Lecture 13: Adverse Reaction Reporting

Question 1

Define Adverse Drug Event (ADE)

Answer 1

Any negative or harmful occurrence that takes place during treatment, that may or may not be associated with a medicine.

Question 2

Define Adverse Drug Reaction (ADR)

Answer 2

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.

Question 3

Define Serious ADR

Answer 3

A noxious and unintended response to a drug that occurs at any dose and that:
‒requires in-patient hospitalization
‒prolongation of existing hospitalization
‒causes congenital malformation
‒results in persistent or significant disability or incapacity
‒is life-threatening or results in death

ADRs that require significant medical intervention to prevent one of the outcomes listed above are also considered serious

Question 4

What is the role of Marketed Health Products Directorate (MHPD)?

Answer 4

works to assure that the Health Products and Food Branch (HPFB) programs take a consistent approach to post-approval safety surveillance, assessment of signals and safety trends, and risk communications concerning regulated marketed health products.

Question 5

Canada Vigilance Program

Answer 5

One of 10 founding countries of the World Health
Organization (WHO) International Program for
Adverse Reaction Monitoring in 1968 (now 140 countries
- Voluntary reporting for Health Professionals and Consumers/patients
- Mandatory reporting for Market Authorization Holders
- Mandatory reporting of Serious ADRs and Medical Device Incidents (MDIs) by Hospitals
- Legislative Framework (e.g., Food and Drugs Act and Regulations, Access to
Information and Privacy Act, Protecting Canadians from Unsafe Drugs Act –Vanessa’s Law)
- Canada’s is supported by 7 regional offices for regional point of contact

Question 6

at what stages is pharmacovigilance important?

Answer 6

whole lifecycle of product from pre to post marketing (clinical trial reviews to post market monitoring nd intervention)
- safety, efficacy, quality must be monitored

Question 7

Why are adverse drug reactions monitored?

Answer 7

• All health products have risks and benefits. Before a product is marketed, safety and efficacy experience is limited to its use in clinical trials. However, these initial clinical trials mostly detect common and frequent adverse reactions (AR’s).
• Some important reactions may take an extremely long time to develop or occur infrequently.
• The controlled conditions under which patients use health products in clinical trials (e.g., under direct medical supervision without necessarily significant exposure to other products and or underlying diseases), do not necessarily reflect the way the product will be used in real life conditions once it is marketed.

Question 8

clinical trials vs real world

setting of observation

Answer 8

C:
• Randomized and double-blinded, controlled conditions
• Limited number of patients
• Short-term observation
P:
• Not usually controlled and never randomized
• Highly variable subjects
• Long-term use

Question 9

clinical trials vs real world

patient factors

Answer 9

C:
• Specially selected cases and diseases
• Healthier patients with fewer risk factors
• Concomitant drugs often excluded 
• Many populations excluded (elderly, pediatric, many women)
P:
• Multiple co-morbidities
• Variations in lifestyle and
demographic factors
• Concomitant drugs, including OTC
• Off-label use

Question 10

clinical trials vs real world

data analysis

Answer 10

C:
Only efficacy amenable to
analysis (sparse ADR data)
• ADRs not usually defined endpoints
P:
• Spontaneous reports of ADRs notquantifiable
• Events may be over- or under- detected, -attributed, -reported
• Potentially subject to media bias
• Efficacy seldom quantified

Question 11

how often are ADRs reported

Answer 11

Under-reporting and poor quality of
reports is an issue in all countries
– International systematic review estimated that only 2-18% (median of approximately 6%) of ADRs are reported1

Question 12

The Role of the Pharmacist in ADR

Reporting

Answer 12

Adverse drug reaction (ADR) reporting is an integral role of the pharmacist
» Considered a fundamental role of the pharmacy profession.1
– Supported and encouraged by professional associations and organizations and incorporated in Professional Standards of Practice.

• Pharmacists are the only healthcare professional that comes in contact with patients on medications, over-the-counter (OTCs) and herbal medicines and therefore should be at the frontline for ADR reporting.
  » Pharmacists play a pivotal role in ADR reporting as they are the connecting link with patients and their use of their medication during a course of treatment.1
  » Pharmacists are medication experts and play a significant role in the prescribing and monitoring of medication to ensure safe and optimal use.2

Question 13

what types of drugs should be reported?

Answer 13

» Prescription drugs
» Non-prescription drugs
» Natural health products
» Biologics
- Biotechnology products
- Vaccines
- Fractionated blood products
- Human blood and blood component products
- Cells, tissues and organs
» Disinfectants and sanitizers with disinfectant claims
» Radiopharmaceuticals

Question 14

which 3 circumstances should be reported by practitioners especially?

Answer 14

• Proof that a health product caused an undesirable patient effect (causality) is NOT a requirement for ADR reporting
• Practitioners should report all clinically significant suspected ADRs, but especially those that are:
  » unexpected (not consistent with product information or labelling),
  regardless of their severity;
  » serious, whether expected or not;
  » related to a health product that has been on the market for less
  than 5 years, regardless of their severity.

Question 15

where to find reporting form?

Answer 15

The ADR reporting form may be obtained from:

• online
• Canada Vigilance Regional Office
• the Compendium of Pharmaceuticals and Specialties (CPS)

Submit online or fax, mail or verbally to Canada Vigilance Regional Office

Question 16

what are mandatory fields?

Answer 16

1. Patient age & sex,
   2.Reporter’s name & contact
   information,
2. Suspected product name, and
   4.An adverse reaction

Pt name, DOB, SIN, PHN not needed

Question 17

which causality term fits this:

• Event or laboratory test abnormality, with plausible time relationship to drug intake
• Cannot be explained by disease or other drugs
• Response to withdrawal plausible (pharmacologically, pathologically)
• Event definitive pharmacologically or phenomenologically (i.e., an objective and specific medical disorder or a recognised pharmacological phenomenon)
• Rechallenge satisfactory, if necessary

Answer 17

certain

Question 18

which causality term fits this:

• Event or laboratory test abnormality, with reasonable time relationship to drug intake
• Unlikely to be attributed to disease or other drugs
• Response to withdrawal clinically reasonable
• Rechallenge not required

Answer 18

probable/likely

Question 19

which causality term fits this:

• Event or laboratory test abnormality, with reasonable time relationship to drug intake
• Could also be explained by disease or other drugs
• Information on drug withdrawal may be lacking or unclear

Answer 19

possible

Question 20

which causality term fits this:

Event or laboratory test abnormality, with a time to drug intake that makes a relationship improbable (but not impossible)

Answer 20

unlikely

Question 21

which causality term fits this:

• Event or laboratory test abnormality
• More data for prober assessment needed, or
• Additional data under examination

Answer 21

Conditional/

Unclassified

Question 22

which causality term fits this:

• Report suggesting an adverse reaction
• Cannot be judged because information is insufficient or contradictory
• Data cannot be supplemented or verified

Answer 22

Unassessible/

Unclassifiable

Question 23

What is Vanessa’s Law (Protecting Canadians from Unsafe Drugs Act)

what are some amendments made to Food and drugs Act?

Answer 23

goal: To improve the quality and increase the quantity of reporting on serious ADRs and MDIs that are reported to Health Canada to optimize detection of potential health product safety issues.

The amendments to the Food and Drugs Act include:
1. Power to require information, tests or studies
2. Power to require a label change/package modification
3. Power to recall unsafe therapeutic products
4. Ability to require and disclose information in certain circumstances
5. Tougher measures for those that do not comply
6. Mandatory reporting of serious adverse drug reactions (ADRs) and medical
device incidents (MDIs) by health care institutions*

Question 24

Mandatory Reporting

who is required to report?

Answer 24

Hospitals
The regulations define a hospital as a facility that:
‒ is licensed, approved or designated as a hospital by a province or territory, in accordance with the laws of the province or territory, to provide care or treatment to persons suffering from any form of disease or illness; or
‒ is operated by the Government of Canada and that provides health services to in-patients.

Question 25

Mandatory Reporting

what events are reportable?

Answer 25

Serious ADR: a noxious and unintended response to a drug that occurs at any dose and that:
‒ requires in-patient hospitalization;
‒ prolongs existing hospitalization;
‒ causes congenital malformation;
‒ results in persistent or significant disability or incapacity; or
‒ is life-threatening or results in death

Medical device incident (MDI) means an incident related to a failure of a medical device or a deterioration in its effectiveness, or any inadequacy in its labelling or in its directions for use that has led to the death or a serious deterioration in the state of health of a patient, user, or other person, or could do so were it to recur.

Question 26

Mandatory Reporting

when must hospitals report?

Answer 26

Hospitals are required to report serious ADRs and MDIs to Health Canada, in writing, within 30
calendar days of first documentation of the reaction or incident within the hospital.

Question 27

what products are excluded?

Answer 27

‒ Vaccines administered as part of a routine immunization program: HCP need to fill out Adverse Events Following Immunization form and send it to provincial health unit instead of Health Canada
‒ Natural health products
‒ Cannabis
‒ Blood and blood components
‒ Cells, tissues and organs
‒ Semen and ova
‒ Drugs for clinical trials, devices for investigational testing, and drugs/devices accessed via Special Access Programme