{
  "schema_version": "chamgap-public-rob2-assessment-1.0",
  "id": "RENEWAL-day6-N50-RoB2-preliminary-2026-09-29",
  "result_id": "RENEWAL-reported-whole-blood-NAD-day6",
  "source_snapshot_date": "2026-09-29",
  "public_source_url": "https://chamgap.com/reviews/422/s3/",
  "status": "preliminary_ai_not_independently_reviewed",
  "status_label": {
    "ko": "AI 기반 예비 평가 · 독립 전문가 검토 없음",
    "en": "Preliminary AI assessment · no independent expert review"
  },
  "review_method": {
    "ko": "별도 AI의 추출·예비 평가 이후, 보존된 논문·등록자료·공식 질문과 분기표를 대조한 평가 기록입니다. 두 외부 전문가의 독립 평가가 아닙니다.",
    "en": "The frozen record combines a separate AI extraction and preliminary assessment with checking against the preserved paper, registry, and official questions and decision tables. It is not independent review by two external experts."
  },
  "presentation_note": {
    "ko": "질문 제목은 공식 질문의 짧은 자체 요약이며 공식 번역이나 직접 인용이 아닙니다. 답·알고리즘·판단은 보존된 평가와 동일합니다. 한국어 원래 사유도 별도 필드에 남겼습니다.",
    "en": "Question labels are short original summaries, not official translations or quotations. Answers, algorithms, and judgements match the frozen assessment. Original Korean reasons are retained in separate fields."
  },
  "effect_of_interest": "assignment_to_intervention",
  "analysis": {
    "ko": "보고된 주분석 50명, MMRM, Day 6 전혈 총 NAD, 위약 대비 53.0% 추정 결과",
    "en": "Reported primary analysis of 50 participants, MMRM, Day 6 whole-blood total NAD, estimated 53.0% contrast versus placebo"
  },
  "scope": {
    "analysis_n": 50,
    "timepoint": "Day 6",
    "outcome": {
      "ko": "전혈 총 NAD",
      "en": "Whole-blood total NAD"
    },
    "original_claim_id": 422,
    "original_claim_s3": null,
    "original_claim_status": "not_transferable",
    "transfer_note": {
      "ko": "리포솜 NAD+의 세포 에너지·미토콘드리아 활력이라는 원 주장에는 적용할 수 없습니다. 원 주장 S3는 null입니다.",
      "en": "This cannot be transferred to the original claim about liposomal NAD+, cellular energy, and mitochondrial vitality. The original claim's S3 remains null."
    }
  },
  "tool": {
    "name": "RoB 2 individually randomized parallel trial, 2019-08-22",
    "url": "https://www.riskofbias.info/welcome/rob-2-0-tool/current-version-of-rob-2",
    "guidance_url": "https://drive.google.com/file/d/19R9savfPdCHC8XLz2iiMvL_71lPJERWK/view"
  },
  "answer_legend": {
    "Y": {
      "ko": "예",
      "en": "Yes"
    },
    "PY": {
      "ko": "아마 예",
      "en": "Probably yes"
    },
    "PN": {
      "ko": "아마 아니오",
      "en": "Probably no"
    },
    "N": {
      "ko": "아니오",
      "en": "No"
    },
    "NI": {
      "ko": "정보 없음",
      "en": "No information"
    },
    "NA": {
      "ko": "질문 흐름상 해당 없음",
      "en": "Not applicable in this question flow"
    }
  },
  "judgement_legend": {
    "low": {
      "ko": "낮은 편향 위험",
      "en": "Low risk of bias"
    },
    "some": {
      "ko": "일부 우려",
      "en": "Some concerns"
    },
    "high": {
      "ko": "높은 편향 위험",
      "en": "High risk of bias"
    }
  },
  "question_count": 22,
  "domains": [
    {
      "id": "D1",
      "label": {
        "ko": "무작위배정",
        "en": "Randomization"
      },
      "algorithm": "some",
      "judgement": "some",
      "override": false,
      "tool_pages": "17–20, Table4",
      "change_trigger": {
        "ko": "배정 은폐와 접근 권한, 60명 전원의 군별 기초특성 자료",
        "en": "Allocation concealment and access records, plus baseline data by group for all 60 randomized participants."
      },
      "recorded_change_trigger_ko": "배정 은폐/접근/60명 군별 기초특성 자료",
      "questions": [
        {
          "id": "1.1",
          "question": {
            "ko": "배정 순서에 무작위 요소가 있었나?",
            "en": "Random element in allocation order?"
          },
          "question_text_status": "plain_language_summary_not_official_translation",
          "answer": "Y",
          "reason": {
            "ko": "성별 층화, 가변 블록, blockrand를 이용한 무작위 순서 생성이 보고되어 있습니다.",
            "en": "The report describes sex-stratified variable blocks and random sequence generation using blockrand."
          },
          "recorded_reason_ko": "성별 층화·가변 블록·blockrand 무작위 생성 보고",
          "source_locator": {
            "paper_section": "Methods / Study design, randomization, and intervention",
            "record_location": "Sex-stratified blocked allocation, replacement of pre-screening losses, and participant flow from 60 randomized to 51 dosed with follow-up sampling.",
            "tool_table": "RoB 2 (22 August 2019), Table 4; signalling question 1.1; guidance pp. 17–20"
          },
          "source_urls": [
            "https://link.springer.com/article/10.1007/s11357-026-02399-1",
            "https://drive.google.com/file/d/19R9savfPdCHC8XLz2iiMvL_71lPJERWK/view"
          ]
        },
        {
          "id": "1.2",
          "question": {
            "ko": "등록과 배정 전까지 다음 배정이 가려져 있었나?",
            "en": "Upcoming allocation concealed until enrolment and assignment?"
          },
          "question_text_status": "plain_language_summary_not_official_translation",
          "answer": "NI",
          "reason": {
            "ko": "등록 전 배정목록 접근 권한과 은폐 절차의 세부는 확인하지 못했습니다. 불투명 용기만으로 순번 관리나 되돌릴 수 없는 배정을 추론하지 않았습니다.",
            "en": "Pre-enrolment access to the allocation list and details of concealment were not established. Opaque containers alone were not taken as evidence of sequential numbering or irreversible assignment."
          },
          "recorded_reason_ko": "등록 전 배정목록 접근·은폐 절차 세부 미확인. 불투명 용기만으로 순번·불가역배정을 추론하지 않음",
          "source_locator": {
            "paper_section": "Methods / Study design, randomization, and intervention",
            "record_location": "Sex-stratified blocked allocation, replacement of pre-screening losses, and participant flow from 60 randomized to 51 dosed with follow-up sampling. Opaque masked bottles and the LNAD/PEG and placebo formulations.",
            "tool_table": "RoB 2 (22 August 2019), Table 4; signalling question 1.2; guidance pp. 17–20"
          },
          "source_urls": [
            "https://link.springer.com/article/10.1007/s11357-026-02399-1",
            "https://drive.google.com/file/d/19R9savfPdCHC8XLz2iiMvL_71lPJERWK/view"
          ]
        },
        {
          "id": "1.3",
          "question": {
            "ko": "시작 시점의 군 간 차이가 무작위배정 문제를 시사하나?",
            "en": "Baseline imbalances suggesting flawed randomization?"
          },
          "question_text_status": "plain_language_summary_not_official_translation",
          "answer": "NI",
          "reason": {
            "ko": "분석 표본에서 기저 차이가 없었다는 보고는 있습니다. 그러나 배정된 60명 전원의 군별 자료와 예정 배정비 대조는 확보하지 못했습니다.",
            "en": "The authors report no baseline differences in the analysed sample. Comparisons covering all 60 randomized participants and the intended allocation ratio were not available."
          },
          "recorded_reason_ko": "분석표본 기저차이 없다는 보고는 있음. 배정된60명 전원의 비교 자료와 배정비 대조 미확보",
          "source_locator": {
            "paper_section": "Methods / Study design, randomization, and intervention; Results / Sample demographics; Table 1",
            "record_location": "Sex-stratified blocked allocation, replacement of pre-screening losses, and participant flow from 60 randomized to 51 dosed with follow-up sampling. Reported baseline comparisons for the analysed sample.",
            "tool_table": "RoB 2 (22 August 2019), Table 4; signalling question 1.3; guidance pp. 17–20"
          },
          "source_urls": [
            "https://link.springer.com/article/10.1007/s11357-026-02399-1",
            "https://drive.google.com/file/d/19R9savfPdCHC8XLz2iiMvL_71lPJERWK/view"
          ]
        }
      ]
    },
    {
      "id": "D2",
      "label": {
        "ko": "의도한 개입 이탈·분석",
        "en": "Deviations and assignment-effect analysis"
      },
      "algorithm": "high",
      "judgement": "high",
      "override": false,
      "tool_pages": "28–32, Table6",
      "change_trigger": {
        "ko": "51명·50명 결과 원표, 제외 대상자의 사전자격, 제외가 수치에 미친 영향",
        "en": "Original N=51 and N=50 result tables, prior eligibility of the excluded participant, and the numerical impact of exclusion."
      },
      "recorded_change_trigger_ko": "N51/N50 결과 원표와 제외 대상 사전자격·수치 영향",
      "questions": [
        {
          "id": "2.1",
          "question": {
            "ko": "참여자가 자신에게 배정된 개입을 알고 있었나?",
            "en": "Participants knew their allocation?"
          },
          "question_text_status": "plain_language_summary_not_official_translation",
          "answer": "PN",
          "reason": {
            "ko": "참여자 눈가림과 가린 용기가 보고되어 있습니다. 눈가림 유지 여부를 독립적으로 확인했다는 뜻은 아닙니다.",
            "en": "Participant blinding and masked containers are reported. This does not establish that maintenance of blinding was independently verified."
          },
          "recorded_reason_ko": "참여자 눈가림과 가린 용기 보고. 유지가 독립확인됐다는 뜻은 아님",
          "source_locator": {
            "paper_section": "Methods / Study design, randomization, and intervention",
            "record_location": "Trial design, blinding, registration timing and reported pre-unblinding specification of endpoints. Opaque masked bottles and the LNAD/PEG and placebo formulations. ClinicalTrials.gov: protocolSection.designModule.designInfo.maskingInfo, including its masking description.",
            "tool_table": "RoB 2 (22 August 2019), Table 6; signalling question 2.1; guidance pp. 28–32"
          },
          "source_urls": [
            "https://link.springer.com/article/10.1007/s11357-026-02399-1",
            "https://clinicaltrials.gov/study/NCT07336836",
            "https://drive.google.com/file/d/19R9savfPdCHC8XLz2iiMvL_71lPJERWK/view"
          ]
        },
        {
          "id": "2.2",
          "question": {
            "ko": "돌봄·개입 제공자가 참여자의 배정을 알고 있었나?",
            "en": "Carers or intervention providers knew allocation?"
          },
          "question_text_status": "plain_language_summary_not_official_translation",
          "answer": "PN",
          "reason": {
            "ko": "연구 인력과 개입 제공자의 눈가림이 보고되어 있습니다.",
            "en": "Blinding of study personnel and intervention providers is reported."
          },
          "recorded_reason_ko": "연구인력/개입 제공자 눈가림 보고",
          "source_locator": {
            "paper_section": "Methods / Study design, randomization, and intervention",
            "record_location": "Trial design, blinding, registration timing and reported pre-unblinding specification of endpoints. ClinicalTrials.gov: protocolSection.designModule.designInfo.maskingInfo, including its masking description.",
            "tool_table": "RoB 2 (22 August 2019), Table 6; signalling question 2.2; guidance pp. 28–32"
          },
          "source_urls": [
            "https://link.springer.com/article/10.1007/s11357-026-02399-1",
            "https://clinicaltrials.gov/study/NCT07336836",
            "https://drive.google.com/file/d/19R9savfPdCHC8XLz2iiMvL_71lPJERWK/view"
          ]
        },
        {
          "id": "2.3",
          "question": {
            "ko": "시험 상황 때문에 계획된 개입에서 이탈했나?",
            "en": "Deviations caused by the trial setting?"
          },
          "question_text_status": "plain_language_summary_not_official_translation",
          "answer": "NA",
          "reason": {
            "ko": "2.1과 2.2가 모두 PN이므로 공식 질문 흐름에서 이 분기로 진입하지 않습니다.",
            "en": "Both 2.1 and 2.2 are PN, so the official question flow does not enter this branch."
          },
          "recorded_reason_ko": "2.1/2.2 모두PN의 분기",
          "source_locator": {
            "paper_section": null,
            "record_location": "Official RoB 2 question flow and decision table for question 2.3.",
            "tool_table": "RoB 2 (22 August 2019), Table 6; signalling question 2.3; guidance pp. 28–32"
          },
          "source_urls": [
            "https://drive.google.com/file/d/19R9savfPdCHC8XLz2iiMvL_71lPJERWK/view"
          ]
        },
        {
          "id": "2.4",
          "question": {
            "ko": "그 이탈이 결과에 영향을 줄 가능성이 컸나?",
            "en": "Deviations likely to affect the outcome?"
          },
          "question_text_status": "plain_language_summary_not_official_translation",
          "answer": "NA",
          "reason": {
            "ko": "2.3 분기로 진입하지 않아 적용하지 않습니다.",
            "en": "Not applicable because the 2.3 branch was not entered."
          },
          "recorded_reason_ko": "2.3 분기 미진입",
          "source_locator": {
            "paper_section": null,
            "record_location": "Official RoB 2 question flow and decision table for question 2.4.",
            "tool_table": "RoB 2 (22 August 2019), Table 6; signalling question 2.4; guidance pp. 28–32"
          },
          "source_urls": [
            "https://drive.google.com/file/d/19R9savfPdCHC8XLz2iiMvL_71lPJERWK/view"
          ]
        },
        {
          "id": "2.5",
          "question": {
            "ko": "그 이탈이 두 군에서 균형 있게 발생했나?",
            "en": "Deviations balanced between groups?"
          },
          "question_text_status": "plain_language_summary_not_official_translation",
          "answer": "NA",
          "reason": {
            "ko": "2.3 분기로 진입하지 않아 적용하지 않습니다.",
            "en": "Not applicable because the 2.3 branch was not entered."
          },
          "recorded_reason_ko": "2.3 분기 미진입",
          "source_locator": {
            "paper_section": null,
            "record_location": "Official RoB 2 question flow and decision table for question 2.5.",
            "tool_table": "RoB 2 (22 August 2019), Table 6; signalling question 2.5; guidance pp. 28–32"
          },
          "source_urls": [
            "https://drive.google.com/file/d/19R9savfPdCHC8XLz2iiMvL_71lPJERWK/view"
          ]
        },
        {
          "id": "2.6",
          "question": {
            "ko": "배정 효과를 추정하기에 분석 방법이 적절했나?",
            "en": "Analysis suitable for the effect of assignment?"
          },
          "question_text_status": "plain_language_summary_not_official_translation",
          "answer": "PN",
          "reason": {
            "ko": "관측값이 있는 위약군 1명을 눈가림 해제 뒤 제외했습니다. 배정 효과에 적절한 분석으로 확정하기 어렵고, 미자격자의 허용된 배정 후 제외 요건도 확인하지 못했습니다.",
            "en": "One placebo participant with observed outcome data was excluded after unblinding. Suitability for estimating assignment effects was not established, nor were the conditions permitting post-randomization exclusion of an ineligible participant."
          },
          "recorded_reason_ko": "관측값이 있는 위약1명을 눈가림 해제 뒤 제외. 배정효과에 적절한 분석으로 확정하기 어려움. 미자격자의 허용된 배정후제외 요건도 미확인",
          "source_locator": {
            "paper_section": "Methods / Statistical analyses",
            "record_location": "N=51 and N=50 analysis sets, exclusion after unblinding, and the authors' comparison referring to Supplementary Figure 2.",
            "tool_table": "RoB 2 (22 August 2019), Table 6; signalling question 2.6; guidance pp. 28–32"
          },
          "source_urls": [
            "https://link.springer.com/article/10.1007/s11357-026-02399-1",
            "https://drive.google.com/file/d/19R9savfPdCHC8XLz2iiMvL_71lPJERWK/view"
          ]
        },
        {
          "id": "2.7",
          "question": {
            "ko": "배정군대로 분석하지 않은 일이 결과를 크게 바꿀 수 있나?",
            "en": "Potentially important impact of departures from randomized-group analysis?"
          },
          "question_text_status": "plain_language_summary_not_official_translation",
          "answer": "NI",
          "reason": {
            "ko": "51명과 50명 분석의 유사성은 저자의 보고이며 정확한 수치는 확보하지 못했습니다. 제외 비율이 작더라도 관측 결과와 관련된 제외의 실질적 영향이 작다고 확정하지 않았습니다.",
            "en": "Similarity between the N=51 and N=50 analyses is reported by the authors; exact estimates were not available. A small exclusion proportion was not considered sufficient to establish a small impact when exclusion was related to observed outcomes."
          },
          "recorded_reason_ko": "N51/N50 결과 유사성은 저자 보고이며 정확 수치 미확보. 작은 비율이라도 관측결과와 관련된 제외의 실질 영향이 작다고 확정하지 않음",
          "source_locator": {
            "paper_section": "Methods / Statistical analyses; Discussion / Limitations",
            "record_location": "N=51 and N=50 analysis sets, exclusion after unblinding, and the authors' comparison referring to Supplementary Figure 2. Authors' claim of robustness across analysis sets and methods.",
            "tool_table": "RoB 2 (22 August 2019), Table 6; signalling question 2.7; guidance pp. 28–32"
          },
          "source_urls": [
            "https://link.springer.com/article/10.1007/s11357-026-02399-1",
            "https://drive.google.com/file/d/19R9savfPdCHC8XLz2iiMvL_71lPJERWK/view"
          ]
        }
      ]
    },
    {
      "id": "D3",
      "label": {
        "ko": "결과 결측",
        "en": "Missing outcome data"
      },
      "algorithm": "high",
      "judgement": "high",
      "override": false,
      "tool_pages": "40–47, 특히 Table10 p47",
      "change_trigger": {
        "ko": "60명의 군별 Day 6 관측 상태·탈락 사유·결측 가정 민감도. 관측값이 있는 제외라면 D2에서 다룹니다.",
        "en": "Day 6 observation status and dropout reasons by group for all 60, with sensitivity analyses of missingness assumptions. Exclusion despite observed data belongs in D2."
      },
      "recorded_change_trigger_ko": "60명 군별Day6 관측/탈락 사유·결측가정 민감도. 관측값이 있는 제외라면D2로재분류",
      "questions": [
        {
          "id": "3.1",
          "question": {
            "ko": "배정된 거의 모든 참여자의 해당 결과를 확보했나?",
            "en": "Outcome availability across the randomized population?"
          },
          "question_text_status": "plain_language_summary_not_official_translation",
          "answer": "PN",
          "reason": {
            "ko": "60명이 배정되었고, 51명이 투여 및 최소 1회 추적 채혈 조건을 충족했습니다. Day 6 결과가 거의 전원에서 확보되었다는 근거는 부족합니다. 나머지 9명 전원을 확정 결측으로 계산한 것은 아닙니다.",
            "en": "Of 60 randomized participants, 51 met the dosing and at-least-one follow-up blood-draw criteria. Availability of Day 6 outcomes for nearly everyone was not established. All remaining nine participants were not assumed to have confirmed missing outcomes."
          },
          "recorded_reason_ko": "60명배정→51명투여/최소1회추적채혈 충족. Day6 결과가 거의 전원에서 확보됐다는 근거 부족. 나머지9명 전원을 확정 결측으로 계산한 것은 아님",
          "source_locator": {
            "paper_section": "Methods / Study design, randomization, and intervention; Methods / Statistical analyses; Results / Primary endpoints: intracellular and circulating NAD+; Figure 1 caption",
            "record_location": "Sex-stratified blocked allocation, replacement of pre-screening losses, and participant flow from 60 randomized to 51 dosed with follow-up sampling. N=51 and N=50 analysis sets, exclusion after unblinding, and the authors' comparison referring to Supplementary Figure 2. Displayed primary-analysis sample sizes and baseline, Day 4 and Day 6 measurements.",
            "tool_table": "RoB 2 (22 August 2019), Table 10; signalling question 3.1; guidance pp. 40–47"
          },
          "source_urls": [
            "https://link.springer.com/article/10.1007/s11357-026-02399-1",
            "https://drive.google.com/file/d/19R9savfPdCHC8XLz2iiMvL_71lPJERWK/view"
          ]
        },
        {
          "id": "3.2",
          "question": {
            "ko": "결측이 결과를 왜곡하지 않았다는 근거가 있나?",
            "en": "Evidence against distortion from missing outcomes?"
          },
          "question_text_status": "plain_language_summary_not_official_translation",
          "answer": "PN",
          "reason": {
            "ko": "MAR 가정의 MMRM은 특정 가정에 따른 분석입니다. 60명에서 51명으로 줄어든 누락에 대해 다른 합리적 가정에서도 강건하다는 자료를 확인하지 못했습니다. 51명과 50명 비교는 별도의 1명 제외 문제입니다.",
            "en": "MMRM under a missing-at-random assumption depends on that assumption. Robustness to other plausible missingness assumptions for the reduction from 60 to 51 participants was not established. The N=51 versus N=50 comparison addresses a separate one-person exclusion."
          },
          "recorded_reason_ko": "MAR 기반MMRM은 특정가정하 분석.60→51의누락에 대해 관계가 다른 합리적가정에도 강건하다는 자료를 확인하지 못함.51/50 비교는 별도1명제외 문제",
          "source_locator": {
            "paper_section": "Methods / Statistical analyses; Methods / Changes to trial protocol-statistical analysis plan",
            "record_location": "MMRM implementation and the missing-at-random assumption. N=51 and N=50 analysis sets, exclusion after unblinding, and the authors' comparison referring to Supplementary Figure 2. Authors' claim of robustness across analysis frameworks.",
            "tool_table": "RoB 2 (22 August 2019), Table 10; signalling question 3.2; guidance pp. 40–47"
          },
          "source_urls": [
            "https://link.springer.com/article/10.1007/s11357-026-02399-1",
            "https://drive.google.com/file/d/19R9savfPdCHC8XLz2iiMvL_71lPJERWK/view"
          ]
        },
        {
          "id": "3.3",
          "question": {
            "ko": "실제 결과값이 결측 발생과 관련될 수 있나?",
            "en": "Possible link between outcome values and missingness?"
          },
          "question_text_status": "plain_language_summary_not_official_translation",
          "answer": "NI",
          "reason": {
            "ko": "60명에서 51명으로 줄어든 군별 사유와 Day 6 관측 상태가 없어, 실제 NAD 값과 누락이 관련 없다고 추론할 근거가 부족합니다.",
            "en": "Group-specific reasons for the reduction from 60 to 51 and Day 6 observation status were unavailable, leaving insufficient grounds to infer that missingness was unrelated to actual NAD values."
          },
          "recorded_reason_ko": "60→51 군별사유·Day6 관측상태가 없어 실제NAD값과누락이관계없다고 추론할근거부족",
          "source_locator": {
            "paper_section": "Methods / Study design, randomization, and intervention",
            "record_location": "Sex-stratified blocked allocation, replacement of pre-screening losses, and participant flow from 60 randomized to 51 dosed with follow-up sampling.",
            "tool_table": "RoB 2 (22 August 2019), Table 10; signalling question 3.3; guidance pp. 40–47"
          },
          "source_urls": [
            "https://link.springer.com/article/10.1007/s11357-026-02399-1",
            "https://drive.google.com/file/d/19R9savfPdCHC8XLz2iiMvL_71lPJERWK/view"
          ]
        },
        {
          "id": "3.4",
          "question": {
            "ko": "실제 결과값과 결측이 관련되었을 가능성이 큰가?",
            "en": "Likely link between outcome values and missingness?"
          },
          "question_text_status": "plain_language_summary_not_official_translation",
          "answer": "NI",
          "reason": {
            "ko": "군별 누락 비율, 사유, 결과와의 관련성 자료를 확보하지 못했습니다. 관련성이 실제로 관측되었다고 판단한 것은 아닙니다.",
            "en": "Group-specific missingness proportions, reasons, and evidence about outcome dependence were unavailable. The assessment does not claim that such a relationship was observed."
          },
          "recorded_reason_ko": "군별누락비율/사유·관련성자료 미확보. 관계있음을관측했다고쓰기않음",
          "source_locator": {
            "paper_section": "Methods / Study design, randomization, and intervention",
            "record_location": "Sex-stratified blocked allocation, replacement of pre-screening losses, and participant flow from 60 randomized to 51 dosed with follow-up sampling.",
            "tool_table": "RoB 2 (22 August 2019), Table 10; signalling question 3.4; guidance pp. 40–47"
          },
          "source_urls": [
            "https://link.springer.com/article/10.1007/s11357-026-02399-1",
            "https://drive.google.com/file/d/19R9savfPdCHC8XLz2iiMvL_71lPJERWK/view"
          ]
        }
      ]
    },
    {
      "id": "D4",
      "label": {
        "ko": "결과 측정",
        "en": "Outcome measurement"
      },
      "algorithm": "low",
      "judgement": "low",
      "override": false,
      "tool_pages": "54–57, Table12",
      "change_trigger": {
        "ko": "군별 검사 절차·눈가림·측정 타당도 결함의 확인. 활력의 대리 지표인지 불분명하다는 이유만으로 D4를 high로 바꾸지 않습니다.",
        "en": "Evidence about group-specific assay procedures, blinding, or measurement-validity defects. Uncertain surrogacy for vitality alone does not change D4 to high."
      },
      "recorded_change_trigger_ko": "검사군별절차/눈가림/타당도결함확인.활력대리성부족만으로D4를high로바꾸지않음",
      "questions": [
        {
          "id": "4.1",
          "question": {
            "ko": "그 결과를 측정하는 방법이 부적절했나?",
            "en": "Measurement unsuitable for the specified outcome?"
          },
          "question_text_status": "plain_language_summary_not_official_translation",
          "answer": "PN",
          "reason": {
            "ko": "전혈 총 NAD라는 측정 목적에 맞춘 검사와 중복 측정 정밀도가 보고되어 있습니다. 이를 미토콘드리아 기능의 대리 지표로 사용할 수 있는지는 별도의 연결 문제입니다.",
            "en": "The report describes an assay for whole-blood total NAD and duplicate-measurement precision. Whether it is a valid surrogate for mitochondrial function is a separate transferability question."
          },
          "recorded_reason_ko": "전혈 총NAD라는 측정목적의검사/중복정밀도보고. 미토콘드리아기능의대리성은 별도연결관문",
          "source_locator": {
            "paper_section": "Methods / Primary endpoints: intracellular and circulating NAD+",
            "record_location": "Laboratory and whole-blood versus plasma assay descriptions. Assay procedure, total-NAD measurement and duplicate-measurement precision.",
            "tool_table": "RoB 2 (22 August 2019), Table 12; signalling question 4.1; guidance pp. 54–57"
          },
          "source_urls": [
            "https://link.springer.com/article/10.1007/s11357-026-02399-1",
            "https://drive.google.com/file/d/19R9savfPdCHC8XLz2iiMvL_71lPJERWK/view"
          ]
        },
        {
          "id": "4.2",
          "question": {
            "ko": "결과 측정이나 확인 방식이 군별로 달랐을 수 있나?",
            "en": "Potential differences in outcome measurement between groups?"
          },
          "question_text_status": "plain_language_summary_not_official_translation",
          "answer": "PN",
          "reason": {
            "ko": "동일한 채혈·운송·검사 절차가 보고되어 있습니다. 군별 검사 방식이 달랐다는 근거는 확인하지 못했습니다.",
            "en": "Common blood collection, transport, and assay procedures are reported. Evidence of different testing procedures between groups was not identified."
          },
          "recorded_reason_ko": "같은채혈·운송·검사절차보고.군별상이한검사증거미확인",
          "source_locator": {
            "paper_section": "Methods / Blood collection; Methods / Primary endpoints: intracellular and circulating NAD+",
            "record_location": "Collection, cold-chain transport and scheduled blood-sampling visits. Heading introducing NAD measurement methods. Laboratory and whole-blood versus plasma assay descriptions. Assay procedure, total-NAD measurement and duplicate-measurement precision.",
            "tool_table": "RoB 2 (22 August 2019), Table 12; signalling question 4.2; guidance pp. 54–57"
          },
          "source_urls": [
            "https://link.springer.com/article/10.1007/s11357-026-02399-1",
            "https://drive.google.com/file/d/19R9savfPdCHC8XLz2iiMvL_71lPJERWK/view"
          ]
        },
        {
          "id": "4.3",
          "question": {
            "ko": "결과 평가자가 참여자의 개입을 알고 있었나?",
            "en": "Assessors knew which intervention participants received?"
          },
          "question_text_status": "plain_language_summary_not_official_translation",
          "answer": "PN",
          "reason": {
            "ko": "등록부에 보고된 평가자와 분자검사 시설의 눈가림을 근거로 잠정 추론했습니다.",
            "en": "This is a provisional inference from the registry's report of blinding for assessors and the molecular testing facility."
          },
          "recorded_reason_ko": "등록부의평가자·분자검사시설눈가림보고를근거로잠정추론",
          "source_locator": {
            "paper_section": null,
            "record_location": "ClinicalTrials.gov: protocolSection.designModule.designInfo.maskingInfo, including its masking description.",
            "tool_table": "RoB 2 (22 August 2019), Table 12; signalling question 4.3; guidance pp. 54–57"
          },
          "source_urls": [
            "https://clinicaltrials.gov/study/NCT07336836",
            "https://drive.google.com/file/d/19R9savfPdCHC8XLz2iiMvL_71lPJERWK/view"
          ]
        },
        {
          "id": "4.4",
          "question": {
            "ko": "그 지식이 결과 평가에 영향을 줄 수 있나?",
            "en": "Could that knowledge affect assessment?"
          },
          "question_text_status": "plain_language_summary_not_official_translation",
          "answer": "NA",
          "reason": {
            "ko": "4.3이 PN이므로 공식 질문 흐름에서 이 분기로 진입하지 않습니다.",
            "en": "The official question flow does not enter this branch because 4.3 is PN."
          },
          "recorded_reason_ko": "4.3 PN 분기",
          "source_locator": {
            "paper_section": null,
            "record_location": "Official RoB 2 question flow and decision table for question 4.4.",
            "tool_table": "RoB 2 (22 August 2019), Table 12; signalling question 4.4; guidance pp. 54–57"
          },
          "source_urls": [
            "https://drive.google.com/file/d/19R9savfPdCHC8XLz2iiMvL_71lPJERWK/view"
          ]
        },
        {
          "id": "4.5",
          "question": {
            "ko": "그 지식이 실제 평가에 영향을 주었을 가능성이 큰가?",
            "en": "Was such influence on assessment likely?"
          },
          "question_text_status": "plain_language_summary_not_official_translation",
          "answer": "NA",
          "reason": {
            "ko": "4.4 분기로 진입하지 않아 적용하지 않습니다.",
            "en": "Not applicable because the 4.4 branch was not entered."
          },
          "recorded_reason_ko": "4.4 분기 미진입",
          "source_locator": {
            "paper_section": null,
            "record_location": "Official RoB 2 question flow and decision table for question 4.5.",
            "tool_table": "RoB 2 (22 August 2019), Table 12; signalling question 4.5; guidance pp. 54–57"
          },
          "source_urls": [
            "https://drive.google.com/file/d/19R9savfPdCHC8XLz2iiMvL_71lPJERWK/view"
          ]
        }
      ]
    },
    {
      "id": "D5",
      "label": {
        "ko": "보고 결과 선택",
        "en": "Selection of the reported result"
      },
      "algorithm": "some",
      "judgement": "some",
      "override": false,
      "tool_pages": "63–67, Table14",
      "change_trigger": {
        "ko": "원 SAP, 날짜별 변경 기록, 예정 결과·분석과 실제 보고의 대조",
        "en": "The original SAP, dated amendments, and comparison of planned outcomes and analyses with those reported."
      },
      "recorded_change_trigger_ko": "원SAP·날짜별변경·실제예정결과/분석대조",
      "questions": [
        {
          "id": "5.1",
          "question": {
            "ko": "눈가림 해제 전 확정한 계획대로 이 결과를 분석했나?",
            "en": "Result analysed under a plan fixed before unblinding?"
          },
          "question_text_status": "plain_language_summary_not_official_translation",
          "answer": "PN",
          "reason": {
            "ko": "원 SAP가 사전에 정해졌다는 보고는 있으나, 50명 결과에는 눈가림 해제 후 제외가 포함됩니다. 변경 시점과 원 SAP를 확보하지 못해 해제 전 분석이 확정되었다는 요건을 인정하기 어렵습니다.",
            "en": "A pre-existing SAP is reported, but the N=50 result includes an exclusion after unblinding. The original SAP and timing of changes were unavailable, so finalization of the analysis before unblinding was not established."
          },
          "recorded_reason_ko": "원SAP사전보고가있지만50명결과는눈가림해제후제외를포함.변경시점/원SAP미확보로해제전고정분석충족을인정하기어려움",
          "source_locator": {
            "paper_section": "Methods / Study design, randomization, and intervention; Methods / Statistical analyses; Methods / Changes to trial protocol-statistical analysis plan",
            "record_location": "Trial design, blinding, registration timing and reported pre-unblinding specification of endpoints. N=51 and N=50 analysis sets, exclusion after unblinding, and the authors' comparison referring to Supplementary Figure 2. Reported January 2022 SAP and changes to blood sampling and visit windows. Change from mixed ANOVA/ANCOVA to MMRM. Change to two-sided tests and addition of bootstrap intervals. Authors' claim of robustness across analysis frameworks.",
            "tool_table": "RoB 2 (22 August 2019), Table 14; signalling question 5.1; guidance pp. 63–67"
          },
          "source_urls": [
            "https://link.springer.com/article/10.1007/s11357-026-02399-1",
            "https://drive.google.com/file/d/19R9savfPdCHC8XLz2iiMvL_71lPJERWK/view"
          ]
        },
        {
          "id": "5.2",
          "question": {
            "ko": "결과에 따라 보고할 측정·시점을 골랐을 가능성이 큰가?",
            "en": "Likely result-driven selection among eligible measurements or time points?"
          },
          "question_text_status": "plain_language_summary_not_official_translation",
          "answer": "NI",
          "reason": {
            "ko": "여러 시점과 결과 중 보고할 결과를 선택했는지 확정하지 못했습니다. 원래 계획을 확보하지 못했습니다.",
            "en": "Selection among multiple time points and outcome measurements could not be determined because the original plan was unavailable."
          },
          "recorded_reason_ko": "다중시점·결과에서선택했는지확정못함.원계획미확보",
          "source_locator": {
            "paper_section": "Methods / Changes to trial protocol-statistical analysis plan",
            "record_location": "Reported January 2022 SAP and changes to blood sampling and visit windows. Change from mixed ANOVA/ANCOVA to MMRM. Change to two-sided tests and addition of bootstrap intervals. Authors' claim of robustness across analysis frameworks. ClinicalTrials.gov: protocolSection.statusModule, including registration submission and first-posted dates.",
            "tool_table": "RoB 2 (22 August 2019), Table 14; signalling question 5.2; guidance pp. 63–67"
          },
          "source_urls": [
            "https://link.springer.com/article/10.1007/s11357-026-02399-1",
            "https://clinicaltrials.gov/study/NCT07336836",
            "https://drive.google.com/file/d/19R9savfPdCHC8XLz2iiMvL_71lPJERWK/view"
          ]
        },
        {
          "id": "5.3",
          "question": {
            "ko": "결과에 따라 보고할 분석을 골랐을 가능성이 큰가?",
            "en": "Likely result-driven selection among eligible analyses?"
          },
          "question_text_status": "plain_language_summary_not_official_translation",
          "answer": "NI",
          "reason": {
            "ko": "여러 분석 방법이 보고되었고 원 SAP는 확보하지 못했습니다. 유리한 결과를 골랐다는 사실을 입증한 것은 아닙니다.",
            "en": "Multiple analysis methods are reported and the original SAP was unavailable. This does not demonstrate selection of a favourable result."
          },
          "recorded_reason_ko": "여러분석방법보고와원SAP미확보.유리한결과선택을입증한것은아님",
          "source_locator": {
            "paper_section": "Methods / Statistical analyses; Methods / Changes to trial protocol-statistical analysis plan",
            "record_location": "N=51 and N=50 analysis sets, exclusion after unblinding, and the authors' comparison referring to Supplementary Figure 2. Reported January 2022 SAP and changes to blood sampling and visit windows. Change from mixed ANOVA/ANCOVA to MMRM. Change to two-sided tests and addition of bootstrap intervals. Authors' claim of robustness across analysis frameworks.",
            "tool_table": "RoB 2 (22 August 2019), Table 14; signalling question 5.3; guidance pp. 63–67"
          },
          "source_urls": [
            "https://link.springer.com/article/10.1007/s11357-026-02399-1",
            "https://drive.google.com/file/d/19R9savfPdCHC8XLz2iiMvL_71lPJERWK/view"
          ]
        }
      ]
    }
  ],
  "overall": {
    "algorithm": "high",
    "judgement": "high",
    "override": false,
    "tool_pages": "4, Table1",
    "bias_direction": "unpredictable",
    "reason": {
      "ko": "D3는 공식 질문 흐름에서 high이며, 보존된 D2 판단도 high입니다. 하나 이상의 영역이 high여서 전체도 high입니다. 이 판단은 실제 편향 발생, 효과 없음, 부정행위의 입증이 아닙니다.",
      "en": "D3 follows the official question flow to high, and the retained D2 judgement is also high. At least one high domain leads to overall high. This is not proof of actual bias, absence of an effect, or misconduct."
    },
    "recorded_reason_ko": "D3 high(공식 NI 기본분기), 주담당판정D2도high. 하나이상high이면overallhigh. 실제편향발생/효과없음/부정행위입증은아님",
    "interpretation": {
      "ko": "정보 없음(NI)을 일괄 high로 바꾸지 않았습니다. 질문별 경로를 적용했으며, 이 기록에서도 D1과 D5는 some입니다.",
      "en": "No blanket NI-to-high conversion was used. Question-specific routes were applied; D1 and D5 remain some concerns in this record."
    }
  },
  "disagreements": [
    {
      "domain_id": "D2",
      "question_id": "2.7",
      "retained_assessment": {
        "answer": "NI",
        "reason": {
          "ko": "51명과 50명 분석의 유사성은 저자의 보고이며 정확한 수치는 확보하지 못했습니다. 제외 비율이 작더라도 관측 결과와 관련된 제외의 실질적 영향이 작다고 확정하지 않았습니다.",
          "en": "Similarity between the N=51 and N=50 analyses is reported by the authors; exact estimates were not available. A small exclusion proportion was not considered sufficient to establish a small impact when exclusion was related to observed outcomes."
        }
      },
      "separate_ai_assessment": {
        "answer": "PN",
        "reason": {
          "ko": "저자의 51명·50명 결과 유사성 보고에 근거한 잠정 추론입니다.",
          "en": "A provisional inference based on the authors' report that N=51 and N=50 results were similar."
        }
      },
      "impact": {
        "ko": "D2는 some에서 high로 달라집니다. D3가 high여서 전체 판단은 바뀌지 않습니다. 두 응답을 모두 보존합니다.",
        "en": "D2 differs between some concerns and high. Overall remains high because D3 is high. Both responses are retained."
      },
      "recorded_reasons_ko": {
        "retained_assessment": "NI (관측값연관제외영향을정확수치없이작다고확정하지않음)",
        "separate_ai_assessment": "PN (저자51/50유사성보고에근거한잠정추론)",
        "impact": "D2 some→high. D3가high여서overall변경없음.불일치보존."
      },
      "independent_expert_review": false
    }
  ],
  "limits": [
    {
      "ko": "AI 기반 예비 판단이며 외부 전문가 심사가 아닙니다.",
      "en": "This is a preliminary AI-based assessment, not external expert review."
    },
    {
      "ko": "보충 원표와 원 SAP를 직접 확보하지 못했습니다.",
      "en": "Original supplementary result tables and the SAP were not directly available."
    },
    {
      "ko": "NI는 모든 영역에서 high로 변환되는 값이 아닙니다.",
      "en": "NI does not map to high risk in every domain."
    },
    {
      "ko": "판단은 보고된 50명 분석의 전혈 결과에 한정하며 원 주장으로 옮길 수 없습니다.",
      "en": "The assessment is confined to the reported N=50 whole-blood result and cannot be transferred to the original claim."
    },
    {
      "ko": "51명 민감도 분석이나 다른 분석의 RoB 판단에 자동 복제하지 않습니다.",
      "en": "Risk-of-bias judgements are not automatically copied to the N=51 sensitivity analysis or other analyses."
    }
  ],
  "recorded_limits_ko": [
    "AI 기반예비판단이며외부전문가심사아님",
    "보충원표/SAP 직접미확보",
    "NI는모든영역에서high로매핑되는것이아님",
    "현재판정은보고된N50혈액결과에한정.원주장으로이식불가",
    "N51민감도/다른분석결과의RoB를자동복제하지않음"
  ],
  "assessment_application": {
    "ko": "초기 미평가 기록은 보존하고, 별도 적용 기록의 핵심 분석에만 이 예비 overall high를 연결했습니다. 다른 미확인 입력은 유지했습니다.",
    "en": "The initial unassessed record was preserved. Only the core analysis in a separate application record received this preliminary overall-high judgement; other unknown inputs were retained."
  },
  "sources": {
    "paper": {
      "url": "https://link.springer.com/article/10.1007/s11357-026-02399-1",
      "doi": "10.1007/s11357-026-02399-1",
      "title": "Oral LNAD+ rapidly elevates whole blood intracellular NAD and metabolic flux without elevating plasma NAD: evidence from a randomized controlled trial",
      "snapshot_date": "2026-09-29",
      "snapshot_type": "previously_preserved_publisher_text",
      "sha256": "71bb84c2f10a6bc600b72f79834f155446613a87a3b948be1f55afe6b4d094f3"
    },
    "registry": {
      "url": "https://clinicaltrials.gov/study/NCT07336836",
      "identifier": "NCT07336836",
      "snapshot_date": "2026-09-29",
      "snapshot_type": "previously_preserved_registry_json",
      "sha256": "104d54ebc73a5d356ab8501dcfa5335fc958583c98d492637a81e2f2cf2e986f"
    },
    "guidance": {
      "url": "https://drive.google.com/file/d/19R9savfPdCHC8XLz2iiMvL_71lPJERWK/view",
      "tool_url": "https://www.riskofbias.info/welcome/rob-2-0-tool/current-version-of-rob-2",
      "version": "2019-08-22",
      "snapshot_date": "2026-09-29",
      "snapshot_type": "preserved_official_guidance_pdf",
      "sha256": "a9e9c4fdc4be2d29b5c0a1a6b828e09f2014a34f6d5c302a532f6153ea0fd670"
    },
    "assessment": {
      "id": "RENEWAL-day6-N50-RoB2-preliminary-2026-09-29",
      "snapshot_date": "2026-09-29",
      "sha256": "e8685ae05bae741901e5c54a4388272d205f5d44870e7df0e3f237253519e5ef"
    },
    "application_record": {
      "rule_version": "CG-S3-DECISION-0.3",
      "snapshot_date": "2026-09-29",
      "sha256": "0ac10447cd1abe2dfc0d59b6ad58b4d431f62fc8b2f939521f436e0c8df770f5"
    }
  },
  "preservation_note": {
    "ko": "날짜는 이 공개용 묶음의 기준일입니다. 기존 보존 자료를 재사용했으며 새 문헌 검색이나 재평가는 하지 않았습니다. 해시는 보존한 파일의 바이트를 식별할 뿐 정확성·시각 공증을 뜻하지 않습니다. 논문·지침 전문을 이 JSON에 재배포하지 않습니다.",
    "en": "Dates identify the reference date of this public package. Previously preserved materials were reused without a new literature search or reassessment. Hashes identify preserved bytes, not scientific accuracy or notarized timestamps. Full paper and guidance texts are not redistributed in this JSON."
  }
}