The study objective was to assess the cost effectiveness of prolonged release oxycodone/naloxone tablets and prolonged release oxycodone tablets in patients with moderate to severe non-malignant pain and opioid-induced constipation. The authors concluded that oxycodone/naloxone was likely to be a cost-effective option for treating patients with severe non-malignant pain and opioid-induced constipation. The study methods appear valid and the author's conclusions appear appropriate.

Cost-utility analysis

The objective of the study was to assess the cost effectiveness of prolonged release oxycodone/naloxone tablets and prolonged release oxycodone tablets in patients with moderate to severe non-malignant pain and opioid-induced constipation.

Prolonged release oxycodone/naloxone tables (Targinact) was compared with prolonged release oxycodone tablets. The mean dose of oxycodone was approximately 33mg/day across both treatment groups.

United Kingdom (UK)/Primary care.

Analytical approach:

A decision tree was used to model the probability of constipation given the different treatment options. The cost-effectiveness analysis was based on a single clinical study. The time horizon was 301 days. The stated perspective was that of the UK National Health Service.

Effectiveness data:

Effectiveness data were derived from a phase III randomised controlled double-blind trial by Simpson et al. (see Other Publications of Related Interest). A total of 322 patients were randomised to treatment with oxycodone/naloxone (162 patients) or oxycodone (160 patients) and entered a 12-week double-blind phase. The primary endpoint was an improvement in constipation. Constipation was assessed using the Bowel Function Index (BFI).

Monetary benefit and utility valuations:

SF-36 version 2 (short-form health survey) scores were obtained from the randomised controlled trial by Simpson et al. and were converted to EQ-5D utility scores.

Measure of benefit:

The measure of benefit was the quality-adjusted life-year (QALY).

Cost data:

The economic analysis considered the costs associated with drugs, physician consultations and home visits, hospital visits and procedures, outpatient appointments, enemas and manual evacuations. With the exception of the drugs, resource use was derived from a commissioned survey of UK primary care physicians. Unit costs were derived from a variety of sources including the British National Formulary and the Personal Social Services Research Unit. The currency was pounds sterling (£). The price year was not explicitly stated but the currency conversion year was 2011.

Analysis of uncertainty:

Both deterministic and probabilistic sensitivity analyses were conducted to examine uncertainty. The deterministic analysis included increasing and decreasing the value of a number of key variables, including the incremental QALY gain and dose of oxycodone, by 25%. Monte Carlo simulation was used to examine uncertainty in model outputs with cost-effectiveness acceptability curves generated for various willingness to pay thresholds.

Estimated numbers of QALYs gained were 0.4152 with oxycodone/naloxone and 0.3878 with oxycodone. The total cost of oxycodone/naloxone was £873 and the total cost of oxycodone was £713. The incremental cost per QALY gained of oxycodone/naloxone compared to oxycodone was £5,842.

The sensitivity analysis showed the results to be generally robust to changes in model inputs. At a willingness to pay threshold of £20,000 per QALY gained, the estimated likelihood of oxycodone/naloxone being cost-effective was 96.6%.

The authors concluded that oxycodone/naloxone is likely to be a cost-effective option for treating patients with severe non-malignant pain and opioid-induced constipation.

Interventions:

The rationale for the selection of the interventions was clear. The interventions were the two treatment options in an RCT used as the main source of evidence.

Effectiveness/benefits:

Effectiveness data were derived from a single randomised controlled trial (RCT). RCTs can produce valid results, but relatively few details were provided on trial methods (such as the randomisation process and sample size calculation) and this made it difficult to comment meaningfully on the validity of the effectiveness estimates. Uncertainty in some clinical estimates was evaluated in the sensitivity analysis. QALYs were an appropriate measure of benefit to capture the impact of both pain and constipation on quality of life.

Costs:

The relevant costs for the stated perspective were included in the economic analysis. The sources of the unit costs and resource use were reported and appeared appropriate. Many of the unit costs and resources were varied in the sensitivity analysis. Discounting was appropriately not conducted given the relatively short time horizon of the study.

Analysis and results:

The results were presented clearly. An incremental approach was used to combine the costs and benefits of the alternative treatment options in order to identify the preferred strategy. Valid approaches were used to investigate uncertainty. The authors identified limitations of their analysis.

Concluding remarks:

The study methods appear valid and the author's conclusions appear appropriate.

Simpson K, Leyendecker P, Hopp M, et al. Fixed-ratio combination oxycodone/naloxone compared with oxycodone alone for the relief of opioid-induced constipation in moderate-to-severe noncancer pain. Curr Med res Opin 2008; 24; 3503-3512.