UNIT 3 (Pharmacovigilance)

 VACCINE SAFETY SURVILLANCE

 PHARMAOVIGILANCE METHOD
 COMMUNICATION IN PHARMACOVIGILANCE

By

Rakesh Meher
Assistant Professor
School of Pharmacy, Bolangir
Vaccine safety surveillance
Vaccine Pharmacovigilance
Definition- According to the CIOMS/WHO working group on vaccine pharmacovigilance, Vaccine
pharmacovigilance is defined as “the science and activities relating to the”
o Detection,
o Assessment,
o Understanding and
o Communication
of adverse events following immunization and other vaccine or immunization-related issues, and to the
prevention of untoward effect of the vaccine or immunization.

Importance of vaccine safety

⚫ Decreases in disease risk and increased attention on vaccine risks
⚫ Public confidence in vaccine safety is critical
⚫ Low tolerance for vaccine risks
– Higher standard of safety is expected
– Vaccinees generally healthy
– Lower risk tolerance = need to search for rare reaction
Steps of vaccine pharmacovigilance

Detect signal suggesting AEFI is related to vaccine.

Develop hypothesis about causal association between an AEFI and vaccination

Test hypothesis through appropriate epidemiological method

Vaccine provide by Govt. of India

Govt. of India is providing vaccination to prevent 7-vaccine preventable disease (VPDs) namely,
 Diphtheria,
 Pertussis,
 Tetanus,
 Polio,
 Measles,
  Hepatitis B,
 BCG
 JE vaccination,
 Hib (given as pentavalent containing Hib+DPT+Hep B)

Other vaccines......
 Pneumococcal vaccine
 Rotavirus vaccine
 Hepatitis A
 MMR
 Influenza
 Meningococcal
 Cholera
 JE
 HPV
 Varicella
 Typhoid

Source for vaccine safety

⚫ Local health workers
⚫ Health education campaigns
⚫ Visiting experts
⚫ Online resources and communication network
⚫ Religious and/or community leader
⚫ Parents, guardians and vaccine
⚫ Radio and telivision
⚫ printed material
⚫ Video or DVD

Which AEFIs should be reported?

• Serious AEFI
 • Signal and events associated with newly introduced vaccine
• AEFI that may have been caused by an immunization error
• Significant events of unexplained cause occurring within 30 days after a vaccination
• Event causing significant parental or community concern
• Swelling, redness, soreness at the injection site IF it lasts for more than 3 days or swelling
extended beyond nearest joint

Adverse event following immunization (AEFI)

Definition-
An AEFI is any untoward medical occurrence which follows immunization and which does not
necessarily have a causal relationship with the usage of the vaccine. The adverse event may be
any unfavourable or unintended sign, abnormal laboratory finding, symptoms or disease.

Classification of AEFIs
 Vaccine product-related reaction – An AEFI that is caused or precipitated by a vaccine
due to one or more of the inherent properties of the vaccine product. Extensive limb
e.g. swelling following DTP vaccination.
 Vaccine quality defect-related reaction – An AEFI that is caused or precipitated by a
vaccine that is due to one or more quality defects of the vaccine product inducing its
administration device as provide by the manufacturer.
Ex. Failure by the manufacturer to completely inactivate a lot of inactivated polio vaccine leads
to cases of paralytic polio.
 Immunization error-related reaction – An AEFI that is caused by inappropriate
vaccine handling, prescribing or administration.
Ex. Transmission of infection by contaminated multidose vial.
 Immunization anxiety-related reaction – An AEFI from anxiety about the
immunization.
e.g. Vasovagal syncope in an adolescent following vaccination.
 Coincidental event- An AEFI that is caused by something other than the vaccine
product, immunization error or immunization anxiety.
e.g. A fever after vaccination (temporal association) and malarial parasite isolated from
blood
AEFI Frequency Terminology

Two type of vaccine reaction-

⚫ Minor reaction
⚫ Severe reaction

Minor reaction
o Usually occur within a few hours of injection.
o Resolve after short period of time and pose little danger.
o Local (includes pain, swelling or redness at the site of injection).
o Systemic (includes fever, malaise, muscle pain, headache or loss of appetite).
Severe reaction
o Usually do not result in long-term problems.
o Can be disabling.
o Are rarely lives threatening?
o Include seizures and allergic reactions caused by the body’s reaction to a particular
component in a vaccine.

Serious AEFI cases (formats and timelines)

Vaccine Evaluation
Pre-licensing
Randomised, Blinded, Controlled Clinical Trials
Vaccine efficacy:
Protective Effect under Idealised Conditions
RTC: controlled experiments, simple interpretation
Post-licensing
Observational Studies
Vaccine effectiveness
Protective Effect under Ordinary Conditions of a public health programme
Prone to bias, more complex interpretation

Basic Calculation of Vaccine Evaluation

VE(%) = (ARU-ARV/ARU).100

Precaution-
⚫ A condition in a recipient which may increase the chance or severity of an adverse event,
or
⚫ May compromise the ability of the vaccine to produce immunity.

Pharmacovigilance Methods
Objective
 To establish a functional reporting system to monitor the safety of all medicines
 To learn more about the safety profile of new medicines in the early post-marketing
phase
 To learn more about the ADR profile of a specific medicine(s) in your population
 To estimate the incidence of a known ADR to a specific medicine in your population
  To gather more information on the safety profile of a new chemical entity in early
post-marketing phase

 To make use of existing electronic health records and registries to support

pharmacovigilance activities

Methods
 Passive surveillance
Spontaneous reports
Case series
 Stimulated reporting
 Active surveillance
Sentinel sites
Drug event monitoring
Registries
 Targeted clinical investigations
 Comparative observational studies
Cross sectional study
Case control study
Cohort study
 Descriptive studies
Natural history of disease, Drug utilization study

Spontaneous Reports
 A communication by consumers or healthcare professionals to a company or
Regulatory Authority, that describes one or more ADR in a patient, who has given the
drug.
 It plays a major role in the, identification of safety signals once the drug is marketed.
 Gives alerts on rare AEs that were not detected in earlier clinical trials or pre
marketing studies.
 Provides important information on at risk groups, risk factors and clinical features of
known serious ADRs.
Case series
 Series of case reports can provide evidence of an association of a drug and AEs.
 Generally more useful for generating hypothesis than for verifying an association
between drug exposure and outcome.
 Certain distinct adverse events occur more frequently with drug therapy, such as
anaphylaxis, aplastic anemia and Stevens-Johnson syndrome events such as these are
spontaneously reported for detailed and rapid follow-up.

Stimulated Reporting
 A method used to encourage and facilitate reporting by health professionals for new
products, or for limited period.
 Online reporting of AE, systematic stimulation of reporting of AEs.
 Drawbacks- data are often incomplete.
Not useful to generate accurate incidence rates.

Active surveillance
 To ascertain completely the no. of AEs via a continuous pre-organized process.
E.g. follow up of patient treated with a particular drug.
 More feasible to get comprehensive data on individual AE reports.

Sentinel Sites:- Active surveillance carried out at Institutions, Nursing Homes and Hospitals
etc. provides information such as data from specific patient subgroups, drug abuse etc.

Drug Event Monitoring: - Patients are identified by electronic prescription data or automated
health insurance claims. A follow up questionnaire can be sent to each physician or patient at
specified intervals. Information on patient demographics, indication for treatment, duration of
therapy, dosage, clinical events, and reasons for discontinuation can be included in the
questionnaire.

Registries: - A registry is a list of patients presenting with same characteristics. E.g. Disease
registry, drug registry, pregnancy registry etc. Differs from each other depending on type of
patient.
Comparative Observational Studies:-
 Traditional epidemiologic methods are a key component in the evaluation of AEs.
 Observational study designs are useful in validating signals from spontaneous reports
or case series.

Cross Sectional Studies:-

 Data collected from a population of patients at a single point in time regardless of
exposure or disease status.
 Primarily used to gather data for surveys or for ecological analysis. Best used to examine
the prevalence of a disease at one time point or to examine trends over time, when data
for serial time points can be captured.

Case Control Study:- In this case of disease are identified. Controls or patients without the
disease or event of interest, are selected from the source population. Exposure status of the two
groups is compared using the odds ratio.

Cohort Study:- A population at risk for the disease is followed over a time for the occurrence of
the disease or events. Information on exposure status is known throughout the follow up and
hence incident rates can be calculated.
Comparison cohorts of interest are selected on the basis of drug use and followed over time.
Multiple AEs can also be investigated using the same data source in a cohort study.

Targeted Clinical Investigations:-

 When significant risks are identified from pre-approval clinical trials, further clinical
studies might be called, to evaluate the mechanism of action for ADRs.
 PK and PD studies might be conducted.
 Specific studies to investigate potential drug-drug interactions and food-drug interactions
might be called.

Descriptive Studies:-
 Primarily used to obtain the background rate of outcome events and/or to establish the
prevalence of the use of drugs in specified populations.
  Natural History of Disease- Focused on the natural history of disease, including the
characteristics of diseased patient and the distribution of disease in selected populations,
as well as estimating the incidence and prevalence of potential outcomes of interest.
Drug Utilization Study- These studies provide data on specific populations, such as the elderly,
children, or patients with hepatic or renal dysfunction, often stratified by age, gender,
concomitant medication, and other characteristics.

Communication:
The act of sharing or exchanging information, ideas or feelings.

Principles of Good Pharmacovigilance Communication

 Relate the messages to the audience’s perspective
 Avoid comparisons which trivialize the concern
 Ensure completeness of the message
 Be balanced, honest and sympathetic
 Focus on the specific issue that needs to be handled
 Pay attention to what the audience already knows
 Be respectful of people’s right to be concerned
 Be honest about the limits to scientific knowledge
 Acknowledge uncertainty
 Evaluate the impact of your message

Effective Communication in Pharmacovigilance

One can achieve effective way of communication just by following the principles of good
pharmacovigilance communication.

Why do we need to improve our communication?

 Improve patient care and understanding
 Eradicate disease / improve disease control
 Promote transparency and accountability
Why do Communications matter in Drug Safety?
  For Welfare of millions of people worldwide
 To overcome Extreme dangers of failure
 Communications are commonly poorly executed, second-rate and ineffective, so to
improve the quality.
Communication Challenges:
 The importance of ADRs and reporting them
 Information about benefit – harm and effectiveness – risk
 Encouraging rational drug use/adherence
 Communicating uncertainty
 Dealing with traditional beliefs and practices
 Involving patients; reaching informed consent
 Preventing or resolving crises
Problematic issue in Drug Safety:
all reliant on communications for safety
 Adverse effects: ‘no drug 100% safe’
 Risk as a concept in medicine
 Safety and medicines (prescribing, dispensing)
 Benefit-harm
 Effectiveness-risk
 Public health and commercial goals
 Public health and individual welfare
 Access to medicines
 Uncertainty

Principles of Effective Communications

 Be clear about your message and purpose
 Know your audience(s): empathy; tailor the message
 Choose appropriate methods/media
 Present message with impact
 Make benefits clear
 Pre-test and revise message
 Repeat message
  Seek feedback, monitor effects, start again

Qualities of Modern Communications:

 Intimacy
 Immediacy and high impact
 Peer-to-peer
 Addressing competition and low attention levels
 Benefits

Planning Communications:
 Today’s modern standards and methods
 Simple, clear message
 Stimulating motivation and offering benefits (including rewards and feedback)
 The use of specialist skills and creative imagination

Summary:
• Our communications must:
– Be strong and visible
– Be precisely targeted and tested
– Change attitudes, values, behaviour
– Be followed up and revised
– Embrace modern standards and skills
1. Communication in Drug Safety Crisis Management
 Crisis will happen (fire, death, ADRs…)
 Assess risks
 Anticipate and plan for all likely and unlikely events
 Create, rehearse and revise crisis plans
 In crisis, communicate
– Quickly
– Openly and honestly
– Express regret, apologise
– Explain what is being done to solve the crisis and prevent repetition

2. Communicating with Regulatory Agencies, Business partners, Healthcare facilities

& Media

Media

Regulatory

Patient Healthcare

Business

Partners

Communication with Media:

Who are the media?
 Print -magazines, newspapers, community newspapers
 Electronic -radio, TV, internet
 Local and national levels
□ Some basic questions a reporter will ask you….
 WHO-is affected, responsible
 WHAT-has happened and what is being done about it
 WHERE-has it happened
 WHEN-did it happen
 WHY-did it happen
 WILL-it happen again

□ Communications practices to avoid

 “Spinning”! (distortion or decoration of facts for beneficial effects)
 All communications are subjective, but do not be manipulative or dishonest
 Avoid “No comment”–rather say why there’s nothing to say and what is being
done
 Avoid confusing statistics
 Do not avoid taking responsibility
 Don’t attack the messenger/accuser
 Don’t deny, justify or excuse your mistakes

□ Partners & Audiences in Drug Safety:

Partners Audiences

• Manufacturers • The public

• Regulators • Patients

• Politicians • Consumer groups

• Employees • Lawyers

• Health professionals • The media

• Academics • International community

• Bosses/managers