Drug Interactions with Natural Health Products: A Research Priority-Setting Conference

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Table of Contents

• Executive Summary
• 1 Introduction
• 2 Objectives
• 3 Process
• 4 Two Broad Areas of Research
  • 4.1 NHP-Drug Interactions
  • 4.2 Reporting, Dissemination and Use of Information about NHP-Drug Interactions
• 5 List of Research Priorities
  • 5.1 NHP-Drug Interactions
  • 5.2 Reporting, Dissemination and Use of Information about NHP-Drug Interactions
• 6 Considerations with regard to Top Four Priorities
  • 6.1 NHP-Drug Interactions
  • 6.2 Reporting, Dissemination and Use of Information about NHP-Drug Interactions
• Appendices
• Appendix A: Agenda
• Appendix B: List of Participants
• Appendix C: Reports from Groups on Top Five Priorities in Two Broad Areas of Research

Executive Summary

In 2001 and 2002, the Natural Health Products Directorate (NHPD) conducted a series of consultations to identify priorities for research on natural health products (NHPs). These consultations will guide the NHPD in its own research program and in its partnerships with other funders, such as the Canadian Institutes of Health Research (CIHR).

Interactions between NHPs and pharmaceutical drugs (NHP-drug interactions) is one area identified during stakeholder consultations as a research focus for the NHPD. An increasing number of Canadians are using NHPs, and many are taking prescription or over-the-counter drugs at the same time. This occurrence alone is reason to investigate potential or clinical NHP-drug interactions for both their positive and negative effects.

The Research Priority-Setting Conference on Drug Interactions with Natural Health Products involved approximately 70 participants drawn from many fields with an interest in NHP-drug interactions.

The objectives of the conference were:

• to identify, process and assess the current state of evidence related to NHP-drug interactions
• to explore the implications for biomedical research; clinical research; research related to health systems, policy and legislation; and research related to communication and knowledge transfer
• to identify priorities, facilitate dialogue and foster collaboration between all relevant stakeholders to promote interest in research in this area

The primary objective of the conference was to assist in identifying research priorities concerning drug interactions with NHPs. This information will be used by the NHPD to work with other funders (such as CIHR) to advance research on these priorities and to issue requests for applications on these priorities.

This final report on the conference summarizes the outcomes of the conference at each of the following key points in the process:

• two broad areas of research
• a list of priorities in these two areas of research (with a description of each priority)
• the top four priorities in these two areas of research, with a summary of considerations identified at the end of the conference

The research priorities identified by participants in the first day of the conference fell into two broad areas:

1. biomedical, clinical and epidemiological research on NHP-drug interactions
2. research related to reporting, dissemination and use of information about interactions

In general, participants suggested that priority should be given to research dealing with:

• NHPs that are in high use
• populations that are at risk of NHP-drug interactions (e.g., populations defined by age, gender, diseases or conditions, genetic factors, etc.)
• interactions with drugs that have critical dose or plasma concentration requirements
• interactions with potential or known severe outcomes

The top four priorities in biomedical, clinical and epidemiological research on NHP-drug interactions were (numbered in order of priority):

1. characterize NHPs being used
2. identify pharmacologic actions of NHPs related to benefits, harms and interactions
3. determine the clinical relevance of potential NHP-drug interactions
4. determine the use of NHPs in the population

The four top priorities for research in relation to reporting, dissemination and use of information about NHP-drug interactions were (numbered in order of priority):

1. research into early warning systems for NHP-drug interactions
2. assessment of the needs of stakeholders (consumers, practitioners, regulators, distributors and delivery systems) regarding information on NHPs and NHP-drug interactions
3. the use of a focused, population-based approach to determine areas of greatest risk for NHP-drug interactions and mechanisms for collecting information about NHP-drug interactions
4. ways to facilitate the reporting of adverse drug reactions/drug interactions by all stakeholders

1 Introduction

In 2001 and 2002 the Natural Health Products Directorate (NHPD) conducted a series of consultations to identify priorities for research on natural health products (NHPs). These consultations will guide the NHPD in its own research program and in its partnerships with other funders, such as the Canadian Institutes for Health Research.

One of the areas identified during stakeholder consultations as a focus for the NHPD with regards to research is interactions between NHPs and pharmaceutical drugs (NHP-drug interactions). The importance of this area has been underscored by all stakeholders as the NHPD has moved forward to establish a regulatory framework for NHPs in Canada. More and more Canadians are using NHPs, and they are taking prescription or over-the-counter drugs at the same time. This occurrence alone is reason to investigate potential or clinical interactions for both their positive and their negative effects.

The Research Priority-Setting Conference on Drug Interactions with Natural Health Products was developed by a planning team consisting of Dr. Frank Chandler, Chair (former Director of Pharmacy, Dalhousie University), Dr. Heather Boon (Faculty of Pharmacy, University of Toronto), Mr. Pravin Patel (Drug Information Pharmacist, Drug Information Research Centre), Dr. Paul Saunders (Chair of Materia Medica, The Canadian College of Naturopathic Medicine), Dr. Sunita Vohra (Assistant Professor of Paediatrics/Clinical Pharmacology/Clinical Epidemiology/Population Health Sciences, Hospital of Sick Children), and Dr. Michael J. Smith (Senior Advisor, NHPD). For the agenda, see Appendix A.

There were approximately 70 participants at the conference, drawn from many fields, with an interest in NHP-drug interactions: Canadian researchers (biomedical, clinical, sociocultural); practitioners (conventional and complementary/alternative); representatives from industry, consumer organizations, several areas of Health Canada and research funding agencies; as well as international participants. For a list of participants, see Appendix B.

2 Objectives

The objectives of the conference were:

• to identify, process and assess the current state of evidence related to NHP-drug interactions
• to explore the implications for biomedical research; clinical research; research related to health systems, policy and legislation; and research related to communication and knowledge transfer
• to identify priorities, facilitate dialogue and foster collaboration between all relevant stakeholders to promote interest in research in this area

The primary objective of the conference was to assist in identifying research priorities concerning drug interactions with NHPs. This information will be used by the NHPD to work with other funders (such as CIHR) to advance research on these priorities and to issue requests for applications on these priorities.

3 Process

A background document entitled "Drug Interactions with Natural Health Products: A Discussion Paper," written by Dr. Heather Boon and Dr. Tannis Jurgens, was commissioned by the NHPD prior to the conference. This document was distributed to all participants to orient them to the current state of knowledge about NHP-drug interactions.

The conference began with a plenary session that provided an overview of the issues. The overview included presentations on current knowledge, a perspective from the United Kingdom, and a perspective from the United States. The overview also included presentations on the perspectives of the researcher, the conventional practitioner, the complementary/alternative practitioner and the consumer.

Following the plenary presentations, the conference broke into groups organized according to the four main areas of research under consideration: biomedical research; clinical research; research related to health systems, policy, and legislation; and research related to communication and knowledge transfer. Participants were assigned to the group that best matched their expertise, and were asked to identify three priorities for research or related action with regard to NHP-drug interactions. The groups reported on their priorities in a plenary session at the close of the first day of the conference.

At the beginning of the second day, the facilitator summarized the main priorities that had been identified by the groups on the previous day. Two broad areas of priority for research emerged, which participants debated and refined in a plenary session: (1) biomedical, clinical and epidemiological research on NHP-drug interactions; and (2) research on reporting, dissemination and the use of information about NHP-drug interactions.

The conference then broke into multidisciplinary groups to identify priorities within each of these two broad areas of research. There were four groups for each area of priority. The groups were asked to identify the top three to five priorities for research or related action in their area. The groups reported on their top priorities in a plenary session.

The priorities identified by the groups were consolidated into a list of priorities for each of the two broad areas, and participants were asked individually to select by vote five priorities in each of the two areas. On the basis of the votes, the priorities were ranked and five top priorities were identified in each area.

Finally, the conference broke into groups to discuss the top four priorities in each area and to identify important considerations that should be taken into account when advancing research on that priority. Each group was assigned one of the priorities, and participants were free to select the group and the priority they wished to discuss. The groups reported on their considerations in the final plenary session of the conference.

This report summarizes the outcomes of the conference at each of the key points in the process:

• the two broad areas of research
• the list of priorities in these two areas of research (with a description of each priority)
• the top four priorities in these two areas of research (with a summary of the considerations identified at the end of the conference)

4 Two Broad Areas of Research

On the first day of the conference, participants described two broad areas of research:

• biomedical, clinical and epidemiological research on NHP-drug interactions
• research related to reporting, dissemination and use of information about interactions

4.1 NHP-Drug Interactions

The first broad area of research dealt with questions related to the biomedical, clinical and epidemiological aspects of NHP-drug interactions. These included such questions as:

• What NHPs are in greatest use by the population or by sub-populations? What combinations of NHPs and drugs or interactions between NHPs and drugs are most prevalent in the population and entail the greatest potential or known risk? The answers to these questions can be used to direct research on specific NHP-drug interactions.
• How can we ensure research quality reference standards for the NHPs used in research? In the absence of such standards, it is difficult to be certain of the content of NHPs used in research, and it is impossible to generalize from studies conducted in different centres.
• What are the pharmacologic actions of NHPs related to their benefits, harms and interactions? Information about the pharmacokinetics, toxicology and efficacy of NHPs can be used to identify potential NHP-drug interactions and understand known NHP-drug interactions. It was noted that interactions can be positive as well as negative. Both types of interactions merit investigation, but the standards for measuring benefit are different than the standards for establishing and quantifying harm.
• What is the clinical relevance of potential (or theoretical) NHP-drug interactions? Potential NHP-drug interactions, identified on the basis of in vitro studies and existing biomedical knowledge, do not necessarily appear in clinical use. It is important to identify NHP-drug interactions that appear in clinical use and to understand the factors that result in such interactions. Priority should be given to interactions between NHPs and drugs with critical dose or plasma concentration requirements.
• What is the current state of knowledge with regard to specific, high-priority NHP-drug interactions? Reviews of the literature and meta-analyses of research can assist researchers in Canada. However, the quality of this research needs to be assessed before its results are accepted or a study is translated for use in Canada.
• What are appropriate methods for evaluating NHP-drug interactions? What spectrum of expertise is required to analyze and evaluate cases of NHP-drug interaction? There are concerns that, without appropriate methods and expertise, data on NHP-drug interactions could be overlooked or misinterpreted. Discipline-specific expertise is also required to determine the generalizability of the data. For example, herbalists can inform biomedical researchers of the commonly used formulations of products for analysis.

Participants identified a number of criteria that should be used to determine priority within the above area of research. Priority should be given to research dealing with:

• NHPs that are in high use
• populations that are at risk of NHP-drug interactions (e.g., populations defined by age, gender, diseases or conditions, genetic factors, etc.)
• interactions with drugs that have critical dose or plasma concentration requirements
• interactions with potential or known severe outcomes

4.2 The Reporting, Dissemination and Use of Information about NHP-Drug Interactions

The second broad area of research dealt with questions about approaches and systems to gather, disseminate and facilitate the use of information about NHP-drug interactions. Participants identified the types of capabilities they desired in this regard. These included capabilities to:

• provide early warning signals of NHP-drug interactions
• recognize negative (adverse) NHP-drug interactions
• recognize positive (beneficial) NHP-drug interactions (which may require systems different than those used to recognize negative NHP-drug interactions)
• collect key epidemiological and sociodemographic data (e.g., sex, age, diseases or conditions, lifestyle, determinants of health, other NHPs or drugs used, etc.)
• evaluate and sort reports according to the quality of the data, severity of the interaction, etc.
• gather information from and disseminate information to all stakeholders (consumers, practitioners, manufacturers, distributors)
• encourage the reporting of NHP-drug interactions
• provide easy access to information about NHP-drug interactions, tailored to different users (consumers, practitioners, manufacturers, distributors)
• make use of existing tools of pharmacovigilance, both those developed for pharmaceutical drugs and those developed for NHPs
• be integrated with other databases (pharmacy databases, international databases)

In discussing these capabilities and barriers to realizing them, participants identified a variety of research questions:

• What systems are available or needed to provide early warning signals of possible NHP-drug interactions? What types of studies could provide early warning signals? Such systems and studies are necessary because of limitations in the existing passive adverse drug reaction reporting system. They can also help to identify priority NHP-drug interactions for further biomedical and clinical research.
• What forms of education do practitioners (conventional and complementary/alternative) need to enable them to recognize, assess and report NHP-drug interactions with the requisite specificity? How can practitioners be trained to take inclusive medical histories, support disclosure of NHP use by their patients and report all of the required information on suspected or known NHP-drug interactions?
• What education do consumers need to increase their awareness of NHP-drug interactions, to encourage them to report NHP-drug interactions and to enable them to provide information to and retrieve information from reporting systems? What are the barriers to increased recognition and reporting of NHP-drug interactions by consumers?
• What is needed to foster a 'culture of disclosure' between consumers, practitioners and regulators about the use of NHPs and about possible adverse reactions or interactions? The attitudes and behaviours of practitioners, as well as the objectives and outcomes of regulatory systems, are important factors in the willingness of consumers to disclose their use of NHPs and adverse reactions or interactions.
• What are the benefits and limitations of information reported directly by consumers to regulatory systems about NHP-drug interactions? What can be done to improve the quality of information reported directly by consumers?
• How can reporting tools and systems facilitate and support the gathering of information from multiple users or stakeholders? How can technology be used to improve the reporting of NHP-drug interactions by all stakeholders - by working, for example, interactively through a series of key questions with the reporter by telephone or on-line to gather all the relevant information relating to an interaction?
• What mechanisms could be used or developed for post-marketing surveillance of NHPs? Data from manufacturers (e.g., sales data), consumers (e.g., population-based data) and distributors (e.g., pharmacy data) could conceivably contribute to post-marketing surveillance and early warning systems of NHP-drug interactions.
• What do the various stakeholders want or need to know about NHP-drug interactions? A needs assessment of consumers, practitioners, manufacturers and distributors would contribute to the design of reporting and dissemination systems that meet those needs.
• What is required for effective communication and uptake of information about NHP-drug interactions? Information needs to be easily accessible at appropriate levels of literacy, in various languages and via different media.

5 List of Research Priorities

On the basis of the above preliminary consideration of the two broad areas of research, conference participants identified a list of priorities for each of the two areas, and then voted on their top five priorities. The priorities are described below as ranked by the participants (numbered in order of priority).

5.1 NHP-Drug Interactions

1. Characterize NHPs in use (64 votes)
   The variability and inconsistency of NHPs pose challenges both for research on NHP-drug interactions and for the reporting of NHP-drug interactions. It is necessary to characterize NHPs in their natural form and in prepared formulations, to develop standards for NHPs used in research and practice, and to publish monographs that provide a complete characterization of NHPs used in research and practice. Since the characterization of NHPs requires appropriate methodologies, this research priority cannot be separated from research to develop methodologies to characterize NHPs (priority no. 5).

   Top of Page

2. Identify pharmacologic action related to benefits, harms and interactions (53 votes)
   The pharmacologic effects of NHPs need to be understood. Knowledge of pharmacologic actions can assist in determining the potential efficacy of a product, identifying potential NHP-drug interactions and understanding clinical NHP-drug interactions. Pharmacological and toxicological investigations of clinical NHP-interactions are required. Investigation of both positive and negative interactions is needed.

3. Determine clinical relevance of potential NHP-drug interactions (47 votes)
   Potential NHP-drug interactions can be identified through in vitro studies or on the basis of known properties of the agents in question. The relevance of such findings for clinical practice needs to be determined, however, given that clinical outcomes do not necessarily correspond to theoretical hypotheses or in vitro findings.

4. Determine the use of NHPs in the population (35 votes)
   Baseline data on the use of NHPs in the population as a whole and in specific populations (distinguished by gender, age, disease or condition, etc.) are needed to determine the priority to be given to research on a particular NHP, to assess the relative significance of clinical NHP-drug interactions and to determine the priority to be given to research on potential NHP-drug interactions.

5. Develop methodologies to characterize NHPs (29 votes)
   The characterization of NHPs cannot proceed without the development of appropriate and effective methodologies to do this. Methodologies are required to develop standard characterizations of NHPs both in their natural form and in their various therapeutic formulations. The latter can be difficult, given not only different types of formulations but also that formulations may be individually prepared by the practitioner.

6. Develop methodologies for appropriate design of clinical trials (28 votes)
   Clinical trials involving NHPs present numerous challenges in developing research reference standards for the products under investigation; in developing control arms, if required or appropriate; and in designing studies that can be generalized to the use of a product in the population; etc. Research on the design of clinical trials involving NHPs is required.

7. Conduct literature-based research (22 votes)
   Researchers in other countries, such as Germany or China, have gathered data on NHPs and NHP-drug interactions. Literature reviews should be conducted to assess the quality of studies from other countries in areas that are priorities for Canadian research. High-quality studies should be translated (if necessary) and their findings should be summarized. (Databases of existing literature are available: see, e.g., NAPRALERT.¹)

8. Investigate beliefs, attitudes and behaviours with regard to NHP-drug interactions (14 votes)
   The beliefs, attitudes and behaviours of consumers and practitioners affect their awareness of, recognition of, and response to NHP-drug interactions. For example, the belief that NHPs are 'good' because they are 'natural' can prevent people from recognizing interactions. The perception that government regulation will reduce access to NHPs can prevent people from reporting interactions. Practitioners' skepticism or lack of knowledge about NHPs can prevent them from considering NHPs when taking a medical history or assessing an adverse event. Research is needed to understand and change such beliefs, attitudes and behaviours.

9. Identify risk factors for specific NHP-drug interactions (9 votes)
   There are many factors that affect the risk of NHP-drug interactions: genetic constitution, age, dose, context of use, etc. These factors should be investigated with regard to specific NHP-drug interactions. Information about these risk factors can serve as an early warning system to alert consumers and practitioners as to where NHP-drug interactions are most likely to occur.

10. Conduct observational studies of identified potential NHP-drug interactions (2 votes)
    Observational studies are required to determine whether potential NHP-drug interactions occur in vivo and to identify the factors associated with any such interactions in vivo. Priority should be given to potential NHP-drug interactions in NHPs that are widely used in the population or where interactions can influence therapies (natural or conventional) with critical dose requirements.

11. Conduct incidence and prevalence studies of NHP-drug interactions (0 votes)
    Information is needed about the incidence and prevalence of specific NHP-drug interactions in the population. Epidemiological studies can help to determine further priorities in research, surveillance, clinical practice, practitioner and public education, etc.

5.2 Reporting, Dissemination and Use of Information about NHP-Drug Interactions

1. Research into early warning systems for NHP-drug interactions (40 votes)

The current adverse drug reaction reporting system is a passive system: it relies on practitioners and consumers to take the initiative to report adverse events. However, there are strategic approaches to gathering information, which focus on situations where adverse events are more likely to occur or on factors that are most likely to indicate the possibility of adverse events. These include population-based monitoring (e.g., based on age, gender, disease or condition, determinants of health) and product-based monitoring (e.g., high-use products). The potential of using or developing such early warning systems needs to be studied with regard to NHP-drug interactions. This research should include reviews of existing early warning systems and protocols in Canada and, internationally, reviews of current literature on early warning systems, etc.

2. Assessment of the needs of stakeholders (consumers, practitioners, regulators, distributors, delivery systems) regarding information on NHPs and NHP-drug interactions (28 votes)

Stakeholders are more likely to participate actively in an NHP-drug interaction reporting system when the system is tailored to their needs, both in reporting interactions and in obtaining information about interactions. The stakeholders are diverse - consumers, practitioners, regulators, distributors, delivery systems - and their needs are diverse. An assessment of their needs is an important first step in improving the existing adverse drug reaction reporting system and in developing complementary early warning systems. The needs assessment should gather information with a view to stakeholders' roles both in contributing information about NHP-drug interactions and in receiving and using information about NHP-drug interactions.

3. Using a focused population-based approach to determine areas of greatest risk for NHP-drug interactions and mechanisms for collecting information about NHP-drug interactions (23 votes)

It is possible to identify populations that make greater use of NHPs or that are at greater risk of NHP-drug interactions. Research that focuses on these populations [defined, e.g., by gender, age, disease or condition, determinants of health, type of consumer (user of NHPs, user of complementary/alternative health services)] is likely to obtain more information about NHPs being used in the population, to gather contextual information related to the use of NHPs, and to capture indications of NHP-drug interactions. (This research is related to the research proposed at number 5 below).

4. How to facilitate the reporting of adverse drug reactions/drug interactions by all stakeholders? (21 votes)

Various factors affect the ease with which stakeholders report adverse drug reactions/drug interactions, their willingness to do so and the quality of the information that they report. What can be done to make it easier for stakeholders to report, to make them more willing to report, and to make them more capable in providing good information? Research should explore mechanisms and strategies to facilitate reporting, the role of education and training (practitioner education, public education) in increasing and improving reporting, and other enablers and motivators.

5. Population-based epidemiological utilization data regarding NHPs (19 votes)

Data on the utilization of NHPs can contribute to research and action on NHP-drug interactions in several ways. They can provide denominator data for analyses of the incidence and prevalence of NHP-drug interactions. They can contribute to the generation of hypotheses about the effectiveness of the use of NHPs in combination with other NHPs or with drugs. They can identify populations or products that could be or should be included in an early warning system for NHP-drug interactions. They can help to establish the safety of NHPs.

6. Effectiveness of current education for health care providers and the public about adverse drug reaction/drug interaction reporting (18 votes)

Health-care providers and the public require education and training in the recognition and reporting of adverse drug reactions/drug interactions. How effective are current initiatives to educate and train practitioners and the public in recognizing and reporting NHP-drug interactions? For practitioners, such education and training should include taking medical histories that include the use of NHPs, identifying and describing NHPs, recognizing and describing NHP-drug interactions, and reporting NHP-drug interactions. For the public, such education and training should include how to recognize adverse events or interactions, how to report these events and interactions, the consequences of reporting, and how to communicate with health care providers about the use of NHPs, etc.

7. Can a reporting system be developed or modified to capture "synergistic" NHP-NHP or NHP-drug properties? (11 votes)

Systems that gather information only about adverse drug reactions/drug interactions do not capture information about beneficial or synergistic interactions between NHPs or between NHPs and drugs. However, such beneficial or synergistic interactions can be important and valuable in managing individual therapy and in managing drug utilization and costs in the health system. Can existing reporting systems be modified to capture information about beneficial or synergistic NHP-NHP or NHP-drug interactions? Are different systems required, with appropriate standards and methods, to establish beneficial or synergistic NHP-NHP or NHP-drug interactions?

8. Request for applications to call for a system or approach to NHP-drug interaction reporting that would meet the desired criteria (10 votes) NHP-drug interaction reporting systems should:

• provide early warning signals of NHP-drug interactions
• recognize negative (adverse) NHP-drug interactions
• recognize positive (beneficial) NHP-drug interactions (which may require systems different than those used to recognize negative NHP-drug interactions)
• collect key epidemiological and sociodemographic data (e.g., sex, age, diseases or conditions, lifestyle, determinants of health, other NHPs or drugs used, etc.)
• evaluate and sort reports according to the quality of the data, the severity of the interaction, etc.
• gather information from and disseminate information to all stakeholders (consumers, practitioners, manufacturers, distributors)
• encourage the reporting of NHP-drug interactions
• provide easy access to information about NHP-drug interactions, tailored to different users (consumers, practitioners, manufacturers, distributors)
• make use of existing tools of pharmacovigilance, both those developed for pharmaceutical drugs and those developed for NHPs
• be integrated with other databases (pharmacy databases, international databases)

Research should be undertaken to identify systems or approaches that would meet these desired criteria for NHP-drug interaction reporting.

9. What contributes to changes in behaviour in stakeholders to prevent NHP-drug interactions? (9 votes)

Relationships between stakeholders - consumers, practitioners, regulators, manufacturers and distributors - can influence their participation in efforts to prevent NHP-drug interactions. Why are consumers reluctant to report the use of NHPs or adverse events associated with NHPs? Why are practitioners not including the use of NHPs or other alternative therapies when they take medical histories? What are the bases (real or perceived) of consumers' concerns about losing access to NHPs as a result of regulatory controls? These and other questions should be studied with a view to understanding how to encourage and support action by stakeholders to prevent NHP-drug interactions.

10. What are the core components of an integrated or holistic medical history-taking that would facilitate a better understanding of NHP-drug interactions? (7 votes)

Inadequate medical histories - histories that do not gather information about the use of NHPs, alternative therapies, lifestyle and other contextual factors - limit the capacity of practitioners to recognize and identify NHP-drug interactions. What are the core components, in format and content, of a medical history that would support the recognition, description and identification of NHP-drug interactions?

11. What is the best way to disseminate information collected in a non-threatening, meaningful manner? (6 votes)

The way in which information about NHP-drug interactions is disseminated can influence consumers' attitudes toward and participation in adverse drug reaction/drug interaction reporting systems. Lack of easy access to information, information that is hard to understand or interpret and information that creates an undue amount of fear and anxiety can deter consumers from participating in reporting systems, can lead them to perceive these systems to be of little use, and/or can make them distrustful of outcomes of reports. Research should identify how information about NHP-drug interactions should be disseminated to facilitate access to information, instill confidence in information and encourage the reporting of information.

12. What are the components of an environment that fosters optimal/maximum reporting of adverse drug reactions/drug interactions? (3 votes)

Research should identify and explore the characteristics of an environment that fosters the reporting of adverse drug reactions/drug interactions, specifically in relation to NHPs. Important factors in such an environment include:

• the recognition of significant events
• how to report and to whom
• the purpose for contributing or participating
• why people are reluctant to report
• (perceived) consequences of disclosure of adverse events
• the barriers to disclosure and reporting (time, cost)
• values, beliefs, trust and judgement
• integrated/holistic medical history-taking

13. What are the mechanisms and components of a practical and effective adverse drug reporting system that facilitates two-way flow of information about drug interactions? (2 votes)

Information about drug interactions, including NHP-drug interactions, needs to flow in two directions: from practitioners and the public to adverse drug reporting systems, and from these systems back to practitioners and the public. What is required to facilitate this two-way flow of information?

14. How does or how could regulation of complementary and alternative practitioners contribute to better reporting and communication of NHP-drug interaction information? (1 vote)

The regulation of health care providers contributes to their incorporation in adverse drug reaction systems, both on account of the organizational infrastructure of regulated professions (such as professional associations, regulatory bodies, required qualifications, accredited colleges and continuing education programs) and on account of the legislated or regulated obligations of these professions. What is the current state of regulation of complementary and alternative practitioners? How does regulatory status (regulated or unregulated) affect practitioners' participation in reporting and disseminating information about NHP-drug interactions?

15. Evaluate the current adverse drug reaction reporting system (0 votes)

Research on the existing 'passive' adverse drug reaction reporting system is required (in addition to research on 'active' early warning systems) to determine how the existing system could better gather and disseminate information about NHP-drug interactions. This research should include an evaluation of the existing system, particularly with regard to NHP-drug interactions.

16. Assessment of the needs of stakeholders in the current adverse drug reaction reporting system (0 votes)

Research on the existing 'passive' adverse drug reaction report system should also include an assessment of the needs of stakeholders in the current system, particularly with regard to NHP-drug interactions.

NAPRALERT (NAtural PRoducts ALERT) contains bibliographic and factual data on natural products, including information on the pharmacology, biological activity, taxonomic distribution, ethno-medicine and chemistry of plant, microbial and animal (including marine) extracts. In addition, NAPRALERT contains data on the chemistry and pharmacology of secondary metabolites that are derived from natural sources and have known structure. See
www.cas.org/ONLINE/DBSS/napralertss.html.

6 Considerations with regard to Top Four Priorities

Finally, participants identified important considerations that should be taken into account when advancing research on the top four priorities in each of the two broad areas. They noted connections with other research priorities. They elaborated on components of a research program. They identified infrastructure and models that could be used. They highlighted certain factors that could be the keys to success.

6.1 NHP-Drug Interactions

1. Characterize NHPs in use

Research-quality reference standards, and products meeting those standards, are required for research into NHPs and into NHP-drug interactions. This involves:

• the analysis of the product in its natural form (the herb) by Agriculture Canada or private laboratories
• the analysis of the product in any prepared formulations in use (e.g., voucher, specific parts, tincture, etc.)
• the production of research-quality reference standard products under contract from a supplier
• the availability of research-quality reference standard products for proactive investigation and verification of interactions of major NHPs (widely used in the population) with likely drugs in particular target populations

It is essential that detailed analysis be undertaken to identify the natural form of the product, the constituents of the product in its natural form and in prepared formulations, and the purity of prepared formulations, etc.

The characterization of NHPs should build on existing resources. These include:

• American Herbal Pharmacopoeia (http://www.herbal-ahp.org/)
• Institute for Nutraceutical Advancement Methods Validation Program
  (www.inanetwork.com/index.html)
• Association of Official Agricultural Chemists (AOAC) Method Validation Program (www.aoac.org/)
• World Health Organization monographs and guidelines
  (www.who.int/)

The role of the NHPD with regard to characterizing NHPs should be:

• to review and adopt product standards and monographs
• to develop a format for NHP-drug interaction reporting that includes the lot number and other information from the label related to good manufacturing practices

Financial support for research can be increased through collaboration with other countries or with disease-specific foundations.

2. Identify pharmacologic action related to benefits, harms and interactions

Suggested areas of investigation, given suitable representation of exposure:

• pharmacokinetic studies: administration, distribution, metabolism and excretion of the product; target tissues
• pharmacodynamic studies: target tissue, dose, pharmacodynamics of the parent compound and of its metabolites, genetics, target protein/signaling
• pharmacogenetic studies

Level of organization:

• first level of studies: gene regulation, protein expression, biological activity, organism
• second level of studies: efficacy and safety in vitro, in animal models and in human beings

3. Determine clinical relevance of potential NHP-drug interactions

Biomedical and clinical research contribute to one another in investigating positive (beneficial) and negative (adverse) NHP-drug interactions:

• Biomedical research can identify potential interactions on the basis of available data, in vitro studies, animal data, pharmacologic actions, etc. It can suggest further avenues of research with regard to potential beneficial interactions (clinical trials, pharmacoeconomic studies).
• Clinical research can identify interactions through clinician surveys, patient surveys, etc. It can further explore the frequency, extent and possible causes of potential interactions through case-finding surveys or case-control studies. It can also contribute to further biomedical research by conducting pharmacokinetic studies and investigating interactions in human models.

4. Determine use of NHPs in the population

There are existing surveys and studies in Canada and elsewhere that could contribute data on the use of NHPs. These include:

• a six-province study, funded in part by the National Cancer Institute of Canada, on the use of complementary therapies among people diagnosed with cancer (prevalence, characteristics and change in use) - Principal Investigator: A. Leis, University of Saskatchewan
• the National Population Health Survey (longitudinal data on the Canadian population gathered at the level of provinces/territories)
• the Canadian Community Health Survey (cross-sectional data on the Canadian population gathered at the level of health regions)
• analyses of the National Population Health Survey data and the Canadian Community Health Survey data by Statistics Canada
  (In some instances, such as the National Population Health Survey and the Canadian Community Health Survey, further work may be required to introduce questions that are relevant to the use of NHPs.)

New studies that could be undertaken include:

• studies of specific populations (e.g., the elderly, people with HIV, people with cancer, people with cardiovascular conditions, people with mental health needs, etc.)
• the development and use of a generic protocol to collect similar or common data on NHP and drug use longitudinally
• cross-sectional surveys of under-studied populations
• cohort studies
• case-control studies

Preference for funding should be given to grant submissions that have funding partners (e.g., funding from industry, disease-specific foundations, etc.) and that are added onto existing, ongoing studies.

6.2 Reporting, Dissemination and Use of Information about NHP-Drug Interactions

1. Research into early warning systems for NHP-drug interactions

Existing approaches, methods and tools should be evaluated for their applicability with regard to NHPs. These include:

• spontaneous reports (e.g., through a review of the literature or a review of the UK Medicines Control Agency/Committee on Safety of Medicines 'yellow card' scheme)
• Prescription Event Monitoring (e.g., the UK St. John's Wort Prescription Event Monitoring Study)
• epidemiological studies (cohort studies, case-control studies, etc)
  • by drug
  • by adverse drug reaction
  • by population
  • by disease or condition (identified though registers)
• active surveillance of specific populations:
  • people with HIV
  • infants and children
  • pregnant women
  • people who use Traditional Chinese Medicine
• the model of the General Practice Research Database:
  • develop a Pharmacy Practice Research Database
  • conduct pharmacy practice-based studies (e.g., recruit people who purchase St. John's Wort in pharmacies)
  • explore attitudes and behaviours of health-food store staff regarding adverse drug reaction/drug interaction reports

In addition, it will be important to liaise with other countries. For example, how can video conferencing be used to facilitate communication and collaboration? How can Canada contribute to or benefit from the World Health Organization's Traditional Remedies Surveillance Programme? Would it be possible to merge Canada's database on NHP-drug interactions with the US database?

It will be important to publicize early warning systems to conventional practitioners, complementary/alternative practitioners and consumers, and to encourage communication between these three groups about NHP-drug interactions.

All of this work will require substantial financial resources.

2. Assessment of the needs of stakeholders (consumers, practitioners, regulators, distributors, delivery systems) regarding information on NHPs and NHP-drug interactions

Each of the stakeholders presents challenges with regard to gathering and disseminating information on NHPs and NHP-drug interactions:

• Consumers: Consumers are a key group, given that their use of NHPs is increasing. However, they are difficult to access for information about NHP-drug interactions.
• Practitioners: Conventional and complementary/alternative practitioners have different needs and capabilities with regard to gathering and disseminating information about NHPs and NHP-drug interactions. The regulation of practitioners, as well as the organizational infrastructure that accompanies regulation (such as professional associations, regulatory bodies, required qualifications, accredited colleges and continuing education programs) is relevant when looking to address practitioners' needs or to improve their capability to gather and disseminate information.
• Regulators: Consumers and practitioners look to the regulator for quick and easy access to experts and to information that can be trusted. It can be challenging for regulators to meet such expectations.
• Manufacturers: Consumers look to manufacturers and distributors for access to NHPs, as well as accountability for the quality of the products and the information provided about the product (dose, efficacy, safety, interactions, etc.). Cooperation from manufacturers and distributors in providing information is an important part of any system to prevent NHP-drug interactions.
• Delivery systems: Delivery systems (the point of purchase of NHPs) are huge and varied. There are concerns about lack of or insufficient training of personnel with regard to NHPs and NHP-drug interactions.

The kinds of questions that might be asked of each of these stakeholders in a needs assessment include:

• What do they know now?
• What do they need and/or want to know?
• How accessible are they?
• How cooperative are they?
• How knowledgeable are they?
• How is consumer feedback accessed?

3. Using a focused population-based approach to determine areas of greatest risk for NHP-drug interactions and mechanisms for collecting information about NHP-drug interactions

This research should consist of multicentre, collaborative initiatives to promote the pooling of data. It could begin with feasibility studies that develop and test templates for gathering data. Both individual variables (age, gender, sexual identity, weight/height, lifestyle, nutrition, lifestage, etc.) and social variables (ethnicity, socioeconomic status, education, urban/rural, social and physical environment, etc.) would be relevant, building on Health Canada's framework for the determinants of health (www.hc-sc.gc.ca/hppb/phdd/determinants/index.html). Given that the use of NHPs is often individualized and is related to other health behaviours, it is likely that observational studies would gather more accurate and useful information - a 'real-world snapshot.' Evidence of a lack of interactions would be as useful as evidence of interactions.

4. How to facilitate the reporting of adverse drug reactions/drug interactions by all stakeholders

There are numerous ways in which adverse drug reaction/drug interaction reporting could be facilitated. All of these need to be explored through research or other avenues (such as program development, modification or evaluation):

• The reporting form must be practical, concise and easy-to-use. The Australian model, which is very simple, should be considered.
• Practitioners currently feel that they are reporting into a black hole. Therefore they will not spend a lot of time and energy on reporting. This must be addressed.
• Incentives for reporting, such as prompt and personal feedback on reports, need to be identified and implemented.
• All practitioners (conventional and complementary/alternative) should receive education and training (or continuing education) in assessing and reporting NHP-drug interactions. This should include training in taking a holistic medical history that includes the use of NHPs.
• There should be public education about NHP-drug interactions and about reporting. Avenues for public education include special interest groups, magazines and other publications, health-food stores and pharmacies. The positive aspects of reporting as well as the importance of reporting should be advertised.
• Patients tend not to tell their physician about their use of NHPs. They may also believe that they will lose access to the NHPs they are using if they report NHP-related adverse events. These beliefs and behaviours need to be addressed.
• Reports of adverse drug reactions/drug interactions involving NHPs need to be screened and evaluated before being entered into a central database and made available to practitioners and the public.

Appendix A - Agenda

Thursday, 10 January 2002

Breakfast at the Hotel

8.30am Welcome

Philip Waddington
Frank Chandler

Welcome and opening remarks from Health Canada and the Chair of the Conference, including a description of the objectives of the Conference.

9.00am Key-note Presentations

Overview of Existing Information: Heather Boon
UK Perspective: Joanne Barnes
US Perspective: Rebecca Costello

Presenters will make 20- minute presentations offering information on the current state of drug interactions with natural health products. The presentations will be followed by 30 minutes of "table talk." (Participants will be assigned to tables of about 8 people for the plenary sessions. The tables will be mixed. During the "table talk" participants can discuss key ideas or new ideas that they heard during the presentation. The "table talk" will enable participants to become acquainted with each other, become aware of diverse perspectives, and become engaged in substance of the presentations.)

10.30am Break

11.00am Perspective Presentations

View of the Researcher: Tannis Jurgens
View of the Conventional Practitioner: Sunita Vohra
View of the CAM Practitioner: Paul Saunders
View of the Consumer: Sean Hosein

Presenters will make 10-12-minute presentations offering different perspectives on the subject of drug interactions with natural health products. Questions of clarification may follow if time allows (15 minutes per presenter, including the 10-12 minute presentation). The presentations will be followed by 30 minutes of "table talk" during which participants can discuss key ideas or new ideas.

12.30pm Lunch

1.30pm Small Group Session within Theme Areas (8 groups)

Biomedical
Clinical
Health Systems, Policy and Legislation
Communication and Knowledge Transfer

Participants will move into 8 groups which are pre-selected according to participants' primary expertise, 2 groups per theme area. There will be a facilitator for each group. The objective will be to come up with 3 priorities for research or related action with regard to drug interactions with natural health products.

3.30pm Break

4.00pm Report Back in Plenary on Priorities

Each group will have 5 minutes in plenary to report back on the priorities it identified. The facilitator will then guide the participants in identifying similarities and differences within and between theme areas, and in generating a consolidated list of priorities.

5:30pm Adjourn

Friday, 11 January 2002

Breakfast at hotel

8:30am Re-cap of the Outcomes of Day One

9:00am Small Group Session to Determine Top 3-5 Priorities (8 Groups)

Participants will move into 8 groups which are pre-selected to include expertise in all four theme areas. There will be a facilitator for each group. The objective will be to determine the top 3-5 priorities for research or related action with regard to drug interactions with natural health products, out of the priorities identified on Thursday.

10.30am Break

10.45am Report Back in Plenary on Priorities

Each group will have 5 minutes in plenary to report back on the priorities it identified. The facilitator will then guide the participants in identifying similarities and differences in the priorities identified by each group, and in generating a short list of 3-5 overall priorities. If necessary, the facilitator will guide the participants in an exercise to determine the top priorities.

12.30pm Lunch

1.30pm Small Group Session to Identify Next Steps

A group will be formed for each priority to determine next steps. Participants can select the group they wish to join. There will be a facilitator for each group. The objective will be to identify the next steps in taking action on that priority and a timeline for those next steps.

2:45pm Break

3:15pm Report Back in Plenary on Next Steps

Each group will have 5 minutes in plenary to report back on the next steps it identified. The rest of the plenary will have an opportunity to comment on and validate the identified next steps.

4:15pm Wrap-up

4:30pm Adjourn

Appendix B - Participants list

1. Frank Chandler - Chair
   Chandler Herbal Consulting
   Halifax, NS
2. Tannis Jurgens - Speaker
   Dalhousie University
   Halifax, NS
3. Sean Hosein - Speaker
   Canadian AIDS Treatment Information Exchange
   Toronto, ON
4. Sunita Vohra - Speaker
   University of Toronto/Toronto Hospital for Sick Children
   Toronto, ON
5. Robin J. Marles
   Brandon University
   Brandon, MB
6. Joanne Barnes - Speaker
   University of London
   London, England
7. Scott Sawler
   Non-Prescription Drug Manufacturers Association of Canada
   Ottawa, ON
8. Gail Bradley
   Saskatchewan Drug Plan
   Regina, SK
9. Barb Findlay
   Tzu Chi Institute for Complementary and Alternative Medicine
   Vancouver, BC
10. Kymm Feldman
    Sunnybrook & Women's College Health Sciences Centre
    Toronto, ON
11. Maeve O'Beirne
    University of Calgary
    Calgary, AB
12. Ken Potvin
    Canada's Research-Based Pharmaceutical Companies
    Ottawa, ON
13. Donna Herringer
    Canadian Health Food Association
    White Rock, BC
14. Allison McCutcheon
    University of British Columbia
    Vancouver, BC
15. Adrienne Einarson
    The Motherisk Program
    The Hospital for Sick Children
    Toronto, ON
16. Thomas Chang
    University of British Columbia
    Vancouver, BC
17. Cheng Xia
    Bodymind Synergy Health Centre
    Calgary, AB
18. Francis Brinker
    Tucson, AZ
    USA
19. Paul Saunders - Speaker
    Canadian College of Naturopathic Medicine
    North York, ON
20. Raffaele Filice
    Tzu Chi Institute for Complementary and Alternative Medicine
    Vancouver, BC
21. Valerie Lanctot-Bedard
    Guilde des Herboristes
    South Stukely, QC
22. Aileen Burford-Mason
    DRS Consulting
    Toronto, ON
23. John Ruedy
    Academic Affairs CDHA
    Halifax, NS
24. Emma Guns
    The Prostate Centre at Vancouver General Hospital
    Vancouver, BC
25. Colin Briggs
    University of Manitoba
    Winnipeg, MB
26. Heather Boon - Speaker
    University of Toronto
    Toronto, ON
27. David Gardner
    Dalhousie University
    Halifax, NS
28. Pravin Patel
    Ontario Pharmacists' Association
    Don Mills, ON
29. Rebecca Costello - Speaker
    National Institutes of Health
    Bethesda, MD
    USA
30. Robin O'Brien
    BC Cancer Agency
    Vancouver, BC
31. Yves Gariepy
    Laval University
    Sainte Foy, QC
32. Mary Wu
    Toronto School of Traditional Chinese Medicine
    Toronto, ON
33. Silvano A. Mior
    Canadian Memorial Chiropractic College
    Toronto, ON
34. Sharon Segal
    MS Society of Canada
    Winnipeg, MB
35. Randy Wong
    College of Traditional Chinese Medicine Practitioners and Acupuncturists of British Columbia
    Burnaby, BC
36. Tom Paton
    Sunnybrook & Women's Health Sciences Centre
    Toronto, ON
37. Brian Foster
    Health Canada
    Ottawa, ON
38. Wayne Snook
    Health Canada
    Ottawa, ON
39. Michel Sasseville
    Santé Naturelle
    Repentigny, Quebec
40. Roger St-Laurent
    Les Laboratoires du Saint-Laurent E.H. Ltée
    La Pocatière, QC
41. Tasleem Kassam
    Elemental Naturopathic Clinic
    Calgary, AB
42. J. Robert McNeill
    University of Saskatchewan
    Saskatoon, SK
43. Warren Foster
    McMaster University
    Hamilton, ON
44. Deborah Phair
    Healthtrends Naturopathic Medical Clinic
    Prince George, BC
45. Timothy Lee
    Dalhousie University
    Halifax, NS
46. Morris Barer
    Canadian Institutes of Health Research
    University of British Columbia
    Vancouver, BC
47. Susie Dallaire
    Québec regional ADR Centre
    Centre d'information pharmaceutique
    Hopital du Sacré Coeur
    Montreal, QC
48. Scott Walker
    Sunnybrook & Women's Health Sciences Centre
    Toronto, ON
49. M. Brenda Robertson
    DIVA Foundation
    Ottawa, ON
50. Bill Wilson
    Health Canada
    Ottawa, ON
51. Bill Casley
    Health Canada
    Ottawa, ON
52. Elizabeth Contestablie
    Ottawa Hospital
    Ottawa, ON
53. Lisa Carter
    Health Canada
    Ottawa, ON
54. Claudia McKeen
    Glebe Apothecary
    Ottawa, ON
55. Susanne Geertsen
    Health Canada
    Ottawa, ON
56. Marie Lemaire
    Health Canada
    Ottawa, ON
57. Joan Simpson
    Health Canada
    Ottawa, ON
58. Linda Rankin
    WETV
    Ottawa, ON
59. Susan Robertson
    Health Canada
    Ottawa, ON
60. David Hoe
    Centre for Infectious Disease Prevention and Control (HIV/AIDS Policy)
    Ottawa, ON
61. Philip Waddington
    Health Canada
    Ottawa, ON
62. Michael J. Smith
    Health Canada
    Ottawa, ON
63. Micheline Ho
    Health Canada
    Ottawa, ON
64. Siddika Mithani
    Health Canada
    Ottawa, ON
65. Cathy Mattern
    Women's Health Bureau
    Ottawa, ON

Regrets

1. Peter Singer
2. John Hoffer
3. Zoey Ryan
4. Michelle Boudreau
5. Neal West
6. Ron Rosenes
7. Wenda MacDonald

Appendix C - Reports from groups on top five priorities in two broad areas of research

Research on NHP-Drug Interactions

Group 1

• development of methodologies to characterize NHPs (in prepared as well as natural forms) and implementation of these methodologies (this is an underlying pre-requisite of research on NHP-drug interactions)
• mechanisms of action: efficacy and toxicology
• validation of 'suspected' or 'theoretical' NHP-drug interactions
• incidence/prevalence of NHP-drug interactions
• understanding behaviours, beliefs, perceptions with regard to NHP-drug interactions

Group 2

• determine clinical relevance of potential NHP-drug interactions
• characterize NHPs in use: the herb, preparation form; develop standards, monographs (this research should be targeted in accordance with priority NHPs and/or interactions, available partnerships, specific populations, etc.)
• literature-based research: translation; reviews
• determine mechanism of action of NHPs: understand demonstrated interactions, identify potential interactions
• develop methodologies for appropriate design of clinical trials in priority areas

Group 3

• known interactions: characterization and mechanism of action
• potential interactions: clinical relevance
• population usage

Group 4

• clinical relevance of NHP-drug interactions:
  • identification of risk factors for specific NHP-drug interactions: genetic, environmental, dose, characterization, age, etc. (research into an 'early warning system' should have the highest priority)
  • observational studies of NHP-drug combinations of identified potential interactions
• mechanism of action: pharmacological (pharmacokinetic, pharmacodynamic) and toxicologic investigations of NHPs as related to NHP-drug interactions
• product characterization: evaluating variability/inconsistency (among products and within products) as a variable in NHP-drug interaction risk

Research on reporting, dissemination, and use of information about nhp-drug interactions

Group 5

• research on a new, 'active' system to identify NHP-drug interactions: request for proposals to research early warning systems for NHP-drug interactions (population-based approach; product-specific approach)
• research on current, 'passive' system to identify NHP-drug interactions:
  • evaluation of the current system
  • assessment of the needs of stakeholders in the current system
  • effectiveness of current education about reporting
    • education of health care providers in medical history-taking that is inclusive of NHPs
    • education of public in recognition and reporting of interactions

Group 6

• what are the components of an environment that fosters optimal/maximum reporting of adverse drug reactions/drug interactions?
  • recognition of significant events
  • how to report and to whom
  • purpose for contributing or participating
  • why are people reluctant to report?
  • (perceived) consequences of disclosure of adverse events
  • barriers to disclosure and reporting (time, cost)
  • values, beliefs, trust, judgement
  • comprehensive/holistic medical history-taking
• what are the core components of an 'integrated' medical history-taking that would facilitate a better understanding of NHPs and NHP-drug interactions?
  • format
  • content
  • inclusive of complementary/alternative and conventional practitioners
  • lifestyle and other individual variables
• using a focused population approach (defined by, e.g., gender, age, disease or condition, determinants of health), determine:
  • greatest risk areas
  • existing mechanisms for collecting NHP-drug interaction information
• what are the mechanisms and components of a practical and effective adverse drug reaction reporting system that facilitates a two-way flow of information about drug interactions (from the practitioner/public to the system, and from the system to the practitioner/public)?
• regulation of complementary/alternative practitioners: what is the current state of regulation and how does regulatory status (regulated or unregulated) affect capacity to establish and maintain an adverse reaction reporting system?

Group 7

• what are the limitations of existing adverse drug reaction/drug interaction data and how could they be improved with specific attention to NHPs?
  • specific product identification
  • completeness of information provided
  • analysis of samples of product submitted in relation to an interaction (it is important to identify all the ingredients in a product, including non-therapeutic ingredients)
  • report positive outcomes as well as negative outcomes
• how to facilitate the reporting of adverse drug reactions by all stakeholders?
  • mechanisms
  • strategies
  • educational methods
  • enablers and motivators
• what is the best way to disseminate collected information in a non-threatening, meaningful manner?
  • barriers
  • concerns over access
  • avoid fear-mongering
  • encourage reporting
• what are the currently available early warning systems that can be adapted or applied to NHPs?
  • use what is working
  • review international protocols used or studied
  • literature reviews
  • theoretical and actual risks
  • investigate other cultures and societies
• what contributes to changes in behaviour in stakeholders to prevent NHP-drug interactions?
  • increased communication between groups
  • enhanced relationships
  • "culture of disclosure"
  • identify who is taking what
  • negative versus positive effects
• can a reporting system be developed to capture 'synergistic' properties of NHP-NHP interactions and NHP-drug interactions?
  • positive benefits
  • education of health-care providers about beneficial outcomes

Group 8

• global assessment of best early warning system and potential implementation in connection with the current system
• collect population-based epidemiological utilization data regarding NHPs
• request for applications to call for a system or approach to NHP-drug interaction reporting that would meet the desired criteria (see above)
• assessment of the needs of stakeholders (consumers, practitioners, regulators, distributors, delivery systems) regarding NHPs and NHP-drug interactions
  • information about the absence of interactions is as important as information about the presence of interactions