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 {
  "local_id": "C1",
  "type": "empirical",
  "core": true,
  "statement": "In 23 randomized trials (3,202 participants) that gave ketamine or esketamine only while patients were unconscious under general anesthesia for surgery or cesarean delivery, depressive symptoms 1 to 3 days after the procedure were lower than with an inert control (Hedges' g −0.61, 95% CI −0.81 to −0.40; Holm-adjusted p < 0.001), and the difference remained among the 15 of these trials that passed the pre-registered integrity screen (g −0.48, −0.65 to −0.31), among the 16 left when trials whose last dose could still act at waking are set aside (g −0.64, −0.93 to −0.34), and with any single trial left out (largest p < 0.001).",
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    "result": "R1.k",
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   {
    "result": "R1.n",
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   {
    "result": "R1.g",
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    "tolerance": 0.01
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   {
    "result": "R1.lower",
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   {
    "result": "R1.upper",
    "produced_by": "code/analyze.R",
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   {
    "result": "R1.p_holm_text",
    "produced_by": "code/analyze.R"
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   {
    "result": "R1.loo_max_p_text",
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   {
    "result": "R5.P1.trustworthy.k",
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   {
    "result": "R5.P1.trustworthy.g",
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   {
    "result": "R5.P1.trustworthy.lower",
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   {
    "result": "R5.P1.trustworthy.upper",
    "produced_by": "code/analyze.R",
    "tolerance": 0.01
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   {
    "result": "R5.P1.strict_masking.k",
    "produced_by": "code/analyze.R"
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   {
    "result": "R5.P1.strict_masking.g",
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    "tolerance": 0.01
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   {
    "result": "R5.P1.strict_masking.lower",
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    "tolerance": 0.01
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   {
    "result": "R5.P1.strict_masking.upper",
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  ],
  "depends_on": [],
  "falsified_if": "A re-run of the analysis on the bundle's data gives a 95% CI for the masked effect that includes 0, overall, among trustworthy trials, or with strict masking; or a re-extraction from the trials' sources moves these estimates by more than their stated precision.",
  "confidence": 0.85
 },
 {
  "local_id": "C2",
  "type": "negative_result",
  "core": true,
  "statement": "Among trials in surgery (37 comparisons: 22 masked, 15 with some dosing while patients were awake), the effect was not larger with awake dosing: allowing for trials that enrolled only depressed patients, awake dosing changed g by +0.12 (95% CI −0.24 to 0.48; p = 0.51), which excludes an awake advantage larger than 0.24 standard deviations; the pooled effects in surgery were g −0.62 with masked and −0.45 with awake dosing.",
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   {
    "result": "R2.k",
    "produced_by": "code/analyze.R"
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   {
    "result": "R2.masked.k",
    "produced_by": "code/analyze.R"
   },
   {
    "result": "R2.awake.k",
    "produced_by": "code/analyze.R"
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   {
    "result": "R2.g",
    "produced_by": "code/analyze.R",
    "tolerance": 0.01
   },
   {
    "result": "R2.lower",
    "produced_by": "code/analyze.R",
    "tolerance": 0.01
   },
   {
    "result": "R2.upper",
    "produced_by": "code/analyze.R",
    "tolerance": 0.01
   },
   {
    "result": "R2.p_text",
    "produced_by": "code/analyze.R"
   },
   {
    "result": "R2.masked.g",
    "produced_by": "code/analyze.R",
    "tolerance": 0.01
   },
   {
    "result": "R2.awake.g",
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    "tolerance": 0.01
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  ],
  "depends_on": [],
  "falsified_if": "A re-run gives a 95% CI for the awake-minus-masked coefficient that excludes 0, or whose lower bound is below −0.30.",
  "confidence": 0.75
 },
 {
  "local_id": "C3",
  "type": "empirical",
  "core": false,
  "statement": "The masked doses were active, and their psychoactive effects showed less: masked ketamine lowered pain on day 1 or 2 after the procedure (g −0.53, 95% CI −0.93 to −0.13; 23 trials), as awake ketamine did (g −0.37, −0.61 to −0.14; 34 trials), with no difference between them in surgery (awake minus masked +0.28, −0.23 to 0.78), and it raised the odds of each trial's most frequent psychotomimetic adverse event less than awake ketamine did (Mantel–Haenszel odds ratio 2.11, 1.48 to 2.99, in 22 masked trials, against 3.75, 3.07 to 4.57, in 43 awake trials; p = 0.0051 for the difference).",
  "evidence": [
   {
    "result": "R3.masked.g",
    "produced_by": "code/analyze.R",
    "tolerance": 0.01
   },
   {
    "result": "R3.masked.lower",
    "produced_by": "code/analyze.R",
    "tolerance": 0.01
   },
   {
    "result": "R3.masked.upper",
    "produced_by": "code/analyze.R",
    "tolerance": 0.01
   },
   {
    "result": "R3.masked.k",
    "produced_by": "code/analyze.R"
   },
   {
    "result": "R3.awake.g",
    "produced_by": "code/analyze.R",
    "tolerance": 0.01
   },
   {
    "result": "R3.awake.lower",
    "produced_by": "code/analyze.R",
    "tolerance": 0.01
   },
   {
    "result": "R3.awake.upper",
    "produced_by": "code/analyze.R",
    "tolerance": 0.01
   },
   {
    "result": "R3.awake.k",
    "produced_by": "code/analyze.R"
   },
   {
    "result": "R3.difference.g",
    "produced_by": "code/analyze.R",
    "tolerance": 0.01
   },
   {
    "result": "R3.difference.lower",
    "produced_by": "code/analyze.R",
    "tolerance": 0.01
   },
   {
    "result": "R3.difference.upper",
    "produced_by": "code/analyze.R",
    "tolerance": 0.01
   },
   {
    "result": "R4.masked.or",
    "produced_by": "code/analyze.R",
    "tolerance": 0.01
   },
   {
    "result": "R4.masked.lower",
    "produced_by": "code/analyze.R",
    "tolerance": 0.01
   },
   {
    "result": "R4.masked.upper",
    "produced_by": "code/analyze.R",
    "tolerance": 0.01
   },
   {
    "result": "R4.masked.k",
    "produced_by": "code/analyze.R"
   },
   {
    "result": "R4.awake.or",
    "produced_by": "code/analyze.R",
    "tolerance": 0.01
   },
   {
    "result": "R4.awake.lower",
    "produced_by": "code/analyze.R",
    "tolerance": 0.01
   },
   {
    "result": "R4.awake.upper",
    "produced_by": "code/analyze.R",
    "tolerance": 0.01
   },
   {
    "result": "R4.awake.k",
    "produced_by": "code/analyze.R"
   },
   {
    "result": "R4.p_difference_text",
    "produced_by": "code/analyze.R"
   }
  ],
  "depends_on": [],
  "falsified_if": "A re-run gives a 95% CI for the masked pain effect that includes 0, or odds ratios for psychotomimetic events whose difference between masked and awake trials has p ≥ 0.05.",
  "confidence": 0.8
 },
 {
  "local_id": "C4",
  "type": "empirical",
  "core": false,
  "statement": "The masked effect was also present in the 7 masked trials that enrolled only patients with depression or depressive symptoms (g −0.78, 95% CI −1.24 to −0.31), and later after the procedure: on days 4 to 14 (g −0.51, −0.90 to −0.13; 18 trials) and days 15 to 90 (g −0.54, −0.75 to −0.33; 11 trials).",
  "evidence": [
   {
    "result": "R5.P1.selected_only.k",
    "produced_by": "code/analyze.R"
   },
   {
    "result": "R5.P1.selected_only.g",
    "produced_by": "code/analyze.R",
    "tolerance": 0.01
   },
   {
    "result": "R5.P1.selected_only.lower",
    "produced_by": "code/analyze.R",
    "tolerance": 0.01
   },
   {
    "result": "R5.P1.selected_only.upper",
    "produced_by": "code/analyze.R",
    "tolerance": 0.01
   },
   {
    "result": "R6.P1.middle.g",
    "produced_by": "code/analyze.R",
    "tolerance": 0.01
   },
   {
    "result": "R6.P1.middle.lower",
    "produced_by": "code/analyze.R",
    "tolerance": 0.01
   },
   {
    "result": "R6.P1.middle.upper",
    "produced_by": "code/analyze.R",
    "tolerance": 0.01
   },
   {
    "result": "R6.P1.middle.k",
    "produced_by": "code/analyze.R"
   },
   {
    "result": "R6.P1.late.g",
    "produced_by": "code/analyze.R",
    "tolerance": 0.01
   },
   {
    "result": "R6.P1.late.lower",
    "produced_by": "code/analyze.R",
    "tolerance": 0.01
   },
   {
    "result": "R6.P1.late.upper",
    "produced_by": "code/analyze.R",
    "tolerance": 0.01
   },
   {
    "result": "R6.P1.late.k",
    "produced_by": "code/analyze.R"
   }
  ],
  "depends_on": [],
  "falsified_if": "A re-run gives a 95% CI that includes 0 for the depressed-only masked trials or for either later window.",
  "confidence": 0.7
 },
 {
  "local_id": "C5",
  "type": "empirical",
  "core": false,
  "statement": "In the only trial that randomized when esketamine was given (77 participants in its two esketamine arms), those given it two hours before induction of anesthesia, while awake, had fewer depressive symptoms (PHQ-9) on the first day after surgery than those given it after induction (g −0.72, 95% CI −1.18 to −0.26).",
  "evidence": [
   {
    "result": "R8.within_trial.T097.n",
    "produced_by": "code/analyze.R"
   },
   {
    "result": "R8.within_trial.T097.g",
    "produced_by": "code/analyze.R",
    "tolerance": 0.01
   },
   {
    "result": "R8.within_trial.T097.lower",
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    "tolerance": 0.01
   },
   {
    "result": "R8.within_trial.T097.upper",
    "produced_by": "code/analyze.R",
    "tolerance": 0.01
   }
  ],
  "depends_on": [],
  "falsified_if": "A re-run from the bundle's data gives a within-trial 95% CI that includes 0.",
  "confidence": 0.7
 },
 {
  "local_id": "C6",
  "type": "empirical",
  "core": false,
  "statement": "Of the 39 eligible ClinicalTrials.gov registrations whose primary completion was at least 12 months before the search, 18 (46%) had neither a report naming them nor posted results; among the masked trials Egger's test found no funnel-plot asymmetry (p = 0.7), and the PET estimate of the masked effect, allowing for small-study effects, was g −0.47 (95% CI −1.23 to 0.29).",
  "evidence": [
   {
    "result": "D.registry.due",
    "produced_by": "code/summarize.R"
   },
   {
    "result": "D.registry.unreported",
    "produced_by": "code/summarize.R"
   },
   {
    "result": "D.registry.unreported_pct",
    "produced_by": "code/summarize.R"
   },
   {
    "result": "R7.egger_p_text",
    "produced_by": "code/analyze.R"
   },
   {
    "result": "R7.pet_peese.g",
    "produced_by": "code/analyze.R",
    "tolerance": 0.01
   },
   {
    "result": "R7.pet_peese.lower",
    "produced_by": "code/analyze.R",
    "tolerance": 0.01
   },
   {
    "result": "R7.pet_peese.upper",
    "produced_by": "code/analyze.R",
    "tolerance": 0.01
   }
  ],
  "depends_on": [],
  "falsified_if": "A search of the listed registrations finds reports or posted results that change the count, or a re-run gives an Egger p below 0.05.",
  "confidence": 0.8
 },
 {
  "local_id": "C7",
  "type": "empirical",
  "core": false,
  "statement": "Of the 51 trials with a depression effect on days 1 to 3, 21 failed the pre-registered integrity screen: 13 named no trial registration, 5 were registered after enrollment began, 2 reported two or more depression means that no whole-number scores could produce for their sample sizes (GRIM), and 1 reported an effect beyond |g| = 2.",
  "evidence": [
   {
    "result": "D.early.trials",
    "produced_by": "code/summarize.R"
   },
   {
    "result": "D.early.untrustworthy",
    "produced_by": "code/summarize.R"
   },
   {
    "result": "D.early.unregistered",
    "produced_by": "code/summarize.R"
   },
   {
    "result": "D.early.retrospective",
    "produced_by": "code/summarize.R"
   },
   {
    "result": "D.early.grim",
    "produced_by": "code/summarize.R"
   },
   {
    "result": "D.early.implausible",
    "produced_by": "code/summarize.R"
   }
  ],
  "depends_on": [],
  "falsified_if": "A re-check of the trials' registrations, dates, or printed means against their sources finds these counts wrong.",
  "confidence": 0.85
 }
]