The Need for Speed, Accuracy, and Efficiency in Clinical Safety Data Management
As in the words of Maverick and Goose in the movie Top Gun, “I feel the need…the need for speed,” it is critical that serious adverse events (SAEs) in clinical trials are logged, reported, and acted upon quickly.
The trial sponsor is accountable for reporting SAEs to the regulatory authorities. The relevant authority is typically associated with where the trial participant is domiciled. Sponsors commonly delegate such PV (pharmacovigilance) duties to a contract research organization (CRO). Ultimately, though, the sponsor is accountable for compliance with the various authorities' guidance and regulations.
SAEs are typically created at clinical investigator sites, often following participant visits. The site's clinical research coordinator (CRC) is generally expected to enter the SAE details into the EDC (electronic data capture) system for the trial. However, it is common for the CRC to have to additionally communicate the SAE to the PV function of the sponsor (or the delegated CRO). Typically, this communication involves a separate electronic form or email, or at best, exporting the information from the EDC system into a PDF document and emailed to the sponsor/CRO. The CRC must also directly report the AE/SAE to the local regulatory authority in many jurisdictions.
Sites must report SAEs to the sponsor or delegated CRO within 24 hours. If the SAE is an unexpected fatal or life-threatening suspected adverse reaction, the FDA requires that the SAE is reported within seven calendar days after the site notified the sponsor/CRO. If the SAE suggests a significant risk to trial subjects, it must be reported to the authorities within 15 calendar days. The EMA and other regional regulatory bodies have similar SAE reporting guidelines.
Standardization of Safety Reporting in Clinical Trials
To help streamline safety reporting in clinical trials to meet the regulatory requirements and standardize the format of safety reports, the ICH (International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use) created the E2B standard for electronic transmission of individual case safety reports (ICSRs). ICH revised the standard, ICH E2B (R3), to extend its applicability beyond drug and biologics safety to vaccines, animal products, cosmetics, and other domains. ICH E2B (R3) uses the HL7 (Health Level Seven) international standards for the transfer of clinical and administrative data between software applications used by various healthcare providers. Typically, ICH E2B has been used to standardize the reporting of safety cases by sponsors/CROs to the regulatory authorities and has been adopted by safety system vendors such as Oracle and ArisGlobal.
Challenges with Dual Recording/Reporting of SAEs
Dual reporting/duplicate data entry of SAEs is inefficient for sites; this could lead to inconsistencies between the safety case data in the EDC and safety teams, as well as requiring reconciliation checks by the sponsor/CRO to make sure the two sets of data match. It's also time-consuming, taking sites away from patient-facing activities and potentially delaying the reporting of the SAE by the sponsor/CRO to the authorities.
Rave Safety Gateway
Medidata developed Rave Safety Gateway to address the challenges outlined above. Safety Gateway automates collecting, transmitting, and tracking adverse event data from Rave EDC to the sponsor's/CRO's safety system in ICH E2B (R2) or (R3) format, dramatically expediting the PV team's receipt of clean and timely safety data.
Rave Safety Gateway delivers:
Speed: The site no longer has to enter the SAE data twice, and the reconciliation check by the PV team is quick and easy. And, if the principal investigator doesn't sign off the SAE data in the EDC system within a pre-specified period, Safety Gateway automatically generates the new safety case or updates to an existing safety case to avoid delays in the data making its way to the safety team.
Accuracy: The risk of errors or missing data is significantly lowered, reducing the volume of queries and the need to re-transmit the safety case.
Efficiency: The burden of safety data entry, query, and reconciliation efforts for sites, data managers, and safety teams is significantly reduced.
A Case Study
A global pharmaceutical company developing treatments for substance use disorders and mental illnesses uses Rave EDC and a 3rd-party safety system. Capturing the data in both systems has historically involved printing the EDC forms and manually entering the data into the safety system, a separate electronic SAE form (duplicating the data already entered into EDC), or generating a PDF from EDC and emailing it to the PV team's mailbox. The sponsor implemented Rave Safety Gateway using Medidata's Professional Services team to improve their SAE reporting process's speed, accuracy, and efficiency.
“The Medidata team has been great at coordination, flexibility in meeting sooner when issues arise, and keeping the implementation on track. I appreciate their efforts to do everything they can to make the implementation successful.”
– Director of PV at the Sponsor
The sponsor realized the following benefits from their implementation of Safety Gateway:
- Elimination of duplicate data entry into the safety system lets teams focus more time on the quality review of the safety case data.
- Reduced reconciliation effort. Through Safety Gateway's automation and support for ICH E2B, the safety cases match in the two systems, and it's just a quick check to verify this.
- Faster safety reporting and filing the safety case in the eTMF (electronic Trial Master File).
- Reduced time to triage safety cases. The PV team receives instant notification from Safety Gateway of a new safety case arriving in the safety system.
Ultimately, this streamlined process helps protect the patients' safety in the sponsor's trial. Without Rave Safety Gateway, there could be a delay of 1 business day before the monitor would be made aware of the event.
“Using Safety Gateway, they get an automatic notification of the event. The safety case is scrutinized faster, and action is taken quickly to reduce the impact on the affected patient,”
– Senior Clinical Data Manager at the Pharmaceutical Company.