Comparative Effectiveness Research Trial of Alzheimer’s Disease Drugs: COMET-AD

1. Comparative Effectiveness Research Trial of Alzheimer’s Disease Drugs: COMET-AD • Malaz Boustani, MD, MPH • Network Director, Indianapolis Discovery • Network for Dementia • Associate Professor of Medicine, IU School of Medicine • Research Scientist, Regenstrief Institute, Inc www.indydiscoverynetwork.org

2. Goals • Conduct a 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. • Add new comparative effectiveness research (CER) knowledge on Alzheimer’s disease to our existing information technology infrastructure. • Field test new information technology capacities (PROSPECT study). www.indydiscoverynetwork.org

3. COMET-AD • Patients participating in the study will be randomized to treatment with donepezil, rivastigmine, or galantamine; no patients will be allocated to a placebo. • The study is open-label and the memory care practice physicians will make determinations about initial drug dosage and any dosage changes and the timing of those changes. • Each of these medications already has FDA-approval for Alzheimer’s. The primary outcome measure is the discontinuation rate among the three medications. www.indydiscoverynetwork.org

4. Recruitment • Recruitment completed by designated memory care practice staff member: • The nurse, research assistant, or other designated staff member in each memory care practice will • Identify eligible patients and their caregivers • Discuss study • Obtain informed consent from the patient and/or an informal caregiver • Patient blood draw • Surveys completed by Research Assistant (RA): • Telephone interview to administer study instruments • Physician Involvement: • Amount of involvement based on own preferences and availability • Possible activities: inform patients of study, participate in knowledge dissemination as author on related papers • Minimal impact on day to day operations www.indydiscoverynetwork.org

5. Inclusion/Exclusion Criteria Inclusion criteria include: • 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 Exclusion criteria include: • prior serious adverse event from the study medications www.indydiscoverynetwork.org

6. Recruitment Procedure • The proposed CER study will be conducted in five memory care practices representing the four health care systems affiliated with Indianapolis Discovery Network for Dementia (IDND) • Wishard, Clarian, St. Vincent, and Community Health Network • The nurse will approach eligible patients and request consent for study. Upon enrollment, the nurse will draw the patient’s blood at the beginning of the study and at the patient’s next office visit. A little over 2 teaspoons of blood will be drawn on each occasion, for a total of 20mL (or a little over 4 teaspoons) of blood. • A research assistant, blinded to the subject’s allocation, will call the patient and their caregiver to administer three different instruments: • The medication survey (caregiver only) • Neuropsychiatric Inventory (NPI) (caregiver only) • HABC Monitor for the patient and/or caregiver www.indydiscoverynetwork.org

7. Recruitment Procedure • The RA will call the patient and the caregiver to re-administer the three instruments again at 6, 12, and 18 weeks into the study. • Each telephone interview takes approximately 45 minutes to complete. • The patient and caregiver dyad will receive a $75 gift card at the completion of the study www.indydiscoverynetwork.org

8. Recruitment Flow Chart www.indydiscoverynetwork.org

9. Budget Analysis • Items to consider will depend on the site to some extent: • Informed consent:  $25 - $50 • Blood draw, process, and ship: $25 - $50 per each • IRB fees (per site basis): IU charges between $2,000 and $2500 for initial review depending on if it qualifies for expedited review. • Research Assistant’s time for phone calls to patients and data collection:  to calculate that into your budget, take their base hourly rate plus % for fringe benefits (we use 35% to 40%), multiplied by the number of hours of work required for calls and data entry. • Other costs: shipping costs of specimens, lab processing, storage fees for samples, etc. www.indydiscoverynetwork.org