1. When low quality evidence suggests benefit in a life-threatening situation (evidence regarding harms can be low or high) |
e.g. Very low quality evidence for intravenous silibinin for life-threatening amatoxin mushroom poisoning [91, 92], or intravenous ascorbate for life-threatening viral infections [93, 94]. Recommend to use if there are no alternate proven interventions. |
2. When low quality evidence suggests benefit and high quality evidence suggests harm or a very high cost |
e.g. Low quality evidence that intravenous ascorbate improves quality of life and reduces chemotherapy toxicity in cancer treatment, and high quality of evidence of very high costs compared to oral ascorbate [95]. If there are significant opportunity costs to the patient, recommend not to use intravenous. |
3. When low quality evidence suggests equivalence of two alternatives, but high quality evidence of less harm for one of the competing alternatives |
e.g. Low quality evidence of equivalence of glucosamine and non-steroidal anti-inflammatory drugs (NSAIDS) for the long-term symptomatic management of osteoarthritis; but high quality evidence of increased gastrointestinal and cardiovascular risks for NSAIDs only [96, 97]. Recommend glucosamine as first-line treatment, especially for patients with a higher risk of complications from NSAIDs. |
4. When high quality evidence suggests equivalence of two alternatives and low quality evidence suggests harm in one alternative |
e.g. High quality equivalence of certain proprietary extracts of St. John’s Wort and selective serotonin reuptake inhibitors (SSRIs) for depression; and low quality evidence of a higher risk of suicide with SSRIs [98–100]. If these certain proprietary St. John’s Wort extracts are available and affordable, then recommend as first-line treatment before an SSRI. |
5. When high quality evidence suggests modest benefits and low/very low quality evidence suggests the possibility of catastrophic harm |
e.g. High quality evidence of modest benefit from peri-operative use of fish oil for elective Coronary Artery Bypass Surgery; and low quality evidence for catastrophic haemorrhage [80–82]. Recommend not to cancel CAB surgery if the patient has taken fish oil pre-operatively. |