data quality

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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
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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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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
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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.
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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
MSSO-DI-6225-12.0.0 © 2009 Northrop Grumman Corporation. All Rights Reserved.

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Regulatory Status of Mandate
• US FDA
– Used in FDA’s 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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Regulatory Status of Mandate (cont)
• 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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Regulatory Status of Mandate (cont)
• 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
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OUT IN

Patient demographic terms

Clinical trial study design terms

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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

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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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Problems With Coding Data (cont)
• 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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Problems With Coding Data (cont)
• 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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Problems With Coding Data (cont)
• 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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Problems With Coding Data (cont)
• 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
MSSO-DI-6225-12.0.0 © 2009 Northrop Grumman Corporation. All Rights Reserved.

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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 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
© 2009 Northrop Grumman Corporation. All Rights Reserved.

Miscellaneous Verbatims: Coding Challenges

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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
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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
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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)
MSSO-DI-6225-12.0.0 © 2009 Northrop Grumman Corporation. All Rights Reserved.

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• To Subscribe by – E-mail • [email protected] – 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 • [email protected]
MSSO-DI-6225-12.0.0 © 2009 Northrop Grumman Corporation. All Rights Reserved.

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
© 2009 Northrop Grumman Corporation. All Rights Reserved.

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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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