# Presentation: 873174

## Standardized MedDRA Queries (SMQs) 

- Search Strategies, Communication, and Analyzing Results Using SMQs: A Regulatory Perspective

- Melissa M. Truffa, R.Ph.
- CDER Office of Drug Safety
- FDA
- DIA Annual Meeting
- June 15, 2004
*The opinions expressed are those of the author and not necessarily those of the FDA.*

## Definition of Standardized MedDRA Queries (SMQs)

- Groupings of MedDRA terms from one or more System Organ Classes (SOCs) that relate to a defined medical condition or area of interest.
- A tool intended to aid in the retrieval of potentially relevant safety reports that includes a broad selection of terms that may relate to signs, symptoms, diagnoses, syndromes, physical findings, laboratory and other physiologic test data, etc., that are associated with the medical condition or area of interest
- Intended to provide a standardized frame of reference

## Potential Benefits of Using SMQs

- Uniformity of search strategies and results
- Reproducibility of  search strategies and results
- Convenience of pre-defined grouping of MedDRA terms based on a medical condition of interest
- Maintenance by MSSO

## Scope of SMQ Utility 

- Search and retrieval tool
- Not necessarily comprehensive or universally acceptable
- SMQs are not case Case Definitions
- Case report evaluation is needed to answer specific safety questions.
- No regulatory implications or requirements for use

## General Queries of Safety Databases

- AEs must be coded in MedDRA terminology to use SMQs
- How many reports of a particular AE are represented in the safety database?

## Search Strategies

- Standardized Queries
- Narrow: Accommodates the circumstances in which the user may look to identify/retrieve cases that are highly likely to represent the medical condition of interest.
- Broad: accommodates circumstances in which the user seeks to identify/retrieve all clinically relevant cases.
- Customized Search Strategies may need to be developed and existing SMQs may need to be modified based on individual safety issues.
*   *

**Notes:**
Narrow Search
Appropriate when increased specificity is needed to identity probably reports with a greater certainty than the broad search
Mostly identify a smaller number of reports that represent the precise condition of interest
 Do not identify relevant cases that are only coded with signs and symptoms and not a specific diagnosis
Broad Search 
identity a possible cohort of reports for further review/analysis 
Because of inclusion of non-specific terms may retrieve cases that are not indicative of the presence of absence of the condition under review
May be appropriate when the condition is not well defined or the preliminary stages of generating a safety hypothesis

## Search Strategies cont. 

- SMQs are mixture of very specific and very broad terms
- Each SMQ has accompanying  documentation of how the individual SMQs were developed and defined.
- Introduction
- Definition of condition of interest
- Methodology for development
- Search Strategy
- Pre-Release Testing

## Acute Renal Failure SMQ (narrow)Preferred Terms (n=14)

- Acute prerenal failure, Anuria, Azotemia, Dialysis, Hemodialysis, Neonatal anuria, Nephropathy toxic, Oliguria, Peritoneal dialysis, Renal failure acute, Renal failure neonatal,  Renal impairment neonatal, and Renal impairment, and Renal insufficiency.

## Acute Renal Failure SMQ (broad)Preferred Terms (n=32)

- Acute prerenal failure*, Albuminuria, Anuria*, Azotemia*, Blood creatinine abnormal, Blood creatinine increased, Blood urea abnormal, Blood urea increased, Blood urea nitrogen/creatinine ratio increased, Creatinine renal clearance decreased, Dialysis*, Edema due renal disease, Hemodialysis*, Hepatorenal failure, Neonatal anuria*, Nephritis, Nephritis interstitial, Nephropathy toxic*, Oliguria*, Peritoneal dialysis*, Proteinuria, Renal clearance decreased, Renal failure acute*, Renal failure neonatal*, Renal function tests abnormal, Renal impairment neonatal*, Renal impairment*, Renal insufficiency*, Renal transplant, Renal tubular disorder, Renal tubular necrosis, Tubulointerstitial nephritis.

## Development and Pre-Testing of the ARF SMQ

- Team within the CIOMS WG of 3 regulators and one industry member
- Steps in Developing the ARF SMQ
- Defined Acute renal failure
- Searched MedDRA hierarchy for clinically relevant MedDRA terms for inclusion
- Established inclusion/exclusion criteria for term selection
- Tested initial SMQ on FDA’s AERS database and an industry safety database
- Modified the SMQ based on  results of pre-testing
- Retested the SMQ:  level of comfort that it can be applied to a safety database and retrieve relevant cases of ARF
- Presented the SMQ to entire CIOMS WG for comment

## Number of Cases Identified by the Narrow and Broad Searches for Acute Renal Failure

**	****	****Product A    Product B    Product C    Product D     Product E**
**Search**
- Narrow  		192 		 235 	         724 	277  		23
- Broad   	   	227 (+35)        311(+76)     999 (+275)     297 (+20)           26 (+3)
**Cases in **
**Database   ****	**1565		1081	        9742	3665		294

## Summary 

- SMQs are for searching and retrieval
- An important step in the retrieval of case reports for evaluating potential safety signals
- International effort to develop a standardized tool
- Feedback on the development and utility of SMQs is welcome