Using EDC-Rave to Conduct Clinical Trials at Genentech

1. Using EDC-Rave to Conduct Clinical Trials at Genentech Susanne Prokscha Principal CDM PTM Process Analyst February 2012

2. Objectives At Genentech, we use an electronic data capture (EDC) system called Rave for all clinical trials. • Background to EDC • What exactly is EDC? • Activities for clinical data management (CDM) for EDC • The regulatory environment for EDC • Case study for large Phase III Trials • Study startup • Study conduct • Study closeout • Summary and Rave Demo

3. Background to EDC

4. What is Electronic Data Capture? In order to have data that can be analyzed to draw a conclusion, values have to be collected the same way across all investigator (research) sites. In clinical trials, we use structured forms known as Case Report Forms (CRFs) to collect data. These can be paper forms or electronic forms. EDC refers to collection of clinical trial data on electronic CRFs (eCRFs). The primary function of EDC systems is to support data collection from the sites but they will also support data management activities/tasks.

5. CDM Activities for EDC

6. CDM Activities (continued)

7. CDM Activities (continued)

8. EDC Regulatory Environment Any system used to collect data that may be included as part of an NDA to the FDA must be compliant with 21 CFR Part 11 – the rule on electronic records and signatures. • The rule includes system requirements such as: • Time-stamped, automatic audit trail • Secure account management and access controls • The rule also includes procedural elements: • System and study level validation • Standard operating procedures

9. EDC Regulatory Environment A regulatory concern that is not in the rule but is showing up in FDA and EMEA guidance documents has an important implication for EDC systems. Regulatory agencies are clear: the sponsor cannot have “full control” over the site data. • If the sponsor has the system on its own servers, it has access to changing the site data. • Most companies currently have the EDC system “hosted” by service providers who manage site accounts, access to the application, and access to the underlying database.

10. Rave at Genentech

11. Rave at Genentech Rave, a product from Medidata Solutions, is used for all new studies for both Genentech and Roche worldwide. • Medidata • Hosts a Roche-Genentech URL on restricted servers • Grants site access and manages site accounts • Clinical Data Management • Study Data Managers: define the system, approve and test the build, run the study… • Clinical programmers: build the study and create custom functions and reports • Informatics Rave Support, System Support Services

12. Study Startup – Prep for “First Patient In” Study startup activities begin when the protocol summary is firm and rely on the final protocol to move forward until it is ready for subject data. • Specify and build the eCRF • There will be 50-75 unique eCRFs for a Phase III study • Specify and build the edit checks • There can be from 600 to 2000 individual edit checks • Estimate 1000 edit checks for a Phase III study • Test the study application and release for production (“go live”)

13. Study Conduct – Collect and Clean Data • Monitor site entry of data and responses to queries • Perform Data Reviews • Some checks are more easily done by a humans via listings or reports • Medical review is performed by clinical science • Create Manual queries • Example: MS Phase III trial with 105 sites and 450 subjects had 5000 manual monitor and data review queries • Example: Phase II trial with 32 sites and 120 subjects had about 800 manual queries

14. Study Conduct – Other Activities • Collect non-CRF data (labs, etc.) • Code adverse events and medications • Collect and reconcile serious adverse events against the safety database An important event during study conduct that occurs in most Phase II and III trials is a database change or “amendment”. This is a time and resource consuming event.

15. Study Closeout – Prepare for Lock • Ensure data is complete (both eCRF and non-eCRF) • Perform final data reviews • Final Data listing review • Review all coding assignments • Check that all SAEs are accounted for • Obtain resolution for or close all open queries • Obtain Principal Investigator Signature • Prepare archival versions of eCRF for the sites and the sponsor files

16. Data Management Impact • Even though data management is only 12% of the cost of a large trial (20% if biostatistics and statistical programming are included), it is an essential component. • If the data is not complete or accurate enough to be analyzed and sustain a conclusion then the entire cost of the trial is wasted.

17. References • For electronic records in clinical trials in general: • (FDA) 21 CRF Part 11; Electronic Records; Electronic signatures • (FDA) Guidance for Industry: Computerized Systems used in Clinical Investigations • (EMEA) Reflection Paper on Expectations for Electronic Source Documents used in Clinical Trials • Using EDC vendors or hosts: • FDA presentation: “Guidance on the Use of Electronic Records and Electronic Signatures;” P. M. Beers Block, 12/2009 • (FDA) DRAFT Guidance for Industry: Electronic Source Documentation in Clinical Trials