_required_estimator_gives. |
In this section: Paper · Title · Abstract · Introduction · Methods — search · Methods — eligibility criteria · Methods — how many studies at each stage · Methods — outcomes sought at every registered rank · Methods — synthesis · Results · Certainty of the evidence · Limitations · Data availability · Software availability · Reporting guidelines · Note on registration · References · Figures · Trial characteristics · Submission conformance · Not reported in this record
Each statement below cites the record it came from; those sources are listed at the end of every section. Where the record holds nothing, the section says so by name rather than being left out, so a procedure that was not carried out can be told from one that simply was never mentioned.
Apixaban thromboprophylaxis: four trials, four different primary composites, and one estimand all four register below the primary1
titleQuestion. In adults at risk of venous thromboembolism, what is the effect of apixaban thromboprophylaxis compared with enoxaparin, another anticoagulant, or no anticoagulation on symptomatic venous thromboembolism and on bleeding?1
Methods. ClinicalTrials.gov API v2 and PubMed (ncbi e-utilities esearch) were searched; estimates were pooled under a random-effects model with the REML estimator; and certainty was rated with GRADE.2
Results. Proximal DVT, non-fatal pulmonary embolism, or VTE-related death: risk ratio 0.743 (0.437 to 1.26) across 4 trials; no statistical heterogeneity was detected (I-squared 71.5%); and certainty of the evidence was very low.3
questionsearch.databases, screening.eligibility, results.by_outcome, grade.by_outcomegrade.by_outcome, results.by_outcomeBackground. This review asks: In adults at risk of venous thromboembolism, what is the effect of apixaban thromboprophylaxis compared with enoxaparin, another anticoagulant, or no anticoagulation on symptomatic venous thromboembolism and on bleeding? It pools 4 randomised trials, against enoxaparin. The outcome pooled is Proximal DVT, non-fatal pulmonary embolism, or VTE-related death.1
manuscript.introductionSearches were executed in ClinicalTrials.gov API v2 on 2026-08-19 with the query, verbatim: Executed 2026-08-19 against ClinicalTrials.gov API v2, raw. query.cond="venous thromboembolism OR deep vein thrombosis OR pulmonary embolism"; query.intr="apixaban"; filter.advanced=area[StudyType]interventional -- no phase filter. 82 records, returned == totalCount, nextPageToken null.. It returned 82 record(s).1
Searches were executed in ClinicalTrials.gov API v2 -- first query, recorded because it missed this review's only trial on 2026-08-19 with the query, verbatim: same terms with filter.advanced=... And area[Phase](PHASE3 OR PHASE4). It returned 49 record(s).2
Searches were executed in PubMed (ncbi e-utilities esearch) on 2026-08-19 with the query, verbatim: apixaban and venous thromboembolism. It returned 50 record(s).3
Primary trials. No bibliographic search for primary trials was run. The 5 included trials were identified by reading named registrations on the dates recorded on each entry.4
search.databases[0]search.databases[1]search.databases[2]bookkeeping_2026_08_21.the_search_its_date_and_its_databasesPopulation: adults at risk of venous thromboembolism receiving thromboprophylaxis -- surgical, medically ill, or cancer-associated. Intervention: apixaban thromboprophylaxis as the randomised intervention. Comparator: enoxaparin or another anticoagulant, or placebo / no anticoagulation. Estimand, which governs poolability and not eligibility: symptomatic venous thromboembolism, or major bleeding, at any registered rank. And the boundary with the treatment review: primary prophylaxis in patients who have not had a venous thromboembolism belongs here; extended anticoagulation in patients who have belongs to the sibling. The discriminator is read from each trial's eligibility criteria, because the registry's coded `primaryPurpose` does not carry it -- ADVANCE-2 is knee-replacement thromboprophylaxis coded treatment, and it is admitted here. Criteria are derived post hoc and say so.1
Each criterion above is recorded with the source it was derived from in `screening.eligibility_provenance`; none is asserted here without one.2
screening.eligibilityscreening.eligibility_provenanceThe PRISMA 2020 flow counts are held for this review and reconcile with the executed searches above; they are set out in the flow figure and its accompanying counts.1
The unscreened remainder is 0.2
| Stage | Records |
|---|---|
| Records surfaced by the executed searches | 82 |
| Records where the topic drug's role in the trial could be located | 80 |
| Records where the topic drug is the randomised intervention | 54 |
| Records where the topic drug is the comparator instead | 19 |
| Records where the topic drug is background therapy in both arms | 7 |
| Records where the role could not be decided either way | 2 |
| k candidate pool | 73 |
| k screened | 73 |
| k excluded | 42 |
| k eligible | 31 |
| k eligible no results yet | 22 |
| k eligible not poolable | 4 |
| k eligible poolable | 5 |
| Trials included in this review | 5 |
| k pooled | 4 |
| Surfaced records not yet screened | 0 |
prisma_flowk_cascade.k_unscreened_remainderk_cascadeBefore deciding which outcomes could be combined, every trial was read at every registered rank -- primary, secondary and other -- asking: does each trial report, at any rank -- primary, secondary or other -- an outcome matching what the others report, before any decision about which pools are possible? Yes, and it is a secondary in all four1
withholding_question.question, withholding_question.why_before_decidingFor proximal DVT, non-fatal pulmonary embolism, or VTE-related death, a random-effects model was fitted with the REML estimator.1
Intervals are 95% confidence intervals.2
Risk of bias was assessed with RoB 2 (Cochrane risk-of-bias tool for randomized trials) , following . 0 result-level assessments were made.3
Certainty of evidence was rated with GRADE, following Cochrane Handbook for Systematic Reviews of Interventions version 6.5.1, Chapter 14. HIGH for a body of randomised evidence, then rated down. 1 pooled outcome(s) were rated. No domain is rated up.4
results.by_outcome.major_vte.model, results.by_outcome.major_vte.estimator_usedconfig.confidence_levelrisk_of_bias.tool, risk_of_bias.by_outcomegrade.approach, grade.by_outcomeThe pooled risk ratio for proximal DVT, non-fatal pulmonary embolism, or VTE-related death was 0.743 (0.437 to 1.26, 95% interval) across 4 trials, against enoxaparin.1
The trials' results were loosely consistent with one another: I-squared, the share of the variation between them that is more than chance alone would produce, was 71.5%; the estimated variance of the true effects between trials (tau-squared) was 0.204, the heterogeneity test statistic Q was 9.31, on degrees of freedom 3. computed2
The grounds for pooling are recorded as: All four register the same composite -- proximal DVT, non-fatal PE, or VTE-related death -- at secondary rank, and each title was read rather than matched by name. Where a later pool on this page rests on the same grounds, they are not restated.3
The full model output for every pooled outcome -- the call, the estimator, the heterogeneity statistics and the back-transformed interval -- is stored verbatim on this review object at `results.by_outcome.<outcome>.r_output.verbatim`. It is not reproduced as an Extended data section in this article; an earlier version of this sentence said it was, and no such section exists.4
outcomes[id=major_vte].name, results.by_outcome.major_vte.pooled, config.confidence_level, outcomes[id=major_vte].comparatorresults.by_outcome.major_vte.heterogeneity.i2, results.by_outcome.major_vte.heterogeneity.tau2, results.by_outcome.major_vte.heterogeneity.q, results.by_outcome.major_vte.heterogeneity.df, results.by_outcome.major_vte.heterogeneity_statusresults.by_outcome.major_vte.poolable_reasonresults.by_outcomeCertainty was rated with GRADE. HIGH for a body of randomised evidence, then rated down.1
No domain is rated up.2
| Outcome | Certainty | k | Started at | Rating steps |
|---|---|---|---|---|
| proximal DVT, non-fatal pulmonary embolism, or VTE-related death | VERY_LOW | 4 | HIGH | risk of bias: HIGH to MODERATE, down 1 level(s) -- No result-level RoB 2 assessment exists for this outcome, so risk of bias is not assessed rather than absent. Rated down one level because unassessed is not low.; inconsistency: MODERATE to LOW, down 1 level(s) -- I-squared 71.48% over k=4, with per-trial risk ratios running from 0.40 to 1.41 -- two intervals excluding the null in opposite directions. Rated down, and note that this is inconsistency of result and says nothing either way about whether the estimand is shared, which was established by reading the four titles. [restated 2026-08-20 with the REML values; the original is beside this under reason superseded 2026 08 20.] (reason superseded 2026 08 20: I-squared 67.8% over k=4, with per-trial risk ratios running from 0.40 to 1.41 -- two intervals excluding the null in opposite directions. Rated down, and note that this is inconsistency of result and says nothing either way about whether the estimand is shared, which was established by reading the four titles.); indirectness: not rated down -- One comparator (enoxaparin) in all four, and one endpoint definition verified by reading each trial's registered text.; imprecision: LOW to VERY_LOW, down 1 level(s) -- The interval 0.4371 to 1.264 spans a 55% reduction and a 23% increase. k=4, and tau-squared estimated by REML which the house rule says is biased low at this k -- so the interval is if anything narrower than it should be. [restated 2026-08-20: the pool is now fitted with REML under DECISIONS-COCHRANE-2026-08-18.md section 1, on Cochrane Handbook 6.5 section 10.10.4.4: "Decision: REML, everywhere." The clause that read 'tau-squared estimated by DerSimonian-Laird which the house rule says is biased low at this k -- so the interval is if anything narrower than it should be' named a reason that is now discharged, and the interval it described has in fact widened from (0.4532, 1.2309) to (0.4371, 1.264). The original wording is beside this under reason superseded 2026 08 20.] (reason superseded 2026 08 20: The interval 0.4532 to 1.2309 spans a 55% reduction and a 23% increase. k=4, and tau-squared estimated by DerSimonian-Laird which the house rule says is biased low at this k -- so the interval is if anything narrower than it should be.); publication bias: not rated down -- k=4. Not assessed; not counted as absent. |
grade.approachgrade.not_rated_upgrade.by_outcome.major_vteWhat this review does not give a clinician: the number of events in each arm, any absolute effect or number needed to treat and any measure of harm. A relative effect cannot be turned into the benefit or the risk facing one patient without them, so this review can support a judgement about what these trials found and not a judgement about what to do.1
results.by_outcomeEvery trial in this review is keyed to a registration identifier, verified by live fetch of the raw ClinicalTrials.gov v2 record and comparison of the returned nctId against the id stored on this object on 2026-08-19.1
| Registration | Verified | Link |
|---|---|---|
| NCT00457002 | True | https://clinicaltrials.gov/study/NCT00457002 |
| NCT00423319 | True | https://clinicaltrials.gov/study/NCT00423319 |
| NCT00371683 | True | https://clinicaltrials.gov/study/NCT00371683 |
| NCT00452530 | True | https://clinicaltrials.gov/study/NCT00452530 |
| NCT02366871 | True | https://clinicaltrials.gov/study/NCT02366871 |
registration_identity.methodregistration_identity.trialsAnalyses were computed under R 4.6.0 with metafor 5.0.1.1
Intervals are reported at the 95% level.2
results.by_outcomeconfig.confidence_levelThis review reports against PRISMA 2020. A screening record is held on this object and the flow it supports is shown in the Methods. The completed PRISMA checklist and FLOW diagram are not held here: the venue requires them deposited in an approved repository with a DOI cited in the Data Availability Statement, and minting that DOI is an author action rather than a build step.1
screeningProtocol status. Prespecified: False. A protocol specified before data collection is a historical fact about the past and cannot be created retrospectively. Writing one now and calling it prespecified would invalidate every other refusal on this page, because a reader who caught it would be right to disbelieve all of them.1
Eligibility criteria were derived post hoc when `apixaban-vte` was split in two on 2026-08-19, after the parent object's included set existed. The derivation is recorded element by element in `screening.eligibility`, and the criterion that separates this review from its sibling is stated in full at `screening.boundary_criterion`.2
Authority: Mecir R107 permits post-hoc eligibility criteria provided they are declared as such. They are declared, here and on the page.3
No PROSPERO registration or protocol record is held on this object. That is not the same as knowing this review was not registered, and neither claim is made. It is recorded here as an absence so that a reader does not have to infer it from silence.4
protocolprotocol.what_was_actually_doneprotocol.authority_permitting_itbookkeeping_2026_08_21.whether_this_review_was_prospectively_registered| Trial | Registration | Registry | Read |
|---|---|---|---|
| NCT00371683 | ClinicalTrials.gov | ||
| NCT00423319 | ClinicalTrials.gov | ||
| NCT00452530 | ClinicalTrials.gov | ||
| NCT00457002 | ClinicalTrials.gov | ||
| NCT02366871 | ClinicalTrials.gov |
| Cited for | Reference |
|---|---|
| certainty of the evidence | Schunemann HJ, Higgins JPT, Vist GE, et al. Chapter 14: Completing 'Summary of findings' tables and grading the certainty of the evidence. In: Cochrane Handbook for Systematic Reviews of Interventions version 6.5. Cochrane; 2024. |
| the model fitted, as R 4.6.0 with metafor 5.0.1 | Viechtbauer W. Conducting meta-analyses in R with the metafor package. J Stat Softw. 2010;36(3):1-48. doi:10.18637/jss.v036.i03 |
| the reporting guideline this manuscript is written against | Page MJ, McKenzie JE, Bossuyt PM, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ. 2021;372:n71. doi:10.1136/bmj.n71 |
manuscript.referencesmanuscript.referencesresults.by_outcome.major_vte.per_trial, results.by_outcome.major_vte.pooledresults.by_outcome.major_vte.per_trial, results.by_outcome.major_vte.pooled| Registration | Trial | Participants | Randomised | Primary outcome measured over | Design |
|---|---|---|---|---|---|
| NCT00371683 | ADVANCE-1 | registered condition: Deep Vein Thrombosis; Pulmonary Embolism | 2481 | From Day 1 or Day 2 to last dose, plus 2 days or 14 days post randomization; First dose of study drug to last dose, plus 2 days post last dose; Last dose of study drug to Day 72 (60 days) | randomised thromboprophylaxis, apixaban against enoxaparin. |
| NCT00423319 | ADVANCE-3 | registered condition: Deep Vein Thrombosis; Pulmonary Embolism | 4394 | Day 1 (first dose of study drug) to later of 2 days after last dose or 38 days after first dose | randomised thromboprophylaxis, apixaban against enoxaparin. |
| NCT00452530 | ADVANCE-2 | registered condition: Deep Vein Thrombosis; Pulmonary Embolism | 2394 | Day of randomization to later of 2 days after last dose or 14 days after first dose; 14 days after randomization for those who did not receive study drug | randomised thromboprophylaxis, apixaban against enoxaparin. |
| NCT00457002 | ADOPT | registered condition: Venous Thrombosis; Pulmonary Embolism | 4494 | Intended Treatment Period; Day 1, first dose of study drug, to last dose of study drug plus 2 days; Day 1, first dose of drug to last dose of drug plus 2 days | randomised thromboprophylaxis, apixaban against enoxaparin. |
| NCT02366871 | apixaban vs enoxaparin, pelvic malignancy | not recorded | 400 | Day 1 post-op/standard of care first medication dose to day 90 (+/-14 days) post-op/standard of care; Day 1 post-op/standard of care first dose of medication to day 90 (+/- 14 days) post-op/standard of care | randomised, apixaban against enoxaparin in suspected pelvic malignancy. |
inputs.trialsThis review was built to page standard 1.14.0-2026-08-19 (PAGE-STANDARD.md), by ssot/build_to_standard.py on 2026-08-19. A page built below the current standard is knowably below it rather than silently stale.1
11 machine-checked properties were verified for this page before it was published; the checks and their names are recorded with the build rather than here.2
build_stamp.page_standard_versionbuild_stamp.heldThe items below were not written because the record does not hold what they would be composed from. They are named here so that an absence is not mistaken for an omission.
| Article area | Item not reported | Reason |
|---|---|---|
| Abstract | The Background sentence of the abstract | Background is argument -- why this question matters -- and no arrangement of the quantities this object holds yields it. It is emitted only from an authored field and there is no composition path for it here |
| Abstract | The Conclusions sentence of the abstract | A conclusion is argument -- what a reader should now believe -- and it is emitted only from an authored field. Composing one from the estimate would be this renderer telling the reader what to conclude, which no field supports |
| Methods — synthesis | The claim that records were screened in duplicate | And this topic owes one rather than merely lacking one: |
| Methods — synthesis | The claim that the review methods were prespecified before data collection | This refusal is permanent and is not a gap to be filled. A protocol specified before data collection is a historical fact about the past and cannot be created retrospectively. Writing one now and calling it prespecified would invalidate every other refusal on this page, because a reader who caught it would be right to disbelieve all of them. Eligibility criteria were derived post hoc when `apixaban-vte` was split in two on 2026-08-19, after the parent object's included set existed. The derivation is recorded element by element in `screening.eligibility`, and the criterion that separates this review from its sibling is stated in full at `screening.boundary_criterion`. Mecir R107 permits post-hoc eligibility criteria provided they are declared as such. They are declared, here and on the page. |
| Risk of bias in the included results | The risk-of-bias distribution | No further reason is recorded. |
| Comparison with published syntheses | The comparison with published syntheses | No published synthesis is recorded for this topic, so no denominator can be given |
| Disagreements between sources | The reconciliation against other sources | No further reason is recorded. |
| Author contributions | The author-contributions statement | Who did what is a fact about people, and this object records none |
| Competing interests | The competing-interests declaration | F1000Research requires this section on every article, and requires explicit text where there is nothing to declare. It is a statement about the author and not about the evidence: no field of this object implies it and none is invented here |
| Grant information | The grant information | The venue requires each funder's name, the grant number where applicable, and the person the grant was assigned . None of that is derivable from a synthesis |
| Funding and conflicts of interest | The funding and conflict-of-interest statement -- a content gap | A submission requires it and this object does not carry it; it is not inferable from anything held here |
| Registration | A registration statement: no prospective registration is recorded for this review, and whether one exists elsewhere has not been established | No further reason is recorded. |
Built 2026-08-19 by ssot/build_to_standard.py against PAGE-STANDARD.md. 11 held, 3 refusing. A refusal is a complete outcome; nothing is generated to fill a slot.
| property | state | reason |
|---|---|---|
| P1_executed_search | HELD | 3 database queries recorded verbatim with dates and counts; PRISMA arithmetic reconciles and the 0-trial unscreened remainder is stated as a number rather than omitted. |
| P2_k_cascade | HELD | k at every stage: surfaced 82, located 80, experimental 54, comparator 19, included 5, unscreened remainder 0. |
| P3_inclusion_criteria | HELD | Criteria provenance block present with predefined=False on its face (state 'DERIVED_POST_HOC'). |
| P4_preconditions | HELD | All 8 recorded with verdict and cited authority: 1 FAIL, 3 NOT-ASSESSABLE. criteria_predefined is FAIL -- post hoc criteria, which R107 permits and C5/C7 does not satisfy. |
| P5_extraction_table | HELD | 8 cells: 6 READ with source path and verbatim text, 2 DERIVED with the method named. |
| P6_analysis_output | REFUSING | No quotable model output exists: k=4 and the pool on this page was computed outside R, so there is a synthesis and no quotation. The absence is recorded as a finding with its cause and what would close it. |
| P7_published_comparison | REFUSING | No denominator yet. Blocked on external registration-id resolution; citation-string matching explicitly refused rather than substituted. |
| P8_registration_identity | HELD | 5 of 5 trial(s) verified live against the registry. |
| P18_restatement_is_reproducible | REFUSING | No restatement block on this cascade, so there is nothing to re-derive. This is NOT_ASSESSABLE dressed as a refusal rather than a pass: a topic that has never been restated has not demonstrated that a restatement of it would be checkable. |
| P19_promotion_reaches_derived_blocks | HELD | inputs.trials, k_cascade.k_included_in_object and prisma_flow.included all say 5; no first-person field in published_comparison declares a k the pooled outcome(s) do not. |
| P20_cascade_reconciles | HELD | k2_role_located=80 == k3+k4+k5, and k0_surfaced=82 == k3+k4+k5+kNA. Both checked, and every failing limb would be reported rather than the first. |
| P21_ambiguous_question_split | HELD | Split from 'apixaban-vte' into this review and 1 sibling(s) apixaban-vte-treatment, with the decision recorded at None. Nothing was dropped to resolve the ambiguity. |
| P22_sharing_recorded | HELD | 1 shared trial(s), each recorded with the topics holding it and why: NCT02366871 in apixaban-vte and enoxaparin-vte. The object also states that summing per-topic k double-counts. |
| P23_recall_measured | HELD | All 3 recorded quer(ies) state their recall against this review's own included set: 1/1, 0/1 -- IT MISSED NCT02366871 ENTIRELY and NOT MEASURED. |
| stage | k |
|---|---|
| k0_surfaced | 82 |
| k2_role_located | 80 |
| k3_experimental | 54 |
| k4_comparator | 19 |
| k5_background | 7 |
| kNA_not_assessable | 2 |
| k_candidate_pool | 73 |
| k_screened | 73 |
| k_excluded | 42 |
| k_eligible | 31 |
| k_eligible_no_results_yet | 22 |
| k_eligible_not_poolable | 4 |
| k_eligible_poolable | 5 |
| k_included_in_object | 5 |
| k_pooled | 4 |
| k_unscreened_remainder | 0 |
| reproduced_by | scripts/screen_apixaban_split_2026_08_19.py, scripts/adjudicate_apixaban_split_2026_08_19.py and scripts/repool_apixaban_prophylaxis_2026_08_19.py. |
| reconciliation | 82 surfaced = 54 + 19 + 7 + 2; 80 of the 82 had a role located. 73 are the candidate pool; 1 was in the parent object and 72 were screened. 42 excluded + 31 eligible = 73. Of the 31 eligible, 22 have posted no results, 4 are eligible and not poolable, and 5 are eligible and poolable, of which 4 contribute. REMAINDER ZERO. |
| why_the_remainder_is_now_ZERO_and_was_71 | The whole remainder has been screened. 33 of this review's 39 mechanical exclusions fail on POPULATION -- they are treatment trials in patients who have already had a venous thromboembolism, which is exactly the population the sibling review holds. |
| AND ITS DOMINANT DISPOSITION IS NOT EXCLUSION | TWENTY-TWO OF THE THIRTY-ONE ELIGIBLE TRIALS HAVE POSTED NO RESULTS -- more than twice this review's excluded-on-comparator count and more than four times the number that pool. Under the reading in PAGE-STANDARD.md, a remainder dominated by NOT-YET-REPORTED means the query is well aimed and THE FIELD IS STILL IN FLIGHT. The largest pending trial in either apixaban remainder is NCT06581965, n=10,078, individualised versus standard thrombosis prophylaxis -- larger than every trial in this pool combined. It is what will change this answer, and it is named for that reason. |
| keyed_on | registration id |
predefined: False | post_hoc: True — derived —
—
| limb | value | derived from |
|---|---|---|
| — | — | — |
| — | — | — |
| — | — | — |
| — | — | — |
does each trial report, AT ANY RANK -- primary, secondary or other -- an outcome matching what the others report, before any decision about which pools are possible?
YES, AND IT IS A SECONDARY IN ALL FOUR
THE WHOLE POOL. Every contributing result is below the primary; a review reading primaries only would have found four incompatible composites and reported no pool. The poolable set went from 3 to 8 candidates and settled at 4 contributing trials and 13,570 participants. THE SIBLING REVIEW RAN THE IDENTICAL DISCIPLINE AND ITS POOLABLE SET FELL, 8 to 3. Asking is not a way of finding more trials.
—
| registration | trial | two-component | three-component |
|---|
| review | poolable set | direction |
|---|---|---|
| apixaban-vte-prophylaxis | 3 -> 8 | UP -- the question RECOVERED a pool |
| apixaban-vte-treatment | 8 -> 3 | DOWN -- the question DISSOLVED a pool |
THE SAME QUESTION, ASKED THE SAME WAY, ON THE SAME DRUG, ON THE SAME NIGHT, MOVED ONE REVIEW'S POOLABLE SET UP AND THE OTHER'S DOWN. Every earlier instance in this corpus recovered a pool, and a check that has only ever returned the convenient answer cannot be told apart from no check at all. This pair is the refutation, and it arose on its own rather than being sought: it cost the treatment review the two largest trials in its field. Asking the withholding question is not a way of finding more trials. It is a way of finding out.
NOT that either pool is correct -- both were judged by reading endpoint definitions, and that judgement stands or falls on its own. NOT that the direction is unpredictable in general; two instances are two instances. What it establishes is narrow and it is the thing that was missing: THE PROCEDURE HAS NO BUILT-IN DIRECTION, demonstrated rather than asserted.
—
k after screening: —. —
| failing limb | n | registrations |
|---|
—
—
| registration | rank | matching outcome |
|---|
| registration | verdict | limb | reason |
|---|
— | call: Rscript ssot/fit_from_per_trial.R apixaban-vte-prophylaxis major_vte
R version 4.6.0 (2026-04-24 ucrt) metafor 5.0.1 run_utc 2026-08-21 ================================================================ TOPIC apixaban-vte-prophylaxis OUTCOME major_vte STORED RR 0.7433 (0.4371 to 1.2640), k = 4, random-effects / REML INPUTS READ FROM THE OBJECT (log scale, SE derived from the published interval): ADOPT 0.9247 (0.6559 to 1.3036) yi=-0.078286 sei=0.175227 ADVANCE-3 0.3993 (0.1922 to 0.8293) yi=-0.918042 sei=0.372978 ADVANCE-1 1.4068 (0.7636 to 2.5919) yi=+0.341318 sei=0.311767 ADVANCE-2 0.5017 (0.2590 to 0.9715) yi=-0.689753 sei=0.337254 ---------------------------------------------------------------- CALL: rma(yi = yi, sei = sei, method = "REML", test = "knha") Random-Effects Model (k = 4; tau^2 estimator: REML) logLik deviance AIC BIC AICc -2.5205 5.0410 9.0410 7.2383 21.0410 tau^2 (estimated amount of total heterogeneity): 0.2042 (SE = 0.2398) tau (square root of estimated tau^2 value): 0.4519 I^2 (total heterogeneity / total variability): 71.48% H^2 (total variability / sampling variability): 3.51 Test for Heterogeneity: Q(df = 3) = 9.3122, p-val = 0.0254 Model Results: estimate se zval pval ci.lb ci.ub -0.2967 0.2709 -1.0953 0.2734 -0.8275 0.2342 --- Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 1 --- SAME FIT WITH HARTUNG-KNAPP (test = "knha") --- Random-Effects Model (k = 4; tau^2 estimator: REML) logLik deviance AIC BIC AICc -2.5205 5.0410 9.0410 7.2383 21.0410 tau^2 (estimated amount of total heterogeneity): 0.2042 (SE = 0.2398) tau (square root of estimated tau^2 value): 0.4519 I^2 (total heterogeneity / total variability): 71.48% H^2 (total variability / sampling variability): 3.51 Test for Heterogeneity: Q(df = 3) = 9.3122, p-val = 0.0254 Model Results: estimate se tval df pval ci.lb ci.ub -0.2967 0.2781 -1.0666 3 0.3644 -1.1818 0.5885 --- Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 1 BACK-TRANSFORMED: unadjusted 0.7433 (0.4371 to 1.2639) Hartung-Knapp 0.7433 (0.3067 to 1.8013) [t crit 3.1824 on 3 df] <- HOUSE INTERVAL, inflation factor floored at 1 (raw 1.0269) metafor raw 0.7433 (0.3067 to 1.8013) [test=knha, UNFLOORED] tau^2 0.204237 Q 9.3122 on 3 df, p = 0.0254 I^2 71.48% AGREES WITH THE STORED POINT TO 4 dp: YES
Denominator: —. Not established, and the obstacle is that no candidate synthesis has been identified for this estimand. The PubMed search at search.databases[2] reported 439 record(s) and retrieved 50; 389 were not retrieved, and 0 published benchmark(s) are recorded on this object. There is nothing yet to form a denominator over.
Explicitly not done: CITATION-STRING MATCHING. It would produce a comparison-shaped answer tonight and it is not identity: two syntheses citing the same trial under different labels would read as different, and the same label on different trials as the same. That is the substitution class this project audits for.
Blocked on: lane 2 registration-id resolution
Authority: Cochrane Handbook for Systematic Reviews of Interventions 6.5, 2024, verified 2026-08-19. Publishable: True.
| precondition | verdict | reason | authority |
|---|---|---|---|
| population_stated | PASS | present: question carries 220 characters | MECIR C62 'Ensuring meta-analyses are meaningful' (Mandatory, READ 2026-08-19): 'Undertake (or display) a meta-analysis only if participants, interventions, comparisons and outcomes are judged to be s |
| arm_role_resolved | NOT-ASSESSABLE | cannot assess: inputs.trials has 1 trial(s) with no readable arms ['NCT02366871'] and 0 with a blank arm role []. Absent role data is not a wrong role. | MECIR C62 (Mandatory), 'interventions' limb -- this is a PRECONDITION FOR ASSESSING C62, not an enforcement of it: you cannot judge whether interventions are 'sufficiently similar' without knowing whi |
| comparators_identified | PASS | every outcome names a comparator type ['active']; none declares 'mixed'. Within-outcome consistency is visible only through the declared type, and cross-outcome differences are not judged. | MECIR C62 (Mandatory), 'comparisons' limb -- a synthesis pools one contrast. NOT cited to C7: C7 governs PREDEFINITION, and this check reads recorded comparator fields and tests them for consistency. |
| estimand_named | PASS | outcomes.estimand: all 1 outcome(s) name a quantity | MECIR C8 'Clarifying role of outcomes' (Mandatory, READ 2026-08-19); MECIR C62 (Mandatory), 'outcomes' limb |
| criteria_stated | PASS | present: screening.eligibility carries 891 characters | MECIR R29 'Eligibility criteria for types of participants', R30 '...types of interventions', R31 'Role of outcomes' -- ALL Mandatory REPORTING standards (READ 2026-08-19). Their verb is STATE. A block |
| criteria_predefined | FAIL | screening.eligibility_provenance.predefined is false: the criteria were DERIVED post hoc from this object's own question and recorded exclusions. That is auditable (R29/R30/R31) and is not pre-specification (C5/C7). This | MECIR C5 'Predefining unambiguous criteria for participants' AND C7 '...for interventions and comparators', BOTH Mandatory (READ 2026-08-19): 'Predefined, unambiguous eligibility criteria are a fundam |
| eligibility_met | NOT-ASSESSABLE | cannot assess: criteria are stated, but sources is an empty dict -- no full text was available this pass, and inclusion logic is conditional prose | MECIR C5/C7 (Mandatory) with C6 'Predefining a strategy for studies with a subset of eligible participants' (Highly desirable, READ 2026-08-19) -- eligibility is assessed against the full report |
| contributes_a_randomised_contrast | NOT-ASSESSABLE | cannot assess: 1 of 5 trial(s) carry no readable arm roles ['NCT02366871'] | Handbook 6.5 s23.3.4 'How to include multiple groups from one study' (READ 2026-08-19) and s23.3.6 'Factorial trials'; MECIR C7 'Predefining unambiguous criteria for interventions and comparators' (Ma |
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Every number on this page is projected from a single canonical object, and each measured cell names the source analysis it was read from. That is what is machine-checked. It does not establish that the underlying sources are right, only that this page faithfully reports them.