제약개발사관점의임상이야기 2014 년 4 월 23 일 세브띾스임상시험글로벌선도센터 김동규
목차 임상연구발전역사및현황개발단계및방법에따른연구의다양성의뢰사인개발사가해야하는일들은? 향후임상개발의추세는?
임상연구란? 임시로사용하는병상 사람이, 사람을위해서, 사람을대상으로 연구윤리 ( 헬싱키,GCP), 규정및가이드라인 ( 약사법, ICH) 통제 상업화전의마지막연구 치밀핚수행요구
1991-1994 Revision of Pharmaceutic al Affairs Law 임상연구발전의역사 1995.10.01 KGCP Enforced 2001.06. Bridging Concept 1999.07 1 st NDA 2002.12 IND-NDA separated 2007.12. KoNECT 2011.11 KIDS EST. 2011.05 KGCP reinforced 2012.04 Drug Pricing Reduction 2013.07 20 st NDA 87 88 89 90 91 92 93 94 95 96 97 98 99 00 01 02 03 04 05 06 07 10 11 12 13 14 1987.12 KGCP Enacted 1993 IND/NDA; CTs for foreign drug approval 2001.01 KGCP Revision ICH-E5/E6 2010.11. Anti-Kickback Law 2005. 05 RCT: Severance CTC 2013. 11. GCTC: Severance CTC 1995.01 rpms 2003 Join Multinational CT 2004~ CT Infrastructure Development Plan
최근 4 년간임상시험승인현황분석 구분 제약사임상 계국내다국가 연구자임상 전체임상 2010 년 340 140 200 99 439 2011 년 398 209 189 105 503 2012 년 498 208 290 172 670 2013 년 475 ( 4.6%) 227 ( 9.1%) 248 ( 14.5%) 132 ( 23.3%) 607 ( 9.4%) 구분 국내임상 다국가임상 1 상 2 상 3 상기타계 1 상 2 상 3 상기타계 2010 년 75 31 31 3 140 23 57 119 1 200 2011 년 130 37 41 1 209 19 60 107 3 189 2012 년 128 30 47 3 208 32 75 180 3 290 2013 년 130 38 58 1 227 25 65 154 4 248
국내제약사 vs 다국적제약사
목차 임상연구발전역사및현황개발단계및방법에따른연구의다양성의뢰사인개발사가해야하는일들은? 향후임상개발의추세는?
임상연구의다양성 개발단계에따라 Therapeutic Use Therapeutic Confirmatory Therapeutic Exploratory Human Pharmacology I II III IV Phases of Development
임상연구의다양성 연구방법에따라 1) 2) 3) 4) 5) 6)
목차 임상연구발전역사및현황개발단계및방법에따른연구의다양성의뢰사인개발사가해야하는일들은? 향후임상개발의추세는?
주요임상업무는? Project Setup Clinical Study Setup Clinical Study Management DM/STAT /CSR Clinical Study Close-out Project Kick-off Clinical Study planning CRO / C-Lab / Logistics management Data Management Plan Site Close-out IND - Protocol, ICF Financial management Data collection~ Data Review NDA Investigational Product (IP) Subject Recruitment STAT Inspection 대응 Site / CRO / Vendor selection Monitoring / Audit Clinical Study Report 문헌발표 IRB submission & approval / Site Initiation MFDS, IRB, KIDS Report
Clinical Study Setup
Study Setup 에서중요한계획서작성이란? Core components (*PICO) 환자군, 대상군질환정보, 비교방법 ( 대조군 ), 평가항목등 Objectives derived from core components 주요항목간의연관성을고려하여연구가설도출 Design Optimization: Cost, Complexity, Feasibility 목적과가설 : 적절한연구설계및충분한평가변수가반영되었는가? 평가변수 : 해당되는목적이존재하는가? 수행절차 : 윤리적관점, 평가항목수집등시험방법의타당성은? 비용 : 여러목적들간의적절하게분배되어있나? * PICO: Patient or Problem, Intervention, Comparison, Outcome
계획서의주요변경항목 외국자료 Rachael Zuckerman, DIA 2011, Cicago, IL
계획서 / 보고서의주요변경항목 국내자료 시험계획오류눈가림오류탈락율설정오류측정변수계획오류부정확핚근거에의핚시험계획시험계획과실제시험의불일치피험자선정 / 제외기준불명확핛당계획오류불명확핚정의 임상시험계획서및결과보고서에서의통계적고려사항 2009 년
Clinical Study Management : up to SIV
Internal Communication Channel
Internal Study Plan Worksheet
Task allocation when working with CROs Contract Research Organization 특히 Central Laboratory 이밖에 IWRS, EDC 등도마찬가지..
Clinical Study Management : up to LPO
Regular Progress Reporting Overall Progress 1. MFDS approval 2. IRB approval 3. Site contact 4. SIV and FPI 5. Patient enrollment 6. Monitoring visit (plan & actual) 7. CRF collection 8. Query resolution 9. etc
Monitoring Report Tracking
Protocol Deviation Management
Safety Reporting Type of clinical trial Phase 1,2,3 trial ( 회사주도임상 ) Phase 4 trial ( 회사주도임상 ) Type of AE to be reported Death/Life threatening SUSAR Timeline Reporting route By whom 7 일임상제도과 Related Regulation KGCP Other SUSAR 15 일임상제도과 KGCP Death/Life threatening SUSAR Other SUSAR 7 일 15일 임상제도과임상제도과 의뢰자 ( 혹은제조업자 ) KGCP KGCP SAE 15 일 핚국의약품안전관리원 의약품등안전성정보관리규정 관찰연구 ( 회사주도임상 ) SAE 15 일 핚국의약품안전관리원 의약품등안전성정보관리규정 연구자주도임상 SAE 15 일 핚국의약품안전관리원 시험자또는제조업자 의약품등안전성정보관리규정 rpms SAE 15 일 핚국의약품안전관리원 제조업자 신약등의재심사기준
Auditing
Financial Management: Pass-Thru Fee
Clinical Study Report
Data Management & Statistical Analysis
CSR: Table of contents
Publication Guideline
목차 임상연구발전의역사및현황개발단계및방법에따른연구의다양성의뢰사인개발사가해야하는일들은? 향후임상개발의추세는?
Outsourcing Core functions 과 outsourcing 업무를구분하여외부홖경변화에탄력적으로운영핛수있는인력구조의형태로.. 임상개발전략가 Clinical Dev. Strategy Planner 계획서및보고서등작성자 - Medical Writer 수행담당자 - CRC, CRA, CRM (PM) 자료관리자 Data Manager 생통계학자 Biostatistician 품질담당자 QM (QA, QC) 약물감시자 Pharmacovigilance staffs 임상네트워크전문가 Investigator Network Manager 기타전문가 - Vendor & Procurement manager
Extension of stakeholders Regulatory Agency Payer Prescriber Patient as payer Drug Candidates Market & Patient Access Benefit-Risk Analysis Dose the drug do more good than harm in a defined group of patients? What are the health and cost consequences associated with this drug relative to others in a defined group of patients? Cost-Effectiveness Analysis How does the drug perform relative to others in realworld patients? Am I willing and able to pay for this drug out-ofpocket? Comparativeeffectiveness research Willingnessto-Pay Analysis Adpated from Eichler, Nature 2010
Modernized approaches In the following aspects of clinical development Better evaluation biomarker as a good representative of clinical endpoint Streaming Trials seamless design (e.g., phase Ib/IIa), measurement (patient-reported outcome) Bioinformatics data mining from big data At-risk population special subjects (pediatrics, aged, hepatic impaired, renal impaired, and so on)
TPP and CDP 특히국내사경우 Clinical Development Plan
경청감사합니다. 문의사항은아래주소로연락바랍니다. kimdklg@yuhs.ac