|A cost-utility comparison of four first-line medications in painful diabetic neuropathy
|O'Connor AB, Noyes K, Holloway RG
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.
The objective was to examine the cost-effectiveness of four first-line treatments (desipramine, gabapentin, pregabalin, and duloxetine) in patients with painful diabetic peripheral neuropathy. The authors concluded that both desipramine and duloxetine were more effective and less expensive than gabapentin and pregabalin, with duloxetine providing borderline value for money in comparison with desipramine, which was the reference treatment. The study was based on valid methodology and was well presented. The authors’ conclusions appear to be valid.
Type of economic evaluation
The objective was to examine the cost-effectiveness of four first-line treatments (desipramine, gabapentin, pregabalin, and duloxetine) in patients with painful diabetic peripheral neuropathy (PDPN), but without cardiac conduction disorders or recent myocardial infarction.
The first-line oral treatments were: desipramine 100mg per day in one dose, gabapentin 2,400mg per day in three doses, pregabalin 300mg per day in three doses, and duloxetine 60mg per day in one dose.
USA/primary and secondary care.
This economic evaluation was based on a decision analytic model with a three-month time horizon. The authors stated that the perspective of the third-party payer was adopted.
The clinical data were identified through a systematic review of the literature in the PubMed database. Randomised controlled trials (RCTs) were also identified through recently published systematic reviews and official treatment guidelines. In total, 15 published and three unpublished RCTs were found. The unpublished information was obtained from authors and manufacturers. No head-to-head trial was available. The key clinical endpoint was the treatment efficacy, which was defined as the probability of achieving good pain relief. Good pain relief was defined in two ways: patient-reported subjective pain relief; and much improved or better on the Patient Global Impression of Change scale.
Monetary benefit and utility valuations:
Most of the utility valuations were derived from a cross-sectional survey of 255 patients with PDPN in the USA using the European Quality of life (EQ-5D) questionnaire and official UK tariffs. Other data mainly relating to the disutility of adverse events were based on published studies or authors’ opinions.
Measure of benefit:
Quality-adjusted life-years (QALYs) were the summary benefit measure.
The economic analysis included the costs of medications, visits, screening electrocardiogram, and treatment of serious adverse effects. The resource use data appears to have been based on authors’ opinions and a breakdown of cost items was not given. Drug costs were based on average wholesale prices from the Red Book. The costs of visits reflected Medicare reimbursement rates. The cost of treatment of serious adverse effects was derived from a previous study. All costs were in US dollars ($) and the price year was 2006.
Analysis of uncertainty:
Various sensitivity analyses were carried out to investigate the issue of uncertainty. A deterministic approach was used on the definition of pain relief, the exclusion of serious adverse effects, the exclusion of adherence, the time horizon (one month and six months), alternative utility estimates from the European population, various dosages and reduced generic gabapentin price, and other model inputs. Alternative assumptions were based on published evidence. A probabilistic analysis was also undertaken using a Monte Carlo simulation with 1,000 repetitions and specific probability distributions for the model inputs. An alternative scenario was assessed, in which the efficacies for duloxetine and gabapentin were based on a statistical analysis conducted by the Food and Drug Administration (FDA) instead of RCTs, conducted by manufacturers and using the last-observation-carried-forward method for missing data.
Over three months, the expected costs were $312.35 with desipramine, $419.60 with duloxetine, $525.08 with pregabalin, $748.39 with gabapentin. The QALYs were 0.1200 with desipramine, 0.1222 with duloxetine, 0.1186 with pregabalin, and 0.1176 with gabapentin.
The incremental analysis showed that both pregabalin and gabapentin were dominated, because desipramine and duloxetine were both less expensive and more effective. The incremental cost per QALY gained with duloxetine over desipramine was $47,700.
The base-case findings were generally robust. Gabapentin and pregabalin remained dominated in almost all cases, and the incremental cost-effectiveness of duloxetine compared with desipramine remained around $50,000. The most influential model input was the probability of achieving a 50% pain score reduction for good pain relief.
When using FDA estimates instead of RCT data, the incremental cost per QALY gained with duloxetine over desipramine rose to $867,000. Other influential inputs were the probabilities of obtaining pain relief with duloxetine and of developing intolerable adverse effects with desipramine.
At a threshold of $50,000 per QALY, the probability of being cost-effective was 48% for desipramine and 50% for duloxetine. When using FDA data, it was 87% for desipramine and 13% for duloxetine.
The authors concluded that both desipramine and duloxetine were more effective and less expensive than gabapentin and pregabalin, with duloxetine providing borderline value for money in comparison with desipramine, which was the reference treatment.
The selection of the comparators was appropriate as the four treatments were approved by the US health authority for the treatment of PDPN. Gabapentin was the most commonly prescribed first-line treatment for PDPN in Europe and the USA. The selection of specific dosages was justified.
The best available evidence appears to have been used to populate the decision model, as a systematic literature review, which is a valid method, was conducted to identify the relevant sources of data. The inclusion of RCTs enhances the validity of the clinical inputs due to the strengths of their design. The basic characteristics of the RCTs, such as their design, sample size, and clinical results, were extensively reported, which improves the validity of the clinical analysis. The authors acknowledged the limitation that there was a lack of head-to-head trials. QALYs were an appropriate benefit measure, given the impact of PDPN on quality of life. Some key details of the derivation of the utility values were reported.
The categories of costs reflected the perspective stated. Extensive information on the unit costs, dosages, and sources of data were presented for the drugs, but other cost categories, such as those relating to the management of adverse effects, were not clearly described. The cost estimates were varied in the sensitivity analysis. The authors stated that costs common to the four treatments were not included.
Analysis and results:
The synthesis of costs and benefits was appropriately performed using an incremental approach, which allowed the identification of dominated strategies. The study findings were clearly presented. The structure of the decision tree and the key assumptions were reported. The authors acknowledged that a longer time horizon would have been more appropriate given the chronic nature of PDPN, but a longer time frame was impractical and the reasons for this were described and mainly related to the validity of the available data and the uncertainty around the natural history of the disease. The issue of uncertainty was appropriately investigated in the various sensitivity analyses and their findings were clearly presented.
The study was based on valid methodology and was well presented. The authors’ conclusions appear to be valid.
Supported by grants from the National Institute of Aging, the National Institute of Neurological Disorders and Stroke, and the National Institutes of Health (NIH).
O'Connor AB, Noyes K, Holloway RG. A cost-utility comparison of four first-line medications in painful diabetic neuropathy. PharmacoEconomics 2008; 26(12): 1045-1064
Other publications of related interest
Cepada MS, Farrar JT. Economic evaluation of oral treatments for neuropathic pain. Journal of Pain 2006; 7(2): 119-128.
O’Connor AB. Cost-effectiveness of duloxetine versus routine treatment for US patients with diabetic peripheral neuropathic pain. Journal of Pain 2006; 7(11): 867.
Tarride JE, Gordon A, Vera-Llonch M, et al. Cost-effectiveness of pregabalin for the management of neuropathic pain associated with diabetic peripheral neuropathy and postherpetic neuralgia: a Canadian perspective. Clinical Therapeutics 2006; 28(11): 1922-1934.
Subject indexing assigned by NLM
Amines /adverse effects /economics /therapeutic use; Analgesics /adverse effects /economics /therapeutic use; Antidepressive Agents, Tricyclic /adverse effects /economics /therapeutic use; Cost-Benefit Analysis; Cross-Sectional Studies; Cyclohexanecarboxylic Acids /adverse effects /economics /therapeutic use; Desipramine /adverse effects /economics /therapeutic use; Diabetic Neuropathies /classification /drug therapy /economics; Duloxetine Hydrochloride; Economics, Pharmaceutical; Humans; Middle Aged; Pregabalin; Quality-Adjusted Life Years; Randomized Controlled Trials as Topic; Thiophenes /adverse effects /economics /therapeutic use; derivatives /economics /therapeutic use; gamma-Aminobutyric Acid /adverse effects /analogs &
Date bibliographic record published
Date abstract record published