Adverse events and medical histories are coded using MedDRA (Medical Dictionary for Regulatory Activities). Drug names (generic or brand names) are coded using WHO-DD (World Health Organization – Drug Dictionary). Early dates, there are different dictionaries available for performing the medical coding. Nowadays, the coding dictionaries are fixed on MedDRA and WHO-DD.
Both MedDRA and WHO-DD dictionaries are updated periodically - specifically, MedDRA is updated twice a year and WHO-DD is updated four times a year.
When we do a clinical trial, we will start with the latest version of the coding dictionaries. The clinical studies usually take several years to complete. By the time we reach the completion of the study, we will do the database lock (i.e., no data changes after the database lock). The coding dictionaries selected for use at the beginning of the study will be several years old and become obsolete.
One way to resolve this issue is to perform the upversion (or up-version, upversioning) of the medical dictionaries. For a clinical trial (especially a trial with extended study duration), it is good to update the medical coding dictionaries periodically. If upversion can not be performed periodically during the study, it is better to do an upversion at least at the end of the study (before the database lock).
Historically, there was no requirement/mandate for upversion, different companies had different practice in terms of the upversion. Here is the survey result about the upversoin in practice.
However, upversion will soon become a mandate for both MedDRA and WHO-DD dictionaries.
There are two Federal Registers pertinent to the upversion of the MedDRA and WHO-DD (or WHODG) dictionaries: one for MedDRA and one for WHO-DD. Notice that WHO-DD is now called WHODG (World Health Organization Drug Global) in the Federal Register.
Electronic Study Data Submission; Data Standards; Support for Version Update of the Medical Dictionary for Regulatory Activities
“Generally, the studies included in a submission are conducted over many years and may have used different MedDRA versions to code adverse events. The expectation is that sponsors or applicants will use the most current version of MedDRA at the time of study start. However, there is no requirement to recode earlier studies. The transition date for support and requirement to use the most current version of MedDRA is March 15, 2018. Although the use of the most current version is supported as of this Federal Register notice and sponsors or applicants are encouraged to begin using it, the use of the most current version will only be required in submissions for studies that start after March 15, 2019….”
“FDA currently supports the use of WHODG for the coding of concomitant medications in studies submitted to CBER or CDER in NDAs, ANDAs, BLAs, and certain INDs in the electronic common technical document format. Generally, the studies included in a submission are conducted over many years and may have used different WHODG versions to code concomitant medications. The expectation is that sponsors and applicants will use the most current B3-format annual version of WHODG at the time of study start. However, there is no requirement to recode earlier studies. The transition date for support of the most current B3- format annual version of WHODG is March 15, 2018. Although the use of the current B3-format annual version of WHODG is supported as of this Federal Register notice and sponsors or applicants are encouraged to begin using it, the use of the most current B3- format annual version will only be required in submissions for studies that start after March 15, 2019.”Additional Readings: