An economic evaluation of short-acting opioids for treatment of breakthrough pain in patients with cancer.

OBJECTIVE: Breakthrough cancer pain (BTCP) represents a considerable economic burden. A decision-analysis model was developed to evaluate the cost-effectiveness of intranasal fentanyl spray (INFS) compared with oral transmucosal fentanyl citrate (OTFC) and fentanyl buccal tablet (FBT) for the treatment of BTCP. METHODS: The model was parameterized for Sweden to estimate the costs and benefits associated with treatments. Expected reductions in pain intensity (PI; measured on a numeric rating scale ranging from 0 to 10) per BTCP episodes were translated into resource use and quality-adjusted life years (QALYs). Relative analgesic efficacy of interventions was derived from a mixed treatment comparison of six randomized controlled trials. The relationship between PI and utility was obtained from a time-trade off study in the general population. Resource use and unit cost data were obtained from the literature and validated by Swedish clinical experts. The base case scenario assumed three BTCP episodes/day, a background PI of 2, and a time horizon of 180 days. Prices of INFS and OTFC were assumed to be equal with FBT ∼14% less. Uncertainty in the source data was incorporated by probabilistic sensitivity analyses and different scenario analyses. RESULTS: With INFS, 55% of BTCP (95% uncertainty interval [UI]: 46-68%) was avoided, which is greater than expected with OTFC (29%; UI 22-38%) or FBT (31%; UI 25-39%). INFS was dominating OTFC (resulting in 0.046 QALY gain and saving 174 Euros with a time horizon of 180 days) and cost-effective versus FBT (incremental cost-effectiveness ratio 12203 Euros/QALY). Despite uncertainty in the source data, there is a >99% probability that INFS is the most cost-effective intervention. CONCLUSION: Given inherent limitations of modelling studies, the greater efficacy of INFS translates to cost and QALY advantages over competing interventions in the treatment for BTCP in Sweden.

Efficacy of intranasal fentanyl spray versus other opioids for breakthrough pain in cancer.

OBJECTIVE: To compare the efficacy of intranasal fentanyl spray (INFS), oral transmucosal fentanyl citrate (OTFC), fentanyl buccal tablet (FBT) and oral morphine (OM) for the treatment of breakthrough cancer pain (BTCP). METHODS: A systematic literature review (Medline, EMBASE, BIOSIS; 1996-2007) identified six randomised controlled trials (RCTs) investigating the effects of INFS, OTFC, FBT and OM for the treatment of BTCP. The endpoint of interest was pain intensity difference (PID, reported on a 0-10 numeric rating scale [NRS]) up to 60 minutes after intake. Results of all trials were analysed simultaneously with a mixed treatment comparison (extended meta-analysis). MTC can be considered a valid method when included studies are comparable regarding effect modifying baseline patient and study characteristics. RESULTS: INFS provided the greatest reduction in pain relative to placebo: PID 1.7 points (95% CrI: 1.4; 1.9) at 15 minutes, 2.0 (1.6; 2.3) at 30 minutes, 2.0 (1.5; 2.4) at 45 minutes and 1.9 (1.5; 2.4) at 60 minutes. PID for OTFC and FBT relative to placebo were 0.4 (0.0; 0.8) and 0.5 (0.3; 0.7) at 15 minutes. Both treatments provided a reduction in pain superior to placebo at other time points. INFS displayed a more than 99% probability of providing the greatest pain reduction out of all interventions compared at 15 minutes after intake. This was maintained for any measured time point before 45 minutes when compared to FBT and for any measured time point before 60 minutes when compared to OTFC. Only from 45 minutes onwards did OM show a greater pain reduction than placebo. CONCLUSION: Based on currently available evidence, INFS is expected to provide the greatest improvement in the treatment of BTCP. Due to its slow onset to effect OM cannot be considered an efficacious treatment for BTCP.