Gathered or reported during clinical trials:
- Adverse reactions (Solicited)
- Unsolicited adverse events (Non-serious)
- Serious Adverse Events (SAEs)
Solicited vs Unsolicited Reports
Reported after vaccine is approved by FDA:
- Post-Marketing Experience
ADVERSE REACTIONS (Solicited)
Participants in clinical trials are typically monitored for 3 - 7 days following an experimental vaccine (or control), for injection-site and systemic reactions.
In general, vaccines may be associated with the following injection-site reactions:
- Pain, tenderness, soreness, erythema/redness, ecchymosis (bruising), pruritus (severe itching of the skin), induration or nodule formation, swelling, warmth, increase in arm circumference.
And the following systemic reactions:
- Irritability/fussiness, crying, persistent crying, abnormal crying, inconsolable crying, unusual high-pitched crying, prolonged crying (>4 hr), restlessness, malaise, decreased activity, lethargy, somnolence, drowsiness, fatigue, asthenia, change in eating habits, decreased appetite or loss of appetite, anorexia, arthralgia, myalgia, nausea, vomiting, diarrhea, fever, dizziness, headache, pain, rash, otitis media (ear infection), pharyngitis, nasopharyngitis, bronchospasm, lymphadenopathy, allergic reactions, upper respiratory tract infection.**
**Infants and toddlers may be unable to communicate their symptoms to a parent. Therefore, systemic adverse events for young children may be reported by parents as "irritability", "fussiness", and "abnormal crying" as opposed to "headache", for example.
Source: Vaccine package inserts.
"People often dismiss all these reactions as 'minor', but they aren’t necessarily. They can be severe enough to interfere with daily life, and some can become serious – 'serious', in adverse-event-speak, is worse than 'severe'.
The most common grading is probably the one from the US FDA, and these terms and grades are widely used (even if they might be defined somewhat differently):
Mild (or grade 1): This equates to what pretty well everyone would agree is 'minor'. It’s a symptom or discomfort that doesn’t interfere with your usual activities, like feeling feverish, or some soreness where you were injected.
Moderate (or grade 2): This is more uncomfortable, but still generally manageable – you might use a mild pain reliever, for example, but still get on with your day. A mild fever ranks here, or a few bouts of nausea.
Severe (or grade 3): This can be so uncomfortable, it would be a battle to continue your day as normal – people generally take time off work if they can. You might take narcotic-level pain relief, or vomiting could get bad enough for you to need an IV – but nothing so bad that you would need to go to hospital. A fever of 39º to 40ºC ranks here (102.1º – 104º F).
Grade 4 is potentially life-threatening: This is an emergency room visit, or hospitalization. A fever over 40ºC [104º F] ranks here."
Source: A Reader’s Guide to Safety & Adverse Event Data From Vaccine Trials
UNSOLICITED ADVERSE EVENTS (Non-serious)
An unsolicited adverse event is any undesirable non-serious experience associated with the use of a vaccine, which is reported spontaneously by a clinical trial participant, as opposed to adverse events participants are specifically asked to document and report. There is typically a time limit on these kinds of reports, for example, one week to one month post administration.
See also: Solicited vs Unsolicited Reports
SERIOUS ADVERSE EVENTS (SAEs)
Adverse events are considered serious when an individual experiences any of the following after administration of a vaccine:
- Death
- Life-threatening event
- Disability or permanent damage
- Hospitalization or other required intervention to prevent permanent damage
Or if "the event may jeopardize the patient and may require medical or surgical intervention (treatment) to prevent one of the other outcomes. Examples include allergic brochospasm (a serious problem with breathing) requiring treatment in an emergency room, serious blood dyscrasias (blood disorders) or seizures/convulsions that do not result in hospitalization."
SAEs are typically collected for 30 days, but sometimes up to 6 months post-vaccination.
Source: What is a Serious Adverse Event?
SOLICITED VS UNSOLICITED REPORTS:
"The collection of AE [Adverse Event] data... is generally either intentionally solicited (meaning that the data are part of the uniform collection of information...) or unsolicited (meaning that the AE information is volunteered [spontaneously] or noted in an unsolicited manner and not as a required data element through a case report form)."
Source: Registries for Evaluating Patient Outcomes, 3rd edition.
"Reporting rates were greater when events were solicited than when the spontaneous reporting approach was used."
"Solicited adverse events are a list of events/symptoms that [clinical trial] participants are specifically asked to record. If that’s not done in a consistent, structured way, the rate of adverse events is likely to be under-estimated. The less thoroughly researchers look, the fewer they’ll find – and the rate of adverse events they report could be artificially low... People ideally keep a diary for the first week, filling in details according to clear instructions about what to look for and record."
"The solicited symptoms can also occur after the diary-keeping period – as well as unexpected adverse events that aren’t on the solicited list, or any safety issues that people are asked to watch out for and notify. Those are grouped into unsolicited adverse events (also called spontaneously reported events) – that may be time-limited, for example, to the month after vaccination."
Source: A Reader’s Guide to Safety & Adverse Event Data From Vaccine Trials
Post-Marketing Experience:
"The testing that helps to establish the safety of [drugs and vaccines] is typically conducted on small groups [in clinical trials] before FDA approves the products for sale. Some problems can remain unknown, only to be discovered when a product is used by a large number of people [after the drug or vaccine is licensed]."
The FDA requires drug manufacturers to report adverse events they receive after their vaccines are approved and licensed for use. Typically, post-marketing adverse events are grouped according to the system affected (e.g. neurological, skin, respiratory).
"Monitoring product safety has been traditionally done by passive surveillance (voluntary reports) or the collection of spontaneously reported adverse events from healthcare providers and consumers following the administration of a medicinal product."
Source: Postmarketing Adverse Event Reporting Compliance Program, Monitoring Product Safety in the Postmarketing Environment, Code of Federal Regulations, Best Practices in Drug and Biological Product Postmarket Safety Surveillance for FDA Staff
