Introduction and history of pharmacovigilance

Presented By: Dr. Bhargav M.Purohit Associate Professor Department of Pharmacology Government Medical College Bhavnagar. 364001 purohitbhargav@rediffmail.com

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Dept. of Pharmacology, Govt. Medical College, Bhavnagar.

 To undergo treatment you have to be very healthy, because apart from your sickness you have to withstand the medicine.- Moliere

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Dept. of Pharmacology, Govt. Medical College, Bhavnagar.

 Relevant terms

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Dept. of Pharmacology, Govt. Medical College, Bhavnagar.

Pharmacovigilance
Science and activities relating to the detection, assessment, understanding and prevention of adverse effects or any other drug related problem.[WHO] pharmakon (Greek for drug) and vigilare (Latin for to keep watch).

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Dept. of Pharmacology, Govt. Medical College, Bhavnagar.

Adverse drug reaction(ADR)

Response to a drug,that is noxious or unintended,and that occurs at the doses,used in man for prophylaxis, diagnosis or therapy of the disease or for modification of immune function. [WHO]

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Dept. of Pharmacology, Govt. Medical College, Bhavnagar.

To be precise Harmful effects of drugs seen at usual doses. So.... Poisoning is not included in ADR. Therapeutic failure is not included in ADR Prescription errors are not included in ADR.

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Dept. of Pharmacology, Govt. Medical College, Bhavnagar.

Serious ADR
Those which Result in death Are life threatening Require inpatient hospitalization or prolongation of existing hospitalization Result in persistent or significant disability/incapacity or Produce a congenital anomaly/birth defect Is an important medical event or reaction, that may jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the outcomes listed above.
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Dechallenge
Stopping of the drug following ADR. Positive dechallenge: when an adverse event abates or resolves completely following the drug's discontinuation.

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Dept. of Pharmacology, Govt. Medical College, Bhavnagar.

Rechallenge
Restarting medication following cessation of ADR. Positive rechallenge:when the adverse event re-occurs after the drug is restarted.

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Dept. of Pharmacology, Govt. Medical College, Bhavnagar.

Signal
Reported information on a possible causal relationship between an adverse event and a drug, the relationship being unknown or incompletely documented previously.[WHO]

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Dept. of Pharmacology, Govt. Medical College, Bhavnagar.

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Why we encounter so many ADRs????

Formerly when religion was strong and science was weak at that time men mistook magic as medicine. Now science is strong and religion is weak and men mistake medicine as magic -Thomas szasz, the second sin, 1973

.Perception of medicine as magic is precisely the reason we have so many ADRs.

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 History of Pharmacovigilance

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Dept. of Pharmacology, Govt. Medical College, Bhavnagar.

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Before 18th century

In 1780 BC Babylonian Code of Hammurabi states
If a physician make a large incision with open knife, and kill him, or open a tumor with the operating knife, and cut out the eye, his hands shall be cut off.

In 10th century Salerno Medical School was empowered to punish for adulterated drugs.
Whosoever shall have or sell any poison or noxious drug not useful or necessary to his art, let him hanged.

In 13th century the Oath of Apothecaries(Switzerland) states..

Drugs should be of such good quality and of such usefulness that he knows, upon his oath, that it will be good and useful for the confection what the physician is making.

In 1599 King James VI issued a charter to supervise approval of sales of drugs in Glasgow.
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In 18th century.
William Withering (1785) : ADRs seen with digitalis obtained from foxglove. Wouter van Doeveren ( 1789) : Hazards of blood letting and perspiration inducing drugs. Detriments caused by empirical therapy. HgCl2 used for yellow fever produced damage to various oral structures like teeth, mucous membrane, mandible etc. Oliver Wendall Holmes (1861) famously stated
If whole Materia Medica as it is used now would be sunk to the bottom of the sea, it would all the better for mankind and all the worse for the fishes.

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Dept. of Pharmacology, Govt. Medical College, Bhavnagar.

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In 19th century
1808 :First organized Pharmacovigilance activity for cowpox vaccine was carried out in Netherland. 1848 : adulterated quinine imported for US army prompted to pass a statute to control the quality of drugs marketed. Safety of chloroform anesthesia : Following a death by chloroform Glasgow Committee was recruited by BMA in 1880 which stated safety of ether over chloroform. In 1888 First Hyderabad Chloroform Commission : chloroform can be a safe anesthesia if respiration in carefully monitored Second Hyderabad Chloroform Commission : confirmed the findings
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 1906 : FDA was established and Pharmacopoeias were published. This century witnessed two drug tragedies. Sulfanilamide disaster [1937] :
Sulfanilamide elixir with ethylene glycol by Harold Watkins. Death of 105 patient + chemist 1938 Food, Drug, and Cosmetic Act, which increased FDA's authority to regulate drugs. Safety testing + effective labelling.

In 20th century

Thalidomide disaster [1961]:

Used for morning sickness Between late 1950s to early 1960s 10000-20000 children affected. Adverse effects :phocomelia, dysmelia, amelia, bone hypo plasticity, and other congenital defects affecting the ear, heart, or internal organs.
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 Digitalis tragedy [1969]: Due to production error high dose of digitalis was given claiming 19 lives in Veenendal. Blood dyscrasias registry was set up by Council on Drugs of the AMA[1950] after reports of aplastic anemia because of chloramphenicol.

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Dept. of Pharmacology, Govt. Medical College, Bhavnagar.

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Drug Tegaserod Phenformin Terfenadine Cisapride Rofecoxib Rimonabant Phenylproponalamine Pioglitazone Nimesulide Pediatric formulations

Cause of withdrawal MI and stroke Lactic acidosis Arrhythmias Arrhythmias MI Severe depression and suicide Stroke MI and Death Hepatotoxicity

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Dept. of Pharmacology, Govt. Medical College, Bhavnagar.

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How ADRs harm patient ?

Physical harm Psychological trauma May increase hospitalization duration Increase the need of more and more drugs Raise the cost of therapy

..Therapeutic effects and adverse drug reactions are two sides of the same coin
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Scope of pharmacovigilance
It includes . Modern drugs Herbals Traditional and complementary medicines Blood products Biologicals Medical devices Vaccines Many relevant fields are Substandard medicines Medication errors Lack of efficacy reports Off label use of drugs Acute and chronic poisoning Assessment of drug related mortality Abuse and misuse of drugs D/I with other chemicals and food

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Dept. of Pharmacology, Govt. Medical College, Bhavnagar.

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Aims of Pharmacovigilance..
WHO bulletin 2002 states following aims : 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 risks of medicine, encouraging their safe, rational and more effective (including cost effective) use. Promote understanding, education and clinical training in Pharmacovigilance and its effective communication to the public.
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Why ADR monitoring and reporting is necessary ?

Unreliability of preclinical data Changing pharmaceutical marketing strategy. Changing physician and patient preferences Easy accessibility. You may be the First one.. Try to report ALL the adverse events. It can be a suspected/confirmed ADR. May be it will help picking up adverse reaction at an early stage and warning may be issued. May be timely detection prevent a catastrophic drug tragedy because of you.
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How to do ADR reporting ?

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How to do assessment of ADR?

By Naranjos scale. By WHO-UMC scale.

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Dept. of Pharmacology, Govt. Medical College, Bhavnagar.

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How to check preventability of ADR ??

Modified schumock and thronton preventability scale

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Dept. of Pharmacology, Govt. Medical College, Bhavnagar.

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How to check severity of ADR?

Modified Hartwig and Siegel criteria 1992.

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Dept. of Pharmacology, Govt. Medical College, Bhavnagar.

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Knowledge Obseration

Reporting

Success of Pharmacovigilance
Dept. of Pharmacology, Govt. Medical College, Bhavnagar.

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FAQs

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Which information is mandatory ?

For an ADR form to be credible, 4 details are needed :
1. 2. 3. 4. An identifiable patient An identifiable reporter A suspect drug An adverse event

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Dept. of Pharmacology, Govt. Medical College, Bhavnagar.

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What should I report ?

EVERYTHING noxious/unintended/unintentional. May or may not be related to drug. ADRs not because of only drugs because of devices as well.

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Dept. of Pharmacology, Govt. Medical College, Bhavnagar.

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Can I report common ADRs?

Yes It can be as common as .. Aspirin induced gastritis Ampicillin induced diarrhoea Chloroquine induced nausea,vomiting etc.

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Dept. of Pharmacology, Govt. Medical College, Bhavnagar.

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What about patients confidentiality ?

The patients identity is held in strict confidence and protected to the fullest extent..

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Dept. of Pharmacology, Govt. Medical College, Bhavnagar.

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What about MY confidentiality?

It is held in strict confidence. What ever is written in the form will NOT be disclosed any where. Programme staff is not expected to and will not disclose the reporters identity in response from the public or authority.

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Dept. of Pharmacology, Govt. Medical College, Bhavnagar.

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Can reporting an ADR go against me?

Absolutely Not . Scientific fraternity is Indebted to you.

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Dept. of Pharmacology, Govt. Medical College, Bhavnagar.

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To sum up
ADR reporting is service to the medical fraternity and patients Anything gone wrong due to or not due to drug should be reported Doctor and patients confidentiality is strictly preserved. Reporting ADR can not and will not go against you

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Dept. of Pharmacology, Govt. Medical College, Bhavnagar.

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What these kind of CMEs do ?

They highlight What to report ? Why to report ? How to report ? Whom to report ? What happens to reports generated ? They bring healthcare professionals together and encourage collaboration between them. Sometimes they give sleepless nights to last minute speakers

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Dept. of Pharmacology, Govt. Medical College, Bhavnagar.

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Thank You

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Dept. of Pharmacology, Govt. Medical College, Bhavnagar.

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