Sanjeev Miglani MD Sanjeev Miglani MD

COO and Scientific DirectorCOO and Scientific Director

CIDP Biotech IndiaCIDP Biotech India

International Conference and CME workshop on Pharmacovigilance Systems and Rational Use of Drugs: An integrated approach ; 27 Nov 2010

Overview

Importance of Pharmacovigilance

Source of ADRs

Triage

Case Processing

Different PharmacovigilanceSoft Wares

Collection of the information

Processing in a Database

Medical Evaluation, Analysis and Signal Detection

Pharmacovigilance

Reporting

Importance of Safety Monitoring

Capture of Complete safety data

Regulatory agencies becoming proactive

Ethical requirements

Serious consequences due to Non compliance

SOURCE OF REPORT

Spontaneous Reports

Unsolicited communication by a healthcare professional or consumer to a company, regulatory authority or other organization that describes one or more ADRs in a patient who was given one or more medicinal products and that does not derive from a study or any organized data collection scheme.

Literature Each MAH is expected to regularly screen the worldwide

scientific literature by accessing widely used systematic

literature reviews or reference databases.

The frequency of the literature searches should be

according to local requirements

A copy of the article might be requested by the local

regulatory authority to accompany the report.

Solicited Sources

Solicited reports are those derived from organized data collection systems, which include clinical trials, registries, post-approval named patient use programs, other patient support and disease management programs, surveys of patients or healthcare providers, or information gathering on efficacy or patient compliance.

Contractual Agreements

The marketing of many medicines increasingly takes place through contractual agreements between two or more companies, which may market same product in the same or different countries/region.

Arrangements vary considerably with respect to inter-company communication and regulatory responsibilities.

Regulatory Authority Sources

Individual serious unexpected ADRs originating from foreign RAs are subject to expedited reporting to other authorities by each MAH.

Re-submission of serious ADR cases without new information to the originating RA is not usually necessary, unless otherwise specified by local regulation.

Call Centers

A centralized office used for the purpose of receiving and transmitting a large volume of requests by telephone.

They provide service to pharmaceutical companies with a complete post-marketing surveillance solution including adverse event monitoring and reporting; drug information services; and product complaint management.

TRIAGE OF CASES

Once the complaint is received at PV department of a company, it must be properly classified for processing.

The initial triage should be to determine whether the report needs urgent processing in order to be transmitted to the RAs, or business partners.

Experienced and qualified personnel should always supervise triage

Triage should cover, at the least, the following: ADRs PQCs associated with ADRs PQCs Medical Inquiries legal

ADRs can further be triaged using the following criteria:Serious or non seriousExpected or unexpectedCausality (Specially for SAEs from Clinical Trials)

The minimum information required for

reporting purposes is: An identifiable patientthe name of a suspect medicinal productan identifiable reporting source, and, an event or outcome that can be identified as serious and

unexpected and for which, in clinical investigation cases, there is a reasonable suspected causal relationship.

Case Processing

Data entry into safety databaseMedical codingQC reviewMedical review

Data Entry:For user friendliness, the front end of these software are

made in such a way that end user can enter data very easily and more accurately.

These systems generally require additional mandatory fields like date of receipt of ADR, Source Country, type of source.

Once the case with minimum information for reporting is entered, the case is saved

Information can be divided into following fields,

Subject (data related to subject like name or initials, height, weight, gender, age ,pregnancy etc)

Suspect Drug (data relate to suspected medicinal product like name, start date, end date, duration of exposure, formulation, dose and dosage form, indication etc),

Event (which includes fields like, reporter’s verbatim, company’s verbatim, MedDRA terms, event onset date, event end date, etc).

Reporter’s information may include (reporter’s name, contact address, phone number, e-mail id, whether reporter is a Health care professional or not, secondary or tertiary reporter, etc),

Reportability or submission fields may include country where the case is reportable, schedule of reports, including due date of submission, etc)

Narratives

The objective of the narrative is to summarize all relevant clinical and related information

The narrative should serve as a comprehensive, stand-alone “medical story”.

The information should be presented in a logical time sequence; ideally this should be presented in the chronology of the patient’s experience, rather than in the chronology in which the information was received.

MedDRACoding of:

– Adverse events– Medical history– Signs and symptoms– Diagnoses– Physical examination data– Laboratory tests

WHO-DDThe WHO Drug Dictionaries consist of medicinal product

names - both proprietary and nonproprietary - from more than 90 countries.

All drugs in the WHO Drug Dictionary and the WHO Drug Dictionary Enhanced are classified according to the Anatomical Therapeutic Chemical classification – ATC.

FOLLOW-UP INFORMATION All efforts should be made to seek additional information

for good assessment of caseThe priority of cases for follow-up should be as follows:

Serious and unexpected, Serious and expected, and Non-serious and unexpected

In addition to seriousness and expectedness as criteria, cases “of special interest” also deserve extra attention as a high priority

QC Review

After Data entry, a drug safety specialist reviews the data entry against the source documents and reviews the case narrative.

A clear methodology on the quality check should be developed

Follow-up information should be requested when the initial case is incomplete or unclear.

Medical Review

The medical review should generally cover the medical content of the case with particular attention paid to the narrative, the suspect and concomitant drugs (including dosages), the past medical history, and coding.

The review should also include, but is not limited to, the following considerations:

•Is a diagnosis possible? •Have the relevant diagnostic procedures been

performed? •Were alternative causes of the reaction(s)

considered? •What additional information is needed? .

Tracking and Metrics

It is critical that all cases reports be trackedThe tracking of cases should base on the

workflow stepEach drug safety specialist and manager should

be aware of status of all the cases The manager can reallocate cases or other work

to ensure that the time-critical cases are handled appropriately.

Similarly, non expedited cases that need to be completed for aggregate reports should be tracked so that they are completed by the time of data lock.

Line Listings: ExampleMnf Ctrl #

Ctry Srce Sex AgeYr Dose Treatment dates

Onset React ion Outcome Comments

Gastric disorders

CLINI00 IND HCP M 24 50mg 25 to 27-

Aug-2009

25-AUG-2009

Abdominal pain Recovered

Hospitalised.

Hepatic disorders

951114 USA LIT F 41 25mg 26 to 29-August 2009

26-AUG-2009

Elevated LFTs, swollen

abdomen,

Unknown

Abnormal on

ult rasound liver, gallbladder, pancreas.

Vigiflow

Safety data Base is hosted by the Uppsala Monitoring Center

Internationally recognised standards–E2B report format–WHO-ART and ICD or MedDRA–WHO Drug Dictionary

One server installation –maintained in UMC

Oracle's Argus Safety suite

Oracle Argus Affiliate: local affiliates and among partners, lowering risk from unanticipated reporting delays.

Oracle Argus Interchange: Electronic exchangeOracle Argus Reconciliation: SAE reconciliationOracle Argus Dossier: Periodic safety update reportOracle Argus Insight: Multidimensional analysis of

drug safety data. It can generate preformatted filterable safety reports

Oracle Argus Perceptive: an integrated solution for signal management.

Aris G Safety Soft ware SuiteARISg™: Used for the Collection, coding, Assessment

and Reporting of Adverse events dataARISj™: Japanese pharmacovigilance system agXchange ESM™: Electronic exchange agXchange IRT™: Inbound receipt and triage of

ADRsagConnect™: Clinical safety reconciliation system agComposer™:Comprehensive periodic and

aggregate reporting system agSignals™:Advanced signal detection and data

mining system