week 12 part 1 Flashcards
Who does EMA work for?
European Union
What is the European union built on?
A single market
How many people are living in the European Union?
Over 500 million people
How many member states in the European Union?
28
What does the European Union make up?
Just over a quarter of the global sales of medicine in terms of value
How many official languages in the European Union, why?
- 24 official language
2. Highly relevant to the way we communicate as a medicine regulator
What do the EMA do?
- Protect human and animal health
- Facilitate development and access to medicine
- Evaluate applications for marketing authorisation
- Monitor the safety of medicine across their life cycle
- Provide information on human and veterinary medicine to healthcare professionals and patients
Who are the European Union?
- 4000 scientific expert from right across Europe
- 7 scientific committees
- Over 1000 marketing authorisation recommended
- 1995 - EMA established to evaluate medicine for use in the EU
- 28 working parties
- ~890 staff members
What is the expert advice not influenced by?
Particular financial interest
What is the recently born committee called?
- PRAC
[ Pharmacovigilance Risk Assessment Comittee]
Who are the UK regulator?
MHRA
[Medicine and Healthcare product Regulatory Agency]
Who are the EU regulator?
European Medicine Agency (and European Commission]
who does WHO support?
Member states with standards, information, guidelines etc
Does pre-qualification - gives opinion on medicine, meets the established standard of quality, can be used by countries
What does EMA and European Commission do?
- EMA - does the science
2. European Commission - Legal act that grants a marked authorisation as well as he industrial policy
What are the roles of EMA?
- Development of medicine
- Authorisation of new innovative medicine
- EU level pharmacovigilance
- ‘Decisions’ on major benefit risk questions
- Coordination of EU activities/ EU databases
What are the roles of National agencies?
- Oversight of national manufacturing
- National pharmacovigilance
- Authorisation of national generics
- Clinical trial approval
- Inspection and enforcement
EU in medicine oversight
- EMA
- National Agencies
- Marketing authorisation holders
- Healthcare professionals
- Patients
What is the professional bodies of Healthcare professional?
The general medical council
What is pharmacovigilance?
The science and activities relating to the detection, assessment, understanding and prevention of adverse drug effects or any other drug related problems
What does pharmacovigilance assure?
Any aspect which could impact the safety profile of a medicine is detected and assessed and that necessary measures are taken
How was regulation being enforced?
Different major drug safety issues
What are some examples of different major drug safety issues?
- Thalidomide tragedy from late 1950’s to 1969’s
letter to medical journal - describing limb deformities - Vioxx - Cox 2 inhibitor - taken off market in 2003 because of cardiovascular side effect
- Razoiglizaone treatment of diabetes - cardiovascular side effect - heart valve condition
What is pharmacovigilance about?
- Managing risks
- Detecting these issues early
- Detect and assess
- Take action to minimise risks
Why do we need pharmacovigilance?
- Dossier of evidence submitted by companies on safety, quality, efficacy; full assessment by regulators
- What we do not know: Full safety profile in normal clinical practice e.g. rare ADR, delayed ADRs, ADR from chronic exposure, ADR in special population, ADR from ‘‘off-label’’ use
Pre-marketing data have important limitations
- Pre-clinical data: low predictive value
- Clinical trial data provide provisional evidence of safety but:
- Too small (~1500 patients)
- Limited duration
- Do not represent the real world
Delayed ADR
If it is a side effect that only occurs some years after expsoure e.g. cancer
the medicine taken is mutagenic/carcinogenic
Cancer takes years to develop
damage to cells and DNA might occur when taken drug
Wont detect during clinical trial because the clinical trial only tend to last months or maybe a year or 2 whereas cancer may come much layrt
ADR from chronic exposure
Treatment for diabetes
On for decades because diabetes is a chromic disease
If the drug increases risk of heart attack, you wont detect it in initial clinical trial, only detect once the product is on the market
Who are ADRs in special population for?
- Children
- Elderly
- Pregnant women
- Breast feeding women
What does the real world correlate with?
Normal clinical practice term
What are the burden of adverse drug reactions (EC impact Assessment 2008)
Medicine saved lives and relieve suffering, but:
- 5% of all hospital admissions are for ADR
- 5% of all hospital patients suffer an ADR
What are ADRs?
5th most common cause of hospital death
What are the estimated death per year in EU from ADRs?
197,000 deaths per year
What is EU societal cost of ADRs?
Euro 79 billion/year
What can pharmacovigilance reduce?
Death and suffering caused by adverse reactions
What are the objectives of Pharmacovigilance?
- Identify previously unrecognised hazard
- Evaluate changes in risks and benefit and improve safety of marketed medicine
- Take action to promote safer use to optimise safe and effective use of medicine
- Provide optimal information to users
What is pharmacovigilance a very refined part of?
- Society
2. Government
What are the prerequisite of pharmacovigilance?
- Functioning state (law and order)
- Responsibilities can then be laid down by law - Functioning healthcare system
- Operation can be embedded in the healthcare system - Science and resource (people, data, knowledge etc)
What works together collectively in drug safety monitoring?
- EMA
2. National complement atuhority
What are the EU network?
- International partners
- Patients
- Professionals
- Industries
- Payers
- Media
- Government
What are key EMA roles?
- Coordination, standard, training
- Maintain and develop information management systems
- Manage alert + incident
- Planning of studies and risk minimisation
- Collection and manage data
- Detect and manage new safety issues
- Provide data and analyses to MSs
- Run the committees and processes
- Initiate actions to optimise safe and effective use
- Coordinate communcations
- Support stakeholder collaboration
What are the pharmacovigilance process steps?
- Risk management planning
- Collect data
Detect safety ‘signals’ - Evaluate risk
- Benefit risk assessment
- Take action to reduce risk
- Communicate
- Audit (were measures effective)
What is Audit?
to make sure that the actions taken has been effective in terms of how doctors prescribe medicine, how pharmacist dispense medicine and how patients take their medicine
What is the pharmacovigilance: cycle?
- Identification and data collection (monitor, reporting, collection of new data e.g. signal detection)
- Assessment (risk quantification and benefit assessment)
- Decision making on preventive/corrective measure, Risk minimisation
- Communication of risk and benefit/risk
- Evaluation of effectiveness of measures (e.g. via post authorisation studies)
What are the data sources in pharmacovigilance?
- Non-clinical studies
- animal toxicology studies - Clinical trials
- Epidemiological (observational) studies
- Spontaneous reports of suspected adverse drug reactions
- Systemic reviews and meta-analysis of observational data
- Systemic reviews and meta-analysis of clinical trials
What does toxicology studies have?
preauthorisation of drug development
What are epidemiological method?
Study design and data analytic method used in real world data e.g. electronic health records, prescribing data, dispensing data from pharmacy, drug utilisation and drug registry
How to increase power of one study?
Methodologies for combining either at the study level or individual patient level
Adding results to lots of other studies
What is one of the longest standing safety monitoring system in the world?
Yellow card scheme run by MHRA
What are the reports of suspected ADRs?
- Reports from patients and professionals (=yellow card in UK)
- Are received by national agencies (MHRA) and by companies
- National agencies and companies report on to EudraVigilance
- EMA (through EudraVigilance) makes report available for analysis by EMA expert safety staff and expert safety staff in the national agencies respecting data protection for signal detection
- Evaluating safety issues to identify way to reduce harm
What does EMA make?
A subset of data available to general public
Reports of suspected ADR
- Main source of safety issues/evidence of harm leading to action to protect public health
- Large data sets detect safety issue faster
- Issues may be detected many decades after product enters market
What is Eudravigilance?
EU data processing network and management system reporting and evaluating suspected adverse reactions during the development and following the marketing authorisation of medicinal product in European Economic Area
What are received and processed?
Over 13 million adverse reaction reports
1.5 million new reports per year
What are the actions to reduce risk?
- Inform patients via warnings in product information
- Stop use (contra-indicate) in at risk patients
- Reduce the top dose (if dose dependent risk)
- Introduce monitoring for early warning signs (e.g. blood test or X-rays)
- Restrict the use to only the most severe patients
- Withdraw the product
What is summary of product characteristic?
Document for healthcare professional
Legal contract between company and the regulator which constrains how the product is marketed
What are most side effects?
Dose dependent
What is the consequence of reducing top dose?
Reducing the effectiveness of the medicine as well
Communicating on benefit risk
- Product package
- Product leaflet
- Summary of product characteristic
- Letter (email etc) to doctors/pharmacist
- Educational material (brochures/training) for patients or healthcare professionals
- Website
- Apps
