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Basic
Pharmacovigilance
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Part 1

01.What is Pharmacovigilance?
Pharmacovigilance is the science of collecting, monitoring, researching, assessing and evaluating information from healthcare providers
and patients on the adverse effects of medications, biological products, herbalism and traditional medicines.

02.What is the minimum criterion required for a valid case according to WHO?
a. An identifiable reporter
b. An identifiable patient
c. A suspect product
d. An adverse drug event

03.What is an Adverse Drug Event (ADE)?

Any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does
not necessarily have to have a causal relationship with this treatment.

04.When do you consider an event to be serious?

If an event is associated with any one of the following, it is considered to be serious
a. Death
b. Life threatening
c. Hospitalization or prolongation of hospitalization.
d. Congenital anomaly
e. Disability
f. Medically significant

05.Name the regulatory bodies in USA, UK, Japan and India?

USA: United States Food and drug administration (USFDA).
UK: European Medicines Agency (EMEA).
Japan: Ministry of Health, Labour and Welfare (MHLW).

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06.What is Volume 9A?
Volume 9A brings together general guidance on the requirements, procedures, roles and activities in the field of pharmacovigilance, for both
Marketing Authorisation Holders (MAH) and Competent Authorities of medicinal products for human use; it incorporates international
agreements reached within the framework of the International Conference on Harmonisation (ICH).

Volume 9A is presented in four parts:

Part I deals with Guidelines for Marketing Authorisation Holders;
Part II deals with Guidelines for Competent Authorities and the Agency;
India: Central Drugs Standard Control Organization (CDSCO)

Part III provides the Guidelines for the electronic exchange of

pharmacovigilance in the EU
Part IV provides Guidelines on pharmacovigilance communication.

07.When do you consider a case to be medically confirmed?

A case is considered to be medically confirmed if it contains at least one event confirmed or reported by an HCP (Health Care Professional)

Note: HCP can be a physician, nurse, pharmacist, coroner or psychologist

(only in Germany).

08.What do you mean by causality?

Causality is the relationship between a set of factors. In Pharmacovigilance, causality is the relationship between the suspect product and the
adverse drug event.
• Is there a convincing relationship between the drug and the event?
• Did the drug actually cause the event?

09.Name some data elements in ICSR

Patient demographics: Age, gender and race.
Suspect product details: Drug, dose, dosage form, therapy dates, therapy duration and indication. Adverse event details: Event, event onset date,
seriousness criterion, event end date and latency.

10.What should a narrative consist of..?

A narrative should consist of precise and concise information about the source of report, patient demographics, patient’s medical history,
concomitant medications, suspect product details and adverse event details in an orderly manner.

11.Explain the hierarchy in MedDRA.

System Organ Class (SOC)
High Level Group Term (HLGT)
High Level Term (HLT)
Preferred Term (PT)
Lower Level Term (LLT)

12.What do you know about E2a, E2b and E2c guidelines?

E2a: E2a guidelines give standard definitions and terminology for key aspects of clinical safety reporting. It also gives guidance on mechanisms
for handling expedited (rapid) reporting of adverse drug reactions in the investigational phase of drug development.
E2b: E2b guidelines for the maintenance of clinical safety data management and information about the data elements for transmission of
Individual Case Safety Reports.

E2c: E2b guidelines for the maintenance of clinical safety data management and information about the Periodic Safety Update Reports for
marketed drugs.

13.State the benefits of Pharmacovigilance program.

This program will increase the knowledge and importance of Pharmacovigilance in drug discovery process and Clinical Research,
Pharmacovigilance is becoming an important part of drug development as it deals with the patients’ safety & efficacy of drug resulted into new
job avenues. The participants after the completion of this would have new economic pursuits as Pharmacovigilance potential opportunities &
growth prospects are huge.

14.Role of Drug Safety Associate:

Manage and relay d rug safety information, maintain current knowledge of global drug safety regulations, summaries clinical safety data,
participate in meetings with potential and actual study sponsors, write narratives with medical input from
a physician, report SADRs to the Regulatory Authorities, participate in the training of operational staff on drug safety issues, quality control work
o f other staff in the department, take on any other task as assigned by the manager or Medical Director within the capabilities of the Drug Safety
Associate.

15.What are the objectives in Pharmacovigilance?

Understanding the concepts of ADR, Medical Errors, Public Health Significance, Regulatory Interventions, ADR Monitoring schemes.

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16.What are the types of Pharmacovigilance (PV)?
A. Two types. 1. Active PV and 2.Passive PV

Active PV: Active (or proactive) safety surveillance means that active measures are taken to detect adverse events. This is managed by active
follow-up after treatment and the events may be detected by asking patients directly or screening patient records. The most comprehensive
method is cohort event monitoring (CEM)

Passive PV: Passive surveillance means that no active measures are taken to look for adverse effects other than the encouragement of health
professionals and others to report safety concerns. Reporting is dependent on the initiative and motivation of the potential reporters. This is the
most common form of pharmacovigilance. It is commonly referred to as “spontaneous” or “voluntary” reporting.

17.What are the due dates for safety reporting?

A. Safety reporting due dates are 7days for IND Reporting and 15 days for NDA Reporting

18.What are Data assessments in Pharmacovigilance?

Data assessments are:
Individual case report assessment
Aggregated assessment and interpretation

Signal detection
Interactions and risk factors
Serial study
Frequency
Estimation

19.Aim of pharmacovigilance:
• rapid identification of events that are likely to affect adherence to treatment and determination of their rates, and identification of the risk
factors that make these events more likely, with the aim of reducing their occurrence;
• identification of signals (i.e., possible causal relationships between an adverse event and a medicine; see Glossary) of ADRs of concern following
the introduction of a new drug or drug combination;
• assessment of signals to evaluate causality, clinical relevance, frequency and distribution of ADRs in particular population groups;
calculation of rates of events so that:
— risk can be measured;
— the safety of different medicines can be compared and informed choices made;
— risk factors can be clearly identified;
• contribution to the assessment of benefit, harm, effectiveness and risk of medicines, leading to the prevention of harm and maximization of
benefit;

• appropriate response or action in terms of drug registration, drug use and/or training and education for health professionals and the public;
• measurement and evaluation of the outcome of the response or of action taken (e.g. reduction in risk, improved medicine use, or improved
outcome for patients experiencing a particular ADR);
• timely communication with and recommendations to authorities and the public; and
• feedback to the clinicians who provided the information.

20.Pharmacovigilance centre (PvC)

The PvC of an individual country is responsible for meeting the requirements for pharmacovigilance of all medicines. It is a centre of
expertise for the art and science of monitoring and analysis of ADRs, and in use of the information analysed for the benefit of patients. National
and regional PvCs should be set up with the approval or involvement of the authority responsible for the regulation of medicines (“regulatory
authority”). The centre may function within the regulatory authority, a hospital, an academic institution or as an independent facility such as a
trust or foundation.

21.What is Spontaneous reporting?

Spontaneous (or voluntary) reporting means that no active measures are taken to look for adverse effects other than the encouragement of health
professionals and others to report safety concerns. Reporting is entirely dependent on the initiative and motivation of the potential reporters.
This is the most common form of pharmacovigilance, sometimes termed passive reporting. In some countries this form of reporting is
mandatory. Clinicians, pharmacists and community members should be trained on how, when, what and where to report.

22.Suitable methods of reporting:

Telephone
Fax
E-mail
Internet

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23. What to report in PV?
Patient details (Name, Address:, Sex, Date of birth, Weight and height).
Patient medical history of significance.
Details of medicines (this may be the brand or generic name, preferably brand) and formulation, mode of administration (e.g. oral, rectal, or
injection), Indication(s) for use, dose).
Reaction details (Date of onset, outcome: resolved, resolving, no change, disabling, worsening, death (with date), or congenital anomaly, Effect of
rechallenge).
Reporter details
Date and place of report

24. What is vigibase?

VigiFlow, a web-based tool which can fulfil the data entry, storage and analysis requirements in the course of pharmacovigilance work. VigiFlow
provides a system for standardized entry of data from reports, as well as search functionalities.

25. What is WHO ART, WHO DD and MedDRA and the difference between them?
The WHO Drug dictionary (DD), MedDRA and the WHO Adverse reactions terminology (WHO-ART).
WHODD= used for drug coding
MedDRA, WHO-ART = coding of events.

26. What is Cemflow?

CemFlow is a tool maintained by the UMC for database management in cohort event monitoring (CEM). It is web based and the fields match the
data elements on the questionnaires. There are screens for patient demographics, treatment initiation, treatment review and assessment of
events. CemFlow as a tool for data entry into an online database maintained by the UMC (Uppsala Monitoring Centre) for CEM. CemFlow
provides for entry of cohort data as well as the events.

27. Seriousness criteria based on intensity?

not severe, mild, moderate, severe.

28. Synonyms for relatedness (causality-related)?

Related: Certain, possible, probable, likely

29. Synonyms for relatedness (causality- unrelated)?

Not related: Unlikely, Unclassified (or conditional), Unassessable.

30. What is Re-challenge?

What happens to the event after restarting of the suspect drug.
+ve: recurrence of the same event
−ve: no recurrence.

31. Odd scenarios in PV?

Pregnancy.
Overdose (>MTD)
Off label use
Medication error
Lack of efficacy.

32. What is Co-morbid conditions?

Patients may be more susceptible to particular ADRs if they also have other health problems, either because of the concomitant condition or from
the interaction of the medicines being used to treat the other condition(s).

33. What is a signal?

Signal is defined as: Reported information on a possible causal relationship between an adverse event and a drug, the relationship being unknown
or incompletely documented previously (WHO).

34. Methods of signal detection?

Methods of signal identification
There are four methods for identifying signals:
1. Clinical assessment of individual events
2. Clinical review of collated events
3. Record linkage
4. Automated signal detection.

35. Full form of PV terms?

ADRs adverse reactions to medicines (adverse drug reactions)
ART antiretroviral therapy
ARV antiretroviral

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36. Outcome of the event
The types of outcome to be recorded are as follows, along with codes that can be used to simplify recording:
R1 resolved;
R2 resolving;
RS resolved with sequelae;
NR not resolved;

37. What is de-challenge?

What happened after the suspect drug withdrawal:
+ve= event resolved
-ve=event was ongoing

38. What is FDA?

=Food and Drug Administration (FDA), USA
This is a useful resource on product information, current issues and regulatory actions.

39. International Society of Pharmacovigilance (ISOP)

This is an important international society. Their web site gives information about meetings and training courses.

40. Definations you should know before applying for PV?

Absolute risk Risk in a population of exposed persons; the probability of an event affecting members of a particular population (e.g. 1 in 1,000).
Absolute risk can be measured over time (incidence) or at a given time (prevalence).

Adverse Event (AE)

Any untoward medical occurrence that may present during treatment with a pharmaceutical product but which does not necessarily have a causal
relationship with this treatment.

Adverse (Drug) Reaction (ADR)

A response which is noxious and unintended, and which occurs at doses normally used in humans for the prophylaxis, diagnosis, or therapy of
disease, or for the modification of physiological function. (WHO, 1972).
“A response to a medicinal product which is noxious and unintended.”

Allopathy
Non-traditional, western scientific therapy, usually using synthesised ingredients, but may also contain a purified active ingredient extracted from
a plant or other natural source, usually in opposition to the disease.

Association
Events associated in time but not necessarily linked as cause and effect.

Attributable risk
Difference between the risk in an exposed population (absolute risk) and the risk in an unexposed population (reference risk). Attributable risk is
the result of an absolute comparison between outcome frequency measurements, such as incidence.

Biological products
Medical products prepared from biological material of human, animal or microbiologic

Causal relationship
A relationship between one phenomenon or event (A) and another (B) in which A precedes and causes

B. In pharmacovigilance; a medicine causing an adverse reaction.

Causality assessment
1. The evaluation of the likelihood that a medicine was the causative agent of an observed
2. adverse reaction. Causality assessment is usually made according established algorithms.

Caveat document
The formal advisory warning accompanying data release from the WHO Global ICSR, Database: it specifies the conditions and reservations
applying to interpretations and use of the data.

Cem-Flow
Software developed by UMC for collection and analysis of data in Cohort Event Monitoring.

Clinical trial
A systematic study on pharmaceutical products in human subjects (including patients and other volunteers) in order to discover or verify the
effects of and/or identify any adverse reaction to investigational products, and/or to study the absorption, distribution, metabolism and excretion
(ADME) of the products with the objective of ascertaining their efficacy and safety.

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Cohort Event Monitoring
Cohort Event Monitoring (CEM) is a prospective, observational study of events that occur during the use of medicines, for intensified follow-up of
selected medicinal products phase. Patients are monitored from the time they begin treatment, and for a defined period of time.

Compliance:
Faithful adherence by the patient to the prescriber’s instructions.

Control group:
The comparison group in drug-trials not being given the studied drug.

Critical terms

Some of the terms in WHO-ART are marked as ‘Critical Terms’. These terms either refer to or might be indicative of serious disease states, and
warrant special attention, because of their possible association with the risk of serious illness which may lead to more decisive action than reports
on other terms.

Data mining:
A general term for computerised extraction of potentially interesting patterns from large data sets often based on statistical algorithms. A related
term with essentially the same meaning is ‘pattern discovery’. In pharmacovigilance, the commonest application of data mining is so called
disproportionality analysis, for example using the Information component (IC).

De-challenge
The withdrawal of a drug from a patient; the point at which the continuity, reduction or disappearance of adverse effects may be observed.

Disproportionality analysis:
Screening of ICSR databases for reporting rates which are higher than expected. For drug- ADR pairs, common measures of disproportionality are
the Proportional Reporting Ratio (PRR), the Reporting Odds Ratio (ROR), The Information Component (IC), and the Empirical Bayes
Geometrical Mean (EBGM). There are also disproportionality measures for drug-drug-ADR triplets, such as Omega (Ω).

41. What is SUSAR:

SUSAR: An unexpected adverse reaction (UAR) is an adverse reaction that is not consistent with the product information in the SPC.
A suspected unexpected serious adverse reaction (SUSAR) is any UAR that at any
dose:
a. Results in death;
b. Is life threatening (i.e. the subject was at risk of death at the time of the event)
c. Refer to an event which hypothetically might have caused death if it were more severe
d. Requires hospitalisation or prolongation of existing hospitalisation;
e. Results in persistent or significant disability or incapacity;
f. Is a congenital anomaly or birth defect.

SUSAR is a serious adverse drug reaction (SAR) that is unexpected or for which the development is uncommon (unexpected issue) observed
during a clinical trial and for which there is a relationship with the experimental drug, whatever the tested drug or its comparator.

42. What is Day zero?

Day zero remain as the day that the first information was received.Or Day zero should be considered the day on which the minimum criteria for a
reportable adverse reaction report becomes available.

43. Medication Errors

Medication errors are mishaps that occur during prescribing, transcribing,dispensing, administering, adherence, or monitoring a drug. Examples
of medication errors include misreading or miswriting a prescription. Medication errors that are stopped before harm can occur are sometimes
called “near misses” or “close calls” or more formally, a potential adverse drug event. Not all prescribing errors lead to adverse outcomes. Some do
not cause harm, while others are caught before harm can occur (“near-misses”).

Medication errors are more common than adverse drug events, but result in harm less than 1% of the time. About 25% of adverse drug events are
due to medication errors.

44. Misuse
This refers to situations where the medicine is intentionally and inappropriately used not in accordance with the authorised PI or the directions
for use on the medicine label.

45. Drug Abuse

This corresponds to the persistent or sporadic, intentional excessive use of a medicine, which is accompanied by harmful physical or
psychological effects.

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46. Beneficial effects
The adverse effect of a drug should not be considered without taking account of its beneficial effects.

47. Pharmacovigilance programme of India (PVPI) was launched in July 2010.

Because of some common issues, Clioquinol-subacute myelo-opticoneuropathy (SMON) in Indians, (Phenylpropanolamine (PPA)-Hemorrhagic
stroke in Indian patients.

48. What is PubMed?

This is a good literature resource. Abstracts are available free.

49. Process in Pharmacovigilance

Collect and record of AEs / ADRs
Causality assessment and analysis of ADRs
Collate and code in database
Compute risk-benefit and suggest regulatory action
Communicate for safe use of drugs among stakeholders

50. Drugs recently banned in India

Rosiglitazone, Sibutramine, Rimonabant, Nimesulide (Under 12 years), Cisapride,

Phenylpropanolamine, Gatifloxacin and Tegaserod.

All The Best

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