ADR Monitoring

8/3/2019 ADR Monitoring

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R&D


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R&D

Adverse Drug Reaction(s)

Adverse Event -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.Adverse Drug ReactionsAre events, thought to be a

response of which is both due to the drug and

considered noxious and un intended.


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R&D

SAE

Serious Adverse Event or reaction - is any untoward

medical occurrence that at any dose: Results in death,

Is life threatening,

Requires inpatient hospitalization or prolongation ofexisting hospitalization.

Results in persistent or significant

disability/incapacity.

Results in a congenital anomaly/birth defect

Results in other medically important conditions


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R&D

ADRs are always under reported

ADRs are the 4th-6th largest cause formortality

ADRs account for approximately 10% ofhospital admissions

ADRs increase the length of hospital stayand medical costs

15-20% of hospital budget may be spentdealing with drug complications

Incidence of ADRs


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R&D

Possible Causes of Adverse Reactions

Intrinsic factors of the drug

Pharmacological Idiosyncratic

Carcinogenicity, Mutagenicity

Teratogenicity

Extrinsic factors

Adulterants

Contamination

Underlying medical conditions Interactions

Wrong usage


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R&D

HOW KNOWLEDGE ABOUT ADRs IS CREATED

Animal experiments

Clinical trials

Epidemiological

methods

Observational studies

Case reports

Case series

Post-Marketing

Surveillance (PMS)

Prescription event

monitoring

Cohort studies Intensive hospital

monitoring

Case-control studies

Record-linkage

Meta-analysis


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Limitations of Clinical Trials

Too few - Normally < than 1500 patients

Too simple - Use patients without

complications, other medical

conditions

Too narrow - Limited indications

Too brief - Limited time

Too median - Very old/very young patients,pregnant women not included


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Identify the suspected drug Identify factors that contributed to the

occurrence of the adverse reaction

such as:

Multiple drug therapy,

Drug-drug interactions

Drug-herbal interactions

Drugfood interactions Excipients, colouring agents

Aim of Surveillance of Drug Related Adverse Reactions


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Increase information on use in at-risk population

Identify unlabeled, rare, delayed adverse reactions Identify abuse potential

Follow-up cases where drugs prescribed intentionally

during pregnancy

Monitor outcome of pregnancy

Effect of drug to the foetus/baby

MAKE CHANGES TO PRODUCT INFORMATION

BASED ON NEW FINDINGS

Aim of Surveillance of Drug Related Adverse Reactions


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R&D

How to Recognize ADRs

Since ADRs may act through the same

physiological and pathological pathways asdifferent disease, they are difficult and

sometimes impossible to distinguish


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R&D

Drug administered

Pt develops a new condition/symptoms

Drug suspected?

Yes

Check literature

Documented ? (for the productor similar class of products)

Yes

Highly suggestive of ADR


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R&D

Not documented in literature

Drug continued Drug discontinued

Worsening ofsymptoms Symptoms improve(+ve dechallenge)

Drug restarted

Symptoms recur(+ve rechallenge)

Any other possible causes? Concomitant therapy Underlyingconditions

I t it f E t


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Intensity of Events

Mild events: Mild events are those, which are easily

tolerated.

Moderate events: Moderate events are those, which

cause sufficient discomfort to the

subject which interferes with dailyactivity and/or require a simple dose

of medication, e.g. analgesics or

antiemetics.

Severe events: Severe events are those, which

incapacitate or prevent usual activity or

require complex medication or

hospitalisation.


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R&D

Severe vs Serious

The term "severe" is often used to describe the intensity

(severity) of a specific event (as in mild, moderate, orsevere myocardial infarction); the event itself, however,

may be of relatively minor medical significance (such as

severe headache).

This is not the same as "serious," which is based onpatient/event outcome or action criteria usually

associated with events that pose a threat to a patient's life

or functioning.

Seriousness (not severity) serves as a guide for defining

regulatory reporting obligations.

C l R l ti hi


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R&D

Causal RelationshipAdverse events can be classified as :

HIGHLY PROBABLE: The event follows a reasonable temporal sequence

from administration of the drug and is confirmed by positive dechallenge andpositive rechallenge.

PROBABLE: The event follows a reasonable temporal sequence from

administration of the drug is confirmed by dechallenge and is not reasonably

explained by the known characterization of patients clinical state.

POSSIBLE: The event follows a reasonable temporal sequence from

administration of the drug and follows a known response pattern to the

suspected drug but could have been produced by the patients clinical state or

other modes of therapy administered to the patient.

REMOTE: Any event that does not meet the above criteria especially if the

event has no temporal association with use of the drug.


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R&D

Product Safety Update Report (PSUR)

The Periodic Safety Update Report (PSUR) is required as part of the

Post Marketing Drug Risk Assessment (PMDRA) program.

The PSUR report is evolving with the ICH initiatives and the

February 2004 FDA Guidance for industry.

The PSUR software is designed to track the submission of Periodic

Safety Update Reports by marketed product and country.

The PSUR is a practical mechanism for summarizing interval safetydata covering short periods of time and for conducting and overall

safety evaluation.


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R&D

Product Safety Update Report (PSUR) PSUR tracks basic information such as International Birth Date (IBD),

Product license number and renewal date, and the date range of the

report.

Information on all indications, dosage forms, and regimens for the

active substance can also be tracked as well as the affiliate requesting

the report. PSUR tracks the initiation date for requests for information and thereceipt of that information from the various corporate departments that

contribute to the PSUR report.

Besides the dates, provision is made to link the various documents andcomponents to the PSUR tracking records for immediate retrieval of

that report component.


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R&D

AE Reporting Form

Documents

ADR Monitoring