Session 14: Pharmacovigilence

This session will provide participants with the skills, knowledge, and attitudes necessary to more effectively become practitioners and trainers for identifying, reporting and preventing adverse drug reactions (ADRs) (side effects) to medicines used in healthcare settings.

Learning Objectives

By the end of this session you will be able to:

• Define pharmacovigilance.
• Explain the importance of pharmacovigilence for assessing and improving medication safety.
• Describe issues and the challenges in the conduct of pharmacovigilance.
• Demonstrate how pharmacovigilance methods and risk management strategies can be used to improve patient care.

• Reading: What Is Pharmacovigilance? (5 min)
  

  Medicines are among the most important health interventions to control disease, morbidity and mortality. For example, because of medicines, we are able to:

  • Vaccinate children
  • Prevent and treat childhood pneumonia, diarrhea, and malaria
  • Attack the spread of HIV
  • Treat tuberculosis

  There are, however, some issues with medicines. Some can cause people to have adverse drug reactions. People may take the wrong dose or mistakenly get fake or substandard medicines. Or healthcare providers might prescribe the wrong medicine.

  As described by the World Health Organization (WHO), pharmacovigilance (PV) is the science and activities relating to the detection, assessment, understanding, and prevention of adverse effects (side effects) or any other possible medicine-related problems. It is crucial for evaluating the benefit-risk profile of marketed drugs and vaccines throughout their life cycle.

• Reading: Sources of Risk and Safety Information (10 min)

  There are many sources of risk of medicines. By learning more about the medications you prescribe, you can prevent injury or death. Avoidable known side effects, medication and device error, and product defects can lead to preventable adverse events, which may lead to injury or death. Unavoidable known side effects, unexpected side effects, and unstudied uses and populations can also lead to injury or death.

  Safety information is generated through many different methods throughout a medicine’s life-cycle, including:

  • Preclinical studies
  • Premarketing studies in humans, including clinical trials
  • Spontaneous reporting of adverse events (side effects)
  • Active surveillance
  • Formal epidemiological studies
  • Medical literature
  • Alerts from other regulatory agencies (such as Medicines Control Authority of Zimbabwe [MCAZ])and WHO
  • Media

  Clinical Trials in Pharmacovigilance

  After discovery, formulation, and pre-clinical testing of medicines, there are pre-marketing phases that are conducted before a medicine is approved for use. This is referred to as phase I, phase II and phase III studies. Phase I trials identify safety issues, phase II trials look at the balance of safety and efficacy, and phase III trials place more emphasis on a medicine’s efficacy. Generally, phase III studies involve several hundreds to a few thousand patients.

  There are some limitations of assessing the adverse events in clinical trials such as:

  • Trial participants and study sites are a selected sample.
  • Limited sample size, limited study power.
  • Inadequate duration for medicines intended for chronic or long-term use.
  • Limited value for detecting unexpected adverse events.

  Why Be Concerned About Side Effects?

  Adverse drug reactions (ADRs) are among the leading causes of deaths in many countries. In some countries ADR-related costs, such as hospitalization, surgery, and lost productivity, exceed the cost of medications. Some countries may spend 15-20% of their hospital budget managing drug complications. Although people in every country of the world are affected by adverse drug reactions, at least 60% of ADRs are believed to be preventable.

  Take a moment to think: What are some causes of preventable ADRs? In the box below, list 2-3 causes, then tap the compare answer button to see more causes.

  Clear Compare Answer

  Compare answer feedback:

  • Incorrect diagnoses
  • Prescription of the wrong drug for the diagnosed condition
  • Prescription of the wrong dosage of the correct drug
  • An undetected medical, genetic or allergic condition that might cause a patient reaction
  • Self-medication with prescription medicines
  • Not following the instructions for taking the medication
  • Reactions with other drugs (including traditional medicines) and certain foods
  • Use of a sub-standard medication whose composition and ingredients do not meet the correct scientific requirements and can be ineffective and often dangerous
  • Use of fake or substandard medicines

  Pharmacovigilance in HIV/AIDS Programmes

  Your help is needed to:

  • Create awareness and consciousness of safety issues
  • Follow-up on safety signals
  • Contribute to treatment guidelines
• Reading: Pharmacovigilance in Zimbabwe (5 min)

  The national pharmacovigilance center in Zimbabwe is the Medicines Control Authority of Zimbabwe (MCAZ). MCAZ is responsible for promoting pharmacovigilance in the country, collecting and managing adverse drug reactions reports, reports of medication errors, and reports of suspected counterfeit/substandard drugs. MCAZ provides feedback to the healthcare practitioners in relevant bulletins and publications and collaborates and harmonizes with other adverse drug reaction collection activities within the country and international adverse drug reactions monitoring programmes. MCAZ identifies signals of drug safety such as unknown or poorly characterized adverse events in relation to a drug and communicates the information in a way that improves therapeutics and promote patient safety. It also undertakes assessment of risk and options for risk management.

• Reading: Pharmacovigilance Process (10 min)

  Much remains unknown during drug and vaccine approval and without systems to improve drug safety, the public’s confidence in medications may be undermined. For example, poor quality products can harm patients and drug resistance can emerge. Public confidence may also be damaged by uncertainties in the benefits or risks of a medication during real-world use or rumoured adverse events. Therefore, the processes for monitoring and evaluating ADRs is a key component of effective drug regulation systems, clinical practice and public health programmes to ensure medication safety.

  As you can see in the image below, there are many steps, people, and functions involved in working to strengthen the pharmacovigilance systems to improve drug safety.

  

  The pharmacovigilance process can be described as having three main components. By understanding and participating in the process, you are critical to the success of pharmacovigilance systems. Tap on each component to learn more.

  • Risk Identification
  • Risk Evaluation
  • Risk Management and Communication

  Risk Identification

  The purpose of risk identification is to identify suspected side effects. Sources include spontaneous adverse event case reports, premarketing studies, preclinical and clinical trials, medical literature, bulletins from other regulatory agencies, spontaneous adverse drug reaction reporting, and voluntary, passive reporting of suspected adverse events during routine clinical practice. The advantages include the ability to identify side effects at a nationwide level and characterize at-risk groups, risk factors, and clinical characteristics through clinical practice.

  Spontaneous adverse event case reports are also referred to as spontaneous case reports generated through passive surveillance. Such reports might be communicated by healthcare professionals or patients to national pharmacovigilance centers, to companies, or reported in the medical literature. Well-documented case reports can be viewed as a safety signal, alerting to the possibility of an adverse event. Spontaneous reports can also provide information on at-risk groups, risk factors, and clinical characteristics of known serious adverse drug reactions. The reporting of adverse events is influenced by several factors, including the elapsed time since its introduction into the marketplace, regulatory activity, and media attention.

  Serious adverse events include:

  • Congenital anomaly
  • Death
  • Hospitalization
  • Life-threatening conditions
  • Disabling conditions
  • Other medically important conditions

  Risk Evaluation

  Once potential risks are identified, for example, through the generation of safety signals, they need to be further assessed and properly evaluated using qualitative and quantative methods.

  Qualitative risk evaluation involves causality assessment, meaning that an algorithm and clinical judgement is used to determine whether there is reasonable possibility that the product is related to the adverse experience. In other words, this assessment looks at whether there is reasonable possibility that the medicine is causing the adverse experience. In Zimbabwe when adverse drug reactions report are submitted to MCAZ, causality assessment is done by the Pharmacovigilance and Clinical Trials Committee, which comprises of a team with various clinical expertise.

  Quantitative risk evaluation primarily uses epidemiological methods to confirm and quantify the relationship between a medicine and ADR using a variety of approaches: registries, cohort studies, case-control studies, phase IV studies, and other studies, which may include clinical trials, pharmacokinetic studies, surveys, drug utilization, and medicine resistance monitoring, and automated databases that contain administrative and clinical information.

  Risk Management and Communication

  Risk management is a process for assessing risks and benefits for minimizing risks and maximizing benefits. Risk communication is an interactive process of exchanging risk information. Risk management options include:

  1. No change
  2. More intensive data gathering
  3. Communicate new or reinforced information to health professionals and the public
  4. Modify treatment guidelines
  5. Restrict product availability
  6. Suspend procurement of products
  7. Withdraw product from local approved or essential medicines list
• Reading: Reporting (5 min)

  It’s important to report any adverse events.

  Qualities of a good individual case safety report include:

  • Description of event
  • Suspected product(s) and concomitant details
  • Patient characteristics, medical history, treatment history
  • Documentation of the diagnosis
  • Clinical course of outcomes
  • Treatment and lab values at baseline, during treatment, and after treatment
  • Response to dechallenge and rechallenge

  Activities to strengthen spontaneous reporting include:

  • Define priorities for reporting
  • Easy contact with and quick access to pharmacovigilance system
  • Information and support for reporting suspected ADRs
  • Feedback on pharmacovigilance activities
  • Training
  • Quality assurance visits
  • Ongoing presence of focal persons

  The reporting forms for spontaneous adverse events can be obtained from MCAZ offices at 106 Baines avenues, Harare or forms can be downloaded from their website at: www.mcaz.co.zw. A sample of the form is in the resources section.

  You can also report spontaneous adverse events using the ADR electronic reporting platform which is also on the MACAZ website.

• Reading: Pharmacovigilance at Multiple Levels (5 min)

  The practice of pharmacovigilance exists at multiple levels.

  When an individual patient has an adverse reaction to a medication, he or she can report it to his or her healthcare practitioner, who in turn can submit a voluntary report to MCAZ, which is the national pharmacovigilance center. Patients can also submit adverse drug reaction reports to the MCAZ without going through a healthcare professional. When an adverse event occurs at the facility level, such as in a hospital, clinic, or nursing home, reports provide insight into clinical experience and pharmacotherapy treatments. Additionally, awareness of adverse events may help facilities take necessary precautions that may lead to a reduction in medication errors.

  Often individuals and facilities report adverse events to province- and district-level health departments, and these reports will be submitted to MCAZ. Data aggregated at this level may reveal certain adverse event trends within or across communities and prompt active surveillance methods, such as the establishment of observational activities, registries, and sentinel sites. National systems take responsibility for assuring the quality, safety, and effectiveness of medicines sold in the country. A national pharmacovigilance programme coupled with a medicine regulatory authority can be effective in preserving the health of the public.

  Internationally, agencies can come together to share data and information about the benefits and risks of pharmaceutical products. There are multiple stakeholders when it comes to PV systems. Traditional stakeholders include the WHO, MOH, drug regulators (such as MCAZ), industry, healthcare providers, and patients. More recently, public-private partnerships, research consortia, donor-organizations such as PEPFAR, PMI, and Global Fund have become engaged in PV practice.

  Pharmacovigilance activities must be conducted and coordinated at each level of the public health system. Developed countries are often capable of monitoring their populations for adverse drug reactions, but developing countries often do not have the resources or capabilities to conduct all the necessary surveillance. For example, there are only seven full national pharmacovigilance centers in Sub-Saharan Africa, seven centers in Central and South America and six centers in resource-poor Asian countries. Thus, there is a need for regional and international cooperation to compile enough ADR reports to generate a signal.

• Quiz: Knowledge Check (10 min)

  1Pharmacovigilence is (Select all that apply.):

  1. The science and activities relating to the detection, assessment, understanding, and prevention of adverse effects (side effects) or any other possible medicine-related problems.
  2. Crucial for evaluating the benefit-risk profile of marketed drugs and vaccines throughout their life cycle.
  3. A guarantee that physicians will never prescribe the wrong medication.
  4. A system that includes fines issued to the prescriber of the medicine that caused the adverse effect.

  Clear Feedback

  A and B are correct.

  2Which of the following are limitations of assessing the adverse events in clinical trials? (Select all that apply.)

  1. Trial participants and study sites are a selected sample.
  2. Allows for determination that a medicine will be approved by a regulatory agency for marketing.
  3. Inadequate duration for medicines intended for chronic or long-term use.
  4. Limited value for detecting unexpected adverse events.

  Clear Feedback

  A, C, and D are correct.

  3The pharmacovigilance process can be described as having three main components. Match each component to its example.

  Assessing whether there is reasonable possibility that the medicine is causing the adverse experience. - select - Finding spontaneous adverse event case reports. - select - Seeking to minimize risks and maximize benefits. - select -

  Clear Feedback

  • Risk evaluation: Assessing whether there is reasonable possibility that the medicine is causing the adverse experience.
  • Risk identification: Finding spontaneous adverse event case reports.
  • Risk management and communication: Seeking to minimize risks and maximize benefits.

  4Spontaneous adverse event case reports are generated through passive surveillance.

  1. True
  2. False

  Clear Feedback

  True is correct.

• Reading: Key Points (5 min)
  • Pharmacovigilance generates useful information on medication safety for benefit-risk assessments.
  • Pharmacovigilance plays an important role in following up on safety signals, practice guidelines for public health programmes, and better defining and reducing the uncertainty about the safety profile of medicines and vaccines.
  • Pharmacovigilance identifies and quantifies side effects and provides vital information for the safe use of medicines.