Canadian Adverse Reaction Newsletter Production Procedures [Stakeholder Information]

This content was archived on June 24, 2013.

September 2008

Cat: H164-92/2008E-PDF
ISBN: 978-1-100-10336-5

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Contact: Marketed Health Products Directorate (MHPD)

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Table of Contents

1.0 Purpose

2.0 Scope

3.0 Background

4.0 Responsibilities of the Canadian Adverse Reaction Newsletter (CARN) Editorial Team

5.0 Employees and Organizations involved in the Production of the CARN

6.0 Procedures

6.1 CARN Topics
      6.1.1 Types of Topics
      6.1.2 Topic Selection Meeting
      6.1.3 Selection of Topics

6.2 Instructions for Authors
      6.2.1 Writing Guidelines
      6.2.2 Article Guidelines
      6.2.3 Case Presentation (CP) Guidelines
      6.2.4 Writing Style
      6.2.5 Caveats

6.3 Consultations
      6.3.1 Internal-External Consultation

6.4 Approval Process
      6.4.1 CARN MHPD Bureau Directors' Approval

6.5 Identification of Spokespersons

6.6 Summary Table of Advisories

6.7 External Scientific Editing and Translation

6.8 CARN Summaries

6.9 Prepublication Notice to Foreign Regulatory Authorities

6.10 Courtesy Faxes to Market Authorization Holder of Health Product Subject of CARN Article

6.11 Publication and Communication

Appendix 1 - Glossary: Definitions and Terminology
Appendix 2 - List of Acronyms
Appendix 3 - CARN Editorial Process - Key Steps
Appendix 4 - CARN Production Schedule Timeline by Fiscal Year
Appendix 5 - Description of CARN Topics
Appendix 6 - Criteria for Selecting a Topic
Appendix 7 - Author Instructions for CARN Topic Proposals
Appendix 8 - Author Checklist before CARN Topic Submission

1.0 Purpose

This document is intended to provide information on the publication process of the Canadian Adverse Reaction Newsletter (CARN) by the Therapeutic Effectiveness and Policy Bureau (TEPB) of the Marketed Health Products Directorate (MHPD). This document is intended to serve as a guide and reference tool for the editorial process of the CARN.

Appendix 1 provides a glossary of definitions and terminology and Appendix 2 provides a list of acronyms.

2.0 Scope

This document is intended to be used as a complement to other tools and information sources which contain more specific directives [e.g., Guidance Document - Description of Current Risk Communication Documents for Marketed Health Products for Human Use,  Food and Drugs Act and Regulations, Fact Sheets, Medical Dictionary for Regulatory Activities (MedDRA)].

3.0 Background

The Canadian Adverse Reaction Newsletter (CARN), which was first published as the Canadian Adverse Drug Reaction Newsletter in 1991, is a reliable source of information regarding adverse reactions (ARs) suspected to be associated with marketed health products in Canada, which would be of interest to Canadians. Marketed health products include pharmaceutical drugs (which include prescription and non-prescription pharmaceutical drugs); biologics (which include biotechnology products, therapeutic and diagnostic vaccines and fractionated blood products); radiopharmaceutical drugs; natural health products; and medical devices. This publication informs health care professionals and consumers (due to its availability on the Health Canada Web site) about potential signals detected through the review of AR case reports submitted to Health Canada and is primarily intended to increase AR reporting. A signal is considered to be the preliminary indication of a product-related safety issue. The identification of a signal is not by itself the proof of the association of an AR to a health product, but it triggers the need to further investigate a potential association.  Signals must be carefully evaluated in order to confirm or to disprove the potential association between the product and the AR.

The CARN is a useful mechanism to disseminate information on suspected ARs to Canadian marketed health products occurring in humans before comprehensive benefit-risk evaluations and regulatory decisions are undertaken. The articles are factual, represent a national focus and refrain from providing medical recommendations which may interfere with the practice of medicine. The CARN is not intended for regulatory decision-making actions concerning the safety of health products. Regulatory actions are based on scientific analysis of case series and other sources of scientific information and are taken according to the regulatory framework in place by pre-market area Directorates in collaboration with MHPD.

The primary audience of CARN is health professionals (e.g., pharmacists, physicians, naturopaths, nurses). Consumers, patients, and other stakeholders (e.g., associations) may also benefit because of its public availability on the Health Canada Web site.

In delivering its service, the CARN focuses on the following key objectives:

• Disseminate information on suspected ARs particularly serious unexpected ARs
  
• Communicate new health product safety information to health professionals
  
• Raise awareness and promote reporting of ARs
  
• Provide feedback to health professionals
  
• Improve transparency, openness and accountability to strengthen public trust and stakeholder relationships 

Risk Communication and CARN's Role:

Developing appropriate mechanisms to disseminate health product safety information in a timely and effective manner is a challenge. Information about the benefits and harm as well as effectiveness and risks of a health product should be openly available. Open, transparent and effective communication of health product safety issues is essential to reach the primary goals of Canadian patient safety. Communication of such information needs to be considered throughout the risk management process. Various risk communication documents can be used to issue safety information regarding marketed health products. (See Guidance Document: Description of Current Risk Communication Documents for Marketed Health Products for Human Use). While some risk communication vehicles are designed and intended to increase AR reporting, it may not be possible at an early point in the risk assessment process to contextualize or perform comprehensive risk-benefit assessments due to the levels of information available at that phase of data collection.

The CARN is a risk communication vehicle that makes it possible to increase transparency on information already available to the public in the Canada Vigilance Database, which consists of domestic AR reports submitted to Health Canada from health professionals, consumers and industry. It is intended to stimulate AR reporting from health professionals who have seen similar ARs or from consumers who have experienced them. The objective is to increase voluntary reporting of ARs and to raise awareness of the importance of reporting ARs. In addition, the feedback provided to AR reporters by publishing case reports is one of the mechanisms that could encourage a reporting culture, especially in view of the internationally recognized problem of under-reporting of ARs.

One of the main aims of international pharmacovigilance programs is to identify early signals of safety problems related to health products. Sharing information internationally concerning health product safety issues provides great additional gains to optimize risk communication effectiveness. The CARN, produced 4 times a year by the MHPD, plays an important role in communicating health product safety information.

The CARN is currently published quarterly in the Canadian Medical Association Journal (CMAJ), which is distributed to approximately 67,000 Canadian physicians.  A summary of topics is also published in Canadian Family Physician and the Canadian Pharmacists Journal depending on availability of space. Electronic copies are sent to over 19,000 subscribers (as of August 2008) of the MedEffect™ Canada e-Notice mailing list. As well, approximately 28,000 hard copies are mailed quarterly to pharmacists in Canada and other interested individuals.  The CARN has been available on the Health Canada Web site since October 1996 and has been part of the new MedEffect™ Canada health product safety information Web site since August 2005. A CARN Fact Sheet summarizes the scope and purpose of the CARN as well as its main features.

4.0 Responsibilities of the Canadian Adverse Reaction Newsletter (CARN) Editorial Team

Members of the CARN editorial team have specialization from a recognized university in pharmacy, or other relevant specialization in health, pharmaceutical or medical sciences. They currently work in the Therapeutic Effectiveness and Policy Bureau (TEPB), and the Marketed Health Products Safety & Effectiveness Information Bureau (MHPSEIB) of the Marketed Health Products Directorate (MHPD), Health Products and Food Branch (HPFB), Health Canada. The CARN editorial team includes representation from:

• Regulatory Advertising and Risk Communications Section Manager
  
• Risk Communications Unit Head
  
• Risk Communications Specialists
  
• Adverse Reaction Specialist

The CARN editorial team coordinates the production of the CARN, including regularly scheduled topic selection meetings, internal-external consultations and publication, in collaboration with authors and the identified scientific editing contact. They review/edit articles and ensure the validity of the information included. This is done through verification of scientific references and review of AR reports submitted by authors. The CARN editorial team provides an unbiased and critical assessment of the drafts submitted, which is an extension of the scientific process. Designated CARN editors ensure that procedures are followed for consistency in the scope of the CARN regarding the selection and approval of topics, format and editing, final approvals as well as associated administrative activities.

5.0 Employees and Organizations involved in the Production of the CARN

• Authors are MHPD or Health Products and Food Branch (HPFB) scientific staff.
  
• MHPD Directors approve topics selected by the CARN editorial team, identify subject matter expert spokespersons, and MHPD Director General approves communication documents concerning the release of the CARN.
  
• Product-Specific Directorates, e.g. Biologics and Genetic Therapies Directorate (BGTD), Natural Health Products Directorate (NHPD), Therapeutic Products Directorate (TPD), and Health Products and Food Branch Inspectorate (HPFBI) Director Generals and Directors provide formal comments and input on product specific issues.
  
• MHPD Web site Coordinator coordinates the posting of the CARN on the MedEffect™ Canada Web site.
  
• Identified scientific contact provides scientific editing.
  
• Printing and distribution of the CARN is done on a contractual basis.

6.0 Procedures

The key steps of the CARN Editorial Process are summarized in Appendix 3. The CARN Production Schedule Timeline by Fiscal Year is outlined in Appendix 4.

6.1 CARN Topics

6.1.1 Types of Topics

The CARN editorial team accepts topics dealing with the publication of information on suspected early signals based on reports of serious or unexpected ARs associated with health products/medical devices marketed in Canada of interest to Canadians. The urgency of publication of early signals is based on alignment with signal prioritization and causality assessment procedures used in the MHPD. Authors are asked to organize their material in 1 of 6 categories of topics. These are referred to as an Announcement, AR Annual Statistics, Article, Case Presentation (CP), Editorial, or Update. Authors are aware that while the readership is professional and mainly composed of physicians and pharmacists, familiarity with specific areas may vary. Attention is given to the concise explanation of new terms or new concepts. Descriptions of each CARN category of topics are available in Appendix 5.

6.1.2 Topic Selection Meeting

Topic Selection Meetings are held 4 times a year, 4 months prior to publication.
Topics are chosen based on the criteria found in the "Checklist of Criteria for Selecting CARN Topics" (Appendix 6). Topics are selected based on factors such as the seriousness of an AR, the importance of a topic for patient care and public health, and the safety issues concerning specific populations (e.g., children, the elderly, etc.). Authors are required to present topics according to "Instructions for CARN Topic Proposals" (Appendix 7), and use the "Author Checklist before CARN Topic Submission" (Appendix 8).

6.1.3 Selection of Topics

Topics which meet the criteria to include in the next issue of the CARN are selected by the CARN editorial team [decision based on importance/urgency of the topic at that time, recommendations from signal detection prioritization meetings, variety of health product types in a CARN issue, space available depending on other articles chosen, criteria for selecting topics (Appendix 6)].

6.2 Instructions for Authors

6.2.1 Writing Guidelines

• In articles which summarize ARs associated with a specific health product, the "preferred terms" in the World Health Organization (WHO-ART) dictionary were used to describe the reactions prior to the implementation of the Medical Dictionary for Regulatory Activities (MedDRA). The MedDRA "preferred terms" terminology is used since January 1, 2008. This is to ensure a consistent approach and to reduce the number of reaction terms.  When individual case reports are described, the use of the reported terms is appropriate. Standardized MedDRA queries, where available, are also recommended for consistent application of search terms.
  
• The generic name is used throughout the article or case presentation (CP).  If only one brand is available on the Canadian market or if all reports used in the article identified only one brand name, this name is mentioned once at the beginning of the article or CP followed by the generic name in brackets, e.g., Tylenol (acetaminophen). If the brand name is not provided in a case report mentioned in the article or CP and cannot be determined (e.g., manufacturer of the health product not provided) then only the generic name will be shown.
  
• For medical devices, the term adverse "incident" is used as per the  Medical Devices Regulations. For other health products, the term "adverse reaction" is used.
  
• In the AR Statistics article published annually the term "cases" is used to describe the number of reports received, to account for the number of reports that may be received in duplicate or follow up, and the smaller number of actual cases. However, articles normally include the term "report" (e.g., Health Canada has received x reports of [ARs] suspected of being associated with [health product]) to describe the cases. The distinction between "cases" and "reports" does not need to be made for regular case report descriptions in the CARN articles.

6.2.2 Article Guidelines

What to Include:

• The selection of a topic for an article will be unbiased in nature and the purpose of an article is to stimulate/prompt reporting in a situation where:
  1. the signal detection/prioritization process has identified a concern requiring stimulation of reporting.
  2. the suspected signal has not been previously published or requires further stimulation of reporting due to further significant developments, e.g., media attention, scientific publication, increased specificity of reports, or change in nature or frequency of AR reporting pattern.
  
• Description of the health product (usually retrieved from the Canadian product monograph) and date of initial marketing of the product in Canada (retrieved from the Drug Product Database).
  
• Official authorized Canadian indication for use (usually retrieved from the Canadian product monograph).
  
• The time period of the review of AR case reports.
  
• Description of the case(s) according to the topic of article (e.g., patient details, relevant clinical information, outcome, dechallenge/rechallenge information).
  
• Relevant emphasis on warnings and contraindications outlined in product monographs or Health Canada terms of market authorization.
  
• Recommendations for medical action or prevention are normally not included as the practice of medicine falls under provincial and territorial regulations, unless mention of previous Health Canada or Industry issued health professional or public risk communication is included in the article and is adequately supported by scientific references.

6.2.3 Case Presentation (CP) Guidelines

What to Include:

• The selection of a CP will be unbiased in nature and the purpose of the CP is to stimulate/prompt reporting in a situation where:
  1. the signal detection/prioritization process has identified a concern requiring stimulation of reporting.
  2. the suspected signal has not been previously published or requires further stimulation of reporting due to further significant developments, e.g., media attention, scientific publication, increased specificity of reports, or change in nature or frequency of AR reporting pattern.
  
• The intent is to be as brief as possible, so that health professionals may remember a specific AR, and report similar cases they may encounter in their practice.
  
• The CP will succinctly outline the details of a specific AR, specifying: basic patient details, clinical information, dosing, time frame, outcome, dechallenge and rechallenge information.
  
• Recommendations for medical action or prevention are normally not included as the practice of medicine falls under provincial and territorial regulations.

6.2.4 Writing Style

All work submitted by authors to the CARN editorial team will be presented as a draft that is logical, evidence-based, focussed, and in sufficient depth to explain content and limitations, as well as objectives and implications of the article. The draft will be accompanied (at the same time) by all references and supporting materials.

Factual and evidence-based statements included in CARN topics are taken from peer-reviewed publications in order to establish scientific rigor.

6.2.5 Caveats

• The following caveat appears on the front cover of the CARN, as a footnote:
  
  Scope
  This quarterly publication alerts health professionals to potential signals detected through the review of case reports submitted to Health Canada.  It is a useful mechanism to stimulate adverse reaction reporting, as well as to disseminate information on suspected ARs to health products occurring in humans before comprehensive risk-benefit evaluations and regulatory decisions are undertaken. The continuous evaluation of health product safety profiles depends on the quality of your reports.

• The following caveat appears throughout the CARN:
  
  ARs to health products are considered to be suspicions, as a definite causal association often cannot be determined.  Spontaneous reports of ARs cannot be used to estimate the incidence of ARs because ARs remain underreported and patient exposure is unknown.
  
  
• The following information appears on the back cover of the CARN:
  
  Canadian Adverse Reaction Newsletter
  
  Health Canada
  Marketed Health Products Directorate
  AL 0701C
  Ottawa ON K1A 0K9
  Tel 613 954-6522
  Fax 613 952-7738
  
  Suggestions?
  Your comments are important to us. Let us know what you think by reaching us at
  mhpd_dpsc@hc-sc.gc.ca
  
  Reporting Adverse Reactions
  Canada Vigilance Program
  Tel 866 234-2345
  Fax 866 678-6789
  Online: www.healthcanada.gc.ca/medeffect
  
  Copyright
  © [YEAR] Her Majesty the Queen in Right of Canada. This publication may be reproduced without permission provided the source is fully acknowledged. The use of this publication for advertising purposes is prohibited. Health Canada does not assume liability for the accuracy or authenticity of the information submitted in case reports.
  
  Due to time constraints relating to the production of this publication, information published may not reflect the most current information.
  
  ISSN 1499-9447, Cat no H42-4/1-[volume number]-[issue number][language: E or F]
  
  
• The following caveat will always be included under the Case Presentation title box:
  
  Recent Canadian cases are selected based on their seriousness, frequency of occurrence or the fact that the reactions are unexpected. Case presentations are considered suspicions and are presented to stimulate reporting of similar suspected ARs.
  
  
• The following caveat will always be included in Tables providing ARs for a class of different health products:
  
  These data cannot be used to determine the incidence of ARs or to make quantitative drug safety comparisons between the products because ARs are underreported and neither patient exposure nor the amount of time the drug was on the market has been taken into consideration.

6.3 Consultations

Articles and CPs are reviewed and edited under the guidance of the CARN editorial team, in accordance with the American Medical Association's Manual of Style. Upon receipt of an article or a CP, the following consultation process is used:

6.3.1 Internal-External Consultation

Articles are submitted for internal comments to Managers, Bureau Directors, Director General and scientific staff within MHPD, to HPFB Bureaux Directors, Managers and Unit Heads within the pre-market Directorates (dependent on health product and area of responsibility), and Canada Vigilance Regional Offices' staff. Other groups or contacts may be part of the internal-external consultation as deemed appropriate by the CARN editorial team and the MHPD Directors. This may include foreign regulatory agencies that have signed a confidentiality agreement [Memorandum of Understanding (MOU)] with Health Canada and Expert Advisory Committees.

All comments received are compiled in a spreadsheet and are reviewed by the CARN editorial team.

6.4 Approval Process

6.4.1 CARN MHPD Bureau Directors' Approval

A consolidated document of the revised articles is then submitted electronically to MHPD Bureau Directors for approval.

6.5 Identification of Spokespersons

At the time of approval of topics by MHPD Bureau Directors, each Bureau Director identifies a spokesperson when CARN topics are related to their Bureau's product area of expertise. Spokespersons are responsible to respond to media requests or public inquiries that arise from the CARN.

6.6 Summary Table of Advisories

A summary table of previous Health Canada posted advisories is included in each CARN publication. This table includes all advisories [Health Professional Communications (HPC), Public Communications (PC), Public Advisories and Warnings, Information Updates, Foreign Product Alerts] posted on the MedEffect™ Canada Web site since the previous publication (and includes both Health Canada issued and Industry issued risk communication documents).

6.7 External Scientific Editing and Translation

The consolidated document of the revised articles, including a summary table of advisories is sent to the identified scientific editing contact, who is the official in the contracted scientific journal/organization publishing the CARN e.g., currently the CMAJ. The CARN editorial team reviews the edited proof and incorporates changes as necessary. The final text is sent for translation and formatting in the CARN layout.

The CARN editorial team reserves the right to defer certain topics to future issues should a serious event arise (e.g., according to signal prioritization procedures) and need to be communicated sooner in the current issue, resulting in deferral of planned article(s). Bureau Directors are notified. Any disagreement will be brought to the attention of the TEPB Director, who will make the final decision on the content of the CARN. The TEPB Director may consult the MHPD Director General in final decisions, if required.

6.8 CARN Summaries

CARN summaries are prepared for each issue of the newsletter. Currently, CARN summaries are submitted 1 week prior to the CARN publication to the Canadian Family Physician and Canadian Pharmacists Journal, and other interested health professional journals for publication depending on availability of space.

6.9 Prepublication Notice to Foreign Regulatory Authorities

Forty eight (48) hours prior to publication, foreign regulatory authorities who have signed a confidentiality agreement [Memorandum of Understanding (MOU)] with Health Canada are sent a copy of the English and French PDF layouts of the CARN prior to the CARN release.

6.10 Courtesy Faxes to Market Authorization Holder of Health Product Subject of CARN Article

Twenty four (24) hours before the posting of the CARN on the MedEffect™ Canada Web site and targeted receipt of CARN hard copies by mail, MHPD sends a copy of the article(s) dealing with specific health products or classes of health products to the manufacturers of these health products. This is done only as a courtesy and not to solicit comments.

Courtesy advance notification is done in keeping with international practices of foreign regulatory agencies, including the procedures adopted by the US Food and Drug Administration (FDA) and the Therapeutic Goods Administration (TGA).

6.11 Publication and Communication

The designated CARN editor is responsible for sending the final approved English and French proofs to the Canadian Medical Association and/or other involved publisher(s) for quarterly publication in their journal, as per contractual agreement.

Final versions of the CARN are posted on the MedEffect™ Canada Web site and distributed via a hard copy mailing list and to MedEffect™ Canada e-Notice subscribers.

Appendix 1 - Glossary: Definitions and Terminology

Adverse Event (AE)
An AE is any untoward medical occurrence in a patient administered a medicinal product and which does not necessarily have to have a causal relationship with this treatment.  An AE can therefore be any unfavourable and unintended sign (for example, an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to this medicinal product. [International Conference on Harmonisation, Post-approval Safety Data Management: Definitions and Standards for Expedited Reporting (ICH E2D) (2003)].

Adverse Reaction (AR)
An AR, for the purpose of this guidance document means a noxious and unintended response to a marketed health product covered by this document and includes "adverse drug reaction" as defined in the Food and Drug Regulations and "adverse reaction" as defined in the Natural Health Products Regulations.

"Adverse Drug Reaction"
Adverse drug reaction as defined in the Food and Drug Regulations is a noxious and unintended response to a drug, which occurs at doses normally used or tested for the diagnosis, treatment or prevention of a disease or the modification of an organic function.

"Adverse Reaction"
Adverse reaction as defined in the Natural Health Products Regulations is a noxious and unintended response to a natural health product that occurs at any dose used or tested for the diagnosis, treatment or prevention of a disease or for modifying an organic function.

An AR is a harmful and unintended response to a health product. This includes any undesirable patient effect suspected to be associated with health product use. Unintended effect, health product abuse, overdose, interaction (including drug-drug, and drug-food interactions) and unusual lack of therapeutic efficacy are all considered to be reportable ARs.

Adverse Reaction Case [Note: this wording is for use only in the AR Statistics article, published once a year in the April issue of the CARN]
The initial AR report and all subsequent information received as follow-up reports are combined and considered to be one case. Cases result from the merger of initial, follow-up and duplicate reports.

Adverse Reaction Reports may be from Domestic or Foreign Origin
Domestic AR: Adverse reaction occurring in Canada.
Foreign AR: Adverse reaction occurring outside Canada.

Health Product
Health products, for the purpose of this guidance document include drugs and natural health products. Drugs include both prescription and nonprescription pharmaceuticals; biotechnology products and biologically-derived products such as vaccines, serums, and blood derived products; cells, tissues and organs; disinfectants; and radiopharmaceuticals.

Incident
An unusual (unexpected) event associated with the use of a medical device. May or may not lead to problems. [ Medical Device Regulations]

MedDRA
The Medical Dictionary for Regulatory Activities (MedDRA) is a clinically validated medical terminology developed by the  International Conference on Harmonization (ICH) to share regulatory information internationally about medical products used by humans. MedDRA provides a set of terms which consistently categorizes medical information.

Public risk perception of a safety issue
Public risk perception is the way that individuals intuitively see and judge risks. People view risks in a way that differs from scientific assessments.
[World Health Organization, "Public Health Monitoring of the Metro Manila Air Quality Improvement Sector Development Program" Main Report. March 2004]
[Meyboon, R.H.B.; Linquist M.; Egberts, A.C.G.;Edwards, I.R., 2002. Signal Selection and Follow-Up in Pharmacovigilance, Drug Safety, 25 (6): 459-465]

Recent Marketed Health Product
Health products on the market for less than 5 years.
Report of Suspected Adverse Reaction due to Health Products Marketed in Canada (Vaccines excluded)

Serious Adverse Drug Reaction
"Serious adverse drug reaction" means a noxious and unintended response to a drug that occurs at any dose and that requires in-patient hospitalization or prolongation of existing hospitalization, causes congenital malformation, results in persistent or significant disability or incapacity, is life-threatening or results in death. [ Food and Drug Regulations - section C.01.001(1)]

Serious Unexpected Adverse Drug Reaction
"Serious unexpected adverse drug reaction" means a serious adverse drug reaction that is not identified in nature, severity or frequency in the risk information set out on the label of the drug. [ Food and Drug Regulations - section C.01.001(1)]

Unexpected Adverse Reaction
An AR whose nature, severity, specificity, or outcome is not consistent with the term or description used in the local/regional product labelling (e.g., Package Insert or Summary of Product Characteristics) should be considered unexpected. When a Marketing Authorization Holder (MAH) is uncertain whether an AR is expected or unexpected, the AR should be treated as unexpected. [International Conference on Harmonisation, Post-approval Safety Data Management: Definitions and Standards for Expedited Reporting (ICH E2D) (2003)]

World Health Organization Adverse Reaction Terminology (WHO-ART)
This is a dictionary of clinical terminology for coding adverse reaction terms, used throughout the WHO Programme by member countries and around the world by pharmaceutical companies and clinical research organisations. The system is maintained by the  Uppsala Monitoring Centre (UMC), the World Health Organization Collaborating Centre for International Drug Monitoring.

Appendix 2 - List of Acronyms

ADR:	Adverse Drug Reaction
AR:	Adverse Reaction
BGTD:	Biologics and Genetic Therapies Directorate
CARN:	Canadian Adverse Reaction Newsletter
CFP:	Canadian Family Physician
CMA:	Canadian Medical Association
CMAJ:	Canadian Medical Association Journal
CP:	Case Presentation
CPJ:	Canadian Pharmacists Journal
HPFB:	Health Products and Food Branch
HPFBI:	Health Products and Food Branch Inspectorate
IC:	Information Component
MDS:	Medical Devices System
MedDRA:	Medical Dictionary for Regulatory Activities
MHPD:	Marketed Health Products Directorate
MOU:	Memorandum of Understanding
NHPD:	Natural Health Products Directorate
PM:	Product Monograph
RARCS:	Regulatory Advertising and Risk Communications Section
RCU:	Risk Communications Unit
TEPB:	Therapeutic Effectiveness and Policy Bureau
TPD:	Therapeutic Products Directorate
WHO:	World Health Organization

Appendix 3 - CARN Editorial Process - Key Steps

Topic Selection

• Preselection Meeting
  
  • Preparation of topics by CARN editors
• Topic Selection Meeting
  
  • Four meetings/year
    
  • Organized by CARN editors
    
  • Input given by MHPD scientific staff, Canada Vigilance Regional Offices
• Selection of Topics
  
  • Primary criteria
    
  • Secondary criteria
    
  • Mandatory requirements
• Approval of Topics & Identification of Spokespersons

Writing of Topics

• Instructions for Authors
  
  • Writing & article guidelines

Consultations

• CARN Editors
  
  • Provide comments
    
  • Author resubmission
    
• Internal-External Consultation
  
  • With pertinent directors/managers of MHPD and pre-market
    
  • Review by CARN editors
    
• MHPD Directors
  
  • Approval
    
• Scientific Editing & Translation
  
  • Scientific review by scientific editors
    
  • Verification of translation by CARN editors

Publications and Communications

• Publication Submissions
  • Submission of final documents as per contractual agreement
    
  • Preparation of CARN webposting, MedEffect e-Notice
    
• Communications
  
  • Preparation of CARN summaries by CARN editors
• Advance Notice
  
  • To foreign regulatory authorities by MHPD
    
  • Courtesy faxes to respective health product manufacturers
    
• Final Release
  
  • Mailing of CARN hard copies
    
  • Webposting on Health Canada Web site

Appendix 4 - CARN Production Schedule Timeline by Fiscal Year

Activities

• April Issue
  
  • Topic Selection /  Approvals / First Drafts - December and January
    
  • Editorial Review / Scientific Coordination - January through March
    
  • Internal / External Communications  - March
    
  • Printing / Webposting / Distribution - March to the beginning of April
    
    
• July Issue
  
  • Topic Selection /  Approvals / First Drafts - February and March
    
  • Editorial Review / Scientific Coordination - April through June
    
  • Internal / External Communications  - June
    
  • Printing / Webposting / Distribution - June to the beginning of July
    
    
• October Issue
  
  • Topic Selection /  Approvals / First Drafts - May and June
    
  • Editorial Review / Scientific Coordination - July through September
    
  • Internal / External Communications - September
    
  • Printing / Webposting / Distribution - September to the beginning of October
    
    
• January Issue
  
  • Topic Selection /  Approvals / First Drafts - September
    
  • Editorial Review / Scientific Coordination - October through December
    
  • Internal / External Communications - December
    
  • Printing / Webposting / Distribution - December to the beginning of January

Appendix 5 - Description of CARN Topics

Announcement
Provides information on health product safety initiatives, e.g., opening of new Canada Vigilance Regional Office, release of reports related to health product safety, It's Your Health article related to health product safety.

AR Annual Statistics
Includes information such as number and type of domestic AR reports and cases received, as well as their source and number of foreign ARs received. These are usually published annually in the April issue.

Article
Utilizes/presents data collected from the Canada Vigilance Program or Medical Devices System (MDS). May focus on a health product (drug, medical device, or natural health product), class of health products, specific reaction or incident or system organ class.

Case Presentation
Outlines details of a specific serious unexpected AR case example. It is intended to raise awareness and prompt additional reporting.

Editorial
Commentary on relevant issues related to the Canada Vigilance Program, Medical Devices System or various aspects of spontaneous reporting.

Update
Provides information further to a previously published article, a regulatory action (e.g., Product Monograph change), or advisories/warnings (e.g., Health Professional Communication, Public Communication, Public Advisory or Warning, etc.).
OR
Reminds health professionals of specific labelling information.

Appendix 6 - Criteria for Selecting a Topic (excluding announcements, AR statistics and editorials)

Primary Criteria

• Canadian cases
  
• Serious reactions
  
• ARs that are unexpected, unlabelled, not yet described
  
• Safety issue with  recently marketed health product
  
• Public health impact and clinical relevance of safety issue
  
• Public risk perception of a safety issue
  
• Safety issues concerning specific populations (e.g., children, elderly, pregnant or nursing women, HIV/AIDS, etc.)
  
• Emerging significant safety information

Secondary Criteria

• Increased frequency of an AR (dependent on seriousness of reaction)
  
• Clinically relevant Product Monograph changes to sensitize health professionals if not adequately addressed by another communication vehicle
  
• Safety concerns identified in pharmacovigilance plans or risk management plans to share findings, stimulate reporting
  
• Safety issues in other countries for products authorized for market in Canada
  
• Other safety concerns, e.g., reminder of ongoing safety issues with inappropriate use of a health product (e.g., drug abuse, misuse, off-label use, medication errors), new health product interactions, health product defects, lack of effect (need several reports)
  
• Suitable timing of topic publication (consideration of environmental context, sensitivities)

Checklist of additional criteria for selecting a Case Presentation

• Recent report (preferably within last 2 years of date of proposed publication)
  
• Not a Case Presentation recently published for this health product (within last year of date of proposed publication - unless different reaction)

MANDATORY for a Case Presentation

• Serious unexpected reaction
• Clinical relevance of safety issue, strong case report with a plausible causality

Appendix 7 - Author Instructions for CARN Topic Proposals

Purpose:
To provide direction to scientific staff regarding the required documentation for the submission of topics at the Topic Selection Meeting for the Canadian Adverse Reaction Newsletter (CARN).

Scope:
To provide a checklist outlining the steps to follow when submitting a topic for the CARN Topic Selection Meeting. It describes the background information that should be provided prior to the meeting as well as the key points that should be included in the discussion at the meeting.

Background information for discussion:
The following is a checklist that is completed prior to the Topic Selection Meeting. It serves as a preparation document for the presenter, and lists relevant key points that should be discussed at the meeting. This checklist, as well as supporting documents, are sent to all scientific staff at least 2 days prior to the CARN Topic Selection Meeting. It assists Topic Selection Meeting participants to gain a good understanding of the proposed topic for discussion.

Checklist For CARN Topic Proposals:
(Fields to be filled below)

CARN Topic Selection Meeting date:

Health product name and active ingredient:

Date of marketing of health product in Canada:

Date of last PM update:

Authorized Canadian indication:

Adverse Reaction (AR) or Medical Device Incident according to MedDRA terminology:
(if applicable)

Total number of AR reports received for this product (Canada Vigilance Database or Medical Devices System):

Total number of AR cases received for this product with this reaction (Canada Vigilance Database or Medical Devices System):

Current labelling in Canada (i.e, Product Monograph, Product Label):
☐ Labelled
☐ Unlabelled

☐ Adverse reactions section
☐ Warnings & Precautions section
☐ Post-market section
☐ Other : (to specify)

Current labelling in the US:
☐ Labelled
☐ Unlabelled

☐ Adverse reactions section
☐ Warnings & Precautions section
☐ Post-market section
☐ Other : (to specify)

Line-listing (Canada Vigilance Database or Medical Devices System):
(to attach)

Summary Table of Information Highlighted in the Topic:
(to attach)

Additional information (if available):
☐  WHO Vigisearch Line Listing
☐  WHO Combination database (IC values)
☐  Literature:

Submission Type:
☐  Article
☐  Case Presentation
☐  Update
☐  Announcement

Rationale for proposal as CARN topic (brief description on objective):
Examples:

• Description of AR or Incident (seriousness, onset of reaction, outcome, ...)
  
• Past medical history
  
• Concomitant medications (including Natural Health Products)
  
• Dechallenge/Rechallenge information
  
• Treatment of the reaction(s)

Appendix 8 - Author Checklist before CARN Topic Submission

• Is the article clearly titled?
  
• Is the document typewritten and double-spaced?
  
• Are the generic and brand names of the health product (if applicable) in the opening paragraph?
  
• Has the issue of concern been defined in the opening paragraph?
  
• Have materials been properly referenced?
  Are the references in the accepted American Medical Association Manual of Style format (see previous issue)?
  
• Is the article within the maximum recommended word length?

Announcement	200-300 words
Editorial	300-400 words
Article	500-600 words
AR Statistics	600-700 words
Update	300-400 words
Case Presentation	100-200 words

• Have the literature/Canada Vigilance Database/ Medical Devices System searches been updated in order to include the most recent information in the text?
  
• Have the supporting files material and information for review by the CARN editorial team been included? In addition to references or other pertinent information, supporting material includes:
  
  • Summary Table of Information Highlighted in the Topic
  • Case reports and line listing  
  • Most recent Product Monograph or Medical Device labelling
• Has the information retrieved from your references and which appears in the text been highlighted?