Download Safety of Patients: Diminishing Risk in Products and Practice (2004)

Mr. Michael Bonett
Safety of Patients: Diminishing Risk
in Products and Practice
The Medicines Regulatory Unit, Malta
 Set-up nearly one year ago
 Will establish the Medicines Agency in Malta
 Currently employs 12 pharmacists
 Headed by Ms. L. Wismayer, Director MRU
 Mr. Michael Bonett,
Post-Licensing Section: Pharmacovigilance
Safety of Patients
Diminishing Risk in
Products
and Practice
Diminishing Risk in Products and Practice
‘…Take two tablets,
three times a day
for five days…’
Some Questions...
 Has the disease been correctly diagnosed?
 Has the right dose of the right strength of the right
formulation of the right drug been prescribed?
 What are the risks of the treatment producing an
adverse drug reaction (ADR)?
 What is the potential seriousness and duration of
possible harmful effects?
More Questions...
 Is the patient taking anything else which might interact
badly with the drug or prevent its working at all?
 Does the patient have any medical or genetic or
allergic condition which might cause a bad reaction to
the drug?
 Is the manufacturing source of the drug safe and
reliable?
 Does the patient understand the instruction and will
they comply with them?
Past, Present and Future
 Risk from the practice of using products such as
plants, tobacco and alcohol
 Thalidomide Tragedy, 1961
 Signal Generation ---> Confirmation
---> Evaluation ---> Response to Signal
 EXPLOSION! ---> Drug development & Use
 Managing Information
CONTENTS
Exchange of information
Pharmacovigilance activities
WHO International Drug Monitoring
Programme
Statistics of Drug Utilisation
Exchange of information
 Network of designated national information officers
 Transmission of new information on serious adverse
effects of pharmaceutical products
 Response to individual requests for information
 WHO Pharmaceuticals Newsletter, One-page Alerts
 UN Consolidated List of Products Whose
Consumption and/or Sale Have Been Banned,
Withdrawn, Severely Restricted or not Approved by
Governments
Uppsala Publications
The Who Collaborating Centre for drug monitoring
in Uppsala, Sweden produces several publications
in order to disseminate drug information
These include:
 Signal
 Uppsala reports
 Viewpoint
 The UMC website
Effective Communication
 A signal is notice of an early concern or hypothesis
about a possible drug safety problem
 Same signal -----> Extremely different actions
 Action planned -----> Effect unknown
 A reciprocal/participatory /democratic
communication system is more effective
Effective Communication
The Players:
 Pharmaceutical companies
 Government
 Health professions,
 Medical schools
 Patients and public
 Media
 Dissemination of information may result in harm
 e.g. MMR vaccines scare in Great Britain
VACCINES
 Immunisation programmes have brought
incalculable benefits to the human race which by far
outweigh the occasional harm
 Scares about speculative damage caused by
vaccines have sometimes compromised
immunisation programmes
 Monitoring the risks of immunisation programmes is
exceptionally difficult
MMR vaccines scare in Great Britain
 Were there better ways of communicating such an
issue?
 Is Britain different from the rest of the world as
regards public trust in health care professionals and
regulators?
 Did the risk with MMR vaccines
publication of such information?
justify
the
Effective Communication
 Public does not understand what is meant by the
concept of risk/benefit analysis
 Mass media need help to understand the difference
between absolute and relative risks
 Regulators, authors, journal editors, and industry
need to diffuse tension by talking to each other
 Must take into consideration the ‘human spirit’
Effective Communication - a problem
‘Brilliant Scientists
are NOT necessarily
Brilliant Communicators’
EDUCATION - a possible solution
 Teaching of pharmacoepidemiology and
pharmacovigilance in medical schools
 Could be included in the clinical pharmacology
section of the curriculum
 Should include lectures and problem-based active
learning
 Also - Education of the consumer
Challenges
 A greater willingness among regulators and
manufactures to show openness and transparency
 A commitment to public health education
 More open and mature relationships with the media
 More discussion and training in benefit/risk analysis
 Healthcare professionals are alerted to the
importance of recognising and reporting ADR’s
WHY PHARMACOVIGILANCE?
 Tests in animals are insufficiently predictive of
human safety
 In clinical trails patients are selected and limited in
number, the conditions of use differ from those in
clinical practice and the duration of trails is limited
 Information about rare but serious adverse
reactions, chronic toxicity, use in special groups or
drug interactions is often incomplete or not
available
Pharmacovigilance - differences
 Drug production
 Distribution and use
 Genetics, diet, traditions of the people
 Pharmaceutical quality and composition (excipients)
of locally produced pharmaceutical products
 Use of non-orthodox drugs which may pose special
toxicological problems
Pharmacovigilance - differences
 Different circumstances/countries ---> Different
relevance and importance
 WHO International Drug Monitoring Programme may
provide information on possible safety issues which
may not yet have emerged within the country’s data
 Medicines on the market need continuous
monitoring in every country
Promoting Pharmacovigilance Activities
Pharmacovigilance is the science of collecting,
monitoring, researching, assessing and evaluating
information from healthcare providers and patients
on the adverse effects of medicines, biological
products, herbals and traditional medicines with a
view of:
 identifying new information about hazards, and
 preventing harm to patients
 Greek - Pharmakon - drug
 Latin - Vigilare - to keep awake or alert, to keep watch
Promoting Pharmacovigilance Activities
The aims of pharmacovigilance are:
 To promote patient care and patient safety in relation to
the use of medicines,
 To improve public health and safety in relation to the use
of medicines by the provision of reliable, balanced
information resulting in more rational use of drugs
 To contribute to the assessment of the risk-benefit
profile of medicines, thus encouraging safer and more
effective use of medicines
Pharmacovigilance
Determination of different adverse effects effects on
human beings:
 “adverse reaction”
 “serious adverse reaction”
 “unexpected adverse reaction”
 “serious unexpected adverse reaction”
Important aspects of Pharmacovigilance
 Health care professionals are encouraged to note,
record and report adverse effects to national
authorities - ‘spontaneous reporting’
 Weaknesses:
Under-reporting
Variable quality reporting
 Reporting rate 10% or lower (early 1990’s- Fletcher)
Important aspects of Pharmacovigilance
 Legal framework is important to ensure follow-up
(e.g. EU Directives and Regulations)
 Manufactures can be obliged to have experts in
Pharmacovigilance
 Close cooperation between stakeholders
Regulators
Industry
Others
Guidelines: Pharmacovigilance Activities
Publishing of Guidelines: for setting up and running
a Pharmacovigilance Centre
Help and guidance in:






the materials and sources required
how to operate
what kind of support is needed
where to find adequate literature sources
what kind of assistance is expected
what is the relationship to be sought with drug information
centres
Further Progress by WHO
 Guidelines on issues of postmarketing surveillance
for regulatory authorities or for national
pharmacovigilance centres
 Guidelines for safety monitoring of drugs in
communities
 Establishment of a high-level advisory committee
on the safety of medicinal products
Challenges in Pharmacovigilance
 Current financial climate forces national authorities
to find ways to contain the cost of pharmaceutical
care
 Self-medication - Does this have consequences for
the patient?
 Use of herbal medicines risks escaping control
 Counterfeit drugs on the market
Programme for International Drug Monitoring
 Established in the wake of the thalidomide disaster
in 1962
 Common reporting form
 Agreed guidelines for entering information
 Common terminologies and classifications
 Compatible systems for transmitting, storing and
retrieving and disseminating data
 WHO Collaborating Centre for International Drug
Monitoring at Uppsala, Sweden
Need for Harmonisation
 Increased globalisation impacts ADR reporting
 Different regulations and guidelines increase
complexity
Variables influencing reporting of adverse events:
 interpretation of rules
 license holder
 location
 expectedness
Harmonisation Initiatives
Council for International Organisation of Medical
Science (CIOMS)
 International Reporting of Adverse Drug Reactions, a
common format for reporting of ADR’s (1990)
 International Reporting of Periodic Drug-Safety Update
Summaries (1992)
 Guidelines for Preparing Core Clinical-Safety Information
on Drugs (1995)
 Benefit-Risk Balance for Marketing Drugs: evaluating
Safety Signals (1998)
 Current Challenges in Pharmacovigilance: Pragmatic
Approaches (2001)
Harmonisation Initiatives
International Conference on Harmonisation (ICH)
 Europe
 USA
 Japan
Topics:
 Medical terminology
 Data elements for individual case reports
 Periodic safety update reports
 Others...
Example of Harmonisation
Medical Terminology
 WHO’s International Classification of Disease (ICD)
 WHOART used to classify ADR’s
 Coding data with different terminologies - problems
 ICH developed MedDRA - a common classification
system
 Allows organisations to analyse clinical information
across the development process
WHO contributions to Harmonisation
 Developing definitions of words commonly used in
pharmacovigilance
 Organising annual meetings of representatives of
national health centres in collaboratin with WHO
Headquarters, Geneva
 Maintaining tools commonly used in drug safety
activities (e.g. WHOART and WHO Drug Dictionary)
 Closely collaborating with other organisations such
as the ISPE, ESOP, DIA and CIOMS
Drug utilization
 WHO Collaborating Centre for Drug Statistics
Methodology at Oslo, Norway
 Classification system: the Anatomical, Therapeutic
and Chemical (ATC) and Defined Daily Dose (DDD)
 International Working Group for Drug Statistics
Methodology
 Globalise Classification System
Pharmacogenetics
 Pharmacogenetics is the study of genetic variability
and its effect on response to drug therapy
 Genes of large populations are searched to see if
known sequences of DNA are commoner in certain
diseases
 Our increased understanding will tailor the riskbenefit ratio to well-defined groups
 Will change the future of clinical medicines and of
pharmacovigilance
The Future
 Driven by integration, convergence and linking
resources together, such as Pharmacogenetics and
Pharmacoepidemiology with Pharmacovigilance
 Requires collaboration between the stakeholders
involved
 Future developments in integrating information and
knowledge management should help
 We must continue to learn and manage information
The Future
 The benefits, harm, effectiveness and risk of
medicinal products as they affect patients and
public health
 The safety of all substances used in medical or
alternative practice – herbals, vaccines, blood
products…
 The communication of complex issues among
healthcare professions and with the media, patients
and the public at large
Diminishing Risk in Products and Practice
‘…Take two tablets,
three times a day
for five days…’
Answers...
Has the disease been correctly diagnosed?
 The need for up-to-date refined and sophisticated diagnostic
skills
 Increased awareness that symptoms may be caused by
adverse reactions to drugs or other substances already being
taken, as well as by disease
Has the right dose of the right strength of the right formulation
of the right drug been prescribed?
 Provision of easy access to clear and comprehensive
information about the drug and its use and about possible
alternative therapies, for the prescriber and the patient
More Answers...
What are the risks of the treatment producing an adverse drug
reaction (ADR)?
 Provision of comprehensive, accessible, up-to-date
information about all known ADRs, the risk of their occuring
generally and for this particular patient, their potential
seriousness and duration
What is the potential seriousness and duration of possible
harmful effects?
 Informed discussion with the patient about their particular view
of the potential benefit and harm in relation to effectiveness
and risk for them
Even more answers...
Is the patient taking anything else which might interact badly
with the drug or prevent its working at all?
 Does the patient have any medical or genetic or allergic
condition which might cause a bad reaction to the drug?
 Training in the expert and thorough taking of case-histories
and in effective interaction with patients
 Continuity of care or, at least, excellent communications
between healthcare providers about their shared patients
 Public education in the way drugs work and on the way they
interact with many other medical and non-medical substances
And even more answers...
 Patient awareness of the critical nature of issues which may
not seem immediately relevant to the present consultation
Is the manufacturing source of the drug safe and reliable?
 Universal requirements for adherence to WHO Good
Manufacturing Practice (GMP), including strict inspection and
quality control by manufactures and regulators
 Reliable and conscientious reporting by health providers and
patients of occasions where drugs cause adverse reactions, or
do not work at all
Final question and answer
Does the patient understand the instruction and will they
comply with them?
 Much more sophisticated communications skills in health-care
providers
 Much greater understanding among patients about how drugs
work and necessity of completing a course of treatment even if
symptoms appear to have gone
Conclusions
 Although harmonisation helps, there is along way
to go before regulators and industry work together
collaboratively enough to improve
pharmacovigilance measurably
 Managing information and knowledge is the key to
the failure or success of drug safety
 The revolution in communications technology
provides an interesting future for pharmacovigilance
Points for Discussion
 Are we communicating in a linear, authoritarian,
bureaucratic, old-fashioned style?
 MMR Vaccines - Was there a better way in
communicating or anticipating this issue?
 ‘It seems now that we may have safety systems in place
that enable effective action to be taken globally before
disturbing numbers of patients are affected.’
Do you agree?
Points for Discussion
 Does society equip the health care professionals, who
work under increasingly difficult circumstances with the
right resources to improve their performance?
 Is drug safety synonymous with pharmacovigilance? Is
pharmacovigilance part of pharmacoepidemiology or
vice versa?
 Will standardisation of spontaneous reporting
requirements have a deleterious effect by limiting the
forwarding of ingenious observations which do not fall
into the specific categories for reporting?
THANK YOU
There is no other official body in the world,
which has a truly independent and global
perspective on drug safety other than the WHO
and its collaborating centre the UMC.
International harmonisation and standardisation
are difficult to achieve without consensus. It is
the WHO’s general mandate to do this work, and
the record of achievement in the field as a whole
is now substantial, authoritative and widely
recognized.
Thank you for your attention
You can visit our website at:
http://www.health.gov.mt/mru