subject diaries

FDA Clinical Inspection Summary: Nerlynx (neratinib maleate) submitted by Puma

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 Nerlynx (neratinib maleate) submitted by Puma. Four sites plus the sponsor were inspected. Site inspections ranged from two to five days, and the sponsor inspection lasted 3 days. Two sites received FDA Form 483s.

Dr. Chan was cited for:

  • Failing to maintain accurate investigational product accountability records. FDA notes that at a time when the IVRS system was down, the site called the IVRS helpdesk for a manual assignment over the phone. The kit assigned over the phone differed that a faxed kit number subsequently sent to the site.

Dr. Tomasevic was cited for:

  • Failing to report adverse events that appeared in subject diaries for three subjects. 

FDA Clinical Inspection Summary: Varithena (Polydocanol Injectable Microfoam) submitted by BTG International

FDA did not post any warning letters to Sponsors/Monnitors/CROs, IRBs or Clinical Investigators this week. From the archives, here is the Clinical Inspection Summary for Varithena (polydocanol injectable microfoam) submitted by BTG. Five sites were selected for inspection, based on enrollment, contribution to treatment efficacy, number of protocol deviations, number of subject discontinuations and number of subjects excluded from the statistical analysis. Site inspections ranged over four days to one month. Three sites received a FDA Form 483.

Dr. Deck was cited for:

  • Failing to ensure proper entry of information into the IVRS system. Three subjects had incorrect assessment scores entered into the IVRS. FDA notes that these protocol deviations were entered late, and therefore were not reflected in the line listings that the FDA inspector had.

Dr. Ferris was cited for:

  • Failing to follow the investigational plan, specifically:
    • Six subjects received e-diaries before inclusion/exclusion criteria review was complete.
    • One subject was treated before review of inclusion/exclusion criteria was complete.

Dr. Stanbro was cited for:

  • Failing to follow the investigational plan, specifically:
    • All subjects were provided with an e-diary before screening procedures were complete.
    • Entering IVRS data at randomization instead of at baseline.

FDA Clinical Inspection Summary: Jentadueto (linagliptin and metformin) submitted by Boehringer Ingelheim

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 Jentadueto (linagliptin and metformin) submitted by Boehringer Ingelheim. Two sites were selected for inspection, based on geographic location (country providing 31% of enrolled patients) and randomization rate. Site inspections lasted four and fourteen days. One site received a FDA Form 483.

Dr. Srikanta was cited for:

  • Failing to adequately review lab reports, clinic  notes and patient diaries, specifically:
    • Patient diaries for two subjects were not signed off by site staff and review was not noted in clinic notes
    • One out of range lab report was not noted in clinic notes
    • Clinic notes did not correctly reflect the initiation of a concomitant medication
  • Failure to fully document the informed consent process in clinic notes. The FDA inspector specifically noted lack of documentation for Legally Authorized Representatives and illiterate subjects. 

FDA Clinical Inspection Summary: Akynzeo (netupitant and palonosetron) submitted by Helsinn Healthcare SA

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 Akynzeo (netupitant and palonosetron fixed dose combination) submitted by Helsinn Healthcare HA. Sites were selected by FDA to ensure coverage of all trials submitted in the application, high enrollment, geographic diversity, previous inspection history with FDA and feasibility of getting the inspections done within FDA timelines. Six sites plus the sponsor were inspected. Site inspections ranged from three to ten days. The sponsor inspection took place overly nearly two weeks. Three sites were issued FDA Form 483s.

Dr. Csoszi was cited for Failing to records two types of concomitant medication ( Mannisol and Suprastin) on the CRF for twenty four and five patients, respectively. 

Dr. Zajad was cited for failing to follow the investigational plan, specifically:

  • Failing to report two adverse events (fatigue and anemia)
  • The loss of one patient diary after it had been returned to the site by the patient

Dr. Alayosova was cited for failure to maintain accurate case histories, specifically:

  • Discrepancies in medications amounts recorded in patient diaries versus the Case Report Form (CRF) for three subjects.

FDA Clinical Inspection Summary: Adlyxin (lixisenatide) by Sanofi

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 Lixisenatide by Sanofi. Sites were selected based on enrollment, receiving speaking fees from the sponsor, larger than average discontinuation rates, higher adverse event rates, high treatment effect and outliers with regards to percent of screened subjects enrolled (100% or low numbers of screened patients enrolled). 

Five sites were inspected. Inspections ranged from one to eleven days. One site received a FDA Form 483. 

Dr. Min was cited for failure to maintain adequate and accurate case histories, specifically:

  • Multiple discrepancies between the CRF and subject diaries for five subjects with regards to dosing of investigational product.