The American Society for Pharmacology and Experimental Therapeutics (ASPET), a professional society representing 4700 pharmacologists, is pleased to submit the following comments in response to the draft five-year Strategic Plan of the National Center for Complementary and Alternative Medicine (NCCAM).  These comments have been developed and approved in consultation with the ASPET Council and Committee on Public Affairs.  ASPET has particular interest in a neglected area of biomedical research, namely botanicals and herbal medicine and we restrict our comments to those areas exclusively.

Since the establishment of NCCAM, ASPET has supported your efforts to raise the level of scientific tradition at NCCAM and to insist on sound evidence-based research as its cornerstone.  ASPET is pleased that the 2005 draft Strategic Plan continues to emphasize support of basic and clinical research on botanicals.  We are glad to see that there has been in increase in the basic research and training portfolio beginning in 2000.  ASPET hopes the updated strategic plan will continue to recognize the need for greater balance between clinical studies of efficacy and those directed to examination of basic mechanisms of action.  Additionally, we hope that the strategic plan will state more explicitly those public health concerns that must be addressed on behalf of a U.S. public that uses non-standardized, unregulated herbal remedies that may harm rather than heal.  NCCAM should continue to expand the goals of identifying key ingredients as molecular entities, and then determine the mechanism of action of these ingredients.  ASPET believes it will be less useful to attempt to determine the mechanism of action of a mixture of ingredients as found in most CAM products. 

We encourage NCCAM to look to ASPET and other pharmacologically based organizations to identify scientists to serve NCCAM in an advisory capacity.

ASPET supports the need for studies on basic mechanisms of action and toxicity and for investigator-initiated research.  Toward this end we recommend that NCCAM employ the RFA and other mechanisms with dedicated funding, to support and encourage investigators to submit grant proposals that address carefully defined research questions concerning actions and toxicity of botanicals. New investigators would be encouraged to pursue research if they recognized the availability of funds for meritorious grant proposals.  Also, investigator-initiated research into botanicals needs to be expanded to promote our understanding of both prescription drug-herbal and herbal-herbal interactions.  NCCAM might also consider use of R21 grants and Supplemental grants to attract established investigators with specialized research expertise to areas that interest them, but in which they may not have realized funding opportunities existed.  

ASPET believes that for both individual CAM products and for combinations of CAM products alone and with conventional drugs and biologicals, more specific safety testing needs to be undertaken.  As with “conventional drugs” for which market approval is sought, there are specific studies and data that are required by the FDA.  Although the requirements change somewhat from drug to drug, there are certain types of studies that could be undertaken by NCCAM, including acute and 5/7 day repeat dosing toxicity studies; subchronic toxicity studies of 28 to 90 day repeated dosing; chronic toxicity studies of one year dosing or more; and carcogencity studies, usually of 18-24 months duration in mice and rats.  More recently, FDA is requiring a specific set of “safety pharmacology” studies under in vivo and in vitro guidelines.  These studies are meant to evaluate the acute effects of compounds on the central nervous, cardiovascular, and respiratory systems.   Undertaking such studies could help identify significant adverse effects and prevent unnecessary continued testing. 

 ASPET believes that NCCAM should place increased emphasis on using both well-established animal models as well as developing new animal models for the intended therapeutic use of botanical products.  In order to establish efficacy, the investigator needs to show that the compound works in a preclinical model of the disease or condition.  Without these kinds of data, it is difficult to convince the scientific community that the compound has a worthwhile place in either maintaining health or reversing a disease. ASPET does not believe that spending resources to provide available databases, particularly from ancient manuscripts/texts, is a wise use of limited funds.  The purity of CAM products being described in ancient papers cannot be ascertained.  Therefore, small contaminants might be responsible for effects observed.  Likewise, the formation of a repository for storing materials for future testing, when more sophisticated methods become available, is also an expense that is unlikely to be the best use of funds. 

 With respect to training of CAM investigators, ASPET encourages NCCAM to consider mechanisms that would enhance post-doctoral training in integrative, whole organ – in vivo systems pharmacology.  

 On behalf of the ASPET Council, thank you for the opportunity to offer public comment to the NCCAM Strategic Plan.