On Monday, 27 October 2008, a live Webinar was held by Alzheimer’s research leaders on a national action plan to accelerate discoveries of treatments to prevent dementia. The plan will be presented to the 111th U.S. Congress in March 2009. Presentations were given by Marilyn Albert, Jeffrey Cummings, Rachelle Doody, Robert Egge, Serge Gauthier, Mike Grundman, June Kinoshita, Ron Petersen, Lon Schneider, Dale Schenk, Peter Snyder, and Zaven Khachaturian (moderator).
The panel was followed by a Q&A session open to audience members. Alzforum members may also submit questions via e-mail after the live Web event. The Alzforum hosted this discussion in collaboration with the 2008 Leon Thal Symposium on Prevention of Dementia (LTS’08) and the Alzheimer’s Study Group (ASG) to solicit suggestions from the scientific community on this important topic. (See our Virtual Town Hall: Early Detection of Alzheimer Disease for our previous live forum to solicit input from the research community for the National Strategic Plan.)
View/Listen to Video Recording
By Leon Thal Symposium organizers
Presently the field of Alzheimer’s research is at a crossroads: transitioning from symptomatic treatments of people with the disease to the prevention of the precursor in asymptomatic people.
The primary focus of this Webinar is to stimulate discussion and identify
1. The most critical barriers and challenges the field faces
2. Strategies to overcome these barriers to progress
3. Factors that would accelerate the development of therapies for the prevention of AD
4. Additional resources or infrastructure needs of ongoing programs or initiatives
5. Issues related to clinical trials, e.g., study design, cost, and study duration
6. Regulatory issues
7. New models to financing the cost of prevention trials
8. Incentives to promote prevention e.g., increased funding of discovery research, extending exclusivity, etc.
The panel members will start the discussions by briefly reviewing and commenting on some of the recommendations proposed by other groups, listed below. These are intended to be illustrative; panelists as well as Webinar participants are encouraged to suggest other ideas or comment/expand on those that are proposed.
Some of the recommendations for public policy initiatives include
1. Mandate National Institutes of Health (NIH) through reauthorization and specific appropriations to
- Redirect current intramural and extramural programs or establish new focused programs to focus specifically on translational medicine, thus addressing the gaps in research and funding of technology transfer from early drug discovery to early commercialization of putative therapeutic agents.
- Substantially increase the pipeline of therapies targeting the pathogenic mechanism.
- Demonstrate the efficacy of compounds designed to modify, slow or stop the pathogenesis of the disease.
- Emphasize discovery, validation, characterization of early biomarkers in prodromal stages of the disease in asymptomatic people, including biochemical markers, proteomics, gene expression, MRI imaging, PET/SPECT/amyloid imaging, neuropsychological, behavioral, non-invasive markers of daily function.
- Modify current merit review process and grant mechanisms to support a) long-term multisite collaborative studies, e.g., Alzheimer’s Disease Neuroimaging Initiatives (ADNI) and b) high-risk, high-payoff projects.
- Increase the efficiency and capacity of integrated clinical trial networks e.g., Alzheimer’s Disease Clinical Studies Program.
- Revamp and expand the Alzheimer’s Center’s program to encourage more integrative and translational research on asymptomatic stages of the disease, early detection, prevention, and therapy development.
2. Mandate Center for Disease Control (CDC) and/or NIH through reauthorization and specific appropriations to
- Plan, develop, and administer (fund) a national infrastructure for a broad spectrum of population-based studies; a national omnibus database (or a registry of people at risk) as shared or public research resource for epidemiological studies on incidence, prevalence, discovery of risks, clinical trials, validation of early risk factors or biomarkers, and topics related to health services research, e.g., resource utilization or health economics.
3. Mandate Food and Drug Administration (FDA) through reauthorization and specific appropriations to
- Require that clinical trials and future studies examine specific sets of biomarkers determined by an expert panel, with data results shared to help rapidly identify successful disease-modifying drugs seeking approval from the FDA.
- Explore viable incentives to encourage investments in large-scale prevention programs.
- Identify attractive inducements to entice drug developers to engage in serious planning and regulatory filings that are initiated in a timely fashion.
- Determine how to extend laws that provide for the marketing of generic drugs.
- Press for laws that protect the continuity of research that make drugs better. Prevention trials could then be expediently initiated, perhaps even before Phase 3 trials are completed.
- Address the increase in the number of applications for neurological therapies by increasing FDA and creating an office for neurological therapies at the FDA, as well as a process for: Priority Review, Accelerated Approval, or Fast Track review of drugs for Alzheimer disease.
- Promote collaboration and information sharing between the NIH and the FDA to accelerate research therapies for people with Alzheimer disease by opening pipelines.
4. Mandate the Center for Medicare and Medicaid Services (CMS) through reauthorization and specific appropriations to
- Create economic incentives to stimulate therapy development.
- Clarify strategies to secure a commitment from the Center for Medicare and Medicaid Services (CMS) to make subjects recruited for longitudinal and other dementia research studies eligible for reimbursement.
- Offset encumbrances of reimbursement.
- Study reimbursement experiences outside of North America.
- Evaluate the consequences of poor or non-existent Medicare and other third-party reimbursements on prevention trials and/or clinical care for dementia patients.
- Assess potential economic incentives (such as a commitment from the Center of Medicare and Medicaid Services to make subjects in longitudinal prevention studies eligible for reimbursement) to stimulate therapy development for prevention.
5. Mandate the Department of Commerce through reauthorization and specific appropriations to
- Amend current patent protection laws, as an incentive for investment and promotion of therapies for prevention.
- Provide incentives for investors, pharmaceutical and biotechnology companies to invest in Alzheimer disease therapies. Incentives could include economic incentives such as tax credits, patent extensions, and partnerships with federal and state agencies to develop and deliver products for treatment and prevention.
Alzforum members may also submit questions via e-mail before and after the live Web event.
Q: Will the national action plan to accelerate discoveries of treatments to prevent dementia also take into consideration, as a group, adults with Down syndrome?
Q: Laypeople are frequently bombarded with advice and advertisements on how to prevent AD. Examples would be advice on keeping your brain active, playing crosswords, Nintendo Wii, taking certain types of vitamins, having an advanced degree, etc. Do you consider these to be a barrier to getting at successful prevention of AD?
Q: Following up on Lon's point, what's wrong with incidence of dementia or AD as a relatively hard endpoint?
Q: Should the application of this policy be restricted to peer-reviewed NIH, VA, Alzheimer's Association, etc., research?
Q: What about the NCI CTEP program as a model? CTEP (Cancer Therapeutic Evaluation Program) is a congressionally mandated program that supports clinical trials in oncology. It is the framework for the cancer co-operative group trials, provides precompetitive space where compounds can be studied in combination without compromising companies’ IP, and has a mechanism for doing screening toxicology and pilot clinical trials for compounds originating in academic laboratories.
Q: Zaven, ask Lew Kuller to comment on the GEM trial.
Q: Could private practice physicians who maintain geriatric practices be tapped in a model to enhance registries or recruitment for prevention trials? This method has been used in the U.K., but will require changes in health care delivery and perhaps HIPAA.
Q: Please discuss potential non-pharmacologic treatments, such as physical exercise, and ways that we might do internally and externally valid studies of such treatments in the U.S.
Q: I think there should be a task force that would look into the epidemiologic methodology involved in participation issues in prevention trials, because participation in asymptomatic people will likely be abysmal.
Q: Discussing prevention is good, but how can we ensure we are doing valid research in an environment where individuals in the general population (asymptomatic) don't want to participate in research? I think we need to address the epidemiologic methodology inherent in this problem.
Q: What about the Welcome to Medicare Kit? Could that be an initial point of screening for AD?
Q: Which neuropsychological test do you recommend for 1) screening of dementia in the epidemiological studies, and 2) for cognitive assessment in the patients with AD, who are illiterate?
Q: While great attention is being placed on a suitable pharmaceutical attack on dementia (as well it should), will equal attention be given to helping caregivers in their struggles, especially if a drug solution is not available in the near future?