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1、Fraud rather, they seemed reluctant to challenge such a prominent figure in the drug-testing business.Dr. Fiddes (cont)Source: “A Doctors Drug Studies Turn Into Fraud,” New York Times, May 17, 1999Several former coordinators for Fiddes said they had reported his unethical conduct to Pat Pryor, an in
2、dependent study monitor working with Pfizer Inc. Tipped off to the discrepancies, Ms. Pryor sharply challenged Fiddes and his staff in her reviews of their paperwork.Dr. Fiddes (cont)Source: “A Doctors Drug Studies Turn Into Fraud,” New York Times, May 17, 1999Fiddes chafed at the challenges, feigni
3、ng outrage. Our integrity and reputation for performing high-quality clinical trial work has been injured, and we are justifiably upset, Fiddes wrote in a July 1995 letter to Pfizer. He insisted Pfizer have a new monitor assigned to our site immediately.Dr. Fiddes (cont)Source: “A Doctors Drug Studi
4、es Turn Into Fraud,” New York Times, May 17, 1999What could the watchdogs have seen that would have allowed them to detect his fraud? Nothing, Fiddes replied.Had it not been for a disgruntled former employee, he would have still been in business.Dr. Fiddes (cont)Source: “A Doctors Drug Studies Turn
5、Into Fraud,” New York Times, May 17, 1999Feb. 1997 Staffers blows the whistle and federal agents storm the siteAug. 1997 plead guilty to felony charge of conspiracy to make false statements to the FDASept. 1998 sentenced to 15 months in federal prison and ordered to pay $800,000 in restitutionDr. Fi
6、ddes (cont)May 1999 profiled on 60 minutes and in the New York Times June 1999 disqualified as a clinical investigator by FDAMar. 2000 medical license revoked Nov. 2002 debarred by FDA along with three study coordinatorsDr. Fiddes (cont)Dr. Fiddes and staff on the FDA Debarment ListFederal Register
7、Notice for Laverne Charpentier DebarmentThomas Jefferson University, Philadelphia - NIH-funded HIV gene therapy studies - False Claims Act settlementMichael McGee, MD - University of Oklahoma - melanoma vaccine trialRichard Borison, MD and Bruce Diamond, PhD - Medical College of Georgia psych and ne
8、uro studiesOther Famous CasesBruce Diamond, PhD “The Lessons of Greed,” PharmaVOICE, July 2004Example “Warning” LetterWarning Letter - Pg 2: Submission of False Information21 CFR 312.56(b): A sponsor who discovers that an investigator is not complying with the signed agreement (Form FDA 1572), the g
9、eneral investigational plan, or the requirements of this part or other applicable parts shall promptly secure compliance or discontinue shipments of the investigational new drug to the investigator and end the investigators participation in the investigation.FDA RegulationsICH E6 - 5.20.1: Noncompli
10、ance with the protocol, SOPs, GCP and/or applicable regulatory requirement(s) by the investigator / institution, or by member(s) of the sponsors staff should lead to prompt action by the sponsor to secure compliance.ICH GuidanceICH E6 - 5.20.2: If the monitoring and/or auditing identifies serious an
11、d/or persistent noncompliance on the part of an investigator/institution, the sponsor should terminate the investigators / institutions participation in the trial and promptly notify the regulatory authorities.ICH Guidance (cont)ICH - E6 4.12: If the trial is terminated prematurely or suspended for
12、any reason, the investigator / institution should inform the trial subjects, should assure appropriate therapy and follow-up for the subjects, and should promptly inform the regulatory authority(ies).ICH Guidance (cont)High staff turnoverStaff are disgruntled, fearful, anxious, depressed, defensive.
13、High pressure work environmentObsession with study paymentsAbsent investigatorsLack of GCP trainingUnusually fast recruitmentGeneral Warning SignsImplausible trends/patterns:-100% drug compliance-Perfect efficacy responses for all subjects-Identical lab/ECG results -No SAEs reported-Subjects adherin
14、g perfectly to visit schedulesData IdentifiersSite data not consistent with other centers (statistical outlier)Perfect diary cards, immaculate CRFsAll source records & CRFs completed with the same penSource records lack an audit trail - no signatures and dates of persons completing documentationData
15、 Identifiers (cont)Subject handwriting and signatures are inconsistent across documents (consents, diaries)Questionable subject visit dates (Sundays, holidays, staff vacations)Impossible events (eg, subject randomized before IP even available at the site)Identifiers (cont)Subject visits cannot be ve
16、rified in the medical chart or appointment schedule Data contains “digit preference” some digits used more frequently than others (0, 5, and even digits)“Halo” around the date or test value indicating the original was obliterated with correction fluidIdentifiers (cont)Ask for all information (data) pertinent to the study (CRFs, study specific source worksheets, clinic charts, sign- in sheets, lab requisitions, shipping records)
