MedDRA & Labelling – European MedDRA User Group · PDF fileMedDRA & Labelling –...
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© NDA Group 2013 MedDRA & Labelling – European MedDRA User Group (MUG) – Vienna March 2014 Use of MedDRA in Summary of Product Characteristics (SPCs) Morell David Principal Consultant- Pharmacovigilance and Drug Safety NDA Regulatory Science
Transcript of MedDRA & Labelling – European MedDRA User Group · PDF fileMedDRA & Labelling –...
© NDA Group 2013
MedDRA & Labelling – European MedDRA User
Group (MUG) – Vienna March 2014
Use of MedDRA in Summary of Product Characteristics (SPCs)
Morell David
Principal Consultant- Pharmacovigilance and Drug Safety
NDA Regulatory Science
© NDA Group 2013 © NDA Group 2013
Disclaimer
o The views and opinions expressed in the following PowerPoint slides are those of the individual presenter.
o These PowerPoint slides are the intellectual property of the individual presenter
and are protected under the copyright laws of the United States of America and other countries.
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Outline o Background o MedDRA Coding vs Labelling o Basis for Using MedDRA in Labelling o Needs of Different Stakeholders o Summary
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MedDRA and International Guidelines – What We Already Know!
o MedDRA developed for use by regulators and biopharmaceutical industry for: o Clinical studies o Spontaneous adverse event/reaction reports o Regulatory submissions o Regulated product information
o MedDRA intended to be used throughout the entire regulatory process, from
pre-marketing through post-marketing, for data entry, retrieval, evaluation, and presentation
o Used for coding adverse events/adverse reactions, signs and symptoms, procedures, investigations, indications, and medical and social histories
o Coding Guidelines based on MedDRA Term Selection: Points to Consider (ICH Endorsed Guide for MedDRA Users)
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How A Typical Safety Surveillance Process might look?
Non-clinical Clinical Ops/ Stats Reg Affairs PVRM CQA
Signal Detection
Safety Review Team (SRT)
Executive Labelling
Committee
CCDS PBRER/ DSUR RTD/RMP IB
Ad Hoc Communication
Non-clinical studies and Literature
Clinical trials Observational Studies
PASS Literature
HA Requests ICSR
Epidemiology
Quality Complaints
Population data Epi Studies
Local Label
Gov
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Eval
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How should we use MedDRA in Regulated Product Information?
o “Best practices” guidelines on the use of MedDRA for labelling was published by MSSO in 2005
o EU SPC Guidelines – 2009
o MSSO proposed 3 tiers of product labelling:
o Labelling for national/regional healthcare professionals (HCPs) o Labelling for patients/consumers o Labelling in the form of a Company Core Data Sheet (CCDS)
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Labelling for Patients/Consumers
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Labelling for national/regional healthcare professionals (HCPs)
Labelling for national/regional healthcare professionals (HCPs)
o Labelling should serve to communicate information on the benefits and risks as well as advice on the effective and safe use of a product to HCPs and other end users
o National/regional HCP labelling is intended to be used by
to determine expectedness of adverse drug reactions (in terms of nature, severity, specificity, or outcome) for purposes of expedited reporting to local regulatory authorities
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Labelling for Patients/Consumers
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Labelling for Patients/Consumers
Labelling for patients/Consumers
o Using MedDRA terms in the patient/consumer labelling could be challenging as most MedDRA terms (PT level and above) are generally not readily interpretable by patients/consumers without some degree of medical or healthcare training
o Although patient information is based upon and must be
consistent with the information provided in the HCP labelling, this labelling must use language that is easily understood by non-professionals, rather than medical terminology
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Labelling for Patients/Consumers
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Labelling for Company Core Data Sheet (CCDS)
Labelling for Company Core Data Sheet (CCDS) 1
o CCDS used by manufacturers as internal reference labelling for local affiliates
o The CCDS generally contains a defined set of data and advice that
the company plan to reflect in national or regional labelling worldwide
o This reference safety information is commonly designated as
Company Core Safety Information (CCSI) o The CCSI information is typically designed to reflect the company’s
view of the essential safety information that will assist in the selection and use of the medicine by healthcare professionals.
o The CCSI can also apply to products that are in clinical development!
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Labelling for Company Core Data Sheet (CCDS) 2
o The CCDS is usually used as a global reference document for the determination of “listedness” for periodic safety reporting (i.e., as reference labelling for Periodic Safety Update Reports [PSURs])
o In the CCDS - MedDRA should be used in narrative and tabular
presentations of information
o The PT level of MedDRA should be used in the adverse reactions section of the CCDS, but supplemented with HLTs, HLGTs and/or SMQs or similar groupings to represent particular conditions, if needed
o In the CCDS it might be possible to supplement PTs with a list of
corresponding LLTs to assist with judging listedness and to facilitate automated expectedness determination
o However, if used, this list of LLTs should not be a substitute for medical
judgement.
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Labelling for Patients/Consumers
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EU Summary of Product Characteristics (SPC) Guideline 2009
MedDRA & Labelling - SPC Guideline 2009 (Rev 2)
o EU Labelling Guidelines based on the SPC Guideline which was first put out for consultation in 2005
o Guideline Introduced in EU 2009 o Guideline included in The Rules Governing Medicinal Products
in the European Union - Volume 2C Notice to Applicants and effective from 01 May 2010
o “Consistent medical terminology should be used
throughout the SmPC, In particular”: o section 4.3 Contraindications o section 4.4 Special Warnings and Precautions o Section 4.8 Undesirable effects
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SPC guideline 2009 – Basic Principles (1)
o Table of ADRs in Section 4.8 Undesirable effects by MedDRA SOC o SOCs should be presented in International SOC order o Events should be arranged by frequency within each SOC, with most
frequent reactions listed first o Pragmatic approach to term location to make ADRs clinically appropriate to
the reader o Adverse reactions descriptions should be based on the most suitable
representation within the MedDRA terminology o This will usually be at the Preferred Term (PT) level, although there may be
instances where the use of Lowest Level Terms (LLTs) or exceptionally group terms, such as High Level Terms may be appropriate
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SOC Order MedDRA Alphabetical SOC Order MedDRA International SOC Order SOC Blood and lymphatic system disorders SOC Infections and infestations SOC Cardiac disorders SOC Neoplasms benign, malignant and unspecified (incl
cysts and polyps) SOC Congenital, familial and genetic disorders SOC Blood and lymphatic system disorders SOC Ear and labyrinth disorders SOC Immune system disorders SOC Endocrine disorders SOC Endocrine disorders SOC Eye disorders SOC Metabolism and nutrition disorders SOC Gastrointestinal disorders SOC Psychiatric disorders SOC General disorders and administration site conditions SOC Nervous system disorders SOC Hepatobiliary disorders SOC Eye disorders SOC Immune system disorders SOC Ear and labyrinth disorders SOC Infections and infestations SOC Cardiac disorders SOC Injury, poisoning and procedural complications SOC Vascular disorders SOC Investigations SOC Respiratory, thoracic and mediastinal disorders SOC Metabolism and nutrition disorders SOC Gastrointestinal disorders SOC Musculoskeletal and connective tissue disorders SOC Hepatobiliary disorders SOC Neoplasms benign, malignant and unspecified (incl cysts and polyps)
SOC Skin and subcutaneous tissue disorders
SOC Nervous system disorders SOC Musculoskeletal and connective tissue disorders SOC Pregnancy, puerperium and perinatal conditions SOC Renal and urinary disorders SOC Psychiatric disorder SOC Pregnancy, puerperium and perinatal conditions SOC Renal and urinary disorders SOC Reproductive system and breast disorders SOC Reproductive system and breast disorders SOC Congenital, familial and genetic disorders SOC Respiratory, thoracic and mediastinal disorders SOC General disorders and administration site
conditions SOC Skin and subcutaneous tissue disorders SOC Investigations SOC Social circumstances SOC Injury, poisoning and procedural complications SOC Surgical and medical procedures SOC Surgical and medical procedures SOC Vascular disorders SOC Social circumstances
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SPC guideline 2009 – Basic principles (2)
o Adverse reactions should be assigned to the most relevant SOC related to the target organ. For example, if the PT ‘Liver function test abnormal’, ‘Hepatitis’ and ‘Hepatic encephalopathy’ are to be included in an SPC, it would be acceptable to handle them as follows:
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MedDRA Coding EU SPC Guidelines
MedDRA PT Primary SOC Proposed SOC Location
Liver function test abnormal Investigations Hepatobiliary disorders
Hepatitis Hepatobiliary disorders Hepatobiliary disorders
Hepatic encephalopathy Nervous system disorders Hepatobiliary disorders
SPC guideline 2009 – Basic principles (3)
o It is acceptable to adapt the names of the MedDRA group terms if this makes their meaning more transparent to the reader of the SmPC; e.g. the use of the suffixes NEC and NOS are not appropriate for inclusion in the SPC e.g. HLGT Genitourinary tract disorders NEC can be represented as Genitourinary tract disorders
o Adverse reaction terms should be expressed in natural word order, e.g.
‘Interstitial pneumonia’ in preference to ‘Pneumonia interstitial’.
o It may be appropriate to modify MedDRA terms in other ways in the interests of comprehensibility.
o The most widely recognised term for a particular condition should be used, e.g. the use of ‘Churg Strauss syndrome’ might be more appropriate than the use of ‘Allergic granulomatous angiitis’
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SPC guideline 2009 – Basic principles (4)
o Appropriate levels of the MedDRA hierarchy should be used in order to group together clinically related conditions in a meaningful way
o For example, if ‘postural dizziness’, ‘exertional dizziness’ and ‘unspecified
dizziness’ were each reported by 2% of patients, this might reasonably be represented in the SmPC as follows:
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Clinical Trial Data SPC Information Clinical Trial AE MedDRA PT Frequency MedDRA Term Frequency
Postural dizziness Dizziness postural 2% Dizziness 8%
Exertional dizziness Dizziness exertional 2%
Dizziness Dizziness 2%
Orthostatic dizziness Dizziness postural 2%
----------------------------------------------------------------------- Note: Assuming that only one report of dizziness applied to each patient
SPC guideline 2009 – Basic principles (5)
o It may also be appropriate to use ad hoc groupings of terms, or to adapt MedDRA group terms if the established MedDRA group terms are not completely suitable, e.g. reports of adverse reactions represented as ‘Diarrhoea’, ‘Diarrhoea aggravated’, ‘Loose stools’, ‘Stools watery’, ‘Intestinal hypermotility’ or other terms might all reasonably be represented as follows:
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Safety Data SPC Guidelines MedDRA Coded Terms SPC Information
Diarrhoea Diarrhoea
Diarrhoea aggravated
Loose stools
Stools watery
Intestinal hypermotility*
------------------------------------------------------------------------------------------- The total number of these cases can be used to estimate the frequency of diarrhoea *Note, PT: GI hypermotility, HLT: Gastrointestinal spastic and hypermotility
disorders
Summary
o MedDRA was originally intended for use by Biopharmaceutical companies, regulators and healthcare professionals mainly for coding and analysing safety data
o Now also used by some device manufacturers and to communicate
information to consumers and patients
o MedDRA-coded data will eventually need to be reflected in product labelling in a language that readily represents as exactly as possible the medical concepts intended to be described
o However safety information needs to be summarized and presented for all end-users to understand and use
o Consequently the rules for use in labelling is more flexible than the
rules for coding and data retrieval (c.f. MedDRA PTC Documents)
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Labelling for Patients/Consumers
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Abbreviations
Abbreviations
o CCDS – Company Core Data Sheet o CQA – Clinical Quality Assurance o DSUR – Development Safety Update Report o HA – Health Authority o IB – Investigators Brochure o ICSR – Individual Case Safety Report o NEC – Not Elsewhere Classified o NOS – Not Otherwise Specified o PBRER – Periodic Benefit Risk Evaluation Report o PVRM – Pharmacovigilance and Risk Management o RMP – Risk Management Plan o RTD – Risk Tracking Document o SPC – Summary of Product Characteristics
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