Introduction to Pharmacovigilance Adverse Drug Reactions Reporting systems

Introduction to Pharmacovigilance & Adverse Drug Reactions Reporting systems Dr. Habab Khalid Elkheir B. Pharm. , M. Pharm. , Ph. D ISOP ISPE IUATLD SSCP 2/22/2021 Habab khalid Elkheir

Objectives of the workshop Learning objectives By the end of this training course 1. The participants should be able to: a. Define PV and related terms b. Fill the ADR form 2. The participants should be acquainted with: i. different methods of ADR reporting ii. The minimum requirements of an ADR report 2/22/2021 Habab khalid Elkheir

Content of this session § Definition of pharmacovigilance (PV) § Major aims of PV § Related definition to PV § Why PV? § Global magnitude of Averse drug reactions § Importance of PV to health care providers & patients 2/22/2021 Habab khalid Elkheir

What is Pharmacovigilance 2/22/2021 Habab khalid Elkheir

Medicine Safety To undergo treatment you have to be very healthy, because apart from your sickness you have to stand the medicine. Molière 2/22/2021 Habab khalid Elkheir

Vigilance Vigilare = to watch Alert Watchfulness Forbearance Of Sleep; Wakefulness Watchfulness In Respect Of Danger; Care; Caution; Circumspection Process Of Paying Close And Continuous Attention 2/22/2021 Habab khalid Elkheir

Definition of pharmacovigilance (PV) The science and activities concerned with the Detection Assessment Understanding Prevention of adverse reactions to medicines (i. e. adverse drug reactions or ADRs). 2/22/2021 Habab khalid Elkheir

Pharmacovigilance • • • Major Aims early detection of unknown safety problems detection of increases in frequency identification of risk factors quantifying risks preventing patients from being affected unnecessarily Rational and Safe use of Medicines (WHO) 2/22/2021 Habab khalid Elkheir

Related Definitions • Drug: A pharmaceutical product, used in or on the human body for the prevention, mitigation, diagnosis and/or treatment of disease, or for the modification of physiological function. This definition includes prescribed medicines, over-the-counter medicines, vaccines, herbal medicines, traditional medicines and biologicals including blood and blood- related products e. g. sera, plasma etc. 2/22/2021 Habab khalid Elkheir

Related Definitions Adverse Drug Reaction (ADR) A response to a medicine used in humans or animals, which is noxious and unintended, including lack of efficacy, which occurs at any dosage and can also result from overdose, misuse or abuse of a medicine 2/22/2021 Habab khalid Elkheir

Related Definitions 2/22/2021 Habab khalid Elkheir

Adverse event 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. 2/22/2021 Habab khalid Elkheir

A Serious Adverse Event (Experience) or Reaction Any untoward medical occurrence that at any dose results in death, is life-threatening, requires patient hospitalization, or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, causes a congenital anomaly or birth defect, and requires an intervention to prevent permanent impairment or damage. 2/22/2021 Habab khalid Elkheir

A side effect Any unintended effect of a pharmaceutical product occurring at doses normally used in humans, which is related to the pharmacological properties of the drug. 2/22/2021 Habab khalid Elkheir

Signal A reported information on a possible causal relationship between an adverse event and a drug; the relationship being unknown or incompletely documented previously. 2/22/2021 Habab khalid Elkheir

Why Pharmacovigilance ? 1 - New Products Information Collected During The Premarketing Phase Are INCOMPLETE ! With Regard To ADR. 2 - Animal Tests Are Insufficient In Predicting Human Safety. 3 - In Clinical Trials Patients Are Selected And Limited In Number. The Condition Of Use Differ From Those In Clinical Practice And Duration Of Trial Is Limited. 4. Information About Rare But Serious ADRS , Chronic Toxicity , Use In Special Groups ( Children , Elderly Or Pregnant Women ) DI Is Often Incomplete Or Not Available 2/22/2021 Habab khalid Elkheir

Limitations Of Pre-approval Clinical Trials • Size (Maximum 3, 000 -5, 000 Subjects) – Sometimes Larger For Vaccine • Narrow Population – Often Does Not Include Special Groups (e. g. , Children, Elderly) • Narrow Indications Not Covering Actual Evolving Uses In Practice • Short Duration (1 -3 Years) – Latent Effects Not Directly Measured 2/22/2021 Habab khalid Elkheir

Limitations of Pre-marketing Trials-1 • Carefully selected subjects may not reflect real-life patients in whom drug will be used • Study subjects may receive better care than real-life patients • Short duration of treatment 2/22/2021 Habab khalid Elkheir

Limitations of Pre-marketing trials-2 • Study size – Studies with 3000 patients cannot reliably detect adverse events with an incidence of < 1 per 1000, even if severe – Studies with 500 patients cannot reliably detect adverse events with an incidence of < 1 per 166, even if severe 2/22/2021 Habab khalid Elkheir

Consequences of Limitations of Pre-marketing Trials • About 20% of drugs get new “black box” warnings after marketing • About 4% of drugs are ultimately withdrawn for safety reasons 2/22/2021 Habab khalid Elkheir

Pharmacovigilance Is Needed In Every Country Differences Between Countries (Even Regions Within The Same Country) In ADR Occurrence & Drug-related Problems Due To : 1 - Differences In Drug Production 2 - Differences In Drug Distribution & Use (Choice, Indications Or Dose. ) 3 - In Genetics, Diets & Traditions Of People 4 - In The Composition, Excipients Or Quality Of Locally Produced Drug. 5 - Traditional Local Remedies May Pose Special Toxicology Problems. 2/22/2021 Habab khalid Elkheir

WHO Global PV Programme Why? ? • World Health Assembly Resolution 16. 36 • INVITES Member States to arrange for a systematic collection of information on serious adverse drug reactions observed during the development of a drug and, in particular, after its release for general use. 2/22/2021 Habab khalid Elkheir

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On September 30, 2004, Merck and Co. voluntary withdrew rofecoxib (Vioxx) due to increased risk of CV events 2/22/2021 B J Clin Pharm 2007 Habab khalid Elkheir

The magnitude of ADR problems globally • Meta-analysis of studies in hospitals: • USA: • • ADRs are the 4 th – 6 th leading cause of death. Overall incidence of serious ADRs was 6. 7% Fatal ADRs accounted for 0. 32%. Hospital admissions due to ADRs (1970 – 1975) were between 4. 2 - 6. 0% with a median of 5. 8%. • 2000, drug related morbidity / mortality costed 177. 4 billion $ 2/22/2021 Habab khalid Elkheir

The magnitude of ADR problems globally cont. . • Meta-analysis of studies in hospitals: • England: • • • ADRs accounted for 6. 5% of hospital admissions fatality 0. 15% Cost the National Health Services (NHS) £ 466 million/year 70% of ADRs were considered avoidable These startling figures do not represent the whole picture They excluded ADRs caused by other drug related problems such as overdose, drug abuse, misuse 2/22/2021 Habab khalid Elkheir

Size or Severity of the ADR Problem in Sudan Unfortunately, due to inadequate research in this area in Sudan, there is a lack of information on the extent of burden due to ADRs in terms of morbidity, mortality and financial drain on the health system. It can only be presumed that it is worse than what is reported in developed countries due to widespread irrational use of medicines 2/22/2021 Habab khalid Elkheir

Benefits of ADR reports to patients and healthcare professionals ADR reporting would benefit healthcare practitioners and patients by: • Improving the quality of care offered to patients • Reducing drug related problems leading to better treatment outcomes • Enhancing patients ‘confidence in practitioners 2/22/2021 Habab khalid Elkheir

Benefits of ADR reports to patients and healthcare professionals • Contributing to global knowledge on drug safety issues • Providing access to feedback information on drug related problems reported within the country and internationally • Providing satisfaction for the fulfillment of a moral and professional obligation • Guaranteeing patient safety 2/22/2021 Habab khalid Elkheir

The Big Three • More than 300 products in the pipeline for neglected diseases, HIV AIDS, TB and malaria • At least half of them will be launched in the coming years in those very settings where there is little or no capacity for post approval monitoring 2/22/2021 Habab khalid Elkheir Developer Analysis, BVGH, 2012

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Thanks for your Attention 2/22/2021 Habab khalid Elkheir