Expressions of Intent for IPY 2007-2008 Activities

Expression of Interest Details

PROPOSAL INFORMATION

CANADA #247: Drug Safety – a Northern Perspective  (Drug Safety)

Outline
In this project a multi-disciplinary team of basic science and clinical support collaborators with expertise in physiology, ethnobiology, pharmacogenetics, medicinal chemistry and pharmacokinetics will work with health care providers (HCPs), community members and elders to: 1) survey Northern residents for their concurrent use of traditional medicines, natural products alone and together with therapeutic products; 2) examine current national and international databases, and determine in a culturally sensitive way the relative frequency of adverse drug events (ADEs) in this population; 3) where ADEs are identified, work with the individual to determine possible intrinsic and extrinsic factors. This project with #1 and 2 will help expand knowledge and aid in the development of strategies to stimulate ADE reporting in this population; 4) obtain local and regional ethics approval for the use of molecular biology pharmacogenetic techniques to screen the allelic profile of known polymorphisms in blinded samples of genomic material for the main cytochrome P450 drug metabolizing enzymes, the conjugative enzymes and ATP-binding cassette (ABC) transporters such as P-glycoprotein in Northern residents, and those having a reported ADE [no other genomic tests will be conducted and genomic samples will be destroyed at the end of the study]; 5) collect samples of traditional medicines and natural products (particularly those used for immunoenhancement) used by Northern residents to determine their potential for interacting with each other alone and in combination with drugs using in vitro enzyme systems and/or human cell lines; 6) extend the studies outlined in #5 to determine the potential of Northern contaminants such as pesticides and heavy metals to affect the safety and efficacy of traditional medicines and other drugs; 7) neurotoxicity assessment of these products alone and in combination with contaminants; and 8) communication and educational activities: undertake/participate in a Northern workshop to bring together investigators, HCPs, elders and the general community. The intent is to establish the state of the knowledge and potential gaps affecting: drug safety and efficacy in Northern residents including potential interactions, identify a culturally sensitive way to collect and then support a surveillance programme, evaluate how the results may be made meaningful to this population for development of risk reduction/prevention communication strategies and training programs to increase the safety and efficacy of traditional and conventional medicines.

What significant advance(s) in relation to the IPY themes and targets can be anticipated from this project?
Human Dimension: to investigate factors including cultural, historical, and social processes that shape the safe use of traditional medicines and other drugs. A traditional medicine or drug which is apparently safe and effective when used for a short period of time may become toxic and/or ineffective over time if used with other products, especially as new drugs are added as a result of climate change or if the individual is exposed to pollutants. The clinical consequences of genetically or environmentally determined variations in drug disposition may be costly, immediate, subacute or delayed, positive, adverse or possibly deadly.

What international collaboration is involved in this project?
Scientists from Canada and China are involved. The WHO Collaborating Centre for International Drug Monitoring, Sweden has expressed interested in working together, and other scientists from Norway and Russia are being approached.

FIELD ACTIVITY DETAILS

Geographical location(s) for the proposed field activities:
All areas of Arctic Canada, including Northern Quebec; N. China. Hopefully this can be expanded to include Norway, Russia and Sweden.

Approximate timeframe(s) for proposed field activities:
Arctic: 04/05 – 03/07      04/07 – 03/08      04/08 – 04/09
Antarctic: n/a

Significant facilities will be required for this project:
Logistic support will be required from health care professionals and community elders to complete the survey and identify potential adverse events, collect samples and work with Northern students. Northern blood collection and processing facilities will be required. There is a strong potential for shared resources.

Will the project leave a legacy of infrastructure?
No buildings but a legacy of capacity building/training of Northerners, health promotion and awareness of factors affecting safety of traditional medicines, natural products and other drugs when used in non-traditional ways and together.

How is it envisaged that the required logistic support will be secured?
National agency

We will seek active collaboration from other government partners, academics, health care professionals (and hospitals), residents and organizations, and elders in Northern communities.

Has the project been "endorsed" at a national or international level?
No. There has been national and international recognition that traditional medicines are important to Northern residents and that there is a potential for adverse interactions between traditional medicines and drugs if used concomitantly, and that environmental contaminants may affect the safety and efficacy of these medicines.

PROJECT MANAGEMENT AND STRUCTURE

Is the project a short-term expansion (over the IPY 2007-2008 timeframe) of an existing plan, programme or initiative or is it a new autonomous proposal?
Yes
This is a new autonomous proposal that will draw together three smaller current studies that encompasses a small portion of this proposal.

How will the project be organised and managed?
The Lead will maintain overall responsibility. Projects will be organized and undertaken where possible in a parallel manner as separate sub-projects under a team leader (TL) who will be responsible for the management and decision making. The Lead will provide guidance and decision making in the event that consensus between team members and TLs is not possible. The work will proceed in stages once initial consultation has resulted in further collaborations (and identification of alternate sites for sample processing in the event of unforeseen problems), training and setting of milestones and deliverables. The TLs will meet monthly with the Lead.

What are the initial plans of the project for addressing the education, outreach and communication issues outlined in the Framework document?
This proposal will be discussed, possibly through a Northern workshop prior to implementation and upon completion. As results are obtained, data and accomplishment summaries will be made available to team members, local participants, and presented at national and international meetings. A final report will be provided to team members and participants.

What are the initial plans of the project to address data management issues (as outlined in the Framework document)?
The principal investigator will communicate with all collaborators on a monthly basis either via telecommunications or electronically to ensure all are of the progress, setbacks and results in a timely fashion. The chief investigators will meet once a year in a Northern location with major participants.

How is it proposed to fund the project?
Funding will come from IPY resource. Some short term funding will continue for 3 projects until 03/2006; it is estimated that an additional $265K/yr for 3 years is required to cover training, surveillance and monitoring, sample collection and testing, educational and communications programs, workshops and conferences and travel.

Is there additional information you wish to provide?
The critical issue for Northern residents is there is little information on the extrinsic (diet, nutrition, environmental: extreme day and night cycles, cold, contaminants including pesticides and heavy metals) and intrinsic (age, gender, genetic, cultural and pathophysiologic) conditions that affect drug safety and efficacy. A genotyping study in a Canadian Inuit population found alleles associated with Gilbert’s syndrome in a higher incidence than in a Scottish population which may lead to increased toxicity to drugs such as acetaminophen which require glucuronidation for detoxification and elimination suggesting this population has increased risk. The overall risk to this community is not known.

PROPOSER DETAILS

Senior Science Advisor / Dr. Brian C Foster
(Principal Investigator) Therapeutic Products Directorate, Health Canada - Office of Science
Holland Cross 3102C3, 1600 Scott Street
Ottawa, Ontario
K1A 1B6
Canada

Tel: (613)-957-3506
Mobile:
Fax: (613)-941-5035
Email:

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Other Information