| Module |
Credits |
Compulsory/optional |
|
Pharmacovigilance Regulations and Guidelines
|
15 Credits |
Optional |
| Europe: Clinical trial regulation, licence applications. MHRA, Medicines Acts Information Letters (MAILs). Association of the British Pharmaceutical Industry (ABPI) Code of Practice (relevant parts). EU Regulations and Directives on Pharmacovigilance (PV), PV Guidelines, CIOMS (I, II, III, IV and V) and ICH guidelines. Biologics, vaccines and medical devices. Summary of product characteristics. FDA Regulations: expedited and periodic reporting, investigational new drugs (IND), new drug applications (NDA). Other countries PV regulations and guidelines as appropriate. Communication between authorities, data sheets and labelling updates. PILs and patient information packs; safety information requirements. Pharmacovigilance System Master File (PSMF) (GVP II). Pharmacovigilance inspections (GVP III) and audits (GVP IV). |
|
Drug Safety in Clinical Trials
|
15 Credits |
Optional |
| Animal toxicology findings and their relevance to clinical trials. Phases of clinical trials: trial design and analysis (including adaptive design), adverse event reporting and monitoring in clinical trials, protocol development and Case Report Form (CRF) design, Good Clinical Practice (GCP), protocol design and safety monitoring aspects of a study, safety biomarkers, safety issues in clinical pharmacology studies, ethics committees; randomisation and the breaking of study codes. Investigator brochures; presentation of safety data from clinical trials; study reports; product licence applications format and organisation of the CTD clinical summaries (in particular the SCS) as per ICH M4E; NDAs, SPC expert reports, large scale end-point studies and safety monitoring boards. Limitations of clinical trials in determining the safety profile of a new medicine. Statistics. DSURs (ICH E2F) including non-clinical information. Clinical trials involving vaccines and biologics. Drug use in paediatrics (PIP). Guidance on 2011/C 172/01 collection, verification and presentation of adverse event/reaction reports arising from clinical trials on medicinal products (including concepts of IMP, non-IMP). Investigator notifications (IND).
Management of urgent safety measures. |
|
Adverse Drug Reactions by Major Body Systems II
|
15 Credits |
Optional |
| The adverse effect of drugs on the renal, cutaneous, gastrointestinal, musculoskeletal, and endocrine systems. Clinical presentations, case histories and practical examples of adverse drug reactions. Drug interactions: pharmaceutical, pharmacokinetic and pharmacodynamic mechanisms and examples. Drug administration in pregnancy: stages in foetal development and sensitivity to teratogens and other toxic effects on foetal tissue. Use of drugs in nursing mothers: effects on lactation, infant toxicity, relevance of animal toxicology data. Other special groups including: drug use in paediatric patients, the elderly and those with hepatic and renal impairment. Drug overdoses - Poisons Information Centres. Lack of efficacy and Off-label use (GVP VI). Reference to Periodic Safety Update Reports (GVP VII) and Post-authorisation safety studies (GVP VIII). |
|
Management of Pharmacovigilance Data
|
15 Credits |
Optional |
| Good pharmacovigilance practices (GVP I): Pharmacovigilance (PV) systems and their quality systems. Company processes and procedures for handling data (methods used for collection and follow-up).
Information Systems and Compliance: Use of SOPs, working practices and guidelines in data management, auditing, quality assurance and inspections.
PV Databases: Database design (vendor and bespoke systems), customisation, implementation and validation (relevant regulations including data privacy), maintenance of company systems and upgrades.
Coding (medical terminology, products and lists of values), PV data values.
Electronic Reporting and Safety Data Exchange: Interaction with agencies for seeking information and for electronic interchange, global electronic reporting of individual case safety reports, safety data exchange procedures inter- and intra-companies.
Signal Detection: Data Mining and Signal Management (GVP IX), use of adverse experience and prescription data to determine signals. Statistical methods for signal detection. |
|
Principles of Pharmacovigilance
|
15 Credits |
Optional |
| Historical perspective of pharmacovigilance, international co-operation in pharmacovigilance (GVP XIV), drug safety terminology and definitions of specific adverse events. Principles of safety evaluation during a drug's life-cycle, risk perception and benefit risk assessment (high-level). Differences between small molecules and biological. Causality assessment, reference sources and drugs withdrawn for safety reasons.
Sources and optimum composition of spontaneous reports (elements of GVP VI),
advantages and limitations of spontaneous report data. Factors affecting spontaneous reporting of ADRs. How the MHRA handles spontaneous data (the Yellow Card System, data collection, signal detection and analysis). MEDWATCH Program in the US, French Regional Pharmacovigilance Centres. Licence partners and safety data exchange agreements (elements of GVP VI). Additional monitoring (GVP X).
Descriptive statistics (populations, mean , median, mode, measures of variation, confidence limits). |
|
Adverse Drug Reactions by Major Body Systems I
|
15 Credits |
Optional |
| Classification of ADRs, pharmaceutical, pharmacokinetic, pharmacodynamic and pharmacogenetic factors leading to ADRs, physiological control systems, clinical chemistry (reference ranges). The adverse effect of drugs on the hepatobiliary, immune, respiratory, cardiovascular, central nervous, haematological.
Investigations including monitoring of vital signs, important laboratory and diagnostic tests.
Clinical presentations, case histories and practical examples of adverse drug reactions. Criteria for defining ADRs. Exercises to evaluate cases and how these can be determined. |
|
Pharmacoepidemiology
|
15 Credits |
Optional |
| The development of pharmacoepidemiology as a scientific entity; hypothesis generation and testing, epidemiology of disease, epidemiological study designs, case reports, case series, case control and cohort studies.
Post-authorisation surveillance; history and critical analysis and epidemiological implications,
non-interventional -v- interventional studies; selection and design examples and critical evaluation. Data selection; quality -v- quantity. A comparative global review of record-linkage databases (strengths and weaknesses) study design considerations. Other sources: Registries and the Cochrane Collaborative database. Performing meta-analysis and handling large data-sets considerations. Integrated benefit risk assessment (GVP VII). |
|
Labelling and Risk Management
|
15 Credits |
Optional |
| Guidelines/directives on labelling: CIOMS III, IV and V initiatives, ICH guidelines, PV aspects of labelling, Good labelling practice. Pharmacoepidemiology and labelling,
Development Core Safety information, Patient Information Leaflets,
Data Sheets, Summary of Product Characteristics and Variations (Type I and Type II). Implications of MedDRA. On-going benefit risk analysis (GVP XII), risk minimisation activities, and measurement of their effectiveness, expert views, pre- and post-authorisation data. Safety communication (GVP XV) including communication of risk and public participation in PV (GVP XI). Mass media, crisis management, Risk Management systems (GVP V), Safety data in decision making; management of identified and potential risks. Practical risk management including effective communication. Risk minimisation measures, selection of tools and indicators (GVP XVI). |
|
Pharmacovigilance Regulations and Guidelines
|
15 Credits |
Optional |
| Students will study a range of content including the topics detailed below. Emphasis is placed on the interpretation and impact of pharmacovigilance regulations on the pharmaceutical industry both pre- and post-authorisation.
EU Regulations and Directives on Pharmacovigilance (PV), PV Guidelines, CIOMS (I, II, III, IV and V) and ICH guidelines. EU Medical Device Regulation. Clinical trial regulation and license applications. The MHRA, Medicines Acts Information Letters (MAILs). Association of the British Pharmaceutical Industry (ABPI) Code of Practice (relevant parts). FDA Regulations: expedited and periodic reporting, investigational new drugs (IND), new drug applications (NDA). New Post Marketing Safety Reporting (PMSR) requirements for combination products (81 FR 92603). Other countries PV regulations and guidelines as appropriate (e.g. Japanese, China) and emerging regional models (e.g. Africa). Communication between authorities, data sheets and labelling updates. PILs and patient information packs; safety information requirements. Difference in requirements for small molecules, biologics, vaccines and medical devices. Summary of product characteristics.
PV System Master File (PSMF) (GVP II). PV inspections (GVP III) and audits (GVP IV). GDPR and its relevance to PV. AI & machine learning in PV; expectations, validation, assessment in PV inspections and potential signal management use. Guidance from FDA CDRH division in 2019 and emerging guidance from MHRA.
The module will be delivered in three parts; students will be provided with pre-module reading to introduce them to the topics of the module. This will be followed by attendance at lectures and workshops during an intensive 3-day residential course in Hatfield. The final part will be a module assignment to be completed after the 3-day block teaching. |
|
Drug Safety in Clinical Trials
|
15 Credits |
Optional |
| You will study the following items: Animal toxicology relevance in protocol development/design (Phases I-III). Ethics Committees and obtaining ethical approval. Safety monitoring: adverse event reporting, breaking the blind, interpretation of laboratory data. Case Report Forms, significance testing & randomisation. Reporting: study reports, Common Technical Document, Reference Safety Information, Development Safety Update Report (DSUR). Risk assessment in clinical development. Real-time monitoring pharmacovigilance. Post authorisation efficacy and safety studies. |
|
Project, Pharmacovigilance
|
60 Credits |
Optional |
| This module will include reviewing literature, appropriate research design, ethics, data analysis including statistical analysis and preparation of the research proposal and report. Students will be supported through one-to-one sessions with their supervisors and a range of formative assessments including a literature review, mock presentation and draft project. Students will be allocated a University supervisor, and have a workplace supervisor, who will guide them in their choice of project, aims/objectives, literature search, research design, data collection/evaluation and report writing through supervisor meetings. |
|
Principles of Pharmacovigilance
|
15 Credits |
Optional |
| You will study the following: Introduction to pharmacovigilance, Good Vigilance Practice, UK, EU and International pharmacovigilance. Pharmacovigilance systems and quality management systems. Principles of safety evaluation pre- and post-authorisation, adverse event causality assessment, risk perception and benefit risk assessment. Sources, advantages & limitations of spontaneous reports Examples of drugs withdrawn for safety reasons. Pharmacovigilance in non-medicinal products i.e., devices, small molecules How Regulators handle spontaneous data Licence partners and safety data exchange agreements Descriptive statistics used in drug safety surveillance. |
|
Pharmacoepidemiology
|
15 Credits |
Optional |
| You will study the following: The development of pharmacoepidemiology. Hypothesis generation and testing, epidemiology of disease, epidemiological study designs, case reports, case series, case control and cohort studies. Post-authorisation surveillance; history and critical analysis and epidemiological implications. Non-interventional-versus-interventional studies; selection and design examples and critical evaluation data selection; quality-versus-quantity. A comparative global review of record-linkage databases (strengths and weaknesses) study design considerations. Using sources: Registries and the Cochrane Collaborative database. Performing meta-analysis and handling large data-sets considerations. |
|
Risk Management and Labelling
|
15 Credits |
Optional |
| You will study the following: Principles of Global Risk Management and risk classification. On-going benefit risk assessment, pre- and post-authorisation data. Practical risk management (GVP V), supporting stakeholders understanding risk and crisis management. Risk minimisation measures, tools, and indicators (GVP XVI) including digital risk minimisation. Patient information leaflets EU Summary of Product characteristics (SmPC) guidance. |
