How side effects are graded

In research studies, side effects are graded from 1 to 4. Grade 1 is very mild and grade 4 is very serious.

How side effects are discovered

Most information about the risk of side effects comes from research studies. This is why it is important to report all side effects if you take part in a study.

Drug studies collect information about:

  • All potential side effects.
  • How often side effects occur.
  • How serious they are.

But studies use small numbers of people for relatively short periods. So sometimes rare side effects are only discovered after a drug is approved and has been widely used for many years.

In studies, each side effect is graded from 1 to 4. Grade 1 is mild and grade 4 is serious, life threatening or requiring hospitalisation.

Knowing about these grades can help understand information about each drug.

Side effect grades

GRADE 1 (Mild)
Transient (goes away after a short time) or mild discomfort; no limitation in activity; no medical intervention/therapy required.

GRADE 2 (Moderate)
Your daily activity is affected mild to moderately – some assistance might be needed; no or minimal medical intervention/therapy required.

GRADE 3 (Severe)
Your daily activity is markedly reduced – some assistance usually required; medical intervention/therapy required, hospitalisation or hospice care possible.

GRADE 4 (Potentially life threatening)
Extreme limitation to daily activity, significant assistance required; significant medical intervention/therapy, hospitalisation or hospice care very likely.

Side effects and grades table

An indication of grading (based on US NIH Division of AIDS) is shown below together with specific details for some of the most common side effects.

Side effect Grade 1 Grade 2 Grade 3 Grade 4
Diarrhoea 3–4 loose stools a day or mild diarrhoea lasting less than one week 5–7 loose stool a day or diarrhoea lasting more than one week Bloody diarrhoea  over 7 loose stools a day or needing IV treatment or feeling dizzy when standing Hospitalisation required (also possible for grade 3)
Fatigue Normal activity reduced by less than 25% Normal activity reduced by reduced by 25-50% Normal activity reduced by over 50% – cannot work Unable to care for yourself
Liver toxicity: AST or ALT levels 1.25–2.5 x Upper Limit of Normal 2.5–5.0 x ULN 5.0–7.5 x ULN More than 7.5 x ULN
Mood disturbance Mild anxiety, able to continue daily tasks Moderate anxiety/disturbance, interfering with ability to work, etc Severe mood changes requiring medical treatment Unable to work Acute psychosis, suicidal thoughts
Nausea Mild or transient reasonable food intake Moderate discomfort or intake decreased for less than 3 days Severe discomfort or minimal food intake for more than 3 days Hospitalisation required
Rash Redness or itchy skin on part or whole body Rash that breaks skin, hard or soft pimples or light peeling/scaling Blistering, open ulcers, wet peeling, serious rash over large areas Severe rash, Stevens-Johnson syndrome. Severe broken skin, etc
Vomiting 2–3 episodes a day or mild vomiting for less than one week 4–5 episodes a day or mild vomiting for more than one week Severe vomiting of all food and fluids over 24 hours needing IV treatment or feeling dizzy when standing Hospitalisation for IV treatment (possibly also for grade 3)

Last updated: 1 November 2021.