{
  "preregistration_schema": "nmd-vcell-dmd-prospective-truth-pilot/2.0",
  "object_id": "STUDY-DRAFT:DMD-MATCHED-PERTURBATION-PILOT:0.1",
  "lifecycle_state": "DRAFT_NOT_REGISTERED",
  "lifecycle_track": "TRUTH_GENERATION",
  "prediction_required_for_registration": false,
  "eligible_model_run_required_for_registration": false,
  "created_at": "2026-08-17",
  "supplemental_release": "v1.2.1-model-intelligence",
  "parent_resource_release": "v1.2.0-measured-dmd-evidence",
  "interface_build": "EA-20260817-57",
  "scientific_question": "Can a prespecified intervention produce a reproducible molecular and functional response in disease-relevant DMD myogenic cells from independent biological donors?",
  "current_outcome_state": "MATCHED_DMD_CANDIDATE_RESPONSE_OUTCOME_MISSING",
  "design_recommendation_not_frozen": {
    "independent_dmd_donors_minimum": 3,
    "independent_reference_donors_minimum": 2,
    "intervention_panel_size_range": "6–12",
    "negative_interventions_minimum": 2,
    "positive_or_assay_controls_minimum": 1,
    "required_response_layers": [
      "transcriptomic response",
      "cell-state distribution",
      "disease-relevant functional endpoint",
      "viability/toxicity"
    ],
    "inference_unit": "independent biological donor or independently randomized culture; never individual cells",
    "holdout": "complete donor and future experimental batch",
    "note": "These are design recommendations for review, not assigned samples or an approved protocol."
  },
  "required_decisions": [
    {
      "decision_id": "DMD-PILOT-DECISION-01",
      "field": "candidate_panel",
      "value": null,
      "state": "UNRESOLVED_AUTHOR_OR_EXPERIMENTAL_AUTHORITY_REQUIRED",
      "resolution_requirement": "Select and justify the intervention panel; model-watch results cannot choose it."
    },
    {
      "decision_id": "DMD-PILOT-DECISION-02",
      "field": "intervention_modality",
      "value": null,
      "state": "UNRESOLVED_AUTHOR_OR_EXPERIMENTAL_AUTHORITY_REQUIRED",
      "resolution_requirement": "Freeze CRISPRi, ASO, small molecule or another modality before registration."
    },
    {
      "decision_id": "DMD-PILOT-DECISION-03",
      "field": "reagent_identity",
      "value": null,
      "state": "UNRESOLVED_AUTHOR_OR_EXPERIMENTAL_AUTHORITY_REQUIRED",
      "resolution_requirement": "Record reagent sequence/identity, target, lot and off-target controls."
    },
    {
      "decision_id": "DMD-PILOT-DECISION-04",
      "field": "dose",
      "value": null,
      "state": "UNRESOLVED_AUTHOR_OR_EXPERIMENTAL_AUTHORITY_REQUIRED",
      "resolution_requirement": "Freeze dose levels and the rule for excluding toxic exposure."
    },
    {
      "decision_id": "DMD-PILOT-DECISION-05",
      "field": "post_intervention_time",
      "value": null,
      "state": "UNRESOLVED_AUTHOR_OR_EXPERIMENTAL_AUTHORITY_REQUIRED",
      "resolution_requirement": "Freeze molecular and functional readout times."
    },
    {
      "decision_id": "DMD-PILOT-DECISION-06",
      "field": "donor_inclusion",
      "value": null,
      "state": "UNRESOLVED_AUTHOR_OR_EXPERIMENTAL_AUTHORITY_REQUIRED",
      "resolution_requirement": "Assign independent DMD and reference biological donors with inclusion/exclusion rules."
    },
    {
      "decision_id": "DMD-PILOT-DECISION-07",
      "field": "molecular_primary_endpoint",
      "value": null,
      "state": "UNRESOLVED_AUTHOR_OR_EXPERIMENTAL_AUTHORITY_REQUIRED",
      "resolution_requirement": "Choose one prespecified molecular endpoint and its statistical unit."
    },
    {
      "decision_id": "DMD-PILOT-DECISION-08",
      "field": "functional_primary_endpoint",
      "value": null,
      "state": "UNRESOLVED_AUTHOR_OR_EXPERIMENTAL_AUTHORITY_REQUIRED",
      "resolution_requirement": "Choose one disease-relevant functional endpoint and assay."
    },
    {
      "decision_id": "DMD-PILOT-DECISION-09",
      "field": "toxicity_endpoint",
      "value": null,
      "state": "UNRESOLVED_AUTHOR_OR_EXPERIMENTAL_AUTHORITY_REQUIRED",
      "resolution_requirement": "Define viability/toxicity failure and abstention thresholds."
    },
    {
      "decision_id": "DMD-PILOT-DECISION-10",
      "field": "decision_rule",
      "value": null,
      "state": "UNRESOLVED_AUTHOR_OR_EXPERIMENTAL_AUTHORITY_REQUIRED",
      "resolution_requirement": "Freeze success, null, discordant and stop rules before outcome access."
    }
  ],
  "registration_gate": {
    "state": "AWAITING_EXPERIMENTAL_AUTHORITY_AND_STUDY_FREEZE",
    "unresolved_decision_count": 10,
    "registered_study_count": 0,
    "registered_prediction_count": 0,
    "outcome_count": 0,
    "prediction_required": false,
    "unlock_condition": "Experimental authority resolves all fields, governance approves the protocol, and the Study object is frozen before execution. No Prediction object is required to generate truth."
  },
  "prediction_template": {
    "prediction_schema": "nmd-vcell-prospective-prediction-template/1.0",
    "object_id": "PREDICTION-TEMPLATE:DMD-MATCHED-PERTURBATION-PILOT:0.1",
    "lifecycle_state": "TEMPLATE_NOT_REGISTERED",
    "study_object_id": "STUDY-DRAFT:DMD-MATCHED-PERTURBATION-PILOT:0.1",
    "model_run_id": null,
    "intervention_id": null,
    "donor_holdout_id": null,
    "predicted_direction": null,
    "predicted_effect_interval": null,
    "predicted_functional_response": null,
    "abstention_rule": null,
    "sealed_at": null,
    "outcome_accessed": false,
    "applies_to_track": "PREDICTION_VALIDATION_ONLY",
    "required_for_truth_generation": false,
    "registration_blocker": "This future validation template remains inactive until a DMD-compatible ModelRun passes eligibility and truth is available for calibration.",
    "prohibited_use": [
      "retrospective filling after outcome access",
      "clinical recommendation",
      "therapeutic efficacy claim"
    ]
  },
  "outcome_states_retained": [
    "POSITIVE",
    "NULL",
    "TOXIC",
    "FAILED_QC",
    "DISCORDANT",
    "ABSTAINED"
  ],
  "prohibited_claims": [
    "approved study",
    "registered prediction",
    "measured DMD response",
    "therapeutic efficacy",
    "clinical decision support"
  ],
  "next_action": "Resolve the ten author/experimental-authority decisions; then issue a new immutable registered truth-generation Study object rather than editing this draft in place.",
  "claim_boundary": "This package prepares a truth-generating study. It does not authorize an experiment, assign donors, select a therapeutic target or report an outcome. Prediction registration is a separate future validation track."
}