Use of Ultrasonic Bone Scalpel in Adolescent Idiopathic Scoliosis - Randomized Clinical Trial
Phase: NA
Conditions: Adolescent Idiopathic Scoliosis, Posterior Spinal Fusion
Sponsor: University of Colorado, Denver

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COMIRB Protocol 
COLORADO MULTIPLE INSTITUTIONAL REVIEW BOARD 
CAMPUS BOX F-490    TELEPHONE:  303-724-1055  Fax:  303-724-
0990 
 
 
 
Protocol #: COMIRB 15-0036 
Project Title: Use of Ultrasonic Bone Scalpel in Adolescent Idiopathic Scoliosis – Randomized 
Clinical Trial 
 
 
 
 
Principal Investigator:  Sumeet Garg, MD 
Version Date: 7/6/2015 
 
 
 
  
 
I. 
Hypotheses and Specific Aims:   
The primary purpose of this randomized trial is to compare the efficacy of an ultrasonic bone 
scalpel (or osteotome device) with standard of care surgical instruments during posterior spine 
fusion with instrumentation. The primary outcome variable in this trial is estimated blood loss per 
spine level fused (EBL/level). Secondary outcome variables include the probability of meeting the 
intraoperative blood transfusion criteria, incidence of adverse events, and incidence of surgical 
site infections. Subjects with adolescent idiopathic scoliosis undergoing planned posterior spinal 
fusion with instrumentation will be recruited from a single tertiary recruitment center for this 
trial.  
 
Primary Aim 1: Compare estimated blood loss per level fused 
 
Hypothesis 1: The average estimated blood loss per level fused will be significantly lower in the 
ultrasonic bone scalpel (USBS) group compared to the standard of care group. 
 
Secondary Aim 1: Compare the incidence of adverse events in the two groups. 
 
Hypothesis 2: There will be no difference in the incidence of adverse events in the bone scalpel 
group compared to the standard of care group. 
 
Secondary Aims 2-3: Compare the proportion of patients meeting intra-operative blood 
transfusion criteria in the two groups. 
 
Hypothesis 3: The proportion of subjects meeting the intra-operative blood transfusion criteria will 
be significantly lower in the bone scalpel group compared to the standard of care group.  
 
II. 
Background and Significance:  
Adolescent idiopathic scoliosis (AIS) is a common spine deformity in children. In 
severe cases posterior spinal fusion surgery (PSF) is indicated to correct the 
deformity and prevent curve progression. Due to the duration and invasiveness of 
this procedure, PSF is associated with high intraoperative blood loss. On average, AIS 
patients typically lose 65-150 mL per vertebral level during spinal fusion surgery.[1] 
With regard to total blood volume, AIS patients typically lose 25-30% of their total 
blood volume during PSF.[1, 2] The percent of patients who receive an 

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intraoperative transfusion during PSF surgery is variable, but has been reported as 
low as 20-30% and as high as 50-75%.[2-6] The amount transfused also widely varies 
and ranges from 1-8 units of red blood cells.[2, 7] Minimizing intraoperative blood 
loss (EBL) is of great importance due to the association between increased blood loss 
and increased risk of postoperative complications.[8-10] 
The utilization of an FDA approved ultrasonic bone scalpel (USBS) may help 
decrease EBL during PSF. The Misonix BoneScalpel® is a device that utilizes ultrasonic 
frequencies to “cut” through osseous structures. At the tip of the device is a blunt 
blade that vibrates longitudinally at a frequency of 22,500 times per second. This 
blunt, vibrating blade is selective between osseous tissue and softer, connective 
tissue. Further, the tip is irrigated by a sterile saline solution which helps to provide 
cooling and reduce the risk for thermal injury.[11, 12] This device has been used for 
various procedures in various specialties. It has been used in maxillofacial surgery in 
order to perform a more precise and controlled osteotomy.[13, 14] It has also been 
used in tumor resection and when performing surgery close to the spinal cord.[12, 
15-18]  
The literature surrounding the use of the USBS in pediatric spine surgery is more 
limited. Several retrospective studies cite the USBS as safe and effective for various 
procedures such as spinal decompression, posterior releases, posterior 
facetectomies, posterior osteotomies, and laminectomies.[16, 19-21] Bydon et al. 
(2014) reported that patients treated with the USBS showed a trend toward 
decreased complications. Bartley et al. (2014) observed a statistically significant 
difference in EBL between groups. Blood loss in the USBS group was 30-40% less 
than blood loss in the historical control group. The majority of studies involving 
pediatric spine surgery are retrospective in nature. The lack of randomization creates 
concern about potential for selection and/or indication bias. Therefore, the purpose 
of this randomized trial is to compare the safety and efficacy of the USBS relative to 
standard of care instruments in a pediatric population undergoing PSF.  
 
III. 
Preliminary Studies/Progress Report:   
No preliminary studies have been performed at this institution. Please see 
the above section for studies performed at other institutions. 
 
IV. 
Research Methods not ony 
 
a. Outcome Measure(s):   
 
Primary Clinical Outcome 
Estimated blood loss/level^ 
 
Secondary Clinical Outcomes 
Intraoperative and postoperative complications (events that cause a deviation from routine 
care)^†‡ 
Probability of meeting blood transfusion criteria (see section )^† 
Procedure Time (first incision to close)^ 
 

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Demographics/Covariates (potential confounding variables) 
Age at surgery* 
BMI percentile at surgery* 
Gender at surgery* 
Weight (kg) at surgery* 
Exposure to second hand smoke* 
Preoperative Lenke Classification* 
Preoperative major Cobb angle* 
Preoperative hemoglobin/hematocrit* 
Postoperative major Cobb angle†‡ 
Postoperative hemoglobin/hematocrit† 
Intraoperative use of intrathecal narcotics^ 
Donor hematocrit^ 
Vertebral levels fused^ 
Intraoperative use of antifibrinolytic^ 
 
Exploratory Variables 
Unplanned return to OR†‡ 
Surgical site infection‡ 
Procedure Time^ 
 
 
* Collected preoperatively or day of surgery (before surgery) 
^ Collected intraoperatively 
† Collected postoperatively: short term follow-up, during initial hospital stay 
‡ Collected postoperatively: long term follow-up, one year postoperative 
 
I. 
Description of Population to be Enrolled:   
All patients with a diagnosis of Adolescent Idiopathic Scoliosis who are scheduled for spinal 
fusion surgery and meet the following criteria will be eligible to participate in the study: 
 
Inclusion Criteria: 
1. 10-18 years of age 
2. Diagnosis of AIS 
3. Scheduled for a posterior spinal fusion (without Schwab Grade II or higher osteotomy) 
 
Exclusion Criteria: 
1. Plan for a posterior column osteotomy of Schwab Grade II or higher 
2. Prior spinal surgery 
3. MRI abnormalities (such as syrinx and/or chiari malformations) 
4. Subjects with medical comorbidities (e.g. heart, lung, kidney disease) 
5. Subjects with bleeding diatheses 
6. Non-idiopathic etiology for scoliosis 
 
II. 
Study Design and Research Methods   
a. Power Analysis 
The purpose of this single blinded, randomized, controlled, superiority trial is to compare 
the efficacy of an ultrasonic bone scalpel with standard of care surgical instruments 
during posterior spine fusion with instrumentation. The primary aim of this study is to 
compare differences in estimated blood loss per fusion level (EBL/level) between 
groups
). We aim to test the null hypothesis that the 
difference between groups is less than or equal to 0 (
.  Based on a previous 
retrospective cohort study in a similar target population[21], we anticipate the EBL/level 
in the proposed study will be 48 mL/level (±30) in the USBS group (
 and 72 
mL/level (±28) in the standard instrument group (
. Although there are no 
universally established thresholds for defining a clinically meaningful difference in 

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EBL/level, the investigators are confident that the 33% reduction in blood loss per level 
observed in the previous study is representative of a clinically meaningful reduction in 
blood loss (
 or 
. Based on a symmetric two sided, two stage 
group sequential design with O’Brien-Fleming stopping criteria and an alpha level of 0.05, 
we determined that a sample size of 62 subjects (31 subjects per group) would provide 
90% power to reject the null hypothesis of no difference between groups (See Trial 
Monitoring section for information about the stopping criteria). This estimate assumes a 
group difference of 24 mL/level and a standard deviation of ±28 in the standard 
instrument group and a standard deviation of ±30 in the USBS group. Assuming a dropout 
rate of approximately 15%, we intend to enroll 36 subjects per group to achieve the 
desired statistical power. The estimated dropout rate is based on previous studies in a 
similar patient population, adolescents with idiopathic scoliosis.  
 
b. Subject Screening: 
All surgical patients under the care of two high volume pediatric orthopedic 
surgeons will be screened for study eligibility. All patients who elect to undergo spinal 
surgery at Children’s Hospital Colorado under the care of the investigators of this study 
will be screened for study eligibility by the research coordinator (research assistant). 
Patients who are determined to meet the inclusion and exclusion criteria from above will 
be approached by the study team. 
 
c. Enrollment and Consent: 
After a patient is determined to be eligible for study participation, they will be 
approached by the study team. Most often consent will be obtained at the preoperative 
appointment. The preoperative appointment occurs before surgery, at least a day prior 
to surgery. During this visit, patients and their families meet with members of the 
surgical team, nurses from the spine team, orthopedic research team personnel, and 
relevant members from hospital support departments. The study will be presented by a 
trained member of the research team who is listed under the COMIRB approved 
personnel form (PI, Co-I, or research coordinator). Informed consent and assent will be 
obtained in this context. As patient schedules and preoperative appointments can vary, 
the timeline of obtaining consent will remain flexible. If a patient does not have a 
preoperative appointment or the study team is for some reason unable to meet with 
them during this time, the patient will be approached during an alternative preoperative 
appointment. If the patient cannot be approached during a preoperative visit, the 
patient will be contacted via phone, email, or mail ahead of their surgical date by the 
surgeon and issued a copy of the consent/assent forms. They will be given contact 
information for any questions and concerns. If interested and willing to participate in the 
study, an initialed and signed copy of the consent/assent form will be obtained before 
surgery. This method will be employed in order to allow the time for informed consent 
to occur as well as not to interfere with “on-time” start goals in the operative room. 
Patients who elect to participate in the study will undergo the informed consent 
process. Assent will be obtained in one of two ways depending on the patient’s age and 
understanding. If the participant is 7-12 years old, or if they are having trouble 
understand the details of the study, they will read and sign a separate assent form. If the 
participant is aged 13-17 years old, or if they understand completely the details of the 
study, they will initial and sign the consent form along with their parents, legal guardians, 

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or legally authorized representative. The patient’s understanding of the protocol will be 
assessed by research team member who is obtaining consent.  
 
d. Randomization and Blinding: 
Patients will be randomized 1:1 into two different treatment groups using a block 
randomization scheme. Using the Proc Plan procedure within SAS 9.4 (SAS Institute, Carey 
NC), blocks will be constructed based on surgeon and patient gender. Each surgeon will 
have a randomization list generated, and patient assignment will be made after the 
informed consent process has been performed to the next assignment on the list. 
Randomization assignments will not be revealed to the study personnel until after the 
patient has been enrolled in the study so as not to unduly bias the consent process.  
Blinded evaluators will be used to calculate the primary outcome variable of interest, 
estimated blood loss per level fused. All other study personnel, including the surgeons, 
will not be blinded to participant treatment assignment which is necessary to ensure the 
correct protocol is followed. Patients and their families will be blinded to study 
assignment to minimize the risk of assignment related study withdrawal.  Patients and 
their families will not have the assignment revealed to them after the surgery as it will not 
affect their plan of care.  If desired, treatment allocation may be revealed at the final 
study visit at one year following surgery. 
 
e. Intraoperative Estimated Blood Loss  
Estimated blood loss will be determined by 3 different methods. The first and 
primary method is to use the estimated blood loss listed on the cell saver report. This 
measurement is generated by the cell saver based on the blood collected. The other two 
methods determine blood loss through a calculation. 
  
Method 2:  
With this method, the EBL measurements will be based on the contents of the blood 
and fluid collection canisters as well as the volume reports generated by the cell saver 
system. To ensure blinding, final levels of fluid bags and canisters will be photographed by 
the study surgeon immediately after the procedure is complete. Photographs will be 
taken by the camera features from an iPhone 6. Photographs will be taken at a distance of 
two feet from the canisters and bags and such that the meniscus of the fluid is at eye-
level with the lens. Photographs will be reviewed by blinded evaluators at two intervals, 
prior to the interim analysis and following final enrollment. Two blinded evaluators will be 
used for each measurement, and their measurements will be averaged for use in the final 
calculation.  
EBL will be calculated in the following manner:  First, the total fluid volume will be 
calculated: The volume of the contents of all of the blood and fluid canisters used during 
the course of the surgical procedure will be recorded based on the photographs. To this 
we will add the cell saver intake fluid, taken from a report generated by the cell saver 
system. Next, the total irrigation volume used during surgery will be calculated. The 
irrigation volume will be estimated as the difference in volume of the irrigation bag at 
surgery cut versus surgery close. For subjects in the USBS group, the total irrigation 
volume will also include the difference in volume of the USBS irrigation bag at surgery cut 
versus surgery close. Estimated blood volume will be calculated as total fluid volume 
minus irrigation volume. 

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Method 3:  
To validate the above described method 2, the study personnel will also use the 
same method of calculated blood loss as was used in a study by Da Cunha et al (2015).[22] 
The blood loss calculation from this study was adapted from the method proposed in 
Brechter et al (1997).[23] This method calculates blood loss through the following 
mathematical model: 
 
EBL = [EBV*(Hbpre-Hbpost)/Hbpre) + [Donor RBCnormalized] + [Cell Salvage RBCnormalized] 
 
Where: 
 EBV = Estimated Blood Volume = Patient Weight (kg) x 70 ml/kg 
Hbpre = preoperative patient Hemoglobin 
Hbpost = postoperative Day One Patient Hemoglobin 
Donor RBCnormalized = [donor RBC volume]x[(donor Hct)/(Hctpre+Hctpost)/2)] 
Cell Salvage RBCnormalized = [cell saver RBC volume]x[(cell saver Hct)/(Hctpre+Hctpost)/2)] 
Hctpre = Preoperative Patient Hematocrit 
Hctpost = Postoperatve Patient Hematocrit 
 
Patient’s weight will be measured the day of surgery. Hctpre and Hbpre will be taken by the 
lead anesthesiologist prior to first incision through an ISTAT. Hctpost and Hbpost will be 
taken 12-18 hours after the end of the procedure through an ISTAT.  Donor and cell saver 
Hct will be taken by the lead hematologist before bags are sent up to the OR.  
 
f. Intraoperative Transfusion Guidelines 
Traditionally, CHCO does not have strict transfusion protocols for patients 
undergoing posterior spinal fusion surgery. Often these decisions are made at the 
discretion of the anesthesia provider in the operating room. This is due to the care 
involved and the differences between cases when caring for these incredibly complex 
patients. This is further complicated by differences in diagnosis, osteotomy procedures, 
and severity/flexibility of the scoliosis. Often in these complex surgeries, intangible 
variables such as estimated time remaining, perceived rate of blood loss, and trend of 
hematocrit levels all factor in to the decision. However, for this study, we have 
established guidelines for determining the need for intraoperative transfusion. The study 
team feels comfortable with these guidelines because all enrolled patients in this study 
will have a consistent diagnosis of adolescent idiopathic scoliosis, low rates of 
intraoperative bleeding, and no complex osteotomies such as a vertebral column 
resection. Our guidelines are below: 
 
• 
Hematocrit will be checked every 30 minutes by the anesthesiologist 
• 
Hematocrit levels below 23% will trigger a transfusion  
• 
Hematocrit levels between 23-28% will trigger a transfusion if hypotension and/or 
tachycardia (>20% different from baseline) is present despite adequate fluid 
resuscitation 
 
g. Study Interventions and Follow Up: 

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After patients have enrolled in the study and been randomized to a treatment 
group, study interventions will take place. The above outcomes will be collected at three 
different time points: preoperatively, intraoperatively, and postoperatively. Depending on 
the treatment randomization assignment, patients will undergo surgery with either the 
powered ultrasonic bone scalpel or with standard of care orthopedic surgical tools such as 
curettes, rongeurs, or high-speed burrs. These tools will be used in either treatment 
group for superior and inferior facetectomies, as well as to aid exposure of the pedicle for 
screw placement. All of these tools are commonly used at CHCO by facility pediatric 
orthopedic surgeons. Selection is most commonly made based on surgeon preference and 
familiarity. All surgeons involved in this study routinely use the surgical instruments being 
investigated. They have all received training and have experience with these instruments.  
 
Study follow up will occur postoperatively. Enrolled patients will return for their 
one month and one year postoperative appointments with their spine surgeon as per 
their plan of care. No unique study interventions will take place, but the above 
postoperative outcomes will be collected from the medical records by research 
personnel. All visits and collected data are considered to be in line with the plan of care 
for these patients and not performed solely for research purposes. Interventions such as 
radiographs and laboratory samples are already performed for clinical purposes.  
 
III. 
Description, Risks and Justification of Procedures and Data Collection Tools: 
a. Associated Risks and Justification of Study Intervention and Procedures 
The ultrasonic bone scalpel was approved by the FDA in May 2011 through 
application number K070313 for use in fragmentation and aspiration of hard and soft 
tissue in Orthopaedic surgery as well as a number of other specialties. The FDA found the 
safety profile of the device equivalent to an existing FDA approved device with the same 
indications.  
Previous research has also validated the safety of the ultrasonic bone scalpel. 
Based on previous reports, risk for iatrogenic dural tears with the USBS is comparable to 
or less than the standard tools mentioned above.[13, 16, 18-20] Matsuoka et al. 
acknowledged the device as good for preserving surrounding soft tissue during bone 
dissection.[17] Concern for thermal injury appears minimal with this device. Brooks et al. 
found that the heat generated by ultrasonic tools in cadaver bone did not differ from 
previously reported temperatures generated by high speed drills and also credits the 
irrigation system with reducing potentially high temperatures that could be produced 
from ultrasonic devices.[24] Hu et al. cited one instance of dural tear associated with 
thermal injury, however also suggests that the USBS, if used properly, can decrease the 
risk of soft tissue injury. The authors of this study recommended not allowing the blade to 
sit too long in one position to avoid thermal injury.[20] One study comparing 
laminectomy procedures with and without the USBS on an ovine model found no 
evidence of thermal injury, attributing the irrigation system with the ability to adequately 
cool surrounding tissues during osteotomies.[12]  
Research shows the USBS to be a safe alternative to historically standard tools 
with the potential for reduced blood loss (see section II. Background and Significance). 
Both methods are commonly employed by pediatric spine surgeons at CHCO for 
performing a variety of orthopedic procedures, including the procedures used in this 
study. Below is a table summarizing incidence of dural tear associated with the USBS in 
spinal surgery reported in previous studies.  

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All other study interventions and procedures (such as hospital visits, radiographic 
analysis, and laboratory procedures) are already performed by the physician care team as 
part of a surgical patient’s normal plan of care. Data collected from these interventions 
will be extracted from CHCO’s electronic medical record system.  
 
 
 
 
Author 
Year 
Surgical Use 
Number Age (year) 
Dural Tear  
in USBS 
Dural Tear in 
Non-USBS  
Al-Mahfoudh et al.[16] 
2014 osteotomy, laminoplasty 
62 
Not Provided
1 (1.6%) 
N/A 
Matsuoka et al.[17] 
2012 
recapping 
hemilaminoplasty 
33 
4-74 
0 
N/A 
Bydon et al.[18] 
2014 spinal decompression 
30 
8-19 
3 (30%) 
9 (45%) 
Bydon et al.[19] 
2013 
spinal decompression in 
achondroplastic patients 
337 
41-78  
5 (5.7%) 
9 (3.6%) 
Hu et al.[20] 
2013 osteotomy 
128 
12-85 
11 (8.6%) 
N/A 
 
b. Data Collection Tools 
Study data will be collected and managed using REDCap (Research Electronic Data 
Capture). REDCap is a secure web application designed to support data capture for 
research studies, providing user-friendly web-based case report forms, real-time data 
entry validation (e.g. for data types and range checks), audit trails and a de-identified data 
export mechanism to common statistical packages (SPSS, SAS, Stata, R/S-Plus). The 
system was developed by a multi-institutional consortium which includes University of 
Colorado–Denver and was initiated at Vanderbilt University. The database is hosted at the 
University of Colorado–Denver Development and Informatics Service Center (DISC), which 
will be used as a central location for data processing and management. REDCap data 
collection projects rely on a thorough study-specific data dictionary defined in an iterative 
self-documenting process by all members of the research team with planning assistance 
from the DISC. This iterative development and testing process results in a well-planned 
data collection strategy for individual studies. REDCap also includes a powerful tool for 
building and managing online surveys. The research team can create and design surveys 
in a web browser and engage potential respondents using a variety of notification 
methods. REDCap is flexible enough to be used for a variety of types of research and 
provides an intuitive user interface for database and survey design and data entry. 
 
c. Potential Scientific Problems: 
One potential scientific problem in this study has to do with the quantification of 
estimated blood loss. Past literature has revealed this measurement to be variable.[2, 25] 
We hope to overcome this problem by strictly adhering to the EBL collection protocol 
outlined above. Two research coordinators will take measurements and their 
measurements will be averaged for a final EBL. In this way, although the measurement is 
prone to misclassification, we anticipate misclassification to be non-differential.  A 
calculated blood loss will be performed to attempt to find reproducibility between the 
two types of measurements and reduce potential bias. Furthermore, the research 
assistants, who will be performing EBL measurements and calculations, will be blinded. 

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A second potential scientific problem could be obtaining 72 study subjects (36 for 
each group) to consent and enroll in the study protocol. Between the two protocol 
surgeons, approximately 80 patients with AIS undergo PSF each year. This population is 
actively involved in research at this institution and study personnel have been very 
successful in the past recruiting this patient population for research purposes. Based on 
the enrollment success rate of a current randomized clinical trial, the authors expect 80% 
of patients who are approached regarding this study to consent for participation. This 
requires 90 eligible subjects to be approached in order to reach the enrollment goal of 72. 
As such, it is expected that enrollment is completed within 2 years of study approval.  
Finally, as this study involves long-term follow-up, there is potential for subjects to 
become lost to follow-up. To accommodate this, our enrollment goal factors in a 10% 
dropout. For subjects who are lost to follow-up, two certified letters will be sent two 
week apart following the first missed clinic visit.  If there is no response, the subject will 
be contacted twice by phone.  If study staff is unable to contact the subject, they will be 
considered lost to follow-up. 
 
d. Data Analysis Plan 
An intent to treat analysis of all randomized subjects will be performed. Descriptive 
statistics will be used to compare the distribution of demographics and clinical 
characteristics in the two groups. Baseline covariates significantly different between 
groups will be considered as potential confounding variables in subsequent statistical 
models. The primary aim of this study is to compare differences in estimated blood loss 
per fusion level (EBL/level) between the USBS and standard of care groups 
(
). We aim to test the null hypothesis that the difference 
between groups is less than or equal to 0(
). An independent sample t-test or 
multiple variable linear regression analysis, as appropriate, will be used to compare total 
EBL/level in the two study groups. For the secondary outcome variables, Chi-square tests 
will be used to compare differences in the categorical variables (the risk of adverse 
events, proportion of subjects meeting the intra-operative blood transfusion criteria) 
between the groups. Independent sample t-tests or Wilcoxon rank sum tests will be used 
to compare differences in the continuous variables (operative time, post-operative length 
of stay, and intraoperative irrigation volume). 
 
e. Trial Monitoring/Human Subjects Research Consideration 
Data Safety and Quality - All data will be collected and stored in a REDCap database. 
Access to the database will be restricted to investigators involved the study protocol per 
study personnel section of the COMIRB protocol application and/or the study delegation 
of duties log. Photographs obtained during surgery will be de-identified, assigned an 
appropriate study ID and will be stored on a secure departmental server that is managed 
by the IT department at Children’s Hospital Colorado. The study coordinators will review 
data stored in the REDCap database on an ongoing basis. Potential outliers and/or 
biologically implausible data points will be identified and reviewed on an individual basis 
with the Principal Investigator.  
 
Safety Monitoring – Based on the advice of our clinical trial study design consultant, Dr. 
John Kittelson, a Data Safety Monitoring Board (DSMB) will review the safety and 
efficacy of the study. The DMSB will consist of an orthopaedic surgeon not directly 

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involved in the study, an administrator, an anesthesiologist not involved in the study, 
and an independent biostatistician. The DSMB will meet a minimum of three times. 
During the first meeting (open session), the progress of the study will be reviewed and 
any issues regarding safety, study feasibility, and/or protocol compliance will be 
discussed. This meeting will occur 1 month after the enrollment of the first study subject. 
The second meeting (closed) will occur after 50% of the study enrollment has been 
achieved. Prior to this meeting, the investigators will send a clean, unblinded dataset to 
the independent biostatistician that includes information regarding the primary clinical 
outcome of interest, estimated blood loss per level fused. This dataset will be used to 
determine whether any of the study stopping thresholds has been met (see 
Decision/Stopping Criteria below). The DSMB will meet a minimum of one additional 
time once 100% of the study enrollment has been achieved. Similarly, a clean, unblinded 
dataset will be sent to the statistician to determine whether the decision thresholds 
have been achieved (see Decision/Stopping Criteria below). Although unlikely, 
additional, emergent meetings will be scheduled as needed. The formation of the DSMB 
and documentation of DSMB related meetings will be done in accordance with CHCO’s 
DSMB policy. See DSMB Charter and DSMB Reporting Form for additional information. 
 
Safety monitoring will also be performed on ongoing basis by the PI and members of the 
study team. All adverse events will be submitted to the DSMB and will be reported to 
COMIRB within 5 business days. 
 
Decision/Stopping Criteria- This study will utilize a two-stage, group sequential design to 
monitor study progress. Under the alternative hypothesis, the two sided rejection 
boundaries at Stage 1 and Stage 2 were calculated according to the Obrien-Fleming 
method (see Figures below). After 16 subjects per group have been enrolled, an interim 
analysis will be performed (Stage 1). If the standardized Z statistic representing the 
difference in estimated blood loss 
) exceeds the upper or 
lower rejection boundary (Z > 2.7965 or Z <- 2.7965), the trial will be stopped. Assuming 
the standard deviation of blood loss per level fused is 30 in the USBS group and 28 in the 
standard group, the trial will stop if 
 29.2 mL/level or  <-29.2 mL/level. If blood loss 
per level fused does not exceed the rejection bounds, the trial will continue until a total 
of 62 subjects have been enrolled (31 per group). At stage 2, the standardized Z statistic 
will be compared to the rejection bounds (Z>1.9774 or Z<-1.9774). Assuming the 
standard deviation of blood loss per level fused is 30 in the USBS group and 28 in the 
standard group, we will conclude the USBS is superior to standard care instrument if  
 mL/level or inferior to standard care instruments if 
 mL/level. 
Sample size and stopping criteria were estimated using the RCTDesign package, R 3.1.2 
(R Foundation of Statistical Computing, Vienna, Austria). 
 
Summary of Decision Criteria - The decision criteria and potential corresponding 
conclusions are described in the table below. 
 
Stop For Harm 
Stop for Benefit 
Stage 
Enrollment 
† 
95% CI 
pvalue* 
† 
95% CI 
pvalue** 
Stage 1 
50% 
-27.1 
-42.2 to -8.55 
0.005 
27.1 
8.55 to 42.2 
0.005 

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Stage 2 
100% 
-13.9 
-29.01 to 0.00 
0.05 
13.9 
0.00 to 29.01 
0.050 
*Probability reject 
 
**Probability reject 
 
†Bias adjusted mean 
 
 
 
 
Figure 1. Plots of Rejection Boundaries (Red Lines) at Stage 1 and Stage 2 Relative to a 
Fixed Sample Design (Black Lines). 1.A Displays Rejection Boundaries on the Z Scale 1.B 
Displays Rejection Boundaries in Terms of EBL/level. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Probability of Stopping at the Interim Analysis  To aid in the interpretation of the stopping 
criteria, the probability of stopping the trial at the interim analysis (for benefit or harm), 
under hypothetical scenarios in which theta is known, has been estimated in the table 
below. 
 
True  
Probability of 
Stopping for Harm 
Probability of Stopping 
for Benefit 
A
B

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-29 
0.4930 
0.0000 
-14 
0.0729 
0.0000 
0 
0.0050 
0.0050 
14 
0.0000 
0.0729 
29 
0.0000 
0.4930 
 
 
 
 
Power/Type I Error Rate The power and type I error rate associated with this group 
sequential design, under hypothetical situations in which theta is known, is outlined in the 
table below.  
 
True  
Power for Lower 
Rejection Boundary  
Power for Upper 
Rejection Boundary  
-29 
0.975 
0.000 
-14 
0.470 
0.000 
0* 
0.025 
0.0250 
14 
0.000 
0.470 
29 
0.000 
0.975 
*Under null hypothesis (
, the design maintains a 
type I error rate of 0.05. 
 
f. Summarize Knowledge to be Gained 
This study will help to identify any potential advantages and disadvantages with 
regard to the use of an ultrasonic bone scalpel used in posterior spinal fusion surgery for 
patients diagnosed with Adolescent Idiopathic Scoliosis. A better understanding of the 
intraoperative outcomes such as estimated blood loss and surgical time compared 
between the two groups could reveal if one technique is able to provide significantly 
better results during surgery. If one method is determined to be more effective or 
efficient than the other, then it could have a positive impact on spinal fusion surgery. 
Decreased blood loss could lead to decreased need of intraoperative and postoperative 
transfusions and the risks associated with them. Further, shorter operative time would 
decrease wound exposure time, which could have an effect on postoperative 
complications. Decreased operative time could also decrease the financial burden of 
surgery. 
 
V. 
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