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 this week. From the archives, here is the clinical inspection summary for Bictarvy submitted by Gilead. Five sites were selected for inspection based on treatment effect, financial disclosure and prior inspection history. One site received a FDA Form 483.
Dr. Charest was cited for:
- Failing to provide a participant with an updated consent form. FDA notes that the participant was provided with a consent form for a different study and notes that procedures performed on Week 60 and Week 72 were performed without appropriate consent.
FDA did not post any warning letters this week to Sponsors/Monitors/CROs, Clinical Investigators or IRBs. From the archives, here is the Clinical Inspection Summary for Rhopressa (netarsudil) submitted by Aerie Pharmaceuticals. Two sites were selected for inspection, based on enrollment and a large number of INDs listing the investigators (27 and 9) and no inspections or no inspections in the last twenty two years. Both sites received FDA Form 483s.
Dr. Cooke was cited for:
- Failing to follow the investigational plan, specifically failing to repeat a test as directed by protocol for three patients
- Assuming lab values were normal when a lab report was not available for one patient's visit
Dr. Logan was cited for:
- Fourteen "transcription deficiencies" across eighteen patients' CRFs
- Five instances of non-serious adverse events and concomitant medications not being captured in the CRF
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 Vyzulta (latanoprostene bunod) submitted by Bausch & Lomb. Two sites were selected for inspection, based on large enrollment and lack of recent inspections. One site received a FDA 483.
Dr. Christie was cited for failing to store Study drug per protocol. FDA notes that the refrigerator which stored study drug was required to be between two degrees and eight degrees Celsius. There were at least 31 days when the refrigerator was below this range, and nineteen days when the temperature was not recorded.
FDA also posted two complete response letters associated with this application. Complete responses cited manufacturing issues noted during inspections requiring correction.
During the approval process, FDA noted and required:
- Missing pages from a batch record be submitted
- Subjects with more than one baseline value in the dataset be explained
- Subjects who discontinued due to potential lack of efficacy should be identified in the data, including specific subjects that FDA identified within the data as experiencing lack of efficacy
- Randomization errors be listed in the patient disposition table
FDA did not post any warning letters this week to Sponsors/Monitors/CROs, IRBs or Clinical Investigators. From the archives, here is the recently posted clinical inspection summary for Calquence (acalabrutinib) submitted by Acerta Pharma. Two sites (out of forty participating in the trial )plus the sponsor were inspected. Site inspections lasted two and five days. Sites were selected on the basis of high enrollment and potential contribution to efficacy. The sponsor inspection lasted two weeks.
The sponsor received a FDA Form 483 for failing to monitor the study properly, specifically:
- Failing to ensure sites submitted protocol amendments to the IRB in a timely fashion. Delays were noted to be four to eleven months.
- Failing to assure investigators and subinvestigators documented training.