The WHO-ISoP Pharmacovigilance Curriculum

1

What is and Why do we Need Pharmacovigilance (PV)?

1.1

Subject and scope of PV

1.1.1

Context, definition and purpose of PV

1.1.2

The adverse event (AE) and adverse drug reaction (ADR) at the centre of PV

1.1.3

The wide scope of PV

1.1.4

Persons and parties involved in PV–their concerns, competences and interactions

1.1.5

The increasing complexity and challenges of PV

1.2

History of PV: important ADRs and methodological and organisational developments

1.2.1

The origin of modern PV: thalidomide and the emergence of ADR reporting and drug legislation

1.2.2

Major disasters and their impact on PV: OCs–VTE, HRT–breast cancer, cerivastatin–rhabdomyolysis, coxibs–cardiovascular death, etc

1.2.3

The shaping of institutions, international cooperation and information exchange

1.2.4

Focus on methods: spontaneous reporting, pharmacoepidemiology, data bases and linkage, data mining, genetic testing

1.2.5

Focus on medication errors, counterfeiting and patient safety

1.2.6

Focus on proactive risk management and legislation

1.3

ADRs and public health

1.3.1

Effects of ADRs in general for patients’ health and treatment and for drug development and acceptance

1.3.2

High risk patient groups, drug groups and settings

1.3.3

Statistics of drug-related harm to patients’ treatment, health and life

1.3.4

Statistics of financial and other resources needed due to drug-related harm

1.3.5

Statistics of wrong medication leading to drug-related harm

1.3.6

Ecological consequences of drug disposal

1.4

Limited risk prediction from molecular analogy, pre-clinical studies and pre-marketing clinical trials

1.4.1

Risk prediction by drug class analogy

1.4.2

Pre-clinical in vitro tests

1.4.3

Animal toxicology, concept and options

1.4.4

Animal toxicology, limitations

1.4.5

Pre-marketing clinical trials, concept, options, limitations

2

Fundamental Clinical Aspects of ADRs

2.1

Types and mechanisms of ADRs

2.1.1

‘Type A’ (pharmacological): exaggeration of desired effect or effect at different site or of different type

2.1.2

‘Type B’ (hypersusceptibility/idiosyncratic)

2.1.3

Other types of ADRs: poisoning, drug resistance or dependence, carcinogenic or teratogenic effect, infection

2.1.4

Other ADR classifications: according to time course, dosage, patient susceptibility, mechanism, expectedness

2.1.5

Seriousness and severity of ADRs

2.1.6

Surrogate markers as diagnostic indicators, non-serious ADRs or precursors of serious ADRs

2.2

Pharmacogenetic causes of inter-individual variability in the susceptibility to ADRs

2.2.1

Definition, biochemical basis, scope and challenges of pharmacogenetics

2.2.2

Genetic polymorphism of enzymes involved in phase I drug metabolism: CYP 1, 2 and 3 oxygenases

2.2.3

Genetic polymorphism of enzymes involved in phase II drug metabolism and in drug transport

2.2.4

Genetic polymorphism of ion channels, receptors and enzymes involved in pharmacodynamics

2.2.5

Genetic polymorphism of genes responsible for immunological and other idiosyncratic Type B ADRs

2.2.6

Drug development and genetically individualised treatment: tailored indications, tests, safeguards

2.3

Non-genetic risk factors for ADRs and complex interactions

2.3.1

Young and old age, gender, social factors

2.3.2

Target- and concomitant diseases including virus infection, history of drug intolerance, temporary situations

2.3.3

Pregnancy and teratogenic effects

2.3.4

Drug–drug interactions at same molecule/site–pharmacokinetic or pharmacodynamic, synergistic or antagonistic

2.3.5

Complex interactions between drugs affecting different molecular sites or organs and other risk factors, e.g. renal or hepatic impairment

2.3.6

Drug interactions with food, alcohol, grapefruit, vitamins as food additives, smoking, sun exposure

2.4

Clinical management of ADRs

2.4.1

Avoiding ADRs of individual patients à priori: personal risk assessment and precautionary measures

2.4.2

Treating symptoms and assessing and eliminating possible causes in case of ADR suspicion

2.4.3

Identifying the ‘culprit’ in case of ADR suspicion

2.4.4

Continuing treatment after an ADR was considered likely

3

Important ADRs and ‘Risk Driving’ ADRs of Important Medicines

3.1

Serious ADRs at organ classes where ‘Type B’ reactions are important. Most involved drugs

3.1.1

ADRs affecting the skin

3.1.2

ADRs affecting haematopoiesis, blood cells and haemostasis

3.1.3

ADRs affecting the liver and the biliary system

3.1.4

ADRs affecting the kidney and urinary tract

3.1.5

ADRs affecting the respiratory tract

3.2

Important ADRs at organ classes where ‘Type A’ reactions are most important, and the mostly involved drugs

3.2.1

ADRs affecting the gastrointestinal tract

3.2.2

ADRs affecting the endocrine system and metabolism

3.2.3

ADRs affecting the cardiac and the vascular system

3.2.4

ADRs affecting the nervous system

3.2.5

ADRs affecting vision, hearing and taste

3.2.6

Tumorigenic and teratogenic effects

3.3

Focus on ADRs of anti-infectives particularly important in limited resource settings and of vaccines

3.3.1

ADRs of anti-HIV medicines

3.3.2

ADRs of anti-tuberculosis medicines

3.3.3

ADRs of anti-malaria medicines

3.3.4

ADRs of medicines used in neglected tropical diseases

3.3.5

Vaccines: peculiarities of their ADRs in general, lack of effectiveness, injection site reactions

3.3.6

Vaccines: generalised ADRs due to immunological reactions, toxicity or replication of infective agents

3.4

‘Risk drivers’ of important drugs for common illness and chronic diseases, biologicals, herbals

3.4.1

ADRs of medicines used in common cold (fever, headache, pain, cough)

3.4.2

ADRs of medicines used in respiratory disorders (asthma, COPD)

3.4.3

ADRs of medicines used in rheumatic disorders (back pain, osteoarthritis)

3.4.4

ADRs of medicines used to treat anxiety, depression and mental discomfort

3.4.5

ADRs of medicines used in metabolic syndrome (hypertension, dyslipidaemia, obesity, diabetes)

3.4.6

ADRs of widely used herbals

4

‘Individual Case Safety Reports’ (‘ICSRs’)

4.1

Concerns about ADRs: medical, psychological and regulatory background and reasons for reporting

4.1.1

Definition of ICSRs and their ‘typology’ with respect of provenance and subject matter

4.1.2

Place value of ICSRs in PV: insights they can and cannot provide and their impact on drug regulation

4.1.3

Healthcare professionals as reporters: their knowledge, diagnostic means, motivations and fears

4.1.4

Patients as reporters: their concerns, expectations, specific knowledge and observations

4.1.5

MAHs as reporters: their information background, sources and obligations

4.1.6

‘Culture’, stimulation and organisation of spontaneous ADR detection and reporting

4.2

Contents, structure and validity of reports and reporting procedures

4.2.1

Minimum necessary information, structured fields on one-page reporting forms, overview of ICH E2B

4.2.2

Case narratives

4.2.3

Case follow-up and validation

4.2.4

Literature reports

4.2.5

Use of AE/ADR terminologies and definitions and drug dictionaries by primary reporters

4.2.6

Use of technical means for reporting

4.3

Case assessment

4.3.1

Completeness, accuracy and precision of the report

4.3.2

Certainty of the diagnosis

4.3.3

Seriousness and severity of the AE/ADR

4.3.4

Causality of the AE: purpose, criteria and problems of the assessment

4.3.5

Causality of the AE: common general and specific assessment methods, outcome ratings, shortcomings

4.3.6

Expectedness of the AE/ADR

4.4

Reports related to vaccines, herbals and specific situations

4.4.1

Reports about adverse events following immunisation (AEFI): specific features

4.4.2

Causality assessment with AEFI

4.4.3

Reports about AEs/ADRs with herbal medicines

4.4.4

Reports about AEs/ADRs related to pregnancy and lactation

4.4.5

Reports about drug-drug interactions, drug abuse and poisoning

5

Pharmacovigilance in Clinical Trials

5.1

Characteristics of pharmacovigilance in clinical trials

5.1.1

Types, objectives and limitations of pre-authorisation studies

5.1.2

Categories of primary hazard data

5.1.3

Safety in focus of early drug development, in particular first-into-man studies

5.1.4

Prevailing patient groups and medicines according to current public health needs

5.1.5

Persons and bodies involved, responsibilities, co-operation

5.2

Collection of hazard data: planning and practical realisation

5.2.1

Study protocol, investigator brochure, informed consent form

5.2.2

Specific vulnerable (sub-) populations

5.2.3

Treatment-related risks

5.2.4

Test parameters

5.2.5

Strategies of data collection

5.2.6

Data presentation

5.3

Risk assessment

5.3.1

Assessment of individual AE observations

5.3.2

Detection of specific ADRs as harmful properties of IMPs and non-IMPs

5.3.3

Statistical quantification of safety data from individual studies

5.3.4

Data pooling and ADR frequency estimation

5.3.5

Development of labelling

5.4

Guidance and regulatory framework

5.4.1

Guidelines and directives

5.4.2

Key documents at the start and during a study

5.4.3

Key documents at and after the end of a study

5.4.4

Reporting obligations

5.4.5

Other communication activities

6

Counterfeiting, Quality Defects and Medication Errors

6.1

Counterfeiting, demarcation against manufacturing-related quality defects

6.1.1

Definition of substandard/spurious/falsely labelled/falsified/counterfeit (SSFFC) medicines and respects of counterfeiting

6.1.2

Pattern and scale of counterfeiting; consequences, in particular antimicrobial resistance

6.1.3

Methods used by counterfeiters

6.1.4

Technical, organisational and political anti-counterfeit measures

6.1.5

How the legitimate MAH can and should help

6.1.6

How to manage unintentional quality defect problems

6.2

Medication error (ME): definition, impact, detection

6.2.1

Definition and typology of MEs, demarcation from off-label use

6.2.2

ME statistics and impact on public health

6.2.3

Victims, medical situations and medications typical for MEs

6.2.4

Detection of MEs: national spontaneous reporting schemes for professionals

6.2.5

Detection of MEs: methods in specific healthcare settings for professionals

6.2.6

Detection of MEs: patient reporting

6.3

ME reports: description and assessment

6.3.1

Description of clinical patient aspects

6.3.2

Description of procedural and patient adherence aspects

6.3.3

Assessment of the proximal/immediate cause

6.3.4

Contributing system factors

6.3.5

Root cause analysis (RCA)

6.3.6

Assessment of avoidability/preventability

6.4

Preventive measures

6.4.1

Education and information material

6.4.2

Culture of the handling of ME incidences and learning from them

6.4.3

Global political and regulatory activities

6.4.4

Local and technical organisational measures

6.4.5

Specific aspect: conflict, synergy and harmonisation with classical PV (challenges)

6.4.6

Legal, ethical and confidentiality aspects

7

Spontaneous ICSR Reporting Systems (SRS)

7.1

Definition, settings, potential and limitations of SRS

7.1.1

Definition, potential and achievements of SRs

7.1.2

SRS settings and resources; sources of spontaneous reports (SRs)–healthcare professionals (HCPs), patients, companies, media

7.1.3

Detecting, documenting and reporting of AEs/ADRs: methods, forms, routes, software

7.1.4

Places and institutions collecting spontaneous reports

7.1.5

Informational limitations of SRs: incomplete, no denominator, biases; proposed caveats

7.1.6

Stimulated, mandatory, solicited and targeted reporting

7.2

Computerised ICSR databases: requirements and structure, administration

7.2.1

Typical ICSR databases: relational model, SQL language

7.2.2

Structure (e.g. separate patient, literature, study reports), scalability, performance

7.2.3

Stability, resilience, security, storage, maintenance

7.2.4

Database management systems: requirements, available report management software

7.2.5

Quality assurance: duplicate-, syntax-, coherence-check, tracking facilitation and follow-up

7.2.6

Specific requirements of pharmaceutical company databases, e.g. reporting functions

7.3

Data transmission and entry

7.3.1

Forms and formats of ICSR transmission: one-page forms, email, phone, ICH E2B, ICH M2

7.3.2

Coding of diseases and ADRs using terminologies WHO-ART, ICD, MedDRA

7.3.3

Coding of drugs using classifications and dictionaries: ATC, WHO-DD (enhanced), EVMPD

7.3.4

Special issues: quality check, anonymisation, case IDs, lab data tables, narratives, language

7.3.5

Correspondence with reporters: confirmation of receipt, requests for additional data

7.4

Data retrieval, descriptive statistics, access and confidentiality

7.4.1

Electronic techniques of data retrieval: formats, networks, browsers and other tools, SGML language

7.4.2

Serving the searcher: standardised entry screens, search support, stratification of data

7.4.3

Descriptive statistics (presenting numbers; not analysing and testing)

7.4.4

Format of retrieval results: line listings, summary tabulations, profiles, sometimes ICSRs

7.4.5

Graded access according to data and interested parties, proactive publications; confidentiality

7.4.6

Important accessible databases, terms of access: WHO/UMC, others

8

Signal Detection and Management

8.1

Definition of a signal; sources, potentials, detection by non-statistical medical means

8.1.1

What is a ‘signal’?–definitions by WHO, CIOMS, others

8.1.2

What a signal may indicate: new ADR, higher severity or frequency, risk factors, wrong medication, product faults

8.1.3

Sources of information which may constitute a signal: ADR databases, case-control surveillance, other sources

8.1.4

Basic requirements for signal detection and management

8.1.5

Stakeholders in the signal detection and management process

8.1.6

Detection of signals for new ADRs from ADR case-series by non-statistical medical means

8.2

Disproportionality statistics for signal detection in spontaneous ISCR databases

8.2.1

Principles of statistical data mining in ICSR databases

8.2.2

Calculating proportional reporting ratios (PRRs) and reporting odds ratios (RORs)

8.2.3

Bayesian methods: information component (IC) and gamma poisson shrinker calculating EBGM

8.2.4

Calculating statistical significance of disproportionate reporting and confidence intervals

8.2.5

Determining sensitivity and specificity of signal detection by defining minimum number of reports, extent of disproportionality and statistical significance

8.2.6

Strengths and weaknesses of different data mining methods, e.g. vulnerability to low and high numbers

8.3

Special issues in disproportionality approaches

8.3.1

Applying disproportionality statistics to ICSRs selected by quality, ADR (group), drug (class), indication, age. Excluding known ADRs

8.3.2

Detecting complex associations: drug-drug interactions, other risk factors, syndromes

8.3.3

Combining ICSR and drug utilisation data (e.g. from IMS) as denominator

8.3.4

Applying disproportionality statistics to longitudinal patient record and exposure data

8.3.5

Sequential probability ratio tests (SPRTs); tree-based scan statistic (ScanTree)

8.3.6

Available software for data mining

8.4

Prioritisation, validation, assessment, risk confirmation or refusal, communication, further action

8.4.1

Prioritisation according to evidence and potential public health impact (seriousness, drug utilisation)

8.4.2

Validation by checking report quality, duplicates, plausibility, consistency, other information, biases

8.4.3

Assessment, absolute: clinically plausible causality, meaning, impact, preventability

8.4.4

Assessment, relative: relating number of reports to utilisation, comparing with other drugs

8.4.5

Consequences of confirmed signals: communication, further investigation, options of action

9

Post-Authorisation Observational Studies and Clinical Trials in PV

9.1

Definition and objectives of post-authorisation studies, general requirements, specific studies

9.1.1

Definition of post-authorisation studies, non-interventional studies, pharmacoepidemiology

9.1.2

Post-authorisation studies for confirmation of signals and providing data on ADR frequency and causality

9.1.3

Observational studies: general formal and scientific requirements, opportunities, limitations

9.1.4

Population-oriented post-authorisation studies: disease studies, drug utilisation studies

9.1.5

Post-authorisation randomised clinical trials, in particular ‘large simple trials’ (LSTs)

9.2

Important observational studies and their strengths and weaknesses

9.2.1

Cohort studies in general: design, conduct, statistical analysis and presentation of results

9.2.2

Cohort-event monitoring (CEM), including PEM as specific applications

9.2.3

Dealing with different hazard functions and different exposure times (person years)

9.2.4

Case-control studies: design (including nested in cohorts), conduct, statistical analysis and presentation of results

9.2.5

Rationale and approaches for within-patient study designs, e.g. case-crossover studies

9.3

Bias, confounding and effect modification in observational studies

9.3.1

Definition of bias and confounding and principles of dealing with them

9.3.2

Important biases: selection (e.g. referral) bias, information (e.g. recall) bias, detection bias; how to deal with these biases

9.3.3

Important confounders, in particular confounding by indication

9.3.4

How to deal with these confounders (e.g. matching, propensity scoring, sensitivity analysis)

9.3.5

Effect modification: principles of measurement and presentation in a study report

9.3.6

Novel designs avoiding with these problems: within-subject or case-crossover designs

9.4

Sources of study subjects and data

9.4.1

De novo data collection (interviews, patient charts), spontaneous reports, surveys, CEM

9.4.2

Large automated health databases (LADs) or electronic medical records: typical structure

9.4.3

Important accessible LADs in North America, Europe and Asia

9.4.4

Registers of diseases, specific ADRs or exposure; pregnancy registers

9.4.5

Record linkage: options and problems (e.g. compatibility, confidentiality)

9.4.6

Choosing data and methods for the estimation of ADR frequencies

10

Benefit-Risk Assessment

10.1

‘Benefit-risk’: definitions, methodological approaches; disease as criterion of benefit

10.1.1

Definition of benefit, harm, chance, risk and their components magnitude, duration, likelihood

10.1.2

Initiatives to develop methods for benefit-risk assessment: PROTECT, BRAT

10.1.3

Frameworks for benefit-risk analysis: Ashby-Smith Bayesian approach, MCDA, SMAA

10.1.4

Complexity of disease-related risks: multiplicity, time dependence, likelihood, subjectivity

10.1.5

Disease-related harm and risk as targets of drug treatment and criteria of benefit and chance

10.2

Drug-related risks (ADRs): analysing, weighting and combining their components

10.2.1

Complexity of ADR-related risks: multiplicity, time dependence, likelihood, subjectivity

10.2.2

Measuring and weighting disease- and drug-related objective and subjective ‘instantaneous harm’

10.2.3

Considering aspects of time: point in time (hazard function), duration of harm

10.2.4

Combining harm and likelihood: the risk (due to drugs as well as diseases)

10.2.5

Weighting, combining, comparing risks using single metrics, or ‘currencies’, and ‘risk equivalents’

10.2.6

Typical discrete and continuous measures of harm: deaths, incidents, hospitalisations, QALYs, etc.

10.3

Balancing benefit/chance vs. harm/risk and comparing different treatment options

10.3.1

Principles of estimating benefit/chance in terms of reducing disease-related harm/risk using single metrics

10.3.2

Expressing benefit/chance and risk using indices like NNTand NNH, adjusted for utility, if applicable

10.3.3

Using the semi-quantitative Markov and Kaplan–Meier methods, including aspects of time

10.3.4

Estimating the difference between risks from untreated disease and treated disease plus ADRs; calculating the INHB

10.3.5

Comparing those differences across alternative treatment options: ‘indirect/mixed treatment comparisons’

10.3.6

Combining and balancing disease-related harm/risks and drug-related benefit/chance and ADRs on the public health level

10.4

Taking into account preferences of stakeholders, uncertainties and options for actions

10.4.1

Determining preferences vs. benefit/chance and harm/risk of different stakeholders: preference values; utility surveys

10.4.2

Non-pharmacological and indirect risks: misuse, errors, further complications

10.4.3

Options for improving the chance-risk balance and their likely impact; aspects of feasibility

10.4.4

Uncertainties in the underlying data: level of evidence, confidence intervals; applying the Probabilistic Simulation Method (PSM)

10.4.5

Analysing sensitivity: worst case–best case scenarios; considering the precautionary principle

10.4.6

Making chance-risk estimates understandable: visualisation and communication

11

Pharmacovigilance and Risk Management Systems, Risk Management Plans (RMPs), Inspections

11.1

Pharmacovigilance systems: definition, stakeholders and operation

11.1.1

Definition and elements

11.1.2

Contents of the ‘Pharmacovigilance System’ document, masterfile concept

11.1.3

Pharmacovigilance systems of pharmaceutical companies, marketing authorisation holders (MAHs) and distributors

11.1.4

Pharmacovigilance systems of regulatory authorities

11.1.5

Standard operating procedures (SOPs)

11.1.6

Maintenance of the pharmacovigilance systems

11.2

Product-related risk management systems

11.2.1

Rationale for establishing risk management systems and objectives

11.2.2

Establishing a risk management system: starting point and responsibilities

11.2.3

Characterisation of the risk profile

11.2.4

Risk management during the lifecycle of a drug, planning of PV activities, updating the risk management system

11.2.5

Legal basis and guidelines, role of relevant stakeholders and partners

11.3

Specific product-related RMPs; other tools and activities

11.3.1

Scope, definitions and responsible persons and institutions to establish risk management tools: RMP, REMS, others

11.3.2

Elements of risk management tools: safety specification, pharmacovigilance plan, risk mitigation measures; SmPC and PIL

11.3.3

When to establish and update a risk management tool and pharmacovigilance plan

11.3.4

Implementation, monitoring and assessing effectiveness of risk mitigation measures

11.3.5

Communication

11.4

Pharmacovigilance inspections and audits, quality assessment

11.4.1

Purpose, frequency and actors

11.4.2

Indicators of capacity and performance of the pharmacovigilance system

11.4.3

External inspections by competent authorities

11.4.4

Internal audits in companies and regulatory authorities

11.4.5

Quality assurance and benchmarking processes

11.4.6

Legislation and guidelines

12

Industry and Regulatory Authorities, Mandatory Procedures from Legislation

12.1

Facilities at pharmaceutical companies, marketing authorisation holders, wholesalers and distributors

12.1.1

Pharmacovigilance system and SOPs, crisis management plan

12.1.2

QPPV, staff resources (scientific and administrative), financial resources, technical equipment

12.1.3

Databases (ADR reports), performance tools, statistical tools and methods for analyses

12.1.4

Product-related archives, correspondence archives, library and access to electronic literature databases

12.1.5

Communication tools, contact details, Internet access, fax, phone, video conference services

12.2

Mandatory tasks and procedures from legislation at industry

12.2.1

ADR collection and reporting to competent authorities, signal detection and management

12.2.2

Study reports, Periodic Safety Update Reports (PSURs), Periodic Benefit Risk Evaluation Reports (PBRERs)

12.2.3

Other documents: DSUR; RMP, REMS; renewal dossiers; reports on request

12.2.4

Regular benefit/chance-to-harm/risk assessment

12.2.5

Decision making, monitoring effectiveness of measures taken

12.2.6

Quality management, determination and assessment of performance indicators, training

12.3

Facilities at regulatory authorities

12.3.1

Pharmacovigilance system and SOPs, crisis management plan

12.3.2

Staff resources (scientific and administrative), technical equipment

12.3.3

Databases (ADR reports), statistical tools and methods for analyses

12.3.4

Product-related archives, correspondence archives, library and access to electronic literature databases

12.3.5

Communication tools, press officer, contact details, Internet access, fax, phone, video conference service

12.3.6

Quality management, determination and assessment of performance indicators, training

12.4

Mandatory tasks and procedures from legislation at regulatory authorities

12.4.1

ADR collection and storing in an electronic database, signal detection and management

12.4.2

Causality assessment and root cause analysis, regular benefit/harm-to-harm/risk assessment

12.4.3

Decision-making processes, monitoring effectiveness of measures taken

12.4.4

Reporting to other competent authorities, international organisations and governments

12.4.5

Quality management system, training

12.4.6

Communication

13

PV Organisation and Public Health

13.1

Detection, documentation and reporting of ADRs on the local level

13.1.1

Reality in rural areas in limited resource settings: patients, diseases, drugs, distributors, HCPs and other health workers

13.1.2

Symptoms of what could be ADRs of drugs used in tropical and other serious infections

13.1.3

What normally happens in the first instance if a patient suffers from such an experience

13.1.4

ADR reporting in industrialised countries on the local level: persons, tools, communication

13.1.5

Industry and drug marketing persons/institutions in ADR reporting in poor and rich settings

13.1.6

Use of e-technology (mobile phones, apps, company websites)

13.2

PV capacity building and organisation on the regional and national level

13.2.1

A national PV policy and legislation

13.2.2

National and regional PV centres and networks; staff, technical equipment, library

13.2.3

System and tools for spontaneous ADR reporting

13.2.4

Concepts for PV capacity building within a centre or health facility, training

13.2.5

Realisation of PV capacity: budget, funds, donors

13.2.6

Co-operation with HCPs, hospitals, professional societies, academia, patient organisations, industry on national and international level

13.3

Public Health Programmes (PHPs) with PV aspects and other PV projects

13.3.1

Major elements of PHPs; WHO as initiator, organiser and co-ordinator of PHPs; co-operation with national regulatory authorities

13.3.2

Tasks and tools related to PV in PHPs: ethnically and socially specific ADRs; CEM, TSR

13.3.3

Important PHPs targeted at AIDS, tuberculosis, malaria: GFATM, BMGF, UNITAID

13.3.4

Vaccination programmes

13.3.5

Other international PV projects: ENCePP, PROTECT, OMOP, MIHARI, ‘Monitoring Medicines’ project

13.3.6

Evaluation of PV data in the context of PHPs

13.4

Co-operative international organisations, industry associations

13.4.1

WHO, WHO Collaborating Centres–Uppsala, Accra, Rabat; ACSoMP, GACVS; CIOMS; regional organisations and initiatives

13.4.2

Patient safety organisations: WAPS, IAPO, EURODIS

13.4.3

International Society of Pharmacovigilance (ISoP), ISPE, IUPHAR

13.4.4

International Conference on Harmonisation (ICH), procedures, deliverables and publications

13.4.5

Mainly pharmaceutical industry: DIA, IFPMA

13.4.6

International Organisation for Standardisation (ISO)

14

Communication

14.1

Context and guidance

14.1.1

Public health goals

14.1.2

Scene and climate

14.1.3

Theories and guidance

14.1.4

Legal framework

14.1.5

Experience on communication effectiveness

14.1.6

Crisis management

14.2

Communication with patients and healthcare professionals: tools, channels and processes

14.2.1

Individual communication

14.2.2

Mass communication

14.2.3

Involvement of the public

14.2.4

Tools and channels

14.2.5

Impact, feedback and evaluation

14.3

Communication with patients and healthcare professionals: contents and presentation

14.3.1

Considering the target population

14.3.2

Typical subject matters and recommendations to patients and healthcare professionals

14.3.3

Selection of data

14.3.4

Information elements and structure of the text

14.3.5

Specific medications and hazards

14.4

Interaction among stakeholders, including the media

14.4.1

Communication for involvement of the public in PV processes

14.4.2

Interactions between stakeholders throughout the communication process

14.4.3

Interaction between stakeholders in relation to RMPs

14.4.4

Specifics for interaction with scientific and general media

14.4.5

Press conferencing

15

Sources of Information

15.1

Primary data: figures, facts, terms, cases

15.1.1

Databases with spontaneous ADR reports

15.1.2

Data from poison control centres: intoxication, contamination

15.1.3

Public health data, epidemiological databases

15.1.4

Sales and exposure data, drug utilisation data

15.1.5

Thesauruses and dictionaries of ADR terms, diseases, drugs

15.2

Secondary information: assessments, judgements, decisions (hardcopy or electronic version)

15.2.1

Study results, ICSR observations, summary assessments

15.2.2

Guidelines, specific recommendations

15.2.3

Drug monographs, regulations, other official decisions

15.2.4

International symposia, local news and advisories

15.2.5

Mixed information, including news, policy, economy, announcements

15.3

Electronic/Internet methods for searching and managing information

15.3.1

Gateways to literature databases

15.3.2

Search engines and attention tools

15.3.3

Software for ADR database searching

15.3.4

Shared networks, discussion groups, chatrooms, weblogs, social media

15.3.5

Services for literature search and drug information management

15.3.6

Strategies for searching for information and literature management

15.4

Materials and training courses, where appropriate, specific for regions or settings

15.4.1

Textbooks

15.4.2

Courses: general or specific methodological (ICSR assessment, signal detection, pharmacoepidemiological studies)

15.4.3

Courses: technical/administrative/procedural topics (e.g. electronic reporting, literature search, PBRERs)

15.4.4

Courses: specific medical topics (e.g. vaccines, anti-HIV drugs, anti-malarials; hepatotoxicity)

15.4.5

‘Hands-on’ practical training