Failing to obtain informed consent prior to randomization
Subjects were added to IVRS prior to consent and could not be removed from the system when parents would not consent
Enrolling subjects who were not eligible
Randomizing three subjects to the wrong study arm
Administering investigational product that had undergone a 30 minute temperature excursion
Failing to perform study required follow up phone calls
Three subjects received prohibited concomitant study medications
EDC audit trails show that procedures originally entered as not done, and not documented in source records were changed to having been done due to a reason of ‘entry error’.
Consent documentation errors, including:
Signing consents prior to the subject’s parents signed
Failing to retain original documents
Changing the time of the consent to appear that consent occurred prior to dosing
FDA did not post any warning letters to Sponsors/Monitors/CROs, IRBs or Clinical Investigators. From the archives, here is the clinical inspection summary for Solosec (Secnidazole oral granules) submitted by Symbiomix Therpeutics. Three sites plus the CRO were inspected. Site inspections ranged from three to seven days. Site selection for inspection were driven by enrollment and site specific efficacy. Site inspections focused on verification of specific line listings from the submissions: subject screening, discontinued subjects, AEs, protocol deviations, and primary / secondary efficacy endpoints. The CRO inspection targeted data management and monitoring activities for ten specific sites. One site received a FDA Form 483.
Dr. Morgan was cited for:
- Failing to adhere to study eligibility criteria, specifically by enrolling one subject who had prior exposure to the investigational product from the Phase 2 study.
Dr. Bhatti was warned for the following, after an inspection that ranged over six weeks:
- Failing to follow the investigational plan, specifically:
- Enrolling two subjects that did not meet inclusion criteria, due to ECG readings. FDA notes that one subject was enrolled prior to the PI reviewing the ECG, and the subject was subsequently removed from the trial.
- Another subject did not meet inclusion criteria due to prior therapy from an earlier trial at the PI's site.
- A number of missed ECGs on the study, which FDA views as an important safety assessment.
- One subject missed required ECGs on three study visits.
- Three subjects missed the week 168 ECG.
- One subject missed the week 120 ECG.
- One subject missed the week 64 ECG.
- One subject had a week 32 post dose ECG twenty minutes prior to the dose.
- One subject missed a required post dose ECG at week 32.
- Failing to retain required records
- ECG tracings were missing for 15 patient visits. FDA notes that the results were reported in medical records, but the actual tracings could not be located.
- One subject questionnaire was not retained at one visit.
FDA did not post any warning letters to Sponsors/Monitors/CROs, IRBs or Clinical Investigators this week. From the archives, here is the Clinical Inspection Summary for Mavyret (glecaprevir/pibrentasavir-ABT-493+ABT-530), submitted by Abbvie. Seven sites were inspected. Inspections ranged from three to seven days. Two sites received FDA Form 483s.
Dr. Jazrawi was cited for:
- Inadequate documentation to support one subject met inclusion criteria for two lab values
Dr. Zogg was cited for:
- Lack of documentation to support kit numbers dispensed and returned. (NOTE: FDA notes that the investigator stated that this function was performed by the Interactive Response Technology provider contracted by the sponsor, but FDA still issued the 483 to the site. FDA further notes that the investigator submitted an acceptable corrective action plan.)
FDA did not post any warning letters to Sponsors/Monitors/CROs, IRBs or Clinical Investigators this week. From the archives, here is the Clinical Inspection Summary for Blincyto (blinatumomab) submitted by Amgen. Three sites plus the sponsor were inspected. Sites were selected for inspection based on response rate, as well as enrollment. Site inspections ranged over five to seven days, and the sponsor inspection took place over nine days. One site received a FDA Form 483.
Dr. Laron was cited for:
- Failing to properly execute informed consent
- Site personnel who were not delegated to obtain informed consent consented two patients
- Three subjects were not consented to a revised consent that contained new risk information.
- Failing to properly report adverse and serious adverse events
- Failing to report febrile neutropenia which prolonged a hospitalization
- Reporting another case of febrile neutropenia within 11 days instead of one day.
- Reporting upper limb tremors within 5 days instead of one day.
- Failing to report a rise in LDH and increased risk of tumor lysis syndrome in one patient.
- Reporting steroid induced myopathy over one month late. Additional events related to this led to the patient's death, which was also reported late.
- Failing to adhere to eligibility requirements for the study
- Enrolling two subjects who did not meet the criteria for hemoglobin values.
Additionally, the FDA notes that subinvestigator Financial Disclosure forms were not collected at the time two subinvestigators began participation in the trial, serious adverse events were not submitted to the IRB as required in some cases and some subinvestigators lacked documented training to the protocol.