|Cost effectiveness of duloxetine in the treatment of fibromyalgia in the United States
|Beard SM, Roskell N, Le TK, Zhao Y, Coleman A, Ang D, Lawson K
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.
This study assessed the cost-effectiveness of duloxetine for the treatment of moderate-to-severe pain from fibromyalgia. It focused on the best position for duloxetine in the treatment sequence. The authors concluded that adding duloxetine to the treatment sequence for fibromyalgia was cost-effective, particularly when it was the second-line treatment after tricyclic antidepressants. The methods were valid and the study was well presented. The authors’ conclusions appear to be robust.
Type of economic evaluation
Cost-effectiveness analysis, cost-utility analysis
This study assessed the cost-effectiveness of duloxetine for the treatment of moderate-to-severe pain from fibromyalgia. It focused on the best position in the treatment sequence for duloxetine.
Six treatment sequences that included duloxetine 60mg were considered. Each sequence included a tricyclic antidepressant, a serotonin-norepinephrine reuptake inhibitor (SNRI), an anticonvulsant, tramadol, and pramipexole in order. Duloxetine was included as first-line, second-line, third-line, fourth-line, fifth-line, or sixth-line treatment.
These options were compared with the treatment sequence without duloxetine.
The analysis was based on a Markov health-state transition model, with a two-year time horizon. The authors stated that the analysis was carried out from the perspective of the health care payer.
The clinical data were from a selection of relevant studies, including three pivotal randomised controlled trials (RCTs) evaluating the efficacy of the 60mg, once daily, dose of duloxetine that was approved by the Food and Drug Administration (FDA). A full mixed-treatment comparison was used to generate the response rates relative to placebo. The long-term efficacy was based on a conservative assumption that all treatments had the same long-term adherence. Additional data were from other published sources. The most important input was the pain response, which was assessed using various instruments, such as the Brief Pain Inventory (BPI), a visual analogue scale, and the Fibromyalgia Impact Questionnaire (FIQ).
Monetary benefit and utility valuations:
The utility values were from patients enrolled in the clinical trials, who completed the European Quality of life (EQ-5D) questionnaire; standard UK tariffs were used.
Measure of benefit:
The two benefit measures were symptom control months (SCMs) and quality-adjusted life-years (QALYs). Symptom control months were defined as the additional time spent in adequate pain symptom control, based on an improvement from baseline pain severity of 30% or more. QALYs were discounted at an annual rate of 3%.
The economic analysis included the costs of drugs, hospitalisation, out-patient services, and physician contacts. The recommended drug dosages and average wholesale prices were used to calculate the drug costs, considering titration to the target dose, where appropriate. The costs of doctors’ visits were based on Current Procedural Terminology codes. The cost of the clinical management of fibromyalgia (excluding drugs) was from a published US study and other published sources. All costs were in US dollars ($) and the price year was 2009. A 3% annual discount rate was applied.
Analysis of uncertainty:
Various one-way sensitivity analyses were carried out, using published confidence intervals or credible ranges of values for assumed parameters. A comprehensive probabilistic sensitivity analysis was performed assigning conventional probability distributions to the model inputs. In alternative scenario, the economic burden of the disease on patients and their families, including supportive care at home, adaptations to the home, and reduced productivity, was considered.
In a hypothetical cohort of 1,000 patients, compared with the sequence without duloxetine, the additional costs were $582,911 with first-line, $143,752 with second-line, $104,118 with third-line, $126,408 with fourth-line, $19,119 with fifth-line, and $49,870 with sixth-line duloxetine. The QALYs were 12.3 with first-line, 8.7 with second-line, 5.9 with third-line, 4.0 with fourth-line, 4.2 with fifth-line, and 5.3 with sixth-line duloxetine. The SCMs were 665 with first-line, 460 with second-line, 334 with third-line, 288 with fourth-line, 277 with fifth-line, and 329 with sixth-line duloxetine.
The incremental cost per SCM over the sequence without duloxetine was $877 with first-line, $312 with second-line, $312 with third-line, $439 with fourth-line, $69 with fifth-line, and $152 with sixth-line duloxetine. The incremental cost per QALY was $47,560 with first-line, $16,565 with second-line, $17,548 with third-line, $31,848 with fourth-line, $4,506 with fifth-line, and $9,471 with sixth-line duloxetine.
When the duloxetine sequences were compared against each other, the incremental cost per QALY was $122,727 with first-line over second-line, and $28,101 with second-line over a later placement. Third-line duloxetine was ruled out through extended dominance, as it was less effective and less cost-effective than second-line treatment.
The two most influential inputs were the pain response assumed with tricyclic antidepressants and the proportion of long-term drop-out patients who were assumed to be lost to any subsequent treatment. There was a 60% chance of second-line duloxetine being cost-effective at a threshold of $50,000 per QALY. This likelihood was 41% for first-line duloxetine.
The authors concluded that adding duloxetine to the treatment sequence for fibromyalgia was cost-effective, particularly when it was the second-line treatment after tricyclic antidepressants.
The comparators appear to have been the possible treatment pathways in typical US clinical practice. The background comparator was from the 2005 American Pain Society (APS) guidelines and was supported by discussions with US clinicians.
A MEDLINE search was carried out to identify published economic models of fibromyalgia management, but not to search for sources of clinical data. Most of these sources were published RCTs, the methods of which should have ensured the validity of the clinical inputs. A mixed-treatment comparison was performed, with placebo as the common comparator, as there were no head-to-head trials for the treatment sequences. Some assumptions were required and the authors pointed out the drawbacks of some data sources, mainly for tricyclic antidepressant efficacy. To overcome these issues, extensive sensitivity analyses were carried out. Both benefit measures were appropriate as they capture the impact of the interventions on pain (SCMs) or global health (QALYs). Appropriate instruments were used to measure them.
The cost categories were representative of the health care payer as stated by the authors. The unit costs were reported for drugs and visits, which were from standard US sources. Some resource quantities were presented. Other costs were aggregated and were from published studies, which were not fully described. An alternative scenario that included societal costs was presented and had similar findings to those of the base case. Details, such as the price year and discount rate, were given. The costs were varied in the probabilistic sensitivity analysis.
Analysis and results:
The results were extensively presented. An incremental approach was used to calculate the cost-effectiveness and cost-utility ratios. A justification was given for the selection of the time horizon, which was sufficient to cover the sequence of possible treatments. Valid approaches were used to assess the uncertainty and the findings were clearly reported and discussed. The inclusion of sequences of treatments was informative as previous studies had only assessed first-line treatment. The transferability of the results was not discussed and the study results appear to be specific to the USA.
The methods were valid and the study was well presented. The authors’ conclusions appear to be robust.
Funded by Eli Lilly and Company, manufacturer of duloxetine.
Beard SM, Roskell N, Le TK, Zhao Y, Coleman A, Ang D, Lawson K. Cost effectiveness of duloxetine in the treatment of fibromyalgia in the United States. Journal of Medical Economics 2011; 14(4): 463-473
Subject indexing assigned by NLM
Analgesics, Opioid /economics /therapeutic use; Anticonvulsants /economics /therapeutic use; Antidepressive Agents /economics /therapeutic use; Cost-Benefit Analysis; Duloxetine Hydrochloride; Female; Fibromyalgia /drug therapy; Humans; Male; Markov Chains; Medication Adherence; Middle Aged; Models, Economic; Quality-Adjusted Life Years; Serotonin Uptake Inhibitors /administration & Thiophenes /administration & United States; dosage /adverse effects /contraindications /therapeutic use; dosage /adverse effects /economics /therapeutic use
Date bibliographic record published
Date abstract record published