[
 {
  "local_id": "C1",
  "type": "empirical",
  "core": true,
  "statement": "Of the 539 interventional studies of GLP-1 receptor agonists with results on ClinicalTrials.gov on 2026-10-12, 234 randomized trials compare a GLP-1 receptor agonist with placebo, in 257 comparisons with 161,309 participants in their adverse-event tables (93,765 on the drugs and 67,544 on placebo). In them, reports of serious gallbladder and biliary disease, counting a participant once for each of the outcome's terms they had, are more frequent on the drugs (Mantel-Haenszel ratio 1.38, 95% CI 1.21 to 1.57), and so are reports of serious nausea and vomiting (2.02, 1.52 to 2.68), as the trials' own publications and the drugs' labels lead one to expect.",
  "evidence": [
   {
    "result": "S.trials.found",
    "produced_by": "code/summarize.py"
   },
   {
    "result": "S.trials.eligible",
    "produced_by": "code/summarize.py"
   },
   {
    "result": "S.trials.comparisons",
    "produced_by": "code/summarize.py"
   },
   {
    "result": "S.trials.participants",
    "produced_by": "code/summarize.py"
   },
   {
    "result": "S.trials.glp1",
    "produced_by": "code/summarize.py"
   },
   {
    "result": "S.trials.placebo",
    "produced_by": "code/summarize.py"
   },
   {
    "result": "S.revised.outcomes.B01.all.rr",
    "produced_by": "code/summarize.py",
    "tolerance": 0.01
   },
   {
    "result": "S.revised.outcomes.B01.all.lo",
    "produced_by": "code/summarize.py",
    "tolerance": 0.01
   },
   {
    "result": "S.revised.outcomes.B01.all.hi",
    "produced_by": "code/summarize.py",
    "tolerance": 0.01
   },
   {
    "result": "S.revised.outcomes.A34.all.rr",
    "produced_by": "code/summarize.py",
    "tolerance": 0.01
   },
   {
    "result": "S.revised.outcomes.A34.all.lo",
    "produced_by": "code/summarize.py",
    "tolerance": 0.01
   },
   {
    "result": "S.revised.outcomes.A34.all.hi",
    "produced_by": "code/summarize.py",
    "tolerance": 0.01
   }
  ],
  "depends_on": [],
  "falsified_if": "A rerun finds a different number of eligible trials, comparisons or participants, or a gallbladder or nausea and vomiting ratio whose interval includes 1.",
  "confidence": 0.95
 },
 {
  "local_id": "C2",
  "type": "empirical",
  "core": true,
  "statement": "Reports of serious bacterial infection, counting a participant once for each of the outcome's terms they had, are less frequent on GLP-1 receptor agonists in these trials (2,409 among 93,765 participants against 2,532 among 67,544 on placebo; Mantel-Haenszel ratio 0.88, 95% CI 0.83 to 0.93, q < 0.001), and so are reports of serious pneumonia (1,442 against 1,568; 0.87, 0.81 to 0.93, q = 0.0020); both stay significant under random effects and with any single trial left out. Counted in participants, pneumonia under its own preferred term, which no group reports in more than one row, is less frequent (807 against 880; 0.86, 0.79 to 0.95). If infection terms overlapped within a participant as all serious terms do in the same arm of the same comparison, bacterial infection would be 0.89 (0.82 to 0.97).",
  "evidence": [
   {
    "result": "S.revised.outcomes.A18.robust",
    "produced_by": "code/summarize.py"
   },
   {
    "result": "S.revised.outcomes.A21.robust",
    "produced_by": "code/summarize.py"
   },
   {
    "result": "S.revised.preferred_terms.A21.pneumonia.merged_rows.groups",
    "produced_by": "code/summarize.py"
   },
   {
    "result": "S.revised.outcomes.A18.all.glp1_affected",
    "produced_by": "code/summarize.py"
   },
   {
    "result": "S.revised.outcomes.A18.all.glp1_at_risk",
    "produced_by": "code/summarize.py"
   },
   {
    "result": "S.revised.outcomes.A18.all.placebo_affected",
    "produced_by": "code/summarize.py"
   },
   {
    "result": "S.revised.outcomes.A18.all.placebo_at_risk",
    "produced_by": "code/summarize.py"
   },
   {
    "result": "S.revised.outcomes.A18.all.rr",
    "produced_by": "code/summarize.py",
    "tolerance": 0.01
   },
   {
    "result": "S.revised.outcomes.A18.all.lo",
    "produced_by": "code/summarize.py",
    "tolerance": 0.01
   },
   {
    "result": "S.revised.outcomes.A18.all.hi",
    "produced_by": "code/summarize.py",
    "tolerance": 0.01
   },
   {
    "result": "S.revised.outcomes.A18.q",
    "produced_by": "code/summarize.py"
   },
   {
    "result": "S.revised.outcomes.A21.all.glp1_affected",
    "produced_by": "code/summarize.py"
   },
   {
    "result": "S.revised.outcomes.A21.all.placebo_affected",
    "produced_by": "code/summarize.py"
   },
   {
    "result": "S.revised.outcomes.A21.all.rr",
    "produced_by": "code/summarize.py",
    "tolerance": 0.01
   },
   {
    "result": "S.revised.outcomes.A21.all.lo",
    "produced_by": "code/summarize.py",
    "tolerance": 0.01
   },
   {
    "result": "S.revised.outcomes.A21.all.hi",
    "produced_by": "code/summarize.py",
    "tolerance": 0.01
   },
   {
    "result": "S.revised.outcomes.A21.q",
    "produced_by": "code/summarize.py"
   },
   {
    "result": "S.revised.preferred_terms.A21.pneumonia.glp1_affected",
    "produced_by": "code/summarize.py"
   },
   {
    "result": "S.revised.preferred_terms.A21.pneumonia.placebo_affected",
    "produced_by": "code/summarize.py"
   },
   {
    "result": "S.revised.preferred_terms.A21.pneumonia.rr",
    "produced_by": "code/summarize.py",
    "tolerance": 0.01
   },
   {
    "result": "S.revised.preferred_terms.A21.pneumonia.lo",
    "produced_by": "code/summarize.py",
    "tolerance": 0.01
   },
   {
    "result": "S.revised.preferred_terms.A21.pneumonia.hi",
    "produced_by": "code/summarize.py",
    "tolerance": 0.01
   },
   {
    "result": "S.revised.outcomes.A18.overlap.adjusted.rr",
    "produced_by": "code/summarize.py",
    "tolerance": 0.01
   },
   {
    "result": "S.revised.outcomes.A18.overlap.adjusted.lo",
    "produced_by": "code/summarize.py",
    "tolerance": 0.01
   },
   {
    "result": "S.revised.outcomes.A18.overlap.adjusted.hi",
    "produced_by": "code/summarize.py",
    "tolerance": 0.01
   }
  ],
  "depends_on": [
   "C1"
  ],
  "falsified_if": "A rerun gives a 95% interval that includes 1 for any ratio given here, a q of 0.05 or more, or p of 0.05 or more under random effects or with a single trial left out.",
  "confidence": 0.85
 },
 {
  "local_id": "C3",
  "type": "empirical",
  "core": false,
  "statement": "In the registered scan without hypotheses of 27 organ systems and 518 preferred terms, with the same variance as the other claims, four organ systems (cardiac disorders; infections and infestations; metabolism and nutrition disorders; respiratory, thoracic and mediastinal disorders) and two preferred terms (acute myocardial infarction and cellulitis) are lower on the drugs with q < 0.05 in a random half of the trials and p < 0.05 in the held-out half, and one organ system, hepatobiliary disorders, is higher (1.36 in the first half, 1.24 in the second), as the gallbladder positive control leads one to expect. Among those lower are serious infection reports as a whole (0.88 and 0.89) and cellulitis (0.64 and 0.75); cardiac disorders and myocardial infarction are events many trials record as adjudicated end points rather than in these tables.",
  "evidence": [
   {
    "result": "S.revised.scans.organ_systems.replicated_lower",
    "produced_by": "code/summarize.py"
   },
   {
    "result": "S.revised.scans.organ_systems.replicated_higher",
    "produced_by": "code/summarize.py"
   },
   {
    "result": "S.revised.scans.preferred_terms.replicated_lower",
    "produced_by": "code/summarize.py"
   },
   {
    "result": "S.revised.scans.preferred_terms.replicated_higher",
    "produced_by": "code/summarize.py"
   },
   {
    "result": "S.revised.scans.organ_systems.tested",
    "produced_by": "code/summarize.py"
   },
   {
    "result": "S.revised.scans.preferred_terms.tested",
    "produced_by": "code/summarize.py"
   },
   {
    "result": "S.revised.scans.organ_systems.items.hepatobiliary_disorders.discovery.rr",
    "produced_by": "code/summarize.py",
    "tolerance": 0.01
   },
   {
    "result": "S.revised.scans.organ_systems.items.hepatobiliary_disorders.replication.rr",
    "produced_by": "code/summarize.py",
    "tolerance": 0.01
   },
   {
    "result": "S.revised.scans.organ_systems.items.infections_and_infestations.discovery.rr",
    "produced_by": "code/summarize.py",
    "tolerance": 0.01
   },
   {
    "result": "S.revised.scans.organ_systems.items.infections_and_infestations.replication.rr",
    "produced_by": "code/summarize.py",
    "tolerance": 0.01
   },
   {
    "result": "S.revised.scans.preferred_terms.items.cellulitis.discovery.rr",
    "produced_by": "code/summarize.py",
    "tolerance": 0.01
   },
   {
    "result": "S.revised.scans.preferred_terms.items.cellulitis.replication.rr",
    "produced_by": "code/summarize.py",
    "tolerance": 0.01
   }
  ],
  "depends_on": [
   "C1"
  ],
  "falsified_if": "A rerun finds a different set of organ systems or preferred terms lower in both halves, or a different set higher in both.",
  "confidence": 0.85
 },
 {
  "local_id": "C4",
  "type": "empirical",
  "core": true,
  "statement": "Of the 49 associations the VA atlas of Xie, Choi and Al-Aly (2025) reported between GLP-1 receptor agonists and non-cardiometabolic outcomes, 44 have at least 10 reports in these trials. Comparing each trial estimate with the atlas's, both with their uncertainty and the differences corrected over the 44, three are significant in the trials in the atlas's direction with no difference from the atlas detected: bacterial infections (ratio of trial to atlas 1.00, 0.94 to 1.06), pneumonia (1.03, 0.96 to 1.12), and nausea and vomiting, whose trial estimate is larger (1.55, 1.17 to 2.06) by a difference that just misses significance after correction (q = 0.052). None is significant against the atlas's direction, the trials differ from the atlas only for acute pancreatitis, whose atlas outcome, drug-induced pancreatitis, is a subtype the trials don't separate, and 40 are inconclusive, among them every substance use, suicidality, psychosis, seizure and dementia association with enough events to test. Only an outcome significant in the trials can be consistent, so how many are is bounded by the trials' power, and none of this tests whether the two estimates are equal.",
  "evidence": [
   {
    "result": "S.revised.atlas.lists.consistent",
    "produced_by": "code/summarize.py"
   },
   {
    "result": "S.revised.atlas.lists.different",
    "produced_by": "code/summarize.py"
   },
   {
    "result": "S.revised.atlas.lists.inconclusive",
    "produced_by": "code/summarize.py"
   },
   {
    "result": "S.revised.outcomes.A49.atlas.comparable",
    "produced_by": "code/summarize.py"
   },
   {
    "result": "S.va.outcomes",
    "produced_by": "code/summarize.py"
   },
   {
    "result": "S.va.testable",
    "produced_by": "code/summarize.py"
   },
   {
    "result": "S.revised.atlas.counts.consistent",
    "produced_by": "code/summarize.py"
   },
   {
    "result": "S.revised.outcomes.A18.atlas.ratio",
    "produced_by": "code/summarize.py",
    "tolerance": 0.01
   },
   {
    "result": "S.revised.outcomes.A18.atlas.ratio_lo",
    "produced_by": "code/summarize.py",
    "tolerance": 0.01
   },
   {
    "result": "S.revised.outcomes.A18.atlas.ratio_hi",
    "produced_by": "code/summarize.py",
    "tolerance": 0.01
   },
   {
    "result": "S.revised.outcomes.A21.atlas.ratio",
    "produced_by": "code/summarize.py",
    "tolerance": 0.01
   },
   {
    "result": "S.revised.outcomes.A21.atlas.ratio_lo",
    "produced_by": "code/summarize.py",
    "tolerance": 0.01
   },
   {
    "result": "S.revised.outcomes.A21.atlas.ratio_hi",
    "produced_by": "code/summarize.py",
    "tolerance": 0.01
   },
   {
    "result": "S.revised.outcomes.A34.atlas.ratio",
    "produced_by": "code/summarize.py",
    "tolerance": 0.01
   },
   {
    "result": "S.revised.outcomes.A34.atlas.ratio_lo",
    "produced_by": "code/summarize.py",
    "tolerance": 0.01
   },
   {
    "result": "S.revised.outcomes.A34.atlas.ratio_hi",
    "produced_by": "code/summarize.py",
    "tolerance": 0.01
   },
   {
    "result": "S.revised.outcomes.A34.atlas.difference_q",
    "produced_by": "code/summarize.py"
   },
   {
    "result": "S.revised.atlas.counts.inconclusive",
    "produced_by": "code/summarize.py"
   }
  ],
  "depends_on": [
   "C1"
  ],
  "falsified_if": "A rerun puts any of the 49 associations in a different category of the comparison described here.",
  "confidence": 0.8
 },
 {
  "local_id": "C5",
  "type": "empirical",
  "core": false,
  "statement": "Reports of serious acute pancreatitis of any cause are not detectably more frequent on GLP-1 receptor agonists in these trials (229 among 93,765 participants against 173 among 67,544; ratio 1.13, 95% CI 0.92 to 1.39, p = 0.26). This cannot test the hazard ratio of 2.46 the VA atlas reported for drug-induced acute pancreatitis: if only that subtype rose by that factor, all pancreatitis would pass the trials' upper limit only if the subtype made up more than 27% of cases on placebo.",
  "evidence": [
   {
    "result": "S.revised.outcomes.A49.all.glp1_affected",
    "produced_by": "code/summarize.py"
   },
   {
    "result": "S.revised.outcomes.A49.all.glp1_at_risk",
    "produced_by": "code/summarize.py"
   },
   {
    "result": "S.revised.outcomes.A49.all.placebo_affected",
    "produced_by": "code/summarize.py"
   },
   {
    "result": "S.revised.outcomes.A49.all.placebo_at_risk",
    "produced_by": "code/summarize.py"
   },
   {
    "result": "S.revised.outcomes.A49.all.rr",
    "produced_by": "code/summarize.py",
    "tolerance": 0.01
   },
   {
    "result": "S.revised.outcomes.A49.all.lo",
    "produced_by": "code/summarize.py",
    "tolerance": 0.01
   },
   {
    "result": "S.revised.outcomes.A49.all.hi",
    "produced_by": "code/summarize.py",
    "tolerance": 0.01
   },
   {
    "result": "S.revised.outcomes.A49.all.p",
    "produced_by": "code/summarize.py"
   },
   {
    "result": "S.revised.outcomes.A49.atlas.hr",
    "produced_by": "code/summarize.py",
    "tolerance": 0.01
   },
   {
    "result": "S.revised.outcomes.A49.atlas.largest_share_percent",
    "produced_by": "code/summarize.py"
   }
  ],
  "depends_on": [
   "C1"
  ],
  "falsified_if": "A rerun gives a pancreatitis ratio whose interval lies wholly above 1.",
  "confidence": 0.85
 },
 {
  "local_id": "C6",
  "type": "empirical",
  "core": false,
  "statement": "Where the records report deaths for every group, death from any cause is lower on GLP-1 receptor agonists (2,556 of 69,064 participants against 2,848 of 50,491; risk ratio 0.87, 95% CI 0.83 to 0.92), and across all comparisons so is having any serious adverse event (0.96, 0.94 to 0.98); both count participants, and both stay significant under random effects and with any single trial left out.",
  "evidence": [
   {
    "result": "S.revised.outcomes.B12.robust",
    "produced_by": "code/summarize.py"
   },
   {
    "result": "S.revised.outcomes.B13.robust",
    "produced_by": "code/summarize.py"
   },
   {
    "result": "S.revised.outcomes.B12.all.glp1_affected",
    "produced_by": "code/summarize.py"
   },
   {
    "result": "S.revised.outcomes.B12.all.glp1_at_risk",
    "produced_by": "code/summarize.py"
   },
   {
    "result": "S.revised.outcomes.B12.all.placebo_affected",
    "produced_by": "code/summarize.py"
   },
   {
    "result": "S.revised.outcomes.B12.all.placebo_at_risk",
    "produced_by": "code/summarize.py"
   },
   {
    "result": "S.revised.outcomes.B12.all.rr",
    "produced_by": "code/summarize.py",
    "tolerance": 0.01
   },
   {
    "result": "S.revised.outcomes.B12.all.lo",
    "produced_by": "code/summarize.py",
    "tolerance": 0.01
   },
   {
    "result": "S.revised.outcomes.B12.all.hi",
    "produced_by": "code/summarize.py",
    "tolerance": 0.01
   },
   {
    "result": "S.revised.outcomes.B13.all.rr",
    "produced_by": "code/summarize.py",
    "tolerance": 0.01
   },
   {
    "result": "S.revised.outcomes.B13.all.lo",
    "produced_by": "code/summarize.py",
    "tolerance": 0.01
   },
   {
    "result": "S.revised.outcomes.B13.all.hi",
    "produced_by": "code/summarize.py",
    "tolerance": 0.01
   }
  ],
  "depends_on": [
   "C1"
  ],
  "falsified_if": "A rerun gives a death or any-serious-event risk ratio whose interval includes 1, or p of 0.05 or more under random effects or with a single trial left out.",
  "confidence": 0.9
 },
 {
  "local_id": "C7",
  "type": "empirical",
  "core": false,
  "statement": "No cancer outcome differs significantly between GLP-1 receptor agonists and placebo after correction in these trials: reports of any malignant neoplasm (1.03, 95% CI 0.97 to 1.09, q = 0.48), of the cancers linked to excess body fat (1.09, 0.99 to 1.19, q = 0.20) and of pancreatic cancer (0.99, 0.75 to 1.32, q = 0.95). Thyroid cancer reports are nominally higher (67 against 32; 1.61, 1.02 to 2.55, p = 0.042; Peto's odds ratio 1.61, 1.07 to 2.41) but not after correction (q = 0.14), so the trials neither confirm nor exclude an increase.",
  "evidence": [
   {
    "result": "S.revised.outcomes.B06.all.rr",
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    "tolerance": 0.01
   },
   {
    "result": "S.revised.outcomes.B06.all.lo",
    "produced_by": "code/summarize.py",
    "tolerance": 0.01
   },
   {
    "result": "S.revised.outcomes.B06.all.hi",
    "produced_by": "code/summarize.py",
    "tolerance": 0.01
   },
   {
    "result": "S.revised.outcomes.B06.q",
    "produced_by": "code/summarize.py"
   },
   {
    "result": "S.revised.outcomes.B07.all.rr",
    "produced_by": "code/summarize.py",
    "tolerance": 0.01
   },
   {
    "result": "S.revised.outcomes.B07.all.lo",
    "produced_by": "code/summarize.py",
    "tolerance": 0.01
   },
   {
    "result": "S.revised.outcomes.B07.all.hi",
    "produced_by": "code/summarize.py",
    "tolerance": 0.01
   },
   {
    "result": "S.revised.outcomes.B07.q",
    "produced_by": "code/summarize.py"
   },
   {
    "result": "S.revised.outcomes.B11.all.rr",
    "produced_by": "code/summarize.py",
    "tolerance": 0.01
   },
   {
    "result": "S.revised.outcomes.B11.all.lo",
    "produced_by": "code/summarize.py",
    "tolerance": 0.01
   },
   {
    "result": "S.revised.outcomes.B11.all.hi",
    "produced_by": "code/summarize.py",
    "tolerance": 0.01
   },
   {
    "result": "S.revised.outcomes.B11.q",
    "produced_by": "code/summarize.py"
   },
   {
    "result": "S.revised.outcomes.B05.all.glp1_affected",
    "produced_by": "code/summarize.py"
   },
   {
    "result": "S.revised.outcomes.B05.all.placebo_affected",
    "produced_by": "code/summarize.py"
   },
   {
    "result": "S.revised.outcomes.B05.all.rr",
    "produced_by": "code/summarize.py",
    "tolerance": 0.01
   },
   {
    "result": "S.revised.outcomes.B05.all.lo",
    "produced_by": "code/summarize.py",
    "tolerance": 0.01
   },
   {
    "result": "S.revised.outcomes.B05.all.hi",
    "produced_by": "code/summarize.py",
    "tolerance": 0.01
   },
   {
    "result": "S.revised.outcomes.B05.all.p",
    "produced_by": "code/summarize.py"
   },
   {
    "result": "S.outcomes.B05.peto.or",
    "produced_by": "code/summarize.py",
    "tolerance": 0.01
   },
   {
    "result": "S.outcomes.B05.peto.lo",
    "produced_by": "code/summarize.py",
    "tolerance": 0.01
   },
   {
    "result": "S.outcomes.B05.peto.hi",
    "produced_by": "code/summarize.py",
    "tolerance": 0.01
   },
   {
    "result": "S.revised.outcomes.B05.q",
    "produced_by": "code/summarize.py"
   }
  ],
  "depends_on": [
   "C1"
  ],
  "falsified_if": "A rerun gives q below 0.05 for any of these cancer outcomes.",
  "confidence": 0.8
 },
 {
  "local_id": "C8",
  "type": "empirical",
  "core": false,
  "statement": "Reports of serious intestinal obstruction or ileus are not detectably more frequent on GLP-1 receptor agonists in these trials (171 against 153; ratio 1.03, 95% CI 0.82 to 1.29), an interval that leaves room for a material increase, and ischaemic optic neuropathy, arteritic and non-arteritic pooled over the drugs, is too rare in them to tell (10 against 5; 1.62, 0.33 to 8.01).",
  "evidence": [
   {
    "result": "S.revised.outcomes.B02.all.glp1_affected",
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   {
    "result": "S.revised.outcomes.B02.all.placebo_affected",
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   {
    "result": "S.revised.outcomes.B02.all.rr",
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   {
    "result": "S.revised.outcomes.B02.all.lo",
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   },
   {
    "result": "S.revised.outcomes.B02.all.hi",
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   {
    "result": "S.revised.outcomes.B03.all.glp1_affected",
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   {
    "result": "S.revised.outcomes.B03.all.placebo_affected",
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   {
    "result": "S.revised.outcomes.B03.all.rr",
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   },
   {
    "result": "S.revised.outcomes.B03.all.lo",
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   {
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  ],
  "depends_on": [
   "C1"
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  "falsified_if": "A rerun gives an intestinal obstruction ratio whose interval lies wholly above 1.",
  "confidence": 0.8
 },
 {
  "local_id": "C9",
  "type": "empirical",
  "core": false,
  "statement": "By two blind coders and a third reader (kappa 0.96), 92 of these trials say they record serious events only while participants take the study drug or for a set time after the last dose; of the other 142, 118 give only the trial's calendar, 21 say nothing usable, and three say they followed every participant to the end. In those 142, bacterial infection reports (0.88, 95% CI 0.83 to 0.94) and pneumonia reports (0.87, 0.80 to 0.94) are lower on GLP-1 receptor agonists, and so is death in the 100 of them that report deaths for every group (0.88, 0.83 to 0.93); in the 118 that give only a calendar, bacterial infection reports are 0.91 (0.84 to 0.97) and pneumonia reports 0.93 (0.84 to 1.02), pneumonia not significant there on its own. No difference was detected between them and the trials that record only on treatment (interaction p = 0.66, 0.98 and 0.72), though the on-treatment intervals are wide.",
  "evidence": [
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   {
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   {
    "result": "S.revised.outcomes.B12.window.not_on_treatment.rr",
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   {
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   {
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   {
    "result": "S.revised.outcomes.A18.window.calendar.rr",
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   {
    "result": "S.revised.outcomes.A18.window.calendar.lo",
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   {
    "result": "S.revised.outcomes.A18.window.calendar.hi",
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   {
    "result": "S.revised.outcomes.A21.window.calendar.rr",
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   {
    "result": "S.revised.outcomes.A21.window.calendar.lo",
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   {
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   {
    "result": "S.revised.outcomes.A18.window.interaction_p",
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   {
    "result": "S.revised.outcomes.A21.window.interaction_p",
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   {
    "result": "S.revised.outcomes.B12.window.interaction_p",
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  "depends_on": [
   "C2",
   "C6"
  ],
  "falsified_if": "A rerun gives an interval that includes 1 for any of the three ratios in the trials not coded as recording only on treatment, or an interaction p below 0.05 for any of them.",
  "confidence": 0.8
 }
]
