Operational Lessons for a Successful Alzheimer’s Trial

Outlining the top operational lessons for a successful Alzheimer’s and related dementias trials.

Central nervous system (CNS) diseases, including Alzheimer’s and related dementias (AD/ADRD) disrupt lives in often profound ways. These diseases are uniquely perplexing because our understanding of neurobiology is still incomplete, and the pathology is unknown.

With an approval rate for CNS therapies that is about half that for other drugs, the distinct challenges of clinical research for AD/ADRD need to be met with an uncommon blend of scientific depth and elegant problem-solving. The National Institute on Aging (NIA) is currently supporting 459 active Alzheimer’s and related dementia clinical trials, all requiring specialized preclinical, translational, regulatory, and commercial capabilities for success. Here are the key operational lessons learned from progress on successful Alzheimer's Disease and related dementias trials:

Address the Competitive Landscape

• Selecting the right sites and countries during the feasibility phase of Alzheimer’s and related dementias clinical trials will help ensure strong historical recruitment rates and a history of delivering high quality data.
• Early site engagement during protocol development and ongoing strong messaging will help keep your study top of mind.
• Undergoing a protocol technical review will anticipate challenges and ensure the most efficient design for reducing patient and site burden, operationalizing your study, and meeting regulatory requirements.

Enroll the Right Patients

Screen failure (SF) rates in AD/ADRD trials can be as high as 70-80% because of the cognitive inclusion criteria and rigorous pre-screening approaches. The best way to mitigate potential SF rates, are to:

• Use biomarkers, imaging, and centralized pre-randomization eligibility review procedures to ensure accurate differential diagnosis.
• Use tailored expertise to understand diagnostic standard of care in each country and work to overcome challenges to the standardization of samples and data.
• Deploy eligibility review tools and engaging principal investigators (PIs) for of Alzheimer’s and related dementias clinical trials in eligibility discussions to minimize SFs and enrollment of ineligible patients. In past AD studies, we found 13% of patients initially enrolled by PIs were later deemed ineligible, per the protocol.

Retain the Right Patients

To retain patients, it is important to remove barriers to participation, making the study visit schedule and procedures less burdensome for patients by:

• Deploying study branding, advocacy engagement, and media campaigns to generate awareness and capture interest of patients and caregivers.
• Creating excitement about the study through strong communications on study rationale and available early phase data on the investigational product (IP).
• Developing a digital campaign and patient website to capture interest and drive enrollment.
• Increasing study access for diverse populations via site diversity analysis during selection and initiative throughout enrollment.
• Using decentralized solutions to appeal to patients and caregivers in a competitive landscape.

Select Appropriate Endpoints

To balance sensitivity to change in a trial population, minimizing burden and maximizing inter-rater reliability, it is important to select appropriate endpoints to control for:

• A high potential for variability in scale administration in a study with a high volume of sites leads to reduced signal reliability.
• A high-rate turnover at sites adds significant additional challenges for inter-rater reliability. Rater training and monitoring of scales can help to reduce variability.
• Appropriate eCOAand ePRO recommendations to increase efficiency and data quality.

The key to success for complex Alzheimer’s and related dementias clinical trials requires empowering site support and purposeful patient identification, retention, and communication. To measure highly subjective endpoints, counter placebo effects, demonstrate clinically meaningful efficacy with uncommon blend of scientific depth, specialized preclinical, translational, regulatory, and commercial capabilities are required.

To learn more about how Syneos Health can help engage patients and drive enrollment in CNS trails, contact our CNS Leadership Team are read more about our capabilities.

Contributors

Susan Honn, Executive Director, Therapeutic Strategy & Innovation, Syneos Health

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