Table 1 Scenarios where detailed evaluation of adverse effects may decisively influence the decision whether to use an intervention or not.

Treatment is of modest or uncertain benefit, with some possibility of harm

• Aspirin for prevention of cardiovascular events in a healthy patient. What is the increased risk of haemorrhage from aspirin?

Treatment potentially very beneficial, but there are major safety concerns

• Carotid artery surgery in elderly patients with ischaemic heart disease who have suffered a stroke. The operation can prevent a future stroke but some patients may die from the intervention.

Treatment potentially beneficial in long-term, or to community. No immediate direct benefit to individual but possibility of harm exists.

• Improving uptake of a childhood vaccine to promote population immunity, while trying to assuage individual parents' fears about early serious vaccine- induced neurological damage to their child.

Several effective treatments have differing safety profiles – which should be preferred?

Examples:

Treatments are similarly effective, but have different safety profiles

• A new insulin injection device is thought to cause less pain than the existing device

The balance of benefits and harms differ substantially, e.g. the most effective intervention may have serious adverse effects, while the less effective one is potentially safer

• Radical mastectomy for breast cancer as opposed to limited, breast-conserving surgery which is less disfiguring but may carry a greater risk of local cancer recurrence.

Adverse effects with an important role in deterring a patient from continuing an effective treatment

Examples:

Treatment offers important benefit but adverse effects threaten patient's adherence

• The options for a patient with severe heart failure who has responded well to an ACE inhibitor, but has persistent cough: stop the medication altogether, try a lower dose, or change to an angiotensin receptor blocker?