QA Talk Research Misconduct - Part II

As previously mentioned I've been involved with overseeing corrective action for three research misconduct sites. I'm going to back it up a a little and talk about how research misconduct was discovered.

CANADA: The first case of research misconduct I investigated occurred when a Clinical Research Coordinator (CRC) decided to throw away the investigational drug (pills) that was suppose to be given to the patient and then document in the patient records that they took it. The Monitor (CRA) found this purely by accident. During a monitoring visit the CRA was checking drug reconciliation and noticed the amount of drug taken by the subjects and the amount returned to the site was recorded in the subject's source notes. But the CRA could not find the bottle to verify the count. So, the CRA opened the CRC's desk drawer to get a sticky note and leave a message inquiring about the missing bottle and guess what she found???? the box of medication in the desk drawer UNOPENED!!..the medication had never been dispensed to the patient. So now the CRA wants to know how the CRC have numbers in the source document indicating the subject took a certain amount of pills when they never even got the box. She tried to lie and say the CRA was mistaken but the CRA had another CRA with her who could verify everything she said. When the PI was finally contacted and informed and he questioned the CRC, she said she was upset and stressed due to person events in her life (i.e. death of a friend, etc.), she had never had a patient that didn't take the drug and she didn't know what to do so she panic and opened the bottle, count the pills that was suppose to be taken and she threw them out.

Now - why should I the auditor believe this was a one time event bought on by stres???? When I audited the site, there were more than 35 EKG's for various subjects with altered dates and initials. For example, the years were changed from 1987 to 2003 or 1998 to 2003, 2001 to 2003, etc. There were vital signs recorded for at least one subject who was suppose to be on vacation outside the country; blood pressures were the same for many of the subjects, and the list went on. There was a lot of things at that site that should have been noted as fraudulent. I wrote my report submitted it to the sponsor and they tried to defend it. I recommended they contact the regulatory authorities. I was "blackballed" by that sponsor. They just didn't want to know about problems with their study. Needless to say, their drug failed and never made it to market. When you leave out quality - you're openly courting failure.

USA: The second case was a real doozie! The CRC allegedly forged the PI's name, took most of the money and bribed the subjects. He was an ex-pharmacist who had gotten his licensed revoked for stealing prescription drugs and forging hospital doctor's names on prescriptions. The doctor had no idea. He had even hit the sponsor up for money and signed the doctor's name on the contract. He allegedly signed the doctor's name on lab reports and several other patient records without the doctor's knowledge. This doctor paid more than $70,000 in lawyer fees after the FDA inspection.

INDIA: The third case involved a CRC wanting to participate in the clinical trial. Therefore, the CRC signed a fake name in the patient section of the informed consent form and his real name in the Consentor section of the ICF. He consented himself under a fake name. He also forged his co-worker's name on research reports, This person was so busy forging other people names and dates until he got all confused and wrote a date that hadn't even happened yet. For example, he claimed a subject was consented November 2008. The subject was consented January 2008.

All of the above cases had the initial discovery by CRAs. As stated previously, fraud is hard to find and sometimes harder to prove. But the main thing to convey here is you need to make sure you're trained on what to look for so that you can spot it during your monitoring visits. The second case with all of the forgeries ran for more than 3 years before the fraud was discovered and reported to the sponsor. One problem was the CRO kept changing Monitors. It's hard for a monitor to get a good grasp of the sites practices if you're rotating them so a sponsor should not allow the CRO to rotate the monitors. Let the CRA develop a relationship with the site's CRC. A good working relationship is important to the success of the trial at that site. Once the fraud is discovered, the CRA should report it in writing. Sponsors are not happy about this information, especially if it's one of their high enrolling sites. They do not want to lose that data, especially if it's 3 years worth of data! They therefore might be real reluctant about reporting the site to the proper authorities. To protect yourself, it's important that you submit to the sponsor in writing, your findings and your suspicions of fraud (if applicable) and keep a copy in your files. If you send by email, make sure you turn on your "read receipt". print it out and file it with your email. Remember, it might be five years down the road before the FDA inspects this trial for marketing purposes. If that's the case, you may have moved on and you don't want fingers pointing at you. This is your career we're talking about and you must protect yourself.

QA Talk - Research Misconduct - Part 1

As many of you know, I specialize in conducting audits of research investigators and various entities in the pharmaceutical and biotechnical industry. I've been auditing for more than 10 years now and in doing so I have been involved with 3 investigator sites guilty of research misconduct (as defined by the Office of Research Integrity or ORI) and countless sites guilty of sloppy practices that looks as bad as research misconduct. These sites were located in Canada, India and the United States. These are only the sites that were discovered because they were unlucky (or lucky depending on your point-of-view) enough to be chosen for an audit.


Do you know that most people go through this job for 20 to 30 years and never identify research misconduct? And I have personally identified 2 and assisted with 1 in less than 5 years. Is research misconduct on the rise or has it been there all along and we've been missing it?

Could you identify alleged research misconduct (i.e. fraudulent practices) if you saw it? Do you know what to look for and how to assess what you find?

I'll be the first to admit that research misconduct is not easy to identify and once you've found it - oh, the work involved! I've spent anywhere from 2 weeks to 1 month investigating misconduct.

In a series of articles on this blog, I will tell you how most of my discoveries come about and then I'll tell you how I handled them.

HEY CRA's! LISTEN UP!!!

Do you know that if you're the CRA for a site that's found to be fraudulent, the FDA could hold you responsible for not identifying the problem?

For one of the sites reported to the Agency, I attended the FDA inspection. The inspector made a point of assessing the CRA's monitoring reports to the site. The investigator also questioned the CRA's experience, and wanted to know why the CRA did not find the problem before I found it. Well, I could not answer that because I honestly did not know. But another colleague told me that the CRA working a clinical site for his company was cited by the FDA for not discovering the misconduct "early enough" in the monitoring practices. I don't know a lot about that situation but I will say that I can imaging any "run-in" with the FDA or any other regulatory agency have got to be pretty unnerving. Finding yourself in a position of defending your expertise, in fact, your performance cannot be stress-free. Additionally, it does not bode well with your company who is probably looking for a scape goat anyway.

For the site where I discovered miscoduct - when I made my report to that company's senior management, the first question asked was "Why didn't the monitors catch this?" then it moved on to "Why didn't the project manager catch it - afterall, they visited the site, too?" The one thing I've learned in the corporate environment is that somebody must always be "blamed". Now, from my standpoint (it's the QA in me), I'm thinking: "How bad is it? Were any subjects hurt? Can the PI be brought into compliance?" Then I realized that management was still stuck on finding a scapegoat so I had to wait for them to play catchup to me. (lol)

Anyway, from my experience, I would caution you to take your monitoring duties seriously and if you don't know the regulations governing monitoring practices, you really should learn them. Compliance is about more than making sure the investigator's site is following the sponsor's instructions (which sometimes contradicts the approved protocol).

In Part 2 of this series, I will discuss "discovering" the misconduct and how it was handled afterwards.

Until then.......

Have a Quality day!