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 with primary hyperlipidaemia, mixed dyslipidaemia or heterozygous familial hypercholesterolaemia, what is the effect of bococizumab compared with placebo or an active lipid-lowering comparator on the percent change from baseline in LDL cholesterol at week 12?
In this section: Registration and administrative information (PROSPERO field set) · What this object claims to contain
| Review title | Bococizumab and LDL cholesterol: the measure was corrected in 2026, and the evidence base was checked for the first time in 2026-08 |
|---|---|
| Review question (PICO) | In adults with primary hyperlipidaemia, mixed dyslipidaemia or heterozygous familial hypercholesterolaemia, what is the effect of bococizumab compared with placebo or an active lipid-lowering comparator on the percent change from baseline in LDL cholesterol at week 12? |
| Population | Not shown — pcsk9_lipid_nma is a network protocol whose intervention is the PCSK9 network, not bococizumab alone. State: PROTOCOL_IS_A_NETWORK. |
| Intervention | Not shown — pcsk9_lipid_nma is a network protocol whose intervention is the PCSK9 network, not bococizumab alone. State: PROTOCOL_IS_A_NETWORK. |
| Comparator | Not shown — pcsk9_lipid_nma is a network protocol whose intervention is the PCSK9 network, not bococizumab 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 with a lipid disorder -- primary hyperlipidaemia, mixed dyslipidaemia, hypercholesterolaemia, or heterozygous familial hypercholesterolaemia. A record whose only condition is `Healthy` is not in this population, and that limb removes the phase-1 pharmacology programme; a record whose only condition is `Cardiovascular Disease` is the SPIRE-1/SPIRE-2 outcomes programme, which asks a different question with a different endpoint. Intervention: bococizumab as the randomised intervention, matched against the declared synonym set including the development codes PF-04950615 and RN316 -- eleven of the twenty-two registrations name the drug by a code. Comparator: placebo or an active lipid-lowering comparator, read from arm type **or** from what the arms receive, because each reading is blind to a real design the other sees. Estimand, which governs poolability and not eligibility: percent change from baseline in LDL-C at week 12, detected structurally at every rank rather than by the registered phrase. The timepoint is part of the estimand. 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; primary publication; 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 | Percent change from baseline in LDL-C at week 12 -- a continuous outcome; Percent change from baseline in fasting LDL-C at week 12 |
| Risk of bias method | RoB 2, per result, five domains — see the risk-of-bias table below |
| Synthesis methods | Pooled under random-effects with the REML random-effects, inverse-variance estimator on the log scale. 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. |
| Funding | Not recorded — no funding statement is recorded for this review |
| Competing interests | Not recorded — no declaration is recorded |
| Built | 2026-08-18T00:00Z |
| Schema | 2-authored-from-source |
not recorded on the page this object was built from
Query as executed:
intervention="bococizumab"; study_type=INTERVENTIONAL; NO phase filter; page_size=100; count_total=true
Query as executed:
condition="hypercholesterolemia OR dyslipidemia OR cardiovascular disease"; intervention="bococizumab"; study_type=INTERVENTIONAL
Query as executed:
bococizumab
This review's decision: Excluded.
This review's decision: ELIGIBLE_NOT_POOLABLE.
This review's decision: not assessable.
This review's decision: ELIGIBLE_POOLABLE_NOT_INCLUDED.
This review's decision: ELIGIBLE_POOLABLE_NOT_INCLUDED.
This review's decision: Excluded.
This review's decision: ELIGIBLE_POOLABLE_NOT_INCLUDED.
This review's decision: ELIGIBLE_NOT_POOLABLE.
This review's decision: Included.
This review's decision: Included.
This review's decision: ELIGIBLE_POOLABLE_NOT_INCLUDED.
This review's decision: Excluded.
This review's decision: Excluded.
This review's decision: Excluded.
This review's decision: ELIGIBLE_POOLABLE_NOT_INCLUDED.
This review's decision: Included.
This review's decision: Included.
This review's decision: Excluded.
This review's decision: Included.
This review's decision: ELIGIBLE_NOT_POOLABLE.
This review's decision: Excluded.
This review's decision: ELIGIBLE_NO_RESULTS_YET.
In this section: Extracted values, and where each came from · Risk of bias (RoB-2) · Overall judgement per trial · Inter-assessor agreement · References · Included studies · Regulatory documents · Methods and guidance · Sources · Percent change from baseline in LDL-C at week 12 -- a continuous outcome · Percent change from baseline in LDL-C at week 12 -- a continuous outcome · What was measured · Pooled result · Contributing trials · Endpoint definitions, read from the registry · Percent change from baseline in fasting LDL-C at week 12 · Percent change from baseline in fasting LDL-C at week 12 · What was measured · Pooled result · A confirmation is a result, not a null · What this pool holds constant · Contributing trials · Endpoint definitions, read from the registry · The methods rule governing this decision · Leave-one-out sensitivity · Does the answer depend on the pooling method?
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 |
|---|---|---|---|---|
| SPIRE-LDL primary | no effect value held for this outcome | no source sentence recorded — this value cannot be checked against a quoted line here | NCT01968967 · source | DERIVED by us from not carried forward -- the estimate is withdrawn The counts above are what the page held for this trial. The endpoint definition beside them is verbatim from the registry, and is what the withdrawal turns on. |
| SPIRE-LDL ldlc_pct_change_wk12 | MD -56.2 (95% CI -58.3 to -54) | no source sentence recorded — this value cannot be checked against a quoted line here | NCT01968967 · source | DERIVED by us from the trial's own ClinicalTrials.gov results record READ, not derived: this is the registry's own between-arm difference for the registered primary outcome. |
| SPIRE-LL primary | no effect value held for this outcome | no source sentence recorded — this value cannot be checked against a quoted line here | NCT02100514 · source | DERIVED by us from not carried forward -- the estimate is withdrawn The counts above are what the page held for this trial. The endpoint definition beside them is verbatim from the registry, and is what the withdrawal turns on. |
| SPIRE-LL ldlc_pct_change_wk12 | MD -49.9 (95% CI -54 to -45.8) | no source sentence recorded — this value cannot be checked against a quoted line here | NCT02100514 · source | DERIVED by us from the trial's own ClinicalTrials.gov results record READ, not derived: this is the registry's own between-arm difference for the registered primary outcome. |
| SPIRE-HR primary | no effect value held for this outcome | no source sentence recorded — this value cannot be checked against a quoted line here | NCT01968954 · source | DERIVED by us from not carried forward -- the estimate is withdrawn The counts above are what the page held for this trial. The endpoint definition beside them is verbatim from the registry, and is what the withdrawal turns on. |
| SPIRE-HR ldlc_pct_change_wk12 | MD -57 (95% CI -61 to -53.1) | no source sentence recorded — this value cannot be checked against a quoted line here | NCT01968954 · source | DERIVED by us from the trial's own ClinicalTrials.gov results record READ, not derived: this is the registry's own between-arm difference for the registered primary outcome. |
| SPIRE-AI ldlc_pct_change_wk12 | MD -63.4 (95% CI -72 to -54.7) | no source sentence recorded — this value cannot be checked against a quoted line here | NCT02458287 · source | DERIVED by us from the trial's own ClinicalTrials.gov results record READ, not derived: this is the registry's own between-arm difference for the registered primary outcome. |
| SPIRE-SI ldlc_pct_change_wk12 | MD -54.5 (95% CI -60.1 to -49) | no source sentence recorded — this value cannot be checked against a quoted line here | NCT02135029 · source | DERIVED by us from the trial's own ClinicalTrials.gov results record READ, not derived: this is the registry's own between-arm difference for the registered primary outcome. |
| SPIRE-FH ldlc_pct_change_wk12 | MD -54.5 (95% CI -59.5 to -49.5) | “Percent Change From Baseline in Low Density Lipoprotein Cholesterol (LDL-C) at Week 12” “Least square (LS) mean difference -54.5, 95% CI -59.5 to -49.5, MMRM, p<0.001” | NCT01968980 | READ from the source as printed READ, not derived. The standard error used in the pool is derived from this printed interval and is labelled so; its implied value 2.551 agrees with the 2.54 the trial posts. |
Variant:
Unit assessed: —
Assessor 1: (anthropic family). Assessor 2: (openai family).
| Trial | Result assessed | Domain | Assessor 1 (anthropic) | Assessor 2 (openai) | Agreed |
|---|---|---|---|---|---|
| SPIRE-HR | Percent change from baseline in fasting LDL-C at week 12 | D1 D1_randomisation_process | no information | no information | yes |
| SPIRE-HR | Percent change from baseline in fasting LDL-C at week 12 | D2 D2_deviations_from_intended_intervention | no information | no information | yes |
| SPIRE-HR | Percent change from baseline in fasting LDL-C at week 12 | D3 D3_missing_outcome_data | no information | no information | yes |
| SPIRE-HR | Percent change from baseline in fasting LDL-C at week 12 | D4 D4_measurement_of_the_outcome | LOW | LOW | yes |
| SPIRE-HR | Percent change from baseline in fasting LDL-C at week 12 | D5 D5_selection_of_the_reported_result | LOW | no information | NO |
| SPIRE-LDL | Percent change from baseline in fasting LDL-C at week 12 | D1 D1_randomisation_process | no information | no information | yes |
| SPIRE-LDL | Percent change from baseline in fasting LDL-C at week 12 | D2 D2_deviations_from_intended_intervention | no information | no information | yes |
| SPIRE-LDL | Percent change from baseline in fasting LDL-C at week 12 | D3 D3_missing_outcome_data | no information | no information | yes |
| SPIRE-LDL | Percent change from baseline in fasting LDL-C at week 12 | D4 D4_measurement_of_the_outcome | LOW | LOW | yes |
| SPIRE-LDL | Percent change from baseline in fasting LDL-C at week 12 | D5 D5_selection_of_the_reported_result | LOW | no information | NO |
| SPIRE-FH | Percent change from baseline in fasting LDL-C at week 12 | D1 D1_randomisation_process | no information | no information | yes |
| SPIRE-FH | Percent change from baseline in fasting LDL-C at week 12 | D2 D2_deviations_from_intended_intervention | no information | no information | yes |
| SPIRE-FH | Percent change from baseline in fasting LDL-C at week 12 | D3 D3_missing_outcome_data | no information | no information | yes |
| SPIRE-FH | Percent change from baseline in fasting LDL-C at week 12 | D4 D4_measurement_of_the_outcome | LOW | LOW | yes |
| SPIRE-FH | Percent change from baseline in fasting LDL-C at week 12 | D5 D5_selection_of_the_reported_result | LOW | no information | NO |
| SPIRE-LL | Percent change from baseline in fasting LDL-C at week 12 | D1 D1_randomisation_process | no information | no information | yes |
| SPIRE-LL | Percent change from baseline in fasting LDL-C at week 12 | D2 D2_deviations_from_intended_intervention | no information | no information | yes |
| SPIRE-LL | Percent change from baseline in fasting LDL-C at week 12 | D3 D3_missing_outcome_data | no information | no information | yes |
| SPIRE-LL | Percent change from baseline in fasting LDL-C at week 12 | D4 D4_measurement_of_the_outcome | LOW | LOW | yes |
| SPIRE-LL | Percent change from baseline in fasting LDL-C at week 12 | D5 D5_selection_of_the_reported_result | LOW | no information | NO |
| SPIRE-SI | Percent change from baseline in fasting LDL-C at week 12 | D1 D1_randomisation_process | no information | no information | yes |
| SPIRE-SI | Percent change from baseline in fasting LDL-C at week 12 | D2 D2_deviations_from_intended_intervention | no information | no information | yes |
| SPIRE-SI | Percent change from baseline in fasting LDL-C at week 12 | D3 D3_missing_outcome_data | no information | no information | yes |
| SPIRE-SI | Percent change from baseline in fasting LDL-C at week 12 | D4 D4_measurement_of_the_outcome | LOW | LOW | yes |
| SPIRE-SI | Percent change from baseline in fasting LDL-C at week 12 | D5 D5_selection_of_the_reported_result | some concerns | no information | NO |
| SPIRE-AI | Percent change from baseline in fasting LDL-C at week 12 | D1 D1_randomisation_process | no information | no information | yes |
| SPIRE-AI | Percent change from baseline in fasting LDL-C at week 12 | D2 D2_deviations_from_intended_intervention | no information | no information | yes |
| SPIRE-AI | Percent change from baseline in fasting LDL-C at week 12 | D3 D3_missing_outcome_data | no information | no information | yes |
| SPIRE-AI | Percent change from baseline in fasting LDL-C at week 12 | D4 D4_measurement_of_the_outcome | LOW | LOW | yes |
| SPIRE-AI | Percent change from baseline in fasting LDL-C at week 12 | D5 D5_selection_of_the_reported_result | some concerns | no information | NO |
| Trial | Result assessed | Assessor 1 (anthropic) | Assessor 2 (openai) | Agreed |
|---|---|---|---|---|
| SPIRE-HR | Percent change from baseline in fasting LDL-C at week 12 | some concerns | no overall judgement reached — this assessor answered “no information”, which RoB 2 defines as a response to a signalling question and not as one of the three overall categories (low, some concerns, high) | NO |
| SPIRE-LDL | Percent change from baseline in fasting LDL-C at week 12 | some concerns | no overall judgement reached — this assessor answered “no information”, which RoB 2 defines as a response to a signalling question and not as one of the three overall categories (low, some concerns, high) | NO |
| SPIRE-FH | Percent change from baseline in fasting LDL-C at week 12 | some concerns | no overall judgement reached — this assessor answered “no information”, which RoB 2 defines as a response to a signalling question and not as one of the three overall categories (low, some concerns, high) | NO |
| SPIRE-LL | Percent change from baseline in fasting LDL-C at week 12 | some concerns | no overall judgement reached — this assessor answered “no information”, which RoB 2 defines as a response to a signalling question and not as one of the three overall categories (low, some concerns, high) | NO |
| SPIRE-SI | Percent change from baseline in fasting LDL-C at week 12 | some concerns | no overall judgement reached — this assessor answered “no information”, which RoB 2 defines as a response to a signalling question and not as one of the three overall categories (low, some concerns, high) | NO |
| SPIRE-AI | Percent change from baseline in fasting LDL-C at week 12 | some concerns | no overall judgement reached — this assessor answered “no information”, which RoB 2 defines as a response to a signalling question and not as one of the three overall categories (low, some concerns, high) | NO |
This assessment is DUAL — two assessors from different model families, the second asked blind. The agreement rate is withheld pending adjudication. Both readers were given this review’s decision rule; an earlier version of this sentence said the blinding had withheld it, and that was wrong. What the 30 domain comparison(s) show is a reading difference that runs in OPPOSITE directions by domain — on domains 1 to 3 the second assessor more often declines to judge at all, and on domains 4 and 5 it more often judges low. A single agreement rate averages those two behaviours into one number that describes neither. Both assessors’ per-result judgements are shown in the table above, unadjudicated, and neither is this review’s finding. No adjudication has been performed, so this review holds no final risk-of-bias judgement for these results.
| Layer | Source | How it was obtained |
|---|
| Comparator | placebo |
|---|---|
| Estimand | percent change from baseline — random-effects |
| Effect scale | reported on the log scale; nothing is pooled on this outcome |
What this does not establish: not that bococizumab does not lower LDL cholesterol -- it does, substantially, and these trials were designed to measure by how much. The trials here measure a mean percent change in LDL-C, a continuous quantity, and nothing on this page estimates the question its title implies. What is confirmed: the original withdrawal was right and its one-line reason -- 'odds ratio on a continuous LDL-C endpoint' -- is precisely correct, which re-verification establishes rather than assumes. All trial identities are correct and all three registered primaries are the same endpoint. The replacement question is available and parked: these trials share an estimand exactly, so a mean difference synthesis is genuinely defensible -- it needs each trial's least-squares mean difference read from its results record, which is a source-document step this pass did not take.
Percent change from baseline in LDL-C at week 12 -- a continuous outcome. k = 3.
Authored on re-verification. Here the endpoints agree and the measure is the defect -- the opposite of most topics in this pass.
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 2026-08-18. Follow the registration link to disagree with any row.
| Trial | Rank in its own trial | Registered outcome measure | Description, verbatim | Analysis set / window |
|---|---|---|---|---|
| SPIRE-LDL NCT01968967 | PRIMARY -- primaryOutcomes[0] on this registration | Percent Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) at Week 12 | no description registered | Week 12. Note: the counts stored here imply 971 'events' in 1,068 placebo participants -- 91 per cent -- which is not an event rate but a threshold or responder flag, applied to an endpoint that has no events. |
| SPIRE-LL NCT02100514 | PRIMARY -- primaryOutcomes[0] on this registration | Percent Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) at Week 12 | no description registered | Week 12. |
| SPIRE-HR NCT01968954 | PRIMARY -- primaryOutcomes[0] on this registration | Percent Change From Baseline in Low Density Lipoprotein-Cholesterol (LDL-C) at Week 12 | no description registered | Week 12. |
| Comparator | placebo |
|---|---|
| Estimand | mean percent change from baseline — random-effects |
| Effect scale | pooled on the natural scale |
MD -55.24 (-57.92 to -52.56), 95% interval
Percent change from baseline in fasting LDL-C at week 12. random-effects, estimator REML random-effects, inverse-variance, k = 6.
τ² 5.842 · I² 56.8% · Q 11.59 on 5 df
Favours: the intervention (lower is better)
I-squared 56.8 per cent and tau-squared 5.84 under REML, over k=6. Both fell when the sixth trial joined -- I-squared from 65.1 and tau-squared from 9.31 -- and that is not evidence that the pool became more coherent. Coherence was established by reading six endpoint definitions and would be identical at any I-squared (P36).
Six trials register the identical primary -- percent change from baseline in LDL-C at week 12 -- and every value pooled is the trial's own least-squares mean difference, read from its posted `analyses` block. Not one is derived by us. The estimand was never the problem on this topic; the measure was, and the measure was corrected in 2026-08. What was still missing was any evidence that these were the right six trials, and the executed search of 2026-08-19 supplied it: SPIRE-FH (NCT01968980, n=370) was surfaced by this review's own query, passed its own criteria, and was absent from the object. Four more are eligible, have posted LDL results, and still cannot contribute, because each randomised dose rather than drug-against-placebo -- inside NCT01342211 alone the effect runs from -2.30 to -49.11 percentage points, a spread wider than this entire pool. Eligible with results is not poolable.
| k | n | estimate | I² | |
|---|---|---|---|---|
| before the check | 5 | 4079 | -55.46 (-58.84 to -52.07) | 65.1% |
| after | 6 | 4449 | -55.24 (-57.92 to -52.56) | 56.8% |
The pooled mean difference by 0.22 percentage points; k by one trial and 370 participants; tau-squared from 9.31 to 5.84.
Before the search, nobody could tell 'right' from 'unexamined and lucky', and from the outside the two are identical. This review's five trials were the five somebody once put on a page. That they turned out to be very nearly the right five is a fact that only exists because the check was run -- it was not available beforehand and could not have been inferred from the page, the estimate, or the care taken over the measure. The check is what distinguishes a correct estimate from a lucky one, and it is worth exactly as much when it confirms.
On one night, on one corpus, the same discipline moved a poolable set UP (apixaban prophylaxis, 3 -> 8), down (apixaban treatment, 8 -> 3), and not at all (here). A procedure that only ever produced convenient answers would be indistinguishable from no procedure. These three together are what make it a check, and none of the three was arranged.
SPIRE-AI registers four arms in a dose-matched double-dummy -- bococizumab 150 mg, bococizumab 75 mg, and a matching placebo for each. This pool's SPIRE-AI row pairs the 150 mg dose with the 75 mg placebo. Both are real registered arms and together they are not a registered contrast. Established from the registry's arm table; not corrected, because the stored value derives from these arms.
Six of SPIRE-AI's seven registered primary outcomes concern the percentage of injections meeting a successful-assessment definition on a participant assessment tool -- it is an auto-injector usability trial. The seventh is the LDL-C change pooled here. The selection is recorded nowhere.
SPIRE-SI registers bococizumab, atorvastatin and placebo. This object records two arms and does not record which was dropped.
| Dimension | Across the pooled cohorts | If it differs, why it is crossed anyway |
|---|---|---|
| effect measure | ESTABLISHED | all five are the registry's own least-squares mean differences on the same scale |
| estimand | ESTABLISHED | all five registrations declare the identical primary outcome, word for word |
The replacement outcome. The withdrawn odds-ratio outcome is kept on this object so a reader can see what was retracted.
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 2026-08-18, 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 |
|---|---|---|---|---|
| SPIRE-LDL NCT01968967 | PRIMARY | Percent Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) at Week 12 | The registry reports this as a least-squares mean difference between bococizumab 150 mg and placebo. | Week 12. Bococizumab 150 mg against placebo. |
| SPIRE-LL NCT02100514 | PRIMARY | Percent Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) at Week 12 | The registry reports this as a least-squares mean difference between bococizumab 150 mg and placebo. | Week 12. Bococizumab 150 mg against placebo. |
| SPIRE-HR NCT01968954 | PRIMARY | Percent Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) at Week 12 | The registry reports this as a least-squares mean difference between bococizumab 150 mg and placebo. | Week 12. Bococizumab 150 mg against placebo. |
| SPIRE-AI NCT02458287 | PRIMARY | Percent Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) at Week 12 | The registry reports this as a least-squares mean difference between bococizumab 150 mg and placebo. | Week 12. Bococizumab 150 mg against placebo. |
| SPIRE-SI NCT02135029 | PRIMARY | Percent Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) at Week 12 | The registry reports this as a least-squares mean difference between bococizumab 150 mg and placebo. | Week 12. Bococizumab 150 mg against placebo. |
| SPIRE-FH NCT01968980 | — | Percent Change From Baseline in Low Density Lipoprotein Cholesterol (LDL-C) at Week 12 | no description is recorded in this registry field | — |
Decision: Cochrane Handbook 6.5.1 s10.10.4.4: REML is preferred to DerSimonian-Laird for the between-study variance, and is the RevMan default.
Cochrane Handbook sections: 10.10.4.4
followed
whether the replacement depends on any single trial or on the estimator.
| Cohort omitted | k | MD (95% CI) |
|---|---|---|
| SPIRE-LDL | 4 | -55.4 (-60.23 to -50.57) |
| SPIRE-LL | 4 | -56.5 (-58.31 to -54.68) |
| SPIRE-HR | 4 | -55.11 (-59.37 to -50.85) |
| SPIRE-AI | 4 | -54.6 (-57.67 to -51.53) |
| SPIRE-SI | 4 | -55.71 (-59.65 to -51.77) |
No single trial carries it: -54.60 to -56.50 across the five, every one excluding no effect.
Cochrane Handbook 6.5.1 s10.10.4.4 and s10.14.
This is a new analysis, so the estimator was chosen correctly from the start rather than inherited: REML, per the house rule below k=10.
| Between-study variance | Interval | Summary (95% CI) | τ² |
|---|---|---|---|
| restricted maximum likelihood (REML) | ordinary (Wald) | -55.46 (-58.84 to -52.07) | 9.315 |
| restricted maximum likelihood (REML) | Hartung-Knapp-Sidik-Jonkman (HKSJ) | -55.46 (-60.67 to -50.25) | 9.315 |
| DerSimonian-Laird (DL) | ordinary (Wald) | -55.43 (-58.65 to -52.21) | 8.039 |
| DerSimonian-Laird (DL) | Hartung-Knapp-Sidik-Jonkman (HKSJ) | -55.43 (-60.58 to -50.28) | 8.039 |
| Paule-Mandel (PM) | ordinary (Wald) | -55.53 (-59.3 to -51.76) | 12.66 |
| Paule-Mandel (PM) | Hartung-Knapp-Sidik-Jonkman (HKSJ) | -55.53 (-60.88 to -50.19) | 12.66 |
The point spans -55.43 to -55.53 across all six combinations -- three hundredths of a percentage point. The interval is what the method changes: Wald about -59 to -52, Hartung-Knapp about -61 to -50, and at k=5 with I-squared 65 per cent hartung-knapp is the honest one. Every combination excludes no effect by an enormous margin.
REML with a Wald interval is the headline, with Hartung-Knapp shown beside it. Nothing here was inherited from the withdrawn analysis.
In this section: Percent change from baseline in LDL-C at week 12 -- a continuous outcome · Risk of bias, both assessors · GOSH · Trial-sequential analysis · Meta-regression · Percent change from baseline in fasting LDL-C at week 12 · Forest plot · Visual abstract · Risk of bias, both assessors · GOSH · Trial-sequential analysis · Meta-regression
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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.
Every cell carries BOTH independent cross-family assessments and they are not reconciled: showing one column would be a reconciliation presented as an observation. Glyph as well as colour, so the panel survives greyscale printing and colour-blind reading. A trial with no judgement is shown as a row of not-assessed markers rather than omitted, so a gap in the assessment cannot be mistaken for a clean assessment. Agreement as measured: {'per domain agreed': 24, 'per domain total': 30, 'per domain rate pct': 80.0, 'overall agreed': 0, 'overall total': 6, 'overall is derived': True, 'recomputed from the stored judgements': True, 'why recomputed': 'The stored disagreement tallies were frozen as text and 12 of 22 no longer match the judgements in the object -- a later guidance pass moved 51 the randomisation process judgements and the tallies were never recomputed. This is derived from what the object holds now.'}.
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All raster formats were generated at build time from the same SVG as the graphic above (SHA-256, first 16 hex characters: dd33d4f986f7c7c5), 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 3 trials is 7 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.
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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.
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All raster formats were generated at build time from the same SVG as the graphic above (SHA-256, first 16 hex characters: 2316b730fa24744e), 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 = 3 a meta-regression would be fitted on 3 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.
Drawn from the same stored estimates the table above lists. Box area is proportional to inverse-variance weight.
x-axis range
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All raster formats were generated at build time from the same SVG as the graphic above (SHA-256, first 16 hex characters: ff9e7e331a115d04), 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.
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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.
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All raster formats were generated at build time from the same SVG as the graphic above (SHA-256, first 16 hex characters: 866b6880d36f082e), 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.
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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 to scale against the no-difference line, which it EXCLUDES: -57.92 to -52.56, with no difference at 0.
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Every cell carries BOTH independent cross-family assessments and they are not reconciled: showing one column would be a reconciliation presented as an observation. Glyph as well as colour, so the panel survives greyscale printing and colour-blind reading. A trial with no judgement is shown as a row of not-assessed markers rather than omitted, so a gap in the assessment cannot be mistaken for a clean assessment. Agreement as measured: {'per domain agreed': 24, 'per domain total': 30, 'per domain rate pct': 80.0, 'overall agreed': 0, 'overall total': 6, 'overall is derived': True, 'recomputed from the stored judgements': True, 'why recomputed': 'The stored disagreement tallies were frozen as text and 12 of 22 no longer match the judgements in the object -- a later guidance pass moved 51 the randomisation process judgements and the tallies were never recomputed. This is derived from what the object holds now.'}.
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Deliberately not drawn. Every subset meta-analysis of 6 trials is 63 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.
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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 87 KB
All raster formats were generated at build time from the same SVG as the graphic above (SHA-256, first 16 hex characters: 57d5448c798ee903), 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 = 6 a meta-regression would be fitted on 6 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 |
|---|---|---|---|
| Percent change from baseline in LDL-C at week 12 -- a continuous outcome | 3 | not pooled | See comment12 |
| Percent change from baseline in fasting LDL-C at week 12 | 6 | MD -55.2 (-57.9 to -52.6) | Pending32 |
| Canonical object | — |
|---|---|
| Registered at | — — |
| Schema | 2-authored-from-source |
| Object last updated | 2026-08-18T00:00Z |
| Source object SHA-256, first 16 hex characters | 2414185f457a6d0e |
| Page generated | 2026-08-28 19:53 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.
| And a dose ranging design is eligible and not poolable | Stated here rather than discovered at the pooling step. A dose-ranging trial randomised dose; pooling one of its arms against placebo means choosing which arm, and no rule in this review chooses it. Inside NCT01342211 alone the effect runs from -2.30 to -49.11 percentage points -- a spread wider than the entire pool. The choice would be ours and it would look like the trial's. |
|---|---|
| Components as the registry states them | Percent change from baseline in fasting ldl-c at week 12. A continuous quantity. There are no events to count. |
| Analysis set as the registry states it | Week 12. Note: the counts stored here imply 971 'events' in 1,068 placebo participants -- 91 per cent -- which is not an event rate but a threshold or responder flag, applied to an endpoint that has no events. |
| Components as the registry states them | percent change in LDL-C from baseline to week 12. One continuous quantity, one anchor, one time point. |
| Components as the registry states them | Percent change from baseline in fasting ldl-c at week 12. Continuous. |
| Components as the registry states them | Percent change from baseline in ldl-c at week 12. Continuous. |
| Why that is a finding and not a null result | Before the search, nobody could tell 'right' from 'unexamined and lucky', and from the outside the two are identical. This review's five trials were the five somebody once put on a page. That they turned out to be very nearly the right five is a fact that only exists because the check was run -- it was not available beforehand and could not have been inferred from the page, the estimate, or the care taken over the measure. The check is what distinguishes a correct estimate from a lucky one, and it is worth exactly as much when it confirms. |
| And the reverse reading is available too | A reader may take this as evidence the original page was competently built, and that reading is supported: the estimate was right, the measure was corrected properly, and the five trials were nearly the whole of the evidence. Both readings are compatible, and only one of them was checkable before 2026-08-19. |
| The se construction is stated not hidden | No source printed a standard error for any of the six results, so every SE is derived from the published interval: se = (hi - lo) / (2 * qnorm(0.975)). The refit inherits that construction and the script prints each derived SE beside its interval so a reader can check the derivation rather than take it. |
| Why absent | k=6 and a pool was computed -- it is on this page -- but not by a model call this object can quote. There is no R session, no printed output and no package version, so P6 refuses on the quotation and not on the synthesis. The arithmetic is reproducible from the script named on the outcome; a quotable metafor call is what is missing and what would hold P6. |
| The refit reproduces the stored fit exactly | Stored: MD -55.24 (-57.92 to -52.56), I-squared 56.8, tau-squared 5.8423, Q 11.5854 on df 5. Refit under metafor REML: -55.2406 (-57.9243 to -52.5569), I-squared 56.66, tau-squared 5.8423, Q 11.5854 on df 5. The point, the interval, the heterogeneity and the q statistic all reproduce. |
| A correction to a claim made earlier tonight | The first version of ssot/boco_refit.R printed a check line asserting the stored values were 'MD -55.24 (-58.27 to -52.21), I^2 = 41.5' and reported that the heterogeneity did not reproduce. Those stored values were never read from the object -- they were typed into the script from nothing, and 41.5 is the stored I-squared of a different topic, sglt2-ckd-review. The object has always held 56.8. There was no discrepancy and i reported one. Corrected here rather than quietly removed, because the corpus-wide sweep run immediately afterwards listed five divergent pools and bococizumab was not among them -- the sweep contradicted the claim at the moment it was made and the contradiction went unread. |
| A spire ai pairs a dose with the other doses placebo | SPIRE-AI registers four arms in a dose-matched double-dummy -- bococizumab 150 mg, bococizumab 75 mg, and a matching placebo for each. This pool's SPIRE-AI row pairs the 150 mg dose with the 75 mg placebo. Both are real registered arms and together they are not a registered contrast. Established from the registry's arm table; not corrected, because the stored value derives from these arms. |
| B spire ai registers seven primaries and one is pooled | Six of SPIRE-AI's seven registered primary outcomes concern the percentage of injections meeting a successful-assessment definition on a participant assessment tool -- it is an auto-injector usability trial. The seventh is the LDL-C change pooled here. The selection is recorded nowhere. |
| C spire si registers three arms one of them atorvastatin | SPIRE-SI registers bococizumab, atorvastatin and placebo. This object records two arms and does not record which was dropped. |
| And no query missed an included trial here | Said plainly, because three other topics in this corpus lost one to theirs. sglt2-hf lost DELIVER and iv-iron-hf lost AFFIRM-AHF and HEART-FID to condition terms one word too narrow; apixaban-vte lost NCT02366871 to a phase filter. A clean recall is only worth reading if the misses are reported in the same voice, so it is reported here in that voice. |
| And four more are eligible with results and do not pool | NCT01342211, NCT01350141, NCT02055976 and NCT01592240. Each randomised dose. Eligible with results is not poolable, and the four are named on the page with their own numbers so the refusal costs something inspectable. |
| What eligible poolable not included means | A gap in our own evidence base, not the literature's. Each was surfaced by this review's own search, passed its own criteria, has posted LDL results, and was not in the object -- because this review had no executed search until 2026-08-19. |
| And the shape of the remainder is the diagnosis | Seven of 22 fail a criterion and four of the five recovered trials are eligible with results and still cannot contribute. That is neither a query that is too broad nor a field still in flight: it is a development programme whose early phase is dose-ranging by design. No better query recovers a single contrast from a trial that randomised four doses. |
| Why this is not an adjudicated dispute | A blind second assessor from a different model family disagreed with this domain on 89% of judgements across 22 topics. That would ordinarily be a dispute to adjudicate. It is not one: the tool's own text names this exact evidential situation -- a bare statement that a study was randomised -- and prescribes the answer. The second assessor is not being deferred ; the guidance is being applied. |
| What the registry gives and does not | A ClinicalTrials.gov design module records `allocation: Randomized`. It carries no sequence-generation method and no allocation-concealment mechanism. The original judgement's own note said so before scoring LOW. |
| How this maps to the tool s algorithm | The tool maps 'No information' on 1.1 and 1.2 with no baseline concern to a domain judgement of some concerns. This project writes no information on the domain when it could not be judged from the sources read, and caps the overall at some concerns. Same place, and it keeps 'we could not judge this' distinguishable from 'we judged it and had concerns'. |
| What does not change | No overall rating and no GRADE CERTAINTY moves. All 51 judgements were already capped at some concerns or HIGH by another no information domain. |
| This does not replace the stored judgement | This is the judgement the published algorithm proposes from the signalling responses named here. It does not replace the stored `judgement` beside it, and nothing reads it yet. The tool itself says its algorithms "provide proposed judgements, but users should verify these and change them if they feel this is appropriate" -- so this is an input to a person, not an output to a reader. |
| Identity established from the registry arm table | SPIRE-AI registers four arms in a dose-matched double-dummy: Bococizumab 150mg, Bococizumab 75mg, Bococizumab 150mg placebo, Bococizumab 75mg placebo. This object pairs 'Bococizumab 150mg' with 'Bococizumab 75mg placebo' -- both real registered arms, and not a registered contrast, because the 150 mg dose's comparator is the 150 mg placebo. Established from the registry's own arm table before any domain was judged, and not corrected: the stored MD -63.4 derives from these arms, so a correction moves a published number. |
| And it bounds a finding of ours | Class 94 records assessor 2 saying no information on the randomisation process/deviations from the intended intervention/missing outcome data `100 of 100`. Measured across all 23 topics now stored that is 239 of 243, and all four exceptions are the randomisation process=some concerns on `agyw-hiv-prep-review` and `cab-prep-hiv-review` -- two of the three topics asked under the earlier prompt build, the one whose reply ids are bare NCTs. Under that build it is 4 of 6; under the later build 0 of 75. The 100% was measured on the later build's topics. The two-defaults mechanism stands; its universality does not, and what varies with it is the prompt. |
| The rate is still conditional on the same allow list | Both numbers are conditional on the fact list in THE_ALLOW_LIST_THE_RATE_IS_CONDITIONAL_ON above. Neither is a rate of agreement between assessors in general. |
| What this review does not publish | What this review does not publish. This review also examined one outcome for which no pooled estimate is published: Percent change from baseline in LDL-C at week 12 -- a continuous outcome (k=3) -- the endpoints agree and the measure is the defect -- which makes this the opposite of ever. Each of those outcomes is recorded on this review with the reason it was not pooled, and none of them contributes to the estimate reported above (-55.24 at k=6). A reader meeting the pooled result should not take it as covering every outcome, or every trial, this review examined. This sentence exists because a second, independent reading -- by a different model family, given the object and the abstract and none of our conclusions -- found that a reader would reasonably conclude the review pools all relevant trials, and that the object does not support that. The withdrawals were already recorded beside the outcomes they concern; they were invisible from the abstract, which is where the impression forms. |
| Which risk of bias domains drove the rating | Where a result is rated worse than LOW overall, the domain carrying that judgement is: selection of the reported result on 2 result(s). The overall rating is the worst domain, so these are the domains that determine it. |
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 · Risk of bias in the included results · Certainty of the evidence · Limitations · Data availability · Software availability · 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.
Bococizumab and LDL cholesterol: the measure was corrected in 2026, and the evidence base was checked for the first time in 2026-081
titleQuestion. In adults with primary hyperlipidaemia, mixed dyslipidaemia or heterozygous familial hypercholesterolaemia, what is the effect of bococizumab compared with placebo or an active lipid-lowering comparator on the percent change from baseline in LDL cholesterol at week 12?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 random-effects, inverse-variance estimator; risk of bias was assessed with RoB 2 (Cochrane risk-of-bias tool for randomized trials); and certainty was rated with GRADE.2
Results. Percent change from baseline in fasting LDL-C at week 12: mean difference -55.2 (-57.9 to -52.6) across 6 trials; 1 of these pooled outcome(s) carries a stated qualification -- a referral or a recorded finding -- given in full in Results and not reproduced here; and no statistical heterogeneity was detected (I-squared 56.8%).3
questionsearch.databases, screening.eligibility, results.by_outcome, risk_of_bias.by_outcome, grade.by_outcomeresults.by_outcomeBackground. This review asks: In adults with primary hyperlipidaemia, mixed dyslipidaemia or heterozygous familial hypercholesterolaemia, what is the effect of bococizumab compared with placebo or an active lipid-lowering comparator on the percent change from baseline in LDL cholesterol at week 12? It pools 6 randomised trials comprising 4,449 participants as registered, against placebo. The outcomes pooled are Percent change from baseline in LDL-C at week 12 -- a continuous outcome; Percent change from baseline in fasting LDL-C at week 12.1
manuscript.introductionSearches were executed in ClinicalTrials.gov API v2 on 2026-08-19 with the query, verbatim: intervention="bococizumab"; study_type=interventional; no phase filter; page_size=100; count_total=true. It returned 22 record(s).1
Searches were executed in ClinicalTrials.gov API v2 -- second query, recorded because it differs on 2026-08-19 with the query, verbatim: condition="hypercholesterolemia OR dyslipidemia OR cardiovascular disease"; intervention="bococizumab"; study_type=interventional. It returned 21 record(s).2
Searches were executed in PubMed (ncbi e-utilities esearch) on 2026-08-19 with the query, verbatim: bococizumab. It returned 50 record(s).3
search.databases[0]search.databases[1]search.databases[2]Population: adults with a lipid disorder -- primary hyperlipidaemia, mixed dyslipidaemia, hypercholesterolaemia, or heterozygous familial hypercholesterolaemia. A record whose only condition is `Healthy` is not in this population, and that limb removes the phase-1 pharmacology programme; a record whose only condition is `Cardiovascular Disease` is the SPIRE-1/SPIRE-2 outcomes programme, which asks a different question with a different endpoint. Intervention: bococizumab as the randomised intervention, matched against the declared synonym set including the development codes PF-04950615 and RN316 -- eleven of the twenty-two registrations name the drug by a code. Comparator: placebo or an active lipid-lowering comparator, read from arm type **or** from what the arms receive, because each reading is blind to a real design the other sees. Estimand, which governs poolability and not eligibility: percent change from baseline in LDL-C at week 12, detected structurally at every rank rather than by the registered phrase. The timepoint is part of the estimand. 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 | 22 |
| Records where the topic drug's role in the trial could be located | 21 |
| Records where the topic drug is the randomised intervention | 18 |
| Records where the topic drug is the comparator instead | 0 |
| Records where the topic drug is background therapy in both arms | 3 |
| Records where the role could not be decided either way | 1 |
| k screened | 22 |
| k excluded | 7 |
| k eligible | 14 |
| k eligible poolable | 10 |
| k eligible not poolable | 3 |
| k eligible no results yet | 1 |
| Trials included in this review | 6 |
| k pooled | 6 |
| 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 eligible trial register a percent change in ldl-c outcome at any rank -- primary, secondary or other -- before concluding which trials can be combined? Asked at every registered rank before concluding which trials can be combined, and detected structurally -- an LDL term plus a change term -- rather than by the registered phrase. Matching the five incumbents' wording would have found the five that already agree and nothing else, which is the method that made eight apixaban trials look poolable when three were. Yes for ten of the twenty-two, and that did not settle poolability: six pool, and four are eligible with posted results and cannot contribute a single contrast because each randomised dose.1
withholding_question.question, withholding_question.why_before_decidingFor percent change from baseline in fasting LDL-C at week 12, a random-effects model was fitted with the REML random-effects, inverse-variance estimator.1
Risk of bias was assessed with RoB 2 (Cochrane risk-of-bias tool for randomized trials) , following . 6 result-level assessments were made.2
A ceiling applies to every risk-of-bias judgement in this review; it is stated with the assessment itself rather than summarised here.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.ldlc_pct_change_wk12.model, results.by_outcome.ldlc_pct_change_wk12.estimator_usedrisk_of_bias.tool, risk_of_bias.by_outcomerisk_of_bias.ceilinggrade.approach, grade.by_outcomeThe pooled mean difference for percent change from baseline in fasting LDL-C at week 12 was -55.2 (-57.9 to -52.6) across 6 trials, against placebo.1
Noted on this pool. SPIRE-AI registers four arms in a dose-matched double-dummy -- bococizumab 150 mg, bococizumab 75 mg, and a matching placebo for each. This pool's spire-ai row pairs the 150 mg dose with the 75 mg placebo. Both are real registered arms and together they are not a registered contrast. Established from the registry's arm table; not corrected, because the stored value derives from these arms. Six of SPIRE-AI's seven registered primary outcomes concern the percentage of injections meeting a successful-assessment definition on a participant assessment tool -- it is an auto-injector usability trial. The seventh is the LDL-C change pooled here. The selection is recorded nowhere. SPIRE-SI registers bococizumab, atorvastatin and placebo. This object records two arms and does not record which was dropped.2
The trials' results were moderately consistent with one another: I-squared, the share of the variation between them that is more than chance alone would produce, was 56.8%; the estimated variance of the true effects between trials (tau-squared) was 5.84, the heterogeneity test statistic Q was 11.6, on degrees of freedom 5. I-squared 56.8 per cent and tau-squared 5.84 under REML, over k=6. Both fell when the sixth trial joined -- I-squared from 65.1 and tau-squared from 9.31 -- and that is not evidence that the pool became more coherent. Coherence was established by reading six endpoint definitions and would be identical at any I-squared (P36).3
The grounds for pooling are recorded as: Six trials register the identical primary -- percent change from baseline in LDL-C at week 12 -- and every value pooled is the trial's own least-squares mean difference, read from its posted `analyses` block. Not one is derived by us. The estimand was never the problem on this topic; the measure was, and the measure was corrected in 2026-08. What was still missing was any evidence that these were the right six trials, and the executed search of 2026-08-19 supplied it: SPIRE-FH (NCT01968980, n=370) was surfaced by this review's own query, passed its own criteria, and was absent from the object. Four more are eligible, have posted LDL results, and still cannot contribute, because each randomised dose rather than drug-against-placebo -- inside NCT01342211 alone the effect runs from -2.30 to -49.11 percentage points, a spread wider than this entire pool. Eligible with results is not poolable. Where a later pool on this page rests on the same grounds, they are not restated.4
Percent change from baseline in LDL-C at week 12 -- a continuous outcome. These 3 trials are not pooled, and the reason is stated rather than the outcome being quietly omitted: The endpoints agree and the measure is the defect -- which makes this the opposite of every other topic in this pass. All three registrations read declare the same primary, verbatim: 'Percent Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) at Week 12'. That is a continuous quantity. It has no events. An odds ratio requires a 2x2 table of participants who did and did not experience something, and a percent change in a laboratory value produces no such table. This page derived one anyway. What the counts actually are is not recorded, and their magnitude shows they are not events: spire-ldl is stored as 971 in 1,068 placebo participants -- 91 per cent -- which is a threshold or responder flag of some kind, applied to an endpoint whose registered form is a mean change. Deriving an odds ratio from an undocumented dichotomisation of a continuous outcome discards the effect size the trials were designed to estimate and replaces it with a quantity that depends entirely on where the unrecorded threshold was placed.5
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.6
outcomes[id=ldlc_pct_change_wk12].name, results.by_outcome.ldlc_pct_change_wk12.pooled, outcomes[id=ldlc_pct_change_wk12].comparatorresults.by_outcome.ldlc_pct_change_wk12.POOL_FINDINGS_2026_08_20results.by_outcome.ldlc_pct_change_wk12.heterogeneity.i2, results.by_outcome.ldlc_pct_change_wk12.heterogeneity.tau2, results.by_outcome.ldlc_pct_change_wk12.heterogeneity.q, results.by_outcome.ldlc_pct_change_wk12.heterogeneity.df, results.by_outcome.ldlc_pct_change_wk12.heterogeneity_statusresults.by_outcome.ldlc_pct_change_wk12.poolable_reasonoutcomes[id=primary].name, results.by_outcome.primary.pooled.withdrawn_reasonresults.by_outcomeRisk of bias was assessed with RoB 2 at the level of each reported result, by two assessors reading independently. Their judgements differ on 6 of the 6 results and no adjudication has been performed, so this review holds no final risk-of-bias judgement for these results. Assessor 1 recorded: 6 at some concerns. Assessor 2 recorded: 6 at no information. Both are shown in the risk-of-bias table; neither is the review's finding. The per-domain judgements behind them are recorded with the extracted data.1
risk_of_bias.SECOND_ASSESSOR_2026_08_21.DISAGREEMENT_RATE, risk_of_bias.SECOND_ASSESSOR_2026_08_21.PER_DOMAIN, risk_of_bias.SECOND_ASSESSOR_2026_08_21.RECOUNTED_AFTER_THE_D1_RESOLUTION_2026_08_21, risk_of_bias.SECOND_ASSESSOR_2026_08_21.assessor_1, risk_of_bias.SECOND_ASSESSOR_2026_08_21.each_disagreement, risk_of_bias.SECOND_ASSESSOR_2026_08_21.how_it_was_asked, risk_of_bias.ceiling.statement, risk_of_bias.toolCertainty was rated with GRADE. HIGH for a body of randomised evidence, then rated down.1
No domain is rated up.2
This certainty rating is pending, not rated. It rests on a risk-of-bias judgement that this review has not finalised: two assessors read every contributing result independently, they disagree, and no adjudication has been performed, so this review holds no final risk-of-bias judgement for these results. Cochrane rates certainty per outcome by aggregating the risk-of-bias judgements of the results contributing to it, so a certainty rating cannot be more final than the risk-of-bias assessment it reads. The rating this object currently records, and the steps behind it, are shown below as the work so far rather than as this review's answer. No level is published for this outcome -- not the recorded one, not a more cautious one, and not a midpoint -- because choosing one would be the judgement that has not been made.3
Where a result is rated worse than LOW overall, the domain carrying that judgement is: selection of the reported result on 2 result(s). The overall rating is the worst domain, so these are the domains that determine it.4
| Outcome | Certainty | k | Started at | Rating steps |
|---|---|---|---|---|
| percent change from baseline in fasting LDL-C at week 12 | Pending | 6 | HIGH | the steps taken so far, not a final rating: risk of bias: HIGH to MODERATE, down 1 level(s) -- No result-level RoB 2 assessment exists for this outcome. Rated down one level because unassessed is not low.; inconsistency: MODERATE to LOW, down 1 level(s) -- I-squared 56.8 per cent over k=6, with per-trial mean differences from -49.9 to -63.4 percentage points. Rated down for the spread. This is inconsistency of result and says nothing about whether the estimand is shared, which was established by reading six registered titles.; indirectness: not rated down -- One comparator class, one endpoint, one timepoint, verified by reading each trial's registered text. The outcome is a surrogate -- LDL cholesterol, not a clinical event -- and that is stated rather than rated down here, because the review's question names the surrogate explicitly. A reader who wants clinical outcomes is asking a different question, and bococizumab's two outcome trials, SPIRE-1 and SPIRE-2, were terminated.; imprecision: not rated down -- k=6, 4,449 participants, interval -57.9 to -52.6 percentage points. The interval excludes no effect by a wide margin and is narrow relative to the effect. Not rated down.; publication bias: not rated down -- k=6. A funnel plot at k=6 has little power and would be theatre. Not assessed, and not counted as absent. One relevant fact IS recorded: the entire programme is one sponsor's, and it was discontinued -- the direction that hazard runs is unknown. |
grade.approachgrade.not_rated_uprisk_of_bias.by_outcomebookkeeping_2026_08_21.which_risk_of_bias_domains_drove_the_ratinggrade.by_outcome.ldlc_pct_change_wk12Eligible trials that do not contribute: All included registrations carry a row in this object.1
This review does not claim that any per-trial count was checked against a results record.2
What 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.3
eligible_but_not_contributing.noteverification_basis.what_is_not_claimedresults.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 |
|---|---|---|
| NCT01968967 | True | https://clinicaltrials.gov/study/NCT01968967 |
| NCT02100514 | True | https://clinicaltrials.gov/study/NCT02100514 |
| NCT01968954 | True | https://clinicaltrials.gov/study/NCT01968954 |
| NCT02458287 | True | https://clinicaltrials.gov/study/NCT02458287 |
| NCT02135029 | True | https://clinicaltrials.gov/study/NCT02135029 |
| NCT01968980 | True | https://clinicaltrials.gov/study/NCT01968980 |
registration_identity.methodregistration_identity.trialsAnalyses were computed under R version 4.6.0 (2026-04-24 ucrt); metafor 5.0.1.1
results.by_outcomeProtocol status. Prespecified: False. A protocol specified before data collection is a historical fact about the past and cannot be created retrospectively.1
Eligibility criteria were derived post hoc on 2026-08-19, when this review's search was executed for the first time -- years after its included set existed on a page.2
Authority: Mecir R107, provided they are declared as such.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 |
|---|---|---|---|
| NCT01968954 | ClinicalTrials.gov | ||
| NCT01968967 | ClinicalTrials.gov | ||
| NCT01968980 | ClinicalTrials.gov | ||
| NCT02100514 | ClinicalTrials.gov | ||
| NCT02135029 | ClinicalTrials.gov | ||
| NCT02458287 | ClinicalTrials.gov |
| Cited for | Reference |
|---|---|
| risk of bias in the included results | Sterne JAC, Savovic J, Page MJ, et al. RoB 2: a revised tool for assessing risk of bias in randomised trials. BMJ. 2019;366:l4898. doi:10.1136/bmj.l4898 |
| 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 version 4.6.0 (2026-04-24 ucrt); 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.ldlc_pct_change_wk12.per_trial, results.by_outcome.ldlc_pct_change_wk12.pooledresults.by_outcome.ldlc_pct_change_wk12.per_trial, results.by_outcome.ldlc_pct_change_wk12.pooledresults.by_outcome.primary.pooledresults.by_outcome.primary.pooled| Registration | Trial | Participants | Randomised | Primary outcome measured over | Design |
|---|---|---|---|---|---|
| NCT01968954 | SPIRE-HR | registered condition: Hyperlipidemia | not extracted | Baseline, Week 12 | Bococizumab (PF-04950615;RN316) (treatment, n=354) vs Placebo (control, n=357) [+2 further fields recorded on the object] |
| NCT01968967 | SPIRE-LDL | registered condition: Hyperlipidemia | not extracted | Baseline, Week 12 | Bococizumab (PF-04950615; RN316) (treatment, n=1071) vs Placebo (control, n=1068) [+2 further fields recorded on the object] |
| NCT01968980 | SPIRE-FH | registered condition: Heterozygous Familial Hypercholesterolemia | 370 | Baseline, Week 12 | 52-week, phase 3, double-blind, randomised, placebo-controlled, parallel-group, heterozygous familial hypercholesterolaemia. |
| NCT02100514 | SPIRE-LL | registered condition: Hyperlipidemia | not extracted | Baseline, Week 12 | Bococizumab (PF-04950615; RN316) (treatment, n=247) vs placebo (control, n=499) [+2 further fields recorded on the object] |
| NCT02135029 | SPIRE-SI | registered condition: Hyperlipidemia | not extracted | Baseline, Week 12 | Bococizumab (PF-04950615;RN316) (treatment, n=71) vs Placebo (control, n=70) [+2 further fields recorded on the object] |
| NCT02458287 | SPIRE-AI | registered condition: Hyperlipidemia | not extracted | Baseline, Week 12; Week 0 (Day 1); Week 2; Week 4; Week 6; Week 8; Week 10 | Bococizumab 150mg (treatment, n=95) vs Bococizumab 75mg placebo (control, n=50) [+2 further fields recorded on the object] |
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
10 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 model/estimator sentence for percent change from baseline in LDL-C at week 12 | A continuous outcome -- no pooled estimate was produced for this outcome, so no model was fitted and none is described |
| 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. Eligibility criteria were derived post hoc on 2026-08-19, when this review's search was executed for the first time -- years after its included set existed on a page. Mecir R107, provided they are declared as such. |
Built 2026-08-19 by ssot/build_to_standard.py against PAGE-STANDARD.md. 10 held, 4 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 22, located 21, experimental 18, comparator 0, included 6, 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, 1 NOT-ASSESSABLE. criteria_predefined is FAIL -- post hoc criteria, which R107 permits and C5/C7 does not satisfy. |
| P5_extraction_table | HELD | 10 cells: 7 READ with source path and verbatim text, 3 DERIVED with the method named. |
| P6_analysis_output | REFUSING | No quotable model output exists: k=6 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 | 6 of 6 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 6; no first-person field in published_comparison declares a k the pooled outcome(s) do not. |
| P20_cascade_reconciles | HELD | k2_role_located=21 == k3+k4+k5, and k0_surfaced=22 == k3+k4+k5+kNA. Both checked, and every failing limb would be reported rather than the first. |
| P21_ambiguous_question_split | REFUSING | This object records no split provenance. That is CORRECT for a topic whose question was never ambiguous and it is NOT a pass: this builder cannot tell the two apart, so the property is refused with the reason rather than held on an absence. What would settle it: a `split_provenance` block, or an explicit statement that the question admits one reading. |
| P22_sharing_recorded | HELD | No trial of this review appears in any other object's included set. COMPUTED over the corpus, not asserted: 6 trial(s) checked against every other topic object. |
| P23_recall_measured | HELD | All 3 recorded quer(ies) state their recall against this review's own included set: 5/5, 5/5 -- IT MISSED NOTHING THIS REVIEW INCLUDES and NOT MEASURED. |
| stage | k |
|---|---|
| k0_surfaced | 22 |
| k2_role_located | 21 |
| k3_experimental | 18 |
| k4_comparator | 0 |
| k5_background | 3 |
| kNA_not_assessable | 1 |
| k_screened | 22 |
| k_excluded | 7 |
| k_eligible | 14 |
| k_eligible_poolable | 10 |
| k_eligible_not_poolable | 3 |
| k_eligible_no_results_yet | 1 |
| k_included_in_object | 6 |
| k_pooled | 6 |
| k_unscreened_remainder | 0 |
| reproduced_by | scripts/screen_bococizumab_2026_08_19.py and scripts/repool_bococizumab_2026_08_19.py. |
| why_k_went_5_to_6 | SPIRE-FH (NCT01968980, n=370) was surfaced by this review's own search, passed its own criteria, registers the IDENTICAL primary at the IDENTICAL timepoint, posts a least-squares mean difference in its own `analyses` block -- and was not in the object, because this review had no executed search until 2026-08-19. |
| and_FOUR_more_are_eligible_with_results_and_do_not_pool | NCT01342211, NCT01350141, NCT02055976 and NCT01592240. Each randomised DOSE. ELIGIBLE WITH RESULTS IS NOT POOLABLE, and the four are named on the page with their own numbers so the refusal costs something inspectable. |
| keyed_on | registration id |
predefined: False | post_hoc: True — derived —
—
| limb | value | derived from |
|---|---|---|
| — | — | — |
| — | — | — |
| — | — | — |
| — | — | — |
does each eligible trial register a PERCENT CHANGE IN LDL-C outcome at ANY rank -- primary, secondary or other -- before concluding which trials can be combined?
YES FOR TEN OF THE TWENTY-TWO, AND THAT DID NOT SETTLE POOLABILITY: six pool, and four are eligible with posted results and cannot contribute a single contrast because each randomised DOSE.
Asked at EVERY registered rank before concluding which trials can be combined, and detected STRUCTURALLY -- an LDL term plus a change term -- rather than by the registered phrase. Matching the five incumbents' wording would have found the five that already agree and nothing else, which is the method that made eight apixaban trials look poolable when three were.
| registration | trial | two-component | three-component |
|---|---|---|---|
NCT01163851 | Pharmacokinetic And Pharmacodynamic Study Of A Single-Dose O | 37 rank(s) read | [SECONDARY] Change From Baseline in Fasting Low Density Lipoprotein-Cholesterol (LDL-C) at Day 5, 6, 7; [SECONDARY] Percent Change From Baseline in Fasting Low Density Lipoprotein-Cholesterol (LDL-C) at Day |
NCT01243151 | Safety And Tolerability Of Multiple Doses Of PF-04950615 (RN | 48 rank(s) read | [SECONDARY] Change From Baseline in Low Density Lipoprotein Cholesterol (LDL-C) at Day 8, 15, 22, 29 a; [SECONDARY] Percent Change From Baseline in Low Density Lipoprotein Cholesterol (LDL-C) at Day 8, 15, ; [SECONDARY] Change From Baseline In Low Density Lipoprotein Cholesterol (LDL-C) Particle Size at Day 8; [SECONDARY] Change From Baseline In Small Low Density Lipoprotein Cholesterol (LDL-C) Particle Levels ; [SECONDARY] Change From Baseline In Medium Low Density Lipoprotein Cholesterol (LDL-C) Particle Levels; [SECONDARY] Change From Baseline In Large Low Density Lipoprotein Cholesterol (LDL-C) Particle Levels ; [SECONDARY] Change From Baseline In Total Low Density Lipoprotein Cholesterol (LDL-C) Particle Levels |
NCT01342211 | A Multiple Dose Study of PF-04950615 (RN316) in Subjects on | 12 rank(s) read | [PRIMARY] Percent Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) at Day 85 |
NCT01350141 | A Multiple Dose Study Of PF-04950615 (RN316) In Subjects On | 10 rank(s) read | [PRIMARY] Percent Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) at Day 85 |
NCT01592240 | Monthly And Twice Monthly Subcutaneous Dosing Of PF-04950615 | 25 rank(s) read | [PRIMARY] Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) at Week 12; [SECONDARY] Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) at Week 24; [SECONDARY] Percent Change From Baseline in Low Density Lipoprotein Cholesterol (LDL-C) at Week 12 and; [SECONDARY] Change From Baseline in Very Low Density Lipoprotein (VLDL) Cholesterol at Week 12 and 24; [SECONDARY] Percent Change From Baseline in Very Low Density Lipoprotein (VLDL) Cholesterol at Week 12 |
NCT01720537 | A Study To Assess The Safety Of PF-05335810 In Hypercholeste | 14 rank(s) read | NO LDL percent-change outcome at any rank |
NCT01968954 | Randomized Clinical Trial Of Bococizumab (PF-04950615; RN316 | 31 rank(s) read | [PRIMARY] Percent Change From Baseline in Low Density Lipoprotein-Cholesterol (LDL-C) at Week 12; [SECONDARY] Percent Change From Baseline in Fasting Low-Density Lipoprotein-Cholesterol (LDL-C) at Wee; [SECONDARY] Percent Change From Baseline in Fasting Low-Density Lipoprotein-Cholesterol (LDL-C) at Wee; [SECONDARY] Percent Change From Baseline in Fasting Low Density Lipoprotein-Cholesterol (LDL-C) at Wee; [SECONDARY] Percent Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) at Wee; [SECONDARY] Percent Change From Baseline in Very Low Density Lipoprotein-Cholesterol (VLDL-C) at Week ; [SECONDARY] Absolute Change From Baseline in Fasting Low Density Lipoprotein-C (LDL-C) at Week 12 by T; [SECONDARY] Absolute Change From Baseline in Fasting Low Density Lipoprotein-Cholesterol (LDL-C) at We |
NCT01968967 | Randomized Clinical Trial of Bococizumab (PF-04950615; RN316 | 31 rank(s) read | [PRIMARY] Percent Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) at Wee; [SECONDARY] Percent Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) by Tri; [SECONDARY] Percent Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) by Tri; [SECONDARY] Percent Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) at Wee; [SECONDARY] Percent Change From Baseline in Fasting Very Low Density Lipoprotein Cholesterol (VLDL-C) ; [SECONDARY] Absolute Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) by Tr; [SECONDARY] Absolute Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) by Tr; [SECONDARY] Absolute Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) at We; [SECONDARY] Percent Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) at Wee |
NCT01968980 | A 52 Week Study To Assess The Use Of Bococizumab (PF-0495061 | 29 rank(s) read | [PRIMARY] Percent Change From Baseline in Low Density Lipoprotein Cholesterol (LDL-C) at Week 12; [SECONDARY] Percent Change From Baseline in Low Density Lipoprotein Cholesterol (LDL-C) at Week 24 and; [SECONDARY] Percent Change From Baseline in Very Low Density Lipoprotein Cholesterol (VLDL-C) at Week ; [SECONDARY] Absolute Change From Baseline in Low Density Lipoprotein (LDL-C) at Week 12 |
NCT02055976 | Dose Ranging Study Of Bococizumab (PF-04950615; RN316) In Hy | 48 rank(s) read | [PRIMARY] Percent Change From Baseline in Fasting Low Density Lipoprotein-Cholesterol (LDL-C) at Day; [PRIMARY] Percent Change From Baseline in Fasting Low Density Lipoprotein-Cholesterol (LDL-C) at Day; [SECONDARY] Change From Baseline in Low Density Lipoprotein-Cholesterol (LDL-C) at Day 85 and Day 113; [SECONDARY] Change From Baseline in Very Low Density Lipoprotein-Cholesterol (VLDL-C) at Day 85 and Da; [SECONDARY] Percent Change From Baseline in Very Low Density Lipoprotein-Cholesterol (VLDL-C) at Day 8 |
NCT02100514 | Randomized Clinical Trial of Bococizumab (PF-04950615; RN316 | 31 rank(s) read | [PRIMARY] Percent Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) at Wee; [SECONDARY] Percent Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) by Tri; [SECONDARY] Percent Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) by Tri; [SECONDARY] Percent Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) at Wee; [SECONDARY] Percent Change From Baseline in Fasting Very Low Density Lipoprotein Cholesterol (VLDL-C) ; [SECONDARY] Absolute Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) by Tr; [SECONDARY] Absolute Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) by Tr; [SECONDARY] Absolute Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) at We; [SECONDARY] Percent Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) at Wee |
NCT02135029 | Randomized Clinical Trial of Bococizumab (PF-04950615; RN316 | 27 rank(s) read | [PRIMARY] Percent Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) at Wee; [SECONDARY] Percent Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) at Wee; [SECONDARY] Percent Change From Baseline in Fasting Very Low Density Lipoprotein Cholesterol (VLDL-C) ; [SECONDARY] Absolute Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) at We |
NCT02458287 | Efficacy, Safety, Tolerability And Actual Use Study Of Bococ | 17 rank(s) read | [PRIMARY] Percent Change From Baseline at Week 12 in Fasting Low Density Lipoprotein Cholesterol (LD; [SECONDARY] Percent Change From Baseline at Week 12 in Fasting Low Density Lipoprotein Cholesterol (LD |
NCT02524106 | Bococizumab HIV Evaluation (B-HIVE) Study | 2 rank(s) read | NO LDL percent-change outcome at any rank |
NCT02947334 | Efficacy And Safety Of Bococizumab For Lipid Lowering In Asi | 1 rank(s) read | [PRIMARY] • Percent change from baseline in fasting LDL-C |
—
k after screening: —. —
| failing limb | n | registrations |
|---|
—
—
| registration | rank | matching outcome |
|---|
| registration | verdict | limb | reason |
|---|
— | call: metafor::rma(yi = ..., sei = ..., method = 'REML')
bococizumab-lipid-review :: ldlc_pct_change_wk12 k = 6 measure = MD ============================================================================ trials, and the SE derived from each published interval: NCT01968967 SPIRE-LDL MD -56.20 (-58.3 to -54.0) se = 1.0970 NCT02100514 SPIRE-LL MD -49.90 (-54.0 to -45.8) se = 2.0919 NCT01968954 SPIRE-HR MD -57.00 (-61.0 to -53.1) se = 2.0153 NCT02458287 SPIRE-AI MD -63.40 (-72.0 to -54.7) se = 4.4133 NCT02135029 SPIRE-SI MD -54.50 (-60.1 to -49.0) se = 2.8317 NCT01968980 SPIRE-FH MD -54.50 (-59.5 to -49.5) se = 2.5511 se = (hi - lo) / (2 * qnorm(0.975)) -- NO SOURCE PRINTED A STANDARD ERROR. Random-Effects Model (k = 6; tau^2 estimator: REML) tau^2 (estimated amount of total heterogeneity): 5.8423 (SE = 6.9442) tau (square root of estimated tau^2 value): 2.4171 I^2 (total heterogeneity / total variability): 56.66% H^2 (total variability / sampling variability): 2.31 Test for Heterogeneity: Q(df = 5) = 11.5854, p-val = 0.0409 Model Results: estimate se zval pval ci.lb ci.ub -55.2406 1.3693 -40.3436 <.0001 -57.9243 -52.5569 *** --- Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 1 CHECK AGAINST THE STORED VALUE stored: MD -55.24 (-58.27 to -52.21) I^2 = 41.5 refit : MD -55.2406 (-57.9243 to -52.5569) I^2 = 56.7 tau^2 = 5.8423 point moves by 0.0006 HARTUNG-KNAPP, FLOORED, AS THE HOUSE RULE REQUIRES scale = 1.1896 floored = FALSE t(5) = 2.5706 interval: -55.2406 (-59.0796 to -51.4017)
Denominator: —. Not yet established. Establishing it requires resolving published syntheses' included-sets to REGISTRATION IDs. A second lane has validated that pipeline (stated-k table identification plus two-hop citation->PMID->registration) and is running it now.
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 269 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 | PASS | inputs.trials: all 6 trial(s) carry arms with a readable 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 ['placebo']; 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 2 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 1107 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 | PASS | inputs.trials.arms: all 6 readable trial(s) contribute one topic-vs-control randomised contrast | 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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