International Society of Pharmacovigilance
Israeli Chapter

Resources

Resources:

This glossary reflects relevant ICH (www.ich.org) and/or European regulatory agency definitions.

 Term

 Description

Adverse event (AE) (largely considered synonymous with  adverse experience)

Any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An adverse event (AE) can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.

Adverse event of special interest (AESI)

A noteworthy event for the particular product or class of products that a sponsor may wish to monitor carefully. It could be serious or non-serious (e.g. hair loss, loss of taste, impotence), and could include events that might be potential precursors or prodromes for more serious medical conditions in susceptible individuals. Such events should be described in protocols or protocol amendments, and instructions provided for investigators as to how and when they should be reported to the sponsor.

Adverse drug reaction (ADR) (largely considered synonymous with adverse drug effect, though see Aronson 2013 for reflections on this[2])

In the pre-approval clinical experience with a new medicinal product or its new usages, particularly as the therapeutic dose(s) may not be established: all noxious and unintended responses to a medicinal product related to any dose should be considered adverse drug reactions. The phrase “responses to a medicinal product” means that a causal relationship between a medicinal product and an adverse event is at least a reasonable possibility, i.e., the relationship cannot be ruled out. Regarding marketed medicinal products, a well-accepted definition of an adverse drug reaction in the post-marketing setting is found in WHO Technical Report 498 [1972] and reads as follows: A response to a drug which is noxious and unintended and which occurs at doses normally used in man for prophylaxis, diagnosis, or therapy of disease or for modification of physiological function. The old term “side effect” has been used in various ways in the past, usually to describe negative (unfavourable) effects, but also positive (favourable) effects. It is recommended that this term no longer be used and particularly should not be regarded as synonymous with adverse event or adverse reaction.

Benefit-risk analysis

Examination of the favourable (beneficial) and unfavourable results of undertaking a specific course of action. (While this phrase is still commonly used, the more logical pairings of benefit-harm and effectiveness-risk are slowly replacing it).

Case control studies

Studies that compare cases with a disease to controls without the disease, looking for differences in antecedent exposures.

Case reports

Reports of the experience of single patients. As used in pharmacoepidemiology, a case report describes a single patient who was exposed to a drug and experiences a particular outcome, usually an adverse event.

Case series

Reports of collections of patients, all of whom have a common exposure, examining what their clinical outcomes were. Alternatively, case series can be reports of patients who have a common disease, examining what their antecedent exposures were. No control group is present.

Causality assessment

Method for assigning probability of causation to a suspected adverse drug reaction.

Clinical development programme

This refers to all clinical trials being conducted with the same investigational drug, regardless of indication or formulation.

Clinical trial/study

Any investigation in human subjects intended to discover or verify the clinical, pharmacological and/or other pharmacodynamics effects of an investigational product(s), and/or to identify any adverse reactions to an investigational product(s), and/or to study absorption, distribution, metabolism, and excretion of an investigational product(s) with the object of ascertaining its safety and/or efficacy. The terms clinical trial and clinical study are synonymous.

Cohort studies

Studies that identify defined populations and follow them forward in time, examining their rates of disease. Cohort studies generally identify and compare exposed patients to unexposed patients or to patients who receive a different exposure.

Company core safety information (CCSI)

For medicinal products, all relevant safety information contained in the company core data sheet prepared by the marketing authorisation holder and which the marketing authorisation holder requires to be listed in all countries where the company markets the product, except when the local regulatory authority specifically requires a modification.

Company core data sheet (CCDS)

For medicinal products, a document prepared by the marketing authorisation holder containing, in addition to safety information, material related to indications, dosing, pharmacology and other information concerning the product.

Cross-sectional studies

These examine exposures and outcomes in populations at one point in time; they have no time sense.

Data Monitoring Committee (synonyms: Independent Data Monitoring Committee, Data and Safety Monitoring Board)

An independent data monitoring committee that may be established by the sponsor to assess at intervals the progress of a clinical trial, the safety data, and the critical efficacy endpoints, and to recommend to the sponsor whether to continue, modify, or stop a trial.

Descriptive studies

Studies that do not have control groups, namely case reports, case series, and analyses of secular trends. They contrast with analytic studies.

Development core safety information (DCSI)

An independent section of an Investigator’s Brochure (IB) identical in structure to the Company Core Safety Information (CCSI) that contains a summary of all relevant safety information that is described in more detail within the main body of the IB. It is the reference safety document that determines whether an adverse drug reaction is listed or unlisted.

Development pharmacovigilance and risk management plan

A plan to conduct activities relating to the detection, assessment, understanding, reporting and prevention of adverse effects of medicines during clinical trials. This plan should be initiated early and modified as necessary throughout the development process for a new drug or drug-use.

Development safety update report (DSUR)

A periodic summary of safety information for regulators, including any changes in the benefit-risk relationship, for a drug, biologic or vaccine under development, prepared by the sponsor of all its clinical trials.

Format and content for periodic reporting on drugs under development.

Drug utilization research

The marketing, distribution, prescription and use of drugs in a society, with special emphasis on the resulting medical, social, and economic consequences.

Ecological studies

These examine trends in disease events over time or across different geographic locations and correlate them with trends in putative exposures, such as rates of drug utilisation. The unit of observation is a subgroup or a population rather than individuals.

Expected adverse drug reaction

One for which its nature or severity is consistent with that included in the appropriate reference safety information (e.g. Investigator’s brochure for an unapproved investigational product or package insert/summary of product characteristics for an approved product).

Good clinical practice (GCP)

A standard for the design, conduct, performance, monitoring, auditing, recording, analyses, and reporting of clinical trials that provides assurance that the data and reported results are credible and accurate, and that the rights, integrity, and confidentiality of trial subjects are protected.

Good pharmacovigilance practice

A set of guidelines for the conduct of pharmacovigilance in the EU, drawn up based on Article 108a of Directive 2001/83/EC, by the European Medicines Agency in cooperation with competent authorities in Member States and interested parties, and applying to marketing authorisation holders in the EU, the Agency and competent authorities in Member States.

Harm (synonymous with adverse drug reaction)

The totality of possible adverse consequences of an intervention or therapy; they are the direct opposite of benefits, against which they must be compared.

Damage qualified by measures of frequency of occurrence, severity or duration.

The nature and extent of actual damage that could be caused by a drug. Not to be confused with risk.

Hazard

The inherent capability of an intervention to cause harm (and a hazard as a potential source of harm).

Important identified risk, important potential risk

An identified risk or potential risk that could impact on the risk-benefit profile of the product or have implications for public health. What constitutes an important risk will depend upon several factors, including the impact on the individual, the seriousness of the risk, and the impact on public health. Normally, any risk that is likely to be included in the contraindications or warnings and precautions section of the product labelling should be considered important.

Individual case safety report (ICSR); synonym: Adverse (drug) reaction report

Format and content for the reporting of one or several suspected adverse reactions to a medicinal product that occur in a single patient at a specific point of time.

Identified risk

An untoward occurrence for which there is adequate evidence of an association with the medicinal product of interest. Examples of identified risks include: an adverse reaction adequately demonstrated in nonclinical studies and confirmed by clinical data; an adverse reaction observed in well-designed clinical trials or epidemiological studies for which the magnitude of the difference compared with the comparator group (placebo or active substance) on a parameter of interest suggests a causal relationship; and an adverse reaction suggested by a number of well documented spontaneous reports where causality is strongly supported by temporal relationship and biological plausibility, such as anaphylactic reactions or application site reactions.

Investigator brochure (IB)

A compilation of the clinical and nonclinical data on the investigational product(s) that is relevant to the study of the investigational product(s) in human subjects.

Investigational product

A pharmaceutical form of an active ingredient or placebo being tested or used as a reference in a clinical trials, including a product with a marketing authorization when used or assembled (formulated or packaged) in a way different form the approved form, or when used for an unapproved indication, or when used to gain further information about an approved use.

Labelled or unlabelled

For a product with an approved marketing application, any reaction which is not mentioned in the official product information is unlabelled. If it is included it is termed labelled.

Medication errors

Any mistake in the medication use process, including prescribing, transcribing, dispensing, administering, and monitoring.

Minimum criteria for reporting

For the purpose of reporting cases of suspected adverse reactions, the minimum data elements for a case are: an identifiable reporter, an identifiable patient, an adverse reaction and a suspect medicinal product.

Missing information

Gaps in knowledge about a medicinal product, related to safety or use in particular patient populations, which could be clinically significant.

Near-misses

Medication errors that have high potential for causing harm but did not, either because they were intercepted prior to reaching a patient, or because the error reached the patient who fortuitously did not have any observable untoward sequalae.

Number needed to harm (NNH)

The number of individuals needed to be treated for some specified period of time in order that one person out of those treated would have one harmful event (during some specified time period).

Observational study

A study where the investigator does not control the therapy, but observes and evaluates the results of ongoing medical care.

Periodic safety update report (PSUR)

Format and content for providing an evaluation of the risk-benefit balance of a medicinal product for submission by the marketing authorisation holder at defined time points during the post-authorisation phase.

Pharmacoepidemiology

The study of the use and the effects of drugs in large numbers of people.

Pharmacovigilance

The science and activities relating to the detection, assessment, understanding and prevention of adverse effects or any other drug related problem.

In line with this general definition, underlying objectives of pharmacovigilance in accordance with the applicable EU legislation for are: preventing harm from adverse reactions in humans arising from the use of authorised medicinal products within or outside the terms of marketing authorisation or from occupational exposure; and promoting the safe and effective use of medicinal products, in particular through providing timely information about the safety of medicinal products to patients, healthcare professionals and the public. Pharmacovigilance is therefore an activity contributing to the protection of patients’ and public health.

Moreover, recently, its concerns have been widened to include: herbals, traditional and complementary medicines, blood products, biologicals, medical devices, vaccines.

Many other issues are also of relevance to the science: substandard medicines, medication errors, lack of efficacy reports, use of medicines for indications that are not approved and for which there is inadequate scientific basis, case reports of acute and chronic poisoning, assessment of drug-related mortality, abuse and misuse of medicines, adverse interactions of medicines with chemicals, other medicines, and food.

Pharmacovigilance system

A system used by an organisation to fulfil its legal tasks and responsibilities in relation to pharmacovigilance and designed to monitor the safety of authorised medicinal products and detect any change to their risk-benefit balance.

Post-authorisation safety study (PASS)

Any study relating to an authorised medicinal product conducted with the aim of identifying, characterising or quantifying a safety hazard, confirming the safety profile of the medicinal product, or of measuring the effectiveness of risk management measures.

Postmarketing surveillance

The study of drug use and drug effects after release onto the market.

Potential risk

An untoward occurrence for which there is some basis for suspicion of an association with the medicinal product of interest but where this association has not been confirmed. Examples of potential risks include: non-clinical safety concerns that have not been observed or resolved in clinical studies; adverse events observed in clinical trials or epidemiological studies for which the magnitude of the difference, compared with the comparator group (placebo or active substance, or unexposed group), on the parameter of interest raises a suspicion of, but is not large enough to suggest, a causal relationship; an event which is known to be associated with other products of the same class or which could be expected to occur based on the properties of the medicinal product.

Randomised controlled trial (RCT)

A study where the investigator randomly assigns patients to different therapies/study arms.

Reference Safety Information (RSI)

In periodic benefit-risk evaluation reports for medicinal products, all relevant safety information contained in the reference product information (e.g. the company core data sheet) prepared by the marketing authorisation holder and which the marketing authorisation holder requires to be listed in all countries where it markets the product, except when the local regulatory authority specifically requires a modification. It is a subset of information contained within the marketing authorisation holder’s reference product information for the periodic benefit-risk evaluation report. Where the reference product information is the company core data sheet, the reference safety information is the company core safety information.

Registry

A list of patients presenting with the same characteristic(s). This characteristic can be a disease (disease registry) or a specific exposure (drug registry). Both types of registries, which only differ by the type of patient data of interest, can collect a battery of information using standardised questionnaires in a prospective fashion. Exposure (drug) registries collect information over time on populations exposed to drugs of interest and/or specific populations. Patients can be included in a cohort study to collect data on adverse events using standardised questionnaires. They can be useful for signal amplification, particularly of rare outcomes.

Risk

The probability that something will happen.

The probability of developing an outcome. Note 1: the term ‘risk’ normally, but not always, refers to a negative outcome. Note 2: contrary to harm, the concept of risk does not involve severity of an outcome.

Risk-benefit balance

An evaluation of the positive therapeutic effects of the medicinal product in relation to the risks, i.e. any risk relating to the quality, safety or efficacy of the medicinal product as regards patients’ health or public health.

Risk management

The overall aim of risk management is to ensure that the benefits of a particular medicinal product (or a series of medicinal products) exceed the risks by the greatest achievable margin for the individual patient and for the target population as a whole. This can be done either by increasing the benefits or by reducing the risks. Risk management has three stages which are inter-related and re-iterative: 1. characterisation of the safety profile of the medicinal product including what is known and not known; 2. planning of pharmacovigilance activities to characterise risks and identify new risks and increase the knowledge in general about the safety profile of the medicinal product; 3. planning and implementation of risk minimisation and mitigation and assessment of the effectiveness of these activities.

Risk management plan

A detailed description of the risk management system. To this end, it must identify or characterise the safety profile of the medicinal product(s) concerned, indicate how to characterise further the safety profile of the medicinal product(s) concerned, document measures to prevent or minimise the risks associated with the medicinal product, including an assessment of the effectiveness of those interventions and document post-authorisation obligations that have been imposed as a condition of the marketing authorisation.

Risk management system

A set of pharmacovigilance activities and interventions designed to identify, characterise, prevent or minimise risks relating to medicinal products including the assessment of the effectiveness of those activities and interventions.

Risk minimisation activity (used synonymously with risk minimisation measure)

An intervention intended to prevent or reduce the probability of the occurrence of an adverse reaction associated with the exposure to a medicine, or to reduce its severity should it occur. These activities may consist of routine risk minimisation (e.g. product information) or additional risk minimisation activities (e.g. healthcare professional or patient communications/educational materials).

Safety

Substantive evidence of an absence of harm. The term is often misused when there is simply absence of evidence of harm.

A judgement about safety is a personal and/or social judgement about the degree to which a given risk is acceptable.

Safety concern

An important identified risk, important potential risk or missing information. It is noted that the ICH definition of safety concern is: an important identified risk, important potential risk or important missing information, i.e. includes the qualifier “important” in relation to missing information (see Annex IV, ICH-E2C(R2) Guideline). The ICH-E2E Guideline (see Annex IV) uses the terms safety issue and safety concern interchangeably with the same definition for safety concern as defined in the ICH-E2C(R2) Guideline.

Safety specification

Part of a Risk Management Plan (RMP) that provides a synopsis of the safety profile of the medicinal product(s) and should include what is known and not known about the medicinal product(s). It should be a summary of the important identified risks of a medicinal product, important potential risks, and missing information. It should also address the populations potentially at risk (where the product is likely to be used i.e. both labelled and off-labelled use), and outstanding safety questions which warrant further investigation to refine understanding of the risk-benefit balance during the post-authorisation period.

Serious adverse event (SAE)

Any untoward medical occurrence that at any dose, results in death, is life-threatening (NOTE: The term “life-threatening” in the definition of “serious” refers to an event/reaction in which the patient was at risk of death at the time of the event/reaction; it does not refer to an event/reaction which hypothetically might have caused death if it were more severe), requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, or is a congenital anomaly/birth defect. Medical and scientific judgment should be exercised in deciding whether other situations should be considered serious such as important medical events that might not be immediately life-threatening or result in death or hospitalisation but might jeopardise the patient or might require intervention to prevent one of the other outcomes listed in the definition above. Examples of such events are intensive treatment in an emergency room or at home for allergic bronchospasm, blood dyscrasias or convulsions that do not result in hospitalization, or development of drug dependency or drug abuse.

Side effect

Any unintended effect of a pharmaceutical product occurring at normal dosage which is related to the pharmacological properties of the drug.

Signal

Information that arises from one or multiple sources (including observations and experiments), that suggests a new potentially causal association, or a new aspect of a known association, between an intervention and an event or set of related events, either adverse or beneficial, that is judged to be of sufficient likelihood to justify further action to verify.

Reported information on a possible causal relationship between an adverse event and a drug, the relationship being unknown or incompletely documented previously. Note 1: a signal is an evaluated association that is considered important to investigate further. Note 2: a signal may refer to new information on an already known association. Note 3: usually more than a single report is required to generate a signal, depending on the seriousness of the event and the quality of the information.

Signal management process

Includes the following activities: signal detection, signal validation, signal confirmation, signal analysis and prioritisation, signal assessment and recommendation for action. It therefore is a set of activities performed to determine whether, based on an examination of individual case safety reports (ICSRs), aggregated data from active surveillance systems or studies, literature information or other data sources, there are new risks causally associated with an active substance or a medicinal product or whether known risks have changed.

Signal validation

Process of evaluating the data supporting a detected signal in order to verify that the available documentation contains sufficient evidence demonstrating the existence of a new potentially causal association, or a new aspect of a known association, and therefore justifies further analysis of the signal.

Solicited reports

Those derived from organized data collection systems, which include clinical trials, registries, post-approval named patient use programs, other patient support and disease management programs, surveys of patients or healthcare providers, or information gathering on efficacy or patient compliance.

Sponsor

An individual, company, institution, or organisation which takes responsibility for the initiation, management, and/or financing of a clinical trial.

Spontaneous report or spontaneous notification

An unsolicited communication to a company, regulatory authority, or other organization that describes an adverse drug reaction in a patient given one or more medicinal products and which does not derive from a study or any organized data collection scheme.

Stimulated reporting

Can occur in certain situations, such as after a direct healthcare professional communication (DHPC), a publication in the press or questioning of healthcare professionals by company representatives, and adverse reaction reports arising from these situations are considered spontaneous reports (see Annex IV, ICH-E2D), provided the report meets the definition of a spontaneous report as specified above. Reporting can also be stimulated by invitation from patients’ or consumers’ organisations to their members. Reporting made in the context of early phase post-marketing vigilance (EPPV), e.g. in Japan, is also considered stimulated reporting.

Summary of product characteristics (SmPC or SPC)

Part of the marketing authorisation of a medicinal product setting out the agreed position of the product as distilled during the course of the assessment process which includes the information described in Article 11 of Directive 2001/83/EC. It is the basis of information for healthcare professionals on how to use the product safely and effectively. The package leaflet is drawn in accordance with the summary of product characteristics (based on A Guideline on Summary of Product Characteristics, Volume 2C of the Rules Governing Medicinal Products in the EU).

Suspected unexpected serious adverse reaction (SUSAR)

A reaction which is both unexpected and serious in nature.

Target population (treatment)

The patients who might be treated with the medicinal product in accordance with the indication(s) and contraindications in the authorised product information.

Target population (vaccine); synonym: Vaccine target population

Persons who might be vaccinated in accordance with the indication(s) and contraindications in the authorised product information and official recommendations for vaccinations.

Tolerability

The degree to which overt adverse effects can be tolerated by the subject.

NB we can find few references for this term – advice would be appreciated to improve the glossary.

Type A adverse drug reaction (augmented)

A dose-related reaction; features of which are that they are common, related to a pharmacological action of the drug, predictable and with low mortality.

Type B adverse drug reaction (bizarre)

A non-dose-related reaction; features of which are that they are uncommon, not related to a pharmacological action of the drug, unpredictable and with high mortality.

Type C adverse drug reaction (chronic)

A dose- and time-related reaction; features of which are that they are uncommon and related to the cumulative dose.

Type D adverse drug reaction (delayed)

A time-related reaction; features of which are that they are uncommon, usually dose-related and they occur or become apparent sometime after the use of the drug.

Type E adverse drug reaction (end of use)

A withdrawal reaction; features of which are that they are uncommon and occur soon after withdrawal of the drug.

Type F adverse drug reaction (failure)

A unexpected failure of therapy reaction; features of which are that they are common, dose-related and often caused by drug interactions.

Unexpected adverse drug reaction

An adverse reaction, the nature or severity of which is not consistent with the applicable product information (e.g., Investigator’s Brochure for an unapproved investigational medicinal product).

An adverse drug reaction whose nature, severity, specificity, or outcome is not consistent with the term or description used in the local/regional product labeling (e.g. Package Insert or Summary of Product Characteristics) should be considered unexpected

Validated signal

A signal where the signal validation process of evaluating the data supporting the detected signal has verified that the available documentation contains sufficient evidence demonstrating the existence of a new potentially causal association, or a new aspect of a known association, and therefore justifies further analysis of the signal.


[1] Edwards IR, Aronson JK. Adverse drug reactions: definitions, diagnosis, and management. Lancet. 2000;356(9237):1255-9.

[2] Aronson JK. Distinguishing hazards and harms, adverse drug effects and adverse drug reactions: implications for drug development, clinical trials, pharmacovigilance, biomarkers, and monitoring. Drug Safety. 2013;36(3):147-53.

[3] Ferner RE, Aronson JK. Clarification of terminology in medication errors: definitions and classification. Drug Safety. 2006;29(11):1011-22.

[4] Lindquist M. The need for definitions in pharmacovigilance. Drug Safety. 2007;30(10):825-30.

[5] Ioannidis JP, Evans SJ, Gotzsche PC, O’Neill RT, Altman DG, Schulz K, et al. Better reporting of harms in randomized trials: an extension of the CONSORT statement. Annuals of Internal Medicine. 2004;141(10):781-8.

[6] Clinical safety data management: definitions and standards for expedited reporting E2A. International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) 1994.

[7] Management of safety information from clinical trials. Council for International Organizations of Medical Sciences (CIOMS) Working Group VI, Geneva. 2005.

[8] Strom BL. Pharmacoepidemiology. 4th ed. Chichester, England: John Wiley & Sons; 2005.

[9] Development safety update report E2F. International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH). 2010.

[10] Guideline for good clinical practice E6 (R1). International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH). 1996.

[11] Periodic Benefit-Risk Evaluation Report E2C (R2). International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH). 2012.

[12] Guidelines on good pharmacovigilance practices (GVP) EMA/501523/2015

[13] The selection of essential drugs: report of a WHO expert committee. Geneva. 1977.

[14] Post-approval safety data management: definitions and standards for expedited reporting E2D. International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH). 2003.

[15] The importance of pharmacovigilance: safety reporting of medicinal products. Geneva: World Health Organisation. 2002.

[16] Pharmacovigilance planning E2E. International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH). 2004.

[17] Uppsala Monitoring centre (http://www.who-umc.org/)

[18] Statistical Principles for clinical trials E9. International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH). 1998.

Access external website resources that have relevance for pharmacovigilance below.

Country-specific societies/groups

ISoP Chapters for Italy, Western Pacific region, Mexico, Latin America, Switzerland-Austria, Africa, South Eastern Europe, North America (NASoP), Israel, Middle East,China, Indonesia & South Asia

ISPE Regional Chapters for Africa, Brazil, Gulf Region, Latin America & Spanish-speaking Chapter

Society of pharmacovigilance India (SOPI)

Pharmaceutical information & pharmacovigilance association (PIPA), UK

American Society of Pharmacovigilance

Centre Anti Poison & Pharmacovigilance du Maroc, Morocco

 

The International Society of Pharmacovigilance (ISoP)

A professional, independent, non-profit society, open to anyone with an interest in the safe and effective use of medicinal products. ISoP considers the scope of pharmacovigilance as any area that contributes better knowledge and understanding of the safe and effective use of medicines, pre- and post-marketing, including but not limited to:

– Problems related to the active components and ingredients of medicinal products – Problems related to medicines use – Substandard/spurious/falsely-labelled/falsified/ counterfeit (SSFFC) medical products – Safety problems in relation to mass medication (e.g. vaccines) – Antimicrobial resistance and other treatment failures – Benefit-harm assessment and risk management – Quality issues related to manufacturing, transport or storage – Environmental effects – Regulatory matters pertaining to the above

The International Society for Pharmacoepidemiology (ISPE)

A non-profit international professional membership organization dedicated to advancing the health of the public by providing a forum for the open exchange of scientific information and for the development of policy; education; and advocacy for the field of pharmacoepidemiology, including pharmacovigilance, drug utilization research, outcomes research, comparative effectiveness research, and therapeutic risk management. ISPE defines pharmacoepidemiology as the science that applies epidemiologic approaches to studying the use, effectiveness, value and safety of pharmaceuticals. ISPE publish the freely available Guidelines for Good Pharmacoepidemiology Practices (GPP).

www.healthtalk.org

See: http://www.healthtalk.org/peoples-experiences/medical-research/clinical-trials/side-effects-and-queries-about-clinical-trials for interviews with clinical trial participants about side effects

ClinRegs online database of country-specific clinical research regulatory information

An online database of country-specific clinical research regulatory information designed to save time and effort in planning and implementing clinical research. Countries and topics included are based on NIAID’s international clinical research priorities.

Clinical Trials Transformation Initiative

The mission of the CTTI is to develop and drive adoption of practices that will increase the quality and efficiency of clinical trials. Projects include the development of tools to improve the quality and efficiency of safety reporting for clinical trials conducted under an (United States) investigational new drug application (IND), recommendations for Data Monitoring Committees and others that may have relevance for pharmacovigilance within clinical trials and registries.

deprescribing.org

A Canadian initiative to share and exchange information about deprescribing approaches and deprescribing research, including useful algorithms and patient information. 

The electronic Medicines Compendium (eMC)

The eMC contains up to date, easily accessible information about medicines licensed for use in the UK. The eMC has more than 10,600 documents, all of which have been checked and approved by either the UK or European government agencies which license medicines.
Browse the site to see UK Summaries of Product Characteristics, Patient Information Leaflets, Risk Minimisation Materials (RMMs)

EQUATOR Network

Reporting guidelines for studies that include harms (e.g. extension to CONSORT, PRISMA-harms, RECORD-PE, systematic reviews including harms)

The Global Health Regulatory Requirements Database

Designed to help researchers and regulatory affairs professionals access the information they need to develop effective strategies for gaining approval to conduct clinical trials and market products. The database provides high-level information on regulatory requirements, timelines, costs, and other basic information required to create product development plans for new tools.

The WHO Programme for Intermnational Drug Monitoring/Global Pharmacovigilance Database & The Uppsala Monitoring Centre (UMC)

An independent foundation and a centre for international service and scientific research improving worldwide patient safety. See UMC also for links to other WHO Collaborating Centres relating to pharmacovigilance, pharmacoepidemiology and lots of information on systems and tools that may facilitate pharmacovigilance work. See the WHO Pharmaceuticals newsletter for the latest information on the safety of medicines and legal actions taken by regulatory authorities around the world. It also provides signals based on information derived from Individual Case Safety Reports (ICSRs) available in the WHO Global ICSR database, VigiBase.

The WHO Collaborating Centre for Advocacy & Training in Pharmacovigilance, based at the Centre for Tropical Clinical Pharmacology & Therapeutics, Ghana Medical School (African Collaborating Centre for Pharmacovigilance) has released a useful Pharmacovigilance Toolkit for low & middle income countries

RxISK

RxISK is a free, independent website where you can research prescription drugs and report a drug side effect – identifying problems and possible solutions when it might still be possible to intervene and find a solution.

MedSafety Scan® (MSS) was developed by scientists at the Arizona Center for Education and Research on Therapeutics (AZCERT), asa platform for therapeutic decision support that incorporates the QTdrugs database from the CredibleMeds website with reliable drug-drug interaction predictions to identify patients at greatest risk of major adverse drug reactions

Medication Without Harm: WHO’s Third Global Patient Safety Challenge

WHO’s goal is to achieve widespread engagement and commitment of WHO Member States and professional bodies around the world to reduce the harm associated with medication. See this page for proposed solutions to address many of the obstacles the world faces today to ensure the safety of medication practices, links to relevant educational materials and real-life stories from patients, families and health care providers about how they have been affected by medication errors and harm, as well as other stories on what they have done to prevent such errors and harm from reoccuring.

Institute for safe medication practices (ISMP)

A US non-profit organisation/independent watchdog dedicated to the collaborative development, education, and advocacy of safe medication practices.

Drug Information Association

A global forum for all those involved in health care product development and life cycle management to exchange knowledge and collaborate in a neutral setting

Cochrane AE methods group

A group aiming to develop the methods for producing high quality systematic reviews and to advise Cochrane on how the validity and precision of systematic reviews can be improved. They aim to raise awareness of the adverse effects of interventions, and to promote the inclusion of adverse effects data in Cochrane reviews; to provide educational help to reviewers and users of reviews to spread and deepen understanding of the principles involved in assessing adverse effects; to provide methodological guidance on specific aspects of evaluating adverse effects; to identify areas of methodological uncertainty, and to develop a toolbox for the assessment of adverse effects. See the website for useful recorded seminars.

See also the free eBook Testing Treatments distributed via the Cochrane Collaboration

The Brighton Collaboration

A non-profit, scientifically independent global research network providing free standardized, validated, and objective methods for monitoring safety profiles and benefit to risk ratios of vaccines to members.

EMA Good Pharmacovigilance Practices

A set of measures drawn up to facilitate the performance of pharmacovigilance in the European Union (EU). GVP apply to marketing-authorisation holders, the European Medicines Agency and medicines regulatory authorities in EU Member States. They cover medicines authorised centrally via the Agency as well as medicines authorised at national level.The chapters on product- or population-specific considerations are available for vaccines, biological medicinal products and the paediatric population. EMA plans two more considerations chapters (Pregnancy/breastfeeding & geriatrics).

FDA Adverse Event Reporting System (FAERS)

and MedWatch: The FDA Safety Information and Adverse Event Reporting Program

FAERS is a database that contains information on adverse event and medication error reports submitted to FDA. The database is designed to support the FDA’s post-marketing safety surveillance program for drug and therapeutic biologic products. See MedWatch for useful case studies about adverse effects, product use errors, product problems and Problems with different manufacturers of the same medicine

See also the FDA Drug safety podcasts produced by FDA’s Center for Drug Evaluation and Research (CDER) and providing emerging safety information about drugs in conjunction with the release of Drug Safety Communications

MedDRA (The Medical Dictionary for Regulatory Affairs)

A single standardised international medical terminology which can be used for regulatory communication and evaluation of data pertaining to medicinal products for human use. For use in the registration, documentation and safety monitoring of medicinal products through all phases of the development cycle.

European network of centres for pharmacoepidemiology and pharmacovigilance

A network coordinated by the European Medicines Agency (EMA). The members of this network (the ENCePP partners) are public institutions and contract and research organisations (CRO) involved in research in pharmacoepidemiology and pharmacovigilance. Research interests are not restricted to the safety of medicines but may include the benefits and risks of medicines, disease epidemiology and drug utilisation. Participation to ENCePP is voluntary. They have a useful Checklist for study protocols and a Guide on Methodological Standards in Pharmacoepidemiology that includes the conduct of systematic reviews and meta-analyses of completed comparative pharmacoepidemiological studies of safety outcomes. Both documents are referenced in Module VIII of the good pharmacovigilance practices (GVP) on post-authorisation safety studies (PASS) relating to authorised medicinal products, published by the European Medicines Agency (EMA).

The Council for International Organizations of Medical Sciences (CIOMS)

An international, non-governmental, non-profit organization established jointly by WHO and UNESCO that represents a substantial proportion of the biomedical scientific community through its member organizations, which include many of the biomedical disciplines, national academies of sciences and medical research councils. CIOMS mission is to advance public health through guidance on health research including ethics, medical product development and safety. CIOMS publications have been the basis for respective ICH guidelines. Recent resources cover vaccine safety communication, active vaccine safety surveillance, evidence synthesis and meta-analysis for drug safety, management of safety infromation from clinical trials, MedDRA issues, practical approaches to risk minimisation and practical aspects of signal detection. New working groups are underway concerned with patient involvement in the development and safe use of medicines, drug-induced liver injury and clinical research in resource-limited settings. 

Association of the British Pharmaceutical Industry (ABPI)

Represents innovative research-based biopharmaceutical companies, large, medium and small. Publications relevant for pharmacovigilance include guidelines for the safe conduct of First in Human and Phase 1 trials, and the collection of adverse events and product complaints from market research programmes.

CredibleMeds®: https://crediblemeds.org/

A website hosted by an independent non-profit organization that includes a list of drugs that have a risk of QT prolongation and cardiac arrhyhthmias to support the safe use of medications. A risk-stratification process includes monitoring and analysis of scientific articles in the published medical literature, information in the official drug label, reports submitted to its website and data in the FDA’s Adverse Event Reporting System (AERS) using Oracle’s Empirica Signal software. Drugs are placed into one of four risk categories based on their relative potential to alter the electrocardiogam (QT prolongation) and/or cause life-threatening ventricular arrhythmias.

SENSE ABOUT SCIENCE – MAKING SENSE OF DRUG SAFETY SCIENCE

An independent charity that challenges misrepresentation of science and evidence in public life, advocating openness and honesty about research, and ensuring the public interest in sound science and evidence is recognised in public debates and policymaking. This guide was produced in collaboration with the MRC-funded Centre for Drug Safety Science (a collaboration between the universities of Liverpool and Manchester). See www.liv.ac.uk/drug safety

Transcelerate BioPharma Inc

A non-profit organisation with a mission to collaborate across the biopharmaceutical research and development community to identify, prioritize, design and facilitate the implementation of solutions to drive efficient, effective and high-quality delivery of new medicines. Pharmacovigilance activities aim to address challenges in drug safety surveillance such as engaging the public, collaborating with regulators, incorporating data and analytics, developing model approaches, and assessing the impact of efforts. A guide for risk-based monitoring (RBM) offers an adaptive approach that directs clinical trial monitoring focus and activities to the evolving areas of greatest need which have the most potential to impact patient safety and data quality. The Common Serious Adverse Events (SAE) Fields Initiative is also conducting a feasibility assessment, and develop best practices for identifying the most critical SAE fields, to increase quality of what is reported, efficiencies for sites, CROs and regulators

WEB-RADR: Recognising Adverse Drug Reactions

Led by a consortium of world-leading experts from industry, regulatory agencies, and academia, WEB-RADR will deliver an EU-wide mobile phone app that enables users to report Adverse Drug Reactions (ADRs) directly to their National Competent Authority (NCA)

Global accelerator for paediatric formulations GAP-f)

Gap-f fosters collaboration across sectors to ensure accelerated development and uptake of the most needed drugs and formulations for children. It has a useful Toolkit (and webinar) for research & development of paediatric antiretroviral drugs & formulations that includes a module on pharmacovigilance. An online version of the Toolkit is also available on the Global Health Network Training Centre.

Sling the Mesh

This is a patient advocacy group for those injured as a result of vaginal mesh surgery. The campaign is working with ISoP to develop a global task force andspecicial interest group for medical devices.

Here you will find some links to national and international institutional websites and published papers on COVID-19. Stay informed with the latest clinical research and resources.

World Health Organization

Centers for Disease Control and Prevention

National Institute of Health

European Medicines Agency

COVID-19 data sources (Knowledge Portal on Innovation and Access to Medicines)

The Lancet

The New England Journal Of Medicine

Oxford Covid-19 Evidence service

The Royal College of Obstetricians and Gynaecologists (RCOG)

Italian Society of Pharmacology – English COVID-19 section

JAMA Network

International Union of Pharmacology and Clinical Pharmacology (IUPHAR)

NIPH-Live map of COVID-19 evidence

Springer Nature

The International Coalition of Medicines Regulatory Authorities (ICMRA)

Safety Monitoring Using WHO Global Database of Individual Case Safety Reports (ICSRs). Descriptive analysis of spontaneous report from VigiBase

Indian Council of Medical Research updated ethical guidance for biomedical and health research

African Vaccine Regulatory Forum (AVAREF) tools for Processing clinical trial applications by Ethics Committees and National Regulatory Authorities in Africa

Landscape of COVID-19 candidate vaccines/Draft

NZ Pharmacovigilance Centre Project encouraging feedback on COVID-19 Medication Safety Challenges in NZ

The Vaccine Centre & London School of Hygiene & Tropical Medicine

Johns Hopkins University-Coronavirus Resource Center

ISoP Member Papers and initiatives

ISoP colleagues in the North American Chapter of ISoP (NASoP) and the Italian Society of Pharmacology (SIF) are working on proposals to monitor the safety of medicines and vaccines to treat and prevent COVID-19. Here you will find also important research documents and initiatives from ISoP members and others.

Official statement of the section of Clinical Pharmacology of the Italian Society of Pharmacology on the use of ACE- inhibitors or angiotensin receptor blockers in COVID-19 infection with commentary

SIF

Official Statement of the section of Clinical Pharmacology of Italian Society of Pharmacology on Non-steroidal anti-inflammatory drugs (NSAIDs) and the increased risk of complications during infections with commentary

SIF

Simplified description of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2). Viral lifecycle and drug repurposing strategies

 

Benefit-Risk evaluation for Remdesivir in COVID-19

DSRU

The challenging times and opportunities for pharmacovigilance in Africa during the COVID‑19 pandemic

African Chapter of ISoP / Executive Committee

*New ISoP infographic ‘Using Medicines Safely during the COVID-19 pandemic’. This infographic is aimed at patients and caregivers – feel free to display it in hospitals, clinics, pharmacies and any other public spaces appropriate to where medicines are obtained in your country

ISoP

Posibles terapias para COVID-19: revision narrativa de seguridad I. Cloroquina / hidroxicloroquina y azitromicina

Raquel Herrera Comoglio

The WHO-ISoP Pharmacovigilance Curriculum gets enrichment

The ISoP PV Curriculum databank pilot

The PV curriculum link is now posted in a pilot form and for a period of time on the open ISoP website.

This fits perfectly with the PV curriculum concept that it can be used by “everybody everywhere”!

We hope that it will support the memberships’ pharmacovigilance teaching in the different regions and that the tool gains supporters, prepared to help it develop further and become an ever more useful tool.

We are conscious that the tool, while adequate for a proof of concept pilot, clearly requires changes for a sustainable optimal future version of the tool.
 We will collect feedback for inclusion from the wider pharmacovigilance community over the coming weeks.

Disclaimer: For this pilot project ISoP takes no responsibility for the accuracy of the links, and no judgement on the content of the educational material. Further choice of linkage is not endorsed by ISoP but entirely a judgement of the uploading individual.

Have a try, test the tool and let us know your suggestions at training@isoponline.org

 

How the PV Curriculum databank works?

Quite simply, click on the link above and follow the instructions on screen. Here are some directions:

‘Search’ Tab of the Curriculum Tool.
This will allow you to select a section that you want to search on. Please note that not all chapters of the curriculum are currently covered.
The WHO – ISoP curriculum as such is neither ready-for-use teaching material nor a description of a course

‘Add link’ Tab
This will allow you to upload your presentation via URL link that you think can benefit the users of the curriculum.
To upload your presentation (you may upload max. 3 presentations), follow the instructions on screen (please do not forget to copy and paste your hyperlink (including http), select which categories*, and finally click the ‘Submit’ button)

Tip 1: You may select a general topic – Level 1 or Level 2 – using the ‘+’ button (when not sure to where to tag), or/and choose any level and you can add the same presentation to several sections and add a presentation to a section even if it only covers part of the topics listed.
You may find that in several places of the curriculum there is some overlap, this is because the same subject could be regarded under different aspects (e.g. pharmacological, organisational, or regulatory).

Tip 2: If a presentation has something significant to say on a specific topic, even though not covering the curriculum topic completely then it is good to link it to that topic.

This Tab allows you to ‘tag’ external links that are relevant to the PV Curriculum.

Therefore, please let us know when you have uploaded your material as we need to publish them in order to show your results in ‘Search’ tab.

The steps are:

Please click on the link above
2
 Select ‘Add link’
3
 Follow instructions to upload your link url and tag the presentation to the PV curriculum
and then
4
 Inform ISoP Administration at administration@isoponline.org


The WHO-ISoP Pharmacovigilance Curriculum is now public!

ISoP is very pleased to inform you that the Pharmacovigilance Curriculum, developed by experts from ISoP, WHO and institutions dedicated to pharmacovigilance, is available electronically on the Springer website. If you are member of ISoP, you may also have access to the document via the ISoP website at the members section. The curriculum contains a theoretical part in a comprehensive modular form, practical tasks and some key literature references.

The PV curriculum can be used by everyone who needs to plan and conduct training courses in pharmacovigilance.