InRAD Observational Study

The study protocol is owned by all InRAD Observational Study Investigators. All centers taking part in InRAD are the data controllers. InRAD is a data processor and is providing operational management and system support.

Study Type: Prospective, non-interventional, multinational observational cohort study.

Study Objective: The primary goal of the InRAD Observational Study is to collect and analyze real-world data (RWD) to evaluate long-term disease outcomes and treatment safety in people with Alzheimer's disease (PwAD). The study aims to:

• Assess disease stage transitions, cognitive and functional changes over time.
• Examine the relationship between demographics, comorbidities, diagnostic and monitoring tests, drug exposures, and outcomes.
• Compare disease demographics and outcomes across countries and regions.
• Characterize the occurrence of medical events, including Serious Adverse Events (SAEs) and Adverse Events (AEs), particularly in relation to AD-specific treatments.

Study Population: Adults undergoing diagnostic work-up for Alzheimer's disease or already diagnosed. Includes treated, treatment-eligible, and untreated patients. Participants must be attending an InRAD Center and provide informed consent for long-term follow-up.

Recruitment and Consent: Recruitment is open to global clinical centers with qualified investigators. Informed consent is obtained from patients and, where applicable, their caregivers. Consent includes authorization to share pseudonymized demographic and medical data with the InRAD Registry.

Data Collection: Investigators use the InRAD Web cloud-based data-entry platform and agree to collect the defined Minimum Dataset at least annually for their patients:

Minimum Dataset (MDS):

• Patient demographics
• Disease characteristics
• Clinical outcomes
• Safety data
• Treatment details

In addition to the Minimum Dataset, Investigators may collect a variety of disease-specific or other data-fields of interest from the Extended Dataset:

Extended Dataset (EDS):

• Lifestyle factors
• Biomarkers and imaging data
• Care partner information
• Quality of life and burden assessments

Centers, through their PIs, and the InRAD SLG (Scientific Leadership Group), may propose research analyses and cohort sub-studies of interest to be conducted using the pooled Registry dataset or subsets of the Registry data.

For each analysis and sub-study proposal, the Center, through its PI, always exclusively decide whether to participate and contribute their Center data for use in the research.

The IT tool is owned, maintained and freely provided by the InRAD Foundation to Member Centers to enable and support the Study.

Pseudonymized data is to be submitted to the InRAD registry at least biannually and may be updated more frequently depending on clinical practice.

Governance and Oversight: The study is coordinated by the InRAD Foundation and governed by its Scientific Leadership Group (SLG). Each participating center is responsible for obtaining Ethics Committee (EC) or Institutional Review Board (IRB) approval unless exempt. No Data Monitoring Committee (DMC) is appointed, consistent with the non-interventional nature of the study.

Safety Monitoring: SAEs and other medical events are recorded using MedDRA coding. Centers are responsible for reporting SAEs to local authorities and manufacturers. The registry supports longitudinal safety analyses to identify treatment-related risks.

Participant Reimbursement: No financial reimbursement is provided. Diagnostic and treatment costs are covered by patients, their healthcare provider or their health insurance.

Sampling: The study does not use randomization or stratified sampling. Instead, it includes all eligible and consenting patients encountered during routine care at participating centers, reflecting a real-world clinical population.

Funding: InRAD is coordinated by the independent International Registry for Alzheimer's Disease and Other Dementias Foundation, a health-related not-for-profit entity incorporated in the Netherlands.

InRAD has received financial contributions from the pharmaceutical industry. InRAD does not endorse any companies or products. InRAD is operated independently from these companies.