Writing Sample: Clinical Trial Gone Wrong

CLINICAL TRIAL GONE WRONG

by Louis Sheehan

As a result of a Food and Drug Administration (“FDA”) inspection, in 2005, Paul H. Kornak (variously as “site coordinator” or “Kornak”) signed a Plea and Cooperation Agreement [1],[2] and in 2008 Dr. James A Holland (variously as “clinical investigator” or “Dr. Holland”) was the subject of a Sentencing Memorandum [3],[4] both due to their involvements, in part, in a clinical trial resulting in the death of Mr. James J. DiGeorgio. Among other fraudulent activities, the site coordinator had misreported test results which had the effect of concealing Mr. DiGeorgio’s insufficient liver and kidney functions, whereby and subsequent to the first trial dose Mr. DiGeorgio expired. In the teeth of numerous indications [5] that the site coordinator was engaging in criminal behavior and acknowledging his responsibility to maintain accurate records, the clinical investigator rationalized the site coordinator’s behavior as being that of a well experienced employee and excusable for varying reasons. Curiously, despite the fact that this matter is thoroughly revealed in both FDA and court documents, none of the peer-reviewed publications of the chemotherapy study make mention of any aspects of the criminal activities. [6]

A component of the FDA’s mandate to evaluate and approve or deny medications for marketing is the performance of audits of clinical trials vis-à-vis statutory, regulatory, and other guidance.[7] At its core, comportment with the FDA’s guidance establishes the effectuation of good clinical practices and the protection of subjects’ human rights. Ipso facto, compliance tends to suggest the acquisition of appropriate clinical data and non-compliance suggest otherwise. Normally a complaint investigation takes about a week, but in this case the FDA remained on-site for 50 days. The FDA reviewed the files of at least 50 subjects and flagged every one. [8]

Among many other (often criminal) violations, Kornak lied [9] about having any prior conviction(s). Additionally in this matter, Kornak falsified records relating to:

  1. electrocardiograms (as well as to whether or not the subjects actually had electrocardiograms),
  2. laboratory analyses,
  3. an ejection fraction,
  4. blood draws on reported dates,
  5. a final surgical pathology report,
  6. an operative note,
  7. a letter,
  8. a radiology report,
  9. an urology progress note, and
  10. an urethrocystogram. [10],[11]

Regarding Dr. Holland, he dismissed a monitor’ expressed concerns about Kornak’s documentation and behavior with the explanation that Kornak was appropriately experienced. Three months later Kornak admitted to Dr. Holland that he had placed information into a subject’s record in this clinical trial that actually related to another subject on another day at another hospital. At this point, Dr. Holland excused Kornak’s behavior on the basis of Kornak’s inexperience! Further and frieghteningly, Dr. Holland admitted he did not look at Mr. DiGeorgio’s blood chemistry test results which showed Mr. DiGeorgio did not fit within the study’s parameters and Mr. DiGeorgio had insufficient liver and kidney functions.

Kornak was disbarred for life vis-à-vis the FDA, sentenced to 71 months imprisonment and to pay restitution to the study sponsors in the amount of $639,000 as well as an additional amount to the victims. Dr. Holland was disbarred for five years.[12] Subsequently, Dr. Holland was employed by Archbold Memorial Hospital in Thomasville, Ga. Archbold Memorial Hospital represented that Georgia’s medical board had found no evidence of misconduct on the part of Dr. Holland. [13]

Interestingly, none of the peer-reviewed articles of and/or referring to this specific clinical trial performed under the auspices of Kornak and Dr. Holland include any allusions – let alone specific references — to the criminal activities.[14] However, the FDA has undertaken no effort to organize and communicate criminal findings [15] thus creating an environment wherein relevant and significant information is difficult or even impossible to find.

[1] United States of America v. Paul H. Kornak, Criminal Action No. 03-CR-436 (FJS). January 18, 2005. http://www.circare.org/lex/03cr436.pdf Accessed March 7, 2015.

[2] See also: NOOH issued to Paul H. Kornak, May 4, 2009

http://www.fda.gov/RegulatoryInformation/FOI/ElectronicReadingRoom/ucm181014.htm Accessed Match 7, 2015.

[3] United States of America v. James A. Holland, Criminal Action No. 07-CR-202 (FJS). http://www.circare.org/lex/07cr202_20080317.pdf Accessed March 7, 2015.

[4] Se also: NIDPOE issued to James A. Holland, September 22, 2004

http://www.fda.gov/RegulatoryInformation/FOI/ElectronicReadingRoom/ucm105756.htm Accessed March 7, 2015.

[5] Records were falsified relating to 69 people in this matter alone.

[6] Charles, S. (2015). Research Misconduct Identified by the US Food and Drug Administration Out of Sight, Out of Mind, Out of the Peer-Reviewed Literature.. JAMA Intern Medhttp://archinte.jamanetwork.com/article.aspx?articleid=2109855 Accessed March 7, 2015.

[7] US Food and Drug Administration, Office of Good Clinical Practice. Information sheet guidance for IRBs, clinical investigators, and sponsors: FDA inspections of clinical investigators. June 2010. http://www.fda.gov/downloads/RegulatoryInformation/Guidances/UCM126553.pdf.%20Accessed%20July%2016 Accessed March.7, 2015.

[8] Sontag, D. (2005). Abuses Endangered Veterans in Cancer Drug Experiments. The New York Times, February, 6, 2005. http://www.nytimes.com/2005/02/06/nyregion/06vets.html?pagewanted=print&position&_r=0 Accessed March 7, 2015.

[9] Kornak had attended a medical school for a limited time period. Previously, Kornak forged his credentials in several states and obtained (and eventually lost) medical licenses. While not part of this particular conviction, Kornak also made representations to subjects that he was a medical doctor. Sontag, D. (2005). Abuses Endangered Veterans in Cancer Drug Experiments. The New York Times, February, 6, 2005. http://www.nytimes.com/2005/02/06/nyregion/06vets.html?pagewanted=print&position&_r=0 Accessed March 7, 2015.

[10] The FDA believes Kornak was involved in five fraudulent studies. Sontag, D. (2005). Abuses Endangered Veterans in Cancer Drug Experiments. The New York Times, February, 6, 2005. http://www.nytimes.com/2005/02/06/nyregion/06vets.html?pagewanted=print&position&_r=0   Accessed March 7, 2015.

[11] Again, while not a component of this conviction, in 2001 Kornak told a Mr. Steubing that Mr. Steubing was well-suited for a clinical trial relating to Mr. Steubing’s gastroesophogel cancer. Subsequently, a three-drug combination was given to Mr. Steubing approximately six times. Each infusion made Mr. Steubing so ill he had to be hospitalized after each administration. Mr. Steubing died in March 2002. Sontag, D. (2005). Abuses Endangered Veterans in Cancer Drug Experiments. The New York Times, February, 6, 2005. http://www.nytimes.com/2005/02/06/nyregion/06vets.html?pagewanted=print&position&_r=0 Accessed March 7, 2015.

[12] Federal Register Volume 75, Issue 42 (March 4, 2010) http://www.gpo.gov/fdsys/granule/FR-2010-03-04/2010-4449 Accessed March 7, 2015.

[13] Sontag, D. (2005). Abuses Endangered Veterans in Cancer Drug Experiments. The New York Times, February 6, 2005. http://www.nytimes.com/2005/02/06/nyregion/06vets.html?pagewanted=print&position&_r=0 Accessed March 7, 2015.

[14] See:

(a) Ajani,J.A.  Docetaxel in combination for advanced gastric cancer. Gastric Cancer. 2002;5(suppl 1):31-34.

(b) Ajani,J.A, Fodor,M.B, Tjulandin,S.A,  et al.  Phase II multi-institutional randomized trial of docetaxel plus cisplatin with or without fluorouracil in patients with untreated, advanced gastric, or gastroesophageal adenocarcinoma. J Clin Oncol. 2005;23(24):5660-5667.

(c) Messing,E., Kim, K.M., Sharkey, F.,  et al.  Randomized prospective phase III trial of difluoromethylornithine vs placebo in preventing recurrence of completely resected low risk superficial bladder cancer. J Urol. 2006;176(2):500-504.

(d) Tannock,I.F, de Wit,R., Berry,W.R.,  et al; TAX 327 Investigators.  Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer. N Engl J Med. 2004;351(15):1502-1512.

(e) Van Cutsem, E., Moiseyenko, V.M., Tjulandin, S.,  et al; V325 Study Group.  Phase III study of docetaxel and cisplatin plus fluorouracil compared with cisplatin and fluorouracil as first-line therapy for advanced gastric cancer: a report of the V325 Study Group. J Clin Oncol. 2006;24(31):4991-4997.

[15] Charles, S. (2015). Research Misconduct Identified by the US Food and Drug Administration Out of Sight, Out of Mind, Out of the Peer-Reviewed Literature.. JAMA Intern Medhttp://archinte.jamanetwork.com/article.aspx?articleid=2109855 Accessed March 7, 2015.

Clinical Trial Gone Wrong3.7.15.1.docx

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Louis Sheehan
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