“Find out what the story is,” Kent Steinriede stressed throughout his session about the quality control (QC) review of safety narratives. Steinriede highlighted the elements of the safety narrative, source documents and tools used in QC review, and tips for best QC work.
What Are Safety Narratives?
A required part of the clinical study report (CSR) provided to drug or device regulators, safety narratives describe deaths, serious adverse events, and adverse events of special clinical interest (usually defined in advance by the sponsor or regulator). Steinriede defined safety narratives as stories that describe what happened. As the QC review person, he said, “you are protecting the story and making sure that the data that support the story are correct.”
The required elements of the safety narrative are outlined by the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) E3 guideline on the Structure and Content of CSRs, (Section 12.3.2).
Elements of the Safety Narrative
- Patient identification number, age, and sex
- Medical history
- Study drug, dose, and length of time administered
- Relevant concomitant and previous medication and dosage
- Description and intensity of adverse event
- Treatment and events leading up to the adverse event and timing relevant to study drug administration
- Relevant laboratory measurements
- Investigator and sponsor opinion on cause of adverse event
- Disease being treated and duration of illness
Documents Provided for QC Review
The QC review involves checking a variety of source documents, templates, and guides.
- Narrative template—provides a consistent structure for the narrative.
- Sample narrative—created by the medical writer and study team.
- Listings—the tables containing all individual patient data gathered.
- Patient profiles—predefined collection of patient-specific data.
- Council for International Organizations of Medical Sciences (CIOMS) or MedWatch forms—describe the adverse event.
- Correspondence from investigators—may add information to the story.
- CSR in progress—remember that the safety narrative is part of the CSR and the documents need to be consistent.
- Study protocol—read it! The protocol details what the patients were supposed to have experienced.
- Safety narrative plan—describes what sort of narratives will be created.
- Client style guide—if not provided, ask the client if they have one.
- QC checklist—list of what needs to be checked. Steinriede recommended developing your own QC checklist.
Safety narratives usually arrive for review in batches of 5 or 10. Steinriede recommended reading through all of them at once and figuring out what happened, how each patient was treated, and how each story ended. “This is not creative writing, but we are telling a story,” Steinriede said. The QC review person ensures that the story makes sense and always keeps the reader in mind; as Steinriede said, “good writing is a treat for everyone.”
Steinriede recommended looking for and creating consistency in the safety narratives before checking the data. Look at the style and presentation. Pay attention to the organization of the narrative (chronologic or thematic), paragraph length, and spacing after periods. Notice inconsistency in use of American or British English, International System of Units or conventional units, number of decimal places for reported values, inclusion of reference ranges and sources of ranges, style of dates (calendar dates or study days), and use of generic or trade names.
Use two computer monitors to compare the safety narrative and source documents, and highlight electronically or on paper the information you have already checked. Steinriede said he finds it easier to search documents in PDF format rather than Word format.
When working with the listings, the QC reviewer should ask if the database has been locked; if not, a final QC may be needed. The listings (quantitative information from the statisticians) and CIOMS (qualitative information from the investigators) forms should match. Use the listings as the primary source for patient identification, MedDRA (Medical Dictionary for Regulatory Activities) terms, start and stop dates of medications, and relatedness to study drug.
Tips for QC Work
Performing QC is repetitive, but it requires focus. Steinriede concluded the session with the following tips for performing QC:
- Work when you are most alert.
- Find a quiet workspace.
- Eliminate distractions.
- Find your groove and go with it.
- Communicate with team members.
- Stop and take a break when you start to lose your attention or make a mistake.