Seminar - Fraud in Clinical Trials

 

UCL, Auditoire SOCR-242, Place du Cardinal Mercier 10, 1348 Louvain-la-Neuve

 

 

Monday, April 20, 2015

Seminar 11:00 am - 12:45 pm  |  Walking lunch 1:00 pm - 2:00 pm

 

 

 

 

Seminar organized jointly by

Prof. Catherine Legrand 
UCL  |  Institut de Statistique, Biostatistique et Sciences Actuarielles 

and Marc Buyse
IDDI  | 30 avenue provinciale | 1340 Louvain-la-Neuve
CluePoints S.A. | Axis Parc  |  Rue Emile Francqui 1 - 1435 Mont-Saint-Guibert 
    

Registration is free but mandatory. Please click on this link to access the registration form

  

Fraud in Clinical Trials: "Definitions, incidence, examples, causes"

Stephen L George, Ph.D.  |  Professor Emeritus of Biostatistics
Duke University School of Medicine |  Durham, North Carolina, USA

 

Abstract

Highly publicized cases of fabrication or falsification of data in clinical trials have occurred in recent years and it is likely that there are additional undetected or unreported cases. I will review the available evidence on the incidence of data fraud in clinical trials; describe several prominent cases; and present information on motivation and contributing factors. There is no reliable evidence that data fraud, the deliberate fabrication or falsification of data, is a common occurrence in clinical trials. Moreover, in multicenter clinical trials, fraud perpetrated by a single investigator or at a single site is very unlikely to affect the scientific conclusions of the trial. However, whatever the true incidence of data fraud in clinical trials, high-profile cases provide sobering evidence that it does occur regularly. When fraud is detected after the results have been announced, the negative impact on the perception of the results of the trial in question as well as on the public perception of the clinical trial enterprise itself can be profound.

Biography

Stephen L George, Ph.D., is Professor Emeritus of Biostatistics in the Department of Biostatistics and Bioinformatics at Duke University School of Medicine. He served for over 20 years as Director of Biostatistics in the Duke Comprehensive Cancer Center and Director of the Statistical Center of the Cancer and Leukemia Group B (CALGB). He has been closely involved in the design, conduct, and analysis of cancer clinical trials and other research projects in cancer throughout his career. Dr. George is a Fellow of the American Statistical Association and of the Society for Clinical Trials; served as Treasurer and a member of the Executive Committee of the International Biometric Society for eight years; is a past President for the Society for Clinical Trials; and served for four years as the biostatistician for the Oncologic Drugs Advisory Committee for the Food and Drug Administration.

 

 

Fraud in Clinical Trials: "The Krebiozen story"

Edmund Gehan, Ph.D. |  Professor Emeritus of Biostatistics
Georgetown University  |  Washington DC, USA

 

Abstract

Krebiozen was initially promoted by Stevan Durovic, a Yugoslavian physician who claimed that the substance came from horse serum inoculated with Actinomyces bovis and had been useful in the treatment of cancer. His claims were backed by Andrew Ivy and by several politicians including Senator Paul Douglas. Ivy tested Krebiozen on patients and called a press conference in 1951 at which he announced that of 22 treated patients, 14 were alive and none had died of cancer. Intrigued by Ivy's announcement, 10 hospitals and cancer research centers followed up on the trial and attempted to reproduce the results. All of these independent researchers observed no effect of Krebiozen on cancer. A compilation of these institutions' negative data was published in JAMA in 1951. In 1964, Durovic and Ivy were indicted for introducing mislabeled drugs into interstate commerce. They were acquitted after a 9-month trial. Krebiozen consists only of the amino acid creatine dissolved in mineral oil. Available scientific evidence does not support claims that Krebiozen is effective in treating cancer, but the FDA has warned that creatine may have dangerous side effects.

Biography

Edmund Gehan, Ph.D., is Professor Emeritus of Biostatistics in the Departments of Biostatistics, Bioinformatics and Biomathematics, and the Department of Oncology at Georgetown University. He has contributed to the coordination, conduct, and leadership of trials, methodologic development and education, in a career spanning more than 50 years. He is one of the founders of the profession of clinical trials biostatistician. He developed a cooperative group model in which trials are conducted by statistical centers with independent status. Some of his ground-breaking papers include a two-stage design for phase II clinical trials in cancer, and the first non-parametric statistical test for the comparison of two survival distributions, using an extension of the Wilcoxon test. He has been instrumental in advancing the role of the biostatistician in clinical research. He has served on the Editorial Board of Statistics in Medicine and as a Statistical Editor of the Journal of the National Cancer Institute.

 

 

We Found Fraud. Now What?

Jay Herson, Ph.D.  |  Senior Associate, Biostatistics
Johns Hopkins University  |  Baltimore, Maryland, USA

 

Abstract

Exciting new statistical software has been developed for central monitoring of clinical trials. It is expected that more cases of fraud in confirmatory trials will be uncovered by this method. This paper describes what offensive and defensive actions a sponsor might take in the face of fraud with the objective of salvaging a trial or protecting against the effects of fraud. The case is made for action rather than reaction to fraud. A Fraud Recovery Plan (FRP) is recommended and should to be approved by regulatory agencies before the start of a trial. This plan would prespecify actions to be taken when fraud is found. The types of fraud discussed in this paper are: falsification of eligibility criteria, underreporting of adverse events, fictional patients, fabrication of patient diaries, propagation of vital signs / laboratory data. The paper concludes with general issues such as the role of intent-to-treat, should we eliminate all or just some patients, effect on planned interim analyses, estimation of effect size and randomization implications. The paper concludes with suggestions of how an FRP be administered and several defensive strategies.

Biography

Jay Herson received his Ph.D. in Biostatistics from Johns Hopkins in 1971. After working on cancer clinical trials at MD Anderson Hospital he formed Applied Logic Associates (ALA) in Houston in 1983. ALA grew to be a biostatistical-data management CRO with 50 employees when it was sold to Westat in 2001. Jay joined the Adjunct Faculty in Biostatistics at Johns Hopkins in 2004. His interests are interim analysis in clinical trials, data monitoring committees, and statistical / regulatory issues. He chaired the first known data monitoring committee in the pharmaceutical industry in 1988. He is the author of numerous papers on statistical and clinical trial methodology and, in 2009, authored the book Data and Safety Monitoring Committees in Clinical Trials, published by Chapman Hall / CRC.