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Data Quality, Coding, and
MedDRA®

MedDRA® is a registered trademark of the International Federation
of Pharmaceutical Manufacturers and Associations (IFPMA)

Overview
To provide an understanding of:

• Importance of good quality data
• How clinical data are coded
• MedDRA background
• Coding examples
• Benefits of good quality data

MSSO-DI-6225-15.0.0 ©2012 Northrop Grumman Corporation.All Rights Reserved. 2

Data Quality in Clinical
Development
• Highly regulated environment with strong
emphasis on safety surveillance and data
quality
• Applies to clinical trials and post-marketing
arena
• Increasing harmonization of safety
reporting regulations globally


What is Meant by
Good Quality Data?
• Complete
• Accurate
• Diagnosis supported by appropriate
investigations
• Causality assessment for adverse
events


Quality of Input = Quality of Output
IN OUT


Coding of Clinical Trial Data
• Most data entered on Case Report Forms are “coded”
in some form
• Facilitates storage, retrieval, analysis, and
presentation of data
• Some coding is performed by investigators at point of
data entry
– For example, numeric codes for severity of adverse event:
1= mild, 2= moderate, etc.
• Other coding of text data is performed by the
sponsor company after data collection
• Accuracy of initial coding determines accuracy of
analysis


What is MedDRA?
Med = Medical
D = Dictionary for
R = Regulatory
A = Activities


MedDRA Definition
MedDRA is a clinically-validated
international medical terminology used
by regulatory authorities and the
regulated biopharmaceutical industry.
The terminology is used through the
entire regulatory process, from pre-
marketing to post-marketing, and for
data entry, retrieval, evaluation, and
presentation.

Key Features of MedDRA
• Standardized terminology
• International scope – currently available
in 11 languages including English,
Spanish, French, Chinese, and Japanese
• Managed by Maintenance and Support
Services Organization (MSSO) and
updated bi-annually with input from
subscribers


Key Features of MedDRA (cont)
• Structure facilitates data analysis and
reporting and electronic communication
• Large terminology with > 70,000 terms at
lowest level - allows greater specificity
• Approx. 19,500 Preferred Terms, each
representing a unique medical concept
• Used for coding adverse events, signs and
symptoms, procedures, investigations,
indications, medical and social histories,
medication errors and product quality issues


Regulatory Status of Mandate
• US FDA
– Used in several FDA databases
– Proposed Rule for Safety Reporting Requirements
(2003): MedDRA for postmarketing safety reports
• Japanese Ministry of Health, Labour and Welfare
– Mandatory use for electronic reports
– Used in Periodic Infection and Safety Reports
– For medical devices with biological components,
infections to be described with MedDRA terms


Regulatory Status of Mandate (cont)
• European Union
– EudraVigilance database
• Clinical trial SUSARs(Suspected Unexpected Serious
Adverse Reactions) and post-authorization Individual
Case Safety Reports (ICSRs) – use MedDRA LLTs
(current version or the one previous to it)
– Volume 9A (To be retired in 2012)
• MedDRA required for adverse reactions in Periodic
Safety Update Report
• Standardised MedDRA Queries (SMQs) recommended
for signal detection


• European Union (cont)
– New PV legislation (Directive and Regulation)
effective July 2012 broadens AR definition:
• Occurring in context of medication errors
• With uses outside terms of marketing authorization
• Misuse and abuse
• In context of occupational exposures
– Implementing measures include use of
international terminologies, standards, and
formats (MedDRA specifically mentioned)

• European Union (cont)
– Interface between EudraVigilance and EU Risk
Management Plan
• To code indications, risks, interactions (potential
and identified)
– Summary of Product Characteristics guideline
• MedDRA to be used throughout; in particular for
Contraindications, Special warnings and
precautions for use, and Undesirable effects
sections


• ICH M4E Guideline on Common Technical
Document
– Recommended in adverse event summary tables
• Canada
– Guidance Document for Industry - Reporting Adverse
Reactions to Marketed Health Products
• Recommended as standard for adverse reaction reports
– Guidance for Industry - Product Monograph (labeling)
• Preferred terminology for adverse drug reactions


Scope of MedDRA
OUT
Not a drug Frequency
IN
dictionary Diseases qualifiers
Diagnoses
Signs
Symptoms
Patient demographic Numerical values for
Therapeutic indications
terms results
Investigation names &
qualitative results
Medical & surgical procedures
Medical, social, family history
Medication errors
Clinical trial study Severity descriptors
Product quality, device issues
design terms Terms from other
terminologies
Not an equipment, device,
diagnostic product dictionary

Making the Most of MedDRA
• To take advantage of MedDRA’s richness and
specificity, the source data should be
– Clear
– Concise
– Complete
– Accurate
• General principles apply to all clinical data


Problems With Coding Data
• Appropriate coding requires clear initial data
• What is clear to the investigator at the point of
data entry may be unclear to the sponsor at the
point of data coding
• Sponsor must only code reported verbatim term;
not permitted to interpret or draw information
from other sources
• Example: Ambiguous information
– Congestion (nasal, liver, sinus, pulmonary?)
– Cramp (muscle, menstrual, abdominal?)
– Pain (pain where?)

Problems With Coding Data (cont)
• Example: Ambiguous abbreviations
– MI (myocardial infarction or mitral incompetence?)
– GU pain (gastric ulcer pain or genito-urinary pain?)
– Decreased BS (breath sounds, bowel sounds or
blood sugar?)
• Exercise caution with abbreviations that could
be misinterpreted
• ECG, COPD, HIV are examples of standard
abbreviations


• Example: Vague information
– Patient felt “fuzzy”, “weird”, “experienced every
adverse event”
Try to use accepted medical terminology
• Example: Non-specific information
– “Left wrist edema” (coded as Peripheral edema)
– More specific - “Injection site edema left wrist”
(coded as Injection site edema)


• Death, hospitalization, and disability are
outcomes and are not usually considered to be
adverse events
• Provide details of the underlying event, if
known
• Examples:
– “Death due to myocardial infarction” (Coded as
Myocardial infarction with death captured as the
outcome)
– “Hospitalization due to congestive heart failure”
(Coded as Congestive heart failure with
hospitalization captured as the outcome)

• Example: Ambiguous laboratory data
– “Glucose of 40”
– (Source of specimen - blood, urine, CSF? What units?)
– Would have to code as Glucose abnormal if additional
clarification is not obtained
• Example: Conflicting laboratory data
– “Hyperkalemia with serum potassium of 1.6 mEq/L”
– Would have to code as Serum potassium abnormal

If using numeric values, provide units and reference
range. Be specific about specimen source and
diagnostic result/clinical diagnosis.

• Example: Combination terms
– Diarrhea, nausea and vomiting

Try to avoid combination terms - these will have
to be split into three individual terms

Diarrhea
Nausea
Vomiting


Reporting a Specific Diagnosis
• Where possible, report the most important
medical event or specific diagnosis rather than
individual signs and symptoms
• Can provide provisional diagnosis e.g.
“possible”, “presumed”, “rule out”
• Accuracy is important in preventing dilution of
safety signals or generating false signals
SIGNS and SYMPTOMS DIAGNOSIS

Chest pain, dyspnea, Myocardial infarction
diaphoresis, ECG changes


Safety Signals
• Accuracy in diagnosis is important for detection
and evaluation of safety signals
• Events of importance in drug safety
surveillance include:
– QTc prolongation
– Hepatotoxicity
– Stevens Johnson syndrome
– Convulsions
– Rhabdomyolysis


Generating Quality Data
• Clear
• Concise
• Complete
• Accurate
• Be specific if necessary - MedDRA can handle
multiple specific medical concepts:
– Headache - more than 50 types, including cluster,
sinus, migraine, lumbar puncture headache
– Organisms - down to species level e.g.
Staphylococcus aureus


Quality Assurance
• Human oversight of automated coding
results
• Qualification of coder/review staff
• Errors in MedDRA should be addressed by
submission of Change Requests to MSSO;
no ad hoc structural alterations to
MedDRA


FDA-Defined Coding Errors
• Missed Concepts
– All medical concepts described after the product is
taken should be coded
– Example: “The patient took drug X and developed
alopecia, increased LFTs and pancreatitis”.
Manufacturer only codes alopecia and increased
LFTs (missed concept of pancreatitis)
– Example: “The patient took drug X and developed
interstitial nephritis which later deteriorated into
renal failure”. Manufacturer only codes interstitial
nephritis (missed renal failure concept)

Acknowledgement: Dr. Toni Piazza-Hepp, Office of Surveillance
and Epidemiology, CDER

FDA-Defined Coding Errors (cont)
• “Soft Coding”
– Selecting a term which is both less specific and less
severe than another MedDRA term is “soft coding”
– Example: “Liver failure” coded as hepatotoxicity or
increased LFTs
– Example: “Aplasticanemia” coded as unspecified
anemia
– Example: “Rash subsequently diagnosed as Stevens
Johnson syndrome” coded as rash

Acknowledgement: Dr. Toni Piazza-Hepp, Office of Surveillance
and Epidemiology, CDER

Miscellaneous Verbatims:
Coding Challenges
– Went to hell
– Recurrent fatal stroke
– Hears New Age music when the furnace turns on
– LK RTCTL UNSP XTRNDL
– Charcoal-like, gritty granules in his underwear
– Can’t control patient during menses
– His nodule is sticking out
– Normally normal after drinking coffee
– Died of cancer of the placebo
– Superior members fornication
– Barely visible posterior
– Seeing people in room, seeing chickens at window
– Seeing stars and chicken farting
– Patient recently began new job where he works around chicken wings and
barbecue sauce


Company-specific conventions

• Insert slides as required to cover company’s
specific data collection and recording
conventions
• Could include instructions on how to complete
data fields for adverse events, medical history
etc. on paper or electronic CRFs
• Could include general principles of how to
record text-based information as well as
specific instructions for particular therapeutic
areas

Benefits of Quality Data
• Accurate and timely information on issues that
affect conduct of clinical trial and affect patient
safety
• Improved communication among sponsors,
investigators, and regulatory agencies about
medicinal products
– Aids in safety signal detection and evaluation
– Ensures accuracy of information about the product
including investigators’ brochures and prescribing
information
– Benefits medical professionals
– Benefits patients

Benefits of Quality Data (cont)
• Fewer queries for investigator and sponsor


Quality Data
IN OUT


MSSO Contacts
• Mail
MedDRAMSSO
15010 Conference Center Drive
Chantilly, VA, USA 20151
• Telephone
– Toll-free Worldwide 877.258.8280 (AT&T)
• Fax (USA)
– +1 571.313.2345
• Products and Services
– Toll-free Worldwide 877.258.8280 (AT&T)


MSSO Contacts (cont)
• To Subscribe by
– E-mail
• mssohelp@mssotools.com
– Web site
• www.meddramsso.com select “How to Subscribe”
• Help Desk
– Phone
• International AT&T Toll Free: 877.258.8280
• Direct Dial (USA): +1 571.313.2574
– E-mail
• mssohelp@mssotools.com

Useful Links
• Points to Consider documents
– http://www.meddramsso.com/subscriber_library_ptc.asp

• Regulatory Information
– http://www.meddramsso.com/public_aboutMedDRA_regulatory.asp


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MED dra Coding -MSSO

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MED dra Coding -MSSO