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Request for Information (RFI) Announcement
RFI Number: HHS-NIH-OD-OLAO-SS-15-030
Project Title: The Development of an Alzheimer's Preclinical Efficacy Database
This is a Request for Information (RFI). This is NOT a solicitation for proposals, proposal abstracts, or quotations. The purpose of this RFI is to obtain knowledge and information for project planning purposes."
a. Background.
Alzheimer's disease (AD) is devastating for patients and their caregivers. 5 Million Americans are living with active symptoms from AD and it is ranked as the 6th largest cause of death in the United States. Furthermore, 15.5 million caregivers provided 17.7 billion hours of unpaid care, with an estimated value of $220 Billion. Health care costs alone for patient care were $214 Billion. These figures do not account for paid caregiver support, which is equally financially staggering. It is estimated that the number of AD patients may be as high as 13.8 million in 2050.
Despite this already large and escalating public health crisis, available treatments are limited to those that produce a modest relief of symptoms. Delaying symptom onset by 5 years could reduce disease prevalence by as much as 50%; this would significantly reduce the human burden and health care costs associated with the disease. Therefore, effective therapies that prevent AD or slow its progression are urgently needed. However, despite significant advances in understanding the neurobiology of AD, the development of effective AD therapies has been challenging, as is evidenced by the extremely high attrition rate for AD treatments with 98% of therapies failing in Phase III.
While there are numerous potential explanations as to why these clinical trials may have failed, one of the major reasons given to account for the high failure rate of AD drugs is the poor predictive power of preclinical efficacy studies performed in AD transgenic (Tg) mouse models. For example, of more than 300 therapeutic agents reported in leading scientific journals to ameliorate pathology and/or cognitive deficits in AD Tg mouse models, none has exhibited significant clinical benefit when tested in large human clinical trials. This problem is not unique to the AD field but, affects therapy development for many CNS diseases and disorders. A number of key factors have been identified as contributors to the unsuccessful translation of therapeutic efficacy, these include:
•· Failure of the models to fully recapitulate human AD.
•· Poor study design and data analysis, often due to studies being under powered.
•· Insufficient attention given to using a standard set of "best practices" in design and reporting of outcomes.
•· Failure to match outcome measures used in preclinical animal studies and clinical studies, which could compensate for studies being under powered.
•· Poor reproducibility of published data and publication bias.
•· Failure to publish negative results.
The National Institute on Aging (NIA) and the National Institutes of Health (NIH) Library have worked closely together to develop the International Alzheimer's Disease Research Portfolio (IADRP) [http://iadrp.nia.nih.gov/] which has quickly grown to include over 14,000 funding records from nearly 31 government and non-government funders around the world. Success in this partnership has encouraged both parties to explore a partnership to build a related website focused on preclinical research studies.
The following data is collected within the AlzPED Database:
Bibliographic Information
APID
Year of Publication
Title
PI Author L Name
PI Author F Name
PI Author M Initial
Primary Reference
Funding Organization
Therapeutic Agent
Model
Therapeutic Target
Therapeutic Agent
Therapy Type
Therapeutic Target
Therapeutic Agent
Links to PubChem, PubMed, Clinical Trials, Patents
Animal Model Information
Species
Model Type
Model
Strain
Experimental Design
Model Age at Beginning
Total Number of Subjects
Number of Groups
Number of Animals in each Group
Gender
Dosage
Formulation
Route of Delivery
Biomarker
Method of Random Subjects into Groups
Agent Administration Interval
Duration of Treatment
Method of Random for Treatment
Pharmacokinetic
Pharmacodynamics
ADMET Measures
Toxicology Notes
Method of Blinding Outcome Measured
Power Calculation
Outcome Information
Objective of the Study
Principle Findings
Outcome Measured
Type Outcome Assessment
Statistical Test
Statistical Significance (P Value)
Conclusion
Number of Premature Deaths
Number of Excluded Animals
b. Purpose and Objectives.
The National Institute on Aging (NIA) and National Institutes of Health (NIH) Library propose to create a data repository, Alzheimer's Preclinical Efficacy Database or AlzPED to mitigate the challenges of animal model studies and increase the translation of AD therapies to the clinic. This database will contain information relating to the preclinical testing of candidate therapeutic agents in Alzheimer's disease (AD) animal models. More specifically, within the scope of this project the NIA is creating a web-based portal for housing, sharing and mining of data relating to the preclinical testing of therapeutic agents in AD animal models. This portal will house experimental details, designs and, analyses of both positive and negative data.
The AlzPED database will be broadly available to scientists from academic centers, industry, disease-focused foundations and the lay public.
Data will be gleaned from at least two sources; 1) the scientific literature; 2) directly from researchers. It will be populated through a public submission form and through subject matter expert curation of relevant literature. Content will include information on the animal models, study design, primary and secondary outcome measures, statistical plan, therapeutic agents (e.g., drugs, biologics), formulation, and route of administration, dose and duration of treatment, data analyses and results.
These features of the database should aid in establishing standardized methods and best practices, thus increasing reproducibility of studies and limiting publication bias against negative results. Specifically the goals for AlzPED are to:
•1 (1) Serve as a resource that provides both successful and unsuccessful experimentation in Alzheimer's disease research.
• (2) Create awareness concerning the frequency of critical information that is left out of study reporting which precludes reproducibility and accurate assessment of those studies.
(3) Provide a single source location for researchers to being the therapeutic agent assessment process, saving them many hours of valuable time.
c. Project Requirements.
With this Request for Information (RFI) Notice, the NIH Library and the National Institute on Aging invite interested and knowledgeable persons to inform the AlzPED development team about the utility of the proposed content, information architecture, personal preclinical literature research practices, and prior completed projects of similar nature.
Please respond to the following questions:
How can data within AlzPED (http://alzped.nihlibrary.com) improve preclinical research methodologies?
Are there changes that could be made to the architecture to encourage participation from researchers, societies, pharmaceutical, and information providers to include neutral or negative studies?
Are there existing best practices or recommendations on how to improve our data dictionary?
Are there public or commercial sources of information that would be relevant to this effort, either for ingesting into this public resource or through linking out to a related resource?
What literature database content or access features would be helpful to consider adding to this resource?
If a REST API were made available for this resource, how would it potentially be used?
What databases do you search for preclinical literature studies?
How much time do you spent searching for literature?
How much time do you spend reviewing the literature?
What percentage of literature to you ultimately end up including in your experimental design? - (Rephrased, how many resources to you use in your proposal, vs. the dataset you started with?)
What information are you trying to find when you review articles?
How often do you feel you find the information you need?
What information drives your experimental design process?
If you were able to have the information listed in the AlzPED database section, how do you think that might impact your experiment design?
Do you know of other project with objectives similar to AlzPED?
d. Anticipated period of performance.
There is no anticipated period of performance at this time.
e. Other Important Considerations.
n/a
f. Capability Statement /Information Sought
(i) Respondents' responses:
• MUST include the heading "AlzPED RFI Reply"
• Can be sent electronically via e-mail to the point of contact listed below
• Need NOT include a capability statement or "white paper"
• There is no size or spacing restrictions
• Responses can be in any format
• Simple e-mail message, Microsoft Word, or Adobe PDF formats are all acceptable.
(ii) In 20 pages or less, any interested business organization should submit a capability statement or any form of response with information about their organization which demonstrates their ability to supply the services described above. Respondents should also include any other information that may be helpful in developing or finalizing the acquisitions requirements. The NAICS Code for this requirement is 519130 with a business size of 500 employees.
Responses must reference the sources sought number HHS-NIH-OD-OLAO-SS-15-030 and include the following:
(1) Name and Address of the organization
(2) Size and Type of business (e.g., 8(a), HUBZone, etc) pursuant to the applicable NAICS code 519130.
(3) Respondents' Points of Contact with names, titles, phone numbers and email addresses.
(4) DUNS number
(5) Contractors responses should address the deliverables described above and other information requested, list of organizations to whom similar types of services have been previously provided to include contract number, dollar value, name and phone number of contracting officer.
All information submitted in response to this announcement must be received on or before the closing date of: August 28, 2015 at 1 P.M. EST.
Emailed responses are authorized (either in Microsoft word or PDF), but it is up to the vendor to ensure that the email is received by the government. Responses by Facsimile (FAX) and hard copies WILL NOT be accepted. All questions and/or comments must be in writing and may be emailed to O. Joy Ajao at [email protected].
"Disclaimer and Important Notes:
This notice does not obligate the Government to award a contract or otherwise pay for the information provided in response. The Government reserves the right to use information provided by respondents for any purpose deemed necessary and legally appropriate. Any organization responding to this notice should ensure that its response is complete and sufficiently detailed. Information provided will be used to assess tradeoffs and alternatives available for the potential requirement and may lead to the development of a solicitation. Respondents are advised that the Government is under no obligation to acknowledge receipt of the information received or provide feedback to respondents with respect to any information submitted.
Any solicitation resulting from the analysis of information obtained will be announced to the public in Federal Business Opportunities in accordance with the FAR Part 5. However, responses to this notice will not be considered adequate responses to a solicitation.
Confidentiality:
No proprietary, classified, confidential, or sensitive information should be included in your response. The Government reserves the right to use any non-proprietary technical information in any resultant solicitation(s)."