SAE Reporting in EDC Trials

It is widely accepted among clinical trial professionals that EDC solutions deliver many benefits with respect to time, productivity, and costs. This is especially true for the collection and cleaning of standard CRF data such as demographics, concomitant medication, medical history, efficacy, and safety. EDC also covers the areas of patient reported outcomes, central laboratory data, and data from other external sources. However, a very important aspect of clinical trial data management is not adequately addressed in many EDC solutions and eCRFs: namely, the collection, processing, and reporting of Serious Adverse Events (SAE).

In many EDC trials the SAE process is still paper- and fax-based. This process is often carried out in isolation from other data management activities and results in redundant activities such as duplicate documentation for the investigator and drug safety unit.

Holding back progress

There are various reasons for such a lack of integration when collecting, reporting, and processing SAEs and SUSARs (suspected unexpected serious adverse reactions) in eCRFs. First of all, one has to understand the special requirements needed when processing SAEs and SUSARs: different as it is to nonsafety data, data from SAEs and SUSARs have to be processed and reported to regulatory authorities at very short notice, and the required expertise differ greatly from those in the field of clinical data management.

Consequently, most medium and large pharmaceutical or biotech companies have highly specialized in-house drug safety departments, which utilize dedicated database applications for the comprehensive management of SAEs and the reporting of SUSARs. Smaller companies frequently outsource these tasks to CROs, which then provide the appropriate database applications and corresponding processes.

As drug safety reporting is of ever-increasing importance throughout the drug development process, most companies are reluctant to change their existing procedures, which are often reliable but inefficient. They feel it would be better to remain with a flawed but familiar system rather than undergoing the upheaval associated with introducing a new one. Another reason for the lack of integration is the historical use of existing applications, which lack the necessary interfaces to enable the smooth exchange of data with other systems.

Importing or synchronizing SAE data from an EDC system into a drug safety application—preferably in XML format—would require an elaborated and validated functionality, enabling users to handle and track changes, update records, manage queries, and carry out numerous other processes. Many EDC systems do not offer such synchronization options and lack an easy-to-use and flexible import/export functionality. But does this mean we should wait for the "perfect" solution of full SAE reporting capabilities within EDC systems? It would perhaps be wise to consider the interim step of incorporating smart SAE forms into eCRFs. This would allow the use of state-of-the-art EDC functionalities and the seamless transfer of SAE information to drug safety applications.

eCRF SAE forms

It should be noted that, in order to implement an efficient electronic SAE process, it is important to take care of the additional requirements for electronic SAE pages in an EDC system. SAE data pages differ from other eCRF pages in various ways:

• Data entry and updates require immediate attention.

• Most of the data on SAE pages already exist on other pages of the eCRF.

• The query-management process differs and involves the drug safety department.

• The data is frequently incomplete and requires updating.

• Additional reporting requirements are necessary.

However, choosing the right EDC solution, designing smart eCRF pages, and making full use of its capabilities will significantly increase data quality and the efficiency of the SAE process.

An eCRF SAE form and the backend EDC system should:

• Automatically display study information, such as demographics and standard baseline data, which has already been entered into the eCRF.

• Allow the investigator to choose data that has been entered on other forms to be linked to the electronic SAE form. The data only has to be entered once, thus avoiding inconsistencies. This greatly simplifies the documentation of SAEs to specify related medical history and concomitant medication records (see Figure 1).

• Offer specific user rights for drug safety managers to perform data reviews and cleaning within the EDC system, or even enter data into predefined fields (if required).

• Contain fields in which the investigator, CRA or drug safety manager can upload/attach certain information (e.g., hospital/discharge letters).

• Automatically synchronize AE and SAE eCRF forms (see bullet point 1).

• Include an alert system that notifies a predefined group of recipients via email, SMS or automatically generated fax reports.

• Generate on-demand SAE reports in PDF format (full or incremental modified information).

• Offer a standardized and incremental transfer of SAE information to a dedicated drug-safety application, preferably in XML format.

Figure 1. Linking of data already collected on other eCRF pages is simple, avoids redundancies, and improves quality of entries in SAE forms.

Benefits

An eCRF SAE form with these features provides a number of benefits by:

• Significantly reducing the collection of redundant data, saving the investigator a lot of time (particularly within studies with a moderate or large number of SAEs) and renders the eCRF SAE form less susceptible to transcription errors.

• Offering more accurate and up-to-date information on the SAE form: changes in the automatically displayed or linked data are available immediately.

• Allowing for more efficient data cleaning, as drug safety managers can utilize the full query management functionality of an EDC system and might achieve a better response to queries. As these queries are processed in the EDC system, they are flagged or listed in specific reports. CRAs can view the queries, assist in answering them, and communicate with investigators.

• Considerably reducing the SAE reconciliation effort required before a database lock, as no redundant information is collected.

• Enabling reporting deadlines to be met with greater ease due to the alert system and electronic data exchange.

• Cutting back the amount of time required for creating follow-up reports by transferring data incrementally from the EDC system to the drug safety application and highlighting the updated information in follow-up reports.

Conclusion

Currently, EDC systems coexist with legacy drug safety applications and paper- or fax-based SAE processes. A state-of-the-art EDC solution should provide features that support electronic SAE handling within the EDC system. Electronic SAE handling has the potential to significantly reduce the workload in drug safety management, especially in studies with a moderate or large number of SAEs. Furthermore, EDC can also improve the quality and accuracy of data in drug safety and SUSAR reporting systems.

With an EDC system that supports the described features, it is possible to establish an efficient electronic SAE management process with only minimum changes to existing processes and systems. Drug safety departments should be able to continue to use their existing systems but observe improvements in the quality and accuracy of data.

The described approach can only be an interim step toward more integrated systems and processes1. However, as interim solutions sometimes tend to last a rather long time in the area of drug development, it would be beneficial to act now and not wait for the "perfect" solution that may come along in the future.

Dieter Meyer* is head of data management and managing director at Metronomia Clinical Research GmbH, Paul-Gerhardt-Allee 42, 81245 Munich, Germany, email: dmeyer@metronomia.net Jens Knoesel is clinical data manager, EDC, at Metronomia Clinical Research GmbH. Henning Lux is chief executive officer at Quadratek Data Solutions, Ltd, Hampshire, UK.

*To whom all correspondence should be addressed.

References

1. R. Bobo and J. Notte; "Safety Reporting in Clinical Trials," Next Generation Pharmaceutical, www.ngpharma.com/pastissue/article.asp?art=26377&issue=159 (accessed January 17, 2008).