A Multicenter Prospective Study of Quality of Life in Adult Scoliosis
Phase: NA
Conditions: Scoliosis
Sponsor: Washington University School of Medicine

Adult Symptomatic Lumbar Scoliosis (ASLS) NIH RO1 AR055176-01A2 
 
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1.0 PROTOCOL 
 
Study Design Overview: This is a Phase III Clinical Trial.  Our overall goals are to evaluate the 
effectiveness of nonoperative and operative interventions in patients with adult symptomatic lumbar 
scoliosis (ASLS) and to identify important clinical and radiographic determinants of change in patient-
reported HRQOL. To accomplish these goals, a 5-year cooperative, multi-center longitudinal randomized 
study with a concurrent observational cohort is proposed. 
 
Specific Aim #1: Compare the outcomes of surgery and nonoperative treatment in patients aged 40 
to 80 with ASLS defined as a lumbar curve with a coronal Cobb measurement of 30° or more, and 
either of the following: Oswestry Disability Index (ODI) score of 20 or more; or Scoliosis Research 
Society Quality of Life (SRS-QOL) instrument score of 4.0 or less, in the domains of pain, function 
and/or appearance. 
Null Hypothesis: Nonoperative and operative treatment groups will have similar outcomes at follow-
up. 
 
Specific Aim #2: Evaluate the impact of patient factors (age, gender, socioeconomic status, 
education) and comorbidities [mental health, body mass index (BMI) and bone mineral density 
(BMD)] on adverse events and treatment outcomes for both the non-operative and operative arms. 
Incorporate these variables into a prediction model to help identify those patients most likely to 
benefit from either a surgical or non-operative approach. 
Hypothesis: Age, gender, socioeconomic status, education, and comorbidities will have an impact on 
the final result at 2-4 years post-intervention. 
 
From the adult section of the SDSG, we will utilize five centers that have consistently enrolled the 
most ASLS patients. From 2004 through 2006 these five centers enrolled 155 non-operative and 141 
operative patients meeting the ASLS criteria  Each center has committed to the enrollment of at least 10 
patients per year, and across all 5 sites we expect to average 20 patients per year, to reach a targeted 
enrollment of 300 patients over 3 years.  
As summarized in the flow chart shown in Figure 1 eligible patients at each site will be informed 
about the study and will be able to participate in one of two ways. Those agreeing to randomization will be 
randomized to operative or non-operative care, while those willing to participate in the study but not 
accepting random treatment assignment will be followed in a prospective observational cohort. The primary 
outcome measure will be longitudinal change in disease-specific quality of life as measured by the Scoliosis 
Research Society-Quality of Life (SRS-QOL) subscore. 
We plan to recruit a total of 300 patients into the trial. Based on our preliminary data, we expect 90% 
participation and about 30% randomization, resulting in a total of about 82 in the randomized trial and 188 in 
the observational cohort. While we will perform both intent-to-treat and as treated analysis, intent-to-treat 
analysis of the randomized trial will provide the most internally valid, un-confounded estimate of the effect of 
surgery, while the inclusion of the prospective observational cohort will help assess the external validity of 
the results and include a much broader spectrum of patients with ASLS than an RCT alone.   
 
 
1.1 Eligible Participants: This is a study of patients 
 
aged 40 to 80 years with  
 
ASLS defined as  
o 
lumbar curve with a coronal Cobb measurement ≥ 30°, and  
o 
either of the following:  
 
Oswestry Disability Index (ODI) score ≥ 20 or  
 
SRS-QOL score ≤ 4.0 in the domains of pain, function and/or appearance.  
 
If assigned to surgical intervention (by randomization or patient preference), the intervention plan 
would include, at a minimum, the Cobb levels of the Thoracolumbar/lumbar spine. 

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Patients 81 years or older are not eligible for inclusion, as most providers would not recommend major 
surgical procedures of this nature for these patients in this age group due to the increased risk of 
perioperative morbidity and mortality. Eligibility for participation is not restricted based on gender, ethnicity 
or principle language. 
Excluded from participation are patients with any of the following factors: 
 Substantial cardiac, pulmonary, renal or metabolic disease that, in the judgment of the surgical 
team, would preclude performing an operative procedure without undue risk of morbidity and 
mortality 
 Concomitant high-grade spondylolisthesis (Grade 3)   
 Prior thoracic or multiple level lumbar laminectomy or decompression [single or two level lumbar 
decompression (e.g., herniated disc) will not be an exclusion] 
 Prior thoracic or lumbar fusion  
 Osteoporosis evidence by a dual-energy x-ray absorptiometry (DEXA) T-score <-3.0 at the 
femoral neck for patients considered to be at risk (post-menopausal females, males > 60 years of 
age, steroid dependent rheumatoid arthritics, status post organ transplantation, etc.).  Patients 
may be randomized prior to obtaining DEXA results.  Non-Surgical patients may initiate non-
surgical treatments prior to completion of DEXA (if required) as non-surgical treatments will not 
affect DEXA results BUT DEXA must be completed and results entered within 3 months of 
enrollment.  Surgical patient must have DEXA prior to surgical intervention.  Waivers will be 
provided for patients meeting inclusion criteria who have had bilateral total hip replacements only 
if t score of spine and wrist are provided.   
 Neuromuscular scoliosis (e.g., spinal muscular atrophy, cerebral palsy, Parkinson’s Disease, post-
polio syndrome, Charcot Marie Tooth disease) 
 Congenital scoliosis in the lumbar spine.  Congenital anomalies of the cervical or thoracic spine 
are acceptable.   
 Spine tumor, infection or connective tissue disorder 
 Cognitively impaired or unable/unwilling to comply with follow-up 
 Pregnancy or planning on conceiving during time of study involvement  
 Ankylosing Spondylitis  
 Past history of vertebroplasty or kyphoplasty of the thoracic or lumbar spine 
 

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Figure 1:  Patient flow and Triage 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1.2 Identification and Enrollment: Site investigators and/or research coordinators will identify potential 
study participants based on patient history, physical exam, radiographs and HRQOL scores. See Section 19 
Administrative Forms:  Screening Checklist. Patients meeting inclusion/exclusion criteria will be offered 
study participation.  Potential patients will view a short video regarding study participation.     
Eligible patients not consenting to study participation will be entered into the electronic database in a 
de-identified manner. Age, gender, inclusion criteria and reason for declining participation will be 
documented.  
  
1.3 Randomization and Observational Cohort Assignments: Patients consenting to randomization will 
be randomized 1:1 to the non-operative or operative intervention arms. A permuted randomized block 
approach1 with blocks of size 4, 6 and 8 and stratified by site, age group (2 levels: 40-59 years of age, 60-
80 years of age), gender and Cobb angle-based severity (2 levels: 30-54°, 55-100°) will be used to ensure 
representative treatment assignment across these demographic and disease-specific categories with 
approximately balanced assignment totals at interim intervals as well. Based on preliminary data, we 
anticipate that 57% of participants will be in the younger age category and 43% in the older age category.  
Patient loss to follow-up can affect the randomization balance and quality. When a patient is lost to 
follow-up prior to treatment or because of an administrative error, such as qualifying a patient for inclusion in 
Not eligible for enrollment 
Patients seeking treatment 
and evaluated by surgeons 
at participating centers  
Eligible for enrollment: 
Discuss Study 
Consent to 
enrollment  
Decline 
enrollment 
Patient and physician determine 
either non-operative or operative 
care
Observational Cohort  
Operative 
Observational Cohort Non-
operative 
 
Recorded as 
eligible but 
declined, in log 
Patient is offered randomization 
into either operative or non-
operative arm 
Patient accepts randomization 
Patient declines randomization 
 
Operative care 
 
Non-operative care 

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the study when, in fact, study inclusion criteria were not met or exclusion criteria were initially missed, these 
patients will be removed from the study along with all study data. The guidelines for removing a patient from 
the study will follow the ICH guidelines; subjects who fail to satisfy an entry criterion will be excluded from 
the analysis under the following circumstances:  
1. the entry criterion was measured prior to randomization;  
2. the detection of the relevant eligibility violations can be made completely objectively;  
3. all subjects receive equal scrutiny for eligibility violations; and 
4. all detected violations of the particular entry criterion are excluded.  
The study management plan is explicitly designed to minimize these events. Specifically, there will 
be electronic registration by site coordinator with explicit inclusion and exclusion criteria assessment on the 
enrollment form and review of registration by the Project Manager (PM) at Washington University.   
In the observational cohort, the choice of nonoperative vs. operative care will be made by the patient 
guided by the provider’s recommendation and presentation of existing data regarding nonoperative and 
operative care based on the following parameters:  Patients with clinical symptoms of pain and functional 
limitations that are well controlled with non-operative care will be encouraged to pursue nonoperative care. 
Patients who have not demonstrated access or utilization to previous nonoperative care for their symptoms 
will be directed to non-operative care as an initial treatment. Enrollments into the observational arms will be 
closed when each arm’s sample size is reached in order to achieve equal numbers of patients in each arm 
at the conclusion of the study. 
 
1.4 Study Interventions: Regardless of study cohort participation (randomized or observational), 
interventions will not be implemented until the PM has confirmed appropriate enrollment. Nonoperative 
interventions will then be implemented as soon as possible. Due to the length and complexity of spinal 
deformity procedures, available dates for elective operative procedures may range from 1 to 6 months. 
Therefore, operative intervention will take place within six months of treatment assignment but baseline 
assessments, specifically MD assessment, patient reported HRQOL and treadmill tests must be completed 
within 6 months prior to intervention. Standardized protocol guidelines for nonoperative and operative 
treatment, as detailed below, will be followed by all sites.    
 
 1.4.1 Non-operative Techniques: To standardize non-operative treatments, sites will utilize one physician 
from their center with experience and expertise in non-operative management of spinal conditions 
(physiatrist, rheumatologist, or internist). For patients who live far from the enrolling center, referral to a local 
physiatrist will be made with a letter of introduction and a review of the proposed treatment plan from the 
study physician. A copy of the non-operative guidelines will be provided to all supervising nonoperative 
physicians. 
   
The strategy for non-operative care for all non-operative patients will include: 
1. Physical Therapy: Physical therapy will consist of treatment guided by one or a combination 
of:  core stabilization, resistance training, directional preference, movement based, manual 
therapy, treatment-based group classification, aquatic therapy.  Modalities will consist of 
strengthening arms and legs, improving aerobic conditioning, improving strength of spinal 
extensor muscles and teaching patients to avoid maneuvers that axially load or flex the lumbar 
spine. Physical therapy will include a combination of the following: water aerobics and/or 
reasonable forms of aerobic conditions. Strengthening of spinal extensor muscles will include 
upper and lower extremity muscles and avoidance of axial loading and flexion of the lumbar 
spine. Modalities for spine pain will include ultrasound, massage and transcutaneous electrical 
nerve stimulation (TENS) units.   
2. Injection Therapies: Injections including epidural steroid and selective nerve root blocks will be 
used for patients with a significant component of radicular pain. Patients with back pain from 
facet joints will be offered facet blocks and medial branch ablation. This care pathway will be 
ordered by the enrolling physician, and enacted by a specialist in injection therapies. For leg 
pain, if a specific lumbar nerve root appears to be involved, a selective nerve root injection will 

Adult Symptomatic Lumbar Scoliosis (ASLS) NIH RO1 AR055176-01A2 
 
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be considered. If leg pain is diffuse and involves both lower extremities, an epidural steroid will 
be considered.  
3. Pain Management: Medications including non-steroidal anti-inflammatory drugs (NSAIDs) and 
narcotic analgesics will be used as appropriate. Medications will be started with non-steroidal 
and/or mild narcotics and only increased if necessary. 
4. Complementary and Alternative Approaches: Patients in this study may access alternative 
healthcare resources including massage, acupuncture, acupressure and behavioral programs in 
an effort to improve pain and function. Alternative modalities will be made available to patients 
on a referral basis and the use of these modalities will be recorded for all patients. Weight loss 
will be strongly encouraged for body mass index (BMI) >27.  
 
 
At each follow-up visit, patients will document the extent to which they have utilized these 4 
modalities.   
 
1.4.2 Operative Techniques: Operative treatments have been standardized across all study centers. Each 
center and surgeon will follow these guidelines. Therefore, surgical interventions should be completed at the 
study center so the kinds of operative treatment the patients receive will be relatively uniform from center to 
center and from surgeon to surgeon.   
1. Extent of fusion: All spinal reconstruction cases will include at a minimum the Cobb levels of the 
curve. Additionally, the surgical reconstruction should include a balanced (neutral in rotation and 
stable, meaning centered on the center sacral line) vertebral segment at each end. All 
degenerative, rotated or listhetic segments will be included in the reconstruction.  
2. Anterior release and inter-body grafting of the lumbar and thoracolumbar curves may be 
considered when the curve is rigid (i.e., does not reduce by 50% on push, side bending films, or 
supine films).   
3. Pedicle subtraction and Smith-Petersen osteotomy can be performed as an alternate to anterior 
release for coronal or sagittal correction in rigid deformities.   
4. All symptomatic spinal cord or nerve root compression will be addressed surgically with 
decompression. 
5. Iliac bone graft and/or local bone will be used for fusion. This may be supplemented with bone 
growth factors and allograft.  
6. Segmental instrumentation (pedicle screw, hook, and rod) will be utilized for all reconstructions. 
A universal goal will be to achieve at least 1.5 fixation points per level and dual fixation points at 
the top and bottom of the construct. Only rigid instrumentation systems will be implanted.  No 
Dynamic Stabilization Devices will be used.  No artificial disc replacements will be used in the 
lumbar spine.  
7. Anterior structural support will frequently/usually be considered at L4-L5 and L5-S1, either as an 
anterior lumbar inter-body fusion (ALIF), posterior lumbar inter-body fusion (PLIF) or 
transforaminal lumbar inter-body fusion (TLIF) approach in patients being fused to the sacrum. 
8. With fusion to the sacrum, 4-point sacropelvic fixation will be utilized in all circumstances, either 
in the form of four sacral screws or two sacral screws and two iliac screws.  
9.   Decompression/laminectomies will be warranted for segments with substantial spinal stenosis, 
 
      both centrally and in the lateral recesses and in some cases in the foramen, when those  
 
      stenotic segments are judged to be substantially stenotic and contributing to the patient’s            
 
      symptoms. 
10.   Surgeon judgment will be trusted on the fractional curve below.  Most lumbar scoliosis consists of 
a curve that more or less goes from T10 to L3 or L4 with another curve that goes the other way 
between L3 or L4 and the sacrum.  It will be expected that in most cases both these curves will be 
addressed and fused and instrumented.  There may be some exceptions.  There may be some 
cases in which the fractional curve is not included and there may be some cases in which the 
main curve is not included and only the fractional curve is included.  If both curves are not 

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included, it would be helpful for the surgical team to give a description of why the decision was 
made to include only one of the two curves. 
 
If a consented patient is later not able to return to the original study center or a participating center for 
surgical intervention, it is expected that the patient will continue in the study and participate as fully as 
possible. 
 
Surgical summary data will not be collected or posted to the database unless the surgery was performed by 
one of the participating investigators.  If the surgery is not performed by a participating investigator, a 
Monitored Events report will be completed to reflect 1.  SAE (Hospitalization) and if applicable, intervention 
cross over and 2.  Discontinued treatment/Follow up continued.      
 
All follow up data will be collected by mail and telephone contact.  Sites will complete MD assessments by 
phone and follow up on any due diligence report reaching contact threshold.  Sites should try to obtain 
copies of radiographic images annually.   
 
Sites and patients will be reimbursed for ‘long distance’ follow up as outlined in the MOOP, Section 25. 
 
 

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1.5 Schedule of Events and Data Collection:  Table 1: Schedule of Events   
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Baseline Variables collected 
within 6 months prior to 
intervention implementation: 
 Patient Information (i) 
 HRQOLs (i) 
 Clinical Assessment (i) 
 Radiographs (ii) 
 Treadmill test ™  (iii) 
 DEXA (iv) 
 
Variables collected at 1-
year follow-up 
 Patient Follow up (i) 
 HRQOLs (i) 
 Clinical Assessment (i) 
 Radiographs (i)  
 Monitored Events (vi) 
 Progress & Satisfaction 
ix   
2-year Follow-up 
Variables collected at 2 
-year follow-up 
 Patient Follow up (i) 
 HRQOLs (i) 
 Clinical Assessment (i) 
 Radiographs (ii) & 
Fusion Assessment (viii) 
 Treadmill test (iii) 
 Monitored Events (vi) 
 Progress & Satisfaction 
ix
3-Year Follow-up 
Variables collected at 3-
year follow-up* 
 Patient Follow up  (i) 
 HRQOLs (i) 
 Clinical  Assessment  (i) 
 Radiographs (ii) 
 Monitored Events (vi) 
 Progress & Satisfaction 
ix 
 DDR (vii) 
Enrollment 
1-year Follow-up 
Initial Follow-up:        
3 months post-treatment 
Variables collected at initial follow-
up  
 
 Patient Follow up (i) 
 HRQOLs (i) 
 Clinical Assessment (i) 
 Radiographs (v) 
 Monitored Events (ME)  (vi)Due 
Diligence Report (DDR) (vii) 
6 & 9 
Month 
Interim 
Contact  
HRQOLs via 
mail &  
DDR (vii), ME 
& Clinical 
assessment 
(i) 
 
15, 18, 
21 
Month 
Interim 
Contact 
HRQOLs via 
mail &  
DDR(vii), 
ME & 
Clinical 
assessment 
(i) 
30-
Month 
Interim 
Contact 
HRQOLs via 
mail &  
DDR (vii), 
ME & 
Clinical 
assessment 
(i) 
Intervention 
Study Day 0 
42-Month 
Interim 
Contact if 
applicable 
HRQOLs via 
mail &  
DDR (vii), ME 
& Clinical 
assessment (i) 
 
(i)    Patient Baseline Information, Patient Follow-up, HRQOL questionnaires (SRS-QOL, ODI, SF 12), and MD clinical assessment.    
(ii)   Standing long cassette coronal (AP) and sagittal (lateral) radiographs of entire spine from C7 to femoral heads. 
(iii)  If Non-Surgical patient crosses over to Surgical arm & surgery is prior to reaching 21 mo follow up, 2 year treadmill test (TM) is to be delayed until the patient is 2 year s/p 
CROSSOVER surgical procedure.  If patient crosses over and surgery is between 21 & 30 mo follow up, pt will be complete TM prior to surgery and asked to complete a 3rd TM 
when 2 years out from crossover surgery.  See Appendix for a description of the standardized treadmill test. 
(iv)  DEXA within 24mo of enrollment for all post-menopausal females, males > 60 years of age, any steroid dependent participant unless, is taking FDA approved drug for treatment 
of osteoporosis, has history of fracture in the past year, has taken steroids on long term basis or most recent DEXA scan t score was -2.5 or worse, in which case, DEXA in the past 
12 months of intervention is required. 
(v)   Standing long cassette radiographs for operative intervention only. 
(vi)  Monitored Events (ME) including:  Serious Adverse Events, Crossovers and Withdrawal from Study Participation 
(vii) Due Diligence Report (DDR) ran by PM after follow up data entered.   
  (viii) Fusion Assessment:  In addition to Standing AP & lateral radiographs, obliques (right & left) images of the surgical site and, if fused to the sacrum, a Ferguson AP L5-S1 will be 
obtain for patients treated surgically at those centers were these radiographs are collected as standard care. 
  (ix) Progress & Satisfaction questionnaire as reported by the patient at annual visits and at time of crossover or revision surgery. 
The only difference between nonoperative & operative interventions is no x-rays are obtained at the initial (3 month) follow-up & Fusion Assessment is not applicable in the 
nonoperative arm. 
 
4 & 5 & 6 Year Follow-up 
if applicable 
 Variables collected at  
follow-up* 
 Patient Follow up  (i) 
 HRQOLs (i) 
 Clinical  Assessment  (i) 
 Radiographs (ii) 
 Monitored Events (vi) 
 Progress & Satisfaction ix 
 DDR (vii) 

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1.5.1 Data Collection and Forms:  (Please note, all Case Report Forms are located in Section 26).  
This is a five year study (with 2 year extension) in which all patients will have a minimum of 2 year 
follow up.  Additional 3, 4, 5 & 6 year follow up will depend upon when patient entered the study.    
If enrolled Year 1, participation in the study will be for 6 years. 
If enrolled Year 2, participation in the study will be for 5 years. 
If enrolled Year 3, participation in the study will be for 4 years.  
If enrolled Year 4, participation in the study will be for 3 years.  
If enrolled Year 5, participation in the study will be for 2 years.  
 
Patient Baseline Information: Baseline covariates will include: age, gender, medical history, socioeconomic 
status, and education level. In addition, we will capture patient symptoms, characterizing the percent of back 
pain and leg pain through numerical rating scales (NRS).   
 
HRQOL: Two HRQOL questionnaires will be collected (SRS-QOL, ODI) at baseline and specified follow-up 
intervals (3, 6, 9, 12, 15, 18, 21, 24, 30, 36, 42, 48, 60 and 72 months post-intervention). In addition, the SF 12 
will be completed at baseline and annually.  All questionnaires will be administered by the site research 
coordinator either at the time of the office visit or by mail. 
 
SRS-QOL: The SRS-QOL is a disease-specific instrument for the measurement of health status in 
patients with spinal deformity. Age-gender norms exist for the non-deformity adult population. The SRS-
QOL questionnaire has been fully validated in adult spinal deformity patients. It is reproducible, reliable, 
and sensitive to change. The questionnaire has four domains: pain, function, self-image and mental 
health. Domain values and subscore (a summary over the 4 domains) are reported as an average 
score for each domain (1-5). A score of 5 implies no pathology and a score of 1 implies maximum 
pathology. There are 2 satisfaction questions scored in similar fashion: 5 implies maximum satisfaction 
and 1 implies maximum dissatisfaction. There are 7 historical recall questions asked post-treatment to 
assess patient feelings regarding QOL improvement and to document satisfaction.  
 
Oswestry Disability Index: The ODI is a disease-specific measure of disability associated with back 
pain. The instrument is a 10-item questionnaire that has been validated and is reproducible and 
reliable. Norms exist for a population without back pain, and thresholds have been established for 
defining a clinically significant difference in scores. The ODI scoring is on a 0-100 point scale (0 implies 
no pathology and 100 implies the maximum pathology). 
 
Short Form-12: The SF-12 is a self-administered, generic HRQOL measure derived from the Rand 
Health Insurance Long Form. The SF-12 is validated for the U.S. with age and gender normal values. 
This instrument provides mental and physical component scales (MCS, PCS) for translating health 
status and changes in health status between cohorts of patients with distinct disorders. Previous 
studies in adult scoliosis have used the SF-12 to measure HRQOL. 
 
All three of these outcomes instruments will be available in Spanish. The Spanish translated HRQOLs have 
been validated. 
 
Progress & Satisfaction questionnaire.  This is a brief, four item questionnaire for the patient to document 
satisfaction with treatment and treatment assignment.  This questionnaire will be completed at the time of the 
office visit or by mail.  The questionnaire is also completed at the time of crossover and prior to any revision 
surgery.  
 
Functional Treadmill test:  All patients will have a standardized functional treadmill test performed at baseline 
and 2 years post-treatment. This test is performed routinely at Washington University and has been published 
in The Journal of Bone & Joint Surgery. (See Appendix for details).  
If a Non-Surgical patient crosses over to the Surgical arm and tentative surgery date is prior to 21 month follow 
up, 2 year post intervention treadmill test will be delayed until the patient is 2 year s/p CROSSOVER surgical 
procedure.   
 

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If Non-Surgical patient crosses over to Surgical arm and tentative surgery date is between 21 and 30 month 
follow up, post intervention TM will be obtained prior to crossover surgery.  These patients will be asked to 
complete a 3rd treadmill test 2 years after CROSSOVER surgical procedure.  If the patient is agreeable, a 
separate, supplemental consent will be obtained for 3rd treadmill test.  Patient and site (physical therapist) will 
be reimbursed for all three treadmill tests.   
 
MD Clinical and Radiographic Assessment: The physician and/or research coordinator will complete clinical 
assessments capturing pertinent neurologic and/or physical findings and comorbidities at baseline and clinical 
follow-up appointments (required at 3, 12, 24, 36, 48 & 60 months post-intervention with capability to compete 
as needed at all study intervals). Baseline clinical assessment will include recording of comorbidities, BMI and 
bone mineral density (BMD). Baseline BMD (femoral neck t score) will be captured by Dual energy X-ray 
absorptiometry, or DEXA, which is most widely used and accepted as an accurate, economic and noninvasive 
predictor of BMD for postmenopausal females, males 60 years or older, or any patient in which it is clinically 
indicated (e.g.  steroid dependent, post organ transplantation, etc.)  DEXA machines have a standard 
reference (called NHANES III) that can be used for all machines, regardless of manufacturer. BMD obtained 
via qualitative CT, peripheral DEXA scan or ultrasound is not acceptable. Since degenerative spinal conditions 
and scoliosis may alter the results of the DEXA BMD femoral neck t scores will be recorded. Waivers will be 
provided for patients meeting inclusion criteria who have had bilateral total hip replacements only if t score of 
spine and wrist are provided.   
 
Specified radiographic parameters (coronal and sagittal balance; coronal and sagittal Cobb 
measurements) based on long cassette radiographs will be captured at baseline and clinical follow-up 
appointments (3 months for operative arm only and at 12, 24, 36, 48 & 60 months post-intervention for both 
arms).  Fusion mass will be assessed by reviewing right and left obliques and Ferguson AP L5-S1 (if fused to 
the sacrum) at two years post intervention for patients treated surgically, if considered standard care at the 
participating centers.           
 
Medical History & Medication Log:  This is a source document to capture baseline medical problems.  It will be 
reviewed at each clinical follow-up to ensure accurate capture and reporting of any adverse events.  Data 
collected on this source document will be used to complete Monitored Events and MD Clinical Assessment 
CRFs.   
 
Surgical Summary: For patients managed operatively, a surgical summary will be completed by the surgeon at 
the time of intervention. Data captured will include, but not be limited to:  blood loss, length of surgery, surgical 
approach, and vertebral levels involved. Equally important will be the reporting of any intra-operative adverse 
events, as well perioperative adverse events occurring prior to discharge. Procedural codes (CPT codes) will 
also be reported. 
 
Patient Intervention Follow-Up: All participants will complete a comprehensive description of the nonoperative 
modalities used, and the frequency of use will be detailed (3, 6, 9, 12, 15, 18, 21, 24, 30, 36, 42, 48, 60 & 72 
months post-intervention). These assessments will be part of the standard questionnaires given at each study 
follow-up. Patient diaries will be used as memory aids but will not be used for primary data collection. Any 
adverse events stemming from nonoperative or operative treatments will be recorded along with changes in 
health history.  
 
Monitored Events: Sites will complete a Monitored Events Case Report Form (CRF) at each clinical follow-up 
appointment to report:  Serious or Unexpected but reasonably related adverse events (AEs), Crossover to the 
other intervention, or exiting the study.   In addition, sites will complete this form as applicable with each patient 
contact, including telephone calls. 
 
Due Diligence Report:  This report will be run by the Project manager after each follow up visit data has been 
entered into database.   The report will calculate differences in previously reported HRQOL value.  Any patient 
with a decrease of -0.5 in the SRS domains or an increase of 10 or more points in the ODI score warrant 
further investigation.   

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The primary outcome variable will be the change in SRS-QOL subscore because the literature supports 
this questionnaire as a more disease-specific tool for assessment of spinal deformities. The concurrent validity 
of the SRS-QOL function domain compared favorably to the SF-12 PCS (r=0.73) and the ODI (r=0.87), as did 
the SRS-QOL mental health domain compared to the SF-12 MCS (r=0.87).  Thus, the SRS-QOL is especially 
suited to our study population and research questions. Changes in ODI and SF-12 will also be assessed as 
they are frequently used measures of QOL and will facilitate comparison of our findings with those of others.  
 
1.5.2 Data Collection Procedures: Site research coordinators will identify, consent and enroll eligible 
participants in the study. After obtaining patient consent, the site coordinator will electronically register 
participants through a secure Web site. Registration information will include demographic information and 
documentation of inclusion criteria to minimize inappropriate enrollment. Randomization software will generate 
an intervention assignment upon completion of registration for patients agreeing to randomization. Site 
coordinators will notify the PM of patient enrollment via alpha pager. Site coordinators will provide 
questionnaire packages at study entry (all patients), at 3 months post-treatment and at each annual post-
treatment clinical visit. In addition, questionnaire packets will be mailed to participants at 6, 9, 15, 18, 21, 30, 
42 & 72 months post-intervention to enhance patient tracking. A self-addressed, stamped envelope will be 
provided for return of questionnaires. Therefore, patients will complete HRQOL at baseline and every 3 months 
post-intervention for the first 2 years, every 6 months years 3 & 4 and annually thereafter.   
Radiographic images will also be electronically uploaded to the database for measurement, future 
retrieval and review. An independent, blinded, experienced orthopedic spine surgeon will perform radiographic 
measurements at baseline and at annual follow-up visits.  The surgeon will be blinded to patient, site and 
surgeon identification and he will not enroll or treat any study participants, thus eliminating the potential threat 
for bias if sites measured their own patient films.  In addition, the blinded surgeon will assess fusion mass on 
participants receiving surgical treatment by reviewing radiographic images (standing AP and lateral, right and 
left oblique views of the surgical site, and, if fused to the sacrum, a Ferguson AP L5-S1).  Results will be 
recorded on the Radiographic Assessment form and entered into the database.  In addition, Clinical 
Assessment forms will be completed at baseline and annual follow-up visits to document physical and medical 
findings, including adverse events and complications. 
Data capture will occur via REDCap, a secure Web-based data input interface available in each 
participating center’s research facility. This Web-based secure data capture, data storage and data 
transmission system is maintained by Washington University. To improve data accuracy, double data entry will 
be implemented. Immediate data clarifications will be generated at the time of data entry for missing 
responses, out-of-range responses, and/or inconsistencies in responses that break established validity rules. 
The REDCap application is fully HIPAA-(Health Insurance Portability Accountability Act) compliant and will 
have thorough testing and validation processes in place. Baseline data will be entered within 24 hours of 
enrollment, before study interventions are activated. Follow-up data will be entered within 1 week of a patient’s 
visit.  
 Site coordinators and PIs will receive a monthly Upcoming Events Report via email. This report will be 
generated by the PM and include any patient who will be due for a clinic visit in the upcoming 3 months. Site 
coordinators will have the capability to run this report more frequently, if they choose. This will allow site 
coordinators adequate time to contact and arrange for appropriate scheduling, including functional treadmill 
testing at the 2-year follow-up. The report will also include all patients who will require HRQOL mailings in the 
upcoming month. Site coordinators will be responsible for mailing, tracking return of and entering data from the 
questionnaires. Failure to obtain and store data on patients within a 1-week period of the expected encounter 
windows will be monitored by the PM through weekly database queries. The PM will follow up with the site 
coordinator to further investigate these situations. Weekly reports of patients with past due follow-up will be 
sent to the site coordinator and PI.   
Patients will be encouraged to return to the primary center for examination, radiographs and 
questionnaires at the designated intervals. If the patient is unable to return to the center, they will be 

Adult Symptomatic Lumbar Scoliosis (ASLS) NIH RO1 AR055176-01A2 
 
MOOP Version12, Protocol amended 1/23/15 
Page 11 
 
encouraged to complete questionnaires and radiographic studies locally and mail them to the primary center at 
the intervals required by the study protocol.  
Acceptable windows for data collection are as follows: 
 
Baseline data must be completed prior to intervention initiation, specifically:  
 
Site and patient completed forms, functional treadmill test completed within 6 months prior 
intervention initiation, 
 
Radiographs (standing AP and lateral entire spine) completed within 6 months prior to 
intervention and  
 
DEXA scan of femoral neck* (if applicable) completed within 24 months prior to enrollment and 
prior to intervention** UNLESS patient meets any of the following criteria, in which DEXA must 
be completed 12 months prior to intervention: 
o Taking an FDA approved drug for the treatment of osteoporosis 
o History of fracture in the past year 
o Has taken Prednisone on a long term basis 
o Most recent DEXA scan t score was -2.5 or worse. 
*Waivers will be provided for patients meeting inclusion criteria who have had bilateral total hip 
replacements only if t score of spine and wrist are provided.   
* *Patients enrolled in the NON surgical arm may initiate non-surgical treatment measures but 
must have DEXA completed (if required) within 3 month 
 
Initial follow-up is to be completed 30 to 120 days post intervention.  
 
Interim questionnaires/assessments will be mailed and posted to database +/- 30 days of scheduled 
event (6, 9, 15, 18, 21, 30,  42, 72 months post intervention).  
 
One year follow-up must be completed11 months to 1 year 4 months post intervention. 
 
Two year follow-up cannot be captured prior to 2 year anniversary date and up to 4 months post 
anniversary date.   
 
Three year follow-up will be captured 2 year 11 months to 3 year 4 months post intervention. 
 
Four year follow-up will be captured 3 year 11 months to 4 year 4 months post intervention.  Patients 
who reach the 4 year milestone prior to end of current grant funding (Aug. 30, 2016) will be asked to sign a 
revised informed consent to include 5 year clinical visit and 72 month interim mailing if applicable).   
 
1.5.3 Patient Compliance: To enhance patient compliance and participation, the site coordinators will mail 
interim questionnaires to all study participants at 6, 9, 15, 18, 21, 30, 42, & 72 months post-intervention. These 
will be completed in addition to the HRQOL questionnaires obtained at baseline and post-intervention clinical 
appointment visits (3, 12, 24, 36, 48 & 60 months). Furthermore, participants will be reimbursed for time and 
travel associated with completion of HRQOLs questionnaires, treadmill tests, radiographic and clinical exams.  
In the event that subjects do not return for a scheduled follow-up visit, or fail to return mailed 
questionnaires in a timely manner (within four weeks of mailing), site coordinators will contact subjects via 
telephone and/or e-mail. After two failed attempts, site coordinators will send a U.S. Postal Service certified 
letter to the subject’s last known address. Address change service will be requested with all mailings. If 
certified mailings are returned undeliverable with no forwarding address, site coordinators will notify the PM, 
who will then conduct Internet searches and fee-based searches, such as ChoicePoint, to locate missing 
subjects. 
Any patient deciding not to return to &/or continue treatment at the study will continue to be followed by 
mail and telephone, if the patient is willing.  A monitored events report will be completed to document this 
change in patient and treatment status (Discontinued treatment/Follow up continued).  Sites will mail QOLs to 
patients at interim and clinical follow up intervals.  Site will follow up with patient if Due Diligence Report 
reaches contact threshold, to clarify any questionable patient information, &/or follow up on any questionnaires 
not returned.  Site will ask patient to mail x-rays at annual milestones, as outlined in the protocol.  Follow up 
MD assessments will only document treatments actually prescribed/recommended the Study PI (not MD from 
outside institutions).   
 

Adult Symptomatic Lumbar Scoliosis (ASLS) NIH RO1 AR055176-01A2 
 
MOOP Version12, Protocol amended 1/23/15 
Page 12 
 
1.6 Project Manager (PM). In addition to confirming appropriate participant study enrollment the PM will be 
responsible for tracking and monitoring productivity at all centers to further ensure complete and accurate data. 
It will be the responsibility of this individual to strive for 100% follow-up in both nonoperative and operative 
arms of the study.  
The PM will have 24 hour/day access to the data collected and stored on study patients. The PM will 
query the database on a daily basis to monitor each site’s productivity (enrollment and follow-up). Likewise, the 
sites will have access to the PM via alpha pager.   
Responsibilities of PM: 
 
Develop an operations manual. 
 
Provide detailed training of site coordinators upon study initiation at start-up meetings and throughout 
the remainder of the study via conference calls and site visits. Conference calls with the PM and site 
coordinators will be held weekly until all sites are actively participating and comfortable with the study 
protocol, with decreasing frequency as study needs dictate.  
 
Visit each site at the time of, or soon after, the first subject has been enrolled to ensure completeness 
of protocol procedures.  
 
Conduct monitoring visits to the sites once per year during active enrollment. 
 
Ensure the appropriate inclusion/exclusion of each patient in the study. 
 
Maintain a list of study participants (site, cohort and intervention arm).  
 
Maintain a list of eligible participants who decline study participation and reason for decline.   
 
Track and ensure complete data entry on all patients. Contact site coordinator and work to resolve any 
issues for patients whose visits have not occurred during the specified interval window. 
 
Create and provide monthly site reports for upcoming study events due (clinical visits and questionnaire 
mailings). 
 
Review each Protocol Variances with Lead Investigator.  Action plans for each variance will be 
determined based on the individual variance.   
 
Perform random checks of critical parameters on films measured by the independent observe.  
Discrepancies >10 degrees in Cobb measurements or 10mm in linear measurements will be resolved 
through discussions with PM and independent observer.  Measurements will include:    
o Major Cobb angle of the lumbar curve 
o Sagittal Cobb angle from T12 to the sacrum 
o Sagittal Cobb angle from T5 to T12 
o Sagittal Cobb angle from T10 to L2 
o C7 plumb relative to the sacrum (coronal balance) on standing long cassette radiographs 
o C7 plumb relative to the sacrum (sagittal balance) on standing long cassette radiographs 
 
Troubleshoot potential site issues through, but not limited to: 
o Tracking frequency and type of data clarifications generated,  
o Tracking unresolved data clarifications,  
o Tracking data collection and entry within appropriate interval windows. 

Adult Symptomatic Lumbar Scoliosis (ASLS) NIH RO1 AR055176-01A2 
 
MOOP Version12, Protocol amended 1/23/15 
Page 13 
 
1.1 Schedule of Events 
CRF = Case Report Form  
*Surgical Arm only  
**Fusion Assessment, Surgical Arm only 
***See Protocol, pg 3 & 9 for details 
  ****See Protocol, pg 7-8 for details 
 
Visit 0 
Day 1 
FU 1 
FU 2 
FU 3 
FU 4 
FU 5 
FU 6 
FU 7 
FU 8 
FU 9 
FU 10 
FU 11 
FU 12 
FU 13 
FU 14 
Visit Description 
Screening/ 
Baseline 
Intervention 
3mo 
6mo 
9mo 
12mo 
15mo 
18mo 
21mo 
24mo 
30mo 
36mo 
42mo 
48mo 
60 mo 
72 mo 
Study Visits (months) 
-6 mo to -
1day except 
as noted 
Day 0 
30 to 
120 
days 
+/-30 
days 
+/-30 
days 
11mo 
to    
16mo 
+/-30 
days 
+/-30 
days 
+/-30 
days 
24mo 
to 
28mo 
+/-30 
days 
35mo 
to 
40mo 
+/-30 
days 
47mo 
to 
52mo 
59 mo 
to 
64mo 
+/-30 
days 
Informed Consent 
x 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Upright AP/lateral 
radiographs entire spine C7 
to sacrum* 
-6mo to -
1day 
 
x* 
 
 
x 
 
 
 
x** 
 
x 
 
x 
x 
 
History & Physical exam 
x 
 
 
 
 
x 
 
 
 
x 
 
x 
 
x 
x 
 
Patient Baseline CRF 
x 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medical History & Medication 
Log 
x 
 
x 
 
 
x 
 
 
 
x 
 
x 
 
x 
x 
 
ODI 
x 
 
x 
mail 
mail 
x 
mail 
mail 
mail 
x 
mail 
x 
mail 
X 
x 
Mail 
SRS-30 
x 
 
x 
mail 
mail 
x 
mail 
mail 
mail 
x 
mail 
x 
mail 
x 
x 
mail 
SF-12 
x 
 
 
 
 
x 
 
 
 
x 
 
x 
 
x 
x 
 
Progress & Satisfaction 
 
 
 
 
 
X 
 
 
 
X 
 
X 
 
x 
x 
 
MD Baseline Clinical 
Assessment CRF  
x 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Treadmill  test 
x 
 
 
 
 
 
 
 
 
X**** 
 
 
 
 
 
 
DEXA*** 
-12mo to -
1day 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Randomization 
x 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Surgical Summary CRF 
 
x 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Non Operative Summary 
Source Document 
 
x 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Patient Follow up Information 
 
 
 x 
mail 
mail 
x 
mail 
mail 
mail 
x 
mail 
x 
mail 
x 
x 
mail 
Due diligence report 
 
 
x  
x 
x 
X 
x 
x 
x 
X 
x 
X 
x 
x 
x 
x 
MD Follow up Clinical 
Assessment CRF 
 
 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Monitored Events CRF 
 
X 
X 
x 
x 
X 
x 
x 
x 
X 
x 
X 
x 
X 
x 
x