21. Narrative writing

Narrative writing is an important part of Pharmacovigilance and in patient safety as well. 

A narrative is a brief summary of specific events experienced by patients, during the course of a clinical trial/treatment. Narrative writing involves multiple activities such as generation of patient profiles, review of data sources, and identification of events for which narratives are required.

Purpose:

To provide a concise summary of identified/specific adverse events (AEs) occurring in a patient to conclude causal relationship between the drug and event.

Objective:

The objective of the narrative is to summarize all relevant clinical and related information, including patient characteristics, therapy details, prior medical history, clinical course of the event(s), laboratory evidence and any other information that supports or refuses a diagnosis for an ADR. The information should be presented in a logical time sequence. 

Regulatory Perspectives:

The ICH guideline (E2B) on data elements and specifications for electronic reporting of individual ADR cases states that company narratives are required for all serious reactions. 

Narratives are expected to be submitted for all cases reported expeditiously to any regulatory authority, but are useful and should be made available when needed for other types of reports and purposes. 

As per International Conference on Harmonisation (ICH) E3, a patient narrative should describe :

• The nature, intensity and outcome of the event
• Clinical course leading to the event
• Timing of study drug administration
• Relevant laboratory measures
• Counter measures
• Action taken with the study drug in relation to the event
• Post mortem findings (if applicable)
• Investigator’s and sponsor’s opinion on causality
• Additionally, patient identifier, age, gender, clinical condition, disease being treated, relevant medical history, concomitant and prior medications should be included.
• All this information is extracted from the source files (e.g. Council for International Organisations of Medical Sciences [CIOMS] form.

Flow of Narrative:

• Report type and reporter information
• Patient demographics
• Patient medical history and concomitant medication information
• Suspect product information timing and conditions surrounding the onset of the reaction(s) 
• Clinical course of the events, with an indication of timing of event corresponding to drug administration
• Nature, intensity/severity, and outcome of the event
• Relevant laboratory findings
• Treatment administered for the event
• Action taken with respect to the drug
• Dechallenge and rechallenge information, if applicable 
• Postmortem findings (if applicable)
• Outcome of event.
• Clinical relation of event with suspect drug
• zthe original reporter’s clinical assessment 
• The narrative preparer’s (sponsor’s) medical evaluation and comment.

Standard narrative template: 

This initial [serious/non-serious] [spontaneous/literature] report, which originated from [country] was received by [Marketing Partner’s Name] on [date DD MMM YYYY].

Information has been received from a [reporter] concerning a [age] year old [male/female]. 

The patient’s medical history of [history, including the duration of concurrent illness, age at diagnosis, date of diagnosis or onset date not reported].

Concomitant therapy included [generic name of relevant concomitant drugs with/without indication if appropriate. Or provide a general statement such as subject was also receiving multiple concomitant medications, with or without indications (for example, he/she was taking multiple medications for pain, hypertension and depression). Note that concomitant medications include those medications taken within a reasonable time frame (30 days) prior to the onset of an adverse event and medications taken by the subject at the time of the reported adverse event.]

The patient commenced treatment with [SUSPECT PRODUCT], dose, frequency, on date for indication.

On [date MM DDD YYYY], the subject presented with event [detailed event description including signs, symptoms and details about hospitalisation including prolongation of existing hospitalisation]. which required hospitalisation.

The patient’s laboratory results on [DD MMM YYYY] were as follows: [list relevant physical findings, exams and laboratory results].

Corrective treatment for the event included [describe medications, procedures, tests, investigations etc.]. 

Action taken with suspect drug included (discontinued/temporarily stopped/dose decreased/dose increased/no change/unknown).

State outcome of event following treatment (recovered, unresolved,recovered with sequelae (describe sequelae), or death). Note if event resolved spontaneously].

Fatal patient outcome details: include date and cause of death, the timing of death in relation to the event onset and suspect drug therapy duration. 

The reporter assessed the events as being serious/non serious [if serious, state reported seriousness criteria] physicians assessment of intensity of event (e.g. mild, moderate, severe) and relatedness of event to products include reported rationale for causality assessment.]

[Company’s medical assessment and comment: Include the facts that the company believe are relevant to the case].

For clinical trial cases narrative should start with:

• Protocol/Study ID: XXXX
• Study Title/Study description: Post-Marketing Surveillance of DRUG mg (ingredient) to Evaluate Its Safety and Efficacy.
• Screening number/ Randomization No: XXX-XX-XXX
• Patient ID/Subject ID: XXXX-XXXX

Follow-up Information:

When relevant new information becomes available, a follow-up narrative may need to be written depending on the amount and importance of the information. There are three options for incorporating the new information: 

1. Prepare an entirely new narrative
2. Add new information in a separate additional paragraph
3. Highlight in some way (e.g., bold or underline) the newly added follow-up material interspersed within the original narrative. 

The Working Group’s preference is as follows: 

Every effort should be made to blend the follow-up details into the original narrative, as usual in chronological order, to avoid repetition and contradictions.

Example:

Follow-up information received on [DD-MMM-YYYY] from [source] (or Source Data Verification received on…., or Data Correction Made on…., etc): (Briefly describe additions, corrections)

Important Points to Remember

• Narrative should be precise and concise.
• Double check spell mistakes, spaces, format, flow of narrative in
• agreed chronology
• Do not repeat the information.
• Avoid using short forms in narrative.
• Do not change the meaning of narrative by adding own supportive words/conclusion. The verbatim should be written as it is presented in source document. Whenever possible, the reporter’s exact (verbatim) words for the suspected adverse reaction(s) should be used. Use quotation marks to present strange verbatim terms.
• Use paragraphs to present narrative in style and logical format.
• Narratives should be written in the third person using the past tense. 
• In general, abbreviations and acronyms should not be used. If used abbreviations should be expanded once. Relevant laboratory results are an exception but it is important that values be quoted in SI units, with an option to include additional units as well. 
• Time to onset of an event from the start of treatment should generally be given in the most appropriate time units (e.g., days or hours or weeks), but actual dates can also be included if considered helpful to the reader. 
• If detailed supplementary records are important to a case (e.g., an autopsy report), their availability should be mentioned in the narrative. 
• Information may be provided by more than one person (e.g., original reporter plus supplementary information from a specialist); all source(s) of additional material should be specified. 
• When there is conflicting information provided from different sources, this should be mentioned and the sources identified. 
• If it is suspected that an adverse reaction resulted from misprescribing (e.g., wrong drug or wrong dose) or other medication error, judgmental comments should not be included in the narrative due to the legal implications. However, it is important to state the facts (e.g., ‘‘four times the normal dose had been administered,’’ ‘‘prescription was misread and a contraindicated drug for this patient was given,’’ etc.).

Example of a Standard Narrative Template:

Case reference number 12345678 is a spontaneous case report sent by a hospital pharmacist.

This report refers to an 84-year-old Caucasian male patient who experienced myocardial infarction while on qweasytrol. 

The patient’s past medical history included gastric ulcer, asthma, and hypertension. At the time of the event the patient had Lyme Disease and severe headache. The patient previously took steroids (1990), cimetidine (1996), and tetracycline (09-Sep-1999). The patient had a history of allergy to penicillin and gin. 

The patient started taking qweasytrol from 01-Jan-2000 at 1:00 PM, at an unspecified dose for vomiting. Some 12 hours later, and 10 minutes following the latest dose, the patient developed rash, dyspnea and queasiness. Over the period of the next two days, the patient also developed chest pain and later unconsciousness. 

Relevant laboratory test results include elevated CK-MB and relevant physical signs were hypertension, fourth heart sound and bradycardia. The patient was hospitalized. Qweasytrol was discontinued on 08-Jan-2000. The eventual diagnosis made on the 10-Jan-2000 was myocardial infarction. The patient was treated for the event with a beta-blocker.

The patient died on 12-Jan-2000 from myocardial infarction; no autopsy was done. Death occurred 12 days after the treatment with qweasytrol began and 4 days after it was discontinued. 

The cardiologist cited in the pharmacist’s report considered the myocardial infarction possibly related to qweasytrol. In his opinion, other possible etiological factors include hypertension and the patient’s age. 

The company believes the following facts were also relevant in this case: as a highly selective epsilon G2 receptor antagonist, there was no known plausible mechanism by which the drug would cause a myocardial infarction. 

Examples of Acceptable Company Clinical Evaluation Comments in narrative: 

• The available pre-clinical data did not suggest a possibility that the subject drug would induce.
• As only limited information has been obtained so far, it is difficult to assess a cause and effect relationship.
• The temporal relationship (6 weeks) between the onset of the event and administration of drug x, which has a one-hour half-life, makes any causal relationship unlikely.
• The reported event is a well-known class effect (specify drug class here). However, this is the first reported case with.
• There is no plausible mechanism to implicate the subject drug.
• It is of interest to note that the patient was subsequently rechallenged at the same dose without recurrence of the adverse effect.
• The skin test with drug x, performed immediately after the event, was negative.
• The co-medications y and z should also be considered causative; the reported event is labeled for both drugs.
• The medication was not administered according to the dosage recommendation for the drug.
• The investigator on follow-up has changed his assessment from ‘‘probably’’ to ‘‘probably not’’ for the following reasons —.
• The benefit-risk relationship of drug x is not affected by this report.

Examples of Unacceptable Company Clinical Evaluation Comments in narrative:

• The investigator changed his assessment from ‘‘probably’’ to ‘‘probably not’’ on follow-up. [Without a reason, such a statement should not be made.]
• The company view is that the event is not due to the subject drug. [Inadequate without a reason given].
• No comment. [Under some regulatory requirements, such as in Germany, Austria and Japan, some company opinion is expected]