HCR 350: Intro Clinical Research - Assignment II: Investigator Disqualification
Dr. Manjeet Kaur Achreja, M.D. worked at the Seagrove Medical Clinic in Seagrove, North Carolina. The FDA conducted an investigation between August 25 and September 3, 2003, and found that Dr. Achreja, M.D. submitted falsified information to the FDA or sponsor. They also found that Dr. Achreja, M.D. repeatedly violated the regulations regarding the proper conduct of clinical studies involving investigational products (Title 21, Code of Federal Regulations (CFR), Part 312). He was given the opportunity to explain why he backdated clinical research logs and the FDA explained that he had lost credibility because of his actions. The FDA audited 37 out of 116 total subjects’ records and they found notes on three subjects (they were redacted) that were backdated.
The progress notes for the subject [redacted] stated that a headache was an adverse event (AE) that started on 02/26/02 and ended on 02/27/02. “However, the progress notes covering the period between 01/18/02 – 02/29/02 indicate that headache occurred on 02/29/02 (February only had 28 days in 2002).” (FDA and Public Health Service. 2007, August 29. CDER: Notice of Initiation of Disqualification Proceeding and Opportunity to Explain (NIDPOE); Date Issued: 08/29/2007. Retrieved from https://www.fda.gov/regulatory-information/electronic-reading-room/cder-notice-initiation-disqualification-proceeding-and-opportunity-explain-nidpoe-date-issued-5 ). The FDA also found that the case histories did not have accurate records in them, and he failed to make sure that the study was following the investigational plan [21 CFR 312.60]. The informed consent [21 CFR 50.27(a)] was also not documented correctly according to the FDA’s findings. The FDA would not accept Dr. Achreja, M.D.’s explanation written on October 7, 2003, about his subjects’ records as the records were inadequate and inaccurate.
Dr. Manjeet Kaur Achreja, M.D. violated to conduct studies in accordance with relevant, current protocol(s) and to only make changes in a protocol after notifying the sponsor, except when necessary to protect the safety, rights, or welfare of subjects. Dr. Achreja, M.D. also violated to report to the sponsor the adverse experiences in accordance with 21 CGR 312.64. He also failed to maintain adequate and accurate records in accordance with 21 CFR 312.62, but he did make those records available for inspection in accordance with 21 CFR 312.86. These were violated due to Dr. Achreja's backdating records and stating that the adverse effects (AE) occurred on 02/26/02 and ended on 02/27/02. However, the progress notes covering 01/18/02 – 02/29/02 that the headache occurred on 02/29/02 when there were only 28 days in February.
However, Dr. Achreja, M.D. did provide all the records to the FDA investigators even though there were violations that were committed. He provided falsified information and provided the wrong dates on events during the study. Also, Dr. Achreja, M.D. did fail to maintain adequate and accurate stories for the cases that recorded all of the observations and the other data that was important to the investigation on each subject [21 CFR 312.62(b)]. “According to the protocol, study visit 3 should have occurred between 02/21/02 and 02/26/02.” (FDA and Public Health Service. 2007, August 29. CDER: Notice of Initiation of Disqualification Proceeding and Opportunity to Explain (NIDPOE); Date Issued: 08/29/2007. Retrieved from https://www.fda.gov/regulatory-information/electronic-reading-room/cder-notice-initiation-disqualification-proceeding-and-opportunity-explain-nidpoe-date-issued-5 ). According to the investigative findings, it was unclear on the study date visit 3 had occurred and which one is the correct progress note.
Dr. Achreja, M.D. failed to provide facts about the studying being conducted according to the investigational plan [12 CFR 312.60]. He also failed to provide laboratory blood test results for ALT, AST, total bilirubin, and alkaline phosphatase for three subjects. Dr. Achreja, M.D. also stated in the October 7, 2003, written response that the lab results were missing. However, he then later stated that they were found or the blood that was drawn was lost. The FDA investigator found that this explanation was unacceptable.
“You failed to adequately document informed consent [21 CFR 50.27(a)].” (FDA and Public Health Service. 2007, August 29. CDER: Notice of Initiation of Disqualification Proceeding and Opportunity to Explain (NIDPOE); Date Issued: 08/29/2007. Retrieved from https://www.fda.gov/regulatory-information/electronic-reading-room/cder-notice-initiation-disqualification-proceeding-and-opportunity-explain-nidpoe-date-issued-5 ). The informed consent document was not approved by the IRB nor was it signed or dated by the subject or the legally authorized representative for the subject on the day to sign the consent form. The FDA found that the two subjects signed the consent forms but did not date them. Dr. Achreja, M.D. stated that the two subjects did sign the consent forms but did not date them, so his assistant instead recorded the date on the consent forms. The FDA did not approve of this explanation as the subjects, or the authorized designees (legally authorized representatives for the subjects) must legally sign and date the consent forms.
I do think that Dr. Manjeet Kaur Achreja, M.D. compromised the goals of demonstrating the safety and efficacy of the clinical trial due to his actions and lack thereof. Understanding side effects is important when it comes to drug safety with patients. However, when documenting the wrong adverse effect (AE) dates can damage not only the credibility of the person conducting the study but also the side effects of the drug. When releasing a drug to the world after FDA approval, it’s important to know when to expect which possible side effects because even though everyone’s bodies react differently to each drug doesn’t mean it’s not important to know when the adverse effect can happen. However, Dr. Achreja, M.D. also stated that there were no side effects and no complaints from the subject, and he stated that the study was completed.
There was also conflicting information when it came to the subject’s medical history, the need for dose reduction due to renal impairment, and the subject’s date of birth. This is important for effective data for research and clinical data. For instance, let’s say I have a medical history that could cause an adverse effect when the drug enters my system. It’s like when it comes to reporting to your physician’s each thing you take including herbs you take due to drug-herb, herb-herb, and drug-drug reactions. This is the same concept because the drug could be more dangerous due to a medical history or cause more or different side effects for the subject than others.
I do believe that his being disqualified was an appropriate call for punishment because of falsifying results, providing inadequate and inaccurate case histories, and failing to ensure the study was being conducted following the investigational plan [21 CFR 312.60] is extremely dangerous for subjects and potential future patients. He also didn’t provide blood laboratory results of the ALT, AST, total bilirubin, and alkaline phosphatase and then lied about them going missing, being found, and then the drawn blood being lost. Falsifying informed consent forms is alarming because how can someone trust that the subject or the legally authorized representative signed the consent form if it was being inaccurately documented by the assistant? There’s plenty of credibilities to be lost in this case so it’s difficult to trust much was being done correctly in the beginning. I deal with ABNs and estimate financial responsibilities with my current job and when a legally authorized representative signs the patient’s name I sometimes must reprint the document(s) because I didn’t ask for a forged signature, I asked for a legally obtained signature either it be the actual patient or the legally authorized representative.
In conclusion, it’s imperative to include all legal documents to be accurately documented and all results to be recorded with accurate dates, times, and findings. If I must be super careful with my current job on documentation for legal purposes and accurate purposes, then so should clinical researchers. I don’t believe in forging results and falsifying findings because it’s dangerous for future use and current subjects. There are researchers who falsify results due to needing their research to work, however, if it doesn’t work then it doesn’t work and that is the whole purpose of clinical research. Researchers must learn that it’s ok when clinical research doesn’t work, it’s also ok to reassess the research and start again later.
Resources
· FDA and Public Health Service. 2007, August 29. CDER: Notice of Initiation of Disqualification Proceeding and Opportunity to Explain (NIDPOE); Date Issued: 08/29/2007. Retrieved from https://www.fda.gov/regulatory-information/electronic-reading-room/cder-notice-initiation-disqualification-proceeding-and-opportunity-explain-nidpoe-date-issued-5
