FDA Warning Letters: Don’t Make the Same Mistakes!

Neysa Rhoads, RN, CCRC

Preventive Medicinenrhoads@utmem.edu

April 22, 2023

“Experience is the name everyone gives to their

mistakes” --Oscar Wilde

What are Good Clinical Practices?

Guidelines for the Investigator

Guidelines for the Trial Sponsor

Guidelines for the Clinical Trial Protocol

Guidelines for the Investigator’s Brochure

Fraud

In the broadest sense, a fraud is a deception made for personal gain. The specific legal definition varies by legal jurisdiction. Fraud is a crime, and is also a civil law violation. Many hoaxes are fraudulent, although those not made for personal gain are not technically frauds. Defrauding people of money is presumably the most common type of fraud, but there have also been many fraudulent "discoveries" in art, archaeology, and science.

From http://en.wikipedia.org/wiki/Fraud

Objectives

Identify different types of misconduct and falsification in research

Discuss causes and consequences of misconduct

Learn from other’s mistakes

Synonyms for Fraud & Misconduct

Wrong Doing Deception

Felony Malpractice

Unethical Behavior Mischief

Cheating Felony

Unprofessional Swindling

Deceit Crime

Misconduct

Three categories of misconduct:– Illusion of Knowledge– Surprisingly Sloppy– Malicious Malfeasance

Detecting, Correcting and Preventing

FDA Sanctions

Resources

Woollen, S.W., n.d.

The Illusion of Knowledge

Lack of understandingMisconduct of the uninformed kind

Examples: Backdating the subject’s signature on a consent form because the subject forgot to date the form, creating source documents from CRF’s, discarding source document after accurate transcription and reporting transcribed data as original.

Surprisingly Sloppy

Lazy

Inaction, inattention to detail, inadequate staff, lack of supervision

Examples: ICF inadvertently not obtained from subjects, blood pressures rounded to the nearest 10mmHg, data estimated rather than actually measured, protocol ignored or shortcuts taken

Malicious Malfeasance

Deliberate action to deceive or mislead

F _ _ _ _

Examples: creating, altering, recording, or omitting data

Data does not represent what actually occurred

Falsification of Data

FDA focus: Falsification of Data– Deliberate or repeated noncompliance can

be considered misconduct and is secondary focus of FDA

Recognizing Research Misconduct

Research misconduct means falsification of data in proposing, designing, performing, recording, supervising or reviewing research or in reporting research results

Consequences

Places subjects at possible safety risk

Jeopardizes the reliability of the data

What Causes Fraud

Study staff that does not have the necessary resources and support to accomplish their tasks

Study staff have unreasonable demands placed upon them

Grand enrollment incentives

Just tell the truth

“Research for Hire: Second of Two Articles. A

Doctor’s Drug Studies Turned Into Fraud”

New York Times, May 1999

Dr. Robert Fiddes

Reports of Fraud by his staff went unnoticed

June 1996, auditors took notice

Plead guilty to fraud

“The Emperor Has No Clothes!”

Do’s and Don’ts

Do– Fill in all blanks– Enter date and times– Make sure information is accurate and matches

throughout the chart– Complete documentation the day of the visit– Write a progress note!– Do the right thing!

Do’s and Don’ts

– Don’t Cut corners– Don’t Backdate– Don’t use liquid paper or pencil– Don’t re-create– Don’t perform study related procedures

before the ICF is signed

FDA Sanctions

Warning Letters

Formal Disqualification

Clinical Hold

Voluntary Agreements

Debarment

Prosecution

Expectations of an Audit

Auditors work on the assumption the records are bogus and the study is a fraudThey are taught to carefully review and evaluate the Labs, ECGs & X-RaysQuestion missing informationLook out for denial and shifting of blameVerify then trust

FDA Misconduct

You failed to obtain informed consent of each human subject in accordance with 21 CRF 50

[21 CRF 312.60]

Lab samples drawn prior to signing and dating the ICF

IRB approved ICF required actual time in which legally effective IC was obtained. No documentation of the actual time. Unable to verify subjects signed & dated prior to protocol specific procedures being conducted on them

You failed to obtain informed consent of each human subject in accordance with 21 CRF 50

[21 CRF 312.60]

ICF not approved by IRB

ICF not signed prior to implanting investigational device

You failed to obtain informed consent of each human subject in accordance with 21 CRF 50

[21 CRF 312.60]

No written documentation that IC was obtained

IRB approved a 3 page document. Found subjects who were consented with a 1 page ICF and unapproved ICF’s

IRB approved ICF signed after study device was utilized

You failed to obtain informed consent of each human subject in accordance with 21 CRF 50

[21 CRF 312.60]

Subject signed consent form for incorrect studyConsent not signed until 11 days after study related procedure. Handwritten note states, “I was informed about study and risk-did not sign consent 6-26-03”No documentation that subject was given copy of the signed informed consent

You failed to obtain informed consent of each human subject in accordance with 21 CRF 50

[21 CRF 312.60]

Prior to any study related procedures being performed, subject was given a copy of the ICF to read. Subject was given the opportunity to have her questions answered and wishes to participate in the TREAT trial. Subject willingly signed consent with witness present and copy of signed consent given to subject for her records. Neysa Rhoads, RN

Characteristics of Quality Data

Accuracy

Immediacy

Legibility

Durability

Integrity

Consistency

Honesty

Warning Letter

Most Recent Warning Letters are on the FDA website

Read Them, See What Others Did Wrong

Learn from the Mistakes of Others

Summary

Knowledge is Power

If it Looks Like a Skunk, Acts like a Skunk and Smells Like a Skunk…… IT’S A SKUNK!!!!

“The only real mistake is the one from which we learn nothing” --John Powell

References

www.fda.gov/foi/warning_letters

Wollen, S.W. (2003). Retrieved on 6/13/08 from http://www.fda.gov/oc/gcp/slideshows/2003/gcp2003.ppt

Wollen, S.W. & Hage, A.E. (2001). Retrieved on 6/13/08 from http://www.fda.gov/oc/gcp/slideshows/misconduct2001/misconduct.ppt

Eichenwald, K. & Kolata G. (1999). A doctor’s drug trials turn to fraud. Retrieved from http://www.nytimes.com