{"bundle_type":"pith_open_graph_bundle","bundle_version":"1.0","pith_number":"pith:2025:DU5C6HLDOX5UFF6756KRSVEP2Q","short_pith_number":"pith:DU5C6HLD","canonical_record":{"source":{"id":"2509.05825","kind":"arxiv","version":1},"metadata":{"license":"http://creativecommons.org/licenses/by/4.0/","primary_cat":"stat.ME","submitted_at":"2025-09-06T20:40:13Z","cross_cats_sorted":[],"title_canon_sha256":"ef4fc508c3b384b33b93a49e8a817477e5c77b03b8fd98ec7b78cb35952fb6ad","abstract_canon_sha256":"417ef4033e19572b93b43442b1b0601c563730bb0aace260ca9211429ba4e38f"},"schema_version":"1.0"},"canonical_sha256":"1d3a2f1d6375fb4297dfef9519548fd409f4bd85263c21d16b9f9d66d974aede","source":{"kind":"arxiv","id":"2509.05825","version":1},"source_aliases":[{"alias_kind":"arxiv","alias_value":"2509.05825","created_at":"2026-07-05T12:06:24Z"},{"alias_kind":"arxiv_version","alias_value":"2509.05825v1","created_at":"2026-07-05T12:06:24Z"},{"alias_kind":"doi","alias_value":"10.48550/arxiv.2509.05825","created_at":"2026-07-05T12:06:24Z"},{"alias_kind":"pith_short_12","alias_value":"DU5C6HLDOX5U","created_at":"2026-07-05T12:06:24Z"},{"alias_kind":"pith_short_16","alias_value":"DU5C6HLDOX5UFF67","created_at":"2026-07-05T12:06:24Z"},{"alias_kind":"pith_short_8","alias_value":"DU5C6HLD","created_at":"2026-07-05T12:06:24Z"}],"events":[{"event_type":"record_created","subject_pith_number":"pith:2025:DU5C6HLDOX5UFF6756KRSVEP2Q","target":"record","payload":{"canonical_record":{"source":{"id":"2509.05825","kind":"arxiv","version":1},"metadata":{"license":"http://creativecommons.org/licenses/by/4.0/","primary_cat":"stat.ME","submitted_at":"2025-09-06T20:40:13Z","cross_cats_sorted":[],"title_canon_sha256":"ef4fc508c3b384b33b93a49e8a817477e5c77b03b8fd98ec7b78cb35952fb6ad","abstract_canon_sha256":"417ef4033e19572b93b43442b1b0601c563730bb0aace260ca9211429ba4e38f"},"schema_version":"1.0"},"canonical_sha256":"1d3a2f1d6375fb4297dfef9519548fd409f4bd85263c21d16b9f9d66d974aede","receipt":{"kind":"pith_receipt","key_id":"pith-v1-2026-05","algorithm":"ed25519","signed_at":"2026-07-05T12:06:24.849974Z","signature_b64":"rlecY6qzlcK2x4B4Ssp8P3eJ69rD7k/7vPtobnFR9y8MLytkpZ4SS+1lHBjctCuoDU9S17VDtxnIiKYoUjjJBw==","signed_message":"canonical_sha256_bytes","builder_version":"pith-number-builder-2026-05-17-v1","receipt_version":"0.3","canonical_sha256":"1d3a2f1d6375fb4297dfef9519548fd409f4bd85263c21d16b9f9d66d974aede","last_reissued_at":"2026-07-05T12:06:24.849525Z","signature_status":"signed_v1","first_computed_at":"2026-07-05T12:06:24.849525Z","public_key_fingerprint":"8d4b5ee74e4693bcd1df2446408b0d54"},"source_kind":"arxiv","source_id":"2509.05825","source_version":1,"attestation_state":"computed"},"signer":{"signer_id":"pith.science","signer_type":"pith_registry","key_id":"pith-v1-2026-05","public_key_fingerprint":"8d4b5ee74e4693bcd1df2446408b0d54"},"created_at":"2026-07-05T12:06:24Z","supersedes":[],"prev_event":null,"signature":{"signature_status":"signed_v1","algorithm":"ed25519","key_id":"pith-v1-2026-05","public_key_fingerprint":"8d4b5ee74e4693bcd1df2446408b0d54","signature_b64":"CH/Spl6HkB5iBMzLDa+QBqt9SCN8oewr49LQsJrRE1ZZdNRlz7NwAeoldY/bG4jx9HBwpShey0da25OlYG86CQ==","signed_message":"open_graph_event_sha256_bytes","signed_at":"2026-07-07T07:09:18.806781Z"},"content_sha256":"aaeb676d00461eadde4c2cc77867b2c6b626ae8d814d871aa4208da6de6e8b2c","schema_version":"1.0","event_id":"sha256:aaeb676d00461eadde4c2cc77867b2c6b626ae8d814d871aa4208da6de6e8b2c"},{"event_type":"graph_snapshot","subject_pith_number":"pith:2025:DU5C6HLDOX5UFF6756KRSVEP2Q","target":"graph","payload":{"graph_snapshot":{"paper":{"title":"LORDs: Locally Optimal Restricted Designs for Phase I/II Dose-Finding Studies","license":"http://creativecommons.org/licenses/by/4.0/","headline":"","cross_cats":[],"primary_cat":"stat.ME","authors_text":"Oleksandr Sverdlov, Weng Kee Wong, Yevgen Ryeznik","submitted_at":"2025-09-06T20:40:13Z","abstract_excerpt":"We propose Locally Optimal Restricted Designs (LORDs) for phase I/II dose-finding studies that focus on both efficacy and toxicity outcomes. As an illustrative application, we find various LORDs for a 4-parameter continuation-ratio (CR) model defined on a user-specified dose range, where ethical constraints are imposed to prevent patients from receiving excessively toxic or ineffective doses. We study the structure and efficiency of LORDs across several experimental scenarios and assess the sensitivity of the results to changes in the design problem, such as adjusting the dose range or redefin"},"claims":{"count":0,"items":[],"snapshot_sha256":"258153158e38e3291e3d48162225fcdb2d5a3ed65a07baac614ab91432fd4f57"},"source":{"id":"2509.05825","kind":"arxiv","version":1},"verdict":{"id":null,"model_set":{},"created_at":null,"strongest_claim":"","one_line_summary":"","pipeline_version":null,"weakest_assumption":"","pith_extraction_headline":""},"integrity":{"clean":true,"summary":{"advisory":0,"critical":0,"by_detector":{},"informational":0},"endpoint":"/pith/2509.05825/integrity.json","findings":[],"available":true,"detectors_run":[],"snapshot_sha256":"c28c3603d3b5d939e8dc4c7e95fa8dfce3d595e45f758748cecf8e644a296938"},"references":{"count":0,"sample":[],"resolved_work":0,"snapshot_sha256":"258153158e38e3291e3d48162225fcdb2d5a3ed65a07baac614ab91432fd4f57","internal_anchors":0},"formal_canon":{"evidence_count":0,"snapshot_sha256":"258153158e38e3291e3d48162225fcdb2d5a3ed65a07baac614ab91432fd4f57"},"author_claims":{"count":0,"strong_count":0,"snapshot_sha256":"258153158e38e3291e3d48162225fcdb2d5a3ed65a07baac614ab91432fd4f57"},"builder_version":"pith-number-builder-2026-05-17-v1"},"verdict_id":null},"signer":{"signer_id":"pith.science","signer_type":"pith_registry","key_id":"pith-v1-2026-05","public_key_fingerprint":"8d4b5ee74e4693bcd1df2446408b0d54"},"created_at":"2026-07-05T12:06:24Z","supersedes":[],"prev_event":null,"signature":{"signature_status":"signed_v1","algorithm":"ed25519","key_id":"pith-v1-2026-05","public_key_fingerprint":"8d4b5ee74e4693bcd1df2446408b0d54","signature_b64":"K8IiyY9k+vCpuMDvM+X7McJ1JEkRZrGQ5vFvy9zQxfyLoDZPkmwdZSJ1YBOfn1w8NriC/681blNwfNzl5KUFAw==","signed_message":"open_graph_event_sha256_bytes","signed_at":"2026-07-07T07:09:18.807389Z"},"content_sha256":"939788f366be7d5fc29c334440b9f471305020581ca4092df60e622371477637","schema_version":"1.0","event_id":"sha256:939788f366be7d5fc29c334440b9f471305020581ca4092df60e622371477637"}],"timestamp_proofs":[],"mirror_hints":[{"mirror_type":"https","name":"Pith Resolver","base_url":"https://pith.science","bundle_url":"https://pith.science/pith/DU5C6HLDOX5UFF6756KRSVEP2Q/bundle.json","state_url":"https://pith.science/pith/DU5C6HLDOX5UFF6756KRSVEP2Q/state.json","well_known_bundle_url":"https://pith.science/.well-known/pith/DU5C6HLDOX5UFF6756KRSVEP2Q/bundle.json","status":"primary"}],"public_keys":[{"key_id":"pith-v1-2026-05","algorithm":"ed25519","format":"raw","public_key_b64":"stVStoiQhXFxp4s2pdzPNoqVNBMojDU/fJ2db5S3CbM=","public_key_hex":"b2d552b68890857171a78b36a5dccf368a953413288c353f7c9d9d6f94b709b3","fingerprint_sha256_b32_first128bits":"RVFV5Z2OI2J3ZUO7ERDEBCYNKS","fingerprint_sha256_hex":"8d4b5ee74e4693bcd1df2446408b0d54","rotates_at":null,"url":"https://pith.science/pith-signing-key.json","notes":"Pith uses this Ed25519 key to sign canonical record SHA-256 digests. Verify with: ed25519_verify(public_key, message=canonical_sha256_bytes, signature=base64decode(signature_b64))."}],"merge_version":"pith-open-graph-merge-v1","built_at":"2026-07-07T07:09:18Z","links":{"resolver":"https://pith.science/pith/DU5C6HLDOX5UFF6756KRSVEP2Q","bundle":"https://pith.science/pith/DU5C6HLDOX5UFF6756KRSVEP2Q/bundle.json","state":"https://pith.science/pith/DU5C6HLDOX5UFF6756KRSVEP2Q/state.json","well_known_bundle":"https://pith.science/.well-known/pith/DU5C6HLDOX5UFF6756KRSVEP2Q/bundle.json"},"state":{"state_type":"pith_open_graph_state","state_version":"1.0","pith_number":"pith:2025:DU5C6HLDOX5UFF6756KRSVEP2Q","merge_version":"pith-open-graph-merge-v1","event_count":2,"valid_event_count":2,"invalid_event_count":0,"equivocation_count":0,"current":{"canonical_record":{"metadata":{"abstract_canon_sha256":"417ef4033e19572b93b43442b1b0601c563730bb0aace260ca9211429ba4e38f","cross_cats_sorted":[],"license":"http://creativecommons.org/licenses/by/4.0/","primary_cat":"stat.ME","submitted_at":"2025-09-06T20:40:13Z","title_canon_sha256":"ef4fc508c3b384b33b93a49e8a817477e5c77b03b8fd98ec7b78cb35952fb6ad"},"schema_version":"1.0","source":{"id":"2509.05825","kind":"arxiv","version":1}},"source_aliases":[{"alias_kind":"arxiv","alias_value":"2509.05825","created_at":"2026-07-05T12:06:24Z"},{"alias_kind":"arxiv_version","alias_value":"2509.05825v1","created_at":"2026-07-05T12:06:24Z"},{"alias_kind":"doi","alias_value":"10.48550/arxiv.2509.05825","created_at":"2026-07-05T12:06:24Z"},{"alias_kind":"pith_short_12","alias_value":"DU5C6HLDOX5U","created_at":"2026-07-05T12:06:24Z"},{"alias_kind":"pith_short_16","alias_value":"DU5C6HLDOX5UFF67","created_at":"2026-07-05T12:06:24Z"},{"alias_kind":"pith_short_8","alias_value":"DU5C6HLD","created_at":"2026-07-05T12:06:24Z"}],"graph_snapshots":[{"event_id":"sha256:939788f366be7d5fc29c334440b9f471305020581ca4092df60e622371477637","target":"graph","created_at":"2026-07-05T12:06:24Z","signer":{"key_id":"pith-v1-2026-05","public_key_fingerprint":"8d4b5ee74e4693bcd1df2446408b0d54","signer_id":"pith.science","signer_type":"pith_registry"},"payload":{"graph_snapshot":{"author_claims":{"count":0,"snapshot_sha256":"258153158e38e3291e3d48162225fcdb2d5a3ed65a07baac614ab91432fd4f57","strong_count":0},"builder_version":"pith-number-builder-2026-05-17-v1","claims":{"count":0,"items":[],"snapshot_sha256":"258153158e38e3291e3d48162225fcdb2d5a3ed65a07baac614ab91432fd4f57"},"formal_canon":{"evidence_count":0,"snapshot_sha256":"258153158e38e3291e3d48162225fcdb2d5a3ed65a07baac614ab91432fd4f57"},"integrity":{"available":true,"clean":true,"detectors_run":[],"endpoint":"/pith/2509.05825/integrity.json","findings":[],"snapshot_sha256":"c28c3603d3b5d939e8dc4c7e95fa8dfce3d595e45f758748cecf8e644a296938","summary":{"advisory":0,"by_detector":{},"critical":0,"informational":0}},"paper":{"abstract_excerpt":"We propose Locally Optimal Restricted Designs (LORDs) for phase I/II dose-finding studies that focus on both efficacy and toxicity outcomes. As an illustrative application, we find various LORDs for a 4-parameter continuation-ratio (CR) model defined on a user-specified dose range, where ethical constraints are imposed to prevent patients from receiving excessively toxic or ineffective doses. We study the structure and efficiency of LORDs across several experimental scenarios and assess the sensitivity of the results to changes in the design problem, such as adjusting the dose range or redefin","authors_text":"Oleksandr Sverdlov, Weng Kee Wong, Yevgen Ryeznik","cross_cats":[],"headline":"","license":"http://creativecommons.org/licenses/by/4.0/","primary_cat":"stat.ME","submitted_at":"2025-09-06T20:40:13Z","title":"LORDs: Locally Optimal Restricted Designs for Phase I/II Dose-Finding Studies"},"references":{"count":0,"internal_anchors":0,"resolved_work":0,"sample":[],"snapshot_sha256":"258153158e38e3291e3d48162225fcdb2d5a3ed65a07baac614ab91432fd4f57"},"source":{"id":"2509.05825","kind":"arxiv","version":1},"verdict":{"created_at":null,"id":null,"model_set":{},"one_line_summary":"","pipeline_version":null,"pith_extraction_headline":"","strongest_claim":"","weakest_assumption":""}},"verdict_id":null}}],"author_attestations":[],"timestamp_anchors":[],"storage_attestations":[],"citation_signatures":[],"replication_records":[],"corrections":[],"mirror_hints":[],"record_created":{"event_id":"sha256:aaeb676d00461eadde4c2cc77867b2c6b626ae8d814d871aa4208da6de6e8b2c","target":"record","created_at":"2026-07-05T12:06:24Z","signer":{"key_id":"pith-v1-2026-05","public_key_fingerprint":"8d4b5ee74e4693bcd1df2446408b0d54","signer_id":"pith.science","signer_type":"pith_registry"},"payload":{"attestation_state":"computed","canonical_record":{"metadata":{"abstract_canon_sha256":"417ef4033e19572b93b43442b1b0601c563730bb0aace260ca9211429ba4e38f","cross_cats_sorted":[],"license":"http://creativecommons.org/licenses/by/4.0/","primary_cat":"stat.ME","submitted_at":"2025-09-06T20:40:13Z","title_canon_sha256":"ef4fc508c3b384b33b93a49e8a817477e5c77b03b8fd98ec7b78cb35952fb6ad"},"schema_version":"1.0","source":{"id":"2509.05825","kind":"arxiv","version":1}},"canonical_sha256":"1d3a2f1d6375fb4297dfef9519548fd409f4bd85263c21d16b9f9d66d974aede","receipt":{"algorithm":"ed25519","builder_version":"pith-number-builder-2026-05-17-v1","canonical_sha256":"1d3a2f1d6375fb4297dfef9519548fd409f4bd85263c21d16b9f9d66d974aede","first_computed_at":"2026-07-05T12:06:24.849525Z","key_id":"pith-v1-2026-05","kind":"pith_receipt","last_reissued_at":"2026-07-05T12:06:24.849525Z","public_key_fingerprint":"8d4b5ee74e4693bcd1df2446408b0d54","receipt_version":"0.3","signature_b64":"rlecY6qzlcK2x4B4Ssp8P3eJ69rD7k/7vPtobnFR9y8MLytkpZ4SS+1lHBjctCuoDU9S17VDtxnIiKYoUjjJBw==","signature_status":"signed_v1","signed_at":"2026-07-05T12:06:24.849974Z","signed_message":"canonical_sha256_bytes"},"source_id":"2509.05825","source_kind":"arxiv","source_version":1}}},"equivocations":[],"invalid_events":[],"applied_event_ids":["sha256:aaeb676d00461eadde4c2cc77867b2c6b626ae8d814d871aa4208da6de6e8b2c","sha256:939788f366be7d5fc29c334440b9f471305020581ca4092df60e622371477637"],"state_sha256":"ec589c94ace60c4f3ed14a13bbe858fe3b8f42536145a0c29875402d2288e044"},"bundle_signature":{"signature_status":"signed_v1","algorithm":"ed25519","key_id":"pith-v1-2026-05","public_key_fingerprint":"8d4b5ee74e4693bcd1df2446408b0d54","signature_b64":"nGDuy9jgHSykcYze4vz7MW1+fRQxVPxJUXV9+qHxll4lwPSDYLkSvtUrnhNj+1TDMHcmZr6RzSJc9er95fGECQ==","signed_message":"bundle_sha256_bytes","signed_at":"2026-07-07T07:09:18.810370Z","bundle_sha256":"362abdb231f1b9c39539efc547e104f12b381c21e2bd23c0072cea9c0402d69b"}}