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MedDRA の基礎知識出典： MSSO-DI-6225-7.1.0 2004 Northrop Grumman Corporation.

PMS 担当者研修テキスト（ 7 ）

PMS フォーラム作成

スライドは英語のままですが、ノート部に訳がついています。保存後確認ください。

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Data Quality, Coding and MedDRA®

MedDRA® is a registered trademark of the International Federation of

Pharmaceutical Manufacturers Associations (IFPMA)

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Course OverviewTo 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 May 1, 2004 – Key provisions include conduct of clinical trials &

pharmacovigilance– Notification of suspected unexpected serious

adverse reactions (SUSARs)• Similar FDA regulations governing pre- &

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 OutputIN 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 – e.g. 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 pre-marketing 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 User Groups (company subscribers)

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Key Features of MedDRA (cont)• Structure facilitates data analysis and

reporting and electronic communication• Large terminology with > 60,000 terms at

lowest level - allows greater specificity• Approx. 16,000 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

– MedDRA used in FDA’s internal adverse event database– Proposed Rule for Safety Reporting Requirements (2003): FDA

proposes to use MedDRA for postmarketing safety reports

• European Union– All reports (electronic) – January 2003– EudraCT (European Clinical Trials Database) requires MedDRA– SUSARs (Suspected Unexpected Serious Adverse Reactions)

require MedDRA

• Japanese Ministry of Health, Labour and Welfare– Electronic reports mandatory from October 2003– MedDRA to be used in Periodic Infection & Safety Reports from

April 2004

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Regulatory Status of Mandate (cont)• Common Technical Document

– A standard format for new drug and biologic product applications to regulatory authorities

– Includes summary documents and reports from individual clinical trials

– MedDRA is the recommended terminology for describing adverse events, both serious and non-serious

– CTD format is mandatory in EU and Japan and is highly recommended in the US from July 2003

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DiseasesDiagnoses

SignsSymptoms

Therapeutic indicationsInvestigation names & qualitative

resultsMedical & surgical proceduresMedical, social, family history

Drug product terms

Equipment, device,diagnostic product terms

Device failure terms

Clinical trial study design terms

Patient demographicterms

Population-level qualifiers

Numerical values forresults

Severity descriptors

OUT

Terms from: COSTART ©

WHO-ART©

HARTS ©

IN

Scope of MedDRA

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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

• A meaning that is clear to the investigator at the point of data entry may be unclear to the sponsor at the point of data coding

• 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, URI, 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 is an outcome and is not usually considered to be an adverse event

• Provide details of cause of death if known• Example:

– “Death due to myocardial infarction”– Myocardial infarction is coded and death is

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 3 individual terms

DiarrheaNauseaVomiting

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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 & SYMPTOMS DIAGNOSIS

Chest pain, dyspnea, diaphoresis, ECG changes

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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Miscellaneous Verbatims: Coding Challenges

• Recurrent fatal stroke• LK RTCTL UNSP XTRNDL ORG• Hears New Age music when furnace turns on• Funk exacerbated• Normally normal after drinking coffee• Went to hell• Patient is intermittently tiresome• Infection in first finger of the right foot• Fireballs in uterus• Blast (menopause)• Flintstone feet• Barely visible posterior

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

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Benefits of Quality Data

• Fewer queries for investigator and sponsor

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Benefits of Quality Data (cont)• 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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Quality DataIN OUT

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Course Evaluation

• Thank you for taking this course• Please take the time to fill out the

evaluation form• Thank you for your feedback

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MSSO Contacts• Mail

MSSOVAR1/MSSO12011 Sunset Hills RoadReston, VA 20190-3285USA

• Telephone– Toll-free Worldwide 877.258.8280 (AT&T)

• Web page– www.meddramsso.com

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Acknowledgements• MedDRA® is a registered trademark of the International

Federation of Pharmaceutical Manufacturers Associations (IFPMA)

• COSTART Thesaurus Fifth Edition Copyright 1995 US Food and Drug Administration (FDA)

• Hoechst Adverse Reaction Terminology System (HARTS)© 1992 Aventis Pharma

• WHO Adverse Reaction Terminology (WHO-ART), Copyright World Health Organization Collaborating Centre for International Drug Monitoring