- Mild: An event that is easily tolerated by the subject, causing minimal discomfort and not interfering with everyday activities.
- Moderate: An event that is sufficiently discomforting to interfere with normal everyday activities.
- Severe: An event that prevents normal everyday activities.
- Mild: awareness of sign or symptom, but easily tolerated
- Moderate: discomfort sufficient to cause interference with normal activities
- Severe: incapacitating, with inability to perform normal activities
- Grade 1 Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; no intervention indicated
- Grade 2 Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental ADL
- Grade 3 Severe or medically significant but not immediately lifethreatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care ADL
- Grade 4 Life-threatening consequences; urgent intervention indicated.
- Grade 5 Death related to AE.
- Mild (grade 1)
- Moderate (Grade 2)
- Severe (Grade 3)
- Potentially Life Threatening (Grade 4)
Record the date the adverse event started. The date should be recorded to the level of granularity known (e.g., year, year and month, complete date) and in the specified format. If a previously recorded AE worsens, a new record should be created with a new start date. There should be no AE start date prior to the date of the informed consent. Any AE that started prior to the informed consent date belongs instead in the medical history. If an item recorded on the medical history worsens during the study, the date of the worsening is entered as an AE with the start date as the date the condition worsened.
Record the date the adverse event stopped or worsened. The date should be recorded to the level of granularity known (e.g., year, year and month, complete date) and in the specified format. If an AE worsens, record an end date and create a new AE record with a new start date and severity.
If the AE increases in severity per the DAIDS Grading Table, a new AE Log CRF should be completed to document this change in severity.
the eCRF Completion Guidelines for adverse events: Enter a new event if action taken, seriousness, causality, severity (intensity), etc. changes over the course of an adverse event. A timestamp for any changes in events can be seen in the data via event start/stop dates.
The second question and answer explicitly stated:
[Redacted] is the sponsor of the study. We have been advised by our data coordinating center to record an AE that changes in severity as two AEs instead of 1 AE - starting a new AE each time the severity changes. This convention is different than that of our previous coordinating center and has caused us great concern.
We have concerns that an approach to adverse event reporting as you described below (i.e., a change in severity of an adverse event necessitates a new adverse event report) may inaccurately reflect the adverse event profile for the product. Therefore, we strongly recommend that you contact the FDA review division regulating this clinical investigation for additional input on the most scientifically and medically sound approach to the adverse event reporting specifically for this trial.
We constantly run into the issue how to record the adverse event in the database in the situation there is a severity change or seriousness change during the course of the adverse event.
A subject in clinical trial reported a mild headache. Two days later, the headache became moderate in severity. Then headache became mild in severity again.
In this case, shall we record this as one headache event with moderate severity or record as three headache events (a new event is record whenever there is a severity change)?
Similarly, a subject in clinical trial reported a non-serious adverse event. Several days later, subject needs to be hospitalized for this adverse event – now the event meets the seriousness criteria.
In a situation of a non-serious adverse event becoming serious, shall we record it as a single AE with seriousness or shall we record as two separate AEs (one non-serious AE and one serious AE)?
Given your brief description that the subject's headache is ongoing, it would seem that this adverse event would best be reported as a single event with variable severity. However, the clinical judgment of the principal investigator (or, if the principal investigator is not a clinician, then a physician consultant to the research) would be helpful in clarifying the symptoms and hence the reporting of the adverse event(s). There are several cogent clinical scenarios the understanding of which would require more information than you have supplied. For example, the subject's symptomatology could represent an unremitting headache of several days duration or episodic headaches of finite duration with varying intensities or a symptom of another event altogether such as a change in blood pressure, etc. The same would apply for the hospitalization event.
To best sort out the adverse event(s) itself and therefore the appropriate reporting, I would recommend a clinical assessment of the headache. In addition, the protocol may have detailed how adverse events should be reported. As well, the sponsor (I'm not sure of [Redacted] status in this trial, i.e., is/is not the sponsor) may have specifications for adverse event reporting that could guide you. If you still feel uncertain, I would strongly recommend contacting the FDA review division regulating this trial.
Lastly, if it becomes apparent that this same "fact pattern" recurs, it may be advisable for the sponsor to clearly articulate standards for adverse event reporting such that there can be consistency in reporting of headaches.