{
  "status": "Exploratory plan frozen after reading published outcome tables, before running synthesis; not preregistered.",
  "question": "What do current public aggregate results from four major outpatient ivermectin platform trials show, and how do control choice and endpoint alignment affect inference?",
  "selection": "Purposive audit of PRINCIPLE, ACTIV-6 (both nonoverlapping dose cohorts), COVID-OUT, and TOGETHER; not an exhaustive systematic review or a new individual-participant analysis.",
  "main_synthesis": "Available-case crude log risk ratios for reported 28-day hospital-or-death outcomes in PRINCIPLE and both ACTIV-6 cohorts; cause-specific and all-cause endpoints are only broadly aligned, a limitation.",
  "estimator": "DerSimonian-Laird tau-squared with modified Hartung-Knapp t confidence interval, scale=max(1,Q_RE/(k-1)); common-effect inverse-variance normal interval also reported. Katz per-contrast intervals.",
  "sensitivities": [
    "Leave each 28-day contrast out",
    "Exclude open-label PRINCIPLE",
    "Add COVID-OUT 14-day outcome, explicitly mixed-window",
    "Exclude accidental death from high-dose ACTIV-6",
    "High-dose ACTIV-6 missing placebo outcomes: all non-events versus all events",
    "Deliberately replace concurrent PRINCIPLE controls with all controls, as invalid-comparator diagnostic only"
  ],
  "not_pooled": [
    "TOGETHER extended-emergency-observation composite",
    "Recovery hazard ratios with unlike definitions",
    "Long COVID outcomes",
    "Mortality alone"
  ],
  "coverage": "Adult symptomatic outpatient treatment, not prevention, hospitalized treatment, all subgroups, or all doses.",
  "inference": "Two-sided 95% intervals; exploratory p values with no multiplicity adjustment; no equivalence test and no proof of exact no effect.",
  "missingness": "Use endpoint-specific published denominators. Cannot reconstruct imputation, covariate adjustment, joint endpoints or patient-level effect modification.",
  "independence": "ACTIV-6 dosing cohorts enrolled in disjoint periods. No deduplication across separate trial platforms is possible with aggregates.",
  "extension": "After the initial arithmetic audit, before computing this extension, add an exploratory enumeration of every hospitalization/death union consistent with the TOGETHER published margins. Pool each hypothetical union with the three 28-day contrasts and report all scenarios and their interval envelope, never presenting any as the observed union."
}