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1 2008 年 CDISC 日本グループワークショップ 4. Seminar 4.2 SDS 年 3 月 7 日マツダ八重洲通ビル 9F ホール 本日の内容 SDS-2グループ 2007 年度活動状況 SDS-2グループ検討のターゲット CDASHについて SDTM Terminologyについて CDASH Terminology SDTMの関連 課題と今後 古野小阪 松葉 JCG-Workshop SDS

2 本日の内容 SDS-2グループ 2007 年度活動状況 SDS-2グループ検討のターゲット CDASHについて SDTM Terminologyについて CDASH Terminology SDTMの関連 課題と今後 JCG-Workshop SDS 年度活動状況 2007 年 8 月 ~2008 年 2 月 : ミーティング開催状況 開催日 2007/8/9 2007/8/ /9/ /10/ /11/ /12/ /1/ /2/ /3/18 場所 アムジェン アムジェン アムジェン アムジェン 萬有 田辺三菱 田辺三菱 大日本住友 人数 8 名 6 名 9 名 7 名 9 名 9 名 8 名 9 名 内容 SDS-1-2 活動の方向性 (Preliminary Meeting) SDS-2 活動の具体的進め方 CDASH Terminology とは AE の検討 CM の検討 DM SC の検討 検討結果のまとめ / 今後 Workshop 発表内容の検討 CDASH Package2~4 JCG-Workshop SDS

3 本日の内容 SDS-2グループ 2007 年度活動状況 SDS-2グループ検討のターゲット CDASHについて SDTM Terminologyについて CDASH Terminology SDTMの関連 課題と今後 JCG-Workshop SDS 関連性 Terminology CDASH SDTM CDASH と Terminology がメイン Clinical Data Acquisition Standards Harmonization 上記を SDTM IG との関連から検討 JCG-Workshop SDS

4 本日の内容 SDS-2グループ 2007 年度活動状況 SDS-2グループ検討のターゲット CDASHについて SDTM Terminologyについて CDASH Terminology SDTMの関連 課題と今後 JCG-Workshop SDS 背景 Critical Path Opportunities List #45 (FDA)(2006) 45. Consensus on Standards for Case Report Forms. Clinical trial data collection, analysis, and submission can be inefficient and unnecessarily expensive. A wide array of different forms and formats are used to collect clinical trial information, and most data are submitted to the FDA on paper. Differences in case report forms across sponsors and trials creates opportunities for confusion and error. Standardization of the look and feel of case report forms could reduce these inefficiencies and also help accelerate progress toward electronic data capture and submission. JCG-Workshop SDS

5 背景 Critical Path Opportunities Initiated During 2006 (Opportunity #45) Private efforts to streamline clinical trial data collection through voluntary standardization of case report forms (CRFs) have recently been formalized under the auspices of the Clinical Data Acquisition Standards Harmonization (CDASH) Initiative. Catalyzed by the Clinical Data Interchange Standards Consortium and the Association of Contract Research Organizations, dozens of product sponsors, investigators, data managers and other stakeholders are working together to agree on a core set of data collection fields to support clinical research studies. FDA is providing input on issues as requested. The CDASH process is open to any participant and will include a public comment process (see JCG-Workshop SDS 含まれる SDTM ドメイン The initial scope will be the safety data/domains. These safety domains cut across all therapeutic areas, beginning with approximately domains. Package-1 Adverse Events(AE), Concomitant Medication(CM), Demographics(DM) & Subject Characteristics(SC) Package-2 Package-3 Package-4 Inclusion/Exclusion Criteria(IE), Medical History(MH) & Substance Use(SU), Physical Exam(PE) & Vital Signs(VS) Drug Accountability(DA) & Exposure(EX), Comments(CO) & Deviations(DV), Disposition/End of Study(DS) Lab(LB) & ECG(EG) JCG-Workshop SDS

6 開発手順 Follow CDISC Operating Procedure for Standards Development (COP-001). Stage I: Standard Definition/Approval Multidisciplinary Team Stage II: Standards Development-Consensus Model Stage III: Education & Support Stage IV: Standards Update & Maintenance Consensus (Initial) Version TLC Review Harmonized Version OK Testing Comments addressed Ex Focused Review O K Review Version Public Review Released (Production) Version 1.0 Comments to address by team CDASH では Collaborative Group Review JCG-Workshop SDS 開発手順 Collaborative Group Members American Medical Informatics Association (AMIA) Association of Clinical Research Organizations (ACRO) Association of Clinical Research Professionals (ACRP) Baylor College of Medicine Biotechnology Industry Organization (BIO) Clinical Data Interchange Standards Consortium (CDISC) Clinical Research Forum Critical Path Institute Duke Clinical Research Institute (DCRI) Food and Drug Administration (FDA) National Institutes of Health (NIH) NCI-EVS NCI-caBIG Clinical Research Policy Analysis & Coordination Program National Clinical Research Resources (NCRR) National Institute of Child Health & Human Development (NICHD) Pharmaceutical Research and Manufacturers Association (PhRMA) Society for Clinical Data Management (SCDM) JCG-Workshop SDS

7 開発コンセプト To develop a set of content standards (element name, definition, metadata) for a basic set of global industrywide data collection fields that support clinical research. CRF Data Collection Variable(CRFの項目名 ) SDTM Variable Name(SDTM 変数名 ) Definition( 定義 / 内容 ) CDISC Approved Controlled Terminology( 使用されるされる用語 ) Applicable Regulations( 適用されるされる法規制等 ) Instruction to Clinical Site( 記入指示 ) Implementation / Rationale( 実装上の留意点留意点や理由 ) JCG-Workshop SDS 項目設定に関する方針 Guiding principles:variables should Ensure that SDTM required elements are addressed directly or indirectly Be standard but flexible to allow customization within defined limits Limit variables to required and necessary Comply with regulatory requirements Reduce redundancies Increase collection of meaningful data Facilitate use of standards by all users Be appropriate for use both pre and post approval studies Allow consistent and efficient data collection/ storage/ transmission and analysis JCG-Workshop SDS

8 作成手順 - 項目設定まで - CDASH: Getting Started Start with Study Data Tabulated Model (SDTM) Data Variable Tables Refer to ACRO CRF Samples (where available) Initial Focus on CRF Content, not CRF Layout Collect CRF samples Evaluate commonalities/differences of CRF samples and SDTM Document data points included/excluded with justifications JCG-Workshop SDS 参考 :ACRO とは ACRO(Association of Clinical Research Organizations) A Part of Collaborative Group Members Purpose ACRO represents the world s leading clinical research organizations. ACRO s members provide specialized services that are integral to the development of drugs, biologics, and medical devices. ACRO advances clinical outsourcing to improve the quality, efficiency, and safety of biomedical research. Members ACRO is an association of leading clinical research organizations dedicated to fostering the continued advancement of medical product development. Covance, Parexel, Quintiles Critical Path Opportunities List が出された時点での主導的立場 JCG-Workshop SDS

9 作成手順 - 項目設定後 - Process Deliverables Reach agreement on basic CRF Data collection variables Map to SDTM - in cooperation with the SDTM development team Terminology Provide Terminology proposals to the Terminology team Add definitions Write completion guidelines/instructions Proceed to the next step in the Consensus Process as specified in COP-001 Technical Leadership Committee (TLC) JCG-Workshop SDS CDASH Project Update(Nov 2007) Pack age Adverse Events Prior & Concomitant Medication Demographics & Subject Characteristics Inclusion/Exclusion Criteria Medical History and Substance Use Physical Exam & Vital Signs End of Study/ Disposition Drug Accountability/ Exposure Protocol Deviations/ Comments Lab ECG Stream Status Collaborative Group Review Collaborative Group Review TLC Review Lab:Initial Consensus Version Public Review:2008 Q1( 全てのドキュメント ) Released Version 1.0:2008 Q2 ( 全てのドキュメント ) Reviewed Version Nov 2007 Oct-Nov 2007 Dec 2007 Feb Consensus Version TLC Review Harmonized Version Collaborative Group Review Review Version Public Review Released Version 1.0 COP-001 StageⅡ JCG-Workshop SDS

10 Package1 SDS-2 グループにて内容を検討した Package1 について紹介 バージョン : Harmonized Version (2007/5/31) Final 版ではありません Package 2 以降と体裁 用語等が異なっています JCG-Workshop SDS General Recommendations and Observations Applicable to all Domains Compliance Mandatory data collection variables must be present on the CRF Recommended Date and Time Format CDASH Date:DD/MMM/YYYY (01/JAN/2003) Time:HH:MM (12:13) SDTM --DTC variable:iso8601 ( T12:13:00) Terminology Production Terminology will be incorporated in the CDASH JCG-Workshop SDS

11 Categories for Data Collection Variables Mandatory A data collection variable that must be on the CRF (e.g., a regulatory requirement (if applicable)). Conditional A data collection variable that must be collected on the CRF for specific cases (may be recorded elsewhere in the CRF or from other data collection sources). Optional A data collection variable that is available for use if needed (may be recorded elsewhere in the CRF or from other data collection sources). JCG-Workshop SDS Categories for Data Collection Variables Other Packages Package2 Highly recommended, Recommended/conditional, Optional Package3 Highly recommended, Recommended/conditional, Optional Package4(LB EG) Scenario1:Central processing Scenario2:Local processing Scenario3:Central processing but CRF includes site assessment of clinical significance JCG-Workshop SDS

12 ADVERSE EVENT_ Mandatory CRF Data Collection Variable Adverse Event 有害事象名 Start Date 発現日 Stop Date 回復日 Serious Event? 重篤性 Relationship 因果関係 Action Taken 処置 Outcome 転帰 AE Severity 程度 SDTM Variable Definition CDISC Approved Controlled Terminology Name (Core) AETERM Verbatim description of the adverse not applicable (required) event. AESTDTC Date when the adverse event started. not applicable (expected) AEENDTC Date when the adverse event resolved. not applicable (expected) Indicates whether or not the adverse AESER event is determined to be serious serious Y, N (expected) according to the protocol. AEREL the investigational product had a causal (expected) effect on the adverse event. not available Action(s) ) taken with the investigational AEACN product in response to the adverse (expected) event. Action Taken with Study Treatment Description of the subject s s status AEOUT associated with an event using a (permissible) controlled terminology list. Adverse Event Outcome Text Type AESEV A description of the severity of the Severity/Intensity Scale for Adverse AETOXGR adverse event using a controlled Events Common Terminology Criteria (permissible) terminology list. for Adverse Events JCG-Workshop SDS ADVERSE EVENT_ Conditional/Optional CRF Data Collection Variable Serious Event Type 重篤性区分 Other Action Taken 他の処置 AE Start Time 発現時刻 AE End Time 回復時刻 Category for Adverse Event 有害事象種類 Subcategory foradverse Event 有害事象種類 Event Pattern Code 発現パターン Event Body Location 発現部位 SDTM Variable CDISC Approved Definition Name (Core) Controlled Terminology Captures the criteria required by AECAN regulation for determining if an event AESCONG is Serious Serious. Y, N or NULL Other Action(s) ) taken in response to AEACNOTH the adverse event. (Does not include (permissible) Investigational products) not applicable AESTDTC (expected) Time when the adverse event started. not applicable AEENDTC Time when the adverse event (expected) resolved. not applicable AECAT Used to define a category of (permissible) related records. not applicable AESCAT A further categorization of adverse (permissible) event. not applicable Time pattern by which Adverse Event AEPATT occurs. Values: Single Episode, (permissible) Intermittent, Continuous. not available AELOC location relevant for the event (e.g., (permissible) Left Arm for skin rash). not available JCG-Workshop SDS

13 本日の内容 SDS-2グループ 2007 年度活動状況 SDS-2グループ検討のターゲット CDASHについて SDTM Terminologyについて CDASH Terminology SDTMの関連 課題と今後 JCG-Workshop SDS CDISC Terminology Formalized CDISC Terminology Initiative in 2005 Primary Objective: to define and support the terminology needs of the CDISC models across the clinical trial continuum (SDTM CDASH) Terminology Initiative is comprised of 50+ team members (Global Sponsors, Regulatory, Academic Institutions, etc.) distributed across 4 project teams Key partnership with the US National Cancer Institute Enterprise Vocabulary Services (NCI EVS) Combined Regulated Clinical Research Information Management (RCRIM) Vocabulary & CDISC Terminology teams to ensure common development SDTM = Study Data Tabulation Model (esubmissions) CDASH = Clinical Data Acquisition Standards Harmonization JCG-Workshop SDS

14 CDISC-NCI EVS Partnership CDISC CT NCI EVS Production Representations CDISC Codelists in Excel (Terms only) Definition developed Concept assigned Harmonized with related work (FDA) Mapped to other CT **EVS Report Writer (via.ftp website) CDISC/FDA Subset files, posted monthly CDISC Codelist Specification CDISC Codelist Values Codelist_Name SEX Codelist_Name Controlled Terms Comment EVS Term. Browser Codelist_Label Sex SEX U Unknown Upper_Case Y SEX M Male Restriction_8char N SEX F Female Extensible_NY N SEX UN Undifferentiated Reference_Description Organization Name: CDISC Document Title: Study Data Tabulation Model Implementation Guide: Human Clinical Trials Document Version: Date: Chapter Page: 36 Field Name: Controlled Terms or Format Reference_URL cadsr CDE Browser JCG-Workshop SDS SDTM Terminology Projects SDTM Package-1: Easier and more welldefined code lists distributed broadly across the SDTM Labtest: Labtest name, Analyte term SDTM Package-2A: ECG, Con Meds, Drug Exposure, and Substance Use, including Units of Measure SDTM Package-2B: AE, Physical Exam, Vital Signs and Subject Chars, including Anatomical Location JCG-Workshop SDS

15 SDTM Package-1 Action Taken with Study Treatment Outcome of Event Age Span Age Unit Category for Inclusion/Exclusion CDISC System Organ Class Common Terminology Criteria for Adverse Events Control Type Country Diagnosis Group Dictionary Name Not Done Patient Ethnic Group Pharmaceutical Dosage Form Completion/Reason for Non-Completion Relation to Reference Period Route of Administration Severity/Intensity Scale for Adverse Events Sex Sex of Participants Size Production Domain Abbreviation Trial Blinding Schema Trial Indication Type Trial Phase Trial Summary Parameter Test Code Trial Summary Parameter Test Name Trial Type Units for Vital Signs Results Vital Signs Test Code Vital Signs Test Name No Yes Response JCG-Workshop SDS Labtest Laboratory Test Name Laboratory Test Code Set of 92 most commonly used Labtest Terms Interventions Production Exposure Findings Labs InclExcl Events AE ConMeds Vitals SubjChar Disp. Subst Use PhysExam ECG MedHist Additional Terms in Development QS MB PG JCG-Workshop SDS

16 SDTM Package-2A Frequency Unit Position ECG Result ECG Test Code ECG Test Name ECG Test Method Interventions Production Exposure ConMeds Subst Use Findings Labs InclExcl Vitals SubjChar PhysExam ECG QS PG Events AE Disp. MedHist MB JCG-Workshop SDS SDTM Package-2B Interventions Findings Events Exposure ConMeds Subst Use Labs InclExcl Public Vitals Review SubjChar PhysExam ECG AE Disp. MedHist QS PG MB JCG-Workshop SDS

17 ここで確認確認です! Controlled Term: それぞれの用語 Ex:M( 男 ), F( 女 ), Y( はい ), N( いいえ ), U( 不明 ) Codelist: Controlled Termの集合 Ex1:Sex M, F, U, UNを含む Ex2:No Yes Response Y, N, U, NAを含む NA:Not Applicable UN:Undifferentiated JCG-Workshop SDS SDTM Terminology Contents Code Column Codelist Code Codelist Extensible (Yes/No) Codelist Name CDISC Submission Value CDISC Preferred Term CDISC Synonym(s) CDISC Definition NCI Preferred Term Pre-release / Production Notes (Reference for CDISC PT) Description 個々のcontrolled term に割り当てられた数字コード Codelistに割り当てられた 数字コード Codelistにcontrolled termが追加可能かどうか Codelistの記述名 SDTMIG3.1.1に従って申請時に要求される値 Codeが割り当てられた用語に対するCDISC preferred term CDISC preferred termに対する同義語用語に対するcdisc definition 用語に対するNCI preferred name ワークフロー上のステータス用語に対する追加参照情報 JCG-Workshop SDS

18 つまり M(Code:C20197) F(Code:C16576) Sex(Codelist Code:C66731) Ex1:Sex M, F, U, UN U(Code:C17998) Ex2:No Yes Response Y, N, U, NA No Yes Response (Codelist Code:C66742) Codelist name JCG-Workshop SDS JCG-Workshop SDS

19 Codelist - Outcome of Event(1) Code Codelist Code Codelist Extensible (Yes/No) Codelist Name CDISC Submission Value CDISC Preferred Term CDISC Synonym(s) C66768 C66768 No Outcome of Event OUT OUT Outcome of Event C48275 C66768 Outcome of Event FATAL FATAL Grade 5; 5 C49494 C66768 Outcome of Event NOT RECOVERED/NOT RESOLVED NOT RECOVERED/NOT RESOLVED C49498 C66768 Outcome of Event RECOVERED/RESOLVED RECOVERED/RESOLVED C49495 C66768 Outcome of Event RECOVERED/RESOLVED WITH SEQUELAE RECOVERED/RESOLVED WITH SEQUELAE C49496 C66768 Outcome of Event RECOVERING/RESOLVING RECOVERING/RESOLVING C17998 C66768 Outcome of Event UNKNOWN UNKNOWN U; Unknown JCG-Workshop SDS Codelist - Outcome of Event(2) CDISC Definition NCI Preferred Term Pre-release/ Production Notes (Reference for CDISC PT) A condition or event that is attributed to the adverse event and is the result or conclusion of the adverse event. (NCI) CDISC SDTM Adverse Event Outcome Terminology Production The termination of life as a result of an adverse event. (NCI) Death Related to Adverse Event Production E2B code Organization Name: EMEA Document Title: ICH E2B (M) Clinical Safety Data Management: Data Element For Transmission of Individual Case Safety Reports Document Version: Not Applicable Date: November 16, 2000 Chapter: 2. Guideline Content of the Data Elements Codelist_Name: B Not known, not observed, not recorded, or refused. (NCI) Unknown Production E2B code Organization Name: EMEA Document Title: ICH E2B (M) Clinical Safety Data Management: Data Element For Transmission of Individual Case Safety Reports Document Version: Not Applicable Date: November 16, 2000 Chapter: 2. Guideline Content of the Data Elements Codelist_Name: B JCG-Workshop SDS

20 Common Terminology Criteria for Adverse Events Code Codelist Code Codelist Extensible (Yes/No) Codelist Name CDISC Submission Value CDISC Preferred Term CDISC Synonym(s) C66784 C66784 No Common Terminology Criteria for Adverse Events TOXGR TOXGR Common Terminology Criteria for Adverse Events C41338 C66784 Common Terminology Criteria for Adverse Events 1 MILD Grade 1; 1 C41339 C66784 Common Terminology Criteria for Adverse Events 2 MODERATE Grade 2; 2 C41340 C66784 Common Terminology Criteria for Adverse Events 3 SEVERE Grade 3; 3 C41337 C66784 Common Terminology Criteria for Adverse Events 4 LIFE THREATENING Grade 4; 4 C48275 C66784 Common Terminology Criteria for Adverse Events 5 FATAL Grade 5; 5 JCG-Workshop SDS 本日の内容 SDS-2グループ 2007 年度活動状況 SDS-2グループ検討のターゲット CDASHについて SDTM Terminologyについて CDASH Terminology SDTMの関連 課題と今後 JCG-Workshop SDS2 JCG-WS SDS

21 検討のカギカギは関連性 Terminology (=Answer) CDASH (=Question) SDTM (=Data Base) CDASH SDTM IG との関連性の確認 Answer としての Terminology の適切性 JCG-Workshop SDS CDASH JCG-Workshop SDS

22 SDTM IG JCG-Workshop SDS 関連性の確認確認と問題点問題点の抽出 SDTM Implementation Guide (Version 3.1.2) CDASH Variable Name Variable Label Core Contr olled Terms, Codeli st or Forma t CDISC Approved Controlled Terminology Cate gory CRF Data Collection Variable Definition 検討事項 STUDYID Study Identifier Req DOMAIN Domain Abbreviation Req AE N Two-character abbreviation for the domain most relevant to the observation. (AE) AESPID Sponsor-Defined Identifier Perm N Optional Sponsor-defined reference number. Perhaps preprinted on the CRF as an explicit identifier or defined in the sponsor's opetational database. Example: Line nummber on an Adverse Event page. SPID が Mandatory でない理由は? AETERM Reported Term for the Adverse Event Req not applicable M Adverse event Verbatim description of the adverse event AESEV Severity/Intensity Perm (AES EV) Severity/Intensity Scale for Adverse Events Name Mild Moderate Severe And/or Common Terminology Criteria for Adverse Events Number Code 1 = Mild Adverse Event 2 = Moderate Adverse Event 3 = Severe Adverse Event 4 = Life-Threatening or Disabling Adverse Event 5 = Death Related to Adverse Event M AE Severity A description of the severity of the adverse event using a controlled terminology list. 一般的にはAESEV or AETOXGR まれにAESEV and AETOXGR Package-1 Adverse Event, Concomitant Medications, Demographics & Subject Characteristics JCG-Workshop SDS

23 CRF Data Cat 有害事象ページ ID Collection eg. No. Variable ページへの CDASHの適用 Variable Name (SDTM) AETERM AESTDTC AEENDTC AESER AEREL Adverse event M AE 1.01 Start Date M AE 1.02 Stop Date M AE 1.03 Serious event? M AE 1.04 Relationship M AE 1.05 A 社 B 社 C 社 D 社 E 社 F 社 CDISC Approved Terminology 名称有害事象名内容有害事象名 有害事象名 Not applicable 発現日発現日発現年月日発現日 発現日 Not applicable 転帰日 転帰日 消失年月日ま たは転帰調査 年月日 1. 重篤でない 2. 重篤である 1. 明らかに関連あり 2. 多分関連あり 3. 関連の可能性あり 4. 関連なし 5. 判定困難 1. 非重篤 2. 重篤 1. 関連なし 2. 多分関連なし 3. 関連あるかもしれない 4. 関連あり 0. 重篤でない 1. 重篤 0. なし 1. 関連あるかもしれない 2. 多分関連あり 3. 明らかに関連あり 確認日 / 死亡日または回復日 重篤な有害事象ですか? 1. 重篤 2. 重篤でない 1. 関連なし 2. 関連あるかもしれない 3. 関連あり 回復日 継続 Y N 否定できる 関連あるかもしれない 多分関連あり 確実になし 考えにくい どちらともいえない たぶんあり 確実にあり Not applicable Not available AEACN Action Taken M AE 継続 2. 減量 3. 休薬 4. 中止 5. 投与終了後に発現 9. その他 1. 継続投与 2. 休薬 3. 投与中止 治験薬投与に関する措置 1. 変更なし 2. 休薬 3. 中止 4. 減量 5. 該当せず 増量 減量 休薬 中止 該当せず なし 休薬 中止 増量 減量 Dose increased Dose not changed Dose reduced Drug interruped Drug withdrawn Not applicable Unknown AEOUT AEACNOTH Outcome M AE 1.07 Other O AE Action 2.02 Taken (O) 1. 消失又は回復 1. 回復 2. 軽快 2. 軽快 3. 未回復 3. 未回復 4. 死亡 4. 回復したが後 5. 回復したが後遺症あり遺症あり 5. 死亡 9. その他 ( ) 6. 不明その他治験薬以外の 1. なし処置 2. あり ( ) 1. なし 2. あり ( 内容 : ) 0. 消失または回 1. 回復復 2. 軽快 ( 回復途 1. 消失せずまた上 ) は未回復 3. 未回復 4. 回復したが後遺症あり 5. 死亡 6. 不明処置の有無この有害事象に 0. なし対して何か新た 1. ありな治療を行いま処置の内容したか? 1. はい 回復回復日 / 継続 Fatal 軽快または Not recoverd/not resolved 未回復有害事象の結果 Recovered/Resolved 回復したが後遺 重度の身体障害 Resolved with sequale 症あり 入院 Recovering/Resolving 死亡 死亡 Unknown 不明 処置: なし Not applicable 処置: 薬剤治療 処置: 療法 処置: その他 JCG-Workshop SDS いいえ 45 Variable Name (SDTM) CRF Data Collection Variable Cat eg. ID No. A 社 B 社 C 社 D 社 E 社 F 社 CDISC Approved Terminology AESCAN Serious Event Type (O) O AE 2.01 癌ですか? はい / いいえで回答 Y N Null AESCONG O AE 2.01 AESDISAB O AE 2.01 重篤理由 死亡 死亡につながるおそれ 入院 入院期間の延長 障害 機能不全 先天異常 その他重篤チェックボックスで選択 判断基準 1. 死亡 2. 死亡につながるおそれのあるもの 3. 治療のために病院又は診療所への入院又は入院期間の延長が必要となるもの 4. 障害 5. 障害につながるおそれのあるもの 6. 上記 1.~5. に掲げる症例に準じて重篤であるもの 7. 後世代における先天性の疾病又は異常を来すもの 1. 死亡 2. 死亡につながるおそれのある症例 3. 治療のために病院または診療所への入院または入院期間の延長が必要とされる症例 4. 障害 5. 障害につながるおそれのある症例 6.1から5までに掲げる症例に準じて重篤である症例 7. 後世代における先天性の疾病または異常 先天異常や出生異常を来すものですか? はい / いいえで回答 重度の身体障害が生じたはい / いいえで回答 Y N Null Y N Null チェックボックスで選択 JCG-Workshop SDS

24 CDASH/SDTM IG 以外の取得取得データ コメント 因果関係判定理由 4 社 /6 社で取得 追跡未実施理由 関連関連なしなし 又は 多分関連多分関連なしなし としたとした理由 経過の詳細 転帰に関するするコメント 発現時期 3 社 /6 社で取得 ( 治療期間開始前 / 後観察期に発現 ) 原疾患またはまたは合併症合併症の悪化 注目すべきすべき有害事象 JCG-Workshop SDS 考察 Mandatory の項目は ほぼデータ取得されていた しかし ばらつきが見られたられた 項目名 (CRF Data Collection Variables) 使用されている Terminology 取得するするデータデータの定義 (SDTM としての問題?) Option の項目で すべての社で取得されていた項目はなかった データ取得の仕方にばらつき SDTM でのデータデータの持たせたせ方は統一統一できる JCG-Workshop SDS

25 Fatal Not Recovered/Not Resolved Recovered/Resolved Recovered/Resolved with Sequelae Recovering/Resolving Unknown Yes No Dose Increased Dose Not Changed Dose Reduced Drug Interrupted Drug Withdrawn Not Applicable Unknown JCG-Workshop SDS 本日の内容 SDS-2グループ 2007 年度活動状況 SDS-2グループ検討のターゲット CDASHについて SDTM Terminologyについて CDASH Terminology SDTMの関連 課題と今後 JCG-Workshop SDS

26 活動に難しさをしさを感じたじた点 検討材料が最終版ではない Releaseを待つとつと時間時間が空くためくため 見切見切り発車 CDASH Harmonized Version SDTM IG 3.1.1をベースベースに作成作成されている Terminology すべてが Production Version ではない SDTM IG Ver.3.1.2が利用可能利用可能になるのは early 2008 CDASH: 必須 任意等の項目の必要性の考え方が Packageごとに異なる JCG-Workshop SDS CDASH Project Update Initial Consensus Version TLC Review Harmonized Version Collaborative Group Review Reviewed Version Public Review Released Version 1.0 Adverse Events Dec March 2007 May 2007 June-July 2007 Nov 2007 Q108 Q Prior & Concomitant Medication Jan 2007 April 2007 May 2007 June July 2007 Nov 2007 Q108 Q Demographics & Subject Characteristics Jan April 2007 May 2007 June July 2007 Nov 2007 Q108 Q Inclusion/Exclusion Criteria February 2007 May 2007 August 2007 Oct 2007 Oct-Nov 2007 Q108 Q Medical History and Substance Use February 2007 May 2007 August 2007 Oct 2007 Oct-Nov 2007 Q108 Q Physical Exam & Vital Signs End of Study/ Disposition Drug Accountability/ Exposure Protocol Deviations/ Comments February 2007 May 2007 August 2007 Oct 2007 Oct-Nov 2007 Q108 Q June 2007 Aug 2007 Nov 2007 Nov-Dec 2007 Dec 2007 Q108 Q June 2007 Aug 2007 Nov 2007 Nov-Dec 2007 Dec 2007 Q108 Q June 2007 Aug 2007 Nov 2007 Nov-Dec 2007 Dec 2007 Q108 Q Lab Oct Nov December 2007 Jan Feb Q108 Q ECG Nov Nov December Jan Feb Q108 Q JCG-Workshop 2007 SDS

27 Terminologyの状況 Public Review Production Package-1 Jun Labtest Package 1 * Jun Package 2 ~Feb Package-2A ECG, Con Med., Drug Exposure, Jun. 2007~ Jan Substance Use, Units Package-2B AE, Physical Exam., Vital signs, Subject Chara., Location ~Feb *:most commonly used Labtest terms JCG-Workshop SDS **:additional terms SDS-2 チーム次年度活動方針 ( 案 ) 継続的な活動 CDASHの内容の紹介の継続 インプリ上の留意点のとりまとめ 例 :SDTM IGで Req, CDASHで Mandatory とされている項目の考え方を整理 CDASH の日本語対応 JCG-Workshop SDS

28 SDS-2 チーム次年度活動方針 ( 案 ) 短期的な活動 CDASH public review 日本からの発信 予定通り進むとむと 日本日本の次年度活動次年度活動とのとの切り替え期間期間と重なりなり レビューできるか? 現 Versionの検討検討を進めておく SDTM IG の重要な変更点に関する解説 JCG-Workshop SDS SDS-2 チームメンバー 小阪英明 : 日本科学技術研修所 水野義久 : アステラス製薬 前田洋一 : クインタイルズ 森田憲司 : 田辺三菱製薬 古野和城 : 持田製薬 梅本涼子 : 大塚製薬 川村教子 : 大日本住友製薬 松葉尚子 : イーピーエス 山口裕志 : 万有製薬 東浩 (J3C) : 田辺三菱製薬 藤本峰子 (J3C) : アムジェン ( 順不同 ) JCG-Workshop SDS