Human Research Protection Program and QI of TMUH

1. Human Research Protection Program and QI of TMUH Sung Hui TsengMD PhD 2019-6-18

2. Objectives :

3. AAHRPP Standards and Philosophy • Self-assessment and peer review • Raises participant protection to an organizational priority • More visible role of IRB/EC • Better efficiencyand streamlining • Improved communication/operational transparency • Attract and retain high level researchers • Increases ability to act nimbly and responsively to ever-changing research landscape

4. AAHRPP精神與人體研究保護方案(HRPP) Share responsibility throughout the organization 2016 AAHRPP Conference, At the Crossroads: Harmonizing Ethics, Efficiency, and Innovation

5. Value of AAHRPP to TMU & TMUH • 國際接軌的試驗品質: 成功的國際臨床試驗關鍵取決於品質與效率。 • 通過美國及歐盟稽核，提升本院臨床試驗能力於國際之競爭力 • 增值臨床試驗 • 成為國際臨床試驗選擇合作機構之重點考量。 • 引進更多國際資源，務實地推動本校之國際臨床試驗發展。 • 自我體系發展之醫療方法發展為治療標竿。 (TMU 103/01/07) 一校三院AAHRPP 評鑑擬於104 年底前完成，有利於105 年評鑑醫學中心。

6. 組織架構與任務確認 再認證主責單位 Domain II 條文: Standard (5) Domain I 條文:Standard (8) Domain III 條文: Standard (2)

7. Flowchart of A TypicalResearchProject Post Publication Audit TMU-JIRB TMUH-DMR Approval HRPP Audit TMUH-DMR Monitor TMU-ICIOC

8. 3 Key Elements Consolidate HRPP Performance

9. TMUH HRPP Organization Structure and Leadership Chair: Superintendent Director: Vice Superintendent of Research

10. 一、人體研究嚴重不良事件(SAE/SUSAR)通報流程(104年9月1日起，三院流程一致)一、人體研究嚴重不良事件(SAE/SUSAR)通報流程(104年9月1日起，三院流程一致) 試驗主持人 位置: Portal/AERS通報系統/不良反應通報系統(SAE/ADR) 立即通報 立即通報 判定SAE/SUSAR 試驗委託者 研究嚴重不良事件 通報系統 所有SUSAR 立即通報 醫療品質部 未預期死亡或危及生 命之SUSAR：< 7天 未預期之其他SUSAR：< 15天 提供詳細書面資料：< 15天 TMU-JIRB 研究部 藥劑部 人體研究保護中心 衛生福利部 (或委託機構) 得知事實後通報：< 7天；提供詳細書面資料： < 15天

11. 再認證準備方向 • 做好受試者保護工作，彰顯研究品質

12. AAHRPP再認證-行動方案 • 檢視JCI過程,補充與修正作業流程 • 邀請院外專家,以他院為借鏡,修正準備方向 • 條文導讀與文件準備(跨部門共6場次) 105.11.23,24 實地訪評 105.03.15 104.10.30 105.03.11 • 所有申請資料完成，光碟寄出譯 • 申請資料提供院外委員審查 105.06.25-11.22 105.06.24 105.01.10 • 持續進行資料修正與完成step1 • AAHRPP再認證-共識營(學分認證) • 教戰手冊製作與提供 • 文件電子化,資訊及通報系統確認 • PI/研究人員教育訓練至少3場次 • 預評(邀請院內外專家指導) • Active Protocal清整 (6/5) • STEP 2.Application(6/24) • 資料夾準備宣導 (7/22) • 臨床研究案全面預約稽核(8/19) • 持續進行資料修正與全院研究案審查

13. Our Goal: Re-Accreditation

14. 他院借鏡 台大醫院臨床試驗中心執行秘書陳怡安醫師 專家特別演講： 時間：105年1月8日(星期五)上午10:00-11:00 (TMS代碼54489) 地點：第一醫療大樓5樓1051會議室 出席：34人出席(包含學校人體研究處同仁) 主辦：臺北醫學大學附設醫院研究部、藥劑部、臨床研究中心 • 總時間縮短0.8日 • 訪談人員與場次減少，每場時間增加 • 文件審查時段減少 • 文件準備量沒有減少，翻譯品質很重要(沒有機會澄清翻譯錯誤)

15. 全面稽核與發現 感謝~Top-Down Engagement

16. AAHRPP再認證 全力準備 最後衝刺 • AAHRPP抽查研究案資料夾-共31件 • 資料夾已交：28件 • 待補文件：21件 (註:包含待翻譯社交件，預計11/11給PI) • 已完成：7件 • 未交資料夾：3件 (劉偉民醫師2件、陳菁徽醫師1件)(請於11/15前交)

17. Accomplishing our Goal: Accreditation

18. Quality Improvement (QI) • “The systematic approach to reduction or elimination of waste, rework, and losses in production process.” • “To identify opportunity for process improvement, address potential problems and promote best practice.” • To correct workflow processes, improve efficiencies, reduce variations in outputs, and address areas of non-compliance. • A Performance enhancement in response to observed trends or findings • QI can take many forms, but the philosophy remains: • The systematic and continuous actions that lead to measurable improved performance.

19. Data and Quality Improvement • Every HRPP wants to improve its processes, its compliance, its efficiency. • Within every HRPP lies a mountain of ‘data” either already collected or collectible • Data includes • Audit and monitor reports • Research team reports to HRPP: non-compliance, deviations, adverse events, etc. • Data collected by the HRPP • From its records • From specific purposeful outreach efforts

20. What Do We QI • Regulatory Compliance • Community Satisfaction/Dissatisfaction • Data Quality • Efficiency • Each Involves Assessments of • Policies • Procedures/work processes • Operations

21. Quality Improvement Plans • To Err is human: the major cause of adverse events is poorly designed system. • Quality improvement activities are an important component of organization operations. • QI activities are systematic, data-driven actitivies and involve human participant, when is IRB approval needed ? • Research ethics committees in the regulation of clinical research: comparison of Finland to England, Canada, and the United States (Hemminki E1, 2016) • Conclusion: In England, quality assurance of REC work was thorough, fairly thorough in the USA, and not performed in Finland. The work of RECs in the four countries varied notably. Various deficiencies in the system require action, for which international comparison can provide useful insights. • Quantify HRPP quality • Creating investigator profile

22. Performance evaluation:measurement of safety,efficiency,effectiveness • Information technology • User survey • Audit findings analysis • JIRB and institution review turnaround time • SAE analysis

23. QI: Compliance • Analysis of Data from Audit Checklist • Improvement of efficiency and effectiveness of research compliance program • Goal: Using minimum data sets as Compliance Quality Indicators to improve outcomes and processes and patient safety

24. Risk based audit • High-risk human trial/study • Having serious unanticipated problems that may harm participants or others. • Participants are vulnerable populations: children, prisoners, minors, pregnant women, handicapped or mentally disabled persons, students, subordinates (affiliate relationship), terminal patients, and so on. • Trials and researches initiated by investigators. • Having serious adverse event reports • Abnormal events or unexpected events occur, such as the appeal cases, exposed by the media, or other non - compliance violations or special cases. • Others if needed.

25. Incidence rates of noncompliance General back ground • Not-for-cause audit in 2016 was 45.5% and 36.2% in 2018. • Risk based audit: 70% What are the patterns of noncompliance in different types of research or researchers ? • Investigator initiated trials vs sponsor trials

26. Comparison of audit findings of Investigator Initiated Clinical Research to risk based audit • People don’t know what they don’t know • even experts are often clueless as to what they don’t know. Investigators initiated research have higher incidence rates of unreported AE/SAE/NC/UP?DSMB reports Why?

27. Comparison of audit findings of Investigator Initiated Clinical Research to sponsor initiated trials PI initiated researches have higher finding rates of deficiencies, less self reported NC/ UAP, and submitted less amendment reviews. "The devil is in the detail“

28. Use minimum data sets as Compliance Quality Indicators to improve outcomes and processes and patient safety • Focus Audit on patient-centered metrics and researchers at risk of jeopardizing the rights and welfare of subjects • Investigators initiated trials • Use areas of higher deficiency rates to guide future oversight activities and education Facilities at risk, while constituting 25% of all facilities, contributed 70% ±25% (M ± SD; range = 32%-100%) of all reported noncompliance/incidents in the following 14 performance metrics : Missing ICDs/Incorrect ICDs used/ICDs not signed by subjects/HIPAA authorization not obtained/Local adverse events determined to be serious, unanticipated, and related to research/Resulted in hospitalization/Resulted in death/Lapsed in IRB continuing reviews/ Suspended due to human subject concerns/Suspended due to investigator-related concerns/ Informed consent not obtained prior to initiation of study/Subjects included in research not meeting inclusion/exclusion criteria/Without initial training/Lapse in continuing training (Tsan MF & Nguyen Y, 2018)

29. Quality Improvement of Research Oversight with Electronic Audit System IRB continuing review

31. New Protocols Reviewed by TMU-JIRB No. Academic Year(Aug-Jul)

32. IRB review efficiency analysis • IRB started on-site consulting service in Feb 2017. The IRB staffs provide face to face meeting at TMUH. • Consulting issues: • Reviewer’s opinion • How to use the IRB submission system. IRB on-site consulting started Web based IRB submission started

33. Satisfaction/Dissatisfaction • Satisfaction/Dissatisfaction monitoring plan • Annual User Surveys on HRPP components • Annual survey of researchers and staff awareness of HRPP • Auditing Satisfaction Survey

34. We believe… • Informed consent is central to the protection of human subjects (Byerly WG, 2009) • IRB review is integral to ensure regulatory compliance and ethical conduct of research involving human subjects (Byerly WG, 2009) • IRB letters are central to the practice of research ethics (Clapp JT, 2017) • Auditing and accreditation programs can improve the quality of ethics review (Coleman CH et al 2008) • Review by research ethics committees is the key in medical research regulation (Hemminki E, 2015)

35. Future directions Actual impact on research practice? (Coleman CH et al 2008) • Does IRB improves participants understanding risk and potential benefit? • Is IRB guidance actually been followed? • Is research risk reduced? • Does it change subject’s experience or attitude about research? • Does it result in more research responsive to local community’s self-identified needs?

36. Publications about HRPP • Minimal risk projects should entail minimal oversight (Fiscella K, 2015) • Unaware practitioners become involved in low-risk research activities without knowing it (Pediatrics 2017) Confidence of IRB members in their assessment of human research risk (Grinnell F, 2017) Regulation complexity High Low As risk increased, confidence decreased (Grinnell F, 2017) Min risk High risk

37. 再評的挑戰 • 收集評鑑資訊 • 2014/12月AAHRPP評定會議，1/4 full accreditation(全為美國機構)，3/4是qualified accreditation或accreditation-pending • 新規定/基準 • Tip Sheets (27份) • AAHRPP top 10 findings • 重新檢視政策與程序(P&P) • 第1次準備較倉促 • 預期會被較嚴格審視 (首爾三星大學第3次評鑑的經驗) • 翻譯確實:用詞精準、意思明確

38. Take home message 要通過AAHRPP 所有PI, 研究助理,CHRP成員都要扮演適當角色 PI負責計畫執行, 從各角度保護受試者 PI準備AAHRPP絕對不是只有簽名, 需要積極參與準備評鑑 人體研究保護計畫結合校院單位運作能有效的評估與監核 人體研究的進行, 並能自我改善(PDCA)

39. THANKYOU!