2004N-0181 - Critical Path Initiative; Establishment of Docket
FDA Comment Number : EC24
Submitter : Ms. Bonnie Hogue Duffy Date & Time: 08/02/2004 07:08:27
Organization : Alzheimer's Association
Consumer Group
Category :
Issue Areas/Comments
Comment Issues
2. Please rank each hurdle identified in Question 1, above, in priority order according to which hurdles create the most severe product development problems.

1) Biomarkers
2) Animals
3) MCI
4) Recruitment

1. Hurdle Identification. Please describe the product development issue, the nature of the evaluation tool that is out-of-date or absent, how this problem hinders product development, and how a solution would improve the product development process.

1) Clinical trials for the treatment of Alzheimer's disease pose hurdles for a variety of reasons. Alzheimer's is under-diagnosed; it is difficult to find people with Alzheimer's in the community; people with Alzheimer's have limited mobility; due to characteristics of the population involved, Alzheimer trials have high rates of drop outs; and, psychometric measures used are fraught with human challenges (subjectivity). All of these challenges make recruitment and retention in AD trials a particular challenge.

2) Animal models for Alzheimer's disease demonstrate limited portions of the pathophysiology of AD and need to be better. This results in limited information from pre-clinical data.

3) The lack of biomarkers for Alzheimer's disease hinders our ability to track the effects of therapy.

4) Mild cognitive impairment (MCI) is emerging as its own entity, but there is no scientific consensus on the definition of MCI and on best practices for clinical trials on MCI. Resolution of any of these hurdles will result in the achievement of the three hallmarks of clinical trial excellence faster, better and cheaper.

3. For each problem identified, please indicate the type of drug, biologic, or device to which the hurdle applies.
All Alzheimer's disease drugs.
5. Nature of the Solution. For each problem identified, please describe the evaluation tool that would solve the problem and the work necessary to create and implement the tool/solution. For example, would a solution come from scientific research to
In general, more rapid and complete dissemination of agency intent would be helpful.

The Alzheimer's Association urges FDA to commit resources for FDA staff to participate in meetings and partnerships with the Alzheimer's Association in order to facilitate an increased level of communication. We believe an increased level of communication would lead to consensus and a more efficient resolution of hurdles. Specifically, we would like FDA staff to:

Participate in meetings of the Alzheimer's Association Pharmaceutical Roundtable;
Continue to contribute to the Sept. 8, 2004 MCI and Clinical Trials meeting;
Participate in the June 18, 2005 Alzheimer's Association's International Conference on Prevention of Dementia;
Attend The Alzheimer's Research Consortia meeting.

In addition, the Alzheimer's Association believes it would beneficial for FDA staff to have the time and resources to be involved in ongoing initiatives on genetics and imaging at the National Institute of Aging, including the following:
Alzheimer's Disease NeuroImaging Initiative;
Alzheimer's Disease Genetic Initiative; and the Alzheimer's Disease Cooperative Study Clinical Trial Group.

7. For each problem identified, what role should FDA play and what role should be played by others?
In the area of biomarkers, there should be an overlapping process of FDA standard setting and scientific consensus on the development of biomarkers ? these processes should not be independent of one another.

In the area of clinical trials, FDA could help by providing more information about what is important in different phases of trials.
All of the problems will respond to FDA presence and input into a variety of discussions.

6. For each solution identified, please indicate which could be accomplished quickly, in less than 24 months, and which require a long-term approach?
Much of what we are suggesting could be accomplished quickly. FDA staff needs the time to do these kind of events, permission to participate, and clear supervisory instruction that participation is expected.
4. For each problem identified, if a solution would facilitate the development of drugs, biologics, and/or devices for a particular disease or categories of disease, please indicate which diseases would be affected?
Our comments address Alzheimer's disease and related dementias.
8. What factors should guide FDA in setting priorities among the hurdles and solutions identified?
With the aging of the baby boomers, the number of people with Alzheimer's will grow from 4.5 million today to an astounding 11 to 16 million by the middle of the century. Left unchecked, Alzheimer's will undermine our families, communities, and basic economic security. It will overwhelm our health care system, bankrupt Medicare and Medicaid, drain billions of dollars from American business, and destroy retirement security for tens of millions of families.

An Alzheimer's Association report released last month, Saving Lives, Saving Money: Dividends for Americans from Investing in Alzheimer Research, showed that funding breakthroughs in medical research could result in nearly 3 million fewer Americans with the disease and $149 billion in annual Medicare and Medicaid savings by 2025. For every dollar spent now on research, the federal government would have a significant return on investment in future Medicaid and Medicare costs -- 12 to 1 by 2015, 30 to 1 by 2025, and more than 100 to 1 by 2050.

The FDA is poised to play a key role in the development of new treatments for people with Alzheimer's. The Alzheimer's Association urges the FDA to make Alzheimer's disease a top priority and to commit the staff resources needed to overcome the present hurdles to getting new treatments to patients. The association stands ready to partner with the agency for the improvement of the health of all American citizens.

The Alzheimer's Association applauds FDA for undertaking the Critical Path Initiative. The association did an informal survey of clinical scientists in the field to develop these recommendations. Through these conversations we identified two more general issues: scheduling of first appointments can sometimes be a challenge and it would be helpful to shorten the time it takes for corporate entities to get an appointment to discuss new drug applications; increased FDA outreach to corporate entities early in the application process can do more to improve the rate of development of new therapies than adjustments later in the process.