Clinical Data Interchange Standards Consortium (CDISC)
August 22, 2024
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Patient safety narratives (PSNs) are an important component of the clinical study reports (CSRs). These narratives contain clear and concise descriptions of adverse events (AEs), serious adverse events (SAEs), or an event of specific interest encountered by participants in a clinical trial. As per the Food and Drug Administration’s (FDA) guidance for the format and content of the clinical data section of an application, ‘for all deaths and all potentially serious adverse experiences, there should be a brief narrative describing each event and assessing the likelihood that the drug was responsible.’1
A patient narrative is written for each patient who experiences at least one of the qualifying events as per the criteria defined or agreed upon with the regulatory authority. The PSNs should be written for all phases of a clinical trial (Phase I-IV) for all therapeutic areas and submitted to the regulatory authorities under the US FDA along with the CSR.
The primary purpose of the PSN is to provide a summary of each AE, SAE, discontinuation from the study, and death and to determine whether an interventional drug is associated with an event of specific interest that occurs in patients. Besides, according to International Conference on Harmonization (ICH) E3 guideline, a PSN serves a vital role in CSR, and the main purpose is to describe the following:2
A PSN provides a detailed and therapeutically relevant sequential outline of an event that occurred during or immediately after a clinical study, which plays a crucial role during regulatory submission. There are several reasons why a PSN is important, a few of which are outlined below:3
Writing PSNs requires a careful and systematic approach to ensure accurate and comprehensive reporting of AEs, SAEs, deaths, and other events of special interest. Usually, there are two ways of generating PSNs: manually or automated.
PSNs are normally produced manually by medical writers (if there are <150 PSNs); however if the narratives in a clinical study are more than that, it might be exhausting and challenging. But in the current modern era of the healthcare industry, automation in narrative writing is the latest efficient and convenient trend being utilized by the pharmaceutical industries to generate large qualitative batches of PSNs within a short time. These tools, which help in the generation of automated PSNs, extract and compile relevant data for all applicable patients in a specified template. Such tools are extremely useful for clinical studies with high numbers of narratives (often >150). The following points are key features of such an automated narrative:3
In the following subsections, we will briefly discuss various tips and tricks for writing PSNs in order to deliver high-quality output.
ICH E3 guideline2: ‘There should be brief narratives describing each death, each other serious adverse event, and those of the other significant adverse events that are judged to be of special interest because of clinical importance. These narratives can be placed either in the text of the report or in section 14.3.3, depending on their number.’
21 CFR 312.32(c)(1)(v)4: ‘The sponsor must submit each IND safety report in a narrative format or on FDA Form 3500A or in an electronic format that FDA can process, review, and archive… Reports of overall findings or pooled analyses from published and unpublished in vitro, animal, epidemiological, or clinical studies must be submitted in a narrative format.’
US FDA for safety reporting requirements 5: As per the US FDA’s guidance for industry for safety reporting requirements for INDs and BA/BE studies, the IND safety reports for individual cases, aggregate reports, and all other reports should be submitted in a narrative format (as explained in the above point of CFR).
Using standardized medical terminologies in clinical research has improved patient data documentation and interpretation with regulatory bodies. It makes no difference where the study was done or what language the data was collected in; adopting standardized terminologies allows for uniform and accurate reporting and interpretation of the clinical data. In PSNs, following standardized terminologies can be used:
A complete PSN has several essential components that should be carefully included while writing. As per ICH E3 guideline, these factors include ‘patient identifier; age and sex of the patient, general clinical condition of patient (if appropriate); disease being treated with duration of illness; relevant concomitant/ previous illnesses with details of occurrence/duration; relevant concomitant/previous medication with details of dosage; test drug/investigational product administered, drug dose, if this varied among patients, and length of time administered.’2
The data which is included in the PSNs is extracted from the Council for International Organizations of Medical Sciences (CIOMS) forms, MedWatch Forms, Study Data Tabulation Model (SDTM) or Analysis Dataset Model (ADaM) datasets, Tables, Listings, and Figures (TLFs) of the study, Case report Forms (CRFs), and Adverse Event of Special Interest (AESI) forms.
The patient information in the narratives should be chronologically outlined as it occurred throughout the clinical study. It means that the narrative should be written in a streamlined and consistent structure, which should be determined before writing the PSN.
A predetermined template, including all of the components of a PSN in chronological order, should be created, and the writers should write the PSNs based on that finalized template. The PSNs should be written in a consistent way. The chronological representation of the information also helps in making the review process easier and more efficient for the reviewer.
In addition, maintaining clarity and objectivity in PSNs is essential for ensuring that the information presented is accurate, unbiased, and easy to understand. It is crucial to provide only the relevant information related to the patient without any speculations or personal opinions to avoid biases.
While writing the PSN of a clinical study report, it is essential to provide supporting evidence for the reported safety data. Supporting evidence strengthens the credibility of the safety findings and helps regulatory authorities assess the reliability and validity of the results. This supporting information (such as patient baseline characteristics) can be provided or added in tables and figures. However, it is also necessary to refer to the source of that evidence, including the data sources (TLFs, CIOMS and AESI forms, and clinical databases, if appropriate).
The internal review and quality control of PSN is an important step to assure accuracy, consistency, and regulatory compliance before sharing the final PSNs with the study sponsors. The following points represent the steps and considerations for conducting a thorough review and quality control:
Moreover, a quality control checklist should be prepared, with each point listed individually with a checkbox on the left or right side. It will be helpful while performing a final review of the narratives, ensuring that every point has been reviewed.
The PSNs are important documentation in regulatory submissions through CSRs. This blog emphasizes how to adopt best practices to ensure that PSNs are of high quality and submitted on time to regulatory authorities. Furthermore, it is critical to follow regulatory standards while writing or automating the narratives using specified templates. In addition, review and quality control of the PSNs are crucial to ensuring accuracy and compliance at each step before submission.
Supporting Healthcare and Pharmaceutical Industries Across Internal, External, and Regulatory Communications. Delivering Top-Tier Support for Our Client’s Success.
Supporting Healthcare and Pharmaceutical Industries Across Internal, External, and Regulatory Communications. Delivering Top-Tier Support for Our Client’s Success.