Statistical Methods Research to Compare the Performance of New Estimators of the Treatment Effect in Alzheimer’s Disease Randomized Trials

Statistical Methods Research to Compare the Performance of New Estimators of the Treatment Effect in Alzheimer’s Disease Randomized Trials

I plan to apply for the Johns Hopkins Alzheimer's Disease Research Center (ADRC)
Pilot Project Funding for Basic, Clinical Or Methodological Aspects Of Aging, Alzheimer's Disease, Or Related Neurodegenerative Disorders.

Dr. Rosenblum has no financial relationships with any of the sponsors involved in this initiative.
Dr. Rosenblum has provided consulting services through his company Evolution Trial Design, Inc., consisting of expert advice on statistical methods for two pharmaceutical companies: Agenebio, Inc., and Axovant Sciences, Inc. These consulting services are completely separate from Dr. Rosenblum's research, and nothing in his agreements with these companies restricts or interferes with his ability to conduct or publish research at Johns Hopkins University (where the work conducted in this proposal will take place). No funds or resources from these companies will be used in any research conducted by Dr. Rosenblum. Dr. Rosenblum will not disclose any information derived from data in this project with these companies.

Clinical trials are the gold standard for measuring the effectiveness of new medical treatments, including new drugs, medical devices, and surgical techniques. After a clinical trial is completed, the data is analyzed to assess whether the new medical treatment is effective and safe. It is of crucial importance to use the best possible statistical analysis, in order to draw clear, reliable conclusions about the new treatment. Newly developed statistical methods (which are used to perform the data analysis) have potential to provide stronger evidence about a medical treatment's effectiveness. However, these new methods have not been tested across multiple different data sets to see whether they consistently outperform existing methods. We plan to do a head-to-head comparison of different data analysis methods using data from 10 completed randomized trials involving treatment or prevention of Alzheimer's disease. The output will be a ranking of how well each data analysis method performs (similar, roughly speaking, to the ratings of new cars by Consumer Reports), which will help inform how data will be analyzed in future clinical trials.

[{ "PostingID": 116, "Title": "GSK-AVA105640", "Description": "A 24-week, double-blind, double-dummy, randomized, parallel-group study to investigate the effects of rosiglitazone (extended release tablets), donepezil, and placebo as monotherapy on cognition and overall clinical response in APOE e4-stratified subjects with mild to moderate Alzheimer’s disease. (REFLECT-1)" },{ "PostingID": 495, "Title": "GSK-49653/461", "Description": "A double-blind, randomized, placebo-controlled, parallel-group study to investigate the effects of rosiglitazone (extended release tablets) on cerebral glucose utilization and cognition in subjects with mild to moderate Alzheimer's Disease (AD)" },{ "PostingID": 499, "Title": "GSK-AVA100193", "Description": "A 24 week double-blind, randomised, placebo-controlled, parallel-group dose-ranging study to investigate the effects of rosiglitazone (extended release tablets) on cognition in subjects with mild to moderate Alzheimer's disease" },{ "PostingID": 501, "Title": "GSK-AVA102670", "Description": "A 54-week, study to investigate the effects of rosiglitazone (extended release tablets) as adjunctive therapy to acetylcholinesterase inhibitors on cognition and overall clinical response in APOE e4-stratified subjects with mild to moderate Alzheimer’s disease (REFLECT-3)" },{ "PostingID": 2630, "Title": "GSK-AVA102672", "Description": "A 54-week, double-blind, randomized, placebo-controlled, parallel-group study to investigate the effects of rosiglitazone (extended release tablets) as adjunctive therapy to donepezil on cognition and overall clinical response in APOE e4-stratified subjects with mild to moderate Alzheimer’s disease." },{ "PostingID": 2721, "Title": "TAKEDA-01-05-TL-375-061", "Description": "A Double-Blind, Randomized, Placebo-Controlled Study of the Efficacy, Safety and Tolerability of 8 Week Treatment of Rozerem 8 mg (QHS) in Sleep Disturbed, Mild to Moderately Severe Alzheimer's Disease Subjects" },{ "PostingID": 3571, "Title": "GSK-H3B110651", "Description": "A randomised, double-blind, placebo-controlled study to evaluate the efficacy and safety of the H3 receptor antagonist, GSK239512 in subjects with mild to moderate Alzheimer’s disease." },{ "PostingID": 4086, "Title": "NOVARTIS-CENA713D1301", "Description": "A 24-week, Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel-group, Dose-finding Evaluation of the Efficacy, Safety, and Tolerability of the Once-daily Rivastigmine Transdermal Patch in Patients With Probable Alzheimer's Disease (MMSE 10-20)

Medicine: rivastigmine, Condition: Alzheimer's Disease, Phase: 3, Clinical Study ID: CENA713D1301, Sponsor: Novartis" },{ "PostingID": 4179, "Title": "NOVARTIS-CENA713 IA07", "Description": "A Prospective, Randomized, Multicenter, Double-Blind, Placebo-Controlled, Parallel-Group Study of the Effect of Rivastigmine on the Time to Clinical Diagnosis of Alzheimer’s Disease in Subjects with Mild Cognitive Impairment (MCI)

Medicine: rivastigmine, Condition: Alzheimer's Disease, Phase: 3, Clinical Study ID: CENA713 IA07, Sponsor: Novartis" },{ "PostingID": 4689, "Title": "NOVARTIS-CENA713D2340", "Description": "A 48-Week, Multicenter, Randomized, Double-Blind, Parallel-Group Evaluation of the Com-parative Efficacy, Safety, and Tolerability of Exelon® 10 and 15 cm2 Patch in Patients with Alzheimer’s Disease Showing Cognitive Decline during an Initial Open-Label Treatment Phase

Medicine: rivastigmine, Condition: Alzheimer's Disease, Phase: 3, Clinical Study ID: CENA713D2340, Sponsor: Novartis" }]

The publication citation will be added after the research is published.