{"bundle_type":"pith_open_graph_bundle","bundle_version":"1.0","pith_number":"pith:2020:JANLBFF7BAVHETOA4GRX2JGEQP","short_pith_number":"pith:JANLBFF7","canonical_record":{"source":{"id":"2012.05301","kind":"arxiv","version":2},"metadata":{"license":"http://creativecommons.org/licenses/by/4.0/","primary_cat":"stat.ME","submitted_at":"2020-12-09T20:33:38Z","cross_cats_sorted":["q-bio.QM","stat.AP"],"title_canon_sha256":"79204dab53ce11f4074d42d46485fd8cb9d738b041da95b9e7177354b9a9db77","abstract_canon_sha256":"9711e9783f2c75b446d10e08795b5882396ecf2b9a953282ce9aa3ca09261224"},"schema_version":"1.0"},"canonical_sha256":"481ab094bf082a724dc0e1a37d24c483ce4ed0d5d51d79c6959deef0d979f620","source":{"kind":"arxiv","id":"2012.05301","version":2},"source_aliases":[{"alias_kind":"arxiv","alias_value":"2012.05301","created_at":"2026-07-05T02:01:55Z"},{"alias_kind":"arxiv_version","alias_value":"2012.05301v2","created_at":"2026-07-05T02:01:55Z"},{"alias_kind":"doi","alias_value":"10.48550/arxiv.2012.05301","created_at":"2026-07-05T02:01:55Z"},{"alias_kind":"pith_short_12","alias_value":"JANLBFF7BAVH","created_at":"2026-07-05T02:01:55Z"},{"alias_kind":"pith_short_16","alias_value":"JANLBFF7BAVHETOA","created_at":"2026-07-05T02:01:55Z"},{"alias_kind":"pith_short_8","alias_value":"JANLBFF7","created_at":"2026-07-05T02:01:55Z"}],"events":[{"event_type":"record_created","subject_pith_number":"pith:2020:JANLBFF7BAVHETOA4GRX2JGEQP","target":"record","payload":{"canonical_record":{"source":{"id":"2012.05301","kind":"arxiv","version":2},"metadata":{"license":"http://creativecommons.org/licenses/by/4.0/","primary_cat":"stat.ME","submitted_at":"2020-12-09T20:33:38Z","cross_cats_sorted":["q-bio.QM","stat.AP"],"title_canon_sha256":"79204dab53ce11f4074d42d46485fd8cb9d738b041da95b9e7177354b9a9db77","abstract_canon_sha256":"9711e9783f2c75b446d10e08795b5882396ecf2b9a953282ce9aa3ca09261224"},"schema_version":"1.0"},"canonical_sha256":"481ab094bf082a724dc0e1a37d24c483ce4ed0d5d51d79c6959deef0d979f620","receipt":{"kind":"pith_receipt","key_id":"pith-v1-2026-05","algorithm":"ed25519","signed_at":"2026-07-05T02:01:55.434805Z","signature_b64":"9lPtixin/cu3BNoZKyuMOinOXO8TfEN8SPxwrA5KiPHA0Ixf/XIB33J/M368gRblVgvpc0WBjjuLIM3r7NDjAw==","signed_message":"canonical_sha256_bytes","builder_version":"pith-number-builder-2026-05-17-v1","receipt_version":"0.3","canonical_sha256":"481ab094bf082a724dc0e1a37d24c483ce4ed0d5d51d79c6959deef0d979f620","last_reissued_at":"2026-07-05T02:01:55.434381Z","signature_status":"signed_v1","first_computed_at":"2026-07-05T02:01:55.434381Z","public_key_fingerprint":"8d4b5ee74e4693bcd1df2446408b0d54"},"source_kind":"arxiv","source_id":"2012.05301","source_version":2,"attestation_state":"computed"},"signer":{"signer_id":"pith.science","signer_type":"pith_registry","key_id":"pith-v1-2026-05","public_key_fingerprint":"8d4b5ee74e4693bcd1df2446408b0d54"},"created_at":"2026-07-05T02:01:55Z","supersedes":[],"prev_event":null,"signature":{"signature_status":"signed_v1","algorithm":"ed25519","key_id":"pith-v1-2026-05","public_key_fingerprint":"8d4b5ee74e4693bcd1df2446408b0d54","signature_b64":"xkqhpJ3n/cTxv+/3ZgkbBkwTNLtbwpH+04/HxHIGIYhREeiMCeMmv+OY5QwaJDkcBxJs8bCUHll3d2nT2IBtDQ==","signed_message":"open_graph_event_sha256_bytes","signed_at":"2026-08-08T11:49:16.258696Z"},"content_sha256":"9b6d74e0eb5e5e1ec1a49efefafd9f368fc1558576925fbad2547fbba8cd0f01","schema_version":"1.0","event_id":"sha256:9b6d74e0eb5e5e1ec1a49efefafd9f368fc1558576925fbad2547fbba8cd0f01"},{"event_type":"graph_snapshot","subject_pith_number":"pith:2020:JANLBFF7BAVHETOA4GRX2JGEQP","target":"graph","payload":{"graph_snapshot":{"paper":{"title":"What Were They Thinking? Pharmacologic priors implicit in a choice of 3+3 dose-escalation design","license":"http://creativecommons.org/licenses/by/4.0/","headline":"","cross_cats":["q-bio.QM","stat.AP"],"primary_cat":"stat.ME","authors_text":"David C. Norris","submitted_at":"2020-12-09T20:33:38Z","abstract_excerpt":"If explicit, formal consideration of clinical pharmacology at all informs the design and conduct of modern oncology dose-finding trials, the designs themselves hardly attest to this. Yet in conducting a trial, investigators affirm that they hold reasonable expectations of participant safety - expectations that necessarily depend on beliefs about how certain pharmacologic parameters are distributed in the study population. Thus, these beliefs are implicit in a trial's presumed conformance to a community standard of safety, and may therefore to some extent be reverse-engineered from trial design"},"claims":{"count":0,"items":[],"snapshot_sha256":"258153158e38e3291e3d48162225fcdb2d5a3ed65a07baac614ab91432fd4f57"},"source":{"id":"2012.05301","kind":"arxiv","version":2},"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/2012.05301/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":"2026-07-05T02:01:55Z","supersedes":[],"prev_event":null,"signature":{"signature_status":"signed_v1","algorithm":"ed25519","key_id":"pith-v1-2026-05","public_key_fingerprint":"8d4b5ee74e4693bcd1df2446408b0d54","signature_b64":"ogRNwjRvPqhMzxfRMF+gZPQVsrbGWalS55lo14s/i5fm6+j83lAfv1/i/5salIoZxKJHpWKUtZIPwY7gxb+OAQ==","signed_message":"open_graph_event_sha256_bytes","signed_at":"2026-08-08T11:49:16.259207Z"},"content_sha256":"92eb418a6003554432700032755c560f233eb0065b389b87faa88326f367e2ce","schema_version":"1.0","event_id":"sha256:92eb418a6003554432700032755c560f233eb0065b389b87faa88326f367e2ce"}],"timestamp_proofs":[],"mirror_hints":[{"mirror_type":"https","name":"Pith Resolver","base_url":"https://pith.science","bundle_url":"https://pith.science/pith/JANLBFF7BAVHETOA4GRX2JGEQP/bundle.json","state_url":"https://pith.science/pith/JANLBFF7BAVHETOA4GRX2JGEQP/state.json","well_known_bundle_url":"https://pith.science/.well-known/pith/JANLBFF7BAVHETOA4GRX2JGEQP/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":"2026-08-08T11:49:16Z","links":{"resolver":"https://pith.science/pith/JANLBFF7BAVHETOA4GRX2JGEQP","bundle":"https://pith.science/pith/JANLBFF7BAVHETOA4GRX2JGEQP/bundle.json","state":"https://pith.science/pith/JANLBFF7BAVHETOA4GRX2JGEQP/state.json","well_known_bundle":"https://pith.science/.well-known/pith/JANLBFF7BAVHETOA4GRX2JGEQP/bundle.json"},"state":{"state_type":"pith_open_graph_state","state_version":"1.0","pith_number":"pith:2020:JANLBFF7BAVHETOA4GRX2JGEQP","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":"9711e9783f2c75b446d10e08795b5882396ecf2b9a953282ce9aa3ca09261224","cross_cats_sorted":["q-bio.QM","stat.AP"],"license":"http://creativecommons.org/licenses/by/4.0/","primary_cat":"stat.ME","submitted_at":"2020-12-09T20:33:38Z","title_canon_sha256":"79204dab53ce11f4074d42d46485fd8cb9d738b041da95b9e7177354b9a9db77"},"schema_version":"1.0","source":{"id":"2012.05301","kind":"arxiv","version":2}},"source_aliases":[{"alias_kind":"arxiv","alias_value":"2012.05301","created_at":"2026-07-05T02:01:55Z"},{"alias_kind":"arxiv_version","alias_value":"2012.05301v2","created_at":"2026-07-05T02:01:55Z"},{"alias_kind":"doi","alias_value":"10.48550/arxiv.2012.05301","created_at":"2026-07-05T02:01:55Z"},{"alias_kind":"pith_short_12","alias_value":"JANLBFF7BAVH","created_at":"2026-07-05T02:01:55Z"},{"alias_kind":"pith_short_16","alias_value":"JANLBFF7BAVHETOA","created_at":"2026-07-05T02:01:55Z"},{"alias_kind":"pith_short_8","alias_value":"JANLBFF7","created_at":"2026-07-05T02:01:55Z"}],"graph_snapshots":[{"event_id":"sha256:92eb418a6003554432700032755c560f233eb0065b389b87faa88326f367e2ce","target":"graph","created_at":"2026-07-05T02:01:55Z","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/2012.05301/integrity.json","findings":[],"snapshot_sha256":"c28c3603d3b5d939e8dc4c7e95fa8dfce3d595e45f758748cecf8e644a296938","summary":{"advisory":0,"by_detector":{},"critical":0,"informational":0}},"paper":{"abstract_excerpt":"If explicit, formal consideration of clinical pharmacology at all informs the design and conduct of modern oncology dose-finding trials, the designs themselves hardly attest to this. Yet in conducting a trial, investigators affirm that they hold reasonable expectations of participant safety - expectations that necessarily depend on beliefs about how certain pharmacologic parameters are distributed in the study population. Thus, these beliefs are implicit in a trial's presumed conformance to a community standard of safety, and may therefore to some extent be reverse-engineered from trial design","authors_text":"David C. Norris","cross_cats":["q-bio.QM","stat.AP"],"headline":"","license":"http://creativecommons.org/licenses/by/4.0/","primary_cat":"stat.ME","submitted_at":"2020-12-09T20:33:38Z","title":"What Were They Thinking? Pharmacologic priors implicit in a choice of 3+3 dose-escalation design"},"references":{"count":0,"internal_anchors":0,"resolved_work":0,"sample":[],"snapshot_sha256":"258153158e38e3291e3d48162225fcdb2d5a3ed65a07baac614ab91432fd4f57"},"source":{"id":"2012.05301","kind":"arxiv","version":2},"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":"sha256:9b6d74e0eb5e5e1ec1a49efefafd9f368fc1558576925fbad2547fbba8cd0f01","target":"record","created_at":"2026-07-05T02:01:55Z","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":"9711e9783f2c75b446d10e08795b5882396ecf2b9a953282ce9aa3ca09261224","cross_cats_sorted":["q-bio.QM","stat.AP"],"license":"http://creativecommons.org/licenses/by/4.0/","primary_cat":"stat.ME","submitted_at":"2020-12-09T20:33:38Z","title_canon_sha256":"79204dab53ce11f4074d42d46485fd8cb9d738b041da95b9e7177354b9a9db77"},"schema_version":"1.0","source":{"id":"2012.05301","kind":"arxiv","version":2}},"canonical_sha256":"481ab094bf082a724dc0e1a37d24c483ce4ed0d5d51d79c6959deef0d979f620","receipt":{"algorithm":"ed25519","builder_version":"pith-number-builder-2026-05-17-v1","canonical_sha256":"481ab094bf082a724dc0e1a37d24c483ce4ed0d5d51d79c6959deef0d979f620","first_computed_at":"2026-07-05T02:01:55.434381Z","key_id":"pith-v1-2026-05","kind":"pith_receipt","last_reissued_at":"2026-07-05T02:01:55.434381Z","public_key_fingerprint":"8d4b5ee74e4693bcd1df2446408b0d54","receipt_version":"0.3","signature_b64":"9lPtixin/cu3BNoZKyuMOinOXO8TfEN8SPxwrA5KiPHA0Ixf/XIB33J/M368gRblVgvpc0WBjjuLIM3r7NDjAw==","signature_status":"signed_v1","signed_at":"2026-07-05T02:01:55.434805Z","signed_message":"canonical_sha256_bytes"},"source_id":"2012.05301","source_kind":"arxiv","source_version":2}}},"equivocations":[],"invalid_events":[],"applied_event_ids":["sha256:9b6d74e0eb5e5e1ec1a49efefafd9f368fc1558576925fbad2547fbba8cd0f01","sha256:92eb418a6003554432700032755c560f233eb0065b389b87faa88326f367e2ce"],"state_sha256":"6ca5783dd0210788e9110de745e16a6b8f5795685690a1986c9cb0a9625b6c1e"},"bundle_signature":{"signature_status":"signed_v1","algorithm":"ed25519","key_id":"pith-v1-2026-05","public_key_fingerprint":"8d4b5ee74e4693bcd1df2446408b0d54","signature_b64":"+nwBuy8Ps8Pd866vDBPZ2PJzjk8EzuL18lDqa/zt1vzUZ6806sv95aZfC/ocP62Z9yJlHmiBahOt2RWR/R6dBQ==","signed_message":"bundle_sha256_bytes","signed_at":"2026-08-08T11:49:16.263975Z","bundle_sha256":"17cd97df9b7bd76d1b24d930155eb9de345c30dbd3ad38000f972647b1ca81e1"}}