Cervical Spondylotic Myelopathy Surgical Trial
Phase: NA
Conditions: Cervical Spondylosis With Myelopathy
Sponsor: Lahey Clinic

PROTOCOL FOR RESEARCH INVOLVING HUMAN SUBJECTS 
TITLE OF PROJECT: Cervical Spondylotic Myelopathy Surgical Trial (CSM-S Trial)
VERSION:  6.0,  DATE:  12-17-24 
Study Sponsor: Patient-Centered Outcomes Research Institute (PCORI) & Alan and 
Jackie Stuart Spine Research Center 
Name 
Signature 
Email Address 
Principal 
Investigator:  
Zoher Ghogawala 
MD 
Zoher.ghogawala@lahey.org 
Other 
Investigator(s): 
Correspondent 
Mailing Address: 
41 Mall Road 
   Phone: 781-744-8984 
Burlington, MA 01805 
       Fax: 781-744-5778 

 
 
 
 
 
II. DESCRIPTION OF STUDY 
 
A. 
Purpose 
 
1a. To determine if ventral surgery is associated with superior SF-36 PCS 
outcome at one year follow-up compared to dorsal (fusion or laminoplasty) 
surgery. 
 
1b. To determine if, compared to pre-operative baseline status, both ventral and 
dorsal surgery for CSM improve symptoms of spinal cord dysfunction using 
mJOA. 
 
2.  To determine if, from a patient perspective, health resource utilization (out-of-
pocket expenses and loss of productivity) for ventral surgery, dorsal fusion, and 
laminoplasty surgery are different. 
 
3.  To determine if cervical sagittal balance post-operatively is a significant 
predictor of SF-36 PCS outcome. 
 
B. 
Background 
 
Surgical decompression for CSM can improve its disabling symptoms, but 
surgical complications are common and many of these complications affect 
patients’ overall health-related quality of life.  The optimal surgical treatment, 
therefore, remains controversial, with disagreement between three main 
approaches:  ventral decompression and fusion, dorsal decompression and 
fusion, or dorsal laminoplasty.  This study aims to test the hypothesis that ventral 
surgery is associated with superior SF-36 PCS outcome at one year follow-up 
compared to dorsal approaches and that both ventral and dorsal surgery improve 
symptoms of spinal cord dysfunction using the mJOA score.  A secondary 
hypothesis is that health resource utilization for ventral surgery, dorsal fusion, 
and laminoplasty surgery are different.  A third hypothesis is that cervical sagittal 
balance post-operatively is a significant predictor of SF-36 PCS outcome. 
 
C. 
Specific Location of Study 
 
This is a multi-center trial.  Subjects will be entered into the study from 10 
separate centers.  
  
D. 
Probable Duration of Project 
 
Subjects will be recruited into the study over an 18 month period.  All subjects will 
be followed for 5 years with clinical questionnaires. 
 

 
 
 
 
 
E. 
Research Plan  
 
1) Prospective, randomized multicenter trial.  Approximately 159 randomized and 
91 non-randomized patients would be recruited over 18 months with follow-up 
through 5 years. 
 
2) Subjects (aged 45-80 years) with CSM (2 or more levels of spinal cord 
compression from C3 to C7) with 2 or more of the following symptoms/signs, 
clumsy hands, gait disturbance, hyperreflexia, up going toes, bladder 
dysfunction, or ankle clonus, will be treated with either ventral 
decompression/fusion, dorsal decompression with fusion, or dorsal laminoplasty.  
(Patients <45 years of age do not generally suffer from degenerative arthritis, 
which is why the lowest age of inclusion is 45). 
 
3) Subjects with C2-C7 kyphosis > 5˚ (measured in standing neutral cervical 
spine radiograph), a segmental kyphotic deformity defined as 3 or more disc-
osteophytes that extend dorsal to a C2-C7 dorsal-caudal line measured on 
cervical spine CT, structurally significant ossification of the posterior longitudinal 
ligament (OPLL), previous cervical spine surgery, or significant active health-
related comorbidity (Anesthesia Class IV or higher) would be excluded from the 
study. 
 
4)  Each subject will be treated with either a Front Decompression/Fusion or 
Back of the Neck Decompression with fusion or Laminoplasty as part of standard 
clinical care. Decompression of the spinal canal to a diameter of at least 13 mm 
with restoration of cerebrospinal fluid flow around the spinal cord will be the goal, 
regardless of the approach. Surgical techniques have been standardized.  Back 
of the neck decompression with fusion and laminoplasty are equivalent and 
preliminary evidence suggests that the outcomes are similar using the SF-36 
PCS, which is the same questionnaire being used in this study (see table in 
Power Analysis section below). 
 
5) Functional outcomes will be determined using well-known quantitative scales 
(SF-36, Oswestry Neck, mJOA, and EuroQol-5D).  These instruments will be 
administered pre-op, 3 months, 6 months, and at 1 year. Additionally, functional 
outcomes instruments (SF-36, Oswestry Neck, and EuroQol-5D) will be collected 
annually at years 2,3,4 and 5.  
 
6) Two independent neuroradiologists will review post-operative imaging at 3 
months, and 1 year.  Post-operative cervical spine MRI will be performed at 3 
months  to document satisfactory spinal cord decompression. Cervical spine 

flexion-extension radiographs will be obtained pre-operatively on all patients and 
at one year after surgery to assess cervical fusion and/ or radiographic 
complications. Standing cervical-thoracic-lumbar-sacral films will be obtained on 
all patients pre-operatively and at one year postoperatively (post-operatively in 
the randomized group only) to assess cervical as well as overall sagittal balance.  
A cervical spine CT will be obtained on patients at 1 year who have an NDI score 
> 30 or whose plain films suggest instability. 
 
7) A study coordinator will collect data at 30 days and at 1 year to document any 
complications or re-operations. Additionally, the study coordinator will assess 
whether the patient is having any swallowing complications following surgery. 
 
8)  Health resource utilization information (including out-of-pocket expenses) will 
be obtained using patient diaries along with copies of all medical bills and 
receipts at 1 month, 3 months, 6 months, and 12 months post-operatively for all 
of the patients.  Participants also will be asked to keep track of days missed from 
work and days unable to perform usual activities, in addition to days missed from 
work for medical treatments or evaluations. 
 
 
 
F. 
Data and Safety Monitoring Plan 
 
1) All serious unexpected adverse events (e.g. death within 30 days of 
operation) will be reported to the IRB within 24 hours.  Any appropriate 
funding agencies or regulatory agencies would be notified as well.   
2) Any serious anticipated adverse event (e.g. wound infection, pulmonary 
embolus) will be reported to the IRB whenever their magnitude or frequency 
exceeds expectations. 
3) All other adverse events (including loss of privacy, significant economic harm) 
will be reported to the IRB on an annual basis or at the time that re-approval 
is sought.  Any adverse event judged unlikely or unrelated to the study will 
also be included in an annual report for the IRB. 
          
G. 
Statistical Considerations 
 
a. Specific data variables being collected for the study.   
 
The data collection sheets will be submitted along with this protocol.  There will 
be several data sheets as follows:   
 
1) Screening/Baseline, 1 Month, 3 Months, 6 Months, and 1 Year Visit Checklist  
2) Informed Consent Process  
3) Inclusion/Exclusion Criteria  
4) Baseline Demographics  
5) Spine surgeon's data sheet  

6) 30-day and 1 Year morbidity data sheet 
7) 1 Month, 3 Months, 6 Months, 1 Year Return to Work Status 
8)  3 Month Swallowing Evaluation 
9) Initial Hospital Admission Data Sheet 
10) 3 Months and 1 Year Radiology 
11) End of Study 
12) Adverse Event Form 
13) Serious Adverse Event Report Form 
14) Serious Adverse Event Follow-up Report Form 
15) SF-36 questionnaires (pre-op, 3 months, 6 months, 1, 2, 3, 4, and 5 years),  
16) Neck Disability Index questionnaires (pre-op, 3 months, 6 months, 1, 2, 3, 4, 
and 5 years) 
17) mJOA, (pre-op, 3 months, 6 months, and1year) 
18) EuroQol-5D (pre-op, 3 months, 6 months, 1, 2, 3, 4, and 5 years) 
19) Health Resource Utilization Diary (1 month, 3 months, 6 months, 1 year) 
20) Report of Second Cervical Surgery 
21) Death Form 
22) Inpatient Hospital and Rehabilitation Utilization Data Sheet 
23) Long term follow-up phone questionnaire (2, 3, 4, and 5 years) 
 
 
 
b. Study endpoints. 
 
Subjects will be followed for 5 years.  The primary endpoint will be the 1-year 
change in SF-36 physical component summary score (PCS) at one year.  
Secondary endpoints will include the 1-year change in mJOA, NDI, and EuroQol-
5D scores as well as the observed complication rates, health service utilization, 
work status, and sagittal balance measurements.   
 
c. Statistical Methods. 
 
Primary analyses will include all subjects randomized using an intent-to-treat 
approach. The primary endpoint is the 1-year change in Physical Component 
Summary of the SF-36 (SF-36 PCS) at one year. A likelihood-based analysis 
using a mixed model will be used to compare SF-36 PCS between groups. This 
model will adjust for baseline SF-36 PCS, as well as study surgeon using a 
random effects model.  All time points will be included in the model, and each 
subject will contribute data for the time points at which they were assessed.  The 
model enables a statistical comparison between treatment groups at each time 
point, though the comparison at the one-year time point will be the primary 
analysis.  The primary advantage of the mixed model, when compared to 
commonly used methods such as complete case analysis and single imputation 
(e.g. last observation carried forward), is its flexibility in handling missing data. 
This analysis will assume that missing data occurs at random (i.e. the missing 
data value can be dependent on observed data, but independent of unobserved 

data). The inclusion of all follow-up time points in the model as well as covariates 
identified to be associated with withdrawal will assist in meeting this assumption 
and minimizing the risk of bias.  Although the assumption for missing data is 
weaker under the likelihood based analysis compared to complete case analysis, 
a non-ignorable missing data mechanism is possible. Sensitivity analysis using 
selection and pattern mixture models will be employed to evaluate the 
robustness of conclusions to the missing at random (MAR) assumption.  
 
Analysis Plan for Year 2 Outcomes 
 
Year 2 outcomes for SF-36 and other continuous outcomes will be 
analyzed using linear mixed effects models (lme) that include both first and 
second year outcomes. The outcomes will be change from baseline. The 
purpose of the lme is to address missing second year outcomes. Since the year 
2 assessments were missing mainly for logistical reasons (at 2 sites, research 
staff neglected to follow up with participants during specific time intervals), the 
missing at random (MAR) assumption of the lme is valid. The model will include 
treatment group, time period, and group*time interaction. To address within-
subject correlation, patient id will be a random effect. There will be no adjustment 
for surgeon, since some surgeons had few patients, and no adjustment for 
baseline variables, since these were similar between groups. The treatment 
effect at year 2 will be tested using model contrasts. The year 1 treatment effect 
will be tested similarly, to confirm previous analyses obtained by t-test and 
anova. The models will be used to compare the 2 randomized groups and the “as 
treated groups.” We will not address multiple comparisons for the “as treated” 
analyses because they are considered to be exploratory.  
 
Analysis Plan for Return to Work 
 
The return to work analysis will include all time periods up to 12 months 
(1, 3, 6, and 12 months). Groups will be compared via Kaplan-Meier plots and 
log-rank tests. To address multiple comparisons when comparing the as-treated 
groups pairwise comparisons will be performed at p=0.025 to account for 2 
comparisons (DL vs DF and DL vs VF).  
 
Analysis Plan for Cost-Effectiveness 
 
The research team has extensive experience conducting economic 
evaluations, including assessment of musculoskeletal interventions alongside 
RCTs and will conduct the proposed patient-oriented health resource utilization 
analysis.  We will collect health resource utilization data as well as health cost 
data alongside this RCT.   
 
Cost Analysis 

 
Costs will be estimated for each patient from a societal perspective from the 
sources listed below, including only patients from the United States. A one-year 
time horizon will be selected to align with the primary outcome measure of the 
CSM-S Trial.  
 
A. Index Hospitalization Costs:  
• 
Hospital Costs: Total hospital charges (TotalHC) will be used to estimate 
costs using hospital-specific and year-specific Medicare cost-to-charge ratios 
(CCR). The costs will be adjusted for inflation to the current year without a 3% 
discount.  
o As a sub-analysis, hospital charges for specific revenue-centers (i.e., 
radiology, pharmacy, physiotherapy and occupational therapy) will be 
converted to costs using hospital-specific and year-specific Medicare 
CCRs.  This will allow the identification of the major drivers of the 
difference in cost between the surgical strategies. A crosswalk between 
the revenue center and the cost center will be created. 
• 
For professional services (identified with either HCPCS code or CPT-4 
codes) provided to patients during the index hospitalization, costs will be 
calculated using national reimbursement amounts from the appropriate Medicare 
fee schedules for the respective year and site.  
 
B. One-Year All-Cause Costs:  
• 
One-year total hospital charges will be utilized in this part of the analysis.  
These include major health resource utilization events in the year following 
surgery including readmission, reoperation, injections, advanced imaging, and 
physical therapy. 
o Year-specific, site-specific Medicare cost-to-charge ratios, will be used to 
determine one-year costs from charges.  These costs will be inflation 
adjusted.  Professional services will also be included (identified with either 
HCPCS code or CPT-4 codes) and costs will be calculated using national 
reimbursement amounts from the appropriate Medicare fee schedules for 
the respective year and site.  
 
C. Costs Due to Lost Productivity:  
• 
We will assume that work was halted for patients on the procedure date.  
• 
Lost wages will be estimated according to patients’ occupations using the 
median weekly earnings in the US (for the current year) as reported by the 
Bureau of Labor Statistics. 

o Lost wages for retirees will be valued at 65% of an employed patient and 
based on time to return to normal activities, which will be assumed to be 
three months 
 
Hospitalization costs and one-year all-cause costs (total direct costs) will be 
combined with costs due to loss of productivity (indirect costs) to estimate total 
costs of each surgical procedure from a societal perspective. 
Statistical Analysis Plan: The three cost outcomes will be reported in US 
Dollars and inflation-adjusted to the current year using the Gross Domestic 
Product Implicit Price Deflator. We will provide the descriptive statistics for the 
three outcomes (mean, median, standard deviation or SD, interquartile range, 
minimum, and maximum). Given that the cost outcomes are expected to follow a 
skewed distribution (non-normal), we will use generalized linear modeling (GLM) 
with Gamma distribution and a logarithmic link for cost. Any baseline patient 
characteristics found to be imbalanced between the cohorts will be adjusted for in 
the GLM. The mean predicted costs for each cohort and the differences in those 
predicted costs along with the 95% confidence intervals will be generated. If 10% 
or more of the overall study population has zero costs for the 1-year outcome, 
two-part modeling will be implemented. This will utilize a logistic regression to 
predict the presence of positive costs and a GLM model to predict non-zero costs 
as described above. 
 
Calculation of Utility and Quality-Adjusted Life Years (QALY) Gained 
 
• 
EQ-5D health-related quality-of-life questionnaires have been collected at 
baseline, 3 months, 6-months, 1-year, and 2-years. 1-year data will be used for 
cost-utility analyses. 
o For patients without complete data (i.e., without responses at all time 
points in the first year), we will assume missingness at random (MAR) and 
multiple imputation will be performed. 
• 
Patient responses to the EQ-5D instrument will be mapped to utilities 
using the U.S. population value set and QALYs will be calculated for cost-utility 
analysis assuming a linear relationship between consecutive survey timepoints.  
 
Incremental Cost-Effectiveness Ratio (ICER) 
 
• 
The ICER will be calculated in a three-way extended dominance analysis, 
comparing each surgical treatment to the others. If a surgical procedure is both 
less costly and provides higher QALYs gained, that treatment will be dominant 

over the others. 
o A comparison of anterior and posterior approaches (namely, grouping the 
two posterior procedures) will be performed independently from the ICER 
model. 
o Probabilistic analysis will be performed to account for sampling variation 
around ICER point estimates. 
• 
Cost/QALY gained will be reported for each surgical treatment and for 
each approach. 
 
 
d. Power Analysis.   
 
Sample size for Specific Aim #1a (Ventral surgery is associated with 
superior SF-36 PCS outcome at one year compared to dorsal (fusion or 
laminoplasty surgery): 
Sample size estimates were calculated based on analysis of covariance model with 
α= 0.05 at 80% and 90% power using Power Analysis and Sample Size software 
(PASS 2008, NCSS, LLC. Kaysville, Utah). The primary endpoint is the SF-36 PCS. 
This component of the SF-36 is derived from the sums of scores of 21 items and 
thus exhibits distributional behavior commensurate with assumptions for parametric 
analysis. Our preliminary data suggest standard deviations for SF-36 PCS between 
10 and 12 and correlations of baseline with one year SF-36 PCS between 0.6 and 
0.7. The following table describes the total sample size (2:3 ventral-dorsal 
randomization) required to detect a five point difference in SF-36 PCS one year 
post-surgery for various combinations of power, standard deviation and one year 
correlations under a fixed design.  
 
A minimum sample size of 137 patients provides at least 90% power (see Tables 
below): 
 
Surgery (N) 
Pre-op 
Post-Op 
Correlation 
between Pre- and 
Post-Op 
Difference 
Ventral (45) 
35.5 ± 10.3 
44.2 ± 11.7 
0.64 
+ 8.7 ± 8.2 
Dorsal (70) 
35.8 ± 11.3 
39.8 ± 11.6 
0.66 
+ 4.0 ± 9.5 
Dorsal Fusion 
(42) 
 35.0 ± 11.7 
 39.6 ± 12.4 
0.65 
+ 4.6 ± 10.0 
Laminoplasty (28) 
 37.0 ± 10.9 
 40.1 ± 10.6 
0.67 
+ 3.1 ± 8.8 
All patients (115) 
35.7 ± 10.9 
41.5 ± 11.8 
0.64 
+ 5.8 ± 9.7 
 
 
Difference 
/ SD 
Correlation 
80% Power /  
5% Type I error (2-
sided) 
90% Power /  
5% Type I error (2-
sided) 
NVentral 
NDorsal 
N 
NVentral 
NDorsal 
N 

5 / SD = 10 
0.60 
38 
56 
94 
50 
74 
124 
5 / SD = 10 
0.65 
40 
59 
99 
53 
78 
131 
5 / SD = 10 
0.70 
42 
62 
104 
55 
82 
137 
 
 
The sample size will be inflated by 5% to accommodate multiple significance testing 
using an Obrien-Fleming stopping boundary. Based on our preliminary data and pilot 
studies, withdrawal and loss-to-follow-up are not expected to be high. The sample size 
will be further inflated by 10% to accommodate attrition during the follow-up. Thus, 159 
total patients will be recruited and randomized. Ten high volume surgeons/ centers 
with the necessary expertise to permit patient randomization (16 randomized CSM 
cases/ site) have been selected to achieve the goal of enrolling 159 randomized 
patients over 18 months.  An additional 91 nonrandomized patients will be 
enrolled into the study. 
 
 
Sample size for Specific Aim #1b (Compared to pre-operative baseline status, 
both ventral and dorsal surgery for CSM improve symptoms of spinal cord 
dysfunction at one year follow-up): 
 
Using the sample size estimate for Specific Aim #1a and assuming ~10% attrition 
during follow-up, we expect to have 55 ventral surgery and 82 dorsal surgery patients 
(total = 137 patients) available for analysis.  We will be able to detect changes from 
baseline pre-operative mJOA status as small as 2.0 points (clinically important 
difference) for both the ventral surgery cohort and the dorsal surgery cohorts at one 
year.   Assumptions for this sample size analysis include Type I alpha = 0.025, power at 
90%, and range of within-subject correlation of 0.60 to 0.70. 
 
 
H. 
Economic Considerations 
 
No subject will incur any additional cost for participating in this study.  All of the 
pre- and post-operative CT, MRI, flexion-extenstion x-rays, and pre-operative 
sagittal balance films are considered standard of care.  The post-operative 
sagittal balance films, which only randomized patients will receive, are not 
considered standard of care and will be billed directly to the research fund.  All 
costs associated with the adminstration of the study will be assumed by the 
Patient-Centered Outcomes Research Institute (PCORI) and/or the Lahey 
Comparative Effectiveness Research Institute. 
 
 
 
 
III.    HUMAN SUBJECTS 
 
 
A. 
Subject Population, Recruitment 

 
Eligibility Criteria: Patients aged 45-80 years with CSM (≥2 levels of spinal cord 
compression from C3 to C7) presenting with ≥2 of the following symptoms/signs: clumsy 
hands, gait disturbance, hyperreflexia, up going toes, bladder dysfunction. 
 
Exclusion Criteria: Any of the following: C2-C7 kyphosis>5º (measured in standing 
neutral cervical spine radiograph), segmental kyphotic deformity (defined by ≥3 
osteophytes extending dorsal to a C2-C7 dorsal-caudal line measured on cervical spine 
CT), structurally significant ossification of posterior longitudinal ligament (OPLL – 
measured on cervical spine CT), previous cervical spine surgery, or significant active 
health-related co-morbidity (Anesthesia Class IV or higher). 
 
EXCLUDE 
 
 
 
INCLUDE 
   
 
 
 
Segmental-Cervical 
Kyphotic Deformity 
 
Yes 
 
 
 
 
No 
 
 
 
 
Figure.  Two cases with sagittal CT reconstructed images are depicted.  A line is drawn from the dorsal 
caudal point of C2 to the dorsal caudal point of C7.  If 3 or more levels of disc-osteophyte extend dorsal to 
the line, then the case has a segmental-cervical kyphotic deformity and the case would be excluded from 
the study.  The C2-C7 Cobb angle is 5 degrees lordosis in both cases 
  
 
Subjects will be enrolled by participating spine surgeons who are investigators in 
the study.  These subjects will be identified within the existing practice of each 
surgeon.  There will be no advertising or any effort to recruit subjects into the 
study from outside the practice of a study surgeon investigator. 
2/1/1937
2/1/1937
FF
Page: 2 of 3
Page: 2 of 3
Acq no: 0
Acq no: 0
KVp: 140
KVp: 140
mA: 200
mA: 200
Tilt: 0
Tilt: 0
RD: 120
RD: 120
CT CERVICAL SP NC W/ REFORMATS
CT CERVICAL SP NC W/ REFORMATS
Average
Average
 7/20/2003 08:28:55
 7/20/2003 08:28:55
000500571
000500571
LOC: 17.98
LOC: 17.98
THK: 3
THK: 3
HFS
HFS
IM: 8 SE: 577
IM: 8 SE: 577
Compressed 8 :1
Compressed 8 :1
W: 1600
W: 1600
C: 400
C: 400
Z: 0.73
Z: 0.73
AA
PP
HH
FF

Once a patient has been screened, identified as having CSM, and agreed to 
participate in the trial by signing consent, the subject will undergo two reviews.  
The patient’s images will first be reviewed by a Central Review Committee 
(Zoher Ghogawala, MD and Robert Whitmore, MD) to confirm eligibility.  If the 
patient is deemed eligible, their images will then be reviewed by the spinal 
experts network.  The patient’s images will be uploaded onto the web-based 
platform, and an email will be generated and sent to all 15 members (15 CSM 
surgeon investigators) of the spinal experts panel. Each surgeon will be asked to 
vote: ‘randomize’ or ‘do not randomize’ and then to characterize his/her 
preferred surgical approach as ventral or dorsal. If after 72 hours, a majority 
(>50%) of the review panel (with at least 9 votes for a quorum) favor 
randomization (equipoise) and less than 80% select one approach (ventral or 
dorsal) over another, then the patient will be eligible for study randomization. 
 
The results of the voting (the number of votes randomize or do not randomize 
and the number of ventral or dorsal votes) will be available to the patient both to 
increase patient trust and confidence in the recommendation for randomization, 
as well as to protect patients from undergoing randomization when one approach 
(ventral or dorsal) might be superior for that patient. 
 
Patient Randomization (See Figure 1 Below) 
Patients will be offered randomization in a subsequent one-hour meeting (following 
spinal experts review of the case) among study coordinator, surgeon, and patient if two 
conditions are met: 
1) Central Review Committee (Zoher Ghogawala, MD and Robert Whitmore, MD) 
checked the images and clinical exam findings and found the patient eligible; and 
2) Spinal Experts Panel confirmed patient’s eligibility (>50% majority vote 
“randomize” and less than 80% select one approach (ventral or dorsal) over 
another). 
The patient can either consent to or decline randomization. There will be two 
categories of patients who have signed an IRB-approved consent to participate in 
the study: 
1. Randomized cohort: Upon confirmation of eligibility and patient acceptance of 
randomization, the study coordinator will access the assignment by logging 
into the secure website (https://pip.acesis.com) with a password and will obtain 
the randomization assignment from the web-based platform with its pre-
programmed blocked (2, 4, or 6 subjects/block) stratified site-specific 
randomization scheme. Randomized patients will be followed for five years.  
2. Non-Randomized cohort: The non-randomized cohort will consist of all 
patients who meet entry criteria but for whom equipoise is not confirmed by 
spinal experts panel.  It also will consist of patients who do not consent to 
randomization.  All non-randomized patients will be asked to complete all the 
study questionnaires and will be followed for five years. The non-randomized 
cohort will not have an independent radiologist evaluation. 

 
 
B. 
Source of Research Material 

 
Subjects will be identified from within the practice of spine surgeon investigators. 
 
C. 
Consent Procedures 
 
Subjects will be identified by investigator spine surgeons within their practice.  
Subjects will be registered by the surgeon's office.  The subjects will be clearly 
told by the surgeon that participation is voluntary and that a decision not to 
participate will not affect their medical care in any way.  The patient will sign a 
consent form with the spine surgeon after having a chance to review the study 
protocol and consent form with family and others.   The subjects will sign the 
consent with the surgeon during a separate office visit prior to surgery.  A spine 
study coordinator will then contact the patient for more detailed questions 
regarding registration for the study (e.g. home phone number and home 
address).  The study coordinator will also ask the patient whether he is 
comfortable enrolling in the study.   
 
D. 
Risks 
 
All of the subjects in the study will be surgical candidates and would have had 
surgery recommended even if they were not involved in a study. 
 
 
E. 
Protection of Subjects 
 
All subjects will receive standard follow-up by the treating surgeon.  All of the 
surgical procedures are considered standard care and none are considered 
investigational.  The results will be made available to the subjects prior to 
publication.  Any significant findings regarding the overall safety of either 
procedure at any site will be brought to the attention of all subjects in the study 
once all of the appropriate IRB committees have been notified.  The 
confidentiality of all subjects will be assured by assigning all subjects a code and 
by removing all identifying information from questionnaires.  Data entered into the 
study web site will be encrypted using the current industry standard to protect 
patient confidentiality. 
 
Once the database is analyzed, all patient identifiers will be removed from the 
final database.   The database will be kept at the Lahey Comparative 
Effectiveness Research Institute.  No patient identification would be linked to the 
data. 
 
F. 
Data and Safety Monitoring Plan 
 
(As outlined above in Research Plan) 
 
G. 
Confidentiality 

 
Each subject will be assigned a code number and no identifying information will 
leave the Lahey Comparative Effectiveness Research Institute.  Data from each 
patient will be sent to the Lahey Comparative Effectiveness Research Institute or 
will be entered into the study web site which is encrypted to protect patient 
confidentiality using the current industry standard.  All patient identifiers will be 
removed from the final database.  
 
H. 
Potential Benefits 
 
Subjects will be followed closely and might gain from the increased observation. 
Each subject will be offered a free review of their radiographic images by a panel 
of spinal experts. The multiple opinions from other surgeons will be used to help 
educate subjects about their condition. The subjects will have the opportunity to 
learn about the results of the study through frequent updates available from the 
Lahey Comparative Effectiveness Research Institute or from the public web page 
(https://pip.acesis.com). 
  
Society at large might benefit from the results of this study.  The study will be 
useful for spine surgeons to determine if health resource utilization differs among 
the three surgical procedures for people with cervical spondylotic myelopathy. 
 
 
I. 
The Risk-Benefit Ratio 
 
All subjects entered into the study would be surgical candidates for either 
surgical procedure in the study.  All of the surgical procedures used in this study 
are routine and constitute standard care.  No procedure is considered 
investigational.  Therefore, no subject will have any increased risk of physical 
injury as a result of participation in the study.  The subjects will have access to 
the Study website and will be informed of the results of the study prior to 
publication.  The increased level of observation will possibly benefit some of the 
subjects.  The subjects will know that they are helping society at large because 
the results of the study will be useful for spine surgeons to help future subjects 
determine which surgical procedure is best for people with cervical spondylotic 
myelopathy. 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
 
 
 
 
 
 
 
 
 
Appendix I: Study Schema 
 
 
 
Patient identified as CSM surgical candidate 
Clinician confirms patient eligibility - Consent form signed 
Assessment of Complications  
Health Cost Diary 
Pre-op Questionnaires  
NDI, SF-36, mJOA, EQ-5D 
Spinal Experts Review 
> 50% majority of Spinal experts vote in favor of 
randomization 
Yes 
No 
 Assessment of Complications 
Health Cost Diary 
Pre-op imaging: Cervical flexion-extension films; sagittal balance films, 
cervical MRI, and cervical CT 
Do Not Randomize 
6 months 
Randomize 
Ventral or Dorsal Surgery 
1 month 
3 months 
SF-36, NDI, mJOA, EQ-5D 
Health Cost Diary 
Cervical Spine MRI 
1 year 
SF-36, NDI, mJOA, EQ-5D 
Health Cost Diary 
SF-36, NDI, mJOA, EQ-5D 
Health Cost Diary 
Flexion-extension cervical plain 
films and cervical CT (if NDI>30 or 
SF-36, NDI, mJOA, EQ-5D 
Health Cost Diary 
SF-36, NDI, mJOA, EQ-5D 
Health Cost Diary 
Flexion-extension cervical plain 
films,sagittal balance films, and 
cervical CT (if NDI>30 or plain films 
CSM Study Flow 
Schema 
Independent 
Radiology Review 
SF-36, NDI, mJOA, EQ-5D 
Health Cost Diary 
Cervical Spine MRI