Transcript 不預警查核

臨床試驗
臨床試驗執行(三)
監測、稽核、查核
授課老師: 劉仁沛教授
國立台灣大學 與 國家衛生研究院
【本著作除另有註明外，採取創用CC「姓名標示
－非商業性－相同方式分享」台灣3.0版授權釋出】
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Cooperative Research Group
Example of Misconduct of Clinical Research
National Surgical Adjuvant Breast and Bowel Project (NSABP), 484 institutions with 5,000
physicians funded by NCI since 1960
NEJM, May 14, 1994, Vol. 330 (20): 1448-62
Chairman: Dr. Bernard Fisher
Principle Statistician: Dr. Carol Redmond
In June, 1990, discrepancy of dates of surgery of two identical operative reports by data managers and
a protocol statistician
Dr. Roger Poisson – L’ Hôpital Saint-Luc, University of Montreal
participated 22 NSABP trials with enrolling about 1500 patients (7%)
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Cooperative Research Group
Changes in the dates of biopsy, surgery, pathology report, and
hormone receptor values
 115 instances of data falsification or fabrication in data from 99
patients
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B-06
B-13
B-14, 16
3
lumpectomy vs. mastectomy
adjuvant chemotherapy
Tamoxifen
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Cooperative Research Group
Funding agency: NCI
Cooperative group: NSABP
Investigative Body: Office of Research Integrity (ORI),
FDA
Finding published in: Federal Register, ORI Newsletters,
NIH Guide for Grants and Contracts,Chicago Tribune
Congressional hearing by John, D. Dingell on 4/13/1994
Dr. R. Poisson was charged of scientific misconduct and as disqualified for
life by the US FDA from receiving investigational drugs
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Gene Therapy
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University of Pennsylvania – 9/99
Death of a 18 year old volunteer after a genetically altered virus to
treated an inherited liver disease in a gene therapy clinical trial.
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FDA inspection (Jay Siegel)
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Problems with the protocol
• Informed consent
• Patient exclusion criteria
• Stopping rule
• Initiating protocol changes
• Reporting adverse events
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Gene Therapy
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Reporting AEs by gene therapy trials to NIH
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Recombinant DNA advisory committee
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Before the death – 39
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After the death – 652
Actions
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Stopping the trial
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Congressional hearings
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Investigations by HHS and University
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Advisory committee meeting
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Asthma Study
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Johns Hopkins University
Alkis Togias, MD, Associate Prof. of Medicine
Hexamethonium
Fluka: Sigma-Aldrich corp.
Approved for HBP, and decrease bleeding (1950) Withdrawal from
market in 1970’s
A 24-year old female healthy volunteer died from lung failure on June 2,
2001.
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Asthma Study
FDA FORM 483 Inspectional Observations
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Failure of submission an IND to FDA
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Failure of reporting an unanticipated AE to the IRB
Failure to follow the protocol
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Changes to the approval protocol without notifying the IRB and without IRB
approval
Failure to obtain effective informed consents from subject:
Similar AE reported by UCSF in 1978
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Contract Research Organization (CRO)
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Eichenwald, K. and Kolata, G. “A Doctor’s Drug Trials Turned into Fraud”. New
York Times, May 17, 1999
Dr. Fiddes, President of Southern California Research Institute, a clinical research
company in Whittier, California
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Conducted over 200 studies for as many as 47 drug companies beginning in the early
1990’s
Engaged in extensive fabrication and falsification of data
Aug. 1997 plead guilty to felony charge of conspiracy to make false statements to the
FDA in connection with the Drug approval process
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Contract Research Organization (CRO)
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Sept. 1998 sentenced to 15 months in federal prison
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Ordered to pay $800,000 in restitution
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June 1999 disqualified as a clinical investigator by
Commissioner of FDA
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Contract Research Organization (CRO)
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Made up fictitious study subjects
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Fabricated lab results by substituting clinical specimens and
manipulating lab instrumentation
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Prescribed prohibited medications to manipulate data
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Contract Research Organization (CRO)
“Another study on an antibiotic required that patients have a certain
type of bacteria growing in their ear. No problem for Fiddes. He
bought the bacteria from a commercial supplier and shipped them
to testing labs, saying they had come from his patients’ ears.”
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Duke Scandal
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Duke Scandal
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Duke Scandal
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Duke Scandal
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Duke Scandal
PREDICTORS OF CHEMOTHERAPY RESPONSE:
BACKGROUND INFORMATION
In relation to the topics and questions suggested by the IOM, the following document outlines some
of the scientific and administrative responses around the attempted development of chemotherapy
sensitivity predictors and is being provided by Duke Medicine administration to the IOM Committee in
advance of its upcoming “Workshop on the Review of Omics-Based Tests for Predicting Patient
Outcomes in Clinical Trials.” The circumstances and events related to work conducted by Dr. Anil
Potti, in collaboration with Dr. Joseph Nevins, at the Duke Institute for Genome Sciences & Policy
that have led to the IOM Committee’s review of this field are regrettable and have led to significant
organizational self evaluation in an attempt to learn from the events of the past two years.
Understanding that the committee is scheduled to receive additional information at future meetings,
this document is limited in scope to some of the thought processes and actions relevant to the topics
defined for this workshop. It is our hope and belief that the work of this committee will serve to
provide much needed guidance for this emerging area of translational research and we are grateful to
the IOM for taking on this project.
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Duke Scandal
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Further analyses revealed corruption of multiple datasets compiled by Dr. Potti that had been used as
sources of validation of the various chemotherapy sensitivity signatures. These included data derived
not only from Duke sources, but also publicly available data. As an example, a dataset of 133
samples from a neoadjuvant breast cancer study at MD Anderson involving patients treated with the
combined regimen TFAC was used for validation of an adriamycin signature. The clinical annotation
that was assumed to be used by Dr. Potti included 34 responders and 99 non-responders, the same
distribution as reported by MD Anderson. However, a detailed comparison of the two datasets
revealed that the response information was reversed for 24 cases with 12 labeled incorrectly in each
direction. In this case, the corrupted data yielded positive validation results whereas the accurate
data did not provide evidence for validation. Similar findings of corruption of data in key validation
datasets were observed in other instances.
As a result, three publications were retracted, a manuscript describing the methods for implementing
signatures in the clinical trials that was under review was removed from further consideration, and
other publications are currently being analyzed. Dr. Potti issued his resignation statement on
November 19, 2010, and a statement of responsibility for the problems with the work. A research
misconduct investigation is in progress.
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Duke Scandal
There are many lessons to be learned from this experience,
but the immediate lessons that Duke and the IGSP have
learned are that all data and methods for clinical research
must be assessed at multiple levels and that quantitative
expertise is needed for complex analyses; furthermore, for
translation to clinical trials these analyses must be done using
systems that maintain independence between the data
generation and the analysis and enable replication of the
results, along with documentation of all changes to data and
analyses.
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小保方晴子與STAP幹細胞
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2014年1月日本理化研究所小保方晴子在Nature期刊發表兩
篇有效製作STAP多功能幹細胞的論文，轟動一時。
發現論文中影像造假。
其他學者及自已無法重複實驗結果。
2014年7月2日Nature期刊撤銷論文。
2014年8月5
2014年8月12日小保方晴子美國哈佛大學指導教授Charles
Vacanti辭職。
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Diederik Stapel and
Marc Hauser
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Diederik Stapel of Tilburg University, Netherlands
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Retracted 55 papers, including the one in Science
and 10 PhD dissertation due to fabrication of data
Marc Hauser of Harvard University
Committed falsification of data
 Forced to resign from Harvard
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ISSUES
◆ Informed consent form
◆ Fictitious trials Subjects
◆ Non-adherence to the protocol
◆ Records and diagnosis unverifiable
◆ Data falsification or fabrication
◆ Failure to notice and report SAEs
◆ Drug Accountability
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Good Clinical Practice
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「藥品優良臨床試驗規範」- 行政規範
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「藥品優良臨床試驗準則」- 法規命令
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8章232條 - 85.11.20 & 91.9.20
8章123條 - 94.1.6
查驗登記用之藥品臨床試驗-應遵守
學術研究用之藥品臨床試驗-建議參考
實施日期
原產國尚未核准上市: 86年7月1日
原產國已上市: 87年1月1日
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監測者
監測者〈Monitor〉：指由試驗委託者或受託研究機構所指派，並直接向試驗委託者或
受託研究機構負責，以監測並報告試驗的進度和驗證試驗資料之人。
根據標準作業程序執行，在試驗執行前、執行中及完成後前往觀察試驗主持人，是否
確實依循試驗計畫書的規定程序進行，並確認所有過程資料均予正確與完整的記錄與報
告；受試同意書均在受試驗者參與試驗前簽署。
與試驗主持人每次之會面、電話及信件等討論後，均應提報試驗委託者一份書面的監
測紀錄。
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品質保證
為確保試驗結論係自原始資料逐步推論獲得，所有觀察結果與發現，特別是資料的可靠
性均得被再確認。
為確保所有資料數據之可靠與被正確處理，資料處理的每一步驟均應實施品質管制。
試驗之稽核應由試驗委託者或由醫療機構委託與該計畫無關之人員執行。
所有本規範提及之文件，含建議書、申請書等均應對試驗委託者及中央衛生主管機關公
開，並接受其稽查。
試驗地點、醫療機構、檢驗室以及所有資料〈包括原始資料〉及文件均應接受中央衛生
主管機關之查核。
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稽核 vs.查核
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稽核
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試驗初期(~20% 收案)
改善試驗流程及順從性
試驗委託者委託獨立稽核者
企求試驗成功
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查核
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試驗中.後期
著重試驗計畫順從性
由主管機關為之
試驗是否成功並非重點
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臨床試驗查核
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確保臨床試驗品質
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保護受試者之權益
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落實GCP之實施
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評估及改進查核小組架構與執行
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提昇國內臨床試驗水準
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臨床試驗查核
實施日期
原產國尚未核准上市
86年7月1日
原產國已上市
87年1月1日
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PROCEDURES
Flow of Data
Source Documents
↓
Case Report Forms
↓
Report and Listings
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PROCEDURES
Inspection of Data Flow:
Source Documents
↓↑investigator
Case Report Forms
↓↑sponsor
Report and Listings
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查核手冊與記錄表格之製定
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藥品臨床試驗查核手冊及記錄表格
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試驗主持人及醫療機構
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試驗委託者、受託研究機構、監測者
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人體試驗委員會
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醫療機構
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藥界、公會
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學術單位
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訓練課程
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臨床試驗查核說明會
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7場382人
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臨床試驗查核工作人員訓練
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模擬查核
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臨床試驗查核結果說明會
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臨床試驗查核作業流程
TFDA
查核小組
通知試驗委託者準備資料
安排查核小組成員及聯絡試驗主持人
確定臨床試驗查核日期＼時間＼地點
資料寄送給查核成員
TFDA行文通知查核
執行查核工作
完成查核 記錄報
告
影本供查核計畫主持人存查
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正本歸檔
影本提供TFDA藥
物諮詢委員會審查
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實地查核作業流程
TFDA查核小組
中途進出人員
雙方簡介並確定在場人員身份
試驗主持人簡報臨床試驗
查核小組開始執行查核工作
拜訪試驗相關之醫院場所
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查核結果報告與討論試驗
主持人列席
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臨床試驗查核委員
1.
2.
3.
4.
5.
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TFDA委員
臨床委員
統計委員
藥物動力學委員
查核計畫召集人
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臨床試驗查核記錄表
1.
2.
3.
4.
5.
6.
7.
8.
9.
授權與管理
試驗計畫書
受試者同意書
人體試驗委員會
受試者資料
研究用藥品之處置與管理
記錄保存
電腦化資料與資訊系統
藥物動力學
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臨床試驗查核記錄表填寫委員
TFDA委員
臨 床委員
統 計 委員
藥 動 委員
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1.
2.
3.
4.
6.
授權與管理
試驗計畫書
受試者同意書
人體試驗委員會
研究用藥品之處置與管理
5.
受試者資料 5.1-5.11項
5.
7.
8.
受試者資料 5.12-5.15項
記錄保存
電腦化資料與資訊系統
9.
藥物動力學
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GCP查核結果
1.備查（通過）
2.補充說明後通過
3.重查
4.不准備查
5.自行撤案
2001年至2008年不准備查的比例為7.66%
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PROCEDURES
Preparation for an inspection:
● Read
thoroughly the protocol (future tense).
● Read thoroughly the report (past tense).
● Review the self-filled inspection forms.
● Check any discrepancy among them.
● Look for changes in conduct and analysis.
● Write down a list of items for your inspection.
● Understand the current status of regulation.
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PROCEDURES
Preparation for an inspection:
● Example
The primary endpoint is the change from baseline
of HbA1c.
The baseline HbA1cs were not provided in the
patient listing of HbA1c
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PROCEDURES
Check the subject identification list:
How many screened?
How many randomized?
How many withdrawal (cf. charts)?
How many AEs?
How many Serious AEs?
Status of the individual site being inspected for multi-center
trials.
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PROCEDURES
Chart: a surrogate for existence of trial subjects.
Check the number of charts.
Reasons for unavailable charts.
Check the date, and demographic
information on the front page of the chart against
those of CRF, report, and subject identification list.
Check whether the subjects were registered through the
center
Electronic form of medical charts???
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PROCEDURES
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Blindness
Check appearance and packages of drugs.
 Check random codes.
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• Original code list with programs and logs with date generated.
• Random codes vs. CRFs vs. patient listings.
• Official document for unblinding codes for analysis with authorized
signature and date
• Documents for breaking codes for other reasons during the study.
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PROCEDURES
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Monitoring
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Check the number of monitoring reports.
Monitoring should be signed by CRAs and their supervisors.
Read thoroughly the monitoring reports of initiation and closeup visits.
Monitoring reports should reflect the conduct of trials.
Important events should be recorded in monitoring reports,
e.g., serious adverse events.
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PROCEDURES
Data should be obtained in a proper order.
Example:
Form for physical exam was completed before the visit by
the CRA and attached to the chart. However, the subject
missed the visit and form was crossed out and left on the
chart.
An example of data fabrication.
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PROCEDURES
Data should be obtained in a proper order.
Example:
Results of one of inclusion criteria for the primary
endpoint were obtained after the date of
randomization
An example of non-adherence to protocol.
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PROCEDURES
Inclusion/exclusion should be checked with documented
data before enrollment.
Example:
One of inclusion criteria for prohibited medicines was
not verified before randomization of patients and was
found out after completion of the study
An example of non-adherence to protocol.
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CURRENT STATUS
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Monitoring failed to identify the patients who were not meet
inclusion/exclusion criteria such as prohibited medicine.
Insufficient training (simulation) at the investigator meeting
and initiation of trial and site visit for adherence to the
protocol.
Inclusion/exclusion criteria were not completely verified and
checked.
Computer system also failed to identify the patients on
prohibited medicines even when they were entered into the
database of concomitant medications.
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CURRENT STATUS
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Only charts for randomized patients available (not screened
patients).
Inconsistent records on SAEs between charts, patient listing
and reporting.
No individual center results available for the center being
inspected.
Incorrect methods for generation of random codes.
Different methods for generation of random codes by
different centers.
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Correct Random Assignment
Patient No.
001
002
003
004
006
007
008
009
010
013
014
016
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Random Code
13
14
15
16
17
18
19
20
21
22
23
24
Date
01022007
01032007
01042007
01062007
01102007
01152007
01202007
02012007
02022007
02152007
02172007
02202007
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Incorrect Random Assignment
Patient No.
001
002
003
004
006
007
008
009
010
013
014
016
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Random Code
20
16
24
14
19
17
15
23
13
22
18
21
Date
01022007
01032007
01042007
01062007
01102007
01152007
01202007
02012007
02022007
02152007
02172007
02202007
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不預警查核 - 臨床試驗A
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多國多中心臨床試驗
台灣共4個醫學中心
標的藥物
非小細胞肺癌
可能會引起心律不整
QT/QTc Prolongation
Torsade de Pointes (TdP)
CYP450 3A4
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不預警查核 - 臨床試驗A
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禁用藥品
引起Torsades de Pointes
Group 1 藥物 (26 個)
Not allowed
During study
Within 2 weeks of study entry
Avoided for up to 4 weeks following
discontinuation of study treatment
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不預警查核 - 臨床試驗A
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禁用藥品
引起Torsades de Pointes
Group 2 藥物 (52 個)
Screening QTc ≤ 460 msec
Additional ECG 4-8 hours after the 1st dose
Closely monitoring
QTc + electrolytes
CYP450 3A4 (15個)
Inducers
Inhibitors
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不預警查核 - 臨床試驗A

QTc Prolongation
QTc > 550 msec or ΔQTc from baseline > 100 msec 
withhold study medication and follow for resolution of
QTc prolongation.
 480 msec  QTc < 550 msec or ΔQTc from baseline > 60
msec ( QTc  460 msec for Group 2 藥物)  continue
double-blind study drug and repeat 3 QTc evaluations
within 48 hours.
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不預警查核 - 臨床試驗A
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QTc Prolongation
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480 msec  QTc < 550 msec or ΔQTc from baseline > 60
msec ( QTc  460 msec for Group 2 藥物)  withhold
study medication and follow for resolution of QTc
prolongation.
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不預警查核 - 臨床試驗A

廠商主動通報三家中心發生服用禁藥。
中心甲: 5位受試者服禁用藥品。
 中心乙: 1位受試者服禁用藥品。
 中心丙: 1位受試者overdose
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衛生署於2008年五月至八月至所有4家參與試驗
的醫學中心進行不預警查核。
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不預警查核 - 中心甲
篩選：17人
 隨機：11人
 5位受試者服用Group 1引起Torsades de Pointes的
禁用藥品。
 一位受試者在隨機指派前即退出
 發生比例：36.4%
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不預警查核 - 中心甲
Baseline日期
03/16/2007
04/10/2007
07/19/2007
09/04/2007
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服用禁用藥品日期
12/28/2006 - 08/28/2007
11/26/2006 - 07/18/2007
06/26/2007 - 07/24/2007
10/16/2006 - 11/27/2007
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不預警查核 - 中心甲
所有受試者均服用同一種Group 1禁用藥品。
 有些受試者在進入試驗前即服用。
 有些受試者是在試驗中服用。
 有些受試者服用Group 1禁用藥品長達11個月。
 所有Group 1禁用藥品開立處方均有試驗主持人之
蓋章。

61
2017/4/11
不預警查核 - 中心甲

62
研究護士未確認受試者未服用Group 1禁用藥品即
在排除條件勾選“No”。
在事件發生後才進行檢查全部受試者是否服用
Group 1禁用藥品後，才將試驗前服用Group 1禁
用藥品改為“Yes”。(Falsification of data)
2017/4/11
不預警查核 - 中心甲

試驗委託者的個案報告表登錄併用藥品時，亦未
檢查併用藥品是否為禁用藥品。

發生服用Group 1禁用藥品事件後廠商並未立刻進
行稽核。
63
2017/4/11
不預警查核 - 中心乙
篩選：16人
 隨機：13人
 查核當天查核人員至中心乙進行查核時才被告知
主持人無法出席，改由協同主持人代為出席。
 因由協同主持人代為出席故無法回答所有委員的
問題。

64
2017/4/11
不預警查核 - 中心乙
一位受試者因肺炎急診，由急診醫師開立並服用
一個劑量的Group 1禁用藥品。
 發生比例：7.69%

三個受試者服用四種Group 2禁用藥品。
 發生比例：23.1%

65
2017/4/11
不預警查核 - 中心乙

二個受試者發生QTc Prolongation。

未按計畫書在48小時內重複三次QTc之評估。

發生比例：11.8%
66
2017/4/11
不預警查核 - 中心丙
篩選：20人
 隨機：17人
 未發生服用Group 1或Group 2禁用藥品。
 一位受試者多服用試驗研究用藥1顆。
 一位受試者發生QTc prolongation後，當天重複三次ΔQTc
from baseline < 60 msec。

67
2017/4/11
不預警查核 - 中心丁
篩選：12人
 隨機：10人
 提供11位受試者病歷。
 僅提供某一位受試者4/28/2008後之病歷。此一受
試者參與試驗所有原始資料均紀錄於4/28/2008前
之病歷。
 Screening log未登錄Screen failure的受試者。

68
2017/4/11
不預警查核 - 中心丁




69
一位受試者由住院醫師開立並服用一個劑量的Group 1禁
用藥品。
同一位受試者又服用另一種Group 1禁用藥品19天。
發生QTc Prolongation後，才檢查併用藥品才發現服用
Group 1禁用藥品19天。
停用研究藥物後QTc恢復正常，但仍然服用Group 1禁用
藥品，至受試者死亡。
2017/4/11
不預警查核 - 中心丁
另一位受試者發生QTc Prolongation，因遇週末晚
4天停藥。
 另一位受試者服用Group 2禁用藥品未發生QTc
Prolongation。
 未通報服用Group 1禁用藥品。

70
2017/4/11
討論
主持人
未按計畫書執行臨床試驗。
 服用禁用藥品長達11個月且均有主持人蓋章，所以
主持人不可能不知自己所開之藥物。
 不暸計畫書的內容與執行步驟，導致所開藥物為
Group 1禁用藥品。
 填寫個案報告表時未確認資料正確性。
 未監督其團隊確實執行臨床試驗。

71
2017/4/11
討論
試驗委託者
主動通報。
 試驗前主持人會議未充分告知禁用藥品之資訊。
 事件發生前不熟悉禁用藥品。
 未發現受試者長期服用禁用藥品。
 試驗委託者併用藥品資料庫亦未能與禁用藥品相互
比對。
 試驗委託者並不重視違反服用禁用藥品之事件。

72
2017/4/11
討論
醫療機構





倫理委員會為功能性單位，無編制內專業人員。
倫理委員會未能做好監督工作。
中心丁之倫理委員會在衛生署告知後，亦未通報違反服用禁用藥品之
事件。
所有參加臨床試驗受試者之病歷應標籤。非主持人開立處方應與主持
人商確。
應確實執行保存臨床試驗受試者之病歷。(醫療法第70條:人體試驗之病
歷，應永久保存。)
73
2017/4/11
討論



74
Disqualified / Totally Restricted List for Clinical Investigators
FDA regulates scientific studies that are designed to develop evidence to support the safety
and effectiveness of investigational drugs (human and animal), biological products, and
medical devices. Physicians and other qualified experts ("clinical investigators") who
conduct these studies are required to comply with applicable statutes and regulations
intended to ensure the integrity of clinical data on which product approvals are based and,
for research involving human subjects, to help protect the rights, safety, and welfare of
those subjects.
The following list contains the names of all clinical investigators who have been disqualified
or "totally restricted." FDA may disqualify a clinical investigator if the clinical investigator has
repeatedly or deliberately failed to comply with applicable regulatory requirements or the
clinical investigator has repeatedly or deliberately submitted false information to the sponsor
or, if applicable, to FDA. A disqualified clinical investigator is not eligible to receive
investigational drugs, biologics, or devices. In the past, the phrase "totally restricted" was
also used to refer to clinical investigators who had been disqualified. Where an investigator
has been reinstated, it is so noted.
2017/4/11

Disqualified / Totally Restricted List for Clinical Investigators

It is important to underscore the difference between "totally restricted" clinical investigators
and "restricted" clinical investigators. "Totally restricted" investigators are ineligible to
receive investigational products (absent reinstatement). "Restricted" investigators, on the
other hand, are still eligible to receive investigational products, provided they conduct
regulated studies in accordance with the restrictions specified in their agreement with FDA
and all applicable regulatory requirements.
FDA maintains separate lists for all clinical investigators who have agreed to certain
restrictions with respect to their conduct of FDA regulated studies; clinical investigators who
were previously subject to restrictions which have been removed; and clinical investigators
who, under regulations in effect until 1987, provided adequate assurances with respect to
their future compliance with requirements applicable to the use of investigational drugs and
biologics

75
2017/4/11
討論
查核作業
十年來未有重大的改變。
 制式化、書面審查。
 無編制內專職、專業查核單位及人員進行獨立查核。
 不同醫療機構的委員互相查核，無法公正、深入，以免得
罪同僚。
 球員vs. 裁判(均為業餘)。
 Conflict of interest and financial disclosure。

76
2017/4/11
討論
77
2017/4/11
建議

查核制度、作業應作重大改變







78
專職機構與專人
方向與重點
方式
查核結果列入查驗登記
查核結果列入醫院評鑑
查核結果列入倫理委員會評鑑
預防重於治療，教育與觀念-建立主持人正確的心態。不要鑽
法規漏洞。按計畫書確實執行試驗。
2017/4/11
建議

國內查核-可延至一天、國外查核-可為一至二天。

建立編制內專職、專業查核單位及人員進行獨立查核。
專業查核人員不一定為醫師、藥動專家、或統計專家。但必須充分授
權，代表政府，行使公權力。
書面審查+人員一對一訪談+場所視查。
查核臨床試驗的執行與過程，而不是聽取結果的報告或詮釋。(結果
發表於NEJM，但資料處理作假，paper仍然被retracted)
建立查核新的SOP及查核結果之分類與處置。




79
2017/4/11
建議
預防重於治療
 主持人會議
模擬臨床試驗
 按計畫書執行試驗
 利用資訊系統執行監測工作
 倫理委員會監督
 教育與觀念

80
2017/4/11
建議

查核作業應作重大改變
專職機構與專人
 方向與重點
 方式

查核結果列入查驗登記
 查核結果列入醫院評鑑
 查核結果列入倫理委員會評鑑

81
2017/4/11
BUZZ WORDS
There is no shortcuts in clinical
trials
82
2017/4/11
版權聲明
頁碼
作品
版權圖示
來源/作者
12
《A Doctor's Drug Studies Turn Into Fraud》-The New York Times
http://partners.nytimes.com/library/national/science/health/051799dru
g-trials-industry-2.html
本作品依據著作權法第 46、52、65 條合理使用。
13
Potti A, Mukherjee S, Petersen R, et al., A genomic strategy to refine
prognosis in early-stage non-small-cell lung cancer. N Engl J Med.
2006 Aug 10;355(6):570-80
本作品依據著作權法第 46、52、65 條合理使用。
14-17
《The Cancer Letter Editor's note》-www.cancerletter.com
www.cancerletter.com/downloads/20100906_7/download
本作品依據著作權法第 46、52、65 條合理使用。
版權聲明
頁碼
作品
版權圖示
來源/作者
18-20
《PREDICTORS OF CHEMOTHERAPY RESPONSE:
BACKGROUND INFORMATION》
http://www.google.com.tw/url?sa=t&rct=j&q=&esrc=s&source=web&c
d=1&ved=0CB4QFjAAahUKEwjY8eyfjv7GAhWBE5QKHfRfClU&url=
http%3A%2F%2Fwww.cancerletter.com%2Fdownloads%2F2011040
1_1%2Fdownload&ei=upu3VdisIYGn0AT0v6moBQ&usg=AFQjCNFV
rPJGlkgewDXxYFZSUVlpUhXjMw&sig2=8tv9TO5jGrPjs18bJFRErw
本作品依據著作權法第 46、52、65 條合理使用。
24-28
《藥品優良臨床試驗規範》
http://www.ibmi.org.tw/client/RuleDetail.php?REFDOCTYPID=0ksvgn
i9wnc2kdx6&REFDOCID=0ksz6i2wow5hc1qd
本作品依據著作權法第 46、52、65 條合理使用。
34-35
《臨床試驗申請書》-財團法人醫藥品查驗中心
本作品依據著作權法第 46、52、65 條合理使用。
版權聲明
頁碼
38
40-48
51
52
作品
版權圖示
來源/作者
台灣大學劉仁沛教授。
以創用CC「姓名標示－非商業性－相同方式分享」臺灣3.0版授權釋出。
《Good Clinical Practice》-- Food and Drug Administration
http://www.fda.gov/AboutFDA/CentersOffices/OfficeofMedicalProducts
andTobacco/CDER/ucm090259.htm
本作品依據著作權法第 46、52、65 條合理使用。
台灣大學劉仁沛教授。
以創用CC「姓名標示－非商業性－相同方式分享」臺灣3.0版授權釋出。
台灣大學劉仁沛教授。
以創用CC「姓名標示－非商業性－相同方式分享」臺灣3.0版授權釋出。
版權聲明
頁碼
作品
版權圖示
來源/作者
74
《Good Clinical Practice》-- Food and Drug Administration
http://www.fda.gov/AboutFDA/CentersOffices/OfficeofMedicalProduct
sandTobacco/CDER/ucm090259.htm
本作品依據著作權法第 46、52、65 條合理使用。
75
《Court Updates and Other Enforcement Activities continued 2001》
-DISQUALIFIED/TOTALLY RESTRICTED LIST FOR CLINICAL
INVESTIGATORS
http://ppt.cc/C9B4A
本作品依據著作權法第 46、52、65 條合理使用。
77
《Review Casts More Doubts on a Lung Cancer Study》- The New
York Times By GARDINER HARRISAPRIL 29, 2011
http://www.nytimes.com/2011/04/30/health/research/30lung.html
本作品依據著作權法第 46、52、65 條合理使用。