Adverse events coding

Errors and Inconsistencies in Adverse Event Coding. Adverse events are also subject to errors and inconsistencies by coders and data entry personnel. Many of these inconsistencies become very important when adverse events are analyzed by automated software. 

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. 

The problem for the statistical programmer in categorizing data comes from text variables, or more specifically, free-text variables. A free-text variable is one that may contain any characters and is typically limited only in length. As an example, let s say you need to summarize the adverse events for a set of patients in a trial. The following SAS code shows the data and a quick summarization of the adverse events. 

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. 

Program 2.3 Summarizing Coded Adverse Event Data... 

You can see the benefit of coding the adverse events in the resulting summary. The headaches and myocardial infarctions are grouped appropriately, and splitting lightheadedness and facial laceration into separate events leads to those data being summarized separately as well. 

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. 

The problem is that the regular-trial adverse events database and the serious adverse events database do not join well if at all programmatically. You can attempt to join or merge the two databases by event start date and coded term, and that will join many regular-trial adverse events to the serious events. However, this is far from foolproof, because of mismatches in adverse event start dates and because the adverse events may have been coded slightly differently in the two systems. The best way to link the serious adverse events and adverse events databases is to have the clinical data management system create a linking variable key for you. In lieu of that, the only way to reliably link the two data sources is manually. 

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. 

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 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 ... 

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. 

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. 

Medical Dictionary for Regulatory Activities a creation of the International Conference on Harmonisation used to categorize and code diseases, disorders, and adverse events. 

In response to the National Childhood Vaccine Injury Act of 1988, which required health workers to report vaccine adverse events, the CDC and the FDA collaborated in 1990 to implement the Vaccine Adverse Event Reporting System (VAERS) to monitor the safety of vaccines in both sectors. Health care professionals and parent or other caretakers are encouraged to report all clinically significant vaccine adverse events. Narrative diagnostic reports are reviewed and assigned standard codes using Coding Symbols for a Thesaurus of Adverse Reaction Terms. The source of the vaccines (public versus private provider) is recorded on the form. 

In a double-bUnded study, both the Investigator and the subjects are unaware of whether they receive the drug or the placebo. The randomization code is held in confidence and is opened at the end of the trial for data analysis or in cases where adverse events occurred. 

Assessment of safety Specification of safety parameters Methodology of assessing safety parameters Handling of serious adverse events Handling of ordinary adverse events Procedure for breaking codes... 

Are there clear instructions for reporting of adverse events and serious adverse events (SAEs) There should be full instructions for the reporting of SAEs (including addresses and fax numbers), with time limits. It should be clear that these rules also apply to SAEs that occur in subjects who have finished the study. All SAEs that come to the knowledge of the trialist should be reported unless the protocol provides guidance or time limit when the authors can justify that the occurrence of the SAE could not be related to the treatment received in the clinical trial. In a blinded study, there should be clear instructions on when and by whom the code for a particular study subject should be unblinded in an emergency. 

The investigator shall report all serious adverse events immediately to the sponsor except for those that the protocol or investigator s brochure identifies as not requiring immediate reporting. The immediate report shall be followed by detailed, written reports. The immediate and follow-up reports shall identify subjects by unique code numbers assigned to the latter. 

Data coding—Adverse events (AE), medications Incorporation of local laboratory data into database Investigation and resolution of data discrepancies Data validation and quality control audit Data transfers (test and final)... 

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