MedDRA codes

Adverse events need to be coded consistently with respect to letter case. Problems can occur when there is discordant coding using all capital letters, all lower-case letters, or combinations thereof, as computer software will interpret these capitalization variations as different events. Letter case sensitivity can be important when two or more words are used to describe an adverse event. For example, some databases utilizing the Medical Dictionary for Regulatory Activities (MedDRA) coding dictionary employ a coding system in which only the first letter of the first word of an adverse event is capitalized (e.g., Atrioventricular block complete ). Failing to adhere to uniform letter case conventions across the data can result in severe errors in data analysis. 

Medical dictionaries often need to be referenced when creating various analysis data sets For instance, perhaps the raw adverse event database in your clinical data management system contains only the MedDRA code. The code is worth having, but you would need the adverse event body system and preferred medical term to provide a useful summary of events. 

The Medical Dictionary for Regulatory Activities (MedDRA) is a creation of the International Conference on Harmonization, and it is used to categorize and code diseases, disorders, and adverse events. The five levels and associated codes to the MedDRA coding hierarchy are as follows ... 

Similar analysis approaches are used to describe the risk, in both the absolute and relative (comparative) sense, of individuals reporting specific AEs. These analyses are much more useful clinically because not all AEs are created equal. One example is to estimate the proportion of individuals in a given group who reported a headache. To do this in a standardized manner it is necessary to "code" the AE descriptions (for example, "tension headache", "achy head"). The use of the MedDRA coding dictionary for this purpose is now widely accepted, and in some instances may be required. Coding is performed before statistical analysis and the "coded" terms are used in statistical summaries that require counting of participants reporting each event. 

Coding capability What are the coding capabilities Does it support MedDRA dictionary Does it support other coding dictionaries ... 

There is only one good solution to handling free-text variables that are needed for statistical analysis. The free-text variables need to be coded by clinical data management in the clinical database. If the adverse events were coded with a dictionary such as MedDRA, the previous example might look like Program 2.3. 

Again, the free-text CRF format is useful in that it allows for explicit description of the historical condition, whereas the pre-categorized CRF format omits that detail. However, the free-text list format necessitates coding with a coding dictionary such as MedDRA in order to be useful for analyses. The pre-categorized format is useful here, as only medical history relevant to the investigational therapy can be captured and the cost of additional coding of the history data is eliminated entirely. 

The adverse event form is fairly standard across clinical trials. The form consists of a list of events for which data are entered as free text and are later coded with a dictionary such as MedDRA and some associated event attribute variables. In just about any clinical trial, an adverse event form very similar to the following sample will be found. 

There are hundreds of proprietary medical dictionaries in circulation. Fortunately, a number of medical dictionaries are headed for retirement. The pharmaceutical industry along with regulators and standards groups is actively working to reduce the number of coding dictionaries. So we will discuss MedDRA for adverse events and WHODrug for... 

The essential pieces of MedDRA to have in SAS are the preferred term and body system, as this is what most clinical summaries and analyses require. The following is a piece of simplified SAS code that brings the lowest-level terms, preferred terms, and body systems together into one data set. 

SORT LOW LEVEL TERM DATA FROM MEDDRA WHERE LOW LEVEL TERM = LOWEST LEVEL TERM, LLT CODE = LOWEST LEVEL TERM CODE, AND PT CODE = PREFERRED TERM CODE. proc sort... 

The final meddra data set in this program contains the lower-level term code (llt code) that can then be merged with the adverse events or medical conditions database. By merging the MedDRA dictionary data with the disease data, you can match the verbatim event text captured on the case report form with the preferred term and associated body system. Then you can summarize these data by body system and preferred term you will see an example of this in Chapter 5. 

There are a couple of items to note about MedDRA and the preceding sample SAS code. First, the example assumes that you have already managed to read the system organ class, preferred term, and lowest-level term data tables from the MedDRA dictionary into SAS. Second, the preferred terms may map to more than one system organ class. In this case, MedDRA provides a variable at the preferred term level to indicate what the primary system organ class is. So, you may need to subset the preferred term data set in the example in order to select just the primary system organ class. 

Note that by changing the aesev variable to the aerel variable throughout Program 5.4, you can easily change the previous adverse event summary to a summary of adverse events by maximum drug relatedness. Also, if you remove the maximum severity steps, you get a typical overall summary of adverse events by body system and preferred term. Since patient medical history data are also often coded with MedDRA, patient medical history data may be summarized much like an overall summary of adverse events. However, frequently medical histories are collected in a checklist/checkbox format so that using a coding dictionary is unnecessary. 

European Union (EU). The European Agency for the Evaluation of Medical Products (EMEA) established January 2002 as the deadline for all electronically filed single case reports to be coded in MedDRA. All ADR drug reporting must be coded in MedDRA by January 2003. 

Methods for handling the safety and tolerability data the safety data will usually be coded using the MedDRA (Medical Dictionary for Regulatory Activities, www.meddramsso.com) coding system in order to aid summary and presentation... 

Pharmaceutical companies, individual regulatory authorities and the WHO have databases which facilitate this overview. The use of a standard coding dictionary of adverse event terms is essential for this sort of analysis, and one, MedDRA (Medical Dictionary for Regulatory Activities) has been accepted as the gold standard to be used. Nevertheless, routine review of individual cases by responsible, experienced reviewers is the most essential factor in identifying new signals and ensuring patient protection. 

There are numerous challenges with spontaneous report databases, including the fact that they are numerator-based, subject to many reporting biases, can be hard to place in population context, clearly dependent on coding practices and given the granularity of the MedDRA Dictionary, there can be a dilution of the signal. 

MedDRA also provides Standardized MedDRA Queries (SMQs) to help summarize the data. SMQs may pull PTs from one or more SOCs. One example is cardiac failure, whose codes may occur both in the cardiac SOC as "cardiac failure" or some variant thereof and the respiratory SOC as "pulmonary edema." Bleeding is another important SMQ because people may experience bleeds in a variety of organ classes. Many SMQs have narrow or broad definitions with the latter necessarily including more PTs. 

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