Pharmacovigilance
1. 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.
2. 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
3. What is an Adverse Drug Event (ADE)?
Any untoward medical occurrence in a patient or clinical investigation subject
administered a pharmaceutical product which does not necessarily have to have a causal relationship with this treatment
4. 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
5. . 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).
-India: Central Drugs Standard Control Organization (CDSCO)
6. 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;
Part III provides the Guidelines for the electronic exchange of
pharmacovigilance in the EU
Part IV provides Guidelines on pharmacovigilance communication.
7. 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).
8.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?
9.. Name some data elements in ICSR? Individual Case Study Report
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)
What is MedDRA used for?
It is used for registration, documentation and safety monitoring of medical products both before and after a product has been authorised for sale.
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 resulting in 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 drug safety information, maintain current knowledge of global drug safety regulations, summarize 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 of other staff in the department, and take on any other task as assigned by the manager or Medical Director within the capabilities of the Drug Safety Associate.
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.
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
48. What is PubMed?
This is a good literature resource. Abstracts are available free
46. Beneficial effects
The adverse effect of a drug should not be considered without taking into account its beneficial effects.
47. Pharmacovigilance programme of India (PVPI)
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.
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.
38. What is FDA?
=Food and Drug Administration (FDA), USA
This is a useful resource on product information, current issues, and regulatory actions.
15. What are the objectives in Pharmacovigilance?
Understanding the concepts of ADR, Medical Errors, Public Health Significance, Regulatory Interventions, ADR Monitoring schemes.
17. What are the due dates for safety reporting?
A. Safety reporting due dates are 7 days for IND Reporting and 15 days for NDA Reporting
22. Suitable methods of reporting:
Telephone
Fax
E-mail
Internet
24. What is vigibase?
VigiFlow, is 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.
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
37. What is de-challenge?
What happened after the suspect drug withdrawal:
+ve= event resolved
-ve=event was ongoing
36. Outcome of the event
The types of outcomes 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;
39. International Society of Pharmacovigilance (ISOP)
This is an important international society. Their website gives information about meetings and training courses.
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.
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
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.
44. Misuse
This refers to situations where the medicine is intentionally and inappropriately used not in accordance with the authorized 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.
43. Medication Errors
Medication errors are mishaps that occur during prescribing, transcribing, dispensing, administering, adherence, or monitoring of 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
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.
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.
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
14. Role of Drug Safety Associate:
Manage and relay drug 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 of 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
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.