Clinical Study Repair

RQMIS Repairs a Clinical Study (FDA)

The situation: an investment firm acquires a medical device start-up in the middle of an Investigational Device Exemption (IDE) study for the FDA. A Contract Research Organization (CRO) manages the study, however, the sponsor has lost the CRO along the way and now has no clinical oversight. The sponsor decides to prioritize other aspects of the new business until they have more bandwidth.

With no clinical oversight, there were a number of issues and discrepancies with the study:

• No active communication with the FDA
• No organized structure in place for study files
• The Trial Master File (TMF) was not up to date
• Although the sponsor was monitoring safety, there was no Data Safety Monitoring Board (DSMB) reviewing and adjudicating Adverse Events (AEs) that had occurred since the acquisition.
• Radiographic image analyses had not been performed
• Minimal communication with the study sites

RQMIS joined the sponsor in late 2016 and took over the clinical management of the study. Right away, RQMIS did the following:

• Restored active communication with the FDA
• Hired personnel to lead the clinical management of the trial
• Rescanned all Case Report Forms (CRFs) for transmission to the data management CRO

RQMIS then looked at the gaps in the study and determined the next steps to take to get the study back on track and compliant:

Data Management

RQMIS worked with the data management CRO to get all data cleaned and queried. The data management CRO created a new database, validated the database, and reentered all data collected via CRFs. The CRO queried all missing or questionable data on the CRF to address any potential data quality issues or concerns.

RQMIS developed and implemented streamlined query resolution, in which queries were processed through the RQMIS data management team before delivery to the sites. This process produced quicker and cleaner resolutions.

Safety Management

RQMIS reestablished a Data and Safety Monitoring Board (DSMB) in the summer of 2017. The reestablished DSMB has adjudicated all AEs and SAEs in the study.

FDA Correspondence

• RQMIS sent the FDA an Annual Report to reestablish contact.
• RQMIS submitted a full Annual Report to the FDA in 2018, which updated the FDA on the study status. The FDA accepted the 2018 Annual Report.

Trial Master File

RQMIS adopted the TMF Reference Model and has worked diligently on identifying, collecting, and organizing documents, including drafting note-to-files when needed. The sponsor now has a fully functioning TMF system – required paper and an electronic copy.

Radiographic Imaging

RQMIS worked with the radiographic core lab to reestablish a contract with the sponsor. In 2017, RQMIS developed a schedule in which the core lab worked to complete all radiographic analyses. This analysis was included in the Annual Report to the FDA. In addition, RQMIS continues to work with the core lab to get all radiographic analyses for the study completed and delivered.

Site Monitoring and Satisfaction

RQMIS utilized its monitors based in the EU and trained/managed the sponsor's field monitor to act as clinical site monitors. The site monitors are listening to the site's concerns and getting them back on track and compliant. As a result of completing the protocol in 2018, RQMIS has closed both of the European sites as well as a handful of the U.S. sites, with the rest of the clinical U.S. sites on track for closure.

RQMIS refocused dissatisfied sites, and now all sites are regularly monitored.

In less than two years, RQMIS was able to get this study back on track and compliant with all regulatory requirements. In addition, the study is on track for a database lock and submission to the FDA for PMA approval within the next year.