# Pharmacovigilance ## Clinical Trials # Phases....

2. MAHRASHI DAYANAND UNIVERSITY ROHTAK
DEPARTMENT OF PHARMACEUTICAL SCIENCE
CLINICAL RESEARCH AND PHARMACOVIGILANCE
SPONTANEOUS REPORTING SYSTEM AND REPORTING TO REGULATORY
AUTHORITIES, GUIDELINES FOR ADRS REPORTING
SUBMITTED BY: UNDER THE GUIDANCE OF:
TARANJUM KHAN DR. ANURADHA PANNU
M.PHARMACY IST YEAR ASSISTANT PROFESSOR
ROLL NO: 1803 MDU, ROHTAK

3. OUTLINES
 Introduction of Spontaneous Reporting process.
 Spontaneous Reporting system.
 Spontaneous reporting in UK.
 Yellow Card Scheme
 Drug Analysis Prints
 Drug Safety updates
 Different Areas of Reporting
 Guidelines of ADR Reporting
 References

4. Basic Introduction & Aim
 Spontaneous reporting system (SRS) is a system that collects information about
adverse drug reactions (ADRs). It's a key part of international pharmacovigilance,
which relies on healthcare professionals and sometimes consumers to identify and
report adverse events.
 In a spontaneous reporting system, healthcare professionals voluntarily submit
case reports to national pharmacovigilance centers or health authorities. The
reports can be submitted on paper or electronically.
 AIM: The primary focus of a spontaneous reporting system is to detect serious
unknown adverse drug reactions (ADRs).

5. Spontaneous Reporting System
 The main function of spontaneous reporting systems is to identify
signals and formulate hypotheses. These can lead to further
investigations or regulatory warnings and changes to product
information.
 Passive surveillance system:
 Health professionals are encouraged to report adverse reactions which
they believe to be drug-related directly to:
 the regulatory authority or
 the company marketing the suspected product on a voluntary basis

6. Spontaneous Reporting Process
Data Acquisition
• Data acquisition which
depends largely on the input of
information derived from
reports submitted by the health
professionals who have
encountered what they suspect
is an ADR.
Data Assessment
• Which involves
assessment of the
individual case reports and
assessment of pooled data
obtained from various
sources such as the
international database of
the WHO.
Data Intrruption
• Based on the available
data and the assessments
made, a signal related to
the adverse reaction may
be generated.

7. Spontaneous reporting UK
Lincencing authority: Ministers, including Sect., of state for
health.
Authority's key function: control of medicines by the UK
Medicines and Healthcare Products Regulatory Agency (MHRA)
formed on 1 April 2003 from merger of Medicines Control Agency
(MCA) and Medical Devices Agency (MDA).
Key functions: safety, quality and efficacy of ward public health.

8. Yellow Card Scheme:
 Introduced in 1964 (Sir Derrick Dunlop) after thalidomide tragedy
 Over 600,000 confidential reports have been received in UK
 Doctors, dentists, pharmacists, coroners, nurses, midwifes, health
visitorsNon medical prescribers and now patients
 MHRA can detect duplicate reportsSurvey in 1984: Only 16% of doctors
who were eligible to report suspected ADRs to the Scheme had actually
submitted a Yellow Card between 1972 and 1980.
 Analysis of Yellow Card reports submitted between 1992 and 1995 showed
that around one- third of practising doctors submitted report

9. What Happens to a Yellow Card One’s received ??

11. Information to be included in Yellows Card:
 Suspected Drugs:
 Name of medicine
 Including brand and batch number
 Route of administration & Daily dose
 Date medicine started and stopped if applicable
 Reason why the medication was given
 Multiple drugs can be listed if more than one drug is suspected of causing
the reaction

12. Purpose & Achievement of Yellow Card:

13. Patients & Reporter Detail:
 Sex of the patient
 Age at time of reaction & Weight if known
 Do not need to know name or DOB as this could identify patient and break patient
confidentiality Patients initials and local identification number (hospital or practice
number) which will identify patient to you in the event of future correspondence
 Reporter Detail:
 Must be completed in all cases
 Name and full addressed
 Need to acknowledge receipt of report and follow up further information if
necessary& Profession.

14. How to yellow Card Data Used to Improve Patients
safety
 1. Changes to SPC e.g. restriction in use, special warnings and
precautions
 2. Publication of Drug Safety Update
 3. Issue of 'Dear Healthcare professional' letters
 4. Drug Analysis Prints (DAPs)
 5. Withdrawal of a medicines if patient safety is threatened

15. Drug Safety Update :

16. Drug Analysis Prints (DAP).
 Complete list of all suspected ADRs reported via yellow card
scheme for named suspect drug
 Inclusion of a particular reaction does not necessarily mean it has
been caused by the drug Certain reported reactions are conditions
which occur spontaneously
 Reporting rates are influenced by seriousness of ADR, ease of
recognition, extent of use

18. Evidence Suggesting Under Reporting
 Reporting may vary between different groups of doctors, with hospital doctors reporting less
frequently than general practitioners
 survey in 1984: Only 16% of doctors who were eligible to report suspected ADRs to the Scheme
had actually submitted a Yellow Card between 1972 and 1980.
 More recent figures are more encouraging; an analysis of the reporters of Yellow Cards submitted
between 1992 and 1995 showed that around one-third of practising doctors submitted a report
during this 4- year period
 Since 1964, over 500,000 reports have been received by the MHRA and the CSM.It is voluntary
for health professionals but pharmaceutical companies have legal obligations to report ADRs to the
MHRA.the annual number of reports has risen significantly since the introduction of the Scheme,
with notable increases in reporting in the mid-1970s and again in 1986.

20. Where to Find ADR Information:
Reference Text
1. British National Formulary (BNF)
2. Summary of Product Characteristics
(SPC)
3. Martindale
4. AHFS Drug information
5. Meyler's 'The Side effects of drugs
6. Davies' textbook Adverse Drug
ReactionsJournals
7. Lee's textbook Adverse Drug Reactions
Journal
1. Adverse Drug Reaction
Bulletin
2. Drug Safety
UpdateMedline/Embase/Pha
rmline search
Electronic source
• Micromedex

21. Work Flow of ADR:

22. (INDIA) ADR SYSTEM :
 Indian Pharmacopoeia Commission (IPC), Ghaziabad is functioning as a National
Coordination Centre (NCC) for Pharmacovigilance Programme of India (PvPI).
 150 ADR monitoring centres (AMCs) were established in various medical
institutions/hospitals across India to monitor and collect ADR reports under NCC-PvPI
 What to Report
 PvPI encourages all types of suspected ADRs reporting whether they are known,
unknown, serious, or nonserious, frequent.
 ADRs related with the use of allopathic medicines, vaccines, traditional medicines,
medical devices, contrast media, etc., can be reported.

23. Continue…….
 Where to Report
 All healthcare professionals (clinicians, dentists, pharmacists, nurses) and
patient/consumers can report ADRs to NCC or AMCs
 The pharmaceutical companies can also send individual case safety reports for their
product to NCC
 How to Report
 Suspected ADR reporting forms for healthcare professionals and consumers are
available on the website of IPC to report ADR.
 To remove language barrier in ADR reporting, the consumer reporting form are made
available in 10 vernacular languages (Hindi, Tamil, Telugu, Kannada, Bengali,
Gujarati, Assamese, Marathi, Oriya, and Malayalam)

24. ADR Reporting Process:
 All the ADR reports from various sources are
collected at ADR Monitering
Centre(AMC).PV staff at AMC study, validate
and prioritize the report and perform
provisional casuality assessment.The assessed
ADR forms are then directed towards
authorized co-ordinating centres for further
proceedings.

25. Continue ….
 The AMCs staff maintains a record of all activities of centre and carries out ADR
monitering of drugs.The coordinating centres then conduct final casuality
evaluation and feed the reports in PV database.
 These centres also prepare an aggregate report of ADRs collected at said time and
send it to WHO- UMC.The finding of PV analysis is then implemented and
integrated into general population health program.
 Fianally, the integrated ADR data is transfered through Vigi-Flow database to
UMC database.
 UMC team analyses the submitted data and detects drug- ADR relationship called
as signal, is very important aspect and communicate with NCC-PvPI via CDSCO
to stop marketing or use of drug in India.

26. Example:

27. Procedure & Guidelines for Reporting
 How do Health Care Professionals Identify ADRs
 1. Obtain proper History and to do Examination
 2.Where possible check the known pharmacology of medicine
 What to Report
 ADRs in Children & Elderly
 ADR report on lack of Efficacy
 Medication Errors & Delayed Medicine
 Interaction & Errors
 Teratogonicity & congenital anomalies
 Serious ADRs
 Reports Relating to the Pregnancy & Breastfeeding

28. Continue
Whom to Report.
• ADR Monitoring cell
• Regulartory Authorities (
DCGI & USFDA)
• To the pharmaceutical
company that markets the
product
• To medical or scientific Journal
• How to Report:
• Fill up ADR Form & report the
Why should Report
• Family physicians
• Medical Specialist
• Dentist
• Pharmacists
• Nurses
• Patients
How to report
• Identify New causal Relations.
• Clinical spectrum of Of a Drug
A-E pair.
• The patient subtype and medical
circumstances With a product
induce Adverse Drug rxn.
• Clues to the Mechanism of action
by which product exposure
Leads to an Adverse Drug
reactions.

29. What Happens in the ADR Form & what to
Report

31. References
 Kalaiselvan V, Mishra P, Singh GN. Helpline facility to assist reporting of adverse drug
reactions in India. WHO South East Asia J Public Health. 2014;3:194.
 Kalaiselvan V, Prasad T, Bisht A, Singh S, Singh GN. Adverse drug reactions reporting
culture in pharmacovigilance programme of India. Indian J Med Res. 2014;140:563-4.
 Vivekananda K, Rishi K, Prasad T, Arunabh T, Singh GN. Status of documentation
grading and completeness score for Indian individual case safety reports. Indian J
Pharmacology.
 World Health Organization The importance of pharmacovigilance. Geneva:: World
Health Organization; 2002. [Google Scholar]
 Avery AJ. Anderson C. Bond C, et al. Evaluation of patient reporting of adverse drug
reactions to the UK ‘Yellow Card Scheme’: literature review, descriptive and
qualitative analyses, and questionnaire surveys. Health Technol Assess. 2011;15:1–
234. iii–iv. [PubMed] [Google Scholar]