Diabetic kidney disease (DKD) patients have an increased cardiovascular (CV) risk in addition to their increased risk of progression to end-stage renal disease. Recognizing that the FDA and other regulatory agencies have great interest in both the CV and renal safety and efficacy of compounds under development, pharmaceutical companies should consider inclusion of an appropriate approach to adjudication of potential CV events early in the course of planning for development of drugs to treat DKD.
Adapting current regulatory perspectives
From the regulatory perspective, there is a lot of emphasis focused on looking at both CV and renal risks during the development of type 2 diabetes treatments.1 However, no specific guidance exists for clinically-evident endpoints in DKD.
Similar to testing the safety of an anti-diabetic therapy, a treatment for DKD should also demonstrate that it will not result in an unacceptable increase in CV risk. Centralized adjudication of clinical endpoints helps control for data variability and enables robust statistical analyses of these outcomes.
The benefits of foresight
Thinking ahead about adjudication makes a difference. When early results from a Phase II trial start to look promising, it’s prudent to get adjudication processes in place to understand how to adjudicate potential events in Phase III.
This early planning ensures that all the design and set-up is ready; steps that include identifying and establishing contracts with adjudication members, defining collection processes along with methods to establish endpoint definitions and adjudication criteria.
Design plans should include methods to collect investigator-identified potential CV endpoint events, strategies to detect unreported endpoints, as well as a definition of project-specific workflows to process these events. Early efforts around these considerations will help drive optimized performance during the adjudication process.
Leveraging a trusted network
Just like choosing the right sites and investigators to support a study, sponsors benefit from working with expert adjudicators that have long-term experience. Contract research organizations (CROs) often tap into their networks of proven adjudicators to support particular studies.
Likewise, CROs have to maintain their reputation with adjudicators by facilitating the workflow process to ensure that they deliver a complete, compiled and accurate endpoint dossier. Many CROs and academic research organizations (AROs) face challenges with gathering complete, timely information, so it’s wise to ensure that a partner that can deliver the entire set of information to adjudicators within the specified time frame.
Gaining efficiencies in electronic data capture
Compiling an endpoint dossier relies on many coordinated efforts, but the backbone of data collection is the electronic data capture (EDC) platform. Today’s advances in information technology allow for automated workflow features, such as document capture to minimize handoff points, eliminate manual processing and deliver on-demand data.
A well-managed EDC platform connects sites, the endpoint data coordinating center and adjudicators with a streamlined workflow. Here, sites can automatically transfer their endpoint reporting electronic case report forms (eCRFs), the data center can compile the relevant information and adjudicators can easily access complete endpoint dossiers and record their findings. As a result, sponsors can receive near real-time updates and perform trend analyses.
The art of endpoint case processing
Beyond collecting, processing and packaging documents through a robust EDC platform, there is an art to endpoint case processing. Endpoint case details must be carefully reviewed to ensure completeness and the team should review materials to determine whether additional, case-specific material is required for a more complete clinical picture as it relates to a specific endpoint.
The system also must support rapid collection of final adjudicated outcomes, which are needed for analysis at multiple time points throughout the lifecycle of adjudication projects. This collection process requires extensive insight into site documentation practices, as well as the implementation of a sophisticated, global strategy to expedite large volumes of supporting endpoint source documents from patient charts.
When a multi-faceted strategy is in place with well-designed clinical endpoints, adjudicators are enabled to evaluate endpoint outcomes, classify CV-related events during a trial and help sponsors reach critical decision points earlier.
- U.S. Dept. of Health and Human Services FDA CDER. Guidance for Industry on Diabetes Mellitus-Evaluating Cardiovascular Risk in New Antidiabetic Therapies to Treat Type 2 Diabetes.
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