Spontaneous reporting is done.

Spontaneous or voluntary reporting involves a doctor or patient describing his or her own clinical observation of a suspected ADR with a marketed drug.

The collection of spontaneous reports has become the foundation of post-marketing surveillance programs largely because of

the high volume of information they supply, their low maintenance costs their demonstrated usefulness when supervised by experienced evaluators .

A large body of post-thalidomide safety experience suggests that spontaneous reporting programs can contribute to a better understanding of the risk-benefit ratio of a product as it is actually used in medical practice.

Spontaneous reporting can be made to

The regulatory authorities To the pharmaceutical company that markets the product To medical or scientific journals

The pattern of reporting varies considerably between countries

In UK
Doctor report to the Committee on Safety of Medicines (CSM)/ Medicines Control Agency (MCA) using yellow cards

In USA and Germany

About 90% of reports to the regulatory authority are from companies.

Disadvantages
Under-Prescription Inman suggested this was due to seven deadly sins
Complacency (self-satisfaction or false satisfaction with an existing situation, condition, etc.) Fear of litigation (A controversy before a court ) Guilt because the patient may have been harmed by the treatment Ambition to collect and publish a personal series of cases Ignorance of how to report Diffidence about reporting mere suspicions Lethargy

An AE signal is defined as a

product-AE relation

potential

that deserves

further attention. which includes developing more detailed information about an already known productAE relation.

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identify new causal relations. identification of non-causal associations. the clinical spectrum of a drug-AE pair. the patient subtypes and medical circumstances associated with a productinduced adverse reaction. clues to the mechanism of action by which product exposure leads to an adverse reaction factors associated with the initiation of reporting behavior

Spontaneous AE signals are generated when statistical or non-statistical methods are applied to spontaneous AE data. signaling methods are better defined as procedures that are independent of content.

AE signaling methods can be termed as report/case sets of one to thousands the detection of AE signals. An AE signal is defined as a

potential product-AE relation that deserves further attention.

Includes a variety of functions from simple sorting procedures for creating workable subsets of reports complex analyses of case series .

Information sources used for pharmacovigilance Information from many sources is used for pharmacovigilance. These include:

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spontaneous adverse drug reaction (ADR) reporting schemes, for example, the Yellow Card Scheme; clinical and epidemiological studies; worldwide published medical literature; information from pharmaceutical companies; information from worldwide regulatory authorities; and morbidity and mortality databases.

Thalidomide tragedy-1960s resulted in establishment of drug regulatory agencies.

In UK- Committee of Safety of Drugs- Sir Derrik Dunlop- reconstituted to committee for Safety of Medicine (1968). Medicine Control Agencies receives 20,000 reports/year

Advantage
New ADR hypothesis Identifying and characterizing new ADR

The aim of the Yellow Card Scheme is to improve patient safety by finding out as much as possible about adverse reactions by pooling health professionals experience and suspicions. To use this information to Provide early warning of unrecognised ADRs Identify predisposing factors Compare drugs in the same therapeutic class Continuously monitor the safety of all drugs

The MHRA and the Commission on Human Medicines (CHM) run the UK's spontaneous adverse drug reaction reporting scheme - called the Yellow Card Scheme These reports are regularly evaluated with clinical trial data and other medical literature to highlight any safety issues or any previously unk This receives reports of suspected adverse drug reactions (ADRs) from healthcare professionals. More recently the scheme was extended to include direct reporting by patients.nown side effects.

prescription medicines; herbal remedies; and over-the-counter (OTC) medicines.

The MHRA and CHM also have five Yellow Card Centres whose role focuses on follow-up of reports in their areas as this has been shown to improve follow-up rates.
Yellow Card Centre Mersey, Freepost, Liverpool. L3 3AB. Yellow Card Centre Wales, Freepost, Cardiff, CF4 1ZZ. Yellow Card Centre Scotland, 51 Little France Crescent, Old Dalkeith Road, Edinburgh. EH16 4SA. Yellow Card Centre Northern and Yorkshire, Freepost ,Newcastle-upon-Tyne. NE1 1BR. Yellow Card Centre West Midlands, Freepost, Birmingham. B18 7BR.

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As the Yellow Card Scheme has been running for more than 40 years, it has been necessary to make some changes in order to reflect changes in the healthcare system. More recently, patients, parents and care givers (nurses) are also now encouraged to report suspected adverse drug reactions directly to the MHRA through the Yellow Card Scheme.

Acknowledgment and registration Data entry Evaluation of reports Regulatory action

Doctors Dentists Pharmacists Nurses, midwives and health visitors from October 2002

Routine issues The Summary of Product Characteristics (SPC) and patient information leaflets (PILs) are updated appropriately when there are new safety concerns Serious issues Three to four times each year the MHRA publishes the bulletin, 'Current Problems in Pharmacovigilance', which is mailed to all doctors, dentists, pharmacists

Urgent issues Occasionally healthcare professionals must be immediately informed about a safety issue. This may be because of the seriousness of a newly identified ADR, because a drug is being withdrawn on safety grounds, or because a quality defect has occurred.

Urgent safety issues health professionals may receive a letter from the Chairman of the Committee on Safety of Medicines which:
outlines the issue; outlines the action being taken; and provides advice on the implications for patient treatment.

These letters are usually distributed via the MHRA's direct fax system for drug alerts or via the Chief Medical Officer's Public Health Link and are also published on the MHRA website. Alternatively, health professionals may receive a letter from the pharmaceutical company responsible for the medicine.

Reports are received by the Yellow Card Scheme in strict confidence. Information revealing the patients identity is never released without consent. No patient personal information is stored i.e. name or date of birth unless this is a direct report from a patient about their experience. Data is held securely.

A Yellow Card requests an identification number for the patient; for example a practice or hospital number. This enables the patient to be identifiable to the reporter but not to anyone else and allows the reporter to know whom the report is referring to for any potential future correspondence.

Very rarely, if the risks of a medicine are found to outweigh the benefits, it may be necessary to remove the medicine from the market More usually, the risk of a side effect may be avoided or reduced by the following: 1. including warnings in the product information or on the package label; 2. restricting the indications for use of a medicine; and 3. changing the legal status of a medicine, for example, from pharmacy to prescription only.

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Patient Information Leaflets (PILs) and Summaries of Product Characteristics (SPCs) for medicines are updated when new safety issues are identified. For urgent warnings about drug hazards, letters are sent to all doctors and pharmacists by post or electronic cascade. The regular drug safety bulletin, 'Drug Safety Update', produced by the MHRA and CHM aimed at all healthcare professionals. Fact sheets are produced for major safety issues for both healthcare professionals and patients Safety alerts are published on the MHRA website