Economic evaluation of Durogesic in moderate to severe, nonmalignant chronic pain in Germany Greiner W, Lehmann K, Earnshaw S, Bug C, Sabatowski R

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1 Economic evaluation of Durogesic in moderate to severe, nonmalignant chronic pain in Germany Greiner W, Lehmann K, Earnshaw S, Bug C, Sabatowski R Record Status This is a critical abstract of an economic evaluation that meets the criteria for inclusion on NHS EED. Each abstract contains a brief summary of the methods, the results and conclusions followed by a detailed critical assessment on the reliability of the study and the conclusions drawn. Health technology The study examined four long-acting opioids used for the treatment of moderate to severe nonmalignant chronic pain. These were transdermal fentanyl (TDF), transdermal buprenorphine (TDB), sustained-release morphine (SRM) and controlled-release oxycodone (CRO). TDF which was the main health technology evaluated in the current study. All of the drugs could be given at different dosages on the basis of treatment effect and adverse events: 25 to 100 microg/hour for TDF, 35 to 70 microg/hour for TDB, and 20 to 80 mg/day for CRO. SRM dose administration was not reported. Type of intervention Treatment. Economic study type Cost-utility analysis. Study population The study population comprised a hypothetical cohort of patients with moderate to severe nonmalignant chronic pain. Setting The setting was primary care. The economic study was carried out in Germany. Dates to which data relate The effectiveness data and most resource use data were derived from studies published between 1986 and The price year was Source of effectiveness data The effectiveness evidence was derived from a synthesis of published studies as well as expert opinion. Modelling A decision tree model was constructed to assess the clinical and economic impact of the different treatments in a hypothetical cohort of patients with moderate to severe nonmalignant chronic pain. The time horizon of the model was 1 year. Patients entered the model during the 8-week titration and stabilisation phase, during which the opioid dose could be adjusted and patients could experience drug-related adverse events (AEs). At the end of the titration and stabilisation phase, patients could switch to an alternative opioid therapy if adequate pain control was not achieved, or if any of the AEs experienced was intolerable. Patients who did not switch moved to the long-term use phase, where they could experience non-compliance, or after 90 days could be given the opportunity to increase their dose. Those who increased their dose in the long-term use phase repeated the 56-day titration and stabilisation phase where they could experience AEs. Patients continuing in the long-term use phase for the rest of the 1-year period had controlled pain and Page: 1 / 6

2 a constant opioid dose and did not experience new side effects. Thus, it was assumed that patients could switch to another opioid only once, and that all patients switched to one of the other long-acting opioids under analysis. A schematic representation of the model was presented. Outcomes assessed in the review The outcomes estimated from the review of the literature were the rates of intolerable AEs and utility values associated with specific conditions. Study designs and other criteria for inclusion in the review A systematic review of the literature was undertaken to find clinical inputs used in the model. Specific inclusion and exclusion criteria were not reported. The authors stated that clinical evidence was derived from both clinical trials and databases, but did not provide details of the primary studies. AEs for CRO were derived from a meta-analysis. Other sources of clinical data were not specified. The utility weights originated from several different sources, including one study with 43 patients suffering from chronic low back pain, one study with 533 pregnant women suffering from nausea or vomiting, and one study with 100 patients suffering from eczema. Sources searched to identify primary studies PubMed and NLM Gateway were searched for relevant studies. Criteria used to ensure the validity of primary studies Not reported. Methods used to judge relevance and validity, and for extracting data Not reported. Number of primary studies included Approximately 18 primary studies provided the data. Methods of combining primary studies The primary estimates appear to have been combined using a narrative approach. Investigation of differences between primary studies The authors stated that there was no head-to-head trial comparing the AEs associated with the four treatments under analysis, thus the data had to be taken from separate sources. The patients in the studies selected were as similar as possible. Results of the review The rate of mild chronic constipation was 32.1% with SRM, 12.0% with TDF, 13.5% with TDB and 18.5% with CRO. The rate of severe chronic constipation was 20.0% with SRM, 5.0% with TDF and with TDB, and 20.0% with CRO. The rate of mental cloudiness and somnolence was 20.9% with SRM, 12.0% with TDF, 10.7% with TDB and 24.3% with CRO. The rate of nausea was 38.7% with SRM, 30.0% with TDF, 23.7% with TDB and 26.2% with CRO. Page: 2 / 6

3 The rate of pruritus and itching was 13.5% with SRM, 7.5% with TDF, 9.0% with TDB and 23.1% with CRO. The rate of sweating was 6.2% with SRM, 8.4% with TDF, 9.2% with TDB and 19.0% with CRO. The rate of local irritation was 9.0% with TDF and 25.0% with TDB. The rate of non-compliance was 1.9% with all medications. The utility associated with pain control was 0.59, while that associated with no pain control was The utility decrement for controlled pain was The utility decrement additive to that for controlled pain was: for uncontrolled pain, for nausea or vomiting, for mild chronic constipation, for severe chronic constipation, and for pruritus. Methods used to derive estimates of effectiveness In the absence of published clinical data, the opinions from a panel of experts were required. Estimates of effectiveness and key assumptions The utility decrement additive to that for controlled pain was for mental cloudiness and somnolence, for both non-compliance and need for increased dose, and 0 for local patch reaction. Measure of benefits used in the economic analysis The summary benefit measure used was the expected number of quality-adjusted life-years (QALYs). This was estimated using the modelling approach. Details of the sources of the utility values and the methods used to calculate QALYs were extensively reported. Most of the primary sources of the utility weights used the SF-36 questionnaire. Utility decrements were calculated to associate utility weights with AEs. Quality-adjusted life-days were also used as an alternative summary benefit measure. Direct costs The analysis of the costs was conducted from the perspective of the third-party payer. It included the costs of daily medication, treatment of AEs and physician visits (examination and prescription). A breakdown of the cost items was provided and, for most items, the unit costs were presented separately from the resource quantities. Resource use was mainly derived from published studies that were identified through the systematic review. Expert opinion was used when data on treatment patterns were not available in the literature. The costs were derived using national charges for medical services and a national formulary (Rote Liste). Discounting was not relevant as the costs were incurred during 1 year. All costs were inflated to 2003 values using the Health Service Cost Index. Statistical analysis of costs The costs were treated deterministically in the base-case. Page: 3 / 6

4 Indirect Costs The indirect costs were not included. Currency Euros (EUR). Sensitivity analysis A probabilistic sensitivity analysis was carried out by assigning triangular distributions to event rates and utilities. The ranges of values were derived from the literature or were based on expert opinion. A total of 10,000 simulations were run. Estimated benefits used in the economic analysis The expected QALYs were with TDF, with TBD, with CRO and with SRM. Cost results The total costs per patient were EUR 3, with TDB, EUR 2, with TDF, EUR 2, with CRO and EUR 2, with SRM. The main cost driver was the cost of pain medication, which amounted to EUR 2, with TDB, EUR 2, with TDF, EUR 2, with CRO and EUR 2, with SRM. Synthesis of costs and benefits Incremental cost-utility ratios were calculated in order to combine the costs and benefits of the alternative strategies. The incremental cost per QALY was EUR 1, with TDF over SRM, EUR 1, with TDF over CRO, and EUR 7, with TDB over SRM. TDB was dominated by TDF, which was both more effectiveness and less expensive. It was stated that, as the cost-utility ratio of TDF was below the conventional threshold of EUR 20,000 per QALY, TDF was considered cost-effective. The probabilistic sensitivity analysis confirmed the robustness of the base-case results. In 93% of the runs, TDF had an incremental cost-utility analysis of EUR 10,000 or less. In particular, in 85% of the runs comparing TDF with CRO, TDF had an incremental cost-utility ratio of less than EUR 10,000. TDF and TDB were similarly effective, thus a sensitivity analysis explored their cost-effectiveness relative to a common comparator such as SRM. Both TDF and TDB were more cost-effective in most of the simulations (92% and 74% of simulations, respectively). However, TDF dominated TDB in the majority of runs. Authors' conclusions Transdermal fentanyl (TDF) was the most cost-effective long-acting opioid for the treatment of moderate to severe nonmalignant chronic pain in Germany. CRD COMMENTARY - Selection of comparators The authors provided a justification for their choice of the comparators, which were all widely used in Germany. Doses and dose titration strategies were reported. You should decide whether they are valid comparators in your own setting. Validity of estimate of measure of effectiveness Page: 4 / 6

5 A review of the literature was undertaken to identify relevant primary studies, but the authors did not report any details of the review apart from the sources searched. There was little information on the types of studies included, the use of specific inclusion and exclusion criteria, or the issue of heterogeneity amongst the primary studies. It was stated that the patient populations were similar across studies, but no statistical tests appear to have been carried out to confirm this. Further, some clinical estimates were based on expert opinion. The probabilistic sensitivity analysis investigated extensively the impact of changes in clinical data, but the use of triangular distributions might not have been appropriate for some estimates. Validity of estimate of measure of benefit The benefit measure used in the analysis was appropriate as quality of life represents a key aspect of health for patients with moderate to severe pain. Clearly, the survival side of QALYs was not relevant for the current analysis, which was restricted to a 1-year time horizon. QALYs have the further advantage of being comparable with the benefits of other health care interventions. The authors reported how the QALYs were calculated and provided details of the sources of data (mainly based on patients and the SF-36 questionnaire). Validity of estimate of costs The costs included were consistent with the perspective adopted in the study. The sources of the costs were reported for all items and they reflected the viewpoint of the study. A detailed breakdown of items was reported, and details of the costs and quantities of resources used were given. These enhance the possibility of replicating the analysis in other settings. The resource use data were mainly derived from published studies and authors' opinions. Data on costs and treatment patterns were not tested in the sensitivity analysis, the costs being treated deterministically and being specific to the study setting. The impact of using alternative cost estimates was not investigated. The price year was reported, which will facilitate reflation exercises in other time periods. Other issues The authors reported the results from other studies, the findings of which were comparable with those from the current analysis. The issue of the generalisability of the study results to other settings was explicitly addressed, the authors stating that the results of the decision model could be transferred to other health care settings, taking into account the peculiarities of some inputs. However, the sensitivity analyses focused only on clinical estimates rather than on costs, which might not be valid for other health care systems. The study referred to patients with moderate to severe nonmalignant chronic pain and this was reflected in the authors' conclusions. The results of the analysis were presented clearly. Implications of the study The study results support the use of TDF for the treatment of moderate to severe nonmalignant chronic pain. The authors stated that further studies should be carried out to corroborate the current findings. Source of funding None stated. Bibliographic details Greiner W, Lehmann K, Earnshaw S, Bug C, Sabatowski R. Economic evaluation of Durogesic in moderate to severe, nonmalignant chronic pain in Germany. European Journal of Health Economics 2006; 7: PubMedID DOI /s Page: 5 / 6

6 Powered by TCPDF ( Other publications of related interest Because readers are likely to encounter and assess individual publications, NHS EED abstracts reflect the original publication as it is written, as a stand-alone paper. Where NHS EED abstractors are able to identify positively that a publication is significantly linked to or informed by other publications, these will be referenced in the text of the abstract and their bibliographic details recorded here for information. Frei A, Andersen S, Hole P, Jensen NH. A one year health economic model comparing transdermal fentanyl with sustained-release morphine in the treatment of chronic noncancer pain. J Pain Palliat Care Pharmacother 2003;17:5-26. Lehmann K, Radbruch L, Gockel HH, et al. Costs of opioid therapy for chronic nonmalignant pain in Germany: an economic model comparing transdermal fentanyl (Durogesic) with controlled-release morphine. Eur J Health Econ 2002;3: Neighbors DM, Bell TJ, Wilson J, Dodd SL. Economic evaluation of the fentanyl transdermal system for the treatment of chronic moderate to severe pain. J Pain Symptom Manage 2001;21: Indexing Status Subject indexing assigned by NLM MeSH Administration, Cutaneous; Analgesics, Opioid /administration & dosage /economics /therapeutic use; Buprenorphine /economics /therapeutic use; Chronic Disease; Cost-Benefit Analysis; Delayed-Action Preparations; Fentanyl /administration & dosage /economics /therapeutic use; Germany; Health Services /utilization; Humans; Morphine /economics /therapeutic use; Oxycodone /economics /therapeutic use; Pain /drug therapy; Quality-Adjusted Life Years AccessionNumber Date bibliographic record published 30/04/2007 Date abstract record published 30/04/2007 Page: 6 / 6