F_Sweeney_EMA__WMA_Capetown_2

An agency of the European Union
Presented by: Fergus Sweeney, PhD
Head of Sector, Compliance and Inspection, European Medicines Agency.
European Medicines Agency
Perspective
WMA Workshop on revision of DoH, 4-6 Dec 2012,
Capetown, South Africa.
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Disclaimer
The views presented in this presentation/these
slides are those of the author and should not be
understood or quoted as being made on behalf of
the European Medicines Agency and/or its
scientific committees
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EU requirements for clinical trials conducted in
support of marketing authorisation submitted to
the EU
This presentation and the documents
referred to relate to the conduct of trials
required to support MAA in EU
Requirements apply:
• To all clinical trials that are included in a MAA submitted in the
EU/EEA
– regardless of the route (Centralised, Mutual Recognition,
Decentralised)
– regardless of the EU or third country involved (legislation
does not differentiate developed, developing etc)
• Apply to the clinical trials included in a MAA
• There is no specific legal framework for review of a clinical
trial dossier by an EU regulator before the conduct of the trial
in a third country
The Dilemna……
Between 2005 and 2011
897,891 Patients in pivotal trials
(38.11% in Europe, 34.05% in North America, 2.58% Africa,
9.36% Middle East/Asia Pacific, 4.44% CIS, 9.36 % Latin
America, 2.1% other)
70,291 clinical trial sites in c. 106countries
c. 485 new MAA applications plus line extensions etc,
265 GCP inspections
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0
10,000
20,000
30,000
40,000
50,000
60,000
70,000
2005 2006 2007 2008 2009 2010 2011
Numerofpatients
Year of MAA
EU/EEA/EFTA North America ROW
Number of patients in pivotal trials submitted in MAAs to the EMA per region
and year. The data are shown as three “global regions” – EU/EEA/EFTA, North
America and ROW (Rest of the World).
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Topic 1. Clarify the practical application of ethical standards for clinical
trials, in the context of EMEA activities
Topic 2. Determine the practical steps to be undertaken during the
provision of guidance and advice in the drug development phase
Topic 3. Determine the practical steps to be undertaken during the
Marketing Authorisation phase
Topic 4. International cooperation in the regulation of clinical trials, their
review and inspection and capacity building in this area
Draft ’Reflection paper on ethical and GCP aspects of clinical trials conducted in third
countries for evaluation in marketing authorisation applications for medicines for
human use, submitted to the EMA’ Public consultation completed 30th September 2010.
Working group – members from CHMP/COMP/PDCO, PCWP, HCPWP, GCP IWG
http://www.ema.europa.eu/Inspections/docs/71239709en.pdf
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Clarification of the practical application of ethical standards for
clinical trials on medicinal products for human use in the context
of the European Medicines Agency activities
• Local ethics committee and national regulatory
authority oversight
• Information/Consent procedure
• Confidentiality
• Fair compensation for study related injury
• Vulnerable populations
• Choice of control – placebo and active comparator
• Access to treatment post trial
• Applicability of data to EEA population – addressed in
other guidance
Vulnerable populations
Current DoH:
17. Medical research involving a disadvantaged or vulnerable population or community is
only justified if the research is responsive to the health needs and priorities of this
population or community and if there is a reasonable likelihood that this population or
community stands to benefit from the results of the research.
18. Every medical research study involving human subjects must be preceded by careful
assessment of predictable risks and burdens to the individuals and communities involved
in the research in comparison with foreseeable benefits to them and to other individuals
or communities affected by the condition under investigation.
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Vulnerable populations
“The inclusion of vulnerable subjects in a clinical trial without the approval of the Ethics Committee and without
implementation of the appropriate consent processes is a serious violation of ethical standards.
EU Regulatory Authorities should disregard data obtained in such an unethical manner, when submitted in support of a
MAA.”
• In this [clinical trials included in MAAs] context it is mainly vulnerability due to poverty, lack of access to adequate
health care systems, lack of access to medicines.
• Need to ensure that vulnerable persons or groups are not exploited for the benefit of EU patients.
• At the same time there are the needs to consider the benefit to the patient of taking part in the study
and the ethics of potentially turning them away simply because they fit one of the vulnerable categories.
• Denying access to research is also not a solution.
• Information on the populations included in clinical trials in a MAA and any particular concerns should be
part of the European Public Assessment report.
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Access to Treatment Post Trial
Current DoH
14. ….. The protocol should describe arrangements for post-study access by study subjects to interventions
identified as beneficial in the study or access to other appropriate care or benefits.
33. At the conclusion of the study, patients entered into the study are entitled to be informed about the
outcome of the study and to share any benefits that result from it, for example, access to interventions
identified as beneficial in the study or to other appropriate care or benefits
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Access to Treatment Post Trial
• Access to innovative medicinal products varies widely.
• Differences mostly reflect …the ….economic situation and social and health care systems
of the country or region.
• Whether the medicinal product is likely to be available in the community or country
should be considered by the sponsor, Ethics Committees and National Regulatory
Authorities. New medicinal products should be intended for marketing in the countries or
regions where the clinical trials are conducted.
• For the individual patient who participated in a clinical trial continued access to the
product that has been identified as beneficial is crucial. It is recognized; however, that
post trial access of patients to treatment or medical care provided by sponsor or
investigator cannot substitute for shortcomings of national or regional health care
systems.
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Access to Treatment Post Trial
Transparency on matters of post trial access to treatment and medical
care is paramount for clinical trials submitted to EMA in support of
European MAA.
This information will be summarised in the European Public Assessment
Report (EPAR).
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Biobanks
Current Declaration of Helsinki
“25. For medical research using identifiable human material or data,
physicians must normally seek consent for the collection, analysis,
storage and/or reuse. There may be situations where consent would
be impossible or impractical to obtain for such research or would
pose a threat to the validity of the research. In such situations the
research may be done only after consideration and approval of a
research ethics committee.”
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Biobanks
• Note for Guidance on definitions for genomic biomarkers, pharmacogenomics, pharmacogenetics,
genomic data and sample coding categories (EMEA/CHMP/ICH/437986/2006)
• Reflection Paper on pharmacogenomics samples testing, testing and data handling
(EMEA/CHMP/PGxWP/201914/2006)
• Reflection paper on pharmacogenomics in Oncology
• Large-scale study of populations may contribute significantly to science’s understanding of the complex
multi-factorial basis of disease and to improvements in prevention, detection, diagnosis, treatment and
cure. Pharmacogenomics ( PGx) offer a potential for better understanding the mechanisms of diseases
and optimizing the development and use of medicinal products.
• optimize the benefit/risk balance evaluation
• provide focussed information as guidance to prescribers and patients.
• may become a valuable tool in risk management and pharmacovigilance strategies.
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Biobanks
• The use and exchange of human genetic material and the information derived from it, is
not without some controversy. Within the scientific community, there is consensus that
progress in understanding disease will depend on the establishment, harmonisation and
broad use of human biobanks and genetic research databases.
• Human biobanks and genetic research databases which bring together and allow the
sharing of human biological material and information derived from its analysis, are a key
element of the scientific infrastructure underpinning such research.
• The potential of the Biotechnology can be developed only if data included in human
biobanks are made available for research.
• The conditions under which the genomic data can be linked back to a subject’s personal
identifiers for any purpose, including the return of genomic data to the subject, should be
described in research related documents, e.g. the informed consent document.
• Data protection and confidentiality have to be considered and ensured. In the EU the
general data security measures have to correspond to the Directive 95/46/EC.
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Enhancement (Medical Enhancement)
Directive 2001/83/EC defines a medicinal product as:
“Medicinal product:
(a) Any substance or combination of substances presented as having
properties for treating or preventing disease in human beings; or
(b) Any substance or combination of substances which may be used in
or administered to human beings either with a view to restoring,
correcting or modifying physiological functions by exerting a
pharmacological, immunological or metabolic action, or to making a
medical diagnosis.”
EMA’s role is to review MAAs for medicines whose proposed function is
to treat or prevent disease. The issue of “enhancement” is therefore
out of the scope of EMA activities and therefore no comment is
offered.17
GOAL
•Subjects/patients participating in trials are fully
protected – wherever the trial takes places
•Availability of safe and effective new medicines, as
early as possible, with data relevant to all regions
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Thank you