Racial and Socioeconomic Differences in Chronic Low Back Pain
Conditions: Back Pain Lower Back Chronic
Sponsor: University of Alabama at Birmingham

Examining Racial and SocioEconomic Disparities (ERASED) in Chronic Low 
Back Pain Study 
 
Study Protocol & Statistical Analysis Plan 
 
NCT03338192 
 
 
12/18/2024 
 
 
Burel Goodin, Professor of Psychology, Principal Investigator 
University of Alabama at Birmingham 
Birmingham, AL 35294 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Methods: 
 
An overview of the study methodology is provided in Figure 7. Following a telephone screening to determine 
initial eligibility, an electronic medical record review will be completed for all potential participants to determine 
continued study eligibility. Each potential participant’s health history and cLBP information will be discussed with 
the study physician to determine appropriateness for ongoing participation. Eligible participants will then 
complete two experimental study sessions for collection of clinical, biomarker, psychosocial, QST, and functional 
performance data. In between the two study sessions, participants will complete 7 nights of actigraphic sleep 
monitoring along with diaries. Following the second experimental study session, participants will complete weekly 
pain and symptoms diaries for 4 consecutive weeks over the telephone. This study will be conducted using 
laboratory space and resources provided by the UAB Clinical Research Unit (CRU), which is supported by the 
UAB Center for Clinical and Translational Science and an NIH Center for Translational Science Award (CTSA; 
UL1TR000165). 
 
D.1.1. Participants: We will recruit a total of 268 adult participants with cLBP with the expectation of 
approximately 10% attrition based upon the preliminary work of Drs. Trost and Goodin. This will result in a final 
sample size of 240 (120 non-Hispanic Black, 120 non-Hispanic White) study completers. Participants between 
19 and 85 years of age will be enrolled. Enrollment will begin almost immediately after funding is awarded 
because most of the study policies and procedures have already been established as part of the pilot work 
previously completed by the PI. The inclusion criteria for participants with cLBP are: 1) non-specific cLBP that 
has persisted for at least 3 months and has resulted in pain on at least half the days in the past 6 months; 2) age 
19 – 85; the lower end of this age range was chosen in order to capture the growing prevalence of young adults 
with cLBP, and participants over 85 years are increasingly likely to meet one or more exclusion criteria; and 3) 
participants report ethnic group as non-Hispanic and racial group as either Black/African American or 
White/Caucasian. Participants with cLBP will be excluded if they have any concurrent medical conditions that 
could confound interpretation of outcome measures or coexisting disease that could preclude successful 
completion of the protocol (specific exclusion criteria are presented in the Protection of Human Subjects section).  
Given that participants will be primarily recruited from a pain treatment clinic, it is reasonable to assume that 
many may be using daily opioid medications. We will not exclude participants using opioids daily as this could 
seriously hinder recruitment efforts or otherwise bias our sampling (e.g., only participants with low severity cLBP 
not receiving opioids). We are aware that both continued use and temporary withdrawal from these medications 
(should we ask participants to withhold) could affect pain perception. Therefore, participants will not be asked to 
withhold pain medications on the day of quantitative 
sensory testing. Rather, all medications currently being 
used for pain (e.g., opioids, NSAIDs, SSRIs, etc.) will be 
recorded and controlled in statistical analyses as 
needed. 
 
D.1.2. Initial screening: All participants will undergo 
a cLBP screening interview using the recently developed 
research standards for defining cLBP proposed by the 
Research Task Force of the NIH Pain Consortium.90 This 
will involve a review of each participant’s UAB electronic 
medical record to confirm cLBP status and assess the 
reported duration of cLBP, current and past treatments 
for cLBP, comorbid conditions, and current medication 
use. Using the joint clinical practice guidelines from the 
American College of Physicians and the American Pain 
Society,58 patients with cLBP will be placed into 1 of 3 
broad categories: 1) nonspecific cLBP, 2) cLBP 
potentially associated with radiculopathy or spinal 
stenosis, or 3) cLBP potentially associated with another 
specific spinal cause. Patients placed into category 3 will 
be excluded if the cause of cLBP is determined to be 
ankylosing spondylitis, cancer or other malignancy, or in 
the context of autoimmune disease or other widespread 
pain condition (e.g., lupus, fibromyalgia). The screening 
will also assess demographic, SES, and health history 
information to ensure that no other exclusion criteria are 

present. To ensure that a relatively equal number of Blacks and Whites with high and low SES are recruited, a 
stratified sampling approach will be incorporated for recruitment. This will be done by determining whether a 
participant falls above or below the poverty line (as a proxy for overall SES) based upon reported annual 
household income and number of occupants residing within the family/household using the 2015 HHS poverty 
guidelines.101 In 2015 Alabama was the 6th poorest state in the Union, with 13% of Whites and 31% of Blacks 
living below the poverty line.102 Therefore, we are confident in our ability to recruit individuals with high and low 
SES. 
D.1.3. Demographic and SES measures: Ethnic and racial group will be determined by participant self-
report using the standard Health and Human Services categories. We will recruit adults who report their ethnicity 
as non-Hispanic and their race as either Black/African American or White/Caucasian. Because racial groups 
often differ in socioeconomic status (SES),103 and lower SES has been associated with increased risk of clinical 
pain104 and increased prevalence of cLBP,105 we will obtain a multidimensional battery of SES measures as part 
of this study. We will collect objective and subjective assessments of SES and social standing for individuals as 
well as the neighborhoods in which they live. The participant’s self-reported educational attainment, annual 
household income, and occupational category will be used as an objective indicator of SES per the Census 
Bureau Index of SES.106 The Hollingshead Four-Factor Index of SES will be used to assess four domains 
including educational attainment, retired/employed status, marital status, and occupational category/prestige.107 
The MacArthur Scale of Subjective Social Status will be used to measure participants’ perceived social 
standing.108 Research incorporating this measure has shown perceived social status to be determined by 
occupational position, education, household income, satisfaction with standard of living, and feelings of financial 
security regarding the future.108,109 We will match U.S. Census tract data to participants’ addresses to define 
neighborhood SES.68 Lastly, participants will self-report whether they currently have health insurance as well 
as quantity and quality of ongoing cLBP management. 
D.2. Experimental session 1 
 
D.2.1. Clinical pain assessment: The Patient-Reported Outcomes Measurement Information System 
(PROMIS) pain intensity, pain interference, and pain behavior items will be used for this study.110-112 For instance, 
patients will be asked to rate the intensity of their cLBP at its “worst” and “on average” over the past 7 days as 
well as the intensity “right now”. The Graded Chronic Pain Scale (GCPS) is a reliable (Cronbach’s alpha ≥ 0.80) 
and well-validated measure that evaluates global pain severity and pain-related interference over the past 6 
months.113 The GCPS yields a “Characteristic Pain Intensity” score and an overall “Disability” score. Taken 
together, the PROMIS pain intensity items and the GCPS will be our primary clinical outcome measures for data 
analytic purposes. The Oswestry Low Back Pain Disability Inventory (ODI) is a low back-specific instrument 
designed to address perceived disability in 10 areas: pain intensity, ability to lift objects, walking ability, sitting 
ability, standing ability, sleep, sex life, social life, traveling, and personal hygiene activities.114  
 
D.2.2. Biomarker measures: All blood will be collected by research nurses at the UAB Clinical Research 
Unit prior to quantitative sensory testing. Vitamin D and CRP assays will be performed by the Physiology and 
Metabolism Core of the UAB University-Wide Interdisciplinary Research Centers (UWIRC) Program under the 
direction of Dr. Barbara Gower. Blood samples will be mailed to Dr. Sue Carter at Indiana University for assay 
of oxytocin. Vitamin D assay: Following blood collection and processing, serum will be stored in a -80 degree 
freezer. Serum 25(OH)D analysis will be completed by high performance liquid chromatography (total 25-
hydroxyvitamin D = 25(OH)D2 plus 25(OH)D3) and enzyme immunoassay (Cayman Chemical) within six months 
of the date of collection. Clinical laboratory assessment of serum 25(OH)D best characterizes vitamin D status 
because it reflects vitamin D synthesized cutaneously as well as through dietary intake. Results of 25(OH)D 
testing will be shared with participants and if levels are found to be ≤ 30 ng/mL, they will be encouraged to 
discuss the result with a primary care provider. Plasma oxytocin assay: Plasma samples for the detection of 
oxytocin will also be collected, processed, and stored in a -80 degree freezer. Plasma oxytocin analysis will also 
be completed using high performance liquid chromatography with sample extraction and enzyme immunoassay 
(Cayman Chemical) within six months of the date of collection. It has been suggested that sample extraction and 
enzyme immunoassay may be the most appropriate way to accurately assess plasma oxytocin.115 These assays 
are specific to oxytocin, but not vasopressin. High sensitivity C-reactive protein (CRP): Plasma samples for 
the detection of CRP will also be collected, processed, and stored in a -80 degree freezer. High sensitivity CRP 
was be quantified using Cayman Chemical CRP (human) ELISA Kits, which is an immunometric assay that can 
be used to measure CRP in plasma without prior sample purification.  
The assay has a range from 46.9-3,000pg/ml and a limit of detection of approximately 46.9pg/ml. 
 
D.2.3. Psychosocial questionnaires: The Center for Epidemiological Studies – Depression Scale 
(CES-D) measures symptoms of depression and is reliable and valid in both general and clinical populations.116 

The CES-D items are relatively free of bias due to the pain and functional limitations associated with 
musculoskeletal disorders, and the CES-D is valid for use among low-income, minority persons as well as among 
middle class, white individuals.117 The Experiences of Discrimination (EOD) measure will be administered to 
assess participants’ self-reported experiences of racial discrimination across 9 different situations.118 Participants 
indicate the frequency of each experience, how they responded to the situation, and their level of worry about 
discrimination. The EOD has shown good reliability and validity across multiple racial groups.118 The Injustice 
Experiences Questionnaire (IEQ) will be used to assess perceptions of injustice.82 The IEQ is a 12 item scale 
that asks participants to indicate the frequency with which they experience different thoughts concerning the 
sense of unfairness in relation to their injury. The IEQ yields two correlated factors that have been labeled 
severity/irreparability of loss and blame/unfairness. The IEQ has been shown to be internally reliable and to 
predict prolonged disability following musculoskeletal injury.80 The Multidimensional Scale of Perceived Social 
Support (MSPSS) measures perceived support from three domains: family, friends, and a significant other.119 
Total and subscale scores range from 1 to 7, with higher scores suggesting greater levels of perceived social 
support. Adequate psychometric properties have been found with the MSPSS in several studies with young 
adults and adults in the United States and in Europe.120 The Pain Resilience Scale (PRS) was developed as a 
pain-specific measure of resilience. In a recent study, this measure was shown to possess good psychometric 
properties, and its predictive validity of experimental pain outcomes was superior to general resilience 
measures.121 
 
D.2.4. Endogenous pain modulation: All participants will undergo quantitative sensory testing for 
assessment of endogenous pain modulation using painful heat, mechanical, and cold stimuli in a laboratory 
session lasting approximately 2 hours. Heat Testing Procedures: Thermal stimuli will be delivered to the lumber 
region (i.e., most affected pain site) and to the non-dominant forearm, in randomized order, using a Medoc 
Pathway Thermal Sensory Analyzer (Ramat Yishai, Israel). Temporal summation of heat pain will involve brief 
repetitive suprathreshold thermal stimuli. The stimulus parameters for the heat testing procedures will be based 
on extensive experience in our laboratory and our previously published work.92,122,123 Punctate Mechanical 
Pain: Punctate mechanical pain will be assessed at the lumber region (e.g., over erector spinae muscles) and 
the dorsal aspect of the non-dominant hand using a nylon monofilament (Touchtest Sensory Evaluator 6.65) 
calibrated to bend at 300g of pressure. As in our previous studies, participants will provide a pain rating following 
a single contact of the monofilament, after which they will provide another pain rating following a series of 10 
contacts at a rate of one contact per second.92,122,123 The percent change (increase) between pain ratings for the 
single versus multiple contacts reflects temporal summation of mechanical pain. Conditioned Pain Modulation 
(CPM): CPM will be used to assess pain inhibitory function. The conditioning stimulus will be the cold pressor 
task (Thermo Scientific) applied to the dominant hand, which will be tailored for each participant to achieve a 
stimulus that produces moderate pain (i.e. a rating of 40-60 on the 0-100 scale) and can be tolerated for a 60-
second period. The test stimulus will be algometry (Algomed, Medoc, Ramat Yishai, Israel) to assess pressure 
pain applied to the lumbar region and opposite ventral forearm. The CPM protocol will be conducted according 
to previously established protocols.56,124 First, baseline PPTs will be assessed, after which the participant will 
immerse their hand in the cold water bath for 60 seconds and immediately afterwards PPTs will again be 
assessed at the testing sites. In order to operationalize CPM, percent change in PPTs from baseline will be 
calculated according to the following formula: [(conditioned PPT – test PPT) / test PPT) *100].29 Higher 
percentages will reflect greater pain inhibition. 
D.3. Actigraphy and daily diaries (7 days between experimental session 1 and 2) 
 
D.3.1. Actigraphy: Objective sleep data will be acquired using the Actiwatch2 (Respironics, Bend, OR), a 
wrist-worn, watch-like actigraph. The Actiwatch2 is a solid-state accelerometer, or movement detector, designed 
to measure ambulatory activity. It will be used to measure daily sleep-wake patterns and record body movement 
(omni-directional, piezoelectric accelerometer with a sensitivity of >0.01 g-force). The Actiwatch2 has good 
reliability and criterion validity.125,126 Actigraphy has been shown to be comparable to polysomnography99 and 
studies have demonstrated the validity of actigraphic measurement in persons with and without chronic 
pain.127,128  
 
D.3.2. Daily diaries: Participants will monitor and report on their sleep between the two experimental 
sessions in real-time using a pencil-and-paper consensus sleep diary.129 This will be done in conjunction with 
the actigraphic measurement of their sleep. Diaries will be completed twice per day, before going to bed at night, 
and then again the following morning, to provide a measure of participants’ self-reported sleep patterns and 
quality. In addition to sleep and napping behavior, the daily diaries will also include questions related to pain and 
mood as well as alcohol, caffeine, and nicotine intake throughout the day, and medication use.  
D.4. Experimental session 2 

 
D.4.1. Clinical pain assessment: For experimental session 2, patients with cLBP will again be asked to 
complete the (PROMIS) pain intensity, pain interference, and pain behavior items in order to address any recent 
changes to the quality of their cLBP over the past 7 days since experimental session 1 as well as at the present 
moment (i.e., “right now”). 
 
D.4.2. Functional performance measures: All cLBP patients will be asked to perform a series of functional 
performance measures consistent with those previously incorporated in Dr. Trost’s pilot work (see section 
C.3.2), including transitioning from a seated to standing position, and then sitting again. Additionally, a Short 
Physical Performance Battery and Timed Up and Go Test will also be completed. The Short Physical 
Performance Battery (SPPB) consists of three measures of lower-extremity function: standing balance, 4-meter 
walking speed, and ability to rise from a chair.97 These measures have been standardized and are widely used 
in older populations as measures of lower extremity function.130 We have experience with the SPPB and have 
successfully incorporated it in a prior project examining a painful musculoskeletal condition.131 The Timed Up 
and Go test (TUG) is a simple test used to assess a person's mobility and requires both static and dynamic 
balance. It measures the time that it takes to rise from a chair, walk three meters, turn around, walk back to the 
chair, and sit down.96 During the test, participants will be expected to wear their regular footwear and use any 
mobility aids that they would normally require. The TUG is used frequently in older populations, as it is easy to 
administer and can generally be completed by older adults.132 The TUG has previously been shown to be related 
to chronic pain-related disability.133 Any pain experienced during completion of the functional performance 
measures will be assessed using the 0-100 numeric rating scale. 
D.5. Follow up data collection 
 
D.5.1. Follow-up component – predicting pain in daily life: As a component of Specific Aim 3 and to 
translate the laboratory findings to participants’ daily environment, all participants will be contacted by phone 
once per week for four weeks following completion of study session 2. Participants will be asked to report on 
symptoms of pain (average and worst intensity), mood, sleep, disability, and interference of pain with daily 
activities over the preceding week using appropriate PROMIS items banks.111 We have successfully used a 
similar approach in a previous project to collect weekly follow up data.92 Given that racial group differences in 
follow up data could be attributed to differences in treatments received or in comorbidities since completion of 
the experimental sessions, we will collect this information and control for these factors statistically, if needed. 
D.6. Statistical methods 
D.6.1. Statistical power: The power analysis for this study was completed with primary focus on the three 
hypotheses that comprise Specific Aim 1. We assumed the following race by SES interaction effect sizes for 
clinical pain severity (Cohen’s f = .24), perceived disability (Cohen’s f = .19), and functional performance difficulty 
(Cohen’s f = .21) derived from out pilot data. Effect size conventions are .10 (small), .25 (medium), and .40 
(large). Probability value was set at .05 and the desired power was set at .85. According to these parameters 
and effect sizes, a total sample size of 240 participants is required to detect all of the race by SES interaction 
effects hypothesized for Specific Aim 1 (Table 5). These 240 participants will be allocated to four groups, such 
that there will be 60 low SES Blacks, 60 high SES Blacks, 60 low SES Whites, and 60 high SES Whites. Group 
sizes of 60 will provide greater than 95% power for detecting pair-wise differences while probing interaction 
effects based upon alpha level set as two-tailed .05/6 contrasts = .008 and Cohen’s d ranging from 0.83 to 1.90 
(see C.2.1. above). We plan to over-enroll by 10% to accommodate for participant attrition. Therefore, 268 
participants will be recruited with the expectation that at least 240 will complete.  
D.6.2. Data analysis: Data analysis will begin with calculating and comparing measures of central tendency 
(sample mean, sample median) and dispersion (sample variance, interquartile range) for all cLBP outcomes 
(e.g., PROMIS pain intensity, GCPS, ODI) as well as other study variables (CPM and TS, oxytocin, vitamin D, 
CRP levels, sleep, Perceived Injustice, Experiences of Discrimination, CES-D, etc.) according to race by SES 
groups. Confounding variables may include age, sex, pain medication use, engagement in treatments during the 
4 week follow up period, and others as appropriate and will be considered as statistical controls.  
Specific Aim 1: General Linear Models incorporating a 2x2 factorial design for Analysis of Covariance 
(ANCOVA) will be used to examine race by SES differences in cLBP outcomes including pain severity, disability, 
and functional performance. Race will include Blacks and Whites, while the Hollingshead Index will comprise the 
primary SES measure with participants split into high versus 
low SES according to previously published work.134,135 
Significant interaction effects will be probed using pair-wise 
contrasts with Bonferroni-adjusted alpha levels to examine 
differences across racial and SES groups, with emphasis on 
low SES Blacks compared to high SES Whites. Additional 

analyses will be completed considering other indicators of high and low SES including subjective social status 
(MacArthur) and neighborhood SES. This will be done to determine which aspects of SES are most relevant to 
consider when addressing cLBP outcomes. 
Specific Aim 2: The hypotheses that comprise this aim suggest that pain-relevant biopsychosocial factors 
including endogenous pain modulation, biomarkers, sleep, and psychosocial functioning will also differ according 
to racial and SES groups. These hypotheses will be tested using 2x2 ANCOVAs in the same manner indicated 
in Specific Aim 1. Significant race by SES interactions will be probed using pair-wise contrasts adjusted for 
multiple comparisons.  
Specific Aim 3: The analytic strategy is designed to test the hypothesis that the biopsychosocial factors 
included in this study will differentially predict cLBP outcomes in Blacks compared to Whites, and furthermore 
that the strength of prediction will vary according to high versus low SES. We will use a multiple regression 
framework to build separate models for Blacks and Whites. Within these models, SES will be included as an 
effect moderator when examining the associations of biopsychosocial predictors (independent variables) with 
cLBP outcomes (dependent variables). To illustrate how models will be built and data used, we offer examples. 
Separate models will be built for Blacks and Whites to determine whether endogenous pain modulatory 
processes (e.g., CPM and TS) predict functional performance (e.g., SPPB and TUG). Within each model the 
SES variables will be added to examine interaction effects (i.e., moderation), such that the strength of prediction 
between endogenous pain modulation and functional performance will be greatest for those with low SES. The 
same process will be used to examine whether aggregated actigraphic sleep and diary data differentially predicts 
pain in everyday life (e.g., average ratings of pain intensity collected across 4 weeks of follow up) according to 
race and SES.