|Year : 2018 | Volume
| Issue : 2 | Page : 103-106
Analysis of serious adverse event: Writing a narrative
BHSc (Home Science), Post Graduate Dietetics, Registered Dietician, Mumbai, India
|Date of Web Publication||24-Apr-2018|
Ms. Indu Nambiar
P. G. Diploma in Dietetics, Registered Dietitian, 1002, Hallmark Business Plaza, Near Guru Nanak Hospital, Near Guru Nanak Hospital Road, Bandra (East), Mumbai - 400 051, Maharashtra
Source of Support: None, Conflict of Interest: None
| Abstract|| |
One of the reasons that a research molecule undergoes through different phases of clinical trials is to establish the safety and efficacy of the drug. To establish the safety profile of any drug, the most important aspect is to evaluate every adverse event (AE) that a clinical trial individual experiences. This detail is provided by any investigator or sponsor through the narratives that is prepared post the analysis of a serious AE. The purpose of this article is to emphasize the importance of these narratives.
Keywords: Communications, Food and Drug Administration, International Council for Harmonisation, narratives, serious adverse event
|How to cite this article:|
Nambiar I. Analysis of serious adverse event: Writing a narrative. Perspect Clin Res 2018;9:103-6
| Introduction|| |
With the entire focus of Indian regulations on the safety of human clinical trials participants, serious adverse event (SAE) reporting has become an important obligation, especially for the sites. Medical management and compensation quantum decisions are dependent on the information provided through the SAE forms (in the Schedule Y Appendix XI format). The most relevant section of a SAE form is the narrative, which details about the SAE experience.
What is an serious adverse event?
A SAE is any untoward medical occurrence that at any dose:
- Results in death
- Is life threatening
- An event is considered life threatening if it is suspected that the individual was at substantial risk of dying at the time of the AE
- Requires inpatient hospitalization or prolongation of existing hospitalization –
- An admission and/or overnight stay or an event that prolongs hospitalization
- Results in persistent or significant disability/incapacity
- Includes an AE which resulted in a substantial disruption of a person's ability to conduct normal life functions, i.e., a significant, persistent or permanent change, impairment, damage or disruption in the individual's body function/structure, physical activities, and/or quality of life
- Is a congenital anomaly/birth defect, or
- Is medically significant
- Other important medical events may be considered serious when, based on appropriate medical judgment, they might jeopardize the individual and/or may require medical or surgical intervention to prevent the event from meeting a serious criterion.
Why is the focus on narratives?
Every stakeholder – health-care professionals, patients, regulators, Ethics Committees, policy makers, and health ministry must have access to high quality, up-to-date information, tailored to their abilities and preferences, about medicines and their use, and about health care in general, and about ways to promote health and prevent any adverse effect. Most important aspect is that doctors, nurses, pharmacists, and patients need to know that reporting patients' experience of medicines, and especially adverse effects, will help improve therapy and protect future patients from harm.
Aspects that any safety communication aims to:
- Prevent patients from experiencing adverse reactions
- Provide timely, evidence-based information on the safe and effective use of medicines and appropriate clinical management of patient treatment
- Facilitate changes to health-care practices (including self-medication practices) where necessary
- Change attitudes, decisions, and behaviors in relation to the use of medicines
- Support risk-minimization behavior; and
- Facilitate informed decisions on the rational use of medicines.
Marketing authorization holders are responsible for collecting, reviewing, and analyzing spontaneous case reports of suspected adverse reactions to medicines by patients and health-care professionals, in scientific literature and elsewhere during postmarketing surveillance of medicines.
When it comes to clinical trial, this communication becomes more important since the “Investigational product” is under experimentation. Hence, narratives become an integral part of every SAE description that is experienced by a trial individual.
What is an serious adverse event narrative?
As per International Conference on Harmonisation (ICH), SAE narrative is a detailed, stand-alone document, which presents a full and clinically relevant, sequential account of the progression of an event or events. It summarizes all relevant clinical and related information including patient characteristics, therapy details, medical history, clinical course of the event(s), diagnosis, and AEs including the outcome, laboratory evidence (including normal ranges), and any other information that supports or alleges an AE.
SAE narrative writing requires a combination of medical and technical writing skills.
Section 12.3.2 of ICH E3 states that “There should be brief narratives describing each death, each other SAE, and those of the other significant AEs that are judged to be of special interest because of clinical importance.”
As per ICH E3 guidelines, a patient safety narrative should describe the following:
- The nature, intensity, and outcome of the event
- The clinical course leading to the event
- An indication of timing relevant to study drug administration
- Relevant laboratory measures
- Action taken with the study drug (and timing) in relation to the event
- Treatment or intervention
- Postmortem findings (if applicable)
- Investigator's and sponsor's (if appropriate) opinion on causality.
Main features of narrative writing:
- Should be thorough and balanced
- In-depth medical record review
- Summary and highlight of relevant clinical information
- Presentation of concise and comprehensive narrative report in chronological sequence.
Food and Drug Administration (FDA) describes narrative as a small document (100–500 words) that is required by the FDA to briefly describe the events in the life of an individual. These are required when the individual enrolled in a study or within 30 days of taking study medication discontinued the study because of an AE, had one or more SAE, or died.
Narratives are written from two sources:
- From safety reports maintained by the safety officer, who is a physician working on-site
- From the clinical database maintained by the statistics department.
How to write an serious adverse event narrative?
For writing the SAE narrative, a step-wise approach is helpful. The steps are as follows:
- Patient details
- Mention the birth year, gender, and race of the clinical trial individual experiencing the event in compliance with local regulatory requirements
- Record the individual's height in cm and weight in kg at the onset of the experienced event.
- Study details
- Document the indication for which the study medication is being administered. Include the details of the protocol and mention about the blind (if any). The phase of the trial to which the individual belongs may also be included to provide clarity on the stage when the event was experienced.
- Patient history (medical history, concomitant diseases, family history, and concomitant drugs)
- Mention every detail about concomitant conditions and their onset dates. Also include relevant past conditions
- The treatment medication received for the event, and the previous medication details need to be provided. This includes background and rescue medications.
- Details of the study drug
- Mention the study medication(s) administered which includes investigational medicinal product/s specified in the protocol
- Enter start date and end date (as applicable) for the study medication mentioning the dosage
- Mention the first date of administration and last date of administration before the event for trials in which the study medication is received by the individual intermittently (e.g., monthly). More details can be provided in the description section.
- Event description and treatment details
- Events must be reported as per guidance provided in the protocol
- Diagnosis is preferred over signs and symptoms. In scenarios where diagnosis is not yet arrived, the signs and symptoms can be used as the event term. This needs to be replaced as soon as the diagnosis is confirmed
- Every minute detail with regard to event experienced should be included in this section. No information should be treated as unimportant
- Detail the treatment provided to treat the event.
- Laboratory tests information
- Mention every reading of the tests performed along with the normal range of the parameters.
- Action taken with the study drug
- Include the decision taken for the study drug when the event was experienced.
- Outcome of event/s
- Mention the status of the individual for each event experienced. The outcomes should be chosen from the below list:
- Recovered: Determines that the individual has recovered completely and has returned to the previous health status with no sequelae
- Not yet recovered: The individual continues in the same state which he/she was when the event was experienced
- Recovered with sequelae: Determines that some permanent impairment to the health status has resulted after the event was resolved. The individual does not achieve previous health status
- Unknown: At this point of time, there is no information on the status of the individual after the event was experienced. Also used when the event is termed as “death-unknown cause” as “death” will always be an outcome and never an event
- Fatal: The individual expired due to the event. Mention the date of death and indicate the exact cause of death. If an autopsy was performed, the result of the same should be transcribed in the narration.
- Causality assessment by investigator
- Causality assessment should always be based on evidences. In case a “reasonable causal relationship” is mentioned that the investigator should have reasons and arguments to prove the same.
Writing a narrating of an SAE is a crucial activity, which requires knowledge of drug, disease, causality assessment, and skill of structured writing as per regulatory requirements.
We would like to thank Ms. Divya Vijayan, Medical writer at Tata Consultancy Service, Thane.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
International Conference on Harmonisation (ICH) Tripartite Guideline on the Structure and Content of Clinical Study Reports (CSRs) E3 (Section 12.3.2).
Dodgson SJ. Writing Narrative Reports Medical Writer; 14 November, 2003.