Pharmacovigilance Introduction

Pharmacovigilance

Definition of pharmacovigilance

The science and activities relating to the detection, assessment, understanding and prevention of adverse effects or any other drug-related problem.

Pharmaco = medicineVigilare = to watch

alert watchfulnessforbearance of sleep; wakefulnesswatchfulness in respect of danger; care;

caution; circumspectionthe process of paying close and continuous

attention

Place where pharmacovigilance is used

Need of pharmacovigilance in society

1.To prevent the deaths by using medicines due to adverse drug reactions.

2.To monitor the clinical trials data whether the drug is safe or nor.

3.To determine any adverse drug reaction of particular drug through the world.

4.Safety data of drugs used in clinical trails5. Promoting rational use of medicines and

adherence.

6. Ensuring public confidence.

The scope of pharmacovigilance

Improve patient care and safety in relation to the use of medicines, and all medical and paramedical interventions,

Improve public health and safety in relation to the use of medicines,

Contribute to the assessment of benefit, harm, effectiveness and risk of medicines, encouraging their safe, rational and more effective (including cost-effective) use, and

Promote understanding, education and clinical training in pharmacovigilance and its effective communication to the public.

Opportunities in pharmacovigilance

1.Ther are many companies providing jobs for pharmacovigilance graduates (cognizant, oracle, mahindra sathyam...)

2.Any science graduate, Pharma graduate and Medical graduate is eligible to do study pharmacovigilance .

3.There are used in management of clinical trails data.

4.Many companies are coming into this field (Pharma, CRO, IT, BPO and KPO orgs).

What is an ADR "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." WHO).

A response to a drug which is noxious and unintended, and which occurs at doses normally used… for the prophylaxis, diagnosis or therapy of disease, or for the modification of physiological function.

DefinationsExpected ADR : An ADR to a drug that has

been previously observed and documented, if the ADR is already listed in the official prescribing information, it is an expected ADR

Unexpected ADR : the nature or severity of which is not consistent with the applicable product information.

Major Aims Of Pharmacovigilance

Early detection of unknown reactions & interactions

Detection of increases in frequency of known ADR

Identification of risk factors & Quantifying risks

Preventing drug induced illness

Rational & safe use of medicines

Major Aims Of Pharmacovigilance

Assessment and communication of benefits /risks of drugs

Educating and informing patients

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PharmacovigilancePharmacovigilance

Investigational products Marketed Products

Why pharmacovigilance?Humanitarian concernsEconomical concerns

check if drugs on the market fulfill their intended role in society i.e. if resources spent on drugs produce optimal results in terms ofalleviating human sufferingreduce disease related economical lossProtection of rights and well being of research

subjectsConduct an ongoing assessments of risks vs benefits

Clinical DevelopmentPhases of Clinical DevelopmentPhase IPhase IIPhase IIIPhase IVAll these phases focus on monitoring the

efficacy and the safety of the investigational product and most of these phases last for 2-3 yrs

Limitations of premarketing clinical trialsShort duration : Effects that develop with

chronic use or those that have a long latency period are difficult to detect in preclinical trials

Relatively small number of patients exposed to the drug

Rare ADR are difficult detect in these trials

Limitations of clinical trials continued….Narrow populationThose trials where efficacy is studied

don’t cover actual evolving usePremarketing trials generally don’t

include special groups (eg children, elderly, coexisting disease)

Not always representative of the population that may be exposed to the drug after approval.

Required sample size for detecting a rare adverse drug reaction

Incidence Incidence of ADRof ADR

Number of patients to be observed Number of patients to be observed in order to detect 1,2 or 3 cases of in order to detect 1,2 or 3 cases of ADRADR

1 2 31 2 3

1 in 1001 in 100

1 in 2001 in 200

1 in 1,0001 in 1,000

1 in 2,0001 in 2,000

1 in 10,0001 in 10,000

300300

600600

3,6003,600

6,0006,000

30,00030,000

480480

960960

4,8004,800

9,6009,600

48,00048,000

650650

1,3001,300

6,5006,500

13,00013,000

65,00065,000

Some of the drugs withdrwn post marketing

Drug Drug Date Date approved approved

Date Date withdrawnwithdrawn

Reason for Reason for withdrawlwithdrawl

Fenfuramine Fenfuramine 19731973 19971997 Valvular Valvular heart heart deffectdeffect

Bromfenac Bromfenac 19971997 19981998 Liver Liver failurefailure

MibafradilMibafradil 19971997 19981998 Interaction Interaction with other with other drugsdrugs

Minimum reportable information for ADR’An identifiable patientAn identifiable reporterA suspect productAn adverse event.

Safety data management becomes an important part of pharmacovigilance.

How can data help a product/patient

Defend a product from false safety claims Influence labelAllow practitioners to feel more comfortable

using a drug Enables better decision making around risk

management

What is the end goalThe data helps in detecting the signal –

something that draws attentionPattern of the ADR’s Trend How frequently is the signal or pattern

observed What is the severity.

US FDA definition of signalsNew unlabeled event, especially if seriousAn apparent increase in the severity of a

labeled eventNew drug interactionMore than a small number of serious events

thought to be extremely rare.Identification of previously unrecognized at risk

populationProduct confusionMisuseConcerns that risk management plan is

inadequateOther

What is the worst that can happen if reportedIf the drug is blatantly unsafe and the

risk/benefit ratio is not favorable its always better to withdraw that drug from the market ( this will not happen unless it really should happen

Label changeRegulatory agencies may request

additional information ( more studies, risk management program etc.)

There are other ways to gather additional safety information Epidemiology studiesRegistriesSurveys

Pharmacovigilance reportingExpedited reportingPeriodic safety update reports Both these can be from the following sourceSpontaneous reports, clinical trial reports,

literature reports, registries, regulatory authorities, PMSS

The pharmacovigilance process

Case reports

Case database

Signal detection

Signal analysis

Action

Follow up

Communication

Reporting processAll serious adverse events should be

reported immediately to the sponsor/ regulatory

For reported deaths, the investigator should supply the sponsor IRB/IEC with any additional requested information( eg Autopsy report, terminal medical report)

Notify IRBS and independent EC’s of all serious adverse events

What to report (both Serious and non serious) • All adverse events suspected to have been caused by

new drugs and ‘drugs of current interest‘• If drug is ineffective  • All suspected drug interactions• Reactions to any other drugs which are suspected of significantly affecting a patient's management, including reactions suspected of causing:

• Death • Life-threatening (real risk of dying)• Hospitalization (initial or prolonged) • Disability (significant, persistent or permanent)• Congenital anomaly • Required intervention to prevent permanent impairment or damage.

Pharmacovigilance in practise. Continued……Data entered in the databaseAssessment of the event (expected or

unexpected).Medical confirmation of the event.Expedited reporting of the event.Source country where the event occurred.Submission to regulatory authorities.

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