IBEJ. Hasford
Munich
Bridging the Gap -Research into Practice
Prof. Joerg Hasford, M.D., Ph.D.
German Pharmacovigilance Study Group
IBE Department of Medical Informatics, Biometry and Epidemiology, University of Munich, Germany
Email: [email protected]
Pharmacovigilance Research and Patient Safety Policies
IBEJ. Hasford
Munich
Frequency of ADR-related Hospital Admissions
Meta-Analysis of 25 publications covering medical departments
Median (all): 5.8%
Median (age > 60): 10.2%
Mühlberger N, Schneeweiss S, Hasford J. Pharmacoepidem Drug Safety 1997; 6 Suppl. 3: S71-S77.
IBEJ. Hasford
Munich
Direct Costs of ADR-related Hospital Admissions in Germany
• 4.5 Mio Admissions to Medicine Departments / year
• 5.8% due to ADR• 8.7 days median length of stay• 310 € costs per day in hospitals (2000)
704,000,000 € / year
IBEJ. Hasford
Munich
Preventability of ADRs
Meta-Analysis of 14 publications
Goettler M, Schneeweiss S, Hasford J. Pharmacoepidem Drug Safety 1996;6 Suppl.3:S79-S90
30.7% (median) of ADRs leading to hospital admission are preventable.
IBEJ. Hasford
Munich
Pharmacovigilance
The science and activities relating to the detection, assessment, understanding and prevention of adverse effects or any other drug-related problem.
WHO
IBEJ. Hasford
Munich
Pharmacovigilance
collects, records, codes ADEs / ADRs
analyses and assesses the reports
promotes the safe use of drugs
creates appropriate structures and means of communication needed to perform its tasks
IBEJ. Hasford
Munich
Aims of Pharmacovigilance
to improve patient care and safety to improve public health and safety to contribute to the assessment of benefit, harm,
effectiveness and risk of medicines to promote education and clinical training to promote effective communication to the public to promote rational and safe use of medicines
IBEJ. Hasford
Munich
Safe Use of Drugs ?Antibiotics use in pregnancy in Germany 2000/2001
Actions in Germany: None
Tetracyclines count among the 10 most prescribed antibiotics during pregnancy (1/1000 pregnant women).
It is well known for more than 30 years that tetracyclines can severely damage teeth and bone structures of the fetus.
IBEJ. Hasford
Munich
Safe Use of Drugs ?
The Case of digitoxin-intoxication
Actions in Germany: None
Intoxications with digitoxin count still among the most common causes of ADR-related hospital admissions (12 - 14/10,000 / quarter year).
The therapeutic benefit of digitoxin is rather limited, however.
Hippius M et al. Int J Clin Pharmacol 2001;39:336-343.
IBEJ. Hasford
Munich
Safe Use of Drugs ?The case of long acting beta agonists
Actions in the U.S.: Dear Dr. LetterBlack Box Warning
Germany: None
There are two large randomized trials, both showed an increased mortality with salmeterol.
Mortality
Castle et al. 1993 Salmeterol vs Salbutamol 0.32% vs 0.24%SMART 2002 Salmeterol vs Placebo 0.31% vs 0.24%
Number needed to harm (kill): 1250 - 1428 patients
IBEJ. Hasford
Munich
The Problem is:
Who is responsible for Patient Safety?
EU-Regulations National Law
IBEJ. Hasford
Munich
Market Authorization Holder
collect, collate, validate and follow up (SAEs) of all reported suspected Adverse Events
screen the relevant world-wide literature at least once / week
report all serious suspected ADRs within 15 days submit PSURs company-sponsored Post-Authorisation Safety
Studies regularly checks risks and benefits and acts
accordingly
IBEJ. Hasford
Munich
Drug Authority collect, validate, code, store and analyse
reports transmit ADR data to the MA holder inform health care professionals and, when
needed, treated patients, of any significant changes
Decision Making Communication with all interested parties Evaluation of the actions taken
IBEJ. Hasford
Munich
Marketing Authorisation Holder
• Establish and maintain a system, accessible at a single point in the EU, to collect, collate, and evaluate pharmacovigilance data
• Meet legal obligations for reporting suspected adverse drug reactions
• Meet legal obligations regarding the preparation and the submission of PSURs
• Respond fully to requests from authorities for additional information necessary for the evaluation of the benefits and risks of a medicinal product
• Ensure the Marketing Authorisation is maintained and reflects the latest information
Member States • Have in place national pharmacovigilance systems
• Inform the European Commission, the CPMP, the Agency, the member states and the MAHs of any relevant actions
• Collect and collate risk / benefit data
• Provide serious ADRs which have occurred in its territory to the Agency and the relevant MAH within 15 calendar days of receipt
• Identify and evaluate drug safety alerts and conduct risk / benefit evaluations
• Provide representation on CPMP, PhVWP and Rapporteurs / Co-Rapporteurs
• Implement Commission Decisions
• In case of urgent action to protect public health, suspend the use of the product in the member state’s territory and inform, in accordance with the legislation, the Agency and the European Commission of the basis for action
Summary of the Role and the Responsibilities
Volume 9 - Pharmacovigilance
IBEJ. Hasford
Munich
There are a lot of laws and regulations, but with very little impact on routine medical care, except when a drug is withdrawn from the market.
There are too many parties involved, e.g. hospitals, physicians, sickness funds, patients, industry, government institutions, media, juris-diction and the like, but there is
No institution solely devoted on Patient Safety
The Problem is:
IBEJ. Hasford
Munich
Patient Safety Policies
October 2004The World Alliance for Patients’ Safety was launched.
AIMS• to coordinate international actions and avoid
duplication of effort in coping with escalating problems of iatrogenic disease and health care misadventures
Edwards RI. The WHO World Alliance for Patient Safety - A New Challenge or an Old One Neglected? Drug Safety 2005;28:379-386.
IBEJ. Hasford
Munich
Pharmacovigilance Planning
starts PV early, i.e. before the license is granted
is proactive tries to demonstrate safety, as opposed to
looking for harm
Tools
Pharmacovigilance Specification Pharmacovigilance Plan
IBEJ. Hasford
Munich
Pharmacovigilance Specification (PVS)
Summary of the identified risks, the potential risks and any important missing information
All relevant data, e.g. preclinical toxicology, pharmacology, target organ findings, potential for interactions and all clinical data collected during the phases of drug development are evaluated.
Assessment of trials population vs. patient population (e.g. women, children)
Consideration of class effects for the medicine
at time of submission / approval
Tsinitis P and La Mache E. Drug Safety 2004;27:509-517.
IBEJ. Hasford
Munich
Pharmacovigilance Plan
is based on PV specification includes appropriate proposals for
key issues as identified in the PVS, e.g. epidemiological studies
provides the rationale for such studies, the objectives and mile-stones for evaluation
IBEJ. Hasford
Munich
A concerted action with transparent and com-prehensive responsibilities is essential
Annual reports about the state of patient safety in health care competition
Access to the data Pharmacovigilance Planning and Risk Manage-
ment Systematic and continuous use of pharmaco-
epidemiologic data bases, e.g. GPRD (UK, PHARMO (NL), MEMO (Scotland)
Starting points for improvement
IBEJ. Hasford
Munich
Low threshold AE-reporting systems regional (i.e. at least EU-member state level)
ADR and Drug Utilisation monitoring Effective strategies to modify physicians’
prescribing and patients’ compliance are urgently needed
More use of modern information technologies
IBEJ. Hasford
Munich
ADEs are a major public health threat with significant financial cost implications.
Pharmacovigilance has made and will make es-sential contributions to the safer use of medicines.
There is still a considerable gap between the results of Pharmacovigilance research and medical practice.
A concerted action of all parties involved and a reliable and proactive partner are essential to gain the full benefit of pharmacovigilance research.
Conclusions