The following is the summary of “An international, open-label, randomised trial comparing a two-step approach versus the standard three-step approach of the WHO analgesic ladder in patients with cancer” published in the December 2022 issue of Oncology by Fallon, et al.
The World Health Organization (WHO) developed a three-tiered analgesic ladder that is universally used to treat cancer pain. Step 2 opioid therapy often involves weak opioids (e.g., codeine), but low-dose strong opioids may be preferable, especially in low- and middle-income countries due to the high cost of weak opioids. Specifically, researchers were interested in determining how skipping WHO Step 2 would affect efficiency, safety, and cost. Investigators conducted a randomized (1 : 1), parallel-group, open-label study around the world.
Patients who met the inclusion criteria (cancer, pain score pain ≥4/10 on a scale from 0 to 10, need for at least step 1 (paracetamol) of the WHO ladder) were randomly assigned to either the control arm (weak opioid, step 2 of the WHO ladder) or the experimental arm (strong opioid, step 3). The primary outcome was the number of days it took to achieve consistent pain control (defined as 3 days with a pain score of ≤3 or less). Distress, opioid-related adverse effects, and financial burdens were secondary outcomes. The primary analysis was performed using an intention-to-treat framework, and patients were followed for 20 days.
A total of 153 patients were randomly assigned (76 control, 77 experimental). When comparing the two groups, there was no statistically significant difference in the amount of time it took to achieve stable pain control (P=0.667). (log-rank test). For the untreated group, the adjusted hazard ratio was 1.03 (95% CI=0.72-1.49). In the control group, 38 out of 86 patients (53% of the total) required a switch to a more potent opioid due to insufficient pain relief. After 6 days, most people had made a decision (interquartile range 4-11). Patients in the experimental arm experienced less nausea (P=0.009) and spent less money than those in the control group. The results of this study suggest that the 2 stage method may be useful for managing the pain associated with cancer.