INDIVIDUAL PARTICIPANT DATA META-ANALYSIS OF DONEPEZIL FOR ALZHEIMER'S DISEASE

INDIVIDUAL PARTICIPANT DATA META-ANALYSIS OF DONEPEZIL FOR ALZHEIMER'S DISEASE

Dementia constitutes a serious human, social and economic burden in today's ageing societies. Donepezil is one of the first anti-dementia drugs which have been shown to delay the progress of Alzheimer's and related diseases. However, this description of efficacy of a drug is based on the group average of people who have participated in randomized controlled trials. Individuals may respond more or less, depending on their individual characteristics. Such “personalization” or “stratification” of efficacy have been only assumed but not evidence-based to this date, because their elucidation would require several times bigger sample sizes than ordinary clinical trials and complex analyses. In this study we propose to conduct such “personalized medicine” or “precision medicine” analyses by pooling together a dozen clinical trials and conducting the cutting-edge statistical analysis called individual participant data meta-analysis.We accordingly propose three primary analyses and several secondary analyses.The primary analysis 1 will link scores of various dementia scales and create the conversion tables matching what a given total score or a change score from baseline on one scale with those on other scales through the equipercentile linking. This step is necessary to conduct the ensuing analyses.The primary analysis 2 will focus on baseline dementia severity as effect modifier (i.e. factors responsible for individual differences of efficacy), because this is an unresolved, hot issue in clinical psychopharmacology and will have a great clinical implication. The primary analysis 3 will explore the role of patient-level characteristics as possible prognostic factors and effect modifiers for efficacy (dementia severity) and acceptability (all-cause dropouts), and will build a prediction model, aiming to predict outcomes given the patient's characteristics.Because the data that we envision to obtain in this study is so rich in contents, we would like to conduct several additional analyses to advance the clinical trial methodology and the understanding of effects of donepezil and Alzheimer's disease symptomatology. The details of the proposed secondary analyses are to be found below.

[{ "PostingID": 19970, "Title": "EISAI-E2020-J081-161", "Description": "Clinical efficacy and safety of donepezil on cognitive and global function in patients with Alzheimer's disease. A 24-week, multicenter, double-blind, placebo-controlled study in Japan." },{ "PostingID": 19971, "Title": "EISAI-E2020-A001-201", "Description": "A Preliminary, Multi-Center, Randomized, Double-Blind, Placebo-Controlled Evaluation of the Safety and Efficacy of E2020 in Patients with Alzheimer's Disease." },{ "PostingID": 19972, "Title": "EISAI-E2020-A001-301", "Description": "A 15-week, Multi-Center, Randomized, Double-Blind, Placebo-Controlled Evaluation of the Safety and Efficacy of E2020 in Patients with Alzheimer's Disease." },{ "PostingID": 19973, "Title": "EISAI-E2020-A001-302", "Description": "A 30-Week, Multi-Center, Randomized, Double-Blind, Placebo-Controlled Evaluation of the Safety and Efficacy of E2020 in Patients with Alzheimer's Disease." },{ "PostingID": 19974, "Title": "EISAI-E2020-A044-304", "Description": "A 30-Week, Multi-Center, Randomized, Double-Blind, Placebo-Controlled Evaluation of the Safety and Efficacy of E2020 in Patients with Alzheimer's Disease." },{ "PostingID": 19975, "Title": "EISAI-E2020-J081-231", "Description": "A Multi-Center, Randomized, Double-Blind, Parallel Group Study With 3 Groups Receiving Placebo, 5 mg of E2020 and 10 mg of E2020" },{ "PostingID": 19976, "Title": "EISAI-E2020-A001-315", "Description": "A 24 Week, Multicenter, Randomized, Double-Blind, Placebo-Controlled Evaluation of the Safety and Efficacy of Donepezil Hydrochloride (E2020) in Patients With Severe Alzheimer's Disease Followed by a 12 Week Open-Label Extension Period" },{ "PostingID": 19977, "Title": "EISAI-E2020-A001-311", "Description": "A Randomized, Double-Blind, Placebo-Controlled Evaluation of the Effects of Donepezil Hydrochloride (E2020) in the Management of Patients with Alzheimer's Disease in a Nursing Home Facility." },{ "PostingID": 19978, "Title": "EISAI-E2020-A001-312", "Description": "A 54-week, Randomized, Double-Blind, Placebo-Controlled Evaluation of the Effects of Donepezil Hydrochloride (E2020) on Functional Outcomes in Patients with Alzheimer's Disease." },{ "PostingID": 19979, "Title": "EISAI-E2020-G000-326", "Description": "Comparison of 23 mg Donepezil Sustained Release (SR) to 10 mg Donepezil Immediate Release (IR) in Patients With Moderate to Severe Alzheimer's Disease" },{ "PostingID": 19980, "Title": "EISAI-E2020-C086-339", "Description": "A 24-weeks, Multi-center, Randomized, Double-blind, Placebo Controlled Study to Evaluate the Efficacy and Safety of Donepezil Hydrochloride in Chinese Subjects With Severe Alzheimer's Disease" }]