May 6, 2016 | The Clinical Informatics News Best Practices Awards program recognizes outstanding examples of applied strategic innovation—partnerships, deployments, and collaborations that manifestly improve the clinical trial process. This year, a team of expert judges evaluated submissions to the program and announced ten finalists. Three grand prize winners were named at the 2016 Summit for Clinical Ops Executives event in Miami, Florida. We have invited the 2016 finalists to present the projects that so impressed our judges in hopes that these best practices can make wide-reaching impacts on the industry.   

--Allison Proffitt, Editor

Project Title:  Implementing risk-based monitoring and remote trial management technologies and processes to enable a small biotech to run a 1000-subject Phase IV study with a clinical/DM staff of four. 

Risk based monitoring (RBM) with remote trial management, as envisioned in the FDA, EMA, and ICH in their guidance on Risk-Based Monitoring and eSource, encompasses changes in technology, process, and new skill sets:

PaxVax, a small vaccine biotech, wanted to run a Phase IV trial with its internal staff. It initially bid the study out to different, traditional CROs. PaxVax desired a more comprehensive method to implement Risk-Based Montitoring (RBM) than traditional CROs offered. It also wanted to incorporate all aspects of RBM within PaxVax’s current budget and build a technology infrastructure and knowledge base reusable in future trials. PaxVax chose MANA Consulting (MANA) to achieve its goals.

To accomplish PaxVax’s goals, MANA selected and configured software systems as follows:               

• EDC Data Collection:
  • EDC was designed for use as eSource. The eDiary was integrated into the EDC to support site assessments. Randomization was integrated into the EDC. EDC data was automatically imported into the data repository.
   
• Site and Team Data Collection:

Implemented a second database within EDC ( Site Level Forms) to collect critical data from sites and team members needed for reporting and not often traditionally collected electronically, including:

• Risk Assessment and Categorization*
• Investigational Product Receipt
• Delegation of Authority
• Training Records and Documentation
• eMonitoring Reports for both onsite and remote monitoring
• Issue Log/Issue Management*

*Items required for RBM and not previously available in audit-trail available system before implementation of the Site Level Forms

• Regulatory and Subject Source Document collection:

Implemented electronic Investigator Site Files (eISF) to  collect and manage certified electronic copies (for subject source and informed consents) and all site regulatory documents directly from the sites. 

• Data Aggregation of RBM reporting and Subject Source Data review

Aggregated data across all the different data sources (including operational metadata) into a data repository with reports generated for RBM oversight. Among the reports MANA created were:

• Key Performance Indicators used by central monitors to evaluate performance of sites (across subjects) and across sites. MANA included these indicators in “drill-down” reports to enable a more comprehensive analysis of the specific issues identified with the overall risk indicators
• “High Risk Data Elements and Process” protocol-specific reports to facilitate oversight of items identified during risk assessment
• Subject Profile Analyzing Risk (SPAR), MANA’s proprietary RBM tool to enable efficient, integrated Source Data Review (SDR) by Monitors. The SPAR synthesized critical data required for the trial, normalized to the study day. This feature enabled the site monitors to rapidly identify and correct issues remotely. It took less than 30 minutes to train the monitors how to use the SPAR and they reviewed a subject’s progess more completely and quickly, saving nearly 80% of the time needed to do review of data using eCRF pages. MANA’s SPAR is currently the basis of a research study to provide more comprehensive metrics on quality improvement and time savings.

Process Changes included incorporating risk analysis prior to study start. MANA set up processes and trained the Sponsor’s team to conduct a risk assessment that translated into enhanced eSource design and custom reports for oversight of high risk data elements and process.

Data review is also different with RBM. The process should be cross functional and should be completed as close to subject visits as possible. Instead of SDV, the monitors conducted SDR using the SPAR and eCRF. The integrated review included review by the DM and Monitor at the subject level, then cross-subject review within a site and cross-site review. Once issues were identified and captured in the issue log, monitors evaluated root causes, provided interventions, and evaluated those interventions. The technology solution MANA developed enabled capturing all aspects of the process electronically.

MANA also provided key documents required for implementing RBM including all plans and the integrated Data and Document Review Guidelines.

MANA trained all Sponsor Team members and Site Users and performed co-monitoring and co-data management with the Sponsor for the first two months of the study. MANA continued to be involved in the study, providing Central Monitoring Oversight on a monthly basis throughout the trial. 

The costs to develop this methodology including contracting for all software systems, configuration, testing, and deployment was similar to using a CRO with one important exception. The Sponsor now owns a significant resource it can use in its upcoming and future trials. PaxVax’s new resource includes an electronic TMF, eISF, Standard reports for RBM and study oversight, EDC forms, templates of key operational documents, and training materials. Minimal modifications are needed to use all the tools of this resource in future trials. The PaxVax team is now trained to take on these new responsibilities confidently—further enhancing the value to the organization. 

Commentary:

Implementing Risk Based Monitoring can be a daunting process for an organization. By using MANA RBM, PaxVax was able to:

1. Adopt processes for RBM that supported the current trial and could be used in all  future trials.  
2. Receive training on all aspects of RBM. PaxVax monitors, data managers, and project managers worked side by side with their MANA counterparts during study start up and the early study implementation. MANA’s central monitors continued to supply monthly study performance review and monthly site progress reports.
3. Adopt a cost effective technology solution that enabled comprehensive oversight of the trial remotely for both data and documents. The SPAR enabled the team to complete source data review for all subjects in a fraction of the time needed for onsite review. 

PaxVax reaped significant benefits in adopting RBM. Its team now identifies and corrects issues rapidly. Rapid feedback helps sites correct errors early and improves trial quality. This technology approach enabled the team to work remotely and still have comprehensive visibility into trial data and documents.  

By working together to deliver a product that included technology, processes, and staff training, a small biotech is more empowered to do trials itself or to implement future trials using more flexible and cost effective staffing approaches.