Patient Reported Outcomes for Bladder Management Strategies in Spinal Cord Injury
Conditions: Neurogenic Bladder, Spinal Cord Injuries, Quality of Life, Incontinence
Sponsor: University of Utah

Protocol Summary (ERICA) 
 
IRB_00082971 
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IRB Approval 8/26/2015 
 
 
Patient Reported Outcomes for Bladder Management in 
Neurogenic Bladder and Spinal Cord Injury 
 
Protocol Summary 
 
 
 
IRB Approval Date of Current Version: 3/1/2017 
University of Utah IRB #: IRB_00082971 
Sponsor: PATIENT CENTERED OUTCOMES RESH INST 
  
Principal Investigator: Jeremy Myers 
Internal Staff and  Sub-Investigators: 
James Hotaling 
Sara Lenherr 
Elizabeth Lignell 
Julie Neuberger 
Mary O'Rourke 
Darshan  Patel  
Angela Presson 
Ashlea Wilkes 
External Sub-Investigators: 
Sean Elliott  
John Stoffel  
Blayne Welk  
 
This document was created using the ERICA Online System at the University of Utah. The document is created 
from study information approved by the IRB on the date listed above.  Any alteration to the original content of this 
document may not be considered to represent the study as approved by the IRB.  
 
 

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Background and Introduction 
 
Nearly 80% of spinal cord injury (SCI) patients have urinary issues, like 
incontinence or increased frequency, which can have a significant burden on 
patients’ physical health and quality of life (QoL). Inappropriate management can 
cause hospitalizations and serious complications like urinary tract infections (UTI) 
and kidney damage. The gold standard for bladder management is clean 
intermittent catheterizations (CIC), where patients or caregivers perform regular 
urethral catheterization to empty the bladder. However, this task may be difficult 
for patients to perform independently due to physical limitations or it’s simply 
inconvenient. Alternatives include an indwelling catheter (IDC) that drains the 
bladder continuously or reconstructive surgery (to divert urine to an different 
location so patients can intermittently catheterize independently). However, each 
IDC and surgery has an increased risk of treatment specific clinical complications 
compared to CIC. Patients believe that both independence and ability to carry out 
daily activities are just as important as physical health in selecting the right 
bladder management strategy. The Research Team agrees that patient centered 
outcomes for CIC, IDC, or surgery in neurogenic bladder patients will identify 
methods with the lowest complication rate, best QoL, and highest patient 
satisfaction. 
Understanding the impact on QoL, particularly on physical, mental, and social 
health, for these three bladder management methods and the impact of urinary-
specific complications using patient reported outcomes is of particular interest for 
patients, caregivers, and clinicians. These factors are important for comprehensive 
QoL assessment among patients with neurogenic bladder and SCI as identified in 
previous studies and by our patient partners and stakeholders.  
 
This is a longitudinal observational study for three different bladder management 
strategies for an estimated 1,500 neurogenic bladder and SCI patients. Patients 
will be identified and recruited at the (1) University of Utah, (2) University of 
Minnesota, and (3) University of Michigan (4) University of Western Ontario. To be 
eligible, a patient must have a spinal cord injury or neurogenic bladder with 
urinary issues and be using one of the three bladder management treatments 
(CIC, IDC or urinary reconstruction). We plan to use the Neuro-QoL developed for 
PROMIS, a computerized adaptive test questionnaire to assess overall QoL and the 
Neurogenic Bladder Symptom Score (NBSS) to capture the impact of urinary 
specific issues and complications on QoL. The primary and secondary aims of this 
study are to compare total Neuro-QoL score and total NBSS score, respectively, 
across the three common bladder treatments. We will also compare scores for the 
sub-domains of these surveys, which include physical, mental and social function 
for the Neuro-QoL, and Incontinence, Storage and Voiding Symptoms, 
Complications, and a QoL item for the NBSS. Additionally, we will determine 
whether complication rates for one of the three methods impact Neuro-QoL scores. 
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20.          Costa P, Perrouin-Verbe B, Colvez A, Didier J, Marquis P, Marrel A, et al. Quality 
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21.          Gershon R, Rothrock NE, Hanrahan RT, Jansky LJ, Harniss M, Riley W. The 
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care and rehabilitation. 2010;19(5):677-85. 
22.          Welk B, Morrow S, Madarasz W, Baverstock R, Macnab J, Sequeira K. The 
validity and reliability of the neurogenic bladder symptom score. The Journal of urology. 
2014;192(2):452-7. 
23.          Perez L, Huang J, Jansky L, Nowinski C, Victorson D, Peterman A, et al. Using 
focus groups to inform the Neuro-QOL measurement tool: exploring patient-centered, 
health-related quality of life concepts across neurological conditions. The Journal of 
neuroscience nursing : journal of the American Association of Neuroscience Nurses. 
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24.          Hicken BL, Putzke JD, Richards JS. Bladder management and quality of life after 
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25.          Khastgir J, Hamid R, Arya M, Shah N, Shah PJ. Surgical and patient reported 
outcomes of 'clam' augmentation ileocystoplasty in spinal cord injured patients. European 
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26.          Zommick JN, Simoneau AR, Skinner DG, Ginsberg DA. Continent lower urinary 
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27.          Walsh K, Troxel SA, Stone AR. An assessment of the use of a continent 
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28.          Pazooki D, Edlund C, Karlsson AK, Dahlstrand C, Lindholm E, Tornqvist H, et al. 
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29.          Legrand G, Roupret M, Comperat E, Even-Schneider A, Denys P, Chartier-
Kastler E. Functional outcomes after management of end-stage neurological bladder 
dysfunction with ileal conduit in a multiple sclerosis population: a monocentric experience. 
Urology. 2011;78(4):937-41. 
30.          Cella D, Yount S, Rothrock N, Gershon R, Cook K, Reeve B, et al. The Patient-
Reported Outcomes Measurement Information System (PROMIS): progress of an NIH 
Roadmap cooperative group during its first two years. Medical care. 2007;45(5 Suppl 
1):S3-s11. 
31.          Cella D, Riley W, Stone A, Rothrock N, Reeve B, Yount S, et al. The Patient-
Reported Outcomes Measurement Information System (PROMIS) developed and tested its 
first wave of adult self-reported health outcome item banks: 2005-2008. Journal of 
clinical epidemiology. 2010;63(11):1179-94. 
32.          Cella D, Lai JS, Nowinski CJ, Victorson D, Peterman A, Miller D, et al. Neuro-
QOL: brief measures of health-related quality of life for clinical research in neurology. 
Neurology. 2012;78(23):1860-7. 
33.          Jones-Dickson C, Dorsey D, Campbell-Warnock J, Fields F. Moving in a new 
direction: computerized adaptive testing (CAT). Nursing management. 1993;24(1):80, 2. 
34.          FM L. Application of item response theory to practical testing problems. 
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39.          Rothrock NE, Hays RD, Spritzer K, Yount SE, Riley W, Cella D. Relative to the 
general US population, chronic diseases are associated with poorer health-related quality 
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(PROMIS). Journal of clinical epidemiology. 2010;63(11):1195-204. 
40.          Magasi S, Ryan G, Revicki D, Lenderking W, Hays RD, Brod M, et al. Content 
validity of patient-reported outcome measures: perspectives from a PROMIS meeting. 

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Quality of life research : an international journal of quality of life aspects of treatment, 
care and rehabilitation. 2012;21(5):739-46. 
41.          von Elm E, Altman DG, Egger M, Pocock SJ, Gotzsche PC, Vandenbroucke JP. 
The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) 
Statement: Guidelines for reporting observational studies. International journal of surgery 
(London, England). 2014. 
42.          Cella D, Nowinski C, Peterman A, Victorson D, Miller D, Lai JS, et al. The 
neurology quality-of-life measurement initiative. Archives of physical medicine and 
rehabilitation. 2011;92(10 Suppl):S28-36. 
  
  
 
 
 
Purpose and Objectives 
 
Our overarching goal is to create a better understanding of patient reported outcomes for 
three bladder management strategies (clean intermittent catheterization (CIC), indwelling 
catheter (IDC), and urinary diversion surgery. We will accomplish this through the 
following specific aims: 
  
1) Compare overall patient reported QoL using the Neuro-QoL and to compare 
subdomains of Neuro-QoL (physical, mental and social function) for three bladder 
management strategies: CIC, IDC, and urinary diversion. 
2) Compare patient reported urinary specific bother and complications using the 
Neurogenic Bladder Symptom Score (NBSS) and to compare specific NBSS 
subdomains (Incontinence, Storage and Voiding Symptoms, Complications, and a 
QoL item) for three bladder management strategies: CIC, IDC, and urinary 
diversion. 
3) To understand the relationship between complication rates and overall QoL 
(using the Neuro-QoL) for three bladder management strategies: CIC, IDC, and 
urinary diversion. 
  
  
  
  

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Study Population 
 
Age of Participants: 18-100 
 
Sample Size: 
At Utah: 
1,500 - 1,800  
All Centers: 
4,200 - 4,400 
 
Inclusion Criteria: 
Inclusion Criteria: 
1. Participants with spinal cord injury. 
2. Participants with neurogenic bladder. 
3. Participants must be undergoing or starting at least one of the three bladder 
management treatments at the time of enrollment. 
     a)  Clean Intermittent Catheterization (CIC) 
     b)  Have an Indwelling Catheter (IDC) 
     c)  Have a Urinary Division/Bladder Augmentation 
4.  Age 18 or older. 
5.  Willingness and ability to comply with study procedures. 
6.  Able to provide informed consent and authorization that the participant has been informed of 
all pertinent aspects of the study prior to enrollment. 
 
 
Exclusion Criteria: 
Patients will be excluded that do not have neurogenic bladder, belong to a vulnerable 
population (pregnant, prisoners, mentally handicapped, etc..), or are less than 18 years 
of age. 
 
 
Design  
 
Survey/Questionnaire Research 
Observational Research 
 
 
 

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Study Procedures 
 
Recruitment/Participant Identification Process: 
1. Participants will be recruited during clinical visits for the Division of Urology.  Participants with 
neurogenic bladder and or spinal cord injury will be asked in clinic if they would like to participate in 
the study.  They will be provided with information about the study.  If they agree to participate a 
study coordinator will obtain consent and authorization and then enroll them in the study.  
  
2. Participants will be referred from the Rehabilitation Clinic and Physical Medicine and other clinics 
where spinal cord injury patients are treated.  In cases such as these, we will go to the respective 
clinic and consent the participant if possible while they are at their clinic visits.  
3. We will have a study website: nbrg.org where participants can click on a link for further 
information about the study and also be able to take a brief survey which will determine eligibility 
and then also have the ability to remote consent if they desire.  
4.  We will also have a Facebook ad that will link to the study's website. The Facebook ad will be 
constructed by the University of Utah's Marketing Department. 
4. Public events where spinal cord injury patients attend will also be a possible recruitment entity 
where we would provide information to interested participants.  
  
 
 
Informed Consent: 
Description of location(s) where consent will be obtained:  
Urology Clinic Physical Medicine and Rehabilitation Clinic Other University of Utah Health 
Care Clinics that involved potential participants At the study website Over the phone At 
public events where spinal cord injury patients would be in attendance  
 
Description of the consent process(es), including the timing of consent:  
Patients will be asked if they would like to participate in the study. If they agree than they 
will be given a consent and allowed to fully review the consent. The consent will specify 
when they will be contacted and how they will be contacted during the course of the 
study. When patients feel they have had enough time to fully review the consent they will 
be enrolled in the study. This process will be the same for patients consenting over the 
phone, except that patients will be either emailed or mailed a copy of the consent prior to 
the review of the consent. For patients that are remote consenting, the consent will be on 
the study website.  
 
Procedures: 
This study is an observational/questionnaire study. Patients will be identified and recruited at the 
(1) University of Utah, (2) University of Minnesota, (3) University of Michigan and (4) University of 
Western Ontario, Canada. To be eligible, a patient must have a spinal cord injury and/or neurogenic 
bladder with urinary issues and be using one of the three bladder management treatments (CIC, 
IDC or urinary diversion). We plan to use the Neuro-QoL developed for PROMIS, a computerized 
adaptive test questionnaire to assess overall QoL and the Neurogenic Bladder Symptom Score 
(NBSS) to capture the impact of urinary specific issues and complications on QoL.  

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Baseline Visit: Patients at this visit will be approached regarding study participation. After providing 
consent and authorization, the patient will have about a 30 minute interview, with a clinician like a 
physician, nurse, or physician assistant, or a study coordinator who will obtain the medical 
history. We will gather the following information for our study: patient name, MRN, address, 
telephone, and email address. If the patient provides consent over the phone or remotely at our 
study website, the 30 minute interview will take place over the phone.  
The patient will be asked very routine questions about his/her health, medication usage, surgical 
history, physical exam findings, and specifics related to bladder management, bladder health, and 
specifics regarding the treatments previously received for treatment of neurogenic bladder. 
At the end of this 30 minutes, if the participant would like to complete the first set of questionnaires 
while he/she is in clinic, he/she will answer the questions on a tablet (or paper if the patient 
prefers) about his/her quality of life, pain and bladder management.  These questionnaires should 
take about 10 minutes to complete. If the participant does not have the time at the current clinic 
visit to complete these questions, a link will be emailed to the participant, which when 
clicked, will take the participant to the Assessment Center, where the questionnaires will 
be completed. For participants who don't have a computer, who are not able to use a 
computer or prefer to have the questions read to them, study personnel will set up a time to call 
and the questions will be completed over the phone.   
The patient will be asked to complete the same questionnaires that were completed at baseline, 
every 3 months for up to 1 year.  This will be accomplished by either 1) sending the participant the 
questionnaire link via email 2) calling the participant and completing the questionnaire via 
phone  3) approaching the participant at his/her next standard of care clinic visit (if this visit falls 
within the 3 month window) to see if he/she would like to complete the next set of questionnaires 
either by paper or table. Also, there is an Exit Interview that will be given when the participant 
finishes the study.  This Exit Interview can be sent to the participant via email with a link to the 
questions, or the participant can do the Exit Interview over the phone with study personnel; 
whichever method the participant prefers. The Exit Interview asks questions about any changes 
over the past year in bladder management, any surgeries that might have affected bladder 
management and any complications that resulted in a change of bladder management for the 
participants.  The Exit Interview questions will take approximately 15 to 20 minutes to complete.  
  
Data from participants that meet the study criteria and are enrolled in the study will be collected for 
research purposes only. A participant list  will be placed on an excel spread sheet that will be stored 
in a secure folder on a secure drive.  Access to this secure folder is only granted by the IT 
department upon request by the Research Manager. The excel database will contain the following 
information: Patient full name, medical record number, phone number, email, where consent was 
obtained, date of consent, date the questionnaires were sent, date questionnaires were completed 
and target date of future questionnaires. Data from the baseline assessment will be stored in 
REDCap and will include the participant's full name, address, phone number, medical record 
number, date of birth, email address,  date of injury, previous medical history information, and 
current medical history information.   
For the questionnaires done at baseline and then again every 3 months, the participants are sent a 
link, which is generated upon study enrollment with a unique participant identification number and 
is specific to each individual participant. The questionnaire link is sent to the participant via 
email, which takes them to the Assessment Center where the questionnaires are completed.  Some 
participants will have difficulty completing these questionnaires themselves either because they 
don't have access to a  computer or because of physical limitations.  For these participants, study 
personnel will call them and read the questions to them over the phone.   The Assessment Center 

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can only be assessed via the link that is sent to the participants, and no PHI is collected for the 
questionnaires at the Assessment Center.  The participants are identified by their unique study ID 
only.  
  
Termination of the project is contingent upon data analysis and manuscript preparation which 
should be completed in six years.  
The University of Utah IRB will review this protocol and any modifications.  
 
 
Procedures performed for research purposes only:  
 
 
Statistical Methods, Data Analysis and Interpretation 
 
  
  
The primary and secondary aims of this study are to compare total Neuro-QoL score and 
total NBSS score, respectively, across three common bladder treatments: CIC vs. IDC vs. 
Urinary diversion/bladder augmentation. While the total scores are our primary outcomes, 
we will also compare scores for the subdomains of these surveys, which include physical, 
mental and social function for the Neuro-QoL, and Incontinence, Storage and Voiding 
Symptoms, Complications, and a QoL item for the NBSS. We will also plan to report 
subgroup summaries to provide details specific to time since injury and/or treatment 
duration. The tertiary aim is to investigate whether the relationship between complication 
rate and total Neuro-QoL varies across treatment groups (i.e. is complication rate an 
effect modifier of the relationship between treatment group and Neuro-QoL). For this aim 
we will also describe and compare complication rates across bladder treatment groups. 
  
Analysis Plan Overview: 
The benefit of this longitudinal design is that it will allow us to capture QoL and 
complications data on a large cohort for a fairly rare condition.  Furthermore, the 
subjects captured with this design resemble a typical patient population, where 
subjects present at various times since injury and with varying treatment 
durations.  This is a typical patient population encountered in clinical practice, 
where the goal is to appropriately council these patients on their treatment 
options.  Because treatment history, outcomes, and covariates are recorded only 
for a 12-month period and are not available prior to the baseline assessment, it is 
not possible under our proposed design to evaluate the causal effects of the 
patients’ full bladder treatment histories.  Rather, we will characterize the 
association of the QoL score and other outcomes with the patient's bladder 
management treatment at enrollment (CIC, IDC or urinary diversion/bladder 
augmentation) during the 12-month follow-up period for each patient, with 
adjustment for demographic factors and injury characteristics. Thus the goal for 

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our primary analysis for aims 1-3 is to summarize patient experiences over the 12-
month period, defined by his/her treatment at enrollment (i.e., ignoring any 
changes in treatment).  A secondary analysis for aims 1-3 will be to allow 
treatment group to be time varying for the 10-15% who are expected to change 
treatment during the course of the study.  This latter type of analysis provides a 
more general characterization of QoL by treatment type, but it is limited in that it 
is more difficult to adjust for covariates -- more details are provided below. 
  
Primary Analysis for Aims 1-2: 
Our primary endpoints for aims 1 and 2 are the average of total QoL scores over 
time (total Neuro-QoL score and total NBSS score, respectively).  For our primary 
analysis, these outcomes will be analyzed in a linear mixed effects regression 
framework, and our primary predictor variable will be the patient's baseline 
treatment type.  Thus, even if a patient switches treatment during our study, we 
will ignore this change here and consider any change in QoL to just be part of a 
patient's typical one year experience starting from treatment X. Given that there 
are only five time points, it should be feasible to model within patient correlations 
using an unstructured covariance matrix. In these models we will evaluate the 
three possible pair-wise contrasts: CIC vs. IDC, CIC vs. Surgery and IDC vs. 
Surgery for statistical significance at the 0.017 Bonferroni-adjusted significance 
level.  Key covariates that will be included in the aim 1-2 models are: time since 
injury at baseline (coded as a categorical variable with levels <1 year, 1-5 years, 
and >5 years), physical limitations severity (mild, moderate severe), time on 
bladder management strategy recorded at baseline (<6 months, 6m-1.5 years, 
>1.5 years), age at baseline (coded as <20, 20-30, 30-40, 40-50, >50), sex, 
follow-up time point and BMI.  In addition, we hypothesize that interaction effects 
exist between treatment group at baseline and time on baseline treatment, time 
since injury, injury severity and patient age.  This is because different treatments 
may have different complication rates, and longer times on a particular treatment 
may differ from shorter times on the treatment in terms of QoL.  Similarly, patient 
satisfaction (and thus potentially QoL) with treatment type may vary with patient 
age, time since injury and injury severity. The possibility of additional pair wise 
interactions between treatment group and the covariates will be investigated in an 
exploratory fashion. Stata v.12 software will be used to extract the marginal 
coefficients, 95% confidence intervals (CIs) and p-values for each treatment group 
contrast in the presence of these interactions using the "margins" command 
(http://www.stata.com/stata11/margins.html).  To summarize patient outcomes 
by treatment group, we will provide average QoL estimates and 95% CIs for some 
combinations of treatment group, treatment duration, time since injury, injury 
severity and age subcategories.  While this corresponds to 3^5=243 possible 
different subcategory combinations, these descriptive results will be estimated 
from our model based on the full available sample size.   Thus these results will 
provide a profile of expected outcomes for each treatment group given different 
combinations of patient and injury characteristics. 
  
Secondary and Additional Analyses for Aims 1-2: 

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As a secondary analysis, we will allow treatment group to be a time-varying 
predictor given that patients can change treatment during the course of the 
study.  This analysis will characterize the average relationship between treatment 
type and QoL.  The key covariates will be the same as for the main analysis, 
except that we will not consider the interaction between treatment group and time 
on treatment at baseline, since it is no longer sensible in the context of a changing 
treatment group (given that time on treatment at baseline corresponds to one 
particular treatment). 
  
It is also interesting to study patients who switch treatments during the 12m 
follow-up period.  We will investigate potential predictors of switching treatment 
groups in an exploratory fashion, by modeling treatment change (yes/no) as an 
outcome and baseline treatment group as a main predictor.  This will allow us to 
evaluate whether the rates of change during the 12 month follow-up period vary 
by baseline treatment group.  Other potential predictors of treatment change will 
include time on baseline treatment, time since injury, injury severity, patient age, 
sex and BMI. 
  
Finally, we will repeat the primary analysis model for each of the subscales of the 
two surveys (using treatment type at baseline as a primary predictor).  For the 
subscale analyses we will plan to report the marginal coefficients, 95% confidence 
intervals CIs and p-values for each treatment group contrast (3 pair-wise 
comparisons), and statistical significance will be evaluated at the 0.017 level. 
  
Analysis Plan for Aim 3 
For our tertiary aim of evaluating cumulative complication rates (categorized as 0, 
1-3, 3-5, >5) by treatment group on QoL, we will adopt a similar modeling 
framework as described for Aims 1-2, except that complications will be included in 
the model along with its interaction with treatment group. We will use a likelihood 
ratio test to evaluate the statistical significance of this interaction term, i.e. to 
answer our main question of whether or not the relationship between cumulative 
complications and QoL differs by treatment group.  We will also provide average 
QoL estimates and 95% CIs for combinations of subcategories of complications, 
treatment group, treatment duration, time since injury, and age using Stata's 
margins command.  We will also plan to implement the Aims 1-2 secondary 
analysis where treatment group is modeled as a time varying predictor.  Again 
these models will include the additional interaction term between treatment group 
and cumulative complications. 
While our original analysis for our PCORI grant funding specified data collection for 12 
months follow-up, any additional longitudinal data follow-up would be useful and novel 
data for the field and will be collected as available. 

Protocol Summary (ERICA) 
 
IRB_00082971 
Page 13 of 13 
 
IRB Approval 8/26/2015 
 
A Note on Missing Data 
One benefit of the mixed effects modeling framework is that our models will 
include all available patients even if a patient has a missing value for one or more 
time points.  However, missing data is likely, and we will plan to use multiple 
imputation (MI) to investigate the sensitivity of our results to missing data (36, 
37).