The Art of Storytelling in Clinical Research, or: Adverse Event Narratives and their Pitfalls
In Clinical Study Reports (CSR), a short description (“narrative“) of all Serious Adverse Events (SAE) must be provided. In addition, all Adverse Events (AEs) leading to discontinuation, and AEs of special interest, must be included. Such narratives should provide a concise yet comprehensive overview of each case.
Usually, the following parameters are essential to describe an SAE/AE comprehensively in a narrative:
Adverse Event Narratives
age and sex of patient
general clinical condition of patient
the underlying disease being treated (may be omitted, if this disease is identical in all patients), including duration and further characterization of illness
relevant concomitant/previous diseases with details of occurrence/duration
relevant concomitant/previous medication
test drug administered, including dose (only in case of variation among patients), and duration of administration
the clinical course leading to the event
the nature, intensity, and outcome of the event
most recent study drug administration before event onset
relevant laboratory parameters
action taken with the study drug (and timing) in relation to the event
treatment or intervention
post-mortem findings (if applicable)
investigator’s and sponsor’s (if applicable) opinion on causality
Narratives are derived from multiple data sources including the clinical database and case report forms. Additionally, safety data base (ARGUS etc.) or CIOMS forms are used for further information on the AEs.
Crucially, output from those sources should be easily readable, and should be provided in a table format which allows filtering and sorting to facilitate retrieval of relevant information. If the medical writer has to scroll through unsorted and unfiltered heaps of data, the writing process is prolonged and not as efficient as it could be. Excel might be a good data format because the writer can customize the view for an optimal overview.
While using different data sources (e.g., CIOMS forms vs. clinical data base), discrepancies can occur, and there should be some person at the sponsor’s end, who takes the responsibility for the resolution and description of irreconcilable discrepancies.
If possible, narrative writing should not start before the data have already been cleaned and reconciled completely: it is much more efficient to write narratives on the basis of clean and reconciled data. However, if timelines are short and if numbers of narratives are high (e.g. > 150), it might be prudent to start the writing process already with unclean data. Obviously, if written based on pre-data-base lock data, narratives have to be updated or modified upon data-base lock.
For the entire process of writing and reviewing, it helps to define simple and consistent wording conventions for specific events and scenarios. By the use of templates, such consistency is much easier to achieve. If the number of narratives is high, various templates for the most common scenarios should be developed and agreed upon by all responsible parties. Typically, templates should include 5-10 common scenarios; and ideally, they should be based on real data.
In addition to the usage of templates, conventions should be developed for specific content of items such as
- format of date,
- counting method of study days,
- statements regarding relevant previous or concomitant medication or medical history
- drug names: preferably, generic names should be provided; an exception being combination drugs, for which also trade names should be provided (in brackets)
- terminology of diseases: preferably MedDRA Preferred Terms (PT) should be used, unless more specificity is needed warranting the use of the verbatim term.
As for all medical writing documents, an established quality control process is of prime importance to guarantee a consistent high-quality output. All documents should be reviewed by a second medical writer, and also by responsible experts from the sponsor. Importantly, for consistency, the medical writing team should not alternate, e.g. between batches, as this constitutes a potential risk of inconsistencies.
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- Ledade SD, Jain SN, Darji AA, Gupta VH. Narrative writing: Effective ways and best practices. Perspectives in Clinical Research. 2017;8(2):58-62.
- Moores Y. Patient Safety Narratives – Clinical Trials: Medical Writing & Patient Safety Narratives, 2015. Available from: http://www.drug-dev.com/Main/Back-Issues/PATIENT-SAFETY-NARRATIVES-Clinical-Trials-Medical-921.aspx.