Center for Information and Study on Clinical Research Participation (CISCRP)
Founded in 2003 at Washington, DC, USA, the Center for Information and Study on Clinical Research Participation (CISCRP) is a first-of-its-kind nonprofit organization dedicated to educating and informing the public, patients, medical/research communities, the media, and policy makers about clinical research participation and the role that each party plays as a participant in the process. CISCRP’s staff and board of advisors have highly diverse backgrounds - from the clinical research, healthcare and advocacy communities. CISCRP’s funding comes from a wide variety of sources including individual donors, government and research institutions, foundations and corporations.
Association of Clinical Research Organizations (ACRO)
The Association of Clinical Research Organizations (ACRO) represents companies’ worldwide whose focus is clinical research. The association provides an active voice for the global CRO industry, which provides specialized services that are integral to the development of drugs, biologics and medical devices. Through its member companies, ACRO helps improve the quality, efficiency and safety of biomedical research. ACRO member companies employ approximately 70,000 professionals worldwide and annually conduct more than 9,000 clinical trials involving nearly two million participants in 115 countries.Founded in 2002, ACRO represents the CRO industry globally to pharmaceutical, biotech and medical device companies, regulators and legislators, peer associations, academic organizations, patient groups, the media and the public in the U.S. and worldwide.
The Society of Clinical Research Associates(SoCRA)
The Society of Clinical Research Associates, Inc. is a USA based non-profit, professional organization dedicated to the continuing education and development of clinical research professionals.
The Society of Clinical Research Associates, a professional membership organization, was developed to provide educational programs, certification, and a forum for research professionals to exchange information. SoCRA was originally created to benefit researchers at the site, yet our membership has grown to include monitors, data managers, quality assurance, and regulatory representatives from industry, academia, research centers, NIH and regulatory agencies. Our mission is to provide a forum in which our members can learn and exchange information to grow professionally in clinical research and to build strong foundations for successful clinical research outcomes. We encourage professionals working in clinical research to collectively support each other and participate in our educational programs.
Association of Clinical Research Professionals (ACRP)
ACRP is the primary resource for clinical research professionals in the pharmaceutical, biotechnology and medical device industries, and those in hospital, academic medical centers and physician office settings. ACRP was founded in 1976 to address the distinct educational and networking needs of research nurses and others who supported the work of clinical investigations. With its own professional society came the recognition of a new distinctive profession — that of the clinical researcher. More than 30 years later, ACRP is a global association comprised of more than 20,000 individuals in over 60 countries dedicated to clinical research and development. ACRP is headquartered in Alexandria, Virginia-USA, with an additional office in Windsor, U.K.
Society for Clinical Data Management
The Society for Clinical Data Management was established in 1994 to advance the discipline of clinical data management and promote excellence and quality among clinical data managers and related professionals. SCDM has more than 2,600 members and is considered the industry leader in professional development resources.
SCDM’s Certified Clinical Data Manager (CCDM®) program sets the standard for quality in clinical research labs across the United States and around the world. . SCDM’s Good Clinical Data Management Practices (GCDMP) program establishes best practices for all facets of clinical data management and is the resource of choice for CDM professionals.
Association for Clinical Data Management (ACDM)
The Association for Clinical Data Management (ACDM) was founded in 1987. We have a large, diverse membership and aim to lead the development and appreciation of the essential activities of the Clinical Data Management profession.
ACDM provides explicit settings for the membership to develop standards within the profession. We also seek to enhance the individual skills, knowledge and professional development of our members. The intent is to equip them to participate more effectively in the mainstream of drug development.
ACDM is an independent, nonprofit making organization with an international perspective.
Indian Society for Clinical Research(ISCR)
Indian Society for Clinical Research is an association of clinical research professionals registered under the Societies Registration Act (1860) India. The Society brings together all those who are engaged in clinical research activities in India and provides a forum for exchange of information and learning. ISCR aims to build awareness of clinical research as a specialty in India and to facilitate its growth in the country while helping to evolve the highest standards of quality and ethics.
Association of Contract Research Organizations (ACRO)-India
ACRO (India) was founded and registered in India in February 2005. The Association has been formed under the aegis of Confederation of Indian Industries (CII) for putting all CRO's operating in India on one common platform will be used to promote quality research, uphold ethics, share best practices, promote synergies amongst member, to deliberate and action on common concerns, especially with regard to Indian regulations and industry environment.
ACRO will represent the interests of Indian CROs to regional, national and international authorities and organizations. The Association is an independent, non-profit organization with a global perspective.
Regulatory Affairs Professionals Society (RAPS)
The Regulatory Affairs Professionals Society (RAPS) is a US based leading worldwide member organization devoted to the health product regulatory profession. With more than 12,000 individual members from industry, government, research, clinical and academic organizations in more than 50 countries, RAPS develops professional standards for knowledge, competency and ethics and is the leading source of information on the scope of practice of regulatory professionals and their critical roles in the healthcare products sector.
Founded in 1976, RAPS advances learning and fosters knowledge exchange in regulatory, scientific, business, legal and other areas essential to effective product development and regulation. RAPS also administers the only recognized credential specifically for regulatory professionals—Regulatory Affairs Certification (RAC)
The coding of patient data is critical in the grouping, analysis, and reporting of data. Coding decisions directly impact submissions for New Drug Applications (NDAs), safety surveillance, and product labeling. The success of a submission to the FDA can be significantly impacted by the analysis of adverse events, medical history and concomitant medications. The analysis relies on the interpretation of what has been transcribed from the subject CRF (Case Report Form). The original clinical term is referred to as the clinician’s term or verbatim term. This term needs to be re-interpreted or coded into a preferred term in order for it to be used during analysis. This is because different verbatim terms can have the same meaning such as in the example of the term “pain in head” or “headache”. In this case, the two distinct verbatim terms are coded to one synonymous preferred term. The identical terms and the consistent classification of the term allow the analysis to draw valid statistical conclusions pertaining to the subject’s experience. The coding process can therefore affect the statistical interpretation of the adverse events or medications in which the subject is taking during the clinical trial.
HISTORY AND STRUCTURE OF STANDARD DICTIONARIES
DICTIONARY FOR ADVERSE EVENTS
For statistical purpose and public health control, the need for an internationally accepted classification system was recognized at the First International Statistical Conference in Brussels in 1853. The standardization effort bore fruit in1969 with the FDA’s use of the COSTART (Coding Symbols for a Thesaurus of Adverse Reaction Terms) dictionary.
For the next quarter century, adverse event coding was dominated by WHOART (WHO Adverse Reaction Terminology, required by EU) and COSTART (required by FDA). For regulation purposes, in 1994 the ICH (International Conference on Harmonization) began to standardize international medical terminology in all the phases of the regulatory process. In 1997 the first version of MedDRA (Medical Dictionary for Regulatory Activities) was born.
The FDA recommends that adverse events are coded in MedDRA. This dictionary was also required by EU starting in 2003. MedDRA became commonly used to translate the Adverse Event verbatim terms into standard terms. It has a distinctive five level hierarchy structure ranging from System Organ Class (SOC), High Level Group Term (HLGP), High Level Term (HLT), Preferred Term (PT), to Low Level Term (LLT). The hierarchy allows the dictionary to
accommodate both linear and multiaxial coding.
DICTIONARY FOR CONCOMITANT MEDICINE
In the pharmaceutical industry, two types of dictionaries are commonly used. One type of dictionary is used to standardize the adverse event terms while the other type of dictionary is used to standardize the drug terms. WHODD (WHO Drug Dictionary) is commonly used for the standardization of drug names. Drug information has been entered into the dictionary since 1968. WHO-DD is the world’s most comprehensive dictionary for medicinal product
information. It is used by pharmaceutical companies, clinical trial organizations and drug regulatory authorities for identifying drug names, active ingredient(s), therapeutic usage, and frequently used drugs in most major drug markets in the world. The organization that maintains this dictionary is named UMC (Uppsala Monitoring Centre).
UMC organizes drug information by classifying them into codes according to the Anatomical-Therapeutic-Chemical classification (ATC). This allows for grouping of drugs in different ways for useful analysis. The information is also classified according to the main therapeutic use of the main active ingredient on the basic principle of only one ATC code for each pharmaceutical formulation.
Who DD Glossary Coding
The WHO Drug Dictionary is used by pharmaceutical companies and drug regulatory authorities for identifying drug names, active ingredients and therapeutic use, in the course of drug safety surveillance.
The long-term success of MedDRA depends on effective maintenance and update support to ensure that the terminology continues to evolve and meet user requirements. The International Federation of Pharmaceutical Manufacturers and Associations (IFPMA) acting as a trustee for ICH, contracted with Northrop Grumman to provide the MedDRA Maintenance and Support Services Organization (MSSO). The MSSO reports to IFPMA and an ICH Board of Directors.
MedDRA Spoken Here
MedDRA (Medical Dictionary for Regulatory Activities) is the global standard medical terminology for adverse event reporting and analysis. Major global regulatory authorities in the United States, Europe, and Japan have adopted MedDRA and have required its use. The FDA, for example, has implemented MedDRA within its Adverse Event Reporting System (AERS). European and Japanese regulators have mandated the use of MedDRA for clinical trials and for marketed product reporting. Most regulatory authorities are using MedDRA as a required part of their electronic submission systems.
The MSSO is responsible for ensuring the terminology is updated regularly and that it remains responsive to user needs. The MSSO is committed to the global success of MedDRA.
MedDRA is intended for use by:
• Pharmaceutical companies
• Biotechnology companies
• Device manufacturers
• Regulatory authorities
• CROs
• System developers
• Other support service organizations
How Do You Use MedDRA?
The first step toward MedDRA implementation is to subscribe to MedDRA. The annual subscription includes periodic updates. Subscribers may request changes to the terminology and gain other important benefits including help desk support and user group membership.
What Support Is Available from the MSSO?
The MSSO offers a wide range of orientation, assessment, training, coding, and implementation support to ensure that each new subscriber achieves a smooth, efficient, and cost-effective transition and implementation. Please contact the MSSO for more detailed information.
www.northropgrumman.com/health
Health Solutions, 3975 Virginia Mallory Drive, Chantilly, VA 20151
Northrop Grumman, 7575 Colshire Drive, McLean, VA 22102 703-556-1000
Northrop Grumman has a long association with MedDRA, including playing an instrumental role in revising and extending the original version of the terminology. To learn about MedDRA and how the MSSO can support you, contact us today by email at mssohelp@ngc.com or visit our website www.meddramsso.com .
MedDRA - the Medical Dictionary for Regulatory Activities - is a medical terminology used to classify adverse event information associated with the use of biopharmaceuticals and other medical products (e.g., medical devices and vaccines). Coding these data to a standard set of MedDRA terms allows health authorities and the biopharmaceutical industry to more readily exchange and analyze data related to the safe use of medical products.
MedDRA was developed by the International Conference on Harmonisation (ICH) and is owned by the International Federation of Pharmaceutical Manufacturers and Associations (IFPMA) acting as trustee for the ICH steering committee.
The MSSO - Maintenance and Support Services Organization - serves as the repository, maintainer, and distributor of MedDRA as well as the source for the most up-to-date information regarding MedDRA and its application within the biopharmaceutical industry and regulators. MedDRA subscribers submit proposed changes to the terminology. The MSSO includes a group of internationally based physicians who review all proposed subscriber changes and provide a timely response directly to the requesting subscriber.
Standardised MedDRA Queries (SMQs)
Standardised MedDRA Queries (SMQs) were developed to facilitate retrieval of MedDRA-coded data as a first step in investigating drug safety issues in pharmacovigilance and clinical development. They were developed in a cooperative effort between the ICH and the Council for the International Organization of Medical Sciences (CIOMS).
SMQs are groupings of terms from one or more MedDRA System Organ Classes (SOCs) that relate to a defined medical condition or area of interest. They are intended to aid in case identification.
MedDRA Translations
As part of their subscription, MedDRA users are able to access all available EU language translations of MedDRA which currently include Czech, Dutch, French, German, Italian, Portuguese, and Spanish. The MedDRA-Chinese translation is available as of MedDRA Version 12.1. A fee is required to access the Chinese and Japanese translations of MedDRA.
Few of these data like Adverse event and Disease History is essentially entered as free text and thus coding is an essential method to harmonize all these data so that it is analysed properly. The data entered is compared and matched with standard libraries or dictionaries and updated with a data which is uniform and acceptable. Coding may be done automatically (Computer Aided) , manually or a combination of both.
This medical coding is different : If you search for "medical coding" on web , you will be driven to websites which deals with the ICD or CPT medical coding which is different from the coding in clinical trials. The ICD (9,10 etc.) medical coding deals with mapping various medical diagnosis and procedures to codes. This mostly deals with medical insurance data and medical billing. The ICD or CPT coding is out of scope here in this tutorial.
Dictionaries are essential for medical coding. These medical dictionaries contains standardized database with which the verbatim terms entered in the CRF's is matched. Few Clinical research organizations even keep their own customized dictionary e.g. Drug dictionary .
Various Medical Dictionaries / Thesaurus :
Dictionary / Thesaurus name
Full name
Primary Use
WHOART
World Health Organization Adverse Reaction Terminology
Adverse event (AE) coding
COSTART
(FDA’s) Coding Symbols for a Thesaurus of Adverse Reaction Terms
Adverse event (AE) coding
MedDRA
Medical Dictionary for Regulatory Activities Terminology (latest V 12.0)
AE / Med. History / Terms coding
ICD (9, 10, 10 CM etc.)
International Classification of Diseases (9th / 10th Revision / 10th revision - Clinical Modification)
Medical diagnosis and procedures coding
WHODD
World Health Organization Drug Dictionary (B1, B2, C)
Medication coding (concomitant)
These Dictionaries follow a hierarchal structure for coding. Dictionaries are always under constant up-gradation and comes with a newer version frequently.
In what form is it available ? : Consider the case of MedDRA where Dictionary is supplied as bunch of flat ASCII files ($ character separated) with proper documentation and defined data types, so that any standard databases can easily import the file e.g. Create a Oracle template (DBT) using the MedDRA documentation and import the dictionary.
MedDRA browser is available as a download from MSSO Website, for those who need to do manual coding. The MedRA ASCII files can be imported to the local computer and used. Automatic coding systems however requires these ASCII data files to be imported to some RDBMS like Oracle, MySQL, PostGRE SQL or as SAS Datasets.
Automatic coding (auto-coding) : The complexity of medical science makes autocoding a failure. The "text (verbatim)" terms entered into the system is matched with the terms found in the dictionaries. Autocoders are efficient with "exact" or '100%' matches for the verbatim term and miss-spellings will lead to erroneous or no result. . Its not a good idea to rely on autocoding entirely (especially when dealing with medical terms) and the results of Higher level terms sometimes turns out to be funny. Autocoders get confused if two terms are reported simultaneously e.g. fever and rash or fever & rash ; this kind of data entry can't be avoided because clinicians are used to such kind of data recordings.
Mostly the autocoders follow fixed and limited algorithms for the medical coding (algorithms are programmed by Software professionals who doesn't care about the essence of Medicine and hence such algorithms turns out to be waste) . The typical algorithms include text replacements (e.g mild raised temp. and low grade fever is transformed to mild fever) , text removal (e.g. low fever changed to fever), numeral removal (e.g. fever-104 replaced with fever).
A combination of auto and manual coding always works for fast and better results.
Medra terms: (details later in this page)
LLT : Lower level terms
HLT : Higher level terms
HLGT : Higher level group term
SCT : Super class term
SOC : System organ class
Example :
Toothache (LLT)
Toothache (PT)
Dental pian and sensation disorders (HLT)
Dental and Gingival conditions (HLGT)
Gastrointerstinal Disorders (SOC)
Example 2:
Back pain (LLT)
Back Pain (PT)
Musculoskeletal and con. tissue signs and symptoms NEC (HLT)
Musculoskeleteal and connective tissue disorders NEC (HLGT)
Musculoskeletal and connective tissue disorders (SOC)
COSTART terms: (details later in this page)
RT :Reported Term
ET :English Term
SBS :Sub-Body System
PBS :Primary Body System
WHODD: WHODD is available in now available in 2 formats - B and C. Previously format. A was available which is now obsolete. C is the current format and is been in place since last 4-5 years; it contains more information than B format. B is still in place as the older set ups find it difficult to migrate to C yet. For coding of the therapeutic use of drugs, Anatomical Therapeutic Chemical classification (ATC) is used. Each drug is assigned at least one ATC code. ATC - Anatomical-Therapeutic Chemical Classification that is the parts and systems of the human body where the drug might have an effect.
WHO Dictionaries :
1. WHODD : WHO Drug Dictionary
2. WHOHD : WHO Herbal Dictionary
3. WHODDE : WHO Drug Dictionary enhanced
ATC codes : The classification categorises substances at five different levels according to the organ or system on which they act and their chemical, pharmacological and therapeutic properties. There are fourteen main groups (1st level), with one pharmacological/therapeutic subgroup (2nd level). The 3rd and 4th levels are chemical/pharmacological/therapeutic subgroups and the 5th level represents the chemical substance
Anatomical Therapeutic Chemical groups - first level
A Alimentary tract and metabolism
B Blood and blood forming organs
C Cardiovascular system
D Dermatologicals
G Genito urinary system and sex hormones
H Systemic hormonal preparations, excl. sex hormones and insulins
J Anti-infectives for systemic use
L Antineoplastic and immunomodulating agents
M Musculo-skeletal system
N Nervous system
P Antiparasitic products, insecticides and repellents
R Respiratory system
S Sensory organs
V Various
Level
Code
Content
1
J
ANTIINFECTIVES FOR SYSTEMIC USE
Anatomical main group
2
J01
ANTIBACTERIALS FOR SYSTEMIC USE
Therapeutic subgroup
3
J01F
MACROLIDES, LINCOSAMIDES AND STREPTOGRAMINS
Pharmacological subgroup
4
J01FA
MACROLIDES
Chemical subgroup
5
J01FA06
ROXITHROMYCIN
Chemical substance
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 postmarketingsafety reporting
•Objective is global harmonization
What is MedDRA?
Med= Medical
D= Dictionary
R=Regulatory
A= Activities
MedDRADefinition
MedDRAis a clinically-validated nternational 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 -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
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
–Used in FDA’s adverse event database (AERS)
–Proposed Rule for Safety Reporting Requirements (2003): MedDRAfor postmarketingsafety reports
•Japanese Ministry of Health, Labourand Welfare
–Mandatory use for electronic reports
–Used in Periodic Infection and Safety Reports
–For medical devices with biological components, infections to be described with MedDRAterms
•SUSARs(Suspected Unexpected Serious Adverse Reactions) –use MedDRALLTs(current or previous version)
–Volume 9A (all authorized medicinal products, including OTC)
•Individual Case Safety Reports (ICSRs) –use MedDRALLTs(current or previous version)
•For adverse reactions in Periodic Safety Update Report
•StandardisedMedDRAQueries (SMQs) recommended for signal detection
–Interface between EudraVigilanceand EU Risk Management Plan
•To code indications, risks, interactions (potential and identified)
–Summary of Product Characteristics guideline
•Use in Undesirable Effects section
Making the Most of MedDRA
•To take advantage of MedDRA’srichness 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?)
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 infarctionwith death captured as the outcome)
–“Hospitalization due to congestive heart failure”(Coded as Congestive heart failurewith 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 abnormalif additional clarification is not obtained•Example: Conflicting laboratory data–“Hyperkalemiawith serum potassium of 1.6 mEq/L”–Would have to code as Serum potassium abnormalIf using numeric values, provide units and reference range. Be specific about specimen source and diagnostic result/clinical diagnosis.
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
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)
The Society of Clinical Research Associates, Inc. is a USA based non-profit, professional organization dedicated to the continuing education and development of clinical research professionals.
The Society for Clinical Data Management was established in 1994 to advance the discipline of clinical data management and promote excellence and quality among clinical data managers and related professionals. SCDM has more than 2,600 members and is considered the industry leader in professional development resources. 
Indian Society for Clinical Research is an association of clinical research professionals registered under the Societies Registration Act (1860) India. The Society brings together all those who are engaged in clinical research activities in India and provides a forum for exchange of information and learning. ISCR aims to build awareness of clinical research as a specialty in India and to facilitate its growth in the country while helping to evolve the highest standards of quality and ethics.
Founded in 1976, RAPS advances learning and fosters knowledge exchange in regulatory, scientific, business, legal and other areas essential to effective product development and regulation. RAPS also administers the only recognized credential specifically for regulatory professionals—Regulatory Affairs Certification (RAC)
