Purpose of Safety Reporting The rights safety and

Purpose of Safety Reporting ± The rights, safety, and well-being of the trial subjects are the most important considerations and should prevail over interests of science and society(ICH GCP 2. 3). Human Being

Investigator ± All SAEs should be reported immediately to the sponsor except for those SAEs that the protocol or other document identifies as not needing immediate reporting.

Sponsor ± The sponsor should promptly notify all concerned investigator/institution and the regulatory authority of findings that could affect adversely the safety of subjects, impact the conduct of the trial, or alter the IRB/IEC’s approval /favorable opinion to continue the trial

Requisites for Safety Reporting

Grades of AEs ± Using the following general guidelines 0 : No AEs or WNL 1 : Mild AEs 2 : Moderate AEs 3 : Severe AEs 4 : Life-threatening or disabling AEs 5 : Death

Intensity of Adverse Event ± Requiring assessment by the investigator Mild : Non-specific or not altering normal activities Moderate : Causing difficulty performing some activities Severe : Loss of ability to perform activities or requiring intensive treatment

Causality Evaluation ± Exposure ± Time Course ± Likely Cause ± Dechallenge ± Rechallenge Investigator’s Decision

Degree of Causality ± Definite – clearly related to… ± Probable – likely related to… ± Possible – may be related to… ± Unlikely – doubtfully related to… ± Unrelated – clearly not related to…

Guideline for safety reporting ± Investigator’s brochure Expectedness ± GCP, Protocol ± Judgment of the Investigator Reporting process Causality, Seriousness

Essential Items in SADR reporting ± Patient Details ± Suspected Medicinal Product(s) ± Other Treatment ± Detail of Suspected ADRs ± Reporter ± Sponsor/Company Details

Flow of Safety Reporting Non-SAE Adverse Event YES No Expedited reporting Seriousness Unexpected ADR? Investigator SAE Investigational agent related? Investigators Sponsor CRF KFDA IRB

Reporting Time Frames ± Fatal or Life-threatening Unexpected ADRs ± Other Serious, Unexpected ADRs SADR by Investigator “Very rapid reporting” First Knowledge by the sponsor 7 calendar days By Telephone, FAX or writing 15 calendar days Report

Practice of Safety Reporting

Case 8 Randomized controlled, Open-label, phase III study of combination chemotherapy in advanced stomach cancer ± 63세 여자로 10일 전 2주기 시험약을 투여한 후 D 5부터 중증 의 구토, 구역이 있어 입원하였으며, Renal tubular damage로 electrolyte unbalance와 중증의 leukopenia, thrombocytopenia를 보였다. Electrolyte교정과 GM-CSF투여 로 상태가 회복 중이다. 이 event는 임상시험자자료집에 언급 되어있다.

SADR reporting form(1) CMC-2003 1945/03/21 58 174 58. 6

SADR reporting form (2) 발열성 호중구감소증 폐렴 03/06 03/12 2 4 1 3

SADR reporting form (3) OOOO주 폐엽 절제술 고혈압 mg 01/11/31 ㅡ 800 I. V. 아니오 예 02/22 Lung Ca 01/11/31 3. 관련가능성 없음 3.

SADR reporting form (4) 03/03/06 ~ 03/14 CBC 호중구감소증 03/03/06 ~ 03/25 Chest PA 활동성 폐렴 03/03/07 Sputum culture Gram(+)

SADR reporting form (5)

The ways of encouraging safety reporting ± Investigator education ® Understand how to monitoring and reporting ® Know what AEs to expect ± Subject education ® Ask investigator’s advice on everything ® Use of patient diary