Transcript Epidemiology

07/07/2015
Risk
Management
Plan
24. April 2008
Helge Gydesen
Epidemiology
Novo Nordisk A/S
07/07/2015
Agenda
1
Motivation: Examples of withdrawals
2
Regulatory environment
3
What is a Risk Management Plan
4
Who, When and How
5
Implications for post marketing activities
6
Conclusions
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Rofecoxib (VIOXX)
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Merck & Co
Introduced: 1999 Withdrawn: 2004
Indications: Osteoarthritis and Acute Pain
Withdrawn due to : Heart attack and stroke
Cerivastatin
•Bayer A. G.
•Introduced: Late 1990’s
Withdrawn: 2001
•Cholesterol lowering
•Withdrawn due to: Rhabdomyolysis leading to renal
failure
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Regulatory guidance
• Three guidelines from FDA
• The ICH E2E Guideline
• EU risk management Guideline
• All can be found on International Society for
PharmacoEpidemiology (ISPE) homepage
www.pharmacoepi.org under the left hand heading
resources
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EU-RMP
• EU-RMP required at MAA submission:
• New active, biosimilar or generic with risk minimisation for
reference substance
• New dosage form, route, indication, manufacture process for
biotech product
• On request of authorities
• If Marketing Authorization Holder (MAH) identifies a safety
concern
• Other situations for centrally authorised product. e.g.
bibliographical applications, fixed combination, certain hybrid
products
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Risk management
- Definition and purpose
• A Risk Management system is a set of pharmacovigilance
activities and interventions designed to proactively identify,
characterise and prevent or minimise risks relating to
medicinal products, including risk communication and the
assessment of the effectiveness of risk minimisation
interventions.
• The purpose of the Risk Management Plan (RMP) is:
 to identify the risks associated with a medicinal product
 develop methods to clarify further the safety profile of a
product
 plan ways to minimise risk to individual patients in clinical use.
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Risk Management Plan Development
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Who is contributing
• International Product Safety (IPS) is the owner of the
document
• Contributions from the pre-clinical and clinical
development area
• BIG contribution from Epidemiology
• Discussions with Marketing on the Post Marketing
Activities
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Risk management
- The role of Epidemiology
• Author and maintain the epidemiological sections of a Risk Management Plan
(RMP) as per guidelines from regulatory authorities and NN SOP on ongoing
basis. Support the updating of RMP periodically. Provide epidemiological
expertise in Risk management activities throughout the life cycle of NN
products.
• Provide timely epidemiology support to project teams to design and
implement epidemiological studies, to review study proposal from internal
and external sources, to analyze adverse events reporting data, and to
interpret and report on data analysis results to other line functions.
• Contribute in safety risk evaluation once a safety signal has been detected
and in communication of safety information and thereby propose and
implement risk minimization activities.
• Provide epidemiology support in preparation of Periodic/ Annual Safety
Reports (PSUR/ASR) if required by the regualatory authorities.
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Risk management
- Future
• Global Epidemiology will be involved in all Risk Management Activities in NN
• Input to design and protocol
• Timely epidemiology support to project teams to design and implement
epidemiological studies to evaluate safety issues.
• Setup an organised collaborative team with IPS as an Integrated Risk
Management Expert Group (IRMEG) within NN.
• Responsible for study design, analysis, interpretation and publication of studies
related to safety issues of NN products.
• Conduct epidemiological studies to support risk management activities
• Review and Meta analysis of LTR to address safety issues
• Make sure resources are allocated when new post approval safety studies (PASS)
are initiated and required
• Resources in budget to conduct or for outsourcing for epidemiological studies to
gather knowledge about target indications.
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When to start the work with the RMP?
Phase IV
FIM
Product
Life Cycle
Phase I
Phase II
Phase III
Exposure
(Potential Denominator)
Approval
Drug Discovery/Preclinical
h
Clinical Development
h
Pharmacovigilance
Post Marketing
h
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RMP: A change in approach
• Proactive in stead of reactive
• Not a defensive approach, in stead: demonstrate safety
• Focus on different type of epidemiological studies in
stead of normal pharmacovigilance
• Pharmaco epidemiology in stead of standard
pharmacovigilance
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Risk management Plans – examples of
identified risks: EXUBERA
• Smoking-induced alterations in Pharmacokinetics (drug
interaction studies/passive smoking)
• Changes in Pulmonary Function (Long term PASS,
Special Asthma study, Paediatric studies)
• Increased Insulin Antibody Levels (Long term PASS,
Paediatric studies)
• Rare Pulmonary Events (Epi Lung Cancer study)
11 studies running until 2019, covering more than 75000
patients
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CONCLUSIONS
• Risk Management is a new area under development
• Clinical Epidemiology is a crucial area of information
• Will create discussions of the right level of post
marketing activities: Observational studies, utilization
of databases (internal/external)
• BUT ABOVE ALL: Epidemiological/statistical expertise
will be needed in the future development of this area
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Any questions or comments?
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