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Overview of Pharmacovigilence

BySUNILBOREDDY

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Introduction Definitions: Drug, PV, AE Drug Development Adverse Event Need for PV-Clinical Trails and Post Marketing PV in countries Reporting Benefits- Public and drug manufacturer Rationale Recall

Day 1 Overview : POP Quiz1. Name the drug regulatory body which governs the approval process in India?

CDSCO (central drugs standards and control organization)

2. Which Clinical Trial phase involves giving drug to large group 100-300 people?

PHASE II

3. Which Clinical Trial Phase takes about 3 years to complete?

PHASE III

4. NDA stands for?

New Drug Application

5. What are the 4 stages of drug development process?

Pre-clinical, Clinical, NDA Review, Post-marketing3

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Introduction• Early 20th century there were no controls over the

drug development process.• Claims over treating diseases and uncontrolled

marketing.• Safety or effectiveness of the drug- NOT a

concern for government.• 1883 Dr. Harvey Wiley initiated the campaign for

Federal law for Food and Drugs Act that was finally passed in 1906.

• The law was further tightened following incidents such as poisoning of children by Sulphanilamide and the Thalidomide tragedy.

• 1938 Federal Food, Drug, and Cosmetic Act.

Drug

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Substance or mixture of substances used for diagnosis, treatment, mitigation or prevention of disease or disorders.Used for restoring correcting or modifying organic functions in human beings or animals.

Drug development

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Preclinical Testing IND Application

Clinical Testing – Phase IClinical Testing – Phase II

Clinical Testing – Phase IIINew Drug

ApplicationClinical Testing–

Phase IVIB,ICF, AE, Placebo, Blinding, randomized, Serious, Concomitant medication, Causality,

IB- comprehensive document summarizing information about an investigational product obtained during a drug trial.

critical importance throughout the drug development process and is updated with new information as it becomes available.

The purpose of the IB is to compile data relevant to studies of the IP in human subjects gathered during preclinical and other clinical trials.

An IB is intended to provide the investigator with insights necessary for management of study conduct and study subjects throughout a clinical trial. An IB may introduce key aspects and safety measures of a clinical trial protocol, such as:Dose (of the study drug) Frequency of dosing interval Methods of administration Safety monitoring procedures 7

An IB contains a "Summary of Data and Guidance for the Investigator" section, of which the overall aim is to "provide the investigator with a clear understanding of the possible risks and adverse reactions, and of the specific tests, observations, and precautions that may be needed for a clinical trial.

This understanding should be based on the available physical, chemical, pharmaceutical, pharmacological, toxicological, and clinical information on the IP.

Guidance should also be provided to the clinical investigator on the recognition and treatment of possible overdose and adverse drug reactions that is based on previous human experience and on the pharmacology of the investigational product".8

•ICF- subject voluntarily confirms to participate, made aware of all aspects•Placebo- A substance containing no medication, given to reinforce a patient's expectation to get well (an inactive substance or preparation used as a control to determine the effectiveness of a medicinal drug) GUIDELINES (declaration of helsinki)•Blinding/Masking- one or more parties kept unaware of the treatment assignment•-Single blinding subjects unaware•-double blinding subjects, investigators, monitor, data analysts are also unaware •Randomized- subjects assigned randomly to treatment or control ( chance to reduce bias) •Serious- death, LT, hospitalization, disability, birth defect•Concomitant medication- medications used by patients in a clinical trial, other than the investigational drug. ( also to treat AE)investigational drug.•Causality- that AE was due to the medicine in question

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Adverse event

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Any unfavorable and unintended sign, symptom or a disease temporarily associated with the use of medicinal product (drug), whether or not considered related to the medicinal product.

can be lab finding too or symptom or disease temporally associated with use of IP, whether or not related to the IP

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Need of pharmacovigilanceThere is a need to monitor the

effects of drugs during the clinical trials and after its launch in a market.

Because adverse events can even happen during the clinical trials and event after its launch market.

pharmakon-a drug or medicinevigilans-watchful or careful

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World health organization (WHO, 2004) defines “pharmacovigilance” as the science and activities relating to the detection, assessment, understanding, and prevention of adverse drug reactions (ADRs), or any other medicine-related problems.

Safety monitoring and evaluation throughout whole life-cycle of a product

Encompasses non-clinical, clinical, post-marketing safety data

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Day:2 Overview: POP QUIZ!

1.When was the Food drug and cosmetic Act passed? 1938

2. When can a case be called Serious?When the outcome of the event is death, LT, hospitalization, disability, birth defect.

3. In which phase is the likelihood of an adverse event maximum of all the 4 phases?Trick question!!! All phases of preclinical and clinical.

4. What does IB stand for?Investigator’s Brochure.

5. What are the uses of Thalidomide?Initially discovered as an painkiller on soldiers, later used on pregnant women for its antiemetic use. Also treats leprosy- but banned now.Anti cancer property exploited by Celgene to treat multiple myeloma marketed as lenalidomide (less sideeffects)

Why pharmacovigilance in clinical trials

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After the completing preclinical studies in animals, first time trial drug will be administered to the human.

At this time the drug will act in different way to the human body.

Chances of adverse will also persist.

Pharmacovigilance in post marketing – Why?

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At the time of approval, clinical trial data are available on limited numbers of patients treated for relatively short periods

Once a product is marketed, large numbers of patients may be exposed, including: Patients with co-morbid illnesses Patients using concomitant medications Patients with chronic exposureGenetic diversity in large population

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The evaluation of risk must be conducted in the context of the

patient benefit derived from treatment, the severity of the condition being

treated, and other objective andsubjective factors (such as the patient’s

values).

Pharmacovigilance – Why?

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After marketing, new safety information may become available: Through use of the product domestically or in

other countries Through use of other drugs in the same class From preclinical studies From pharmacologic studies From clinical trials

Importance of Pharmacovigilance in every country

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There are differences among countries ( and even within countries ) in the occurrence of ADRs (Adverse drug reactions) and other drug related problems

Differences in diseases Prescribing practices Genetics Diet Traditions/lifestyle of people Drug manufacturing processes Drug distribution The use of drugs ( dose, indications and availability)

Who reports about adverse events in Clinical Trials?

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Who reports about adverse events in clinical Trials

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Who reports in post marketing adverse events

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SPONTANEOUS REPORTING

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Spontaneous reporting of suspected adversedrug effects is central to pharmacovigilance—which is the systematic search for signals of drugtoxicity. When such a signal is detected it has to beverified, explored, and understood—realizing thatthe drug may be acceptably safe if used byindividuals who are not at especially high risk byvirtue of genetic constitution, metabolism, or othercharacteristics that could alter individual risk.

Partners in Pharmacovigilance

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Government Pharmaceutical Industry Hospitals and academia Medical and pharmaceutical associations medicines information centers Health professionals Patients Consumers The media?? World Health Organization

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Each of the stakeholders—the patient, physician, pharmaceutical company, academic investigator, government—may have a different perspective on the same set of evidence.

For example,• A patient may be willing to accept a high risk of side-effects for

benefits of the treatment for a condition that might be considered trivial by others.

• A regulatory agency may consider the burden of the same side effects to be too high, given their view of the risk–benefit equation.

• A governmental or third-party payer might see the issue from an even different perspective, since a payer may not wish to bear the cost of the treatment or the cost of treating an adverse event.

• It is not surprising that each group may take a different view of the same evidence.

• These pressures may lead to early decisions based on incomplete scientific data.

What is the role of pharmacovigilance?

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The goal of pharmacovigilance is to:Monitor the quality of drugsIdentify the health risks involved in the

administration of certain drugsPrevent harm to patientsResearch the efficacy of drugs

How does pharmacovigilance help the public?

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Pharmacovigilance helps save thousands of lives each year. By monitoring the adverse effects of drugs right from the lab to the pharmacy and then on for many years, pharmacovigilance keeps track of any drastic effects of drugs. This way, it prevents harm to patients using those drugs.

How does pharmacovigilance help drug manufacturers?

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Pharmaceutical companies spend millions of dollars and a considerably long-time in developing new drugs. They again spend a lot of money in conducting clinical trials before the drugs are approved and launched in the market. But after all this, if there are adverse effects to the drugs, the company again loses millions of dollars in sales and litigations.

Furthermore, the reputation of the company is also severely damaged. Pharmacovigilance monitors the development of the drug across various stages and assesses its effectiveness after its launch for many years. This way it may reduce the adverse risk from drugs, thereby aiding the drug manufacturers.

The Need

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Regulatory agencies are increasingly proactive in seeking out potential safety issues with marketed drugs - you must be ready to respond quickly

Political and social pressures have increased along with faster communication channels

Failure to practice pharmacovigilance can lead to the suspension or withdrawal of license

Rationale for pharmacovigilance

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Prevents DisastersBuilds up customer confidenceEnsures Compliance and retentionBuilds brand image

Rationale for pharmacovigilance

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What to report? ADR associated vaccines, diagnostics,

drugs used in traditional medicine, herbal remedies, cosmetics, medical devices and equipment

lack of efficacy and suspected pharmaceutical defects

overdose (because may cast doubt on safety of a drug)

Rationale for pharmacovigilance

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What to report? Every single problem related to the use of a

drug, because probably nobody else is collecting such information!

NOTE: When in doubt- Always report!!

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