Maltoni, M., Scarpi, E., Modonesi, C., Passardi, A., Calpona, S., Turriziani, A., . . . Amadori, D. (2005). A validation study of the WHO analgesic ladder: A two-step vs. three-step strategy. Supportive Care in Cancer, 13, 888–894.

To determine if, on the WHO analgesic ladder, passing directly from step 1 to step 3 is more effective than the traditional three-step strategy for treating chronic cancer pain; to evaluate the tolerability and therapeutic index of both strategies

Over 24 months, patients were monitored at home by telephone or a home health nurse. The study design included two arms: in one, patients moved from step 1 to step 3 (with treatment with strong opioids); in the other, patients moved from step 1, to step 2 (with treatment with weak opioids), to step 3.

• The sample was composed of 54 patients.
• Patients were age 18 and older.
• The sample was composed of patients with multiple visceral or bone metastases or locally advanced disease.

Italy

Randomized controlled trial

• Numeric Rating Scale (NRS), 0–10, to measure pain
• Five-step scale, 0–4, to measure other symptoms
• Five-step scale, 0–4, to measure degree of patient satisfaction
• Use of coanalgesics, adjuvants, and other treatments (as established by a yes/no answer)

• Going from step 1 to step 3 resulted in a statistically significant advantage over the traditional progression. Authors did not report the P value.
• Authors noted that all patients needed prophylactic treatment of constipation.

Preliminary data suggest that a direct move to the third step is feasible and could reduce some pain scores. The two-step strategy this study supports requires careful management of side effects.

The study had a small sample size.