Innovative Alzheimer's disease clinical trial design in the coming age of biomarkers

Alzheimer's disease (AD) is a field with huge unmet need and only a few symptomatic treatments with limited efficacy have been made available to patients. With the testing of disease-modifying drugs in recent years, the length of AD clinical trials has tripled and the enrollment has gone up drastically. These investigational disease-modifying drugs address new targets including the amyloid beta and tau protein aggregation pathways in the brain. They have opened up a whole research field on biomarkers specific to these pathways. These biomarkers have however never been used to select a subpopulation that would enroll in clinical trials. This thesis defines a framework for assessing any AD biomarker's quality as a selection tool for enrolling a subpopulation into an AD clinical trial. Carefully selecting the patient population with appropriate biomarkers can lead to a reduction in required enrollment in a study to show statistical significance. In turn, the decreased patient enrollment helps sponsors reduce costs and allows them to test several drugs with the same budget. In order to test our framework in an applied and relevant setting, we established from www.clinicaltrials.gov that for disease-modifying drugs the primary endpoint is change in ADAS-cog points at 18 months and that the trials enrolled on average 337 patients per treatment group. These disease-modifying AD trials use the inference on means statistical model.

Department dc:contributor.department

Harvard University--MIT Division of Health Sciences and Technology.

Grantor dc:publisher

Massachusetts Institute of Technology

Year dc:date.issued

2008

Author dc:creator

• Hillerstrom, Hampus

Advisor dc:contributor.advisor

• Joseph V. Bonventre and A. Gregory Sorensen.

• Harvard University--MIT Division of Health Sciences and Technology.

Statement dc:rights

• M.I.T. theses are protected by copyright. They may be viewed from this source for any purpose, but reproduction or distribution in any format is prohibited without written permission. See provided URL for inquiries about permission.

Licence dc:rights.uri

• http://dspace.mit.edu/handle/1721.1/7582

Language dc:language.iso

eng

Handle dc:identifier.uri

http://hdl.handle.net/1721.1/55277

OAI identifier oai:identifier

oai:dspace.mit.edu:1721.1/55277