quality of life, resource consumption and costs of spinal cord stimulation versus conventional...

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European Journal of Pain 12 (2008) 1047–1058

Quality of life, resource consumption and costs of spinal cordstimulation versus conventional medical management in neuropathic

pain patients with failed back surgery syndrome (PROCESS trial)

Andrea Manca a,*, Krishna Kumar b, Rod S. Taylor c, Line Jacques d, Sam Eldabe e,Mario Meglio f, Joan Molet g, Simon Thomson h, Jim O’Callaghan i, Elon Eisenberg j,

Germain Milbouw k, Eric Buchser l, Gianpaolo Fortini m, Jonathan Richardson n,Rebecca J. Taylor o, Ron Goeree p, Mark J. Sculpher a

a Centre for Health Economics, Alcuin A Block, University of York, York YO10 5DD, United Kingdomb Department of Neurosurgery, Regina General Hospital, Regina, Canada

c Peninsula Medical School, Peninsula Technology Assessment Group, Universities of Exeter and Plymouth, United Kingdomd Department of Neurosurgery, Montreal Neurological Institute and Hospital, Montreal, Canada

e Department of Pain and Anaesthesia, James Cook University Hospital, Middlesbrough, United Kingdomf Department of Functional Neurosurgery, Gemelli Catholic University Hospital, Rome, Italy

g Department of Neurosurgery, Santa Creu i Sant Pau Hospital, Barcelona, Spainh Pain Clinic, Basildon and Thurrock University Hospitals, Basildon, United Kingdom

i Pain Clinic, Axxon Pain Medicine, Brisbane, Australiaj Pain Relief Unit, Rambam Medical Center, Haifa, Israel

k Department of Neurosurgery, Namur Regional Hospital, Namur, Belgiuml Pain Management Services and Neuromodulation Centre, EHC-Morges Hospital, Morges, Switzerland

m Pain Clinic, Varese Regional Hospital and Macchi Foundation, Varese, Italyn Department of Pain and Anesthesia, Bradford Hospitals, Bradford, United Kingdom

o Health Economics Facility, Health Service Management Centre, University of Birmingham, United Kingdomp Program for Assessment of Technology in Health, St. Joseph’s Hospital Department of Clinical Epidemiology and Biostatistics,

McMaster University, Hamilton, ON, Canada

Received 22 August 2007; received in revised form 28 January 2008; accepted 28 January 2008Available online 21 March 2008

Abstract

Background: Chronic back and leg pain conditions result in patients’ loss of function, reduced quality of life and increased coststo the society.

Aims: To assess health-related quality of life (HRQoL) and cost implications of spinal cord stimulation plus non-surgical con-ventional medical management (SCS group) versus non-surgical conventional medical management alone (CMM group) in themanagement of neuropathic pain in patients with failed back surgery syndrome.

Methods: A total of 100 patients were randomised to either the SCS or CMM group. Healthcare resource consumption datarelating to screening, the use of the implantable generator in SCS patients, hospital stay, and drug and non-drug pain-related treat-ment were collected prospectively. Resource consumption was costed using UK and Canadian 2005–2006 national figures. HRQoLwas assessed using the EuroQol-5D (EQ-5D) questionnaire. Costs and outcomes were assessed for each patient over their first6-months of the trial.

1090-3801/$34 � 2008 European Federation of Chapters of the International Association for the Study of Pain. Published by Elsevier Ltd. All rights

reserved.

doi:10.1016/j.ejpain.2008.01.014

* Corresponding author. Tel.: +44 (0) 1904321430; fax: +44 (0) 1904321402.E-mail address: [email protected] (A. Manca).

mailto:[email protected]

1048 A. Manca et al. / European Journal of Pain 12 (2008) 1047–1058

Results: The 6-month mean total healthcare cost in the SCS group (CAN$19,486; €12,653) was significantly higher than in theCMM group (CAN$3994; €2594), with a mean adjusted difference of CAN$15, 395 (€9997) (p < 0.001). However, the gain inHRQoL with SCS over the same period of time was markedly greater in the SCS group, with a mean EQ-5D score difference of0.25 [p < 0.001] and 0.21 [p < 0.001], respectively at 3- and 6-months after adjusting for baseline variables.

Conclusions: The addition of SCS to CMM in patients with neuropathic leg and back pain results in higher costs to health sys-tems but also generates important improvements in patients’ EQ-5D over the same period.� 2008 European Federation of Chapters of the International Association for the Study of Pain. Published by Elsevier Ltd.All rights reserved.

Keywords: Costs; Quality of life; Neuropathic pain; Spinal cord stimulation; Randomised controlled trial

1. Introduction

Neuropathic pain has a reported prevalence in thegeneral and primary care population of 1.5–8% (Ben-nett, 1998; Hall et al., 2006; Torrance et al., 2006),although its presence is often under-diagnosed andunder-treated (Taylor, 2006). The healthcare costs asso-ciated with this condition are substantial. A recent Uni-ted States-based analysis revealed that the healthcarecosts of patients with neuropathic pain was three-foldthat of age- and sex-matched patients without neuro-pathic pain (Berger et al., 2004).

The most common location of chronic neuropathicpain is the back and legs (Dworkin et al., 2003), and10–40% of patients who have undergone lumbosacralspine surgery to alleviate neuropathic radicular paininstead experience persistent or recurrent pain (Northet al., 1993; Wilkinson, 1991). In carefully chosenpatients with this condition, which is often referred toas ‘failed back surgery syndrome’ (FBSS), spinal cordstimulation (SCS) has been shown to provide effectivepain relief (Taylor et al., 2005; Turner et al., 2004).

Health policy makers not only expect medical tech-nologies, such as spinal cord stimulation (SCS), to pro-vide added clinical effectiveness, they also expect data ontheir impact on treatment costs, allowing them to makedecisions about ‘value for money’.

A number of studies have reported the costs of SCS(for a review see Taylor et al., 2004) yet the evidenceof cost-effectiveness of SCS for FBSS is currently limitedto one model-based analysis (Taylor and Taylor, 2005).This analysis suggests that SCS for the treatment of painin FBSS patients is cost-effective at two years. However,the authors emphasise the preliminary nature of their con-clusions and the need for additional data, in particular thedirect assessment of health-related quality of life, health-care resources as well as the costs of both SCS and conven-tional medical management (CMM) to be collected in aprospective randomised controlled trial setting.

The PROCESS (prospective, randomized, controlled,multicenter study of patients with failed back surgerysyndrome) trial has recently demonstrated that the addi-tion of SCS to CMM provides better pain relief andimproves the health-related quality of life (HRQoL)and functional capacity of patients with FBSS suffering

from chronic neuropathic back and leg pain (Kumaret al., 2007).

This paper reports the generic health-related qualityof life and costs at 6-months from the PROCESS trial.

2. Methods

2.1. Study design and patients

Full details of the PROCESS trial are reported else-where (Kumar et al., 2005; Kumar et al., 2007). In sum-mary, 100 patients were recruited in a total of 12 centersin Europe, Canada, Australia, and Israel between April2003 and June 2005. Patients of 18 years or older suffer-ing from predominant neuropathic pain of radicular ori-gin in the legs (radiating in dermatomal segments L4and/or L5 and/or S1) with or without associated lesssevere back pain were included. The intensity of painwas at least 50 mm on a visual analogue scale (VAS: 0equalling no pain, to 100 mm representing the worst pos-sible pain) for at least 6-months after at least one ana-tomically successful surgery for a herniated disc. Allpatients had a documented history of nerve injury (i.e.,root compression by herniated disc, compatible withthe pain complaint). The neuropathic nature of the painwas confirmed according to the routine clinical practiceof each investigator and included mapping the pain dis-tribution, examining sensory/motor/reflex changes.

All patients randomised to the SCS group underwenta screening trial. Those experiencing at least 80% over-lap of their pain with stimulation-induced paresthesiaand at least 50% leg pain relief received an implantableneurostimulation system. CMM included oral medica-tion (i.e., opioids, non-steroidal anti-inflammatorydrugs [NSAIDs], antidepressants, anticonvulsants/anti-epileptics, and other analgesic therapies), nerve blocks,epidural corticosteroids, physical and psychologicalrehabilitative therapy, and/or chiropractic care. In eithergroup, implantable drug delivery systems and re-opera-tion were not allowed.

Patients were assessed prior to randomisation (base-line) and at 3- and 6-months after initiation of treatment.Given that SCS therapy induces paraesthesia, it was notpossible to blind patients or investigators during the trial.

A. Manca et al. / European Journal of Pain 12 (2008) 1047–1058 1049

2.2. Measurement of resource consumption

Healthcare resource consumption data relating topre-implant screening, the use of the implantable pulsegenerator (IPG) in SCS patients, associated hospitalstay, and drug and non-drug pain-related treatmentbetween baseline and 6-months after hospital dischargewas collected prospectively for each patient using casereport forms (CRFs). The data collected included:

Pre-implant screening and IPG implant: Hospital staffcollected individual-level information on time intheatre, use of hardware (leads, anchors, extensions,IPG), and length of hospital stay (including the typeof ward).Use of medications: Details on the daily doses andtreatment duration of four main drugs classes (i.e.,opioids, NSAIDs, antidepressants, and anticonvul-sants including gabapentin and pregabalin) wererecorded.Non-drug therapy: Similarly, the utilisation of non-drug therapies (i.e., physical rehabilitation and psy-chotherapy, acupuncture, nerve blocks, massage, chi-ropractic, occupational and osteopathic therapies,acupressure, and the use of transcutaneous electricalnerve stimulation [TENS]) was captured.Complications: SCS and non-SCS related complica-tions, including those related to CMM, wererecorded. In addition, the CRFs were designed to col-lect SCS-specific healthcare resource utilisation suchas additional surgery, initial hospitalisation and read-mission required to overcome complications (e.g.,SCS-lead replacement, repositioning or biologicalcomplications) and non-invasive tests (e.g., X-ray,CT-scan, MRI).

2.3. Unit costs

Healthcare resource consumption was costed at2005–2006 prices using UK and Canadian figures. Toestimate the total cost for each element of resource con-sumption identified in the CRF, country-specific unitcosts were obtained from published sources, comple-mented with data from the literature where needed.Equipment and consumables were costed using manu-facturers’ list prices, whereas drug prices were takenfrom the drug formulary for the country of interest(BNF, 2006; Ontario Ministry of Health, 2006). Simi-larly, the cost of in-patient hospital stay was estimatedusing fully allocated cost figures, while non-drug thera-pies (such as physical rehabilitation) were costed usinga combination of published tariffs and estimates fromthe literature (Curtis and Netten, 2006; UK Departmentof Health, 2006). Where necessary, cost figures were up-rated for inflation using the national healthcare-specific

price index (Curtis and Netten, 2006; Statistics Canada,2007).

Total costs for each of the resource use consumptionobserved in the study were calculated by multiplying thelatter by the relevant national average unit cost. Thecosting exercise was conducted for Canada and theUK since these two countries accounted for the majorityof the patients enrolled in the PROCESS trial. Costresults in this paper are therefore reported in UK Ster-ling (£), Canadian Dollars (CAN$) and, to facilitatethe interpretation of the results among European read-ers, in Euros (€) converting the Canadian figures accord-ing to the exchange rate (CAN$/€: 1.54) available at thetime of writing. While Euro figures could have beenderived from the estimated costs in UK Sterling wedecided against this practice, in view of the fact thatCanada and the UK have different unit costs for thesame item of healthcare resource. For each countrythese unit costs represent essentially ‘weights’ that areapplied to each item of healthcare resource consumedto express them in monetary terms. The resulting totalcost estimate can be seen as a ‘weighted’ average ofthe sum of the resource consumption observed in thetrial. Because prices (i.e., the ‘weights’) differ betweencountries, converting total costs in UK Sterling andCanadian Dollars into Euros would lead to differenttotal cost estimates. To avoid confusion it was decidedto obtain Euro estimates converting from one currencyonly. As Canada was larger recruiter than the UK inthe PROCESS trial it was considered more appropriateto use the figures in Canadian Dollars as a base for theconversion to Euros.

2.4. Health outcomes

In PROCESS, HRQoL was assessed using the Short-Form 36 (SF-36) and the EuroQol-5D (EQ-5D). For thepurposes of economic evaluation, a preference-basedquality of life that weights patient responses accordingto values collected from the general population isrequired. The EQ-5D is one of the most widely usedpreference-based measures (Kind, 1996). It comprisesfive questions, each relating to a different dimension:mobility, self-care, ability to undertake usual activity,pain/discomfort and anxiety/depression. Each dimen-sion has three possible levels of severity: no problems,moderate problems, and severe problems. Based on theircombined answers to the EQ-5D questionnaire, patientscan be classified as being in one of 243 possible healthstates (not including unconsciousness and death). Eachof these health states has an associated utility score(on a 0 [equivalent to death] to 1 [equivalent to goodhealth] scale, where negative values are possible) typi-cally derived from a large sample of the population.The EQ-5D ‘utility’ score ranges from �0.594 to 1,and its interval properties make it the most


commonly-used instrument to measure generic HRQoLwithin economic assessment of health technologies(Drummond et al., 2005). The utility weights used inthe present analysis are those obtained from a large sam-ple of the UK population (Dolan, 1997; Kind et al.,1999). The EQ-5D questionnaire was completed by eachpatient in the trial at baseline, 3- and 6-months followup.

2.5. Statistical analysis

All primary analyses compared groups by intentionto treat (ITT) and, given the time horizon of the analy-sis, costs and EQ-5D have been left undiscounted(CADTH, 2006; NICE, 2004). Ordinary least squaresregression was used to analyse cost and EQ-5D data.Cost data were analysed following the regression-basedmethodology proposed by Hoch and colleagues (Hochet al., 2002). Analysis of covariance was used to estimatethe differential change in EQ-5D weighted indexbetween the SCS and CMM groups in the trial at twotime points: from baseline to 3-months and from base-line to 6-months post SCS implant (Roberts and Torger-son, 1999). The results are presented, firstly reportingthe unadjusted analyses for costs and changes in theEQ-5D weighted index, to estimate absolute differencesin mean total cost, and in change from baseline scorebetween the two treatment arms. A set of exploratoryanalyses was also conducted to facilitate the assessmentof the contributions of a set of patient baseline variables(i.e., gender, age, number of previous back surgeries,time since last back surgery, unilateral or bilateral legpain, and – in the case of the EQ-5D score – its baselinevalue [Manca et al., 2005] to the study results). The lat-ter set of covariates was defined in the study protocol forthe analysis of clinical outcomes, the results of which arereported elsewhere (Kumar et al., 2007).

3. Results

Eligible subjects were randomly assigned to CMMalone (n = 48) or CMM with SCS (n = 52). Patients’baseline characteristics in the trial were equally balancedbetween the SCS and CMM groups and descriptive sta-tistics are fully reported in the main clinical report(Kumar et al., 2007). On average, the age at recruitmentwas 51, with a slightly greater proportion of malepatients in the SCS group (58% vs. 44%). Time since lastback surgery was on average 4.6 years, with a marginallygreater proportion of patients in the SCS group havinghad more than one previous surgery (54% vs. 46%). Thedistribution of leg pain (bilateral vs. unilateral) was wellbalanced.

Three patients randomised to CMM requested to bescreened for SCS (and thus were implanted with trial

leads), but did not receive an IPG during the 6-monthperiod. Following an ITT analysis strategy they wereanalysed as CMM group patients.

3.1. Resource use

Table 1 reports the results in terms of healthcareresources consumption for the treatment strategies com-pared here. There is clearly a difference in the mix andspread of health resource utilisation, which is due tothe different nature of the interventions being comparedover the 6-months follow up period. It is thereforeunsurprising to observe that SCS required hospitalisa-tion during the screening period, the duration of whichwas on average 2.5 days. The majority (69%) of patientsin the SCS arm were implanted with one lead; the lengthof time over which the operation room was occupiedwas on average 105 min. Furthermore, three patientsin the CMM arm underwent a lead implant during thefirst 6-months, but the internalisation (IPG implant)for two of these took place after the 6-months visitand the third patient failed the screening phase.

Nine patients randomised to SCS did not achieve thetrial screening criteria set in the study. However, five ofthese patients requested to continue on SCS therapy.Therefore, a total of 48 patients in the SCS arm receivedan IPG (Synergy, Medtronic, MN), and 67% of thesepatients required hospitalisation with an average in-patient stay of 2.3 days.

Drug treatments were different in SCS and CMMgroups. Opioids were used for an average of 11 days lessby the SCS group (and in a smaller proportion ofpatients, i.e., 75% vs. 77%). NSAIDs were used for anaverage of 38 days less by the SCS patients (68 vs. 106days). Antidepressants were required for almost twoweeks less in the SCS group. Finally, anticonvulsantswere used more intensively by the CMM group with65 prescriptions (i.e., change in drug, or daily dose) asopposed to 37 prescriptions in the SCS group (Table 1).

A substantial reduction in healthcare resource usecan also be observed when looking at non-drug treat-ments for pain (e.g., physiotherapy, massage, etc). Theproportion of patients requiring contacts with health-care professionals for treatment related to neuropathicpain was lower in the SCS group. This can be observedparticularly in the case of physical therapy (7% SCS vs.44% CMM), psychotherapy (4% vs. 14%), and massagetherapy (0% vs. 14%). This pattern is also accompaniedby a reduction in the duration and frequency of contactswith these healthcare professionals.

SCS resulted in complications which reduced the nethealthcare resource reduction for this group (25% ofpatients required extra resources to resolve complica-tions such as lead migrations). These required an over-night stay in most cases, the mean duration of whichwas 2.6 days. In two cases these complications required

Table 1Resource consumption in the PROCESS trial at 6-monthsa

Spinal cord stimulation (SCS)group n = 52

Conventional medicalmanagement (CMM) groupn = 48

Intervention costs

ScreeningHospitalisations for screening

Day care, n (%) 4 (7) – –Required overnight stay, n (%) 49 (92) 3 (6)No hospitalisation, n (%) 1 (1) – –

Duration of in-patient stay, mean (SD) [min–max] 2.5 (1) [1–5] 8 (NAb) [2–19]Leads

Required one lead, n (%) 36 (69) 3 (6)Required two leads, n (%) 16 (31) – –

Duration of the intervention (mins), mean (SD) [min–max] 105 (33) [35–181] 70 (NAb) [45–70]

IPG implantHospitalisations

Day care, n (%) 13 (27) – –Required overnight stay, n (%) 32 (67) – –No hospitalisation, n (%) 3 (6) – –

Duration of in-patient stay, mean (SD) [min–max] 2.3 (1.4) [1–6] – –Leads

Required one lead, n (%) 3 (0.7) 1 (2)Required two leads, n (%) 0 0 – –

Duration of the intervention (mins), mean (SD) [min–max] 70 (23) [30–151] – –IPG implanted, n (%) 48 (100) – –

Failed screeningHospitalisations

Day care, n (%) 1 (2) – –Required overnight stay, n (%) 2 (4) – –No hospitalisation, n (%) 1 (2) – –

Duration of in-patient stay (mins), mean (SD) [min–max] 2.5 (NAb) [2–3] – –Duration of surgery for explant (mins), mean (SD) [min–max] 65 (NAb) [20–125] – –Non-invasive investigations

CT scan, n (%) – – – –MRI, n (%) – – – –X-ray, n (%) 1 (2) – –Myelogram, n (%) – – – –Others, n (%) – – – –

SCS related complicationSurgery, n (%) 13c (25) – –

Duration (mins), mean (SD) [min–max] 62 (NAb) [15–140] – –Hospitalisation

Day care, n (%) 3 (6) – –Required overnight stay, n (%) 9 (17) – –No hospitalisation, n (%) – – – –

Duration of in-patient stay, mean (SD) [min–max] 2.6 (NAb) [1–6] – –Leads, n (%)

Required one lead, n (%) 1 (2) – –Required two leads, n (%) 1 (2) – –

Non-invasive investigationsd

CT scan, n (%) – – – –MRI, n (%) – – – –X-ray, n (%) 5 (10) – –Myelogram, n (%) – – – –Others, n (%) – – – –

Full blood count 8 (15) – –Abdominal wound swab 1 (2) – –Aspiration of seroma 1 (2) – –Scar tissue biopsy 1 (2) – –Microbiology 2 (4) – –

(continued on next page)


Table 1 (continued)

Spinal cord stimulation(SCS) group n = 52

Conventional medicalmanagement (CMM)group n = 48

IPG reprogramming sessions, n (%)

0 14 (27) – –1–2 17 (33) – –3–4 15 (29) – –5–7 4 (11) – –

CMM related/non-SCS related costs

Drug treatment for painOral/transdermal opioidse, n (%) 39 (75) 37 (77)

Total number of prescriptionsf 99 84 –Mean (SD) [min–max] duration (days) per prescription 84 (67) [0–201] 95 (72) [0–193]

NSAIDse, n (%) 33 (63) 30 (62)Total number of prescriptionsf 37 – 40 –Mean (SD) [min–max] duration (days) per prescription 68 (66) [1–182] 106 (80) [0–182]

Antidepressantse, n (%) 21 (40) 29 (60)Total number of prescriptions 35 – 46 –Mean (SD) [min–max] duration (days) per prescription 97 (74) [3–186] 110 (72) [0–182]

Anticonvulsive/antiepilepticse, n (%) 30 (57) 31 (64)Total number of prescriptionsf 37 – 65 –Mean (SD) [min–max] duration (days) per prescription 95 (74) [0–212] 89 (77) [1–197]

Non-drug treatment for painPhysical rehabilitatione, n (%) 4 (7) 21 (44)

Total number of treatment episodesf 6 – 32 –Mean (SD) [min–max] duration (days) per treatment episode 49 (53) [7–150] 66 (52) [4–182]

Psychotherapye, n (%) 2 (4) 7 (14)Total number of treatment episodesf 2 – 12 –Mean (SD) [min–max] duration (days) per treatment episode 49 (NAb) [7–92] 68 (55) [1–182]

Acupuncturee, n (%) 2 (4) 7 (14)Total number of treatment episodesf 2 – 8 –Mean (SD) [min–max] duration (days) per treatment episode 40 (NAb)[5–75] 97 (58) [14–182]

Blockse, n (%) – – 8 –Total number of treatment episodesf – – – –Mean (SD) [min–max] duration (days) per treatment episode – – – –

Massagee, n (%) – – 7 (14)Total number of treatment episodesf – – 7 –Mean (SD) [min–max] duration (days) per treatment episode – – 91 (NAb) [4–182]

Chiropractic sessione, n (%) 1 (2) 2 (4)Total number of treatment episodesf 1 – 2 –Mean (SD) [min–max] duration (days) per treatment episode 35 (NAb) 91 (NAb) [1–182]

Acupressuree, n (%) 3 (5) – –Total number of treatment episodesf 1 – – –Mean (SD) [min–max] duration (days) per treatment episode (NAb) – – –

TENS sessionse, n (%) – – – –Total number of treatment episodesf – – – –Mean (SD) [min–max] duration (days) per treatment episode – – – –

Osteopathic therapye, n (%) 2 (4) 1 (2)Total number of treatment episodesf 2 – 1 –Mean (SD) [min–max] duration (days) per treatment episode 182 (NAb) 182 (NAb)

Occupational therapye, n (%) – – 1 (2)Total number of treatment episodesf – – 1 –Mean (SD) [min–max] duration (days) per treatment episode – – 182 (NAb)

SCS: spinal cord stimulation; CMM: conventional medical management; NSAIDs: non-steroidal anti-inflammatory drugs; MRI: magnetic resonanceimaging; CT: computer assisted tomography; IPG: implantable pulse generator.

a Unless otherwise stated values are mean (SD) and, where appropriate, [min–max].b Insufficient number of observations to estimate SD.c Number of patients needing one or more surgeries following SCS related complication.d Numbers of patients needing one or more investigation following complication.e This section reports the number (%) of patients requiring a given treatment.f Prescription or treatment episodes represents a change in type (e.g., medication brand or molecule), frequency or dose of treatment.


Table 2Unadjusted cost results at 6-months follow-up between randomised groups

Spinal cord stimulation(SCS) group n = 52


Between groupunadjusted differences

Mean (SD) Mean (SD) Difference (95% CI)

UK

Intervention costs

Hospitalisations 1886 (1179) 200 (1390) 1686 (1171–2198)Surgery (excluding devices) 2774 (832) 61 (239) 2713 (2474–2953)Leads 1339 (688) 57 (219) 1282 (1083–1482)Non-invasive investigations – 3 (20) �3 (�8 to 3)SCS related complications 576 (1320) – 576 (213–940)IPG devices 7243 (2641) – 7243 (6515–7969)Reprogramming 33 (30) – 33 (24–41)


Drug pain treatment 1096 (1822) 1417 (1772) �321 (�1035 to 392)Non-drug pain treatment 134 (389) 1835 (3524) �1701 (�2715 to �686)

Total cost (UK £) 15,081 (4194) 3573 (4082)

Canada – – –

Intervention costs

Hospitalisations 2313 (1505) 244 (1690) 2069 (1432–2706)Surgery (excluding devices) 2344 (703) 51 (202) 2293 (2091–2495)Leads 3456 (1966) 133 (522) 3323 (2761–3884)Non-invasive investigations – 1 (10) �1 (�4 to 1)SCS related complications 572 (1329) – 572 (206–938)IPG devices 9461 (3450) – 9461 (8511–10410)Reprogramming 29 (26) – 29 (21–36)


Drug pain treatment 1139 (2489) 1388 (1974) �249 (�1137 to 639)Non-drug pain treatment 172 (373) 2177 (3744) �2005 (�3081 to �927)

Total cost (CAN$) 19,486 (5784) 3994 (4526)

Total cost (€) 12,653 (3756) 2594 (2939)

SCS, spinal cord stimulation; CMM, conventional medical management; IPG, implantable pulse generator.Results are presented separately for the UK and Canada by attaching the relevant country’s unit costs to trial-wide resource consumption.


a new lead, while in eight (15%) patients one or two non-invasive investigations such as X-ray or full blood countwere needed. Optimisation of programming (SCS ther-apy) required 1–4 sessions in 32 (62%) patients. Four-teen (27%) patients did not require any re-programming.

3.2. Costs

Nine main cost categories under two main headings(i.e., ‘Intervention’ and ‘CMM related and non-SCSrelated costs’) – reflecting the pain treatment algorithm– were created for cost comparison purposes (Table 2).

The mean per patient cost of the hospitalisationrelated to leads and IPG implant on an ITT basis was£1,886 [CAN$2313] for SCS patients and £200[CAN$244] for the CMM group. Given the nature ofthe interventions being compared, surgery costs (operat-ing theatre time, staff and consumables other than thedevices themselves) were higher with SCS group (mean£2,774 [CAN$2344]) than CMM (mean £61[CAN$51]). The mean cost of the leads amounted to

£1339 [CAN$3456] and £57 [CAN$133] in the SCSand CMM groups, respectively. The average per patientcosts of the IPG device in the SCS arm was £7243[CAN$9461]. Note that the costs related to leads andsurgery in the CMM group are due to three patientsrequesting trial screening.

The cost of pain medication was £321 [CAN$249]lower in the average SCS patient over the 6-months fol-low up. Similarly, non-drug therapy costs were lower inthe SCS than the CMM arm (£134 [CAN$172] vs. £1835[CAN$2177]).

Apart from the cost associated with reprogrammingsessions and non-invasive investigations in SCS patients,the only other relevant cost component was associatedwith the cost of the SCS related complications, mostlyrelated to lead migrations (mean £576 [CAN$572]).

At the end of the 6-month follow up period, the totalaverage patient cost was £15,081 (CAN$19,486;€12,653) in the SCS group and £3573 (CAN$3994;€2594) in the CMM group, with a statistically significant(adjusted) differential mean cost (Table 3) of £11,373

Table 3Estimation of differential total cost at 6-months follow-up between randomised groupsa

Dependent variable Analysis for the UK Analysis for Canada

Coefficient (95% CI) Coefficient (95% CI)

Unadjusted analysis

Intervention (incremental cost: SCS�CMM) 11,508 (9865–13,150) 15,492 (13,439–17,545)Constant (mean cost in CMM group) 3573 (2404–4742) 3994 (2698–5289)

Analysis adjusted for patients’ characteristicsb

Intervention (incremental cost: SCS�CMM) 11,373 (9513–13,234) 15,395 (12,990–17,799)Male 436 (�1416 to 2289) 912 (�1581 to 3406)Age at recruitment �81 (�171 to 7) �101 �213 to 10)Time since last back surgery (years) �112 (�465 to 242) �72 (�473 to 328)Bilateral leg pain 1352 (�843 to 3548) 1006 (�1627 to 3640)Number of previous back surgeriesc

Two surgeries �562 (�2479 to 1355) �416 (�2899 to 2065)Three surgeries 42 (�2130 to 2215) �395 (�2801 to 2010)Four surgeries or more �966 (�3648 to 1715) 897 (�4078 to 5871)

Constant 3496 (1209–5782) 3589 (986–6193)

SCS, spinal cord stimulation; CMM, conventional medical management; CI, confidence interval.a Values are expressed in national currency (i.e., British pounds and Canadian Dollars).b One surgery is the reference group.c These results allow prediction of the mean cost at 6-months for a hypothetical patient based on a set of baseline characteristics observed in the

trial. For instance, 6-months after receiving SCS, the mean cost of an individual with the following characteristics – male, aged 40 at recruitment inthe trial, with three previous back surgeries, unilateral leg pain, who had the last back surgery 2.5 years before – is expected to be, on average,£14,225. This is obtained as follows: 3496 (constant) + 436 � 1 (coefficient for male � dummy for male) +�81 � (50.39�40) (coefficient forage � departure from the mean age in the trial, i.e., [50.39�40] years) +42 � 1 (coefficient for three previous back surgeries � dummy for threeprevious back surgeries) +1352 � 0 (coefficient for unilateral leg pain � dummy for unilateral) +�112 � 2.5 (coefficient for time since last backsurgery � number of years since last back surgery) + 11,373 � 1 (coefficient for treatment group � dummy for treatment group).


[95%, CI: 9513–13,234] (CAN$15,395 [95% CI: 12,990–17,799]; €9997 [95% CI: 8435–11,557]; p < 0.0001).Fig. 1 shows that while SCS requires an upfront cost,it also brings a considerable saving in terms of CMMrelated and non-SCS related events at 6-months followup.

A further analysis to explore the role of patients’baseline characteristics on determining total costs(Table 3) suggests that none of the baseline variablesinvestigated had a statistically significant impact oncosts.

0

2,000

4,000

6,000

8,000

10,000

12,000

14,000

SCSTreatment st

Tota

l cos

t (Eu

ro)

Intervention costs CMM relate

Note: Intervention costs include: hospitalisations, surgery (excrelated complications. IPG devices, and reprogramm

CMM related / non SCS related costs include

Fig. 1. Composition of total costs

3.3. Health-related quality of life

Patients in the SCS group displayed a similar meanbaseline EQ-5D score than their counterparts in theCMM group (0.13 vs. 0.18) as indicated in Table 4.Fig. 2 shows that the mean EQ-5D score improves at3- and 6-months in both treatment arms, with theCMM group experiencing a non-statistically significantimprovement from its mean baseline value (as repre-sented by the overlapping 95% CI bars). In the SCSgroup, the improvement in the EQ-5D over time is

CMMrategy

d and non-SCS related costs

lude devices), leads, non-invasive investigations, SCS ing sessions.

: drug and non-drug pain treatments

(figures reported in Euros).

Table 4Unadjusted comparison of EQ-5D weighted index score at baseline, 3- and 6-months follow-up between randomised groups

EQ-5D weighted index scorea Spinal cord stimulation(SCS) group n = 52


Between group unadjusted difference Between groupadjusted differenceb

Mean (SD) Mean (SD) Mean (95% CI) Mean (95% CI)

Baseline 0.13 (0.30) 0.18 (0.31) – –3-Months 0.49 (0.31) 0.22 (0.31) 0.27 (0.14–0.39) 0.27 (0.15–0.39)6-Months 0.47 (0.32) 0.25 (0.30) 0.22 (0.09–0.35) 0.23 (0.12–0.35)

EQ-5D, EuroQol-5D; SCS, spinal cord stimulation; CMM, conventional medical management; CI, confidence interval.a Higher score indicates better quality of life.b Adjusted for baseline imbalance in EQ-5D weighted index score.

SCS group CMM group

0

.2

.4

.6

EQ—5

D s

core

EQ—5

D s

core

0 3 6Time period (months)

0

.2

.4

.6

0 3 6Time period (months)

Fig. 2. Mean (95% CI) EQ-5D weighted index score at baseline and follow up by treatment group.


greater compared to CMM, with statistically significantmean improvements of 0.27 (95% CI: 0.15–0.39;p < 0.001) and 0.23 (95% CI: 0.12–0.35; p < 0.001)respectively at 3- and 6-months after adjusting for differ-ences in the baseline EQ-5D scores.

Adjusted for patients’ baseline characteristics (Table5), the difference in change from baseline score at3- and 6-months is consistently in favour of the SCSgroup (mean difference at 3-months: 0.25 [95% CI:0.12–0.37; p < 0.001]; mean difference at 6-months:0.21 [95% CI: 0.09–0.33; p < 0.001]). As expected, themost significant predictor of the value of the EQ-5D atfollow up is its baseline value (Manca et al., 2005; Mor-ton and Torgerson, 2003; Roberts and Torgerson, 1999;Vickers and Altman, 2001). The number of years fromlast back surgery was statistically significant (mean coef-ficient: 0.02 [95% CI: 0.01–0.04; p = 0.009]) in predictingthe difference in the change from baseline between SCSand CMM at 6-months but not in predicting the changeat 3-months. The latter result was investigated further. Itwas found that the statistical significance of the result at

6-months was due to the skewed distribution of the var-iable ‘time from last back surgery’ (mean: 2.6; standarddeviation: 2.3; min–max = 0.2–11.6). When looking atthe effect of SCS among those individuals whose timesince last back surgery was one year or less (resultsnot reported), it was found that in the latter sub-groupSCS was more beneficial compared to those whose lastback surgery occurred earlier. This result was consistentwith the findings of the exploratory analysis conductedon the primary clinical outcome (i.e., leg pain relief) inthe same group of patients.

4. Discussion

While initially expensive due to the upfront implantcosts, SCS proffers improvements in generic HRQoLas measured by the EQ-5D. Of the total mean additionalcost of SCS, 15% is offset in 6-months time by reducingthe use of drugs for pain relief and ‘other’ non-drug paintreatment reduction. Adjusted for baseline covariates,

Table 5Estimation of differential change from baseline in EQ-5D at 3- and 6-month follow-up between randomised groups

Dependent variable Analysis at 3-months Analysis at 6-months

Coefficient (95% CI) Coefficient (95% CI)

Unadjusted analysis

Intervention (differential change from baseline: SCS�CMM) 0.27 (0.14–0.39) 0.22 (0.09–0.35)Constant (mean change from baseline in CMM group) 0.21 (0.12–0.31) 0.25 (0.15–0.34)

Analysis adjusted for baseline EQ-5D

Intervention (differential change from baseline: SCS�CMM) 0.27 (0.15–0.39) 0.23 (0.12–0.34)EQ-5D at baseline 0.36 (0.18–0.55) 0.48 (0.33–0.63)Constant 0.16 (0.07–0.24) 0.16 (0.07–0.24)

Analysis adjusted for patients’ characteristicsb

Intervention (differential change from baseline: SCS�CMM) 0.25 (0.12–0.37) 0.21 (0.09–0.33)EQ-5D at baseline 0.38 (0.19–0.58) 0.47 (0.31–0.63)Male 0.04 (�0.08 to 0.17) 0.05 (�0.08 to 0.17)Age at recruitment �0.001 (�0.008 to 0.005) �0.002 (�0.009 to 0.005)Time since last back surgery (years) �0.03 (�0.03 to 0.02) 0.02 (0.01–0.04)Bilateral leg pain �0.009 (�0.15 to 0.13) �0.08 (�0.22 to 0.06)Number of previous back surgeriesa

Two surgeries 0.0007 (�0.15 to 0.15) �0.05 (�0.19 to 0.08)Three surgeries 0.14 (�0.06 to 0.35) 0.02 (�0.15 to 0.21)Four surgeries �0.20 (�0.42 to 0.02) �0.17 (�0.40 to 0.06)

Constant 0.20 (�0.17 to 0.58) 0.25 (�0.14 to 0.65)

EQ-5D, EuroQol-5D; SCS, spinal cord stimulation; CMM, conventional medical management; CI, confidence interval.a One surgery is the reference group.b These results allow prediction of the mean EQ-5D score, at either 3- or 6-months, for a hypothetical patient based on a set of baseline

characteristics observed in the trial. For instance, 6-months after receiving SCS, the mean EQ5D of an individual with the following characteristics –male, aged 40 at recruitment in the trial, with three previous back surgeries, unilateral leg pain, who had the last back surgery 2.5 years before, andwith an EQ-5D at baseline equal to the observed mean in the trial – is expected to be, on average, equal to 0.63. This is obtained as follows: 0.25(constant) +0.05 � 1 (coefficient for male � dummy for male) +�0.002 � (50.39–40) (coefficient for age � departure from the mean age in the trial,i.e., (50.39–40) years) +0.02 � 1 (coefficient for three previous back surgeries � dummy for three previous back surgeries) +�0.08 � 0 (coefficient forunilateral leg pain � dummy for unilateral) +0.02 � 2.5 (coefficient for time since last back surgery � number of years since last back sur-gery) +0.47 � 0.160449 (coefficient for EQ-5D at baseline � overall mean EQ-5D at baseline in the trial) +0.21 � 1 (coefficient for treatmentgroup � dummy for treatment group).


SCS has an additional mean cost of £11,373[CAN$15,395; €9997] per patient. This additional costrelates to the SCS implant procedure including hospital-isations, surgery, leads, IPG and the management ofcomplications.

The additional cost of SCS over 6-months needs tobe compared with the gains in HRQoL seen from theintervention over the same period. At 6-months followup, patients receiving SCS in the PROCESS trial expe-rienced an adjusted mean gain of 0.23 on the 0 (equiv-alent to death) to 1 (equivalent to good health) utilityscale, compared to those receiving CMM alone. To putthis into context, a recent survey of 36,678 US adultsusing the EQ-5D instrument estimated the HRQoLdecrement associated with a number of illnesses whilstcontrolling for age, co-morbidities and socio-demo-graphic variables (Sullivan and Ghushchyan, 2006). Itestimated mean decrements of 0.02 for asthma, 0.04for angina pectoris, 0.05 for stroke, and 0.06 fordepression. The mean baseline EQ-5D of the patientsin the PROCESS trial was on average 0.15 betweenthe two arms, which is considerably less than the base-line EQ-5D score of patients hospitalised after ischemicstroke (Calvert et al., 2005), which has been reported

to be 0.31 on the EQ-5D scale. The gain in qualityof life of 0.23 on the EQ-5D scale experienced bySCS patients in this study with respect to their baselinevalue is therefore considerable. Moreover, the changesin EQ-5D are consistent with improvements in otherpatient related outcomes seen in the PROCESS trial.As reported elsewhere (Kumar et al., 2007), patientsin the SCS group experienced significant improvementsin pain relief, and improved generic HRQoL as mea-sured by the SF-36 scale as well as functional capacity(as measured by the Oswestry Disability Scale version2). In contrast, patients in the CMM group have littleor no pain relief or other outcome benefits.

Of course, without blinding we cannot rule out a pla-cebo effect, but blinding is a difficult issue with SCS asthe therapy produces paraesthesia, which must be elic-ited in the area of the pain if SCS is to be efficacious.In addition, the implantation procedure might in itselfproduce a placebo effect, but sham operations are ethi-cally difficult to justify (Van Zundert, 2007).

The PROCESS trial randomised patients from eightcountries. The cost estimates presented here are basedon resource consumption data collected on all 100 ran-domised patients, but are valued using unit costs from


the UK and Canada, the two largest recruiting countriesin the study. This trial is the first to confirm (Fig. 1) indi-cations of early analyses that the addition of SCS toCMM brings an important cost offset in terms of ‘othertreatments’. It has been argued that in the medium tolong term SCS has the potential to be cost-saving com-pared to CMM (Kumar et al., 2002; Taylor and Taylor,2005; Taylor et al., 2004).

On the basis of an approximate exchange rate ofCAN$1 = £0.43 used in our analysis, there is variationin unit costs between the countries – most notably inthe cost of day-case visits to hospital and of somenon-drug pain therapies. International differences inunit costs have been noted elsewhere (Schulman et al.,1998). These unit cost differences seem to result in someimportant differences between the UK and Canadiananalyses in the total mean cost of the therapies: for theUK analysis, the mean cost per patient of CMM is44% that of SCS, whereas this proportion is 26% forCanada. Exploratory analyses on potential ‘countryeffect’ (results not reported) indicate that the differencein total costs for both the UK and Canada do notappear to be statistically significantly different fromthe trial overall mean.

The PROCESS trial is the first randomised study inFBSS patients to prospectively compare the additionof SCS to CMM alone, and one of very few in the areaof neuropathic pain management to collect data suitablefor economic analysis (Taylor et al., 2004). This includesdetailed resource consumption information on all keyareas of health service activity including hospitalisation,the cost of devices, drugs, and other pain management.This provides a key source of data to assess the cost-effectiveness of SCS in real life practice. A limitationof PROCESS is that randomised evidence is only avail-able over a period of 6-months follow-up: for ethicalreasons and in order to recruit clinicians and patientsinto the study, it was necessary to permit crossover fromCMM to SCS beyond 6-months. However, our analysesdo show that compared to baseline, quality of lifeimprovements in SCS patients compared to baselineare sustained in the long-term in the subgroup ofpatients who continue to use their stimulator in thelonger-term (Kumar et al., submitted for publication).The limited follow-up period is one reason why the eco-nomic data collected in PROCESS alone are not suffi-cient to assess whether the additional costs of SCS arejustified by the additional benefit patients experience(i.e., the cost-effectiveness of SCS). A full cost-effective-ness analysis would need to consider how costs andHRQoL differences would develop beyond 6-monthstaking into consideration, for example, the maintenanceof SCS hardware, cost of other therapies, and long-termeffectiveness of SCS. In addition, such an analysis wouldneed to include any other relevant evidence, particularlytrial evidence on the effectiveness of SCS, CMM and

other forms of management (Ades et al., 2006; Rivero-Arias et al., 2005).

In conclusion, at 6-months observation and com-pared to CMM alone, SCS increases HRQoL in patientswith chronic back and leg pain with a neuropathic com-ponent after one or multiple surgeries by 0.21 on theEQ-5D scale at additional mean healthcare cost of£11,373 (CAN$15,395; €9997) per patient.

Acknowledgement and declaration of interest

This study was funded by Medtronic Inc. Theauthors had full, non-restricted access to the data. Thefunding source had no role in the analysis or interpreta-tion of the data. The conclusions of the paper areentirely those of authors.

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