To the Editor:—
The Prevention by Epidural Injection of Postherpetic Neuralgia in the Elderly study recently showed that a single epidural injection of local anesthetics and steroids during the acute phase of herpes zoster was not effective for the prevention of long-term postherpetic neuralgia compared with care as usual.1However, it was associated with a modest but significant effect in reducing the presence (relative risk, 0.83; 95% confidence interval, 0.71–0.97) and severity of zoster-associated pain at 1 month after inclusion (median visual analog scale score in the epidural injection group, 2 mm [25th–75th percentiles, 0–23]vs. 6 mm [0–32] in the control group). Here, we report the economic analysis of the Prevention by Epidural Injection of Postherpetic Neuralgia in the Elderly study to assess the balance between the additional costs of a single epidural injection and the associated benefits.
The Prevention by Epidural Injection of Postherpetic Neuralgia in the Elderly study included 598 patients older than 50 yr with acute herpes zoster (rash <7 days) below dermatome C6. All patients received the current herpes zoster standard treatment, i.e. , analgesics and antiviral medication (if rash <72 h). Patients randomly allocated to the intervention group in addition received an epidural injection of bupivacaine and steroids.
Quality of life was assessed using the EQ-5D at various time points: at inclusion and at 1, 3, and 6 months after inclusion. The EQ-5D is a generic measure that defines health-related quality of life in five dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression.2Cost data about units of resource utilization (including doctor visits, medication, additional visits to healthcare providers, and hospitalizations) were also collected. All costs were estimated from a societal viewpoint. Costs of the epidural injection were estimated using two approaches: (1) the actual costs (€186) defined by the sum of labor (32 min by an anesthesiologist, 36 min by a nurse, and 20 min by an administrative employee), costs of material and location (€40), and overhead (€46); and (2) the current charges for an epidural injection (€870) as defined by the recent diagnosis–therapy–combination reimbursement scheme adopted by Dutch medical insurance companies. All other costs were estimated using tariffs. Direct non-healthcare costs included costs of paid and unpaid help. Indirect costs of loss of production owing to absenteeism from work or days of inactivity were not included, because most study participants were retired.
All analyses were performed with an intention-to-treat approach. The balance between costs and effects was expressed in terms of additional costs per additional quality-adjusted life year (QALY). One QALY equals 1 yr of full-health life. QALYs were calculated using the York A1 tariff.3Because the estimate of the costs highly depended on the chosen cost estimate of the epidural injection, we assessed to what extent the results and inferences from our analysis were determined by the chosen cost estimate.
The EQ-5D scores at 1 month significantly differed between both treatment groups. From 3 months onward, however, these differences lost statistical significance. The number of QALYs in the intervention group was 0.412 (SE = 0.006), and that in the control group was 0.403 (SE = 0.005). This leads to an estimated difference of 0.010 QALYs (95% confidence interval, −0.006 to 0.026). After 6 months, the estimated difference in total costs with and without epidural injection—excluding the cost of the injection—was estimated at €6. When the costs of the injection were estimated at €186 (based on resource utilization), the costs per QALY amounted to €17,540. Using the diagnosis–therapy–combination tariff of €870, costs per QALY increased to €79,859.
Figure 1presents the uncertainty surrounding costs and effects as based on these estimates of costs and effects. The probability density in the two southern quadrants (costs savings of epidural injection compared with standard therapy) was zero, that in the northeast quadrant (higher costs and better clinical effectiveness of injection) was 87.9%, and that in the northwest quadrant (higher costs and less clinical effectiveness) was 12.1%.
Hence, the short-term (<1 month) effectiveness of a single epidural injection was confirmed in terms of quality of life. Within the investigated time horizon of 6 months, the gain in QALYs was estimated at 0.01 QALY, i.e. , equivalent of 4 days in perfect health. Because the economic savings of the injection strategy are relatively small compared with the direct costs of the epidural injection, the costs per QALY are equal to approximately 100 times the costs of the injection.
There may be two limitations. Although no participant experienced an adverse event related to the injection, this risk is not absent.4,5Complications such as meningitis and epidural abscess may induce additional costs and reduction of quality of life. Assuming an adverse event risk of 1:10,000 and estimating the associated costs at €10,000, the costs of the injection increase with €1. Similarly, a major loss of QALYs caused by complications (e.g. , 20) may only slightly decrease the gain of effectiveness (i.e. , 20/10,000). Therefore, allowing for the small risk of severe complications does not substantially disrupt the estimated balance between costs and effects of the intervention. Second, the results of the Prevention by Epidural Injection of Postherpetic Neuralgia in the Elderly study do not rule out that the observed short-term analgesic effect by the epidural injection could as well be achieved by adequately administered, and possibly less costly, oral analgesics.
In conclusion, an epidural injection with steroids and local anesthetics modestly relieves the acute pain in older zoster patients with an acceptable balance between actual costs and effects as compared with standard treatment. The balance may tip to the other side, however, when the local tariff for epidural injection is much higher than the actual costs.
*Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands. firstname.lastname@example.org