Serious Adverse Event Narrative Writing

Serious adverse event narratives: background and definitions

Before defining case narrative, it is important to explain the concept of Individual Case Safety Report (ICSR); this well-known pharmacovigilance report captures information about adverse events and product problems that are reported to public health, patient safety/quality improvement organizations or regulatory agencies. The ICSR message supports reporting from a variety of sources such as consumers, hospitals, contract research organizations, clinicians or pharmaceutical product and medical device manufacturers.

Within the structure of an ICSR, the narrative is a text that summarizes all relevant clinical and related information, including patient characteristics, therapy details, medical history, clinical course of the event (s), diagnosis and ADR(s) including the outcome, laboratory evidence (including normal ranges), and any other information that supports or refutes and ADR. Narratives should serve as a comprehensive, stand-alone "medical history". The information should be presented in a logical time sequence; ideally this should be presented in the chronology of the patient's experience, rather than in the chronology in which the information was received. In follow-up reports, new information should be clearly identified.

In the context of clinical trials, narratives are present under the structure of Clinical Study Reports (CSR), that, according to the International Conference on Harmonisation (ICH) tripartite guideline on the Structure and Content of CSRs E3 (Section 12.3.2), a CSR should contain brief narratives describing each death, each other serious adverse event, and other significant adverse events that are judged to be of special interest because of clinical importance.

Pharmacovigilance in clinical trials is the monitoring of the Serious Adverse Events (SAEs) that occur to the participating patients in a trial. Patient safety in clinical trials needs continuous monitoring. All adverse events are documented whether they are considered related or not to the study drug (although only the SAEs / SAEs narratives should be transmitted to regulators). Safety information from clinical studies is used to establish a drug’s safety profile in humans and is a key component that drug regulatory authorities consider in the decision-making as to whether to grant or deny market authorization (market approval) for a drug.

Considering the narratives written for the post-marketing experiences, they have a different nature than those written for subjects in controlled studies, because the only information the Sponsor has about the patient has come from the reporting physician and thus they are entirely written from the safety reports obtained from the Safety Officer. Any numbers on serious adverse events calculated post-marketing are undercounted, reasons for undercounting include patients not telling healthcare professionals which drugs they are taking and, patients not reporting serious adverse events to healthcare professionals. With chemotherapy drugs, this is less likely to be so.

Other considerations for narratives include that abbreviations and acronyms should be laboratory parameters and units. Key information from supplementary records should be included in the report, and their availability should be mentioned in the narrative and supplied on request. Any relevant autopsy or post-mortem findings should also be summarized in the narrative and related documents should be provided according to local regulation and if allowed by local data privacy laws.

SAE narrative example

Subject xxxxxx had cancer [disease needs to be specified], which was diagnosed in Jun 1998. The subject previously received treatment with vincristine, dexamethasone, melphalan, and prednisone. The subject’s pertinent medical history included cardiac arrhythmia, myocardial infarction, deep vein thrombosis, hypercholesterolemia, acute renal failure, and hypertension. On 30 Apr 2001 (Cycle 1, Day 33; 15 days after completing Cycle 1 therapy), the subject was admitted to the hospital for treatment of acute renal insufficiency. The subject complained of a cough one week before admission and was treated with a dose of pentamidine for Pneumocystis carinii pneumonia and reported decreased urine output since that time. A baseline 24-hour urine collection on 14 Mar 2001 revealed 75% lambda light chain Bence-Jones protein, a total protein of 2700 mg/24 hours, and a urine M-protein of 2025 mg/24 hours; the investigator considered that the increase in monoclonal proteins was related to a dental abscess. On 27 Mar 2001, his baseline creatinine was 1.9 mg/dL. On admission, the subject’s creatinine was 4.9 mg/dL, BUN was 72 mg/dL, and potassium was 5.5 mEq/L. His cloudy yellow urine had 30 mg/dL protein and bacteria (cultured as coagulase-negative Staphylococcus). An abdominal ultrasound showed a slight increase in echogenicity and irregular renal cortices that were consistent with renal disease. A physical examination revealed right lung base crackles and a temperature of 38.1ºC. On the following day, 01 May 2001, the subject’s creatinine was 4.9 mg/dL, BUN was 62 mg/dL, and potassium was 4.7 mEq/L. The subject was discharged on 4 May 2001 (Day 38) with a creatinine of 4.6 mg/dL and a BUN of 65 mg/dL, and the event was considered resolved with sequelae. The subject was given levofloxacin at discharge. A 24-hour urine collection on 24 May 2001 revealed 5.24 g/24 hours Bence-Jones protein, total protein of 5 mg/24 hours, urine M-protein of 4 mg/24 hours, and a creatinine of 4.8 g/24 hours. The subject was discontinued from the study because of progressive multiple myeloma on 29 May 2001. Concomitant medications included albuterol, atenolol, atorvastatin, dalteparin, enalapril, enoxaparin, erythromycin, loratadine, omeprazole, pamidronate, pentamidine, and simvastatin. In the opinion of the investigator, the Grade 3 acute renal insufficiency was unrelated to dexamethasone.

References

1. HL7 Version 3 Standard: Pharmacovigilance - Individual Case Safety Report, Part 2: Human Pharmaceutical Reporting Requirements for ICSR, R2. Health Level Seven website. http://www.hl7.org/implement/standards/product_brief.cfm?product_id=267. Accessed on 08/03/16.

2. ICH E2D – Post Approval Safety Data Management. EMEA website. eudravigilance.ema.europa.eu/human/docs/ICH%20E2D.pdf. Accessed on 08/03/16.

3. Patient Safety Narratives - Clinical Trials: Medical Writing & Patient Safety Narratives. Drug Development & Delivery website. http://www.drug-dev.com/Main/Back-Issues/PATIENT-SAFETY-NARRATIVES-Clinical-Trials-Medical-921.aspx. Accessed on 08/03/16.

4. Clinical Pharmacovigilance. PV Net. http://pvnet.sarjen.com/pharmacovigilance/clinical-pharmacovigilance/. Accessed on 08/03/16.

5. Dodgson S. Writing narrative reports. MJota website. http://www.mjota.org/images/Narrative_Preparation_11-14-2003_sjd.doc. Accessed on 07/22/16.

6. Authoral work: Ferreira F.  (2016). Describe serious adverse event narrative writing. Write a sample serious adverse event narrative; Post Graduate Diploma in Pharmacovigilance & Medical Writing, James Lind Institute.

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