Wednesday, April 01, 2015

Standardized MedDRA Queries (SMQs) and Standardized Drug Groupings (SDGs)

Clinical trial data collection usually includes the collection of adverse events, concomitant medications, and medical histories. The data is usually collected as the verbatim term in free text fields. The data collected with free text fields is not possible for meaningful summary and analysis. Therefore, the first step will be to perform the medical coding to group the same type or similar type of events or drugs together.

The industry standard for medical coding in clinical trials is to use MedDRA (Medical Dictionary for Regulatory Activities) for adverse events and medical histories and to use WHO-DD (World Health Organization – Drug Dictionary) for concomitant medications.

MedDRA hierarchy includes five layers from top to bottom:
  • System Organ Class (SOC)
  • High Level Group Term (HLGT)
  • High Level Term (HLT)
  • Preferred Term (PT)
  • Lowest Level Term (LLT)
During the coding, verbatim or reported term will be mapped to LLT ->  PT -> HLT -> HLGT -> SOC. The summary and statistical analysis will typically be based on Preferred Term and / or System Organ Class.

WHO-DD adopts Anatomical Therapeutic Chemical (ATC) Classification System and the hierarchy includes five ATC levels from top to bottom:

  • ATC Level 1: The anatomical main group
  • ATC Level 2: The therapeutic main group
  • ATC Level 3: The therapeutic/pharmacological subgroup
  • ATC Level 4: The chemical/therapeutic/pharmacological subgroup
  • ATC Level 5: The chemical substance
The ATC classifications are often used as starting points in the development of protocol violation lists and other medication of interest lists in clinical trials. The classes are also used to identify class effects in safety signal detection.

During the coding, verbatim or reported drug names will be mapped to ATC Level 5 -> ATC Level 4 -> ATC Level 3 -> ATC Level 2 -> ATC Level 1. Summary and statisitcal analyses will typically be based on ATC level 1 and ATC level 3, but can also be based on ATC level 2 and ATC level 4.

ATC Level is not as obvious as MedDRA hierarchy, however, both dictionaries use the tree structure. From top to bottom, the choice of terms expands.

In certain situations, the typical coding based on these hierarchy levels is not sufficient. Additional grouping may be needed. For example, if we are specifically interested in any pulmonary hypertension adverse event, we will need to group any of the following terms together:

Acute right ventricular failure
Chronic right ventricular failure
Cor pulmonale
Cor pulmonale acute
Cor pulmonale chronic
Portopulmonary hypertension
Pulmonary arterial hypertension
Pulmonary arterial pressure abnormal
Pulmonary artery wall hypertrophy
Pulmonary endarterectomy
Pulmonary hypertension
Pulmonary hypertensive crisis
Pulmonary vascular resistance abnormality
Pulmonary vein occlusion
Pulmonary vein stenosis
Right atrial dilatation
Right ventricular hypertrophy
Right ventricular systolic pressure increased
Vascular resistance pulmonary increased
Angiogram pulmonary abnormal
Portal hypertension
Pulmonary infarction
Pulmonary microemboli
Pulmonary vascular disorder

Similarly, we may be specifically interested in certain type of medications to define the inclusion/exclusion criteria or to identify the protocol deviations for subjects who take the prohibited medications.  In a diabetes study, we could utilize ‘Drugs used in diabetes’ to find patients potentially having diabetes, then prohibit the drugs affecting the insulin level. In a study in menopausal women, we may need to define a broad or narrow scope of Estrogens. The narrow scope will include substances classified as estrogens based on their therapeutic and chemical properties and the broad scope include substances having estrogen like effects.

Fortunately, both  MSSO (the organization for maintaining MedDRA) and UMC (the organization for maintaining WHO-DD) are working on providing these additional groupings. For MedDRA, the additional groupings are called SMQ which stands for Standardized MedDRA Queries; for WHO-DD, the additional groupings are called SDGs which stands for Standardized Drug Groupings.

Standardised MedDRA Queries (SMQs) are developed to facilitate retrieval of MedDRA-coded data as a first step in investigating drug safety issues in pharmacovigilance and clinical development. SMQs are validated, pre-determined sets of MedDRA terms grouped together after extensive review, testing, analysis, and expert discussion. SMQs are a unique feature of MedDRA and provide a strong tool to support safety analysis and reporting. The SMQ topics are intended to address the important pharmacovigilance topics needed by regulatory and industry users. SMQs have been developed with the CIOMS Working Group on Standardised MedDRA Queries that provides pharmacovigilance expertise and validation of SMQs. The SMQs are maintained with each release of MedDRA dictionary by the MSSO.

SMQs are included in each release of the MedDRA dictionary with no additional charge.

The Standardized Drug Queries (SDQs) are new additional classification tools in the WHO Drug Dictionary Enhanced. They have been developed together with a group of expert dictionary users and cover different types of classifications e.g. NSAID, cardiac drugs, Old form, CYP etc.

A SDG is a grouping of medicines having one or several properties in common. The individual grouping can be based on indication, chemical properties, pharmacodynamic properties or pharmacokinetic properties as well as any other property of interest. SDGs can be used in pre-qualification of patients, prohibited medicines, or safety- and subgroup analysis. Standardized Drug Groupings simplify creation of protocol violation lists,  medications of interest, or other relevant
medication groupings.

SDGs are available per request (not automatically provided with WHO-DD release) and are free of charge to all users of the WHO Drug Dictionary EnhancedTM (WHO DDE).  The list of currently available SDGs can be found at SDG product leaflet for drug safety.pdf

There are many presentations describing the use of SDGs.

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