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Cost-Effectiveness and Cost-Utility Analysis of
Spinal Cord Stimulation in Patients With Failed
Back Surgery Syndrome: Results From the
PRECISE Study
Furio Zucco, MD*; Roberta Ciampichini, MSc†; Angelo Lavano, MD‡;
Amedeo Costantini, MD§; Marisa De Rose, MD‡; Paolo Poli, MD¶;
Gianpaolo Fortini, MD**; Laura Demartini, MD††; Enrico De Simone, MD‡‡;
Valentino Menardo, MD§§; Piero Cisotto, MD¶¶; Mario Meglio, MD***;
Luciana Scalone, PhD†; Lorenzo G. Mantovani, DSc†
Objective: To assess the cost-effectiveness and cost-utility of Spinal Cord Stimulation (SCS) in patients with failed back surgery
syndrome (FBSS) refractory to conventional medical management (CMM).
Materials and Methods: We conducted an observational, multicenter, longitudinal ambispective study, where patients with
predominant leg pain refractory to CMM expecting to receive SCS+CMM were recruited in 9 Italian centers and followed up to 24
months after SCS. We collected data on clinical status (pain intensity, disability), Health-Related Quality-of-Life (HRQoL) and on
direct and indirect costs before (pre-SCS) and after (post-SCS) the SCS intervention. Costs were quantified in €2009, adopting the
National Health Service’s (NHS), patient and societal perspectives. Benefits and costs pre-SCS versus post-SCS were compared to
estimate the incremental cost-effectiveness and cost utility ratios.
Results: 80 patients (40% male, mean age 58 years) were recruited. Between baseline and 24 months post-SCS, clinical outcomes
and HRQoL significantly improved. The EQ-5D utility index increased from 0.421 to 0.630 (p<0.0001). Statistically significant
improvement was first observed six months post-SCS. Societal costs increased from €6600 (pre-SCS) to €13,200 (post-SCS) per
patient per year. Accordingly, the cost-utility acceptability curve suggested that if decision makers’ willingness to pay per Quality-
Adjusted-Life-Years (QALYs) was €60,000, SCS implantation would be cost-effective in 80% and 85% of cases, according to the
NHS’s and societal point of views, respectively.
Conclusions: Our results suggest that in clinical practice, SCS+CMM treatment of FBSS patients refractory to CMM provides good
value for money. Further research is encouraged in the form of larger, long-term studies.
Keywords: Cost-effectiveness, cost-utility, failed back surgery syndrome, Spinal Cord Stimulation, quality adjusted life years
Conflict of Interest: The authors reported no conflict of interest.
INTRODUCTION
Failed back surgery syndrome (FBSS) represents one of the main
causes of chronic neuropathic or mixed pain. It has been estimated
to affect 0.61% of the general population, with an annual incidence
of 0.033% (1). In particular, it is estimated that 30% of patients
undergoing lumbar spinal surgery will develop FBSS (2).
Compared to the general population, patients with neuropathic
pain report lower levels of Health-Related Quality-of-Life (HRQoL).
In particular, patients with FBSS have reported the lowest health
utility score (3) among the following categories of patients with
neuropathic pain: diabetic neuropathy, post-herpetic neuralgia,
phantom limb pain, central neuropathy pain, trigeminal neuralgia,
and mixed neuropathy pain.
In patients who experience persistent pain after conventional
medical management, Spinal Cord Stimulation (SCS) might be rec-
ommended (4). Introduced in the treatment of chronic pain more
than 45 years ago (5), SCS has been reported to be effective in
relieving pain, improving HRQoL, and reducing disability in FBSS
patients (6–11).
Address correspondence to: Luciana Scalone, PhD, Centro di Studio e Ricerca
sulla Sanità Pubblica (CESP), Università degli Studi di Milano Bicocca, Villa
Serena, Via Pergolesi 33, I-20052 Monza, Italy. Email: luciana.scalone@unimib.it
* Azienda Ospedaliera Salvini, Garbagnate Milanese, Italy;
†Centro di Studio e Ricerca sulla Sanità Pubblica (CESP), Università degli Studi di
Milano Bicocca, Monza, Italy;
‡Università Magna Grecia, Catanzaro, Italy;
§Ospedale Clinicizzato Ss.Annunziata, Chieti, Italy;
¶Azienda Ospedaliera Universitaria Pisana, Pisa, Italy;
** Azienda Ospedaliero Universitaria Ospedale di Circolo e Fondazione Macchi,
Varese, Italy;
†† IRCCS Fondazione Salvatore Maugeri, Pavia, Italy;
‡‡ A.O.R.N. “S.G. Moscati,” Avellino, Italy;
§§ Azienda Ospedaliera Santa Croce e Carle di Cuneo, Cuneo, Italy;
¶¶ Ospedale “S. Maria di Cà Foncello,” Treviso, Italy;
*** Policlinico Universitario Agostino Gemelli, Roma, Italy; and
For more information on author guidelines, an explanation of our peer review
process, and conflict of interest informed consent policies, please go to http://
www.wiley.com/bw/submit.asp?ref=1094-7159&site=1
Source(s) of financial support: The study was sponsored by Medtronic Italy.
Dr. Piero Cisotto has passed since the writing of this manuscript.
Neuromodulation: Technology at the Neural Interface
Received: November 17, 2014 Revised: January 30, 2015 Accepted: February 17, 2015
(onlinelibrary.wiley.com) DOI: 10.1111/ner.12292
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The impact of FBSS and its management on individuals’ health
and its economic cost to society are considerable (12). Several evalu-
ations have been performed to understand the effectiveness, cost
impact, and cost-effectiveness of SCS treatment in FBSS patients
(6–8,13–16).
The Prospective Randomised Controlled Multicentre Trial of the
Effectiveness of Spinal Cord Stimulation (PROCESS) (14) estimated
the effectiveness of SCS+CMM versus CMM alone in FBSS patients.
Important improvements in pain relief, function, and HRQoL were
reached six months post-SCS implant (8,15) and were sustained at
24 months follow-up (6,7). Manca et al. (15) analyzed data from the
PROCESS trial and found that 15% of the additional mean cost of
SCS is offset within 6-months by a reduced use of drugs and other
non-drug treatments for pain relief. In 2010, Taylor and colleagues
(16) input the results of the PROCESS study into a cost-effectiveness
model, comprised of a short-term decision tree and long-term
Markov model to estimate the cost-effectiveness of SCS+CMM
versus CMM alone over a 15-year time period and found an incre-
mental cost per Quality-Adjusted-Life-Years (QALY) ratio of £5624
with an “89% probability that SCS is cost effective at a willingness to
pay threshold of £20,000.” In 2008, the National Institute of Health
and Care Excellence (NICE) recommended the use of SCS for the
treatment of neuropathic pain, including pain caused by FBSS (17).
However, NICE specified that it is necessary to conduct observa-
tional research able to generate robust evidence regarding the
durability of SCS benefits in a real-world context (17). The present
work compares the effects and costs of SCS as an adjunct to CMM
treatment with those of CMM alone applied in real-world clinical
practice for patients affected by FBSS.
MATERIALS AND METHODS
Subjects and Setting
All consecutive patients who, between June 2005 and October
2007, satisfied the eligibility criteria for receiving SCS were recruited
from 9 Italian specialized centers (6 pain units and 3 neurosurgery
wards). Centers were distributed across the country, and all have at
least five years of experience in the management of patients with
FBSS with spinal cord stimulation. Inclusion and exclusion criteria
used for this study, listed in Table 1, reflect recommendations that
have been recently published (18,19).
Eligible patients received information on: 1) the aim of the study;
2) the SCS surgical procedures and potential clinical outcomes; 3)
the technical variables (e.g., the self-regulation parameters), related
both to the external neurostimulator (ENS) during the stimulation
test period (screening trial) and to the fully implantable neuros-
timulator (INS); 4) the possible complications; 5) the study data col-
lection procedure. Eligible patients had to sign an informed consent
form after receiving all the necessary information on the aim of the
study, the type of data and the method of data collection. The study
participation of each center was previously approved by the Local
Ethics Committee, present in each hospital according to the Italian
regulations on clinical research.
Procedure
All the participants, after the lead implantation, were clinically
studied during the screening trial. Following clinical practice (2) and
according to the study protocol, those who responded positively to
the screening trial were implanted with a non-rechargeable INS and
were observed for up to 24 months. A test screening is considered
positive when patients experience at least 50% pain relief and at
least 80% overlap of pain with stimulation-induced paresthesia. We
did not continue to collect data on patients that did not respond
positively to the test and on patients that for different reasons
stopped the study before the scheduled 24-month follow-up
period.
Observational Period
A schematic definition and duration of the observational period is
reported in Figure 1. Specifically, the observational period included
a pre-SCS and a post-SCS period. The pre-SCS period included the
12-month period before SCS: 11 months before enrollment and 1
month from enrollment to SCS intervention. The post-SCS period
was intended to be up to 24 months after the SCS intervention and
was divided into6-month periods according to the scheduled
follow-up visits.
Table 1. Eligibility Criteria.
Inclusion criteria
• Suffering from FBSS pain that radiates to lower limbs, mono or bilaterally
• Pain intensity >5 NRS 0–10 for at least six months, measured by the NRS 0 to 10
• Being older than 18 years
• Not satisfactory response to previous conservative therapy: physical and functional therapies, >2 painkiller drugs, surgery
• Being capable and willing to undergo the study visits
• Being willing to participate in the study through a signed informed consent
• Capability to manage the devices both during the test phase and after the implantation of the neurostimulator
Exclusion criteria
• Predominance of pain in the lumbar region
• Having other pain condition potentially interfering with the assessment of results of the target treatment (e.g., cancer pain)
• Expected inability to manage the totally implanted neurostimulator and to compile the patient diary
• Contraindications in receiving the SCS system (e.g., coagulation problems)
• Lupuserythematosus, metabolic or other peripheral neuropathy, rheumatoid arthritis, active neoplasia
• Not being a native Italian speaker
• Being illiterate
• Life expectancy of less than two years
• Current or planned pregnancy
• Evidence of major psychiatric disorder or another personal condition known to affect the perception of pain, the treatment compliance or the assessment
of the treatment effectiveness
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Data Collection
We collected data on the sociodemographic and clinical charac-
teristics of the patients, their HRQoL, and resource consumption
(direct and indirect costs) using a Case Report Form (CRF) and a
patient diary.
Data referring to the retrospective pre-SCS period were collected
using a set of questions in the CRF. The physicians answered these
questions by asking the patients to recall what happened in the
specified pre-SCS period. Data relating to the prospective pre-SCS
(i.e., from enrollment to SCS) and the post-SCS period were col-
lected in the CRF at implant and at each scheduled 6-month
follow-up visit. During the follow-up period, the patients had a daily
diary to be completed in the week before the follow-up visit, col-
lecting information on pain intensity and drug consumption, which
were collected during the follow-up visit.
Sociodemographic and Clinical Data
Sociodemographic data comprising age, gender, marital status,
working status, and education were collected by the physician at
enrollment using the CRF. Pain intensity was recorded using the
0–10 NRS (20). The level of disability was measured with the
Oswestry Disability Index (ODI), which consists of 10 questions with
six possible responses to measure the disability level and functional
capability of a person according his/her health status in the last two
weeks (21).
HRQoL Data
The patients self-completed 2 generic questionnaires: the
Medical Outcome Study Short Form36 (SF-36) (22) and the EQ-5D
(now known as the EQ-5D-3L) (23). These questionnaires were
chosen for their capability to assess both physical and psychological
components of health, as they allow comparison within and
between different clinical conditions and with the general popula-
tion. The use of these outcome measures is consistent with other
recent studies on FBSS (3,6,7).
In the present paper we focus on the results obtained with the
EQ-5D descriptive system (or profile), from which we obtained the
QALYs to conduct the economic evaluation. In particular, the EQ-5D
is a generic instrument for describing and valuing individuals’
health. The tool consists of two parts: a descriptive system (EQ-5D
profile) and a visual analogue scale (EQ-5D VAS).With the EQ-5D the
respondents are asked about their HRQoL on the current day. The
responses of the EQ-5D descriptive system can be converted into
utility indexes by means of an algorithm that uses population-based
(social) values. The utility index corresponds to the estimate of value
of health with a score anchored between 0, corresponding to death,
and 1, corresponding to perfect health. Utility indexes are widely
used in different disease areas and recommended for the calcula-
tion of QALYs to be applied in economic evaluations of health tech-
nologies (24).
Resources Consumption and Costs
Data on resource consumption attributable to FBSS and its treat-
ment were collected in the CRF by the physician (e.g., hospitaliza-
tions, medical visits, examinations, travels/accommodations, days of
productivity lost) and in the diary by the patients (drugs). From
these data, we were able to quantify in monetary terms direct
medical, nonmedical, and indirect costs attributable to FBSS and its
treatment.
Direct medical costs were grouped into two groups: costs related
to SCS-related procedures, and costs incurred for other reasons
attributable to FBSS and its treatment. The first group included hos-
pital costs for lead implantation and replacement, implantation and
replacement of the INS, and lead removal after screening trial
failure. The remaining medical costs included costs related to
general practitioner (GP) consultations, specialist consultations and
SCS-related follow-up consultations, Emergency Room (ER) visits,
medical aids, laboratory and instrumental diagnostic examinations,
drug therapies, rehabilitation therapies, complementary therapies,
and hospitalizations. Direct non-medical costs included costs of
travel and/or accommodation to reach the healthcare providers,
and costs of formal care at home. Indirect costs were estimated in
terms of productivity loss of the family caregivers (e.g., spouse,
other relatives or friends) who helped the patients to manage their
condition.
Medical costs were quantified using tariffs and prices applicable
in Italy in 2009 and inflated to€2009 (25). Diagnostic Related Group
(DRG) tariffs (26) were used to value hospitalizations, apart from
those related to SCS procedures; the available DRG tariffs were not
sufficient to cover all the costs of the SCS procedures and devices,
requiring coverage through hospital budget. Therefore, in order to
realistically reflect the cost paid by the Italian National Health
Service (NHS) for these procedures, we used the hospitalization
costs obtained from a previous micro-costing analysis, where all
the cost items attributable to the hospitalization for the SCS proce-
dure were included: trial leads, equipment, personnel, energy
Figure 1. Schematic definition and duration of the observational period.
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consumption, cleaning, housing and food, etc. (27). The cost of the
SCS medical devices were provided by Medtronic (data on file,
Medtronic Italia) and applied to all the devices used during the
study, including devices from other companies. Other medical costs
were quantified using the official outpatient tariffs (28) for ER visits,
diagnostic examinations, rehabilitation therapies and specialist
medical consultations. Specific national tariffs (29) or market prices
(data on file, Medtronic Italia) were used for orthopedic aids,
depending on whether their cost was reimbursed by the NHS or
paid by the patients, respectively. Drug costs were quantified using
market prices (30). GP consultations were quantified using tariffs
that were estimated and published in literature (31). Complemen-
tary therapies, which are not reimbursed by the NHS, were quanti-
fied using the information on out-of-pocket costs reported by the
patients. Direct non-medical costs were quantified according to the
information reported by the patients. Indirect costs were assessed
using the human capital approach (32). With this approach, the loss
of productivity attributable to the disease and its consequences is
quantified in terms of absence from work, and is converted into
monetary terms by multiplying the time (days, hours) lost from work
by the subjects’ remuneration. Because most of the participants in
the study were older than 60 years or female, hence likely retired or
housewives without a paid job, we decided not to calculate
patients’ productivity loss, but to focus on the productivity loss of
their family caregivers. In particular, we obtained the mean remu-
neration per day by dividing the caregivers’ mean income by 220
working days resulting from the Italian National Institute of Statis-
tics (25). This remuneration per day was then multiplied by the
number of days reported as missed from work by the family care-
givers with a paid job.
Data Analyses
Baseline patient characteristics were described using absolute
and/or relative frequencies, while continuous variables such as time
and health status measures were summarized by mean values along
with standard deviation (±S.D) and 95% confidence interval (95% CI)
as dispersion measures. Costs and effects occurring before and after
the SCS intervention were estimated using proportions or means. In
particular, direct and indirect costs were calculated as mean
€/patient-year and reported along with the 95% CI. We used the
EQ-5D descriptive system to calculate utility scores by means of an
algorithm that uses population-based (social) values recently esti-
mated in Italy (33). QALYs were then estimated by multiplying the
utility scores by the time period (years) referring to the correspond-
ing HRQoL (32).
To obtain the disability rating from the ODI, we applied a specific
algorithm (21) grouping patients as follows: 1) 0–20% minimal dis-
ability; 2) 21–40% moderate disability; 3) 41–60% severe disability;
4) 61–80% crippled; 5) 81–100% serious.
To avoid possible bias in favor of the SCS treatment (e.g., if only
patients that benefited from this procedure remained in the
study), missing follow-up data on costs and benefits of patients
who did not continue the study due to screening trial failure or for
other reasons during the observational period, were managed
using the Last Observation Carried Forward (LOCF) approach (34).
In particular, for each patient that did not continue the study until
the scheduled end of observational period, we carried forward to
24 months the mean costs (except the upfront SCS related costs,
which were applied only at the start of the study), the mean
utility indexes and the ODI scores calculated from the last data
available.
Table 2. Patients’ Characteristics at Study Enrollment Time.
Mean or frequency ±S.D. 95% CI (lower-upper)
Total number of patients, N80 – –
Age (years) 58 13 54.9–60.7
Male, N(%) 40 – –
Education, (%)
Primary 49 – –
Lower secondary 34 – –
Upper secondary 15 – –
Graduate 1 – –
None 1 – –
Number of previous surgical interventions, N(%)
1 23 (33%) – –
2 31 (44%) – –
3 13 (19%) – –
4 3 (4%) – –
Not available 10 – –
Age (years) at pain onset 48 14 43.9–51.9
Time (years) between pain onset and recruitment 11 9 8.4–13.6
NRS 7.6 1.5 7.3–7.9
Oswestry class, N(%)
Minimal 0 (0%) – –
Moderate 7 (9%) – –
Severe 31 (39%) – –
Crippled 35 (44%) – –
Serious 7 (9%) – –
EQ-5D utility 0.421 0.303 0.353–0.488
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Comparisons between enrollment and follow-up were performed
using the parametric paired Student’s test or the non-parametric
paired Wilcoxon signed rank test for effect measures, depending on
the type and distribution of data, assessed using the Shapiro-Wilk
test. To compare utilities and costs between pre-SCS and post-SCS
we performed a non-parametric bootstrap with bias corrected and
accelerated (35).
The two following techniques were adopted in the economic
evaluation: Cost-Effectiveness Analysis (CEA) and Cost-Utility
Analysis (CUA) (32), which differ in how the benefits, or outcome
effects, results are calculated. Both techniques compare the two
programs by a ratio, named incremental cost-effectiveness ratio
(ICER) in the CEA, and incremental cost-utility ratio (ICUR) in the
CUA. They correspond to the ratio between the difference in costs
(numerator) and the difference in effects (denominator) of the two
treatment options, expressing the amount of incremental cost per
unit of additional effect. In particular, in the numerator we
included the difference between pre-SCS and post-SCS periods in
the mean of direct plus indirect costs. With regards to the denomi-
nator in the CEA, as a measure of clinical effects, we included the
incremental NRS given by the difference between pre and post
SCS periods in the mean of the Pain Numerical Rating Scale (NRS)
(20). In the CUA, the QALY was used as a parameter that estimates
individuals’ value of health.
The ratio comparison between the above mentioned numerator
and denominators resulted respectively in the incremental Cost/
NRS ratio (ICER) and the incremental Cost/QALY ratio (ICUR). Uncer-
tainty due to estimation of effects and costs was tested calculating
the cost-effectiveness acceptability curve with the non-parametric
bootstrapping approach (36). The ICER and ICUR analyses were con-
ducted by adopting the NHS, the patient and the societal points of
view. NHS in Italy is responsible for providing and paying for most
direct medical costs to manage the target patients (e.g., cost of SCS
surgery and devices, cost of drug treatment, cost of examinations
and medical visits). Patients generally pay for direct non-medical
costs (e.g., formal assistance and travelling/accommodation to
reach the healthcare providers) and sometimes also sustain out-of-
pocket costs for medical resources absorbed in the private sector.
The broadest perspective is the societal one, as it also includes the
two specified above.
All analyses were conducted using Stata SE 12 (StataCorp, College
Station, TX, USA) software.
RESULTS
A total of 80 patients were enrolled in the study. Patients’ sociode-
mographic, clinical and HRQoL description at enrollment are shown
in Table 2. After a mean of 46 days from enrollment, the patients
were implanted with a lead and observed during the screening trial.
Eight patients (10%) had a negative response to the screening trial.
After an average of 30 days from lead implantation, patients with a
positive test response were implanted with an INS. During follow-
up, the INS was replaced in 8 patients (10%; 1 within 12 months and
7 between 12 and 24 months), while lead dislocation occurred twice
in 1 patient, necessitating replacement (1.25% of patients; between
12 and 24 months). During the follow-up, 17 patients withdrew from
the study for the reasons specified in Figure 2.
The proportion of patients classified as “severe,” “crippled” or
“serious” according to the ODI classes (91% at baseline) decreased
significantly (z =5.754, p<0.0001) 24 months post-SCS treatment
(47.5%). Accordingly, the mean ODI decreased significantly
(t =7.9845, p<0.0001) from 61.6 at baseline to 42.4 after 24 months,
with statistically significant (t =6.9333, p<0.0001) improvement
first seen from 61.6 at baseline to 45.6 six months post-SCS
treatment (Table 3). A similar trend was observed with the mean
NRS clinical score and with the mean EQ-5D utility index (Fig. 3). The
mean NRS score decreased from 7.56 to 5.11 after 24 months post-
SCS (t =9.0026, p<0.0001), which is both clinically and statistically
significant. The mean EQ-5D utility index increased from 0.421 to
0.630 post-SCS (bootstrap-t method z =−6.27, p<0.001). Again, the
3 patients had adverse events
1 patient dropped out (consent withdrawal)
1 patient was lost to follow-up
1 patient died of stroke
2 patients had adverse events
2 patients were lost to follow-up
8 patients had SCS test failure
INS implantation
N = 72
Follow-up 6 months
N = 67
Follow-up 12 months
N = 62
Enrolment and lead implantation for
Stimulation Test Period
N = 80
1 patient died for infarction
1 patient had loss of therapeutic effect
2 patients were lost to follow-up
2 patients were lost to follow-up
1 patient had loss of therapeutic effect
Follow-up 18 months
N = 58
Follow-up 24 months
N = 55
Figure 2. Number of participants obser ved during follow-up.
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significant difference in these scores was observed in the first six
months post-SCS. The scores remained stable or increased slightly
in the following period.
Table 4 shows the mean amount per patient per year of health-
care resources utilized in the pre- and post-SCS periods, while
Table 5 focuses on the related mean costs. During the pre-SCS and
post-SCS periods, the overall cost to society was €6600 and €13,200/
patient-year respectively. In regards to the NHS perspective, while
€2600/patient-year were spent before SCS implantation, costs
increased significantly to almost €11,000/patient-year after SCS
(leads and INS). This increase was specifically generated by the high
cost of INS devices. Nevertheless, as shown in Figures 3 and 4, while
total costs run up in the first year after SCS interventions (around
€21,000 per patient in the 0–12 months post 12m post-SCS period),
they decreased in the following months. The costs to society were
even lower (€5500 per patient in the 12–24 months post-SCS
period) than those incurred before SCS implant (€6600/patient-
year). In particular, SCS-related costs were partially offset by savings
obtained in non-SCS-related medical costs (€1129/patient-year) for
the NHS (Table 5). Furthermore, cost savings were estimated for the
patients and their families (€813/patient-year) and in terms of pro-
ductivity gain for society as a whole (€682/patient-year). The utility
gained during the observational period corresponds to a QALY
increase of 0.173, generating a cost per QALY gained of €38,372 and
of €47,000, from the societal and NHS points of view, respectively.
The incremental cost per NRS gained corresponds to €2631 and
€3222, according to the NHS and societal points of view, respec-
tively (Table 6). Furthermore, when considering the patients’ point
of view, the SCS+CMM option is dominant, i.e., it is both more ben-
eficial and less costly than CMM alone, with a cost saving of €800/
patient-year.
The cost utility acceptability curve results (Fig. 5) suggest that SCS
implantation is cost-effective in 80% of cases from the NHS point of
view, and 85% of cases from the societal point of view, at the
willingness-to-pay threshold of €60,000/QALY, which was proposed
for Italy some years ago (37).
DISCUSSION
This real-world study compares from different perspectives
including the societal one, the effects and costs of SCS implant
added to CMM (SCS+CMM) in the treatment of patients with FBSS
with predominant leg pain and refractory to CMM to those of CMM
alone, using the patient, NHS, and societal points of view. Accord-
ingly, this observational study contributes insights on SCS based on
real-world data, as recommended by NICE in 2008 (17). This design
differs from the approach used in the PROCESS study (6–8,14,15), in
which two parallel groups of patients were randomized to
SCS+CMM or CMM alone and followed up in a controlled context.
The approach of this study can provide insights into clinical practice
and the benefits patients can actually achieve in a real-world
Table 3. Oswestry Disability Index.
Oswestry Disability Index Enrollment 6m post-SCS 12m post-SCS 18m post-SCS 24m post-SCS
Mean ODI (±SD) 61.6 (±15.0) 45.6 (±20.1) 45.5 (±19.6) 43.0 (±19.2) 42.4 (±20.1)
ODI classes, N patients (%)
MINIMAL DISABILITY (0–20) 0 (0.0) 9 (11.3) 8 (10.1) 7 (8.9) 10 (12.8)
MODERATE DISABILITY (21–40) 7 (8.8) 26 (32.5) 26 (32.9) 37 (47.5) 31 (39.7)
SEVERE DISABILITY (41–60) 31 (38.7) 25 (31.2) 29 (36.7) 17 (21.8) 19 (24.4)
CRIPPLED (61–80) 35 (43.7) 18 (22.5) 12 (15.2) 15 (19.2) 16 (20.5)
SERIOUS (81–100) 7 (8.8) 2 (2.5) 4 (5.1) 2 (2.6) 2 (2.6)
TOTAL* 80 (100.0) 80 (100.0) 79 (100.0) 78 (100.0) 78 (100.0)
*The total number of patients sum up to the total number of subjects expected to be living at each time period (i.e., excluding the two who died between 6
and 18 months), according to the LOCF approach used to manage missing data from those who dropped out or were lost to follow-up.
Figure 3. NRS and EQ-5D-utility mean (±SD) values during the observational period.
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uncontrolled setting, and has been demonstrated to provide insight
where the clinical superiority of one option over the alternative is
already established (38). Similarly, SCS treatment has been proven
to be effective in pain relief, improvement of HRQoL and disability in
patients that are refractory to CMM (6–9,11,39). Hence, all the eli-
gible patients enrolled during the present study were offered the
more effective option. With our approach, we could obtain com-
parative data attributable to a longer period than those available
from previous research. While we collected data on our patients for
one year before and up to 24 months after SCS, in the PROCESS trial
only six months of follow-up data were available for both groups of
treatment, since for ethical reasons the patients had the opportu-
nity to crossover from CMM to SCS beyond that time period.
A further strength of this study is the relatively high number of
participants, which is particularly notable for being the highest
enrollment so far from a single country.
Our results show that at baseline, patients had low levels of
health, while 24 months after SCS implantation, both clinical out-
comes and HRQoL demonstrated a clinically and statistically signifi-
cant increase. The most important changes were found within the
first six months of SCS treatment, and then maintained or slightly
improved during the following period.
Our results on benefits also are quite consistent with those
observed in previous clinical studies. In particular, patients who
received SCS implantation in the PROCESS study reported a signifi-
cant increase in the mean EQ-5D utility score from baseline (0.13) to
24 months (0.41), with the highest mean value (0.49) estimated
three months from SCS (7,15), as calculated using the UK tariffs.
Actually, these results would be similar to ours (0.07 at baseline and
0.40 at 24 months) if we applied, like the authors of the PROCESS
study, the UK social tariffs (40) to convert the responses from the
EQ-5D descriptive system into utilities. However, because our data
refer to Italian patients, the new and more accurate Italian-specific
social tariffs, which are higher than the UK social tariffs (33), were
applied to calculate utilities in our study, generating higher mean
scores (0.42 at baseline and 0.63 at 24 months) and a consequently
reduced gain between the pre-SCS and the post-SCS period. This
differential gain attributable to the different social tariffs depends
on the maximum limit of the utility index, which is bounded to 1.
Actually, the difference between two higher utilities attributable to
the two alternatives could be influenced by this limit and could be
lower than the difference generated by two lower utilities for the
same health states.
In regards to the ODI in the PROCESS trial, this score decreased
significantly from 60 at baseline to 42 after three months of SCS
therapy, while no further significant changes were found until the
end of the observational period (7). It is worth mentioning that even
though we did not observe outcomes at three months after the
intervention, it cannot be excluded that similar results in our study
were already reached at that time.
The costs for SCS-related procedures in this study, which corre-
spond to €9300 per patient per year paid by the NHS, is partially
offset by the decrease in other costs, resulting in a cost saving for
the patients of €800 per patient per year. Our results are not
directly comparable with those from previous research, since in
the PROCESS trial they were spread out on a much shorter time
period (6 months instead of 24 months). However, similarities in
costs estimated in different health care systems (i.e., with different
unit costs, different payers and payment procedures) generally
cannot be expected. Furthermore, unlike in the PROCESS study, in
which only medical costs from the third party payer were consid-
ered, we estimated also direct -non-medical costs, adopting
Table 4. Mean Number per Patient-Year of Medical Resources
Consumed.
Resource type Number/patient-year
Pre-SCS Post-SCS
Emergency Room Admissions 0.5 0.3
Medical Aids 0.8 0.3
Diagnostic Exams: 3.9 1.6
X-ray spine 0.8 0.5
MNR spine 0.8 0.2
CAT spine 0.6 0.3
Bone scintigraphy 0.1 0.0
ECO abdomen 0.2 0.1
EMG 0.4 0.1
Neurophysiological exams 0.1 0.0
Blood tests 0.8 0.4
ECG 0.0 0.0
Urodynamic exams 0.0 0.0
Urine analysis 0.0 0.0
Drugs* _ _
SCS-related Hospital Admissions: 0.0 1.0
INS implantations 0.0 0.5
LEAD implantations 0.0 0.5
INS replacements 0.0 0.1
Other (lead re-positioning/replacement) 0.0 0.0
Non-SCS Related Hospital Admissions: 0.3 0.2
Surgical admissions 0.1 0.0
Medical admissions 0.2 0.1
Complementary Therapies* _ _
Rehabilitation, Instrumental and
Analgesic Therapies:
23.6 14.1
Motor rehabilitation 6.2 2.2
Postural exercises 2.3 4.3
Assisted exercise in water 2.5 4.6
Massotherapy 2.5 0.9
Lymphdrainage 0.0 0.1
Pain electrotherapy 3.5 0.6
Electromagnetic therapy 2.0 0.1
Iontophoresis 0.5 0.2
Therapy with ultrasound 0.2 0.1
Laser pain therapy 2.2 0.1
Injection of therapeutic substances
in joints or ligaments
1.8 1.1
Mesotherapy 0.0 0.0
Epidural steroids injections 0.0 0.0
GP Consultations: 30.5 14.2
Ambulatory 24.3 11.5
Home visits 6.2 2.7
Medical Specialist Consultations: 4.9 1.5
Neurologist 1.8 0.6
Orthopedist 1.5 0.5
Neurosurgeon 0.6 0.2
Psychologist 0.0 0.0
Geriatrician 0.0 0.0
Physiatrist 0.9 0.2
Anaesthetist/pain therapist 0.3 0.1
SCS-related Follow-up Specialist Consultations: 0.0 1.6
*It would be not informative reporting synthetically the mean amount of
drugs and complementary therapies used, because the patients used
several types and dosages of drug treatments (e.g., opioid, antiepileptic,
analgesic, gastroprotective, antibiotic, anxiolytic, antidepressant drugs
etc.) and several types of complementary therapies (acupuncture,
homeopathic therapy, plantar therapy, pranotherapy).
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Table 5. Comparison of Direct and Indirect Mean Costs/Patient-Year Between the Pre-SCS and Post-SCS Periods.
NHS €/patient-year Patient €/patient-year Society €/patient-year
pre-SCS post-SCS° post-pre †bsppre-SCS post-SCS° post-pre †bsppre-SCS post-SCS° post-pre †bsp
Direct costs, thereof 2,653.6 10,797.6 8,144.0 −8.54** 2,128.1 1,314.9 −813.2 4.66** 4,781.6 12,112.5 7,330.9 −7.46**
Medical, SCS related procedures 0.0 9,273.1 9,273.1 −8.21** 0.0 0.0 0.0 – 0.0 9,273.1 9,273.1 −8.21**
INS implantation 0.0 5,857.2 5,857.2 −6.78** 0.0 0.0 0.0 – 0.0 2,335.8 2,335.8 −6.78**
LEAD impiantation 0.0 2,335.8 2,335.8 −1.74n.s. 0.0 0.0 0.0 – 0.0 5,857.2 5,857.2 −1.74n.s.
Explantation 0.0 84.9 84.9 −5.20** 0.0 0.0 0.0 – 0.0 84.9 84.9 −5.20**
INS replacement 0.0 938.8 938.8 −5.26** 0.0 0.0 0.0 – 0.0 938.8 938.8 −5.26**
LEAD replacement 0.0 56.5 56.5 −3.43* 0.0 0.0 0.0 – 0.0 56.5 56.5 −3.43*
Other medical (nonSCS)
related procedures
2,653.6 1,524.5 −1,129.1 7.12** 919.7 360.8 −558.9 6.82** 3,573.2 1,885.4 −1,687.8 9.25**
Emergency admissions 9.8 6.7 −3.1 1.79n.s. 0.0 0.0 0.0 – 9.8 6.7 −3.1 1.79n.s.
Medical aids 78.9 85.3 6.4 −0.27n.s. 67.3 30.3 −37.0 3.60** 146.2 115.6 −30.6 1.04n.s.
Diagnostic examinations 238.1 74.2 −163.9 10.08** 73.1 33.0 −40.1 2.32*** 311.2 107.2 −204.0 8.98**
Drugs 726.5 482.9 −243.6 2.75* 131.0 35.4 −95.6 4.77** 857.5 518.4 −339.1 3.50**
Hospitalizations 743.4 395.8 −347.6 3.98** 0.0 0.0 0.0 n.s. 743.4 395.8 −347.6 3.98**
Complementary therapies 0.0 0.0 0.0 – 268.6 74.0 −194.6 4.37** 268.6 74.0 −194.6 4.37**
Rehabilitation therapies 194.0 108.9 −85.1 1.40n.s. 0.0 0.0 0.0 – 194.0 108.9 −85.1 1.40n.s.
GP consultations 614.3 329.8 −284.5 5.68** 0.0 0.0 0.0 – 614.3 329.8 −284.5 5.68**
Medical specialist consultations 48.6 12.4 −36.2 7.37** 379.7 188.1 −191.6 6.74** 428.2 200.5 −227.7 7.32**
SCS-related follow-up
specialist consultations
0.0 28.6 28.6 – 0.0 0.0 0.0 – 0.0 28.6 28.6 –
Non-medical 0.0 0.0 0.0 – 1,208.4 954.1 −254.3 1.54n.s. 1,208.4 954.1 −254.3 1.54n.s.
Accommodation 0.0 0.0 0.0 – 68.1 29.3 −38.8 1.77n.s. 68.1 29.3 −38.8 1.77n.s.
Formal assistance 0.0 0.0 0.0 – 578.4 681.9 103.5 −0.52n.s. 578.4 681.9 103.5 −0.52n.s.
Travel 0.0 0.0 0.0 – 561.8 242.9 −318.9 5.06** 561.8 242.9 −318.9 5.06**
Indirect costs 0.0 0.0 0.0 – 0.0 0.0 0.0 – 1,785.2 1,103.3 −681.9 2.65*
Family caregiver’s loss of
productivity
0.0 0.0 0.0 – 0.0 0.0 0.0 – 1,785.2 1,103.3 −681.9 2.65*
Total 2,653.6 10,797.6 8,144.0 −8.54** 2,128.1 1,314.9 −813.2 4.66** 6,566.8 13,215.8 6,649.0 −4.39**
°Mean costs between 12 and 24 months post-SCS.
†Bootstrap-t test and corresponding p-value: *p-value <0.01; **p-value <0.001; ***p-value <0.05.
n.s., p≥0.05; –, not applicable.
Figure 4. Trend of direct and indirect (societal point of view) costs during the observational period.
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the patients’ perspective, and indirect costs, from the patient,
NHS, and societal perspectives. In particular, the importance of
including indirect costs or benefits in economic evaluations has
been recently underlined by Budd (41) and by Taylor and Taylor
(12).
A cost/NRS gain of €3200 and €2600, and a cost/QALY gain of
€47,000 and €38,372 were estimated for the NHS and the
societal perspectives, respectively. Cost-effectiveness or cost-utility
ratios do not themselves provide information on the efficiency of
treatments. This actually depends on the payer’s willingness to
consider those ratios as acceptable or not. In the United Kingdom,
the NICE recommends that interventions are normally considered
not cost-effective if the ICER is higher than 30,000£/QALY (about
€45,000/QALY gained) (17). With this threshold, SCS+CMM would
be cost effective in around 40% (NHS perspective) and 70% (soci-
etal perspective) of cases. However, according to the threshold of
€60,000/QALY gained, which was specifically proposed for Italy
some years ago (37), SCS+CMM would be cost effective in 80%
(NHS perspective) and 85% (societal perspective) of cases. With
these results, budget holders and practitioners can be more
aware of the positive balance between benefits and costs of SCS
compared to standard care, and can be guided towards better
decisions aimed to optimize the management of the target
patients.
This study has some potential limitations. First, although we
included indirect costs in the analyses, we did not consider patients’
loss of productivity because many of them were already retired or
housewives. However, even patients without a paid job could lose
productivity in terms of everyday activities they generally do, but
the available methods (such as the human capital approach) make it
very difficult to correctly quantify them. However, we can consider
our approach as conservative, assuming that similar to their family
caregivers, a gain in productivity also was achieved, although this
was not reflected in the analyses. Our approach is in line with the
results published a number of years ago on this topic (38), when the
extreme difficulties in quantifying productivity loss or gains in these
patients was shown.
A second limitation can be acknowledged because the pre-SCS
data were collected retrospectively, potentially causing some recall
bias, e.g., some cost items or amounts were forgotten or not pre-
cisely remembered by the patients. However, unlike a randomized
clinical trial, the collection of retrospective data in this observational
study was necessary to make comparisons between a pre- and a
post-SCS period. However, we do not expect relevant biases
from this approach, and chose 12 months as a retrospective time
period, since it was considered as reasonable for this category of
chronic and intensively treated patients, to obtain data reliable
enough to be compared with those collected during the prospec-
tive period.
A third limitation could be ascribed to the LOCF approach
adopted to manage the missing data of the 25 patients (31%) that
did not continue the study until the 24th month of follow-up. Actu-
ally, from our analyses applied using the LOCF approach we do not
expect results that are biased in favor of SCS, rather we consider our
approach conservative. From the data that were collected during
the follow-up, we estimated costs that were on average decreasing,
and utility index and ODI results that were on average increasing
after the SCS implantation. Accordingly, mean costs carried forward
to fill missing data were generally higher, and mean utility indexes
and ODI estimates carried forward were generally lower than those
estimated from the data available. In particular for the patients that
failed the SCS test, we assumed that the mean costs and health
indexes of these patients remained equal to those registered before
the test.
Table 6. Incremental Cost-Effectiveness and Cost-Utility ratios.
Perspective Cost (€) difference QALY difference ICUR NRS difference ICER
(post*—pre SCS) (post*—pre SCS) (€/QALY ) (post*—pre SCS) (€/NRS)
NHS 8,144 0.173 47,000 2.528 3,222
Society 6,649 0.173 38,372 2.528 2,631
*Mean cost between 12 and 24 months post-SCS.
Figure 5. Cost-utility acceptability curve for the SCS implantation according to the societal and NHS’s point of view.
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Fourth, although we observed the patients for up to 24 months,
we cannot consider this time horizon as sufficient to capture all
costs and consequences as a result of SCS. There are costs that are
not reflected, including those related to routine INS replacement for
battery depletion and possible hardware complications (e.g., revi-
sions for lead migration or fracture). The results obtained with a
decision analytic model built on the PROCESS findings and simulat-
ing costs and QALYs over a 15-year time horizon are promising, and
reflect the QALY gained in addition to costs over the full life of a
device (16). In our study, the SCS option is cost-effective already
after 24 months, which contributes to support decision processes
based on relatively short-term budget constraints.
CONCLUSION
In conclusion, the results of this study, which is novel in providing
real-world data on both outcomes and costs of the treatment
options compared suggest that in clinical practice SCS+CMM treat-
ment of FBSS patients refractory to CMM provides good value for
money, from the NHS, the patient, and society perspectives. These
results can help clinical practitioners, together with budget holders,
to arrive at more informed and appropriate decisions aimed to opti-
mize the management of FBSS patients responding to the selection
criteria used in this study. However, additional research conducted
for longer observational periods, using high quality routine health-
care data sources such as administrative databases or registries, can
provide more insights on the overall benefits and costs for the
patients and their families, for the third party payer and for the
society as a whole.
Acknowledgements
The authors would like to thank G. Beccagutti, M. Grifi and
D. D’Ostilio from Medtronic Italy and T. De Santo from Medtronic
EMEA Regional Clinical Center for their technical assistance. For the
support provided during data collection, the authors would like
to thank: C. Bonezzi, MD—Unità di Medicina del Dolore IRCCS
Fondazione Salvatore Maugeri, Pavia; B. CIoni, MD—U.O.
Neurochirurgia Funzionale e Spinale Policlinico Gemelli, Roma; G.
De Carolis, MD—U.O. Terapia del Dolore Azienda Ospedaliero
Universitaria Pisana, Presidio Opsedaliero “S. Chiara,” Pisa; G. De
Falco, MD—U.O. Fisiopatologia del dolore e Cure Palliative A.S.O.“S.
Croce e Carle,” Cuneo; E. Obertino, MD—U.O. Algologia e Cure
palliative A.S.O. “S. Croce e Carle,” Cuneo; MG Rusconi,
MD—Dipartimento Anestesia, Rianimazione, Cure Palliative e
Terapia del Dolore Azienda Ospedaliera “ G. Salvini.” The affiliations
are valid at the time of data collection.
Authorship Statements
All the authors contributed to the study design. Dr. Zucco
coordinated the study supported by Drs. Lavano and Costantini.
Drs. Zucco, Lavano, De Rose, Poli, Fortini, De Simone, Menardo,
Demartini, Cisotto, and Meglio recruited the patients and collected
the data. Drs. Zucco, Lavano, and Constantini interpreted the results.
Drs. Mantovani, Scalone, and Ciampichini assisted with data analysis
and results interpretation and prepared the manuscript with impor-
tant intellectual input and review from Drs. Zucco, Lavano,
Constantini, De Rose, Poli, Fortini, De Simone, Menardo, Demartini,
Cisotto, and Meglio. All authors approved the submitted version of
the manuscript.
How to Cite this Article:
Zucco F., Ciampichini R., Lavano A., Costantini A.,
De Rose M., Poli P., Fortini G., Demartini L., De Simone E.,
Menardo V., Cisotto P., Meglio M., Scalone L., Mantovani
L.G. 2015. Cost-Effectiveness and Cost-Utility Analysis of
Spinal Cord Stimulation in Patients With Failed Back
Surgery Syndrome: Results From the PRECISE Study.
Neuromodulation 2015; E-pub ahead of print. DOI:
10.1111/ner.12292
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