Cost-effectiveness analysis for trigeminal neuralgia: Cyberknife vs microvascular decompression
Neuropsychiatric Disease and Treatment
Cost-effectiveness analysis for trigeminal neuralgia: Cyberknife vs microvascular decompression
Rosanna Tarricone 2
Giovanni Aguzzi 2
Francesco Musi 2
Laura Fariselli 1
Andrea Casasco 0
0 Centro Diagnostico Italiano , Milan , Italy
1 Radiotherapy Department, Carlo Besta National Neurological Institute , Milan , Italy
2 Economic Evaluation Area, CERGAS Centre for Research on Healthcare Management-Bocconi University , Milan , Italy
vention. pression, trigeminal neuralgia Background/Aims: We present the preliminary results of a cost-effectiveness analysis of cyberknife radiosurgery (CKR) versus microvascular decompression (MVD) for patients with medically unresponsive trigeminal neuralgia. Methods: Direct healthcare costs from hospital's perspective attributable to CKR and MVD were collected. Pain level caused by trigeminal neuralgia was measured through the Barrow Neurological Institute pain intensity scoring criteria, at admission and after an average of 6 months follow-up. Results: 20 patients for both arms were enrolled, for a total of 40 patients. The two procedures resulted equally effective at 6 month follow-up, with different resources consumption: CKR reducing hospital costs by an average of 34% per patient. The robustness of these results was confirmed in appropriate sensitivity analyses. Conclusion: CKR resulted to be a cost-saving alternative compared with the surgical interTechnological innovation is considered as one of the principal factors of costs escalation in healthcare (Oh 2005). A field in which lot of technological progress has been registered in the last decades is radiotherapy. Radiotherapy began almost a hundred years ago with the discovery of X-rays and the first use of the natural radioactivity. The greatest challenge for radiation therapy is to cure the disease while controlling for side-effects. Theoretically, the simplest way to achieve this with radiation is to encompass all target cells with sufficient doses of radiation, while sparing surrounding Nowadays the new frontier is represented by stereotactic cyberknife radio surgery (CKR) that has been proven to be an effective treatment strategy for trigeminal neuralgia (TN) or “tic douloureux” (Lim et al 2005, 2006). Using noninvasive head immobilization and advanced image-guidance technology, the robotic arm of CKR dynamically tracks skull position and orientation during treatment, thereby ensuring targeting accuracy throughout the entire procedure (Romanelli et al 2005).
decision-making; cost-effectiveness analysis; Cyberknife; microvascular decom-
100,000 population per year, women are more frequently affected than men: 2.5 and
5.7 per 100,000 per year, respectively, while prevalence is approximately 15.5 per
100,000 population per year
(Wilkins 2002; Edlich et al 2006)
. Pain onset is usually
in the fifth through seventh decades of life. The disorder is characterized by unilateral,
episodic, shock-like or stabbing pain involving one or more
divisions of the trigeminal nerve. Patient activities of daily
living are often impaired by fear of experiencing chronic
episodes; something as simple and routine as brushing
the teeth, putting on make-up or even a slight breeze can
trigger an attack, resulting in sheer agony for the patient
(Pollok et al 2005).
Medical therapy (anticonvulsant medications, such as
carbamazepine, phenytoin or baclofen, clonazepam, gabapentin,
etc.) eliminates or significantly reduces the pain in
approximately 75% of patients, and is considered the treatment of
choice for incident cases of TN
the relief provided by medical therapy generally decreases
over time and is frequently resistant to multidrug regimens.
Moreover, many patients quit medical therapy because of
side effects, while drug intolerance is particularly common
in elderly patients
(Zakrzewska et al 2002)
Nonrespondent patients can be surgically treated
through microvascular decompression (MVD), an invasive
procedure that relieves the vascular compression on the
(Burchiel et al 1988; Barker et al 1996;
Broggi et al 2000; Sindou et al 2002; Theodosopoulos
et al 2002)
. Even though MVD represents the first choice
for those patients
(Fujimaki et al 1990; Lee et al 1997;
Apfelbaum et al 2000)
, less invasive procedures such as
(Taha et al 1995; Kanpolat
et al 2001; Tronnier et al 2001)
, glycerol rhizotomy
(Lundsford et al 1984; Saini 1987; Burchiel 1988; Young
1988; North et al 1990)
, balloon compression
(Brown et al
1993; Skirving et al 2001)
and gamma knife stereotactic
(Kondziolka et al 1996; Rogers et al 2000;
Maesawa et al 2001; Pollok et al 2002; Brisman et al 2002)
are preferred for elderly patients suffering from significant
comorbidities, or with recurrent facial pain after prior
(Pollock et al 2005)
In all those cases, CKR is a valid alternative to surgical
treatments for TN. However, in times of resource constraints,
costs and benefits of CKR are to be evaluated against its
closest comparator in order to provide decision makers with
relevant information as to the impact of the new technology
in the hospital system.
In order to perform that, a study on direct healthcare
costs and clinical outcomes of CKR vs. MVD for TN was
conducted, in collaboration with the Italian Diagnostic
Centre (CDI), where a CKR system has been installed
since July 2004, and the teaching clinic “C. Besta” National
Neurological Institute (Besta Institute), a highly specialized
neurological and neurosurgical centre in Milan, Italy.
The main objective of the study was to estimate the
incremental cost-effectiveness ratio of CKR vs. MVD for
patients non respondents to medical treatment.
Materials and methods
Study design and perspective
An observational, incidence-based cost effectiveness study
was designed to compare CKR vs. MVD in treating medically
unresponsive TN patients. The perspective taken was that of
the hospital and the costs included in the analysis were direct
healthcare costs, borne by hospital.
Patients were recruited in the two selected hospitals: Besta
Institute and CDI. More specifically, Besta Institute was in
charge of recruiting medically unresponsive TN patients
treated with MVD surgery, while CDI was in charge of
medically unresponsive TN patients treated by CKR.
All CKR patients were enrolled consecutively in the
period September 2004 (when CKR was first used) until June
2005, and then followed-up for a period of 6 month. MVD
patients were recruited retrospectively (February – August
2004) by going through medical records. Patients were
recruited in the study (both arms) if non respondents to
medical treatment (Barrow National Institute Scale scores
IV or V; see below), and were excluded if they suffered from
a typical pain, multiple sclerosis, younger than 18, or with a
follow-up duration of less than 6 months.
Outcome assessment referred to pain at baseline and at
follow-up (6 months) in the two groups of patients. Pain was
scored level I to V according to Barrow Neurological Institute
(BNI) pain intensity scoring criteria (Table 1)
(Rogers et al
. Outcome was evaluated by a standardized personal
questionnaire administered to patients by physicians. For
CKR patients, the questionnaire was prospectively
administered at follow-up visits. As to MVD, clinicians interviewed
the patients by phone, after a period not inferior of 6 month
from surgery. In both cases, the questionnaires were answered
uniformly, as the same investigators scored the pain intensity
in the two arms.
The full costing methodology was used to measure
resource consumption, and the approach used was the
bottom-up micro-costing. The latter is known to be the most
rigorous approach since it requires data collection for all
single components of care supplied by the hospital
et al 1992; Wolff 1998; Heerey et al 2002; Tarricone 2006)
In the micro-costing approach, estimation of costs can be
divided into three steps: the first is to identify the health inputs
involved in the procedure (personnel, drugs, disposables,
equipment, length of stay, etc.), the second is to estimate the
quantity provided, and the third step is to estimate the unit
costs for each input.
According to the full costing approach, costs of hospital
care were calculated summing up variable and fixed direct
costs exclusively associated with the operations of the wards,
and a fair share of overheads (generally administrative and
other central services). The latter was retrieved from the
hospitals’ accounting department: for Besta Institute,
overheads accounted for 18% of the direct costs, while for CDI,
overheads accounted for 15.4%.
As for MVD, direct fixed costs were represented by the
usage of the operating theatre and equipment, the cost of
labor (ie, surgical, anesthesiologist, and nursing teams), and
the hospital stay, while variable direct costs were drugs,
disposables, specialist visits, laboratory tests, and other
diagnostic investigations done during hospitalization and
As for CKR, direct fixed costs referred to capital
investment (CKR needs a separate bunker to be built or made
available), equipment, and labor costs. The latter was
calculated on the basis of the observed time actually worked by
each type of professional directly involved in the procedure
(nurse, physician, radiology technician, and health physicist),
multiplied by the cost per unit of time. Variable direct costs
were represented by disposables, specialist visits, imaging
tests (in particular, brain magnetic resonance imaging [MRI],
and brain computed tomography [CT] scans), for treatment
In order to assign a monetary value to diagnostic
procedures, the national fee-for-service system adopted by the
National Health Service to fund public and private
providers was used whenever full costs were not available from
the accounting department. Drug costs for antibiotics were
based on official ex-factory prices per unit in Italy
Italiana del Farmaco 2005)
A threshold analysis was performed in order to test the
robustness of cost differences between the two treatments.
Globally, 40 patients were enrolled in the study: 20 for each
arm. The sample characteristics are presented in Table 2.
CKR patients resulted 12 years older than MVD patients
(p-value 0.002). Gender distribution is similar, female being
the larger group in both the procedures (60% and 55%,
respectively). Fewer patients in MVD group had undergone
prior TN treatment compared with the CKR group (30%
for MVD and 40% for CKR). The most frequent treatment
before CKR was thermal rhizothomy (62.5%); followed by
MVD (37.5%), whilst for MVD patients the most frequent
procedure (67%) was another MVD.
At baseline, all patients ranked high in the BNI scale
but CKR patients were the highest with 85% in the V class
At follow-up, 90% of patients in both groups experienced
a reduction of severity, passing from levels V and IV to levels
I, II, or III; while only 10% of patients in both arms did not
experience a significant pain reduction, still non respondent
to medical treatment (Table 3). Nevertheless the difference
was not statistically significant (Chi-test p-value 0.05).
No adverse events or major complications were registered
in the two arms, such as toxicity. In CKR treatment group
the number of patients recording a follow-up BNI level III is
significantly higher than in MVD group (8 cases compared
with 2 cases), this could be explained by the fact that in CKR
arm baseline BNI level V was also more frequent than in
MVD arm (17 cases compared with 5 cases).
As for resources consumption, the results show that MVD
full cost is Euro 6,641.0 (SD 1,798.8) per patient while CKR
treatment is Euro 4,388.5 (SD 12.7) (Table 4). The difference
of Euro 2,252.5 is mostly explained by two factors: the cost
of the surgical procedure, which takes on average 3.5 hours
of operating theatre, compared with 70 minutes of radiation
for CKR, almost a standard procedure time for TN – thus
explaining the minimum full cost variance; and the cost of
hospital stay for MVD patients. Indeed, the length of stay is
on average 10 days per patient (±7.4 SD); while no hospital
stay is required for CKR patients, being it an outpatient
Notably, no drugs or laboratory tests are used specifically
for CKR procedure, whilst MVD required drugs for both the
surgical intervention and post-operation (on average 170
doses per patient over the observation period) and laboratory
tests (patients averaged 5 tests each). Outpatient visits per
patient were more frequent for CKR than for MVD during
the observation period (2.5 units vs. 1.1); on the contrary,
imaging tests resulted less frequent in CKR compared with
MVD (2.2 units vs. 3.1), nevertheless these were more
expensive ones (higher frequency of CT Scans, MRIs for
CKR vs. chest X-rays, ECGs for MVD).
A threshold analysis was performed in order to determine
how much key baseline variables would need to change
to equalize the resources consumption for the treatments
(Table 5). MVD costs would break even CKR costs if the
time of utilization of the operating theatre decreased by
71%: 1.0 hour instead of 3.5 hours. As to the length of stay,
CKR would still result cost saving even if MVD required no
hospital stay at all. Conversely, CKR costs would break even
MVD costs if the annual activity of the machine decreased
by 46%: 155 patients per year instead of 289, or equally, 402
fractions instead of 749.
Technological innovation is one of the main determinants of
healthcare costs and its rapid changes require decision makers
to take allocative decisions in relatively short time. Economic
evaluations are intended to support the health-related decision
making process by informing decision makers as to allocative
decision aimed at maximizing patients’ health by estimating
1997; Apfelbaum et al 2000), nevertheless radio surgery
cyberknife system could represent a feasible first line option
for TN in the close future, once its effectiveness has been
robustly investigated, being it less costly than MVD, as
emerged from this study.
Europe is experiencing a fast growth of CKR technology:
eight CKR systems are already working in its countries at
the time of the study, but – with the exception of the present
study – no economic evaluation analysis has been done on
CKR and its potential applications.
Economic evaluation analysis could be useful as to decide
whether and how much of the technology the European
countries can afford and for what indications it results to
be most effective and efficient. The present study certainly
goes in this direction and represents an important basis for
building further and wider evidence.
This study has some limitations. The two groups of
patients are not directly comparable, therefore it is not
possible to conclude that CKR is as effective as MVD.
CKR group was significantly older than the MVD group,
even if age has not been found to be a predictor of
success/failure for either radio surgery or MDV procedures
(Pollock et al 2005)
, and patients in MVD group had
typically less severe facial pain at baseline. The difference in
patients’ characteristics is explained by the fact that CKR
is not seen as an alternative to MVD for the time being
but, rather, as a second line strategy whenever MVD is not
possible to deliver.
The cost analysis does not include those associated with
patients’ productivity losses during admission time, and
informal care. Had these costs been evaluated, the difference
between the two treatments would have resulted even bigger
in favor of CKR, being an outpatient service.
Finally, more data are needed to assess the effectiveness
of CKR considering follow-ups longer than six months
in order to account also for recurrent trigeminal pain. The
results obtained can be considered as preliminary, and would
need to be further verified by larger samples and longer
follow-ups as long as the technology develops.
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