Data Quality Improvement

Data Quality, Coding, and MedDRA
MedDRA is a registered trademark of the International Federation of Pharmaceutical Manufacturers and Associations (IFPMA)
Course 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
2009 Northrop Grumman Corporation. All Rights Reserved.
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Data Quality and Clinical Trials

Highly regulated environment with increasing emphasis on safety surveillance and data quality EU Clinical Trials Directive effective 1 May 2004
Key provisions include conduct of clinical trials and pharmacovigilance
Similar FDA regulations governing pre- and postmarketing safety reporting Objective is global harmonization
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2009 Northrop Grumman Corporation.
All Rights Reserved.
What Is Meant by Good Quality Data?

Complete Accurate Diagnosis supported by appropriate investigations Causality assessment for adverse events
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Quality of Input = Quality of Output

IN OUT
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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
MSSO-DI-6225-12.0.0 2009 Northrop Grumman Corporation. All Rights Reserved.
MedDRA Background
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What is MedDRA?
Med = Medical D = Dictionary for R = Regulatory A = Activities
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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 premarketing to post-marketing, and for data entry, retrieval, evaluation, and presentation.
Key Features of MedDRA

Standardized terminology International scope - translated into several languages, including Spanish, French, and Japanese Managed by Maintenance and Support Services Organization (MSSO) and updated bi-annually with input from subscribers
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Key Features of MedDRA (cont)

Structure facilitates data analysis and reporting and electronic communication Large terminology with > 67,000 terms at lowest level - allows greater specificity Approx. 18,500 Preferred Terms, each representing a unique medical concept Typically used for coding adverse events, signs and symptoms, procedures, investigations, indications, and medical and social histories MedDRA is not a drug dictionary
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Regulatory Status of Mandate

US FDA
Used in FDAs adverse event database (AERS) 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
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Regulatory Status of Mandate (cont)

European Union
Clinical trials
SUSARs (Suspected Unexpected Serious Adverse Reactions) use MedDRA LLTs (current or previous version)
Volume 9A (all authorized medicinal products, including OTC)
Individual Case Safety Reports (ICSRs) use MedDRA LLTs (current or previous version) For adverse reactions in Periodic Safety Update Report Standardised MedDRA Queries (SMQs) recommended for signal detection
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European Union (cont)
Interface between EudraVigilance and EU Risk Management Plan
To code indications, risks, interactions (potential and identified)
Summary of Product Characteristics guideline

Use in Undesirable Effects section
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ICH M4E Guideline on Common Technical Document
Recommended in adverse event summary tables
Canada
Reporting Adverse Reactions to Marketed Health Products (draft guidance)
Recommended as standard for adverse reaction reports
Product Monograph (labeling)

Preferred terminology for adverse drug reactions
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Scope of MedDRA
Drug product terms Frequency qualifiers Diseases Diagnoses Signs Symptoms Numerical values for Therapeutic indications results Investigation names & qualitative results Medical & surgical procedures Medical, social, family history Terms from: Severity descriptors COSTART WHO-ART HARTS J-ART Equipment, device, diagnostic product terms
OUT IN
Patient demographic terms
Clinical trial study design terms
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Making the Most of MedDRA

To take advantage of MedDRAs richness and specificity, the source data should be
Clear Concise Complete Accurate
General principles apply to all clinical data
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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?)
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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?) COLD (feeling cold, common cold or chronic obstructive lung disease?)
Exercise caution with abbreviations that could be misinterpreted ECG, COPD, HIV are examples of standard abbreviations
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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)
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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)
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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.
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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
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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 Chest pain, dyspnea, diaphoresis, ECG changes DIAGNOSIS Myocardial infarction
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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
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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
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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
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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 Cant 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
Miscellaneous Verbatims: Coding Challenges
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Company-specific conventions
Insert slides as required to cover companys 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
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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 nephritis (missed renal failure concept)
Acknowledgement: Dr. Toni Piazza-Hepp, Office of Surveillance and Epidemiology, CDER
interstitial nephritis which later deteriorated into renal failure. Manufacturer only codes interstitial
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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: Aplastic anemia coded as unspecified anemia Example: Stevens Johnson syndrome coded as rash
Acknowledgement: Dr. Toni Piazza-Hepp, Office of Surveillance and Epidemiology, CDER
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Benefits of Quality Data (cont)

Fewer queries for investigator and sponsor
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Quality Data
IN OUT
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Mail
MSSO Contacts
MedDRA MSSO 3975 Virginia Mallory Drive Chantilly, VA, USA 20151
Telephone
Toll-free Worldwide 877.258.8280 (AT&T)
Fax
703.272.5635
Products and Services

Toll-free Worldwide 877.258.8280 (AT&T)
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To Subscribe by E-mail mssosubscribe@ngc.com Web site www.meddramsso.com click on Subscribe to MedDRA Help desk Phone International AT&T Toll Free: 877.258.8280 Direct Dial (USA): 703.272.5849 E-mail mssohelp@ngc.com
MSSO Contacts (cont)
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Acknowledgements
MedDRA is a registered trademark of the International Federation
of Pharmaceutical Manufacturers and Associations (IFPMA) Food and Drug Administration (FDA)
COSTART Thesaurus Fifth Edition

(HARTS) 1992 Aventis Pharma
Copyright 1995 US
Hoechst Adverse Reaction Terminology System ICD-9-CM

International Classification of Diseases, Ninth Revision, Clinical Modification, Copyright 1998 Medicode, Inc.
Japanese Adverse Reaction Terminology WHO Adverse Reaction Terminology
(J-ART), is a product of the Japanese Ministry of Health, Labour and Welfare (MHLW) (WHO-ART), Copyright World Health Organization Collaborating Centre for International Drug Monitoring
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Useful Links
Points to Consider documents
http://www.meddramsso.com/MSSOWeb/activities/PTC.htm
Regulatory Mandate Status Update

http://www.meddramsso.com/MSSOWeb/evweb/regulatory. htm
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Data Quality Improvement

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Data Quality, Coding, and MedDRA

Data Quality and Clinical Trials

2009 Northrop Grumman Corporation.

All Rights Reserved.

What Is Meant by Good Quality Data?

2009 Northrop Grumman Corporation.

All Rights Reserved.

Quality of Input = Quality of Output

2009 Northrop Grumman Corporation.

All Rights Reserved.

Coding of Clinical Trial Data

2009 Northrop Grumman Corporation.

All Rights Reserved.

2009 Northrop Grumman Corporation.

All Rights Reserved.

Key Features of MedDRA

Key Features of MedDRA (cont)

Regulatory Status of Mandate

Japanese Ministry of Health, Labour and Welfare

2009 Northrop Grumman Corporation.

All Rights Reserved.

Regulatory Status of Mandate (cont)

Volume 9A (all authorized medicinal products, including OTC)

Regulatory Status of Mandate (cont)

Summary of Product Characteristics guideline

2009 Northrop Grumman Corporation.

All Rights Reserved.

Regulatory Status of Mandate (cont)

Product Monograph (labeling)

2009 Northrop Grumman Corporation.

All Rights Reserved.

Patient demographic terms

Clinical trial study design terms

2009 Northrop Grumman Corporation.

Making the Most of MedDRA

General principles apply to all clinical data

2009 Northrop Grumman Corporation.

All Rights Reserved.

Problems With Coding Data

Problems With Coding Data (cont)

Problems With Coding Data (cont)

Example: Non-specific information

2009 Northrop Grumman Corporation.

All Rights Reserved.

Problems With Coding Data (cont)

Problems With Coding Data (cont)

Example: Conflicting laboratory data

Problems With Coding Data (cont)

2009 Northrop Grumman Corporation.

All Rights Reserved.

Reporting a Specific Diagnosis

2009 Northrop Grumman Corporation.

All Rights Reserved.

2009 Northrop Grumman Corporation.

All Rights Reserved.

Generating Quality Data

2009 Northrop Grumman Corporation.

All Rights Reserved.

Miscellaneous Verbatims: Coding Challenges

Benefits of Quality Data

FDA-Defined Coding Errors

FDA-Defined Coding Errors (cont)

Benefits of Quality Data (cont)