Comparative Research of Alzheimer's Disease Drugs

The overarching goal of this proposal is to enhance the existing information technology
infrastructure in Central Indiana to improve the nation's capacity to conduct comparative
effectiveness research (CER). Consistent with the instructions in RFA-HS-10-005, the
investigators propose to apply these new capacities to a novel CER project evaluating
treatment for Alzheimer's disease. Alzheimer's disease has been identified as a first
quartile CER priority. This proposal represents collaboration between the Medical
Informatics Program at the Regenstrief Institute, Inc (a world leader in health information
technology) and two Indiana University research programs: the Center for Aging Research and
the Division of Clinical Pharmacology. These programs have an established track record in
research relevant to under-served populations. Thus, this proposal combines considerable
investigator, environment, and research strengths to continue to build a novel CER
infrastructure in support of the nation's evidentiary CER priorities.

Throughout this proposal, the investigators use the AHRQ definition of CER: the conduct and
synthesis of research comparing the benefits and harms of different interventions and
strategies to prevent, diagnose, treat and monitor health conditions in real world
settings." The investigators also refer to a clinical trial of medication treatment for
behavioral symptoms of Alzheimer's disease as the specific CER proposed to demonstrate the
potential of our new infrastructure. However, the investigators stress that the enhancements
proposed to existing infrastructure would support a broad portfolio of CER across an array
of priority conditions. The investigators are also proposing enhancements in our privacy and
confidentiality technology that would allow researchers from across the country to access
de-identified data in support of CER. In summary, the investigators are proposing to add new
CER knowledge on Alzheimer' disease and thereby field test new information technology
capacities important to a wide range of CER projects while also increasing our capacity to
provide data and opportunities for nationwide CER.

The derivation of meaningful and actionable evidence from CER ultimately depends on
capturing relevant, comprehensive and accurate data about treatment decisions, patients'
clinical status, their care processes and environment, and the health outcomes they
experience and value. Such data must be tracked longitudinally in order to determine
temporal relationships, cause-effect paradigms, and the efficacy of specific clinical
interventions in the context of other conditions, interventions, and goals of care. At
Indiana University and the Regenstrief Institute, the investigators have four decades of
experience and a well-documented, world-class clinical informatics and research
infrastructure for capturing, storing, querying and analyzing treatment patterns and
patients' clinical outcomes.

The maturation of this health information technology is now embodied within the Indiana
Network for Patient Care (INPC), a fully-operational regional health information exchange.
The investigators are well positioned to expand and leverage this infrastructure in support
of local and national multi-site clinical trials in comparative effectiveness. The specific
aims of this proposal are to:

1.0 PROSPECT STUDY: Enhance our existing information technology infrastructure to:

1. provide de-identified access to the INPC database for CER work

2. capture, store, and track a broader array of health care outcomes important to patients
and their caregivers (e.g. behavioral symptoms due to dementia);

3. support providers' and caregivers' and researchers' increasing need to work in teams by
providing new tools for communication and co-management (e.g. collaborative care and
research)

2.0 COMET-AD STUDY: Conduct comparative effectiveness clinical trial of medication treatment
for behavioral symptoms of Alzheimer's disease in a group of real-world memory care clinics
with enhanced access to the Indiana Network for Patient Care.

Inclusion Criteria:

- older adults with a diagnosis of possible or probable Alzheimer's disease

- planning to initiate treatment with a cholinesterase inhibitor

- planning to continue care in the memory care practice

- participation by a family caregiver willing to complete the study outcome assessments

- access to a telephone

- ability to understand English-Language survey instruments

Exclusion Criteria:

• prior serious adverse event from the study medications