Roche has selected PicnicHealth as its partner to study Alzhemier’s disease (AD) in real world patients through their latest project, EMPOWER AD. The partnership leverages PicnicHealth’s end-to-end patient-centric approach to building registries from recruitment, to medical records retrieval, and machine learning (ML)-driven, human-curated data abstraction.  Researchers can then leverage the data to learn about what it’s like to be a patient navigating the medical system in the real world, to ultimately uncover important insights on disease characteristics and clinical outcomes.

It is a particularly exciting time to be studying AD as the long-awaited disease modifying immunotherapies are reaching approval from the FDA. These drugs target the amyloid-beta protein plaques seen in imaging of AD patient brains, a hallmark of the disease. Most companies are trying to target patients early in their disease when therapies are believed to have the greatest chance of slowing or preventing disease progression. In the clinical trial setting, imaging is needed to ensure the right patient population is captured and can be important to demonstrate the drug is effectively hitting the target. However, the path to diagnosis is incredibly variable in the real world and identifying patients with early disease can be challenging. Imaging tools may be impractical for diagnosing and monitoring patients outside of academic clinical sites, which leaves uncertainty for doctors looking to treat patients most likely to benefit from a therapy.

What can RWD do to help researchers?

EMPOWER AD hopes to help relieve some of these pervasive challenges by giving researchers a comprehensive view of medical data curated from several sources including electronic health records (EHR), imaging, diagnostic tests, and cognitive assessments. Understanding how patients are being identified and what tools are being leveraged to assess the state of their disease may help inform strategies for identifying patients earlier, when they may benefit most from these novel therapies.

In an initial peek of 440 patients in the registry, researchers found a nearly 50/50 split of patients self-enrolling and care partners enrolling on behalf of a patient. The ability to register as a care partner is an interesting feature of the registry. In addition, it aligns well with the aim of enrolling early patients by demonstrating that half of the recruited patients have the ability to self-register and manage their care independently. A breakdown of race and ethnicity is shown in Table 1, which mimics the expected population subgroups.  This is important because results generated from the registry are more powerful if they can be generalized to the representative US AD epidemiology.

Clinical evaluations of AD patients

Understanding early AD and the path to diagnosis means that the EMPOWER AD registry needs to capture the full patient journey including an extensive look-back or view of the patient before their AD diagnosis to identify symptoms like impaired executive function or sleep disturbance. These signs and symptoms or diagnoses can also help illuminate trends in clinical records for how patients are initially classified. 

Research priorities include uncovering the frequency at which cognitive, imaging, and genetic assessments are received in early clinical evaluation of patients with symptomology consistent with AD. This means the data must be able to tease apart different subgroups of AD patients on the path to diagnosis, including those with mild cognitive impairment (MCI), dementia that could be AD (i.e. not diagnosed as dementia of another kind), and those with an AD dementia diagnosis. Many symptoms are not specific to AD and/or are not well coded within traditional sources of RWD like administrative claims, making PicnicHealth’s approach to data abstraction crucial for answering these research questions. Finally, linking data from sources outside the EHR is needed to comprehensively capture the diverse array of medical journeys that could lead to an AD diagnosis.

Memory impairment was the most frequently reported symptom in 85% of patients, followed by mood disturbance (80%), and sleep disorder (47%). Less commonly reported symptoms included impaired executive function (30%), disordered language (22%), and agitation (20%). Patient data will continue to be collected prospectively and it will be important to see how the frequency of symptom capture changes throughout the course of the disease.

In this real-world registry, only 5% of patients have been evaluated using imaging methods including Amyloid-PET and MRI. This low frequency reflects how uncommon imaging assessments are for this population within routine clinical practice. This is a prime example of the discrepancy that exists between the real world patient journey and what is defined in clinical trial protocols.

In contrast, 70% of patients had received a cognitive assessment. The most common was the mini-mental state examination (MMSE, 37%), followed by the Montreal cognitive assessment (MoCA, 38%), and Saint Louis University mental exam (SLUMS, 5%). While each test has its own set of questions probing cognitive function, it is clear that these assessments are more universally included in patient exams than imaging when looking at patients in the real world.

Trends in treatments

Researchers, payers, and drug developers are watching with great anticipation to see how the market reacts to the newly approved AD therapies.  This pivotal moment in time for AD treatments makes the EMPOWER AD registry an especially valuable resource. By collecting medical records, both retrospectively and prospectively, the registry enables researchers to observe and account for changes in the treatment landscape over time.

In the initial look at patients, trends in treatments were aligned with symptomatic medications (specifically, donepezil, memantine, and rivastigmine) used more often to treat AD dementia than to treat patients with MCI. Less than 1% of patients had been treated with aducanumab, which is not surprising given its recent approval and the timing of the analysis. However, now with lecanemab also reaching approval, positive reimbursement decisions, and more data demonstrating clinical benefit, doctors and their patients will likely transition to disease-modifying immunotherapies. Any changes to prescribing patterns will be captured in the registry and will continue to inform stakeholders wanting to learn more about AD patient journeys, treatment trends, and clinical outcomes.

PicnicHealth is excited to be at the forefront of AD research and complementing research partners' clinical programs with comprehensive, high-quality RWD.

Additional subgroup analyses of MCI, dementia, and AD dementia subgroups were performed and the analyses reported here and the additional subgroup analyses were reported in full at 2 conferences. Download the AD/PD Annual Meeting Poster to learn more.

Contact us at partnerships@picnichealth.com to speak to a member of the PicnicHealth team.