Clinical Trial Details
— Status: Active, not recruiting
Administrative data
| NCT number |
NCT05448092 |
| Other study ID # |
012022 |
| Secondary ID |
|
| Status |
Active, not recruiting |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
June 1, 2022 |
| Est. completion date |
June 26, 2025 |
Study information
| Verified date |
December 2023 |
| Source |
Unit of neurosurgery, Departement of Neurosciences, University of Torino |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
The study goal of RELApSE is to evaluate the relationships between radiological data and
patients reported outcome. Restoration of Sagittal alignment and Pelvic Index (PI)-Lumbar
Lordosis (LL) mismatch is closely associated with a better outcome in spinal deformities,
while there is still a lack of consistent evidence regarding short-segment arthrodesis for
lumbar degenerative pathology.
Over the past 10 years, an increasing number of publications reported associations between
the presence of PI-LL mismatch, reduced lumbar lordosis, increased pelvic tilt, and outcome
of lumbar arthrodesis for degenerative lumbar disease. Other authors, on the other hand,
reported an absence of correlation between the same parameters and clinical outcome. In
addition, several authors have been reported evidence regarding association of adjacent level
disc degeneration and elevated pelvic tilt, persistent PI-LL mismatch and altered LL4-S1/LL
ratio. Also on this aspect, other studies identify different elements as predisposing factors
for junctional pathology. The definitive value for lumbar degenerative pathology of these
aspects in relation to the surgical outcome remains to be clarified without consolidated
evidence. The RELApSE study is the first prospective and multicenter study on these topics.
Starting from a very heterogeneous population in terms of clinical conditions, pathology and
surgical treatment options, the study methods is to make the population homogeneous on some
data available in all patients end that can be analyzed independently. These data are: pelvic
parameters (pelvic incidence, pelvic tilt, sacral slope), segmental lumbar lordosis (LS),
global lumbar lordosis (LL), PI-LL mismatch and L4-S1/LL lordosis ratio; clinical results
based on administered questionnaires (Oswestry disability index, Short Form-12) and overall
outcome assessment at FU (6 point scale: excellent (completely resolved symptoms), good (good
clinical improvement, minor symptoms), fair (improvement compared to preoperative but still
with relevant symptoms), unchanged (symptoms similar to preoperative), negative (worsening of
symptoms compared to preoperative); severely worsened (reduction of personal autonomy
compared to preoperative due to neurological deficits); occurrence of symptomatic junctional
pathology (yes / no), need for surgical revision of the operated level (yes / no) or of the
adjacent level (yes / no).No interference is foreseen on the patient's diagnostic-therapeutic
path or technical treatment options chosen by partecipating surgeons. Furthermore, no form of
experimentation with techniques or materials is envisaged. Data collection is prospective in
the context of normal clinical activity.
Description:
BACKGROUND AND STUDY RATIONAL
Degenerative pathology of the lumbar spine is very frequent affecting approximately 5.7% of
the European population. Arthrodesis is a frequently adopted surgical treatment with
different technical option, accounting for 30,000 procedures performed every year in Italy
(trovare riferimento bibliografico) and over 450,000 procedures performed in the United
States. However, lumbar vertebral arthrodesis for degenerative disease still remains burdened
by clinical problems with significant occurrence of negative results consisting in lack of
clinical improvement, late symptoms relapse or even clinical worsening. The evidence based
medicine on this topics is still insufficient and generally does not exceed evidence class B.
The available guidelines are mainly based on level II studies and only offer recommendations
that may support practitioners in clinical activity. Thus, surgical treatment of lumbar
degenerative disease still remains extremely heterogeneous also considering the number of
technical options available for the single pathology. Lack of standard of care leads to
treatment stratetegies based on institutional, departmental, or personal experience, planned
on inconsistent scientific evidences. The introduction in the clinical practice of the
sagittal balance assessment, the evaluation of the meaning of pelvic parameters and of
spino-pelvic mismatch has also offered a new evaluation criterion for lumbar degenerative
pathology and for outcome of short lumbar arthrodesis surgery. Restoration of Sagittal
alignment and Pelvic Index (PI)-Lumbar Lordosis (LL) mismatch is closely associated with a
better outcome in spinal deformities, while there is still a lack of consistent evidence
regarding short-segment arthrodesis for lumbar degenerative pathology.
Over the past 10 years, an increasing number of articles reported about associations between
the presence of PI-LL mismatch, lumbar lordosis, pelvic tilt and outcome of lumbar
arthrodesis for degenerative lumbar disease or occurrence of adjacent segment disease (ASD. A
recent systematic meta-analysis highlighted a strong relationship between LBP and reduced
lumbar lordotic curve especially when petients were analyzed with age-matched healthy
controls. In 2000 Lazennec et al firstly analyzed the relationship between radiological
parameters and postfusion pain focusing attention on the vertical position of the sacrum.
Patients with pain persisting after arthrodesis showed both reduced SS and increased PT with
PT reaching almost twice the normal value. Authors postulated that " achieving a strong
fusion should not be the only goal. Appropriate position of the fused vertebrae is also of
paramount importance to minimize muscle work during posture maintenance". An increased LL and
SL was associated with better outcome (VAS, ODI) after unilateral instrumented TLIF
single-level lumbar degenerative disease and after 1 level or 2-level PLIF for 2-level (L3-L4
and L4-L5) degenerative spondylolisthesis. Hioki et al described a positive linear
correlation between increase in lordotic angle and improvement of JOA score at final outcome
evaluation after two level PLIF.
Furthermore, reduction of pelvic tilt was associated with better outcome after PLIF surgery
for spondylolisthesis as well as sacral slope increased to more than 30° after single level
TLIF. The review by Le Huec et al. suggested that the increase in PT after surgery is
associated with significant low back pain while the restoration of a normal PT results in a
good clinical outcome. The study of Aoki et al was the first investigating influence of PI-LL
mismatch on postoperative residual symtoms after 1 or 2 level TLIF. Larger PI-LL mismatch was
significantly associated at 1 year follow-up with VAS for LBP, leg pain and leg numbness but
not with postoperative disability (ODI). Detailed VAS analysis highlights association of
mismatch with stending low back pain but not with LBP while sitting or in motion. Worse ODI
scores were associate at 2 years follow-up with PI-LL mismatch after four-level lumbar fusion
surgery (L2-S1); moreover, a significant correlations between PI-LL mismatch and improvement
in both JOA score-VAS for LBP at 2 year follow up has been described for patients with lumbar
degenerative scoliosis treated with short segment fusion (1, 2 or 3 level TLIF) at the
affected levels. Radovanovic et al reported a better patient reported outcome in patients
with SVA less than 50 mm. Patients with an SVA ≥ 50 mm presented reduced lumbar lordosis with
increased mismatch and had a worse SF-36 PCS and Oswestry Disability Index (ODI; p = 0.043)
as well as more back pain.
Better improvement of PI-LL mismatch with reduced PT and higher LL was found in patients
without residual back pain after OLIF procedure and similarly a significant linear
association with Oswestry Disability Index was reported for independent variables LL, delta
LL and PI-LL status after OLIF for degenerative disc disease.
A cutoff value of 27,5 ° for preoperative PI-LL mismatch is reported as a negative factors
for outcome of patients underwent second PLIF surgery for ASD and as predisposing factor for
need of subsequent long corrective surgery.
Finally, sagittal malalignment with PI-LL mismatch greater than 10° was also associated with
occurrence of pseudarthrosis.
On the contrary, HSU et al reported no correlation between LL or LL restoration ratio and the
outcome of patients undergoing PLIF for degenerative spondylolisthesis while JIA et al
concluded that PI-LL mismatch is not associated with clinical outcome (VAS, ODI) after
MIS-TLIF for lumbar stenosis (25). A comparative study between ALIF and PLIF also showed no
relationship between LL and patients outcome. A 2017 systematic review by Rhee et al. select
only 4 article for final statistical analysis and point out the lack of well-powered studies
on this topic. No statistically significant improvement in both ODI or VAS was related to
restoration of segmental lordosis. So correction of malalignment does not seem to yield
clinical improvements for lumbar short arthrodesis.
A recent large retrospective study show that patient outcomes in short-segment lumbar fusion
for degenerative lumbar disease are equivalent in patients with and without a postoperative
PI-LL mismatch at 1 year follow-up. No differences between groups in preoperative,
postoperative or delta outcome scores (PCS-12, ODI, VAS back, VAS leg) were noted. PI-LL
mismatch was not found to be an independent predictor for patient reported outcome on
multivariate analysis (P> 0.05). This study suggest that limited surgery adressed to focal
neurological disease has equivalent outcomes of corrective surgery.
Adjacent segment degeneration (ASD) after lumbar arthrodesis, both clinical and radiological,
is a well known problem. Many studies in the literature discuss about this topics and several
aspects were analyzed as causes or risk factors. Prospective study by Ekman shows that fusion
accelerates occurrence of degenerative discopathy at the adjacent level compared with natural
history. Reported incidence have a wide range between 2,62 and 84% with prevalence of
proximal level and main associated factors were old age, body mass index (BMI), previous
degenerative disc o facet disease, type of pathology, multiple-level fusio, male,
intraoperative superior facet joint violation, laminectomy, sagittally oriented facet joint
angle, PLIF and progressive fatty degeneration of the multifidus muscle. In 2001 Kumar et al
firstly reported significant association of ASD and C7 sagittal plumb line. A vertical sacrum
was highly associated also with ASD even with normal C7 plumb line. Sacral inclination was
considered an important aspect of sagittal alignment as expression of compensation mechanism.
Several authors reported a correlation between ASD and reduced lumbar lordosis as a major
independent factor or in association with other factors. Also reduced postoperative segmental
lordosis was associated with occurrence of ASD. Soh et al and Bae et al. suggested that the
most important factor for prevention of ASD is restoration of segmental lordosis. Kim KH et
al described association between reduced segmental lordotic angle and symptomatic ASD in
isolated L4-L5 spondylolisthesis treated with interbody fusion and pedicle screw fixations.
Again the pre-postoperative segmental lordosis delta was reported as a major risk factor for
ASD especially with early onset (50,76).
Relationship between pelvic parameters and ASD was also studied. Nakashima et al. identified
high degree of pelvic incidence as a risk factor for early onset radiological ASD probably in
relation to the reduced probability of obtaining appropriate lordosis after surgery. This
association was also confirmed by a recent meta-analysis.
Some authors found a significant reduction of sacral slope angle in patients with occurrence
of ASD and similarly Di Martino et al reported in ASD patients significantly lower SS and
consequent higher PT values related to pelvic retroversion and hyperlordosis compensation
mechanism. In this study Authors defined SS value below 39° or PT above 21° as a strong risk
factor for occurrence of symptomatic ASD (relative risk 1.73 for SS and 3.663 for PT).
Another study confirmed that a PT greater than 24.1 ° can be considered predictive of ASD
after lumbar TLIF (77). Also preoperative PT with 22.5° cutoff was strongly associated with
ASD (risk 5.1 greater).
A meta-analysis by Phan et al conclude that development of ASD may be predicted from
evaluation of Spinopelvic alignment paremeters (PT, SS, PI-LL mismatch, and LL) in patients
with lumbar fusion for degenerative disease. An elevated PI-LL mismatch havee been reported
closely associated with development of symptomatic ASD or radiological ASD. A PI-LL mismatch
greater than 15° was identified as significant independent risk factors for radiographical
ASD also in patients with L5-S1 spondylolytic spondylolisthesis treated with single level
PLIF.
Morover Wang et al reported strong association between symptomatic ASD after lumbar fusion
and greater PI-LL mismatch but identified different PI-LL mismatch cutoff in patiens below 60
years (PI-LL >10°) and older patients (PI-LL > 20°) to reach statistical significance. The
authors hypothesize that the ideal correction of LL may vary with increasing age. Rothenfluh
et al reported 10-times higher risk of ASD occurrence for patients with elevated PI-LL
mismatch (> 10°). Patients with ASD have higher PI, higher PT and lower lumbar lordosis.
Authors conclude that when fusion surgery is carried out without treatment of intrinsic
deformity and PI-LL mismatch patients present elevated risk for ASD.
Finally lumbar distribution index (LDI=L4-S1 lordosis/lumbar lordosis x 100) was strongly
associated with occurrence of ASD: patient with reduced distal L4-S1 lordosis and consequent
low LDI present greater risk of developing ASD (36). Kim et al reported frequent occurrence
of ASD in patients with LDI less than 50% also when PI-LL was satisfactorily corrected to
less than 10°. Obtaining an appropriate postoperative LDI in L4-S1 may have a crucial role in
the prevention of ASD.
In both clinical analysis and mechanistic simulation environment the increased loading and
biomechanical shear forces at fusion adjiacent level have been postulated and discussed for
patinets with PI-LL mismatch. These experimental data offer a further element in the
evaluation of association between ASD occurrence and sagittal malalignment.
On the contrary, some authors have highlighted the absence of a relationship between ASD and
sagittal alignment. Anandjiwala et al reported that LL is not a risk factor for ASD
occurrence while Chen et al reported no differences in lumbar lordosis between patients
presenting ASD and those who did not. Masevin et al analyzing the risk factors for ASD
reported the absence of a role of the sagittal balance in short fixations for which the only
risk factor is preoperative degenerative changes. A meta-analysis by Wang et al, based on 19
papers, showed that postoperative PT and SS are not associated with ASD occurrence.
Multivariate analyses showed that segment distraction was the most significant risk factor
after L4-L5 PLIF or only multilevel surgery associated with high rate reoperation. Finally a
recent study on the prognostic factors of ASD after L4-L5 fusion does not consider sagittal
alignment at all, suggesting that these aspects are still underestimated by many surgeons.
The analysis of these literature data shows sparse and variable evidence and highlights how
clarification and greater understanding on this argument is still needed, evoking the need
for methodologically correct and high-level studies. In fact, most of the works in the
literature are retrospective, generally monocentric, based on small populations and often
address partially the topic evaluation. Certainly, the generation of standards based on
scientific evidence remains very difficult for degenerative pathology of the lumbar spine.
However, the evaluation of data collected on a sufficiently large population in a
prospective, uniform and methodologically correct manner could allow to highlight and
underline some associations. This prospective and multicentric study is based on the
possibility of comparing an heterogeneous population by pathology and different surgical
technical options on some homogeneous clinical and anatomo-radiological measures. The data
analysis will contribute to the understanding of the value that global lumbar and segmental
lordosis, distribution of lordosis, pelvic tilt and PI-LL mismatch may have, as independent
factors, on clinical outcome in lumbar degenerative pathology and on occurrence of adjacent
segment disease. Consequently, it will focus and enhance at least some rational aspects of
lumbar arthrodesis such as, in particular, the need to adopt surgical strategies aimed to
restoring segmental lordosis and correcting the sagittal profile. Carrying on the follow-up
for several years, the study will finally also provide information on long-term evolution and
in particular on the occurrence of symptomatic adjacent level degeneration.
STUDY DESIGN
3.1) Type of study
RELApSE is a purely observational study. No interference is foreseen on the patient's
diagnostic-therapeutic path or on the technical treatment options of the chosen by the single
surgeon participating in the data collection. Furthermore, no form of experimentation with
techniques or materials is envisaged. Data collection is prospective in the context of normal
clinical activity. The study is not sponsored.
The study goal is to evaluate the relationships between radiological data and patients
reported outcome. The study method is to make the population comparable and homogeneous on
some data (and related pre-postoperative delta) Starting from a very heterogeneous population
in terms of clinical conditions, pathology and surgical treatment options, the study methods
is to make the population homogeneous on some data available in all patients end that can be
analyzed independently. These data are: pelvic parameters (pelvic incidence, pelvic tilt,
sacral slope), segmental lumbar lordosis (LS), global lumbar lordosis (LL), PI-LL mismatch
and L4-S1/LL lordosis ratio; clinical results based on administered questionnaires (Oswestry
disability index, Short Form-12) and overall outcome assessment at FU (6 point scale:
excellent (completely resolved symptoms), good (good clinical improvement, minor symptoms),
fair (improvement compared to preoperative but still with relevant symptoms), unchanged
(symptoms similar to preoperative), negative (worsening of symptoms compared to
preoperative); much worsened (reduction of personal autonomy compared to preoperative due to
neurological deficits); occurrence of symptomatic junctional pathology (yes / no), need for
surgical revision of the operated level (yes / no) or of the adjacent level (yes / no).
3.2) Study endpoints
Primary end-point: analysis of the relationship between clinical results (ODI, SF-12, global
outcome) and pelvic parameters, overall lumbar / segmental postoperative lordosis / ratio
L4-S1-overall lumbar lordosis (delta pre-postoperative-follow-up values) in the hypothesis
that the persistence of elevated PI-LL mismatch, reduced LL or altered pelvic parameters
(pelvic tilt) may represent independent negative prognostic factors for patients reported
outcome, occurrence of symptomatic junctional pathology and need for surgical revision.
Secondary end-points: 1) Comparison between different interbody fusion techniques (Anterior
Lumbar Interbody Fusion (ALIF) vs Posterior Lumbar Interbody Fusion (PLIF) vs Transforaminal
Lumbar Interbody Fusion (TLIF) vs Extreme lateral Lumbar Interbody Fusion (XLIF)) in terms of
increasing segmental lordosis; 2) Comparison between different interbody fusion techniques
(ALIF vs PLIF vs TLIF vs XLIF) in terms of changing the global lumbar lordosis, spino-pelvic
parameters and PI-LL mismatch; 3) Long-term evaluation of lumbar lordosis stability in
relation with occurrence of subsidence or pedicular screws failure.
3.3) Sample size e statistical considerations
The sample size is assessed on in relation to the primary objective. We suppose we want to
compare the variation in clinical parameters before and after the intervention (ODI, SF-12:
MCS, PCS, global outcome) between the groups finally identified by the presence / absence of
LL-PI mismatch. In the hypothesis of no difference, the data necessary for the calculation
can be referred to as reported by Divi et al (ref). As regards to MCS-12, the study reports a
delta equal to 4.1 in subjects without mismatch and equal to 4.1 in subjects with mismatch,
consequently no difference is expected and this parameter is not included in the calculation
of sample size. In relation to ODI, the study reports a delta equal to -22.8 in subjects
without mismatch and equal to -20.9 in subjects with mismatch (hypothesized sd equal to 5).
For PCS-12, the study reports a delta equal to 9 in subjects without mismatch and equal to 10
in subjects with mismatch (hypothesized sd equal to 2). With a significance of 0.05, a test
power of 0.95, assuming to compare the two samples using a two-tailed t test, a minimum
sample size of 362 subjects is required. Since the study is multicentric, the enrollment of a
total of 500 patients is considered to be an exhaustive objective. The evaluation of the
secondary end-points, which is not essential, will be carried out on an the same population
sample.
4) PROCEDURE
4.1) Inclusion criteria
All patients with the following requirements can be included in the observational study
1. undergoing an instrumented lumbar arthrodesis operation at 1, 2 or 3 levels.
2. age between 18 and 75 years.
3. agree of inclusion in the study with subscription of informed consent, available for 5
years follow-up, including phone interviews.
4. availability of adequate preoperative radiological documentation: CT or MRI of the
lumbar spine; standing lumbar spine x-ray performed in a neutral position in which the
pelvic parameters (pelvic incidence, pelvic tilt) and all lumbar segments can be
correctly assessed
5. availability of adequate and comprehensive clinical information including the presence
of preoperative ODI (Oswestry Disability Index) and SF-12.
6. availability of adequate information regarding surgery
7. availability of postoperative radiological documentation: lumbar spine X-ray with the
same requirements as point 4 performed in the postoperative period and at 1 year
follow-up.
8. availability of adequate and comprehensive clinical information including ODI score
(Oswestry Disability Index) and SF-12 questionnaire at follow-up. The minimum follow-up
for each patient included must be 12 months, to be continued for a total of 5 years.
4.2) Exclusion or Withdrowal criteria
Patients who, although already enrolled, do not meet the inclusion criteria will be excluded.
Patients who, regardless of age, have a life expectancy of less than 5 years due to
associated diseases, must be excluded from the study. Patients who, for various reasons, have
to withdraw their consent to be included in the study in writing will also be excluded. There
are no other exclusion criteria.
4.3) Informed Consent
The patient will be asked to express informed consent, in coded and anonymous form, for
acceptance of study inclusion. At the same time, consent will be acquired for the processing
of personal data in relation to the current italian privacy law. Consents must be acquired
and preseved from Surgeon performing artrhodesis. Finally, the patient's consent will be
acquired also to be contacted, again anonymously, by the Referring Doctor together with
independent examiners for a remote telephone follow-up. The original informed consent forms
containing the patient's personal details and the identification code assigned must be kept,
for privacy reasons, only by the Referring Doctor. The patient will be given a copy of the
consents containing his / her study identification code with which he will eventually be
contacted by phone anonymously. the patient will also receive an information form with the
aims and characteristics of the study.
4.4) Data collection
For the recruited patients, all the data required (preoperative, postoperative, follow-up) in
the data collection form (CRF) must be entered together with the patient code:
- general: age, sex, smoking habit, previous diagnosis of osteoporosis
- surgical data: type of surgery performed, type of arthrodesis performed, date of
surgery, used cages material, used cage lordosis degrees, intraoperative adverse events
- clinical data: diagnosis (type of degenerative disease), duration of symptoms, presence
of claudication or radicular pain, presence of L5 sacralization L5, ODI score, SF-12
PCS, SF-12 MCS, days of postoperative hospitalization. ODI score (Oswestry Disability
Index) and the SF-12 questionnaire (general health status) are used for clinical and
outcome evaluation.
- radiological data: overall lumbar lordosis, segmental lordosis of all lumbar levels,
pelvic incidence, pelvic tilt, sacral slope. The values will be calculated according to
the criteria reported by Duval-Beaupère. From these data, theoretical pelvic tilt will
be subsequently calculated with reference to Vialle's formula (PT = PI x 0.37 - 7),
pelvic delta tilt (PT - theoretical PT), PI-LL mismatch (expressed on the calculated
ideal lordosis such as PI + 10 °) L4-S1 lordosis/LL lordosis (percentage). The vertical
sagittal axis (SVA C7-S1) is not considered in this study in relation to the need to
obtain teleradiography of the entire spine, a non-routine and normally not required
examination.
All images must be centralized for measurements anonymously and coded as reported below.
(4.5). All radiological data, measured as angles or derived numbers, will be calculated by
independent data managers recruited in the form of volunteers among medical specialists or
fellows (see Study Board). The calculation of the angle values will be done by performing
three successive measurements on the same radiological image by 3 independent examiners not
involved in the surgical management. Subsequent calculation of the average of the 9 values
obtained. The calculation of pelvic angles and parameters can be done with freewere SurgimapÒ
software developed by a group of vertebral surgeons and engineers to support anatomical
evaluation and surgical planning (Nemaris Inc.TM innovation, New York, NY, USA). The software
can be downloaded freely from the website www.surgimap.com where all the policies and
conditions of use are visible.
4.5) Privacy protection
In order to ensure patient privacy, the data will be transmitted completely anonymously.
Patients will thus be identified by a code consisting of the investigator's reference and a
progressive number (eg. FIRENZE001, SIENA002, BERGAMO003 etc). The identification code will
be attributed to the individual investigator at the time of joining the study and reported in
the letter of intent. The list of investigator codes is shown in chapter 1.2 of this
document. Likewise, the transmission of radiological images will be performed through private
images of the patient's data in jpg or dcm format. The files will be given a name consisting
of the patient's code followed by the type of exam (eg FIRENZE001RXpre).
4.6) Follow-up
All patients recruited will have to be followed up, unless the patient withdraws consent
explicitly, for the entire duration of the study initially planned for 5 years. The follow-up
evaluations must include the acquisition of all clinical data indicated in the data
collection form (CRF-FU) including ODI and SF-12 evaluation questionnaires (results to be
reported in the CRF-FU). These data together with the patient code are: months of follow-up,
clinical outcomes, presence of radicular pain, presence of claudication, presence of
neurological deficits, ODI, SF-12 MCS, SF-12 PCS, technical errors, complications, hardware
faillure, need for reoperation, occurrence of junctional pathology, intervention-junctional
pathology time.
The follow-up includes postoperative clinical evaluation 3 months after surgery, 1 year and
up to 5 years annually. Any additional evaluation will be dictated only by clinical needs and
must be added to the follow-up with related time of occurrence. Follow-up is the
responsibility of single investigator. A telephone assessment may be performed on patients
who are not available for outpatient assessments or who cannot be reached by completing ODI
and SF-12 by interview.
The follow-up must also include the acquisition of a lumbar spine standing X-ray (methods
indicated in point 4.1, 4.4) at 3 months and 12 months as normally suggested by good clinical
practice. According to the literature, the implant settlement and cages subsidence occur
mainly in the first 12 months (39,40). Further or subsequent radiological examinations will
be eventually and exclusively performed for clinical needs (persistent symptoms, clinical
worsening)
4.7) Statistical analysis
Quantitative variables will be expressed using means and standard deviations (medians and
quartiles when appropriate). Qualitative data will be expressed as a raw number and a
percentage of the population. Comparison of proportions were performed with Chi-squared test
for categorical variables. Continuous variables will be compared using the Student t-Test and
ANOVA (or non-parametric analogue). The correlation between numerical variables will be
evaluated through Pearson's correlation coefficient and relative test (or similar Spearman
coefficient and test, if appropriate). Any linear or non-linear logistic regressions will be
evaluated for the relationship between lumbar or segmental lordosis, pelvic parameters and
clinical data. Further statistical analyzes may be evaluated during the data evaluation.
Depending on the results provided by the analyzes described, it may be appropriate to set up
mixed effects models to evaluate the longitudinal trend of the study parameters. The possible
implementation of non-parametric models of supervised machine learning (e.g. random forest,
SVM) will be evaluated to verify the actual predictive power of the variables under
consideration with respect to the clinical evaluation. Statistical significance was defined
with a p-value < 0.05.
Due to the nature of the multicentre study and the high sample size, it is planned to create
an interactive report (dashboard) for viewing the statistical results obtained.
5) METHOD OF IDENTIFICATION OF PARTICIPATING SURGEONS
The participants were identified in the Italian context among orthopedists or neurosurgeons
with proven experience in the field of vertebral surgery by direct invitation from one of the
members of the steering committee.
Surgeons who have chosen to participate in the study are required to sign a letter of intent
to underline the commitment required and the roles of the investigator. Each participating
investigator is required to obtain approval from their relevant ethics committee.
6) METHOD OF PATIENTS RECRUITING
Investigators will recruit patients in the context of their regular clinical and surgical
activity. Recruitment must be prospective and the patient must be enrolled prior to surgery
in order to avoid selection bias related to clinical result. Each participating surgeon will
be required to recruit A minimum of 20 complete and evaluable patients is requested to be
included in the investigators while the number of patients enrolled should not exceed 60
cases for single surgeon. This limits are aimed at homogenizing the contribution of
individual investigators and avoiding, within the enrolled population, excessive imbalances
and discrepancies related to the contribution of individual surgeons. Once the programmed
sample size has been reached, recruitment will be closed while careful follow-up must
continue until the study is closed (duration 5 years).
7) ETHICAL CONSIDERATIONS
The study is observational and not sponsored and does not involve any change in the
diagnostic, therapeutic and follow-up path of the patients involved. The study only represent
an analysis and comparison of data obtained from normal clinical and surgical activity. No
additional radiological exposures are foreseen with respect to normally planned follow-up
paths. No other additional diagnostic investigations are requested. Furthermore, no
experimentation with surgical materials or techniques is envisaged. The study guarantees the
transmission and collection of data in a completely anonymous form. There are no conflicts of
interest for any of the members of the board. Consequently, there are no problems of an
ethical nature.
8) STUDY MONITORING AND SUPERVISION
The supervision of the study provides for the verification of the patients record
completeness, the adequacy of the radiographs for the purpose of the study as well as the
correct anonymization of the images, the correct presence of follow-ups. Random evaluation of
the accuracy of the measurements. Evaluation of correct data analysis procedures.
Participation and supervision to the results analysis. Supervision is carried out by
independent figures who are not part of the study board and are not investigators of the
study.
A telephone evaluation will be performed anonymously on a sample of enrolled patients
representative of all investigators to verify the accuracy and truthfulness of the entered
data.
