Management Strategies for Patients With Low Back Pain and Sciatica
Phase: NA
Conditions: Low Back Pain, Sciatica, Physical Therapy
Sponsor: University of Utah

Protocol Summary 
Version: 10/27/2014 
Management Strategies for Patients with Low Back Pain and Sciatica 
Principal Investigator 
Julie M. Fritz 
Distinguished Professor, Department of Physical Therapy & Athletic Training 
The University of Utah 
520 Wakara Way 
Salt Lake City, UT  84108 
(801) 581-6287
julie.fritz@hsc.utah.edu  
Co-Investigator(s) 
 
Gerard Brennan 
Senior Research Scientist and the Director for Clinical Quality and Outcomes Research 
Intermountain Healthcare 
5848 South 300 East  
Murray, UT 84107 
(801) 314-4100
Gerard.Brennan@imail.org 
Tom Greene 
Professor, Division of Clinical Epidemiology 
The University of Utah 
295 Chipeta Way 
Salt Lake City, UT  84132 
(801) 585-6667
Tom.Greene@hsc.utah.edu 
Sponsor Contact Information 
Agency for Health Research Quality 
Kim Wittenberg 
540 Gaither Road 
Rockville, MD  20850 
(301) 427-1321
kim.wittenberg@ahrq.hhs.gov 
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SPECIFIC AIMS 
The research dissemination and demonstration project described in this proposal addresses an important 
evidence gap in the initial management of patients with a common condition; low back pain (LBP) with 
sciatica; a condition that can be disabling and costly for affected individuals and the healthcare system. 
Most patients with LBP and sciatica initially access healthcare in primary care settings. Practice 
guidelines4,33 advocate initial management with first-line medications and patient education.  Imaging (x-ray 
or MRI), opioid medications and invasive interventions such as injections or surgery are not indicated during 
the initial 4 weeks of management for the large majority of patients.  Guidelines further advocate a shared 
decision-making process with respect to whether additional therapies should be used during the initial 
weeks of management, however there is currently very little high-quality evidence that can help inform this 
important decision. Uncertainty about the effectiveness of therapies that may be used early in the 
management of patients with LBP and sciatica is likely contributing to increasing utilization rates of MRI, 
opioids, injections, and surgery for these patients,21,22,39,40 and rapidly growing costs without documented 
improvements in patient-centered outcomes.41  More effective initial management strategies may help to 
curb rapidly escalating use of expensive and invasive tests and interventions.  The window of opportunity to 
avoid these procedures may be in the initial management decisions emanating from the initial primary care 
encounter, but this hypothesis has not been adequately examined.       
Physical therapy is often used at some point in the course of care for patients with LBP and sciatica, 
although its use during the initial 4-week management period is relatively uncommon and highly variable 
geographically.  Our research team has conducted several preliminary studies indicating that the 
effectiveness of physical therapy in improving patient-centered outcomes and reducing risks for subsequent 
healthcare utilization for patients with LBP is enhanced if patients are referred early, instead of later, in the 
course of care.47  Also, our team has conducted a series of studies to identify a physical therapy program 
specifically tailored to patients with LBP and sciatica that optimize clinical outcomes.52,72,73  Based on this 
work we are proposing to evaluate the effectiveness of adding a standardized, evidence-based physical 
therapy program to primary care management early in the care for patients with LBP and sciatica.  We 
hypothesize that the initial weeks of management provide a window of opportunity to avoid progression to 
persistent pain and disability and utilization of progressively more invasive and expensive management 
procedures if an evidence-based strategy is employed. The proposed study evaluates this overall 
hypothesis.  If early physical therapy proves effective, broader dissemination into healthcare delivery could 
be evaluated. We will also seek to identify moderators of improvement with early physical therapy.
Identifying moderators would provide information about the specific characteristics of patients most likely to 
benefit from early physical therapy (e.g, those with higher initial pain severity, etc.) which could inform 
shared decision-making for providers and patients in the future.  This project fits the current AHRQ 
Comparative Effectiveness Research Portfolio. The project examines the impact of translation of new 
scientific information into clinical care, and develops evidence to inform clinical decision-making for an 
important priority condition. 
We will conduct a randomized trial comparing the effectiveness and costs associated with adding physical 
therapy to primary care management during the first 4 weeks of care for patients with LBP and sciatica. 
Patients with LBP and sciatica with a new consultation in primary care will be randomized to receive 
guideline-based primary care management with or without early physical therapy.  Patients will be followed 
for 1 year.  Outcomes will include measures of disability, pain, satisfaction, healthcare utilization and costs.  
Specific aims for the study are the following: 
1. Compare the effectiveness of two initial management strategies for a subgroup of patients with LBP and
sciatica.  We hypothesize that early physical therapy will result in greater improvements in disability and
pain over 1 year compared to a usual care strategy.
2. Compare utilization of specific healthcare procedures [and healthcare costs] associated with two initial
management strategies for a subgroup of patients with LBP and sciatica.  We hypothesize that early
physical therapy will result in decreased utilization of MRI and injections over 1 year compared to a usual
care strategy.
3. Evaluate moderators of improvement with early physical therapy as an initial management strategy. This
aim is exploratory, however we hypothesize that pre-specified psychosocial and clinical factors will
moderate improvement with early physical therapy.
Specific Aims
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clinics for recruitment. These assests will benefit the proposed project by permitting more efficient 
development of data management and recruitment procedures.      
C.2  Overview of Approach
This study will be a pragmatic randomized trial comparing strategies for managing patients with a new 
episode of LBP and sciatica in primary care.  One strategy is usual care (UC) directed within primary care 
during the initial 4 weeks.  The other strategy is early physical therapy (EPT) with patients receiving 6-8 
sessions in the initial 4 weeks.  We will examine patient-centered outcomes and subsequent healthcare 
utilization [and costs] over a 1-year follow-up period.  Based on our hypothesis that the first few weeks 
provide an opportunity to positively influence the clinical course of LBP with sciatica, the difference between 
strategies occurs in the 4 weeks after an initial primary care encounter.  The study will use a pragmatic 
approach comparing these strategies under realistic clinical circumstances.  Recruitment will occur from
primary care clinics in the University of Utah Health Care system.  Dr. Fritz has previously led successful 
clinical trials in this system. Patients visiting a primary care clinic with a chief complaint of LBP and sciatica 
will be potentially eligible. Eligible patients who provide informed consent will undergo baseline assessment 
followed by randomization to a treatment group (UC / EPT).  Both groups will receive first-line medication as 
needed and advice and education emphasizing remaining active and the inappropriateness of early imaging 
or specialist referral as recommended by the APS/ACP guideline.33 The UC group will be managed within
primary care for the next 4 weeks with a stepped approach (ie, referral for additional care considered after 4
weeks if symptoms do not improve).  The EPT group will be referred to physical therapy for 6-8 sessions in 
the first 4 weeks based on current best evidence supporting a centralizing approach. Follow-up evaluations 
will occur 4 weeks, 6 months and 1 year after enrollment. 
C.3  Subjects
We will recruit 220 patients with LBP and sciatica making initial entry into the healthcare system in primary 
care. Initial entry is defined as not having treatment from any provider for LBP or sciatica in the past 6 
months.  Potential candidates must satisfy all inclusion criteria: 
I.
Symptoms of pain and/or numbness between the 12th rib and buttocks, which, in the opinion of the
primary care provider, are originating from tissues of the lumbar region.
II.
Symptoms of pain and/or numbness primarily into one leg that have extended below the knee in the last
72 hours, and correspond to a lower lumbar nerve root distribution (L4, L5, S1)
III. Current symptoms present for 90 days or fewer
IV. Age 18 - 60 years
V.
Oswestry disability score > 20%
VI. One or more of the following symptoms:
1. Positive ipsilateral or contralateral straight leg raise test (reproduction of symptoms at <700)
2. Reflex, sensory, or strength deficits in a pattern consistent with lower lumbar nerve root
These criteria will select patients meeting the operational definition of LBP and sciatica typically used in 
research and practice and are consistent with our preliminary work examining physical therapy treatments.
Consistent with a pragmatic approach we will not require imaging studies because early imaging is not 
advocated by guidelines. Patients will be excluded if they meet any of the following exclusion criteria: 
I.
Any prior spine fusion surgery, or any surgery to the lumbosacral spine in the past year
II.
Current pregnancy
III. Currently receiving treatment for LBP from another healthcare provider (e.g., chiropractic, massage
therapy, injections, etc.) or any treatment for LBP in prior 6 months
IV. Judgment of primary care provider of “red flags” of a potentially serious condition including cauda
equina, major or rapidly progressing neurologic deficit, fracture, cancer, infection or systemic disease
These criteria will exclude patients who do not fit the sub-group with LBP and sciatica.  Patients with red 
flags may require early specialist referral. Patients who are pregnant comprise a separate sub-group 
requiring different management.74,75 Lumbar traction and some exercises are contraindicated for recently 
post-surgical patients or those with a spinal fusion. [Sciatica is very uncommon in adolescents under age 
18.130 Individuals over age 60 are increasingly likely to have lumbar spinal stenosis as an underlying cause 
of LBP and leg symptoms and practice guidelines differ for these patients.12] Reasons for ineligibility will be 
tracked and eligibility and consent rates determined. 
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Subjects will be recruited into the study using procedures we are successfully employing in our ongoing 
LBP trial (R18HS018672). Recruitment will be conducted using the Utah Health Research Network (UHRN), 
a practice-based research network formed to promote collaboration between the University Health Sciences
Center and the Community Physician Group and facilitate clinical research.  Dr. Lisa Gren, UHRN Director, 
will assist in establishing the recruitment procedures through UHRN. Currently the UHRN includes 12 
clinics, with approximately 80 primary care providers. The UHRN has an established recruitment process 
approved by the University Institutional Review Board (IRB). The process uses the electronic medical record 
to identify patients with specific characteristics based on demographic information and ICD-9 codes.  These
patients are informed of the study by clinic staff or by mail.  Interested individuals are contacted within 24 
hours by the study coordinator.  For this project we will identify patients with a primary care visit (with no 
LBP visits in the past 6 months) with an ICD-9 code related to LBP and sciatica (722.1, 722.2, 722.52,
722.93, 724.3, 724.4) between the ages of 18-60.  We performed a query of the EMR for a 12-month period
(7/11 – 6/12) to gauge the number of potentially-eligible patients based on these criteria and identified a total
of 1,886 individuals. This recruitment pool will be adequate to meet our accrual goals. 
C.4   Informed Consent, Randomization and Blinding
When a potentially eligible patient speaks with the study coordinator, the coordinator will explain the project. 
If the patient meets preliminary eligibility criteria and has interest, the coordinator will meet with the patient 
to insure all eligibility criteria are met and have the patient sign an informed consent document approved by 
the University of Utah IRB.  Patients who do not enroll will be instructed to follow-up with their primary care
provider as needed.  Once consent is obtained baseline examination procedures will be performed by a
blinded research assistant.  After the baseline examination the patient will again meet with the coordinator 
to receive the advice and education intervention consistent with current evidence (details below) then the 
coordinator will reveal the patient’s treatment group assignment. All patients will be advised to return to their 
primary care provider as needed, consistent with a pragmatic design. 
We will randomize individual patients instead of cluster-randomizing to avoid the loss of statistical power 
resulting from the latter.77 Randomization will be conducted using a blocked procedure [stratified by primary 
care clinic from which the patient is recruited]  and conducted using a random permuted block procedure.
A random list of differing block sizes (2 or 4) will be generated prior to the study. Sequentially-numbered, 
sealed envelopes will be prepared containing the group assignment for each patient. The envelope will be 
opened by the coordinator after providing the advice and education intervention.  Patients in the EPT group 
will be scheduled for physical therapy to begin within 3 days at [a physical therapy clinic trained in the 
evidence-based physical therapy program.  We selected two physical therapy clinics that will provide good 
geographic coverage of the region.  Physical therapists in these clinics will be trained prior to recruitment 
with ongoing fidelity monitoring and follow-up training as outlined below.]
Consistent with a pragmatic study we will not use placebos to blind patients or attempt to balance provider 
contact.  At baseline the randomization assignment will not be revealed until the patient has completed 
procedures with both the primary care provider and study coordinator, reducing the potential for bias from
the primary care provider offering advice or making medication decisions, or in the delivery of the advice 
and education by the coordinator. Follow-up assessments will be performed by a blinded research 
assistant.  Any occurrences of un-blinding of the research assistant will be recorded. The primary care 
provider cannot remain blind to treatment received if a study patient returns for follow-up.  If a patient 
returns to the primary care provider the provider will base care decisions on the patient’s needs consistent 
with a pragmatic approach. [It is possible that patients randomized to the UC group will eventually receive 
physical therapy, which could occur in a clinic trained in the evidence-based program. Our preliminary 
findings on the percentage of patients with LBP and sciatica who ever use physical therapy suggest this will 
not occur frequently.
We will record the occurrence of patients in the UC group eventually receiving 
physical therapy and whether or not this occurs in a trained clinic. This will permit an exploration of the 
potential confounding impact should this occur with greater frequency than anticipated.] This pragmatic
approach will preserve appropriate patient-provider communication and permit an examination of 
effectiveness and future healthcare utilization under the most realistic clinical circumstances possible. 
C.5  Baseline and Follow-Up Examination Procedures (See Appendix A for paper copies of all forms)
Baseline examination will consist of self-report questionnaires and a physical examination.  The physical
examination includes neurologic testing to confirm eligibility. The physical impairment index(PII)78 composed
of 7 measures of range of motion and strength, will be assessed. Each measure is graded positive (1) or
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negative (0) for a total score of 0-7 with higher numbers indicating more impairment. Each measure has 
excellent reliability and validity.78,79
Study data will be collected using web-based data collection via REDCap (Research Electronic Data 
Capture).  Data collection forms will require only modest modifications from our ongoing randomized trial
(R18-HS018672).  Our experience with web-based data collection is that patients find it easy to use and 
convenient, as reflected by compliance rates in our ongoing study. At baseline and each follow-up patients 
and researchers input data directly into REDCap.  If a patient is unable to directly input data using a 
computer paper forms are used and data are uploaded at a later time.   
Demographic Information 
Patients will provide information including age, sex, ethnicity, race, employment status, and general medical 
and LBP history. Patients will be asked about expectations for treatments including physical therapy, 
injections, and surgery prior to their group assignment.80 This information will be explored as a moderating 
factor and potential covariate in the analysis to mitigate the confounding effect of treatment preference.
Primary/Secondary Outcomes and Potential Moderators 
Oswestry Disability Questionnaire (OSW),81 a measure of LBP-related disability will be the primary outcome 
because functional ability is a primary concern for patients with LBP and sciatica.82  The OSW is a 10-item 
scale scored from 0-100 and higher numbers indicating greater disability.  We will use a modified version 
that replaces the sex life item with an employment/homemaking to improve compliance.83,84 The OSW is 
widely used in research on non-operative management of patients with LBP with and without sciatica85 with 
responsiveness equal or superior to other disability measures.86,87  Our prior research has found this 
modified OSW to have excellent test-retest reliability (ICC=0.90), validity, and responsiveness to change for 
patients with acute LBP, with a minimum clinically important difference (MCID) of 6 points.83  A study of 
patients with LBP and sciatica reported an MCID of 8 points for the OSW.86
Numeric Pain Rating Scale (NPRS):  0-10 NPRS (‘0’ = no pain, ‘10’ = worst imaginable pain) will be used to 
assess pain intensity. We will use separate NPRS ratings of low back and leg pain.  NPRS have excellent 
test-retest reliability.84 Our prior research has found the NPRS responsive to change, with an MCID of 2 
points among patients with acute LBP receiving physical therapy.88 A 2-point MCID is also reported for 
patients with LBP and sciatica.86 [NPRS will be a secondary outcome and explored as a moderator.] 
EuroQol (EQ-5D): A generic quality of life instrument91 will be used to assess health outcomes on a scale 
that may be referenced to other disease conditions.92  The EQ-5D covers 5 domains: mobility, self-care, 
usual activities, pain/discomfort, and anxiety/depression.  Each domain has 3 response categories: “no 
problems”; “some problems”; or “inability or extreme problems.” Responses are combined to 5-digit health 
state classification. The EQ-5D yields a total of 243 possible health states.  Valuation of each health state is 
available.93 The EQ-5D is reliable and responsive to change in patients with LBP94,95 and is commonly used 
in economic evaluation of interventions for LBP. 
Fear Avoidance Beliefs Questionnaire (FABQ): assesses patients’ beliefs about how physical activity and 
work may affect their LBP and perceived risk for re-injury.98  The FABQ has two subscales; a 7-item work 
subscale (FABQW), and 4-item physical activity subscale (FABQPA). Test-retest reliability of the subscales 
is high.98,99  Validity is supported by associations with concurrent and future disability and work loss in 
patients with acute and chronic LBP.100-103 [FABQ will be explored as a potential moderator.] 
Pain Catastrophizing Scale (PCS): a 13-item scale assessing the extent to which people catastrophize in
response to pain.106  Each item is scored from 0 - 4. The PCS is reported as a total score, and is composed 
of three sub-scales: rumination, magnification, and helplessness. Pain catastrophizing plays an important 
role in the transition from acute to chronic LBP.102 [PCS will be explored as a potential moderator.]
Healthcare Utilization and Direct and Indirect Costs:  [We will collect both direct and indirect costs due to 
lost work productivity related to LBP over the 1-year follow-up.] We will use a cost diary method integrated 
into the web-based data collection system to collect utilization and cost data.  Cost diaries offer advantages 
in terms of feasibility and validity as compared with patient-reported questionnaires for collecting cost data 
and provide information at regular intervals instead of relying on patient recall over a long time period, 
minimizing recall error.109 [We will collect cost and utilization data monthly via REDCap using the input 
options outlined below.] The cost diary will be modeled on paper-based methods with high compliance 
(85%) for economic analysis in studies of patients with LBP.108,131 This compliance rate is consistent with 
our experience using this method in our ongoing study.  Prior research reports no differences between cost 
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diaries completed for an entire year and extrapolation of data for limited time periods, indicating a 
robustness to impute scores for random missing data.  Patient-reported cost diary data has been found to 
generally agree with insurance claims, supporting the validity of the self-report cost and utilization data.108
[Each monthly cost diary will ask patients if they have utilized healthcare resources in the past month 
specifically for LBP in 4 categories: 1) provider visits (traditional or complementary/alternative), 2) 
medications (prescription or over-the-counter), 3) interventions (injections, surgery, etc.), or testing (x-rays, 
MRI, etc.), and 4) lost time from work or decreased work productivity.  Conditional logic will be used to 
reduce response burden for patients not seeking any care.  Patients who are seeking care will be given 
follow-up questions to ascertain the number and nature of utilization in each category in the past month.]
Follow-up examinations will be conducted 4 weeks, 6 months, and 1 year after baseline.  The 4-week 
examination permits evaluation of the immediate effects of early physical therapy.  6-month and 1-year 
examinations evaluate intermediate and long-term effects of treatment received during the first 4 weeks.
The 4-week follow-up will be conducted in-person by a blinded research assistant in order to re-assess the 
physical examination. 6-month and 1-year follow-ups will be conducted online by e-mailed links using 
REDCap.  In addition to the self-reports described previously, follow-up assessments will also collect:
Satisfaction: Patient satisfaction with care for LBP will be measured at the 4-week follow-up using a 10-item 
instrument that has been validated and found capable of distinguishing different dimensions of satisfaction 
(caring, information and treatment effectiveness) among patients with LBP attending primary care.111
Global Rating of Change: will be completed at each follow-up using a 15-point scale112 that asks the patient 
to rate the degree of change in his or her condition from enrollment to the present..
C.6    Procedures for Treatment (see Appendix C for copies of treatment forms)
Patients in both groups (UC or EPT) will continue to be managed by their primary care provider. Consistent
with a pragmatic study, decisions about medication or additional referrals will be recorded but not controlled.
All enrolled patients will be recommended by the coordinator to follow-up in primary care as-needed if
unsatisfied with their progress. All patients will receive education on the favorable natural history of LBP
with sciatica and reassurance that imaging and specialist referrals are not indicated early in the course of
care.  Patients will also receive advice to resume normal activity as soon as possible without bed rest.  The
advice and education will be provided by the study coordinator after the baseline assessment but prior to
randomization to avoid bias. Coordinators will be licensed physical therapists and will receive additional
training by the PI in provision of the advice and education intervention.  All patients will be given a copy of
the Back Book (Appendix B), a booklet developed to help modify beliefs and behavior of patients with
LBP.113 Messages are based on research demonstrating beneficial effects of remaining active.  Research
has found the Back Book to be well-accepted by patients, and capable of shifting beliefs about recovery and
activity, particularly when delivered interactively.113,114  The study coordinator will review the Back Book with
the patient and answer any questions.  Management common to all study patients therefore includes; 1)
education and reassurance of the favorable prognosis of LBP with sciatica, the benefits of staying active,
and the appropriateness of delaying imaging or referrals, 2) a copy of The Back Book with a review of its
contents to reinforce key messages, and 3) ongoing primary care management as needed.
Usual Care (UC) Treatment Group   
Patients in the UC group will be managed with a stepped care approach supported by current practice 
guidelines.115  Initial management for the UC group will involve the education and assurance intervention as 
outlined above for the first 4 weeks following the primary care visit.  Patients in the UC group will be 
recommended to follow-up with their primary care provider if unsatisfied with their progress after 4 weeks. 
At that time decisions on further treatments and/or referrals will be made by the primary care provider in 
consultation with the patient consistent with usual care.  
Early Physical Therapy (EPT) Treatment Group: 
Patients in the EPT group will receive the same education and advice intervention described above and will 
receive physical therapy during the initial 4 weeks following enrollment.  Physical therapy treatment will be 
standardized based on evidence and our prior research evaluating a centralizing treatment program for the 
sub-group of patients with LBP and sciatica. The first physical therapy session will be scheduled within 3 
days after enrollment and 6-8 sessions will be administered within the first 4 weeks [in a clinic trained to 
provide the study treatment] (2 weekly sessions in first two weeks and 1-2 sessions in weeks 3-4 based on 
therapist judgment).  Each session will include a brief assessment and treatment with centralizing exercises 
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and spinal mobilizations. Mechanical traction is an optional component.  Centralizing exercises will progress 
according to table 3, and consist of sustained and repeated movements to extend the spine as this most 
often produces centralization.  Modifications can be made by the therapist to maximize centralization. 
Therapists will instruct patients to monitor symptoms and perform exercises in a range to maximize 
centralization and minimize discomfort.  Patients will be provided handouts and instructed to perform 
assigned exercises at home every 4-5 hours on days between sessions.  Spinal mobilizations will be 
performed with the patient prone or side-lying with varied amplitude and velocity to promote centralization of 
symptoms and spine extension.  If mechanical traction is used it will be applied using a 3D ActiveTrac 
device (Empi, Minneapolis).  We have used this 
device in prior studies and have access in our 
facilities.  Static mechanical traction is applied for a 
maximum of 12 minutes with force parameters and 
patient positioning adjusted to maximize symptom 
centralization.  
Therapist Training and Fidelity Monitoring 
[We will train physical therapists in two outpatient clinics in the University of Utah Health Care system in the 
treatment program for EPT patients. These two clinics (University Orthopedic Center and South Jordan 
Health Center) provide good geographic coverage and have the necessary equipment to perform study 
treatments.  There are 14 full-time physical therapists in these clinics that will be trained.  New therapists will 
be trained on an ongoing basis. Dr. Fritz and the coordinator will lead the training.  Dr. Fritz is experienced 
training therapists to successfully perform research-related treatments regardless of clinician experience.142
A written procedure manual including study logistics and treatment techniques will be developed and an in-
person training session held prior to enrollment. This session will explain the research process including 
issues related to human subjects, research ethics and adverse event reporting. Treatment procedures 
outlined above will be described, demonstrated and practiced during the session. Passing a written test 
related to study procedures will be required before a therapist will be able to treat study patients. We will 
conduct follow-up therapist meetings every 6 months to discuss progress and review procedures. More 
frequent sessions will be held if needed.  Treatment fidelity during the first 4 weeks will be monitored by 
identifying off-protocol interventions received at the 4-week follow-up.  Fidelity for the EPT group will be 
monitored on two levels. Therapists will record patient’s self-reported compliance with assigned exercises 
on the treatment form from each session (appendix C). These forms are uploaded into the web-based data 
collection system. The study coordinator will audit at least 20% of forms to identify any concerns regarding 
treatment fidelity during the study.  Off-protocol events will be recorded and feedback given to therapists.  
C.7  Subject Retention Procedures
[We will use several strategies to enhance retention.  At the time of obtaining consent we will clearly outline 
the time that will be required of participants. We will clarify for participants that study-related treatments will 
not be billed to them or their insurance.  We will use reminder calls and e-mails for follow-up assessments. 
We will be in monthly contact with all participants via e-mail during the follow-up period to obtain cost and 
utilization data, helping to keep the participant connected to the study. The 4-week follow-up is done in 
person because this contact relatively soon after enrollment helps to maintain a sense of connection to the 
project for all participants, particularly those in the UC group. Long-term follow-ups are completed 
electronically to reduce the burden of an in person meeting. Our experience in our ongoing trial suggests 
this balance of in-person contact and the convenience of remote long-term follow-ups with frequent 
reminders and small gifts for completing assessments has been quite successful in retaining participants.  
C.8  Data Management and Quality Control Procedures
Data will be entered into REDCap, a software toolset and workflow methodology for electronic collection 
and management of research and clinical trial data. REDCap provides secure and easy data manipulation 
with audit trails for reporting, monitoring and querying records, and an automated export mechanism to 
common statistical packages (SPSS, SAS, Stata) facilitating quicker time to analyses.  Periodically during 
the study data will be exported by the University of Utah Study Design and Biostatistics Center (SDBC) at 
the University’s Center for Clinical and Translational Science (CCTS). The database will be maintained on a 
server supplied and maintained by University of Utah Health Sciences Center. The SDBC, directed by co-
investigator Dr. Tom Greene, will provide additional analyses to monitor progress, including rates of 
recruitment, retention and adherence to study protocols.    
1. Lying on stomach
5. Prone press-up to extended arms with sag
2. Propping on elbows
6. Prone press-up to extended arms with overpressure
3. Prone press-up to 
elbows
7. Repeated extension in standing
4. Prone press-up to extended arms
Goal: Tolerate for 5 minutes or 3 sets of 10 repetitions to maximize centralization
Table 3. Progression of Centralizing Extension Exercises
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Once a patient is enrolled, the Study Coordinator will create a patient profile in REDCap and the patient will 
receive a unique ID generated prior to beginning the study.  The patient profile will be identified by the 
unique ID and will not contain any Personal Health Information in REDCap.  Links between the ID and
patients’ identifying information will be maintained by the PI and will be available only to the Study 
Coordinator.  After a patient profile is created the patient and investigators are able to input data directly into 
REDCap. Once data collection begins, the PI will be in at least weekly communication with the Study 
Coordinator to monitor overall progress, recruitment and identify any issues that could impact the safety or 
ethics of the study (e.g, adverse events, instances of unblinding, etc.).  
C.9  Data Analysis
Data analyses will be carried out by the SDBC directed by Dr. Greene, who has extensive experience as a 
data coordinating statistician for clinical trials with recognized expertise in longitudinal data analysis. The 
SDBC employs biostatisticians with broad expertise, including Molly McFadden, who will carry out project 
analyses directed by Dr. Greene.  The SDBC will internally review data distributions for extreme scores or 
inconsistent results and will notify the PI of problematic data.  Because data quality and completeness will 
be monitored throughout, we expect any data discrepancies to be resolved and the study database closed 
within weeks of completing data collection. Following database closure the SDBC will provide data 
summaries with descriptive statistics including central tendency and dispersion computed for continuous 
data and frequency distributions for categorical data.  Transformations will be sought for variables failing to 
meet distribution assumptions. We are aware that unadjusted between-group comparisons are valid if 
randomization is achieved, however pre-treatment characteristics of the groups will be compared to assess 
for chance imbalances. If differences are found these variables may be used as covariates in post-hoc 
sensitivity analyses.  Intention-to-treat principles will be used with all patients analyzed in their randomized
group regardless of compliance. We will compare compliance between groups and “per-protocol” secondary
analyses may be considered if non-compliance is high or disproportionate between groups.
Multiple imputation (MI) will be used to address missing outcome data.  MI incorporates baseline and follow-
up factors beyond the variable being analyzed into imputation models to account for dependence of missing
data on other factors.  We will use the Markov Chain Monte Carlo method to generate imputed values116
involving 4 steps: 1) preparing the dataset by identifying all outcome variables likely to be involved in later 
analyses and likely predictors of missingness, evaluating distributional assumptions with transformations as 
needed; 2) conducting the MI, with variance and covariance estimates based on observed data used to 
iteratively estimate maximum likelihood values for all subjects. Multiple replacement values for each missing
score are drawn randomly from the posterior distribution and perturbed with error; 3) analyses are done
identically on all versions of imputed data; and 4) parameter estimates and tests are combined and adjusted 
for between-imputation variance to yield final results.  MI is valid if data are missing at random, meaning the 
probability of missingness is independent of the missing outcome values after accounting for predictor 
variables in the imputation model. Moderate violations of this assumption do not substantially bias MI results 
if the proportion of patients with missing data is low.  We will evaluate the assumption with importance 
sampling to evaluate implications of violations of the missing at random assumption after completion of the 
basic MI procedure.117 If this approach suggests strong dependence of the results on the missing at random 
assumption further sensitivity analyses will be performed using formal pattern mixture models.118 Should 
sensitivity analyses indicate strong dependence of our results on untestable assumptions about missing 
data, this limitation to the interpretation of our results will be noted and conclusions appropriately qualified. 
Because this study involves procedures with minimal risk we will not plan interim analyzes to avoid inflating 
type I error rates. Treatment comparisons will be performed separately at each follow-up time to 
characterize treatment effects at critical junctures over the follow-up.  The 4-week assessment will evaluate 
effects at completion of treatment; 6 month and 1 year assessments will evaluate intermediate and long-
term effects respectively.  We now lay out the analysis for each Specific Aim.
Specific Aim #1:  “Compare the effectiveness of two primary care management strategies for a subgroup of 
patients with LBP and sciatica.”
For the primary (OSW) and secondary (NPRS, EQ-5D) outcomes we will use longitudinal mixed effects 
models to compare mean change in the outcome from baseline to each follow-up (4 weeks, 6 months, and 
1 year) between the UC and EPT groups after controlling for the baseline level of the outcome [and 
indicator variables to account for the different primary care clinics.]  An unstructured covariance matrix will 
be used to account for serial correlations in outcome measures within patients.
Baseline adjustment 
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accounts for regression to the mean, increasing statistical power. [Sensitivity analyses will be performed to 
examine the implications of possible clustering of outcomes by the physical therapist providing treatment in 
the EPT group by adding a random effect term for the physical therapist to the models.] The primary 
analysis will compare mean OSW changes at 6 months. Comparisons between groups in mean OSW 
change at other time points and for other outcomes will be interpreted as secondary analyses. We will use a
2-sided alpha level of 0.05.  Secondary analyses will be interpreted without adjustment for multiple
comparisons.  However we will employ a bootstrap procedure to obtain the probability of obtaining at least
one p-value smaller than the minimum observed p-value from the secondary outcomes considered, based
on observed correlations among the estimated treatment effects for each outcome.119 This will provide an
assessment of the probability that a given nominally significant result would have occurred by chance given
the number of tests conducted and the observed association among the different outcome variables.
Specific Aim #2:  “Compare utilization of specific healthcare procedures and [healthcare costs] associated 
with two management strategies and evaluate the cost-effectiveness of the two strategies 
for a subgroup of patients with LBP and sciatica.”
Utilization outcomes evaluated during the year follow-up are: 1) advanced imaging (MRI or CT), 2) lumbar 
epidural injection, 3) emergency department visit, and 4) surgery (discectomy, decompression, laminectomy,
nerve ablation, fusion). Utilization rates will be summarized on a patient basis (proportions of patients) and 
as rates over time (total utilization including multiple events per patient), and compared between groups with 
logistic regression and survival analysis methods for repeated events respectively.127
We will compare 
numbers of patients missing work due to LBP between groups with similar procedures.  [We will examine 
costs from a societal perspective, collecting both direct and indirect costs using cost diaries. As 
recommended, we will value cost data with standard unit prices132 based on University of Utah clinical 
research billing rates.  Lost work productivity will be costed using methods described by Stewart.28,133 Cost
diaries document work absence or reduced performance (as a percentage of normal) due to losing 
concentration, repeating tasks, fatigue, etc, at work due to LBP.  Lost productive time will be calculated as
the number of days of work absence (“absenteeism”) and the number of hours of reduced productivity 
(“presenteeism”) multiplied by the patient’s self-reported salary.28 Patients not employed outside the home 
(homemakers, students) will report absenteeism and presenteeism. Lost productive time will be based on 
average salary for age- and sex-matched individuals according to the Bureau of Labor Statistics.  Sensitivity 
analyses will be used to examine the impact of differing methods of valuing direct and indirect costs.]
[We will use parametric and non-parametric methods to compare costs between treatments.  As the mean is 
the most useful statistic to evaluate costs related to treatment implementation,134 we will calculate means 
and standard deviations for direct, indirect and total cost by group.  We will explore cost data distributions 
graphically and statistically. With univariate and multivariate techniques we will examine the relationship 
between treatment and total cost. As cost data are typically skewed we will use nonparametric bootstrapping 
methods with 2000 pair-wise replications to compare mean costs and avoid distributional assumptions.135
Confidence intervals around the mean cost difference will be calculated with bias corrected and accelerated 
methods.136 Regression analyses will also be used to allow costs to be adjusted for patient factors such as 
socioeconomic status or co-morbidities. We will perform separate analyses for patients with complete cost 
data and those with imputed costs.
Missing cost data will be handled using MI as described.137 MI is 
preferred for missing cost data over alternatives such as last score forward or mean imputation.139 Short- 
and long-term cost-effectiveness (CE) analyses will be conducted. The short-term analysis will use direct 
and indirect costs over the first 4 weeks. The effectiveness of these costs will be based on OSW and EQ-5D 
scores at 4 weeks. Long-term CE analysis will use cost and effect data measured at 1-year.  Costs and 
effects will be measured in the same year; eliminating the need for inflation adjustment or discounts. Once 3
parameters are computed: 1) mean differences in cost and effect between treatments, 2) variances for 
differences in costs and effects, and 3) covariance between effectiveness and cost difference, the 
incremental cost-effectiveness ratio or incremental net benefits summarizing the monetary value of the
intervention will be calculated.140  A CE acceptability curve will be used to quantify and graphically depict 
uncertainty in the analysis.142 To consider uncertainty in parameters, probabilistic sensitivity analysis will be 
conducted. To reflect the uncertainties in costs and in effects, a gamma distribution will be adopted.]
Specific Aim #3: “Evaluate moderators of improvement with early physical therapy.”
Moderators are baseline variables that interacts with the type treatment to predict outcomes.126 We will pre-
specify potential moderators of improvement with early physical therapy based on theory or preliminary 
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findings suggesting a moderating effect including; 1) symptom centralization at baseline (yes/no), 2) severe 
baseline disability (baseline OSW <40 or >40), 3) leg pain rated higher than LBP at baseline (leg NPRS >
LBP NPRS or leg NPRS < LBP NPRS). Mixed effects models described above will be extended by adding 
interaction terms for moderating variables using separate models for each outcome and each variable.  The 
extended models will be used to provide separate estimates of treatment effects within each level of the 
moderator and to provide statistical tests of the dependence of treatment effects on the moderator.  To 
mitigate risk of low power in subgroup analyses, the NPRS, for which the study has high power to detect 
important differences, will serve as the primary outcome for evaluating moderators. We may explore different 
follow-up points or dependent variables, and may consider additional putative moderators if evidence 
emerges suggesting a potentially important variable that may provide information to patients and providers 
about types of patients for whom early physical therapy may be particularly beneficial (or unhelpful).       
C.10  Proposed Time Line
The timeline is based on our preliminary estimate of recruiting 8 patients per month.  At this rate we need 28 
months to recruit 220 patients.  We allow 3 months at the beginning of the study to establish procedures 
and 4 months at the end to complete data analysis, manuscript preparation, etc.   
Month  1 Month  2 Month  3 Month  4 Month  5 Month  6 Month  7 Month  8 Month  9 Month 10 Month 11 Month 12
Year 1 
Establish study procedures
Recruit approximately 8 patients per month 
Year 2 
Recruit 8 patients per month 
Year 3 
Recruit 8 patients per month 
Complete follow-up evaluations 
Year 4 
Complete follow-up evaluations
Data analysis, report writing, etc.
C.11  Sample Size Justification
Assuming at least 90% of patients complete the OSW at 6 months, 110 subjects per group (total = 220) 
provides at least 86% power to detect a difference of 7 points on the OSW to 6 months, assuming a 
standard deviation of 16 points (treatment effect = 43.8% of 1 standard deviation).  MCID for the OSW has 
been estimated at 6-8 points.83,86 This sample size also provides at least 82% power to detect a treatment 
effect on the 1-year OSW change assuming the same standard deviation and 80% follow-up.  In addition, 
this sample size provides > 99% power to detect a clinically important difference of 2.0 on the NPRS 
assuming a standard deviation of 2.4 and at least 80% follow-up. Our prior work with patients with LBP and 
sciatica indicate these estimates of effect are realistic.52,72 Our power calculations are slightly conservative 
as they assume no information will be obtained from patients with missing outcomes; we can expect slightly 
smaller minimum detectable effects (i.e. greater power) with MI.
C.12   AHRQ Priority Populations
This project will include subjects from AHRQ Priority Populations including women, children (age 18-21),
and minority groups as they are represented in the population from which study subjects will be recruited.
Because this project is the first to examine the effectiveness and subsequent healthcare utilization resulting
from the management strategies described in this proposal, we are taking a pragmatic approach to
recruitment instead of targeting the recruitment specifically towards priority populations. Once more
information is known about the effectiveness of these strategies, studies specifically examining translation
into priority populations such as individuals in rural regions, low income or minority groups will be possible.
C.13  Limitations and Contingencies
As with most clinical studies, a primary concern is adequate recruitment.  While we believe our recruitment 
accrual estimate is realistic and obtainable, we will maintain a contingency plan in case accrual falls short of 
our estimates.  The UHRN practice-based research network includes primary care clinics that are not in our 
recruitment estimate because they are greater than 20 miles from Salt Lake City, but could be added if 
necessary.  Another potential limitation would be subjects’ ability to access physical therapy clinical sites for 
treatment.  We are able to use space in physical therapy clinics affiliated with the University of Utah system 
located throughout Salt Lake City and could train additional clinics to provide the study treatment in order to 
increase the likelihood that a subject will be able to access a clinic for treatment. 
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