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 Contrave (Naltrexone HCl and buproprion HCl) submitted by Orexigen. Five sites plus the Contract Research Organization (CRO) were inspected in the second set of inspections that resulted in product approval. Site inspections ranged from three to seventeen days, the CRO inspection took nine days. Two sites plus the CRO received FDA Form 483s.
Dr. Rhee was cited for failing to follow the investigational plan, specifically:
- Failing to discontinue three subjects who met discontinuation criteria
Dr. Casanova was cited for failing to follow the investigational plan, specifically:
- Failing to report a Serious Adverse Event (SAE) of hospitalization for kidney stones in a timely manner. FDA notes that the site became aware of the hospitalization in November and reported it in May.
- Failing to report a SAE of hospitalization in a timely manner. The site was notified of the hospitalization in February and reported it to the sponsor in April.
- Two subjects did not have concomitant medication added after the screening visit recorded in the electronic case report form (eCRF).
PRA, the CRO, was cited for failing to monitor the study properly, specifically:
- Only performing a single onsite study visit which was inadequate in the eyes of FDA. The single onsite visit had noted reportable issues with Informed Consent in 26% of the consents sampled. Additional visits were not conducted in person, only by phone call where no additional ICF issues were reported. Subsequently, the site report problems with 25% of all informed consents to the IRB.
- Four of seven CRO personnel training records sampled indicated that personnel monitored prior to completing all required training. FDA notes that personnel performing monitoring visits by phone were expected by FDA to have adequate training as monitors.
- Performing monitoring visits prior to the finalization of the monitoring plan and the transition plan for the study. FDA notes that the distribution of the draft monitoring plan to monitors violated the CRO's SOPs.
In the original set of inspections for the study, five sites plus the sponsor were inspected. Site inspections ranged from three days to two weeks. The sponsor inspection was one week long. Two sites received FDA form 483s.
Dr. Hill was cited for failing to follow the investigational plan, specifically:
- There was no evidence that the delegated subinvestigators reviewed concomitant medications for study subjects, as required by the protocol.
Dr. Young was cited for failing to follow the investigational plan, specifically:
- Failing to assess elevated blood pressure in four subjects as adverse events, as required by the protocol.
- Failing to reconsent a subject that had transferred from another site.
- Page 21 of the Informed Consent was missing for eight subjects. (FDA notes that this was not a signature page and it was a HIPAA addendum)