A Brief Educational Video for Patients Prescribed Latent Tuberculosis Treatment: A Randomized Trial in an Integrated Healthcare Organization in the United States
Phase: NA
Conditions: Latent Tuberculosis
Sponsor: Kaiser Permanente

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LTBI Video Intervention Trial 
KPSC Research & Evaluation 
 
STUDY PROTOCOL 
 
 
 
 
 
 
 
 
 
 
A brief educational video for patients prescribed latent tuberculosis treatment: 
A randomized trial in an integrated healthcare organization in the United States 
 
 
 
 
 
 
 
Version 1.1 
22 September 2022 

Version History 
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LTBI Video Intervention Trial 
KPSC Research & Evaluation 
 
 
 
 
 
Version 
Date 
Primary 
Author/Reviewer 
Description 
1.0 
June 3, 2022 
Katia Bruxvoort 
First Version 
1.1 
September 22, 2022 
Brigitte Spence 
Updated outreach 
process 

Investigator Roster 
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LTBI Video Intervention Trial 
KPSC Research & Evaluation 
 
 
 
 
Sara Tartof, PhD MPH 
Principal Investigator 
Research Scientist II, Kaiser Permanente Southern California 
Assistant Professor, Kaiser Permanente Bernard J. Tyson School of Medicine 
 
Katia Bruxvoort, PhD MPH 
Co-Investigator 
Assistant Professor, University of Alabama at Birmingham 
Adjunct Investigator, Kaiser Permanente Southern California 
 
Lei Qian, PhD 
Co-Investigator 
Research Scientist Biostatistician, Kaiser Permanente Southern California 
 
Sally Shaw, DrPH, MPH, MCHES 
Project Manager 
Lead Senior Research Project Manager, Kaiser Permanente Southern California 
 
Brigitte Spence, MPH 
Research Associate 
Research Associate III, Kaiser Permanente Southern California 

Table of Contents 
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KPSC Research & Evaluation 
 
 
 
 
Summary ...................................................................................................................................................... 5 
Background .................................................................................................................................................. 7 
Study objectives ............................................................................................................................................ 8 
Primary objectives ................................................................................................................................... 8 
Secondary objectives ............................................................................................................................... 8 
Outcomes ...................................................................................................................................................... 9 
Primary outcome ..................................................................................................................................... 9 
Secondary outcomes ................................................................................................................................ 9 
Table 1: LTBI treatment regimens ......................................................................................................... 9 
Eligibility criteria ...................................................................................................................................... 10 
Procedures.................................................................................................................................................. 11 
Randomization ....................................................................................................................................... 11 
Intervention ............................................................................................................................................ 11 
Follow-up survey ................................................................................................................................... 12 
Analysis ...................................................................................................................................................... 13 
Description of intervention and control groups .................................................................................. 13 
Primary analyses .................................................................................................................................... 13 
Secondary analyses................................................................................................................................. 13 
Sample size and power .............................................................................................................................. 14 
Table 2. Sample size calculation for a 1:2 randomized trial – completion.......................................... 14 
Data management and quality assurance ................................................................................................ 15 
Ethical considerations................................................................................................................................. 16 
References .................................................................................................................................................. 17 

Summary 
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LTBI Video Intervention Trial 
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Almost 1.7 billion people are infected with latent tuberculosis infection (LTBI)1 and nearly 10 
million people per year develop active TB disease.2 In 2017, nearly one-quarter of all new active 
TB cases in the United States occurred in California. LTBI treatment can effectively prevent 
reactivation and development of TB disease.3 However, as treatment courses are very long, many 
patients do not complete treatment. Effective interventions that are low-cost and feasible for 
large-scale implementation are needed to support efforts to eliminate TB. 
Thus, we will conduct a randomized trial of a 3-minute educational LTBI video intervention at 
Kaiser Permanente Southern California (KPSC), a large integrated health care organization. 
Web-based patient education videos are used routinely at KPSC to prepare patients for surgery, 
improve healthy habits, and for other uses. The primary objective of this study will be to 
determine if the LTBI video intervention improves treatment completion compared to standard 
care (no intervention). 
The study will include adult KPSC members who are prescribed treatment for LTBI, identified 
using an electronic health record algorithm. At the time of treatment prescription, patients will be 
randomized to receive the LTBI video intervention or standard care at a ratio of 2 to 1. Those in 
the intervention group will be sent a secure text message or e-mail with a link to the video. 
Individuals who watch the LTBI video will also be invited to participate in a brief follow-up 
survey (4 short questions) about their perceptions of the video accessibility and content. 
The primary outcome of the study is LTBI treatment completion (the required number of doses 
were dispensed) within one year of the prescription order. Secondary outcomes are LTBI 
treatment initiation (at least one dispensation of LTBI treatment) within one year of the 
prescription order; initiation and completion within one year of the prescription order stratified 
by LTBI treatment regimen (if feasible); the proportion of individuals randomized to the 
intervention group who watched the LTBI video; and the perceptions of those who watched the 
video. 
The primary analysis will be based on intention-to-treat. We will describe and compare 
characteristics of individuals in the intervention and standard care groups and calculate rates of 
LTBI treatment completion. To assess the effect of the intervention, we will use Poisson 
regression with robust standard errors to estimate unadjusted and adjusted rate ratios and 95% 
confidence intervals. We will also conduct per-protocol analyses, comparing those in the 
intervention group who watched the LTBI video to those in the standard care group. 
We will use similar methods for the secondary analysis of LTBI treatment initiation and analyses 
stratified by LTBI treatment type (if feasible). For the follow-up survey, we will describe the 
proportions of participants with each response. 
Assuming the completion rate in the standard care group is 0.5 as observed in recent years at 
KPSC, we estimate that we will need 918 patients (612 for the intervention group and 306 for the 

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LTBI Video Intervention Trial 
KPSC Research & Evaluation 
 
 
standard care group) to achieve 80% power with type one error 0.05 to detect an intervention 
effect of 0.10 in the completion rate between groups. As we will conduct trial over 1 year, and 
approximately 1,950 adult patients per year at KPSC receive an LTBI treatment prescription, we 
expect that this estimated sample size will be feasible. 

Background 
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LTBI Video Intervention Trial 
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In 2015, tuberculosis (TB) surpassed HIV as the number one cause of infectious disease deaths 
worldwide.2Almost 1.7 billion people are infected with latent tuberculosis infection (LTBI)4 and 
nearly 10 million people per year develop active TB disease.5 In 2017, California had the highest 
incidence and largest number of TB cases in the contiguous United States, comprising nearly 
one-quarter of all new active TB cases in the nation.6 The annual TB incidence in California was 
nearly double the national incidence rate in that year,6 with a cost of >$78 million spent on 
medical management.7 It is estimated that more than 2 million Californians have LTBI. 
In the United States, an estimated >80% of active TB disease is due to reactivation, which could 
be prevented via successful treatment of LTBI.7,8 Although poor understanding and adoption of 
screening guidelines contributes to lack of diagnosis and treatment, LTBI treatment regimens are 
long (3-9 months) and may cause adverse events.9 Thus, among patients who are prescribed 
LTBI treatment, initiation and completion of the full treatment course are extremely poor.10-14 
Kaiser Permanente Southern California (KPSC) is a large integrated health care organization 
serving more than 4.7 million members, with sociodemographic diversity similar to the 
underlying population.15 Members are enrolled through employer-provided, pre-paid, or 
federally-sponsored insurance plans. KPSC has a substantial burden of latent tuberculosis, with 
114,286 adults testing positive for LTBI from 2009-2018 (13,297 in 2018). 
Our preliminary data from qualitative interviews at KPSC with 39 patients prescribed LTBI 
treatment and 10 physicians identified multiple barriers to LTBI treatment initiation and 
completion. One of the important barriers identified was a lack of knowledge related to LTBI 
and confusion around the need for taking the full course of treatment.16,17 Thus, in consultation 
with an advisory board of culturally and demographically diverse patients recently prescribed 
LTBI treatment, we developed a brief (3-minute) educational video about LTBI and the 
importance of treatment completion. Web-based patient education videos are successfully used 
across KPSC to prepare patients for surgery, improve healthy habits, and for other uses. 
However, this approach has not yet been used to improve medication adherence, and its efficacy 
will be assessed through the randomized trial detailed in this protocol. 

Study objectives 
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Primary objectives 
 
1. Determine the efficacy of a simple, brief video (“LTBI video”) to increase LTBI 
treatment completion among adults 
Primary hypothesis: Patients randomized to receive the LTBI video will have higher 
treatment completion rates than patients randomized to standard care (no intervention) 
 
 
Secondary objectives 
 
1. Determine the efficacy of the LTBI video to increase LTBI treatment initiation 
among adults 
2. Determine the efficacy of the LTBI video to increase LTBI treatment initiation and 
completion among adults, by LTBI treatment type (daily isoniazid for 9 months, daily 
isoniazid for 6 months, daily rifampin for 4 months, daily rifampin plus isoniazid for 
3 months, and weekly isoniazid plus rifapentine for 3 months; some of these 
treatments may be used infrequently, precluding stratified analyses) 
3. Assess patient perceptions of the LTBI video 

Outcomes 
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Primary outcome 
 
1. Proportion of patients prescribed LTBI treatment who complete the treatment within one 
year of treatment prescription 
 
 
Secondary outcomes 
 
1. Proportion of patients prescribed LTBI treatment who initiate the treatment within one 
year of treatment prescription 
2. Proportion of patients prescribed LTBI treatment who initiate the treatment within one 
year of treatment prescription, by treatment regimen (if feasible) 
3. Proportion of patients prescribed LTBI treatment who complete the treatment within one 
year of treatment prescription, by treatment regimen (if feasible) 
 
2. Proportion of patients randomized to the LTBI video who watch the full video 
 
3. Proportion of patients who watch the video who report no difficulties watching the video 
 
4. Proportion of patients who watch the video who report understanding the importance of 
completing LTBI treatment 
 
 
Pharmacy data will be used to define and assess treatment initiation and completion, as follows: 
• Initiation: At least one dispensation* of LTBI treatment 
• Completion: The required number of doses of LTBI treatment were dispensed* 
*Picked up from pharmacy or sent via mail to the patient 
 
 
Table 1: LTBI treatment regimens 
 
LTBI treatment regimen 
Total doses 
Timing of treatment 
Isoniazid 
180 
Daily for 6 months 
Isoniazid 
270 
Daily for 9 months 
Rifampin 
120 
Daily for 4 months 
Isoniazid and Rifampin 
90 
Daily for 3 months 
Isoniazid and Rifapentine 
12 
Weekly for 3 months 

Eligibility criteria 
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Active KSPC members will be eligible to participate in the trial if they are aged ≥18 years and 
receive an LTBI treatment prescription order. 
 
LTBI treatment regimens (medication ID codes) are listed below. To be included in the trial, 
patients must also have a prior LTBI diagnosis code and must not have a prior active TB 
diagnosis code (also listed below). 
• Include patients with prescription orders for the following LTBI treatment 
(medication ID codes): 
o Isoniazid: 12199066, 1214000023, 1216000272, 12022505, 12035328, 
12035329, 12035330, 12035331, 12035332, 12035333, 12035334, 12035335, 
12035336, 12035337, 12015833, 12032230, 12035338, 12035339, 12035340, 
12035341, 12035342, 12035343, 12035344, 12035345, 12024985, 12035346, 
12181973 
o Rifampin: 12199042, 121103412, 1214000029, 1214000030, 1214000340, 
1214000565, 1215200240, 1206096, 12017860, 1209060, 12011205, 
12015920, 190716, 1902899, 190207268, 190210700, 12189972, 12189977, 
12189987 
o Isoniazid (see codes above) + Rifampin (see codes above), also: 12032976, 
12199041, 12029484, 12189973, 12168828 
o Isoniazid (see codes above) + Rifapentine (121100982, 1206442, 12025808, 
12188784, 12189978) 
• Include patients with the following LTBI ICD-10 diagnosis codes: R76.11, R76.12, 
Z22.7 
 
• Exclude patients with the following ICD-10 active TB diagnosis codes: A15, A17, 
A18, A19 

Procedures 
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Randomization 
 
Eligible patients will be identified in near real-time using an electronic health record algorithm 
that will be refreshed daily. Randomization will occur sequentially as patients are identified 
(ideally within <24 hours). For every 2 patients randomized to the intervention group (LTBI 
video), 1 patient will be randomized to receive the standard of care (no LTBI video). Medical 
record numbers and demographic characteristics (e.g. age, gender, race/ethnicity, and preferred 
language) will be captured for all patients. 
Intervention 
 
Patients who are randomized to receive standard of care will not receive any messages or have 
any contact with the research team. 
For patients randomized to the intervention group, a SMS text message will be sent with a link to 
access the LTBI video. The message will be in English or Spanish, depending on the patient’s 
preferred language, as recorded in their electronic health record. The message will be sent from 
KPSC’s Complete Care, a comprehensive health care delivery system with integrated clinical 
information systems, decision support, workflows, and self-management support.18 The message, 
from KAISER (524737), will say “KP: Your provider has an important 3 minute health video for 
you to view. Click [link 1] or sign into [link 2]. Reply STOP to unsubscribe.” 
Patients who have not opted into text messages from KSPC will receive a secure email with the 
same message and link. 
Patients who click on the first link will be directed to REDCap page, with the following text: 
“Please watch this 3 minute Kaiser Permanente video about latent tuberculosis. Your opinions 
will help us evaluate this video. Evaluating the video is voluntary. On the next page, we will ask 
you a few questions and send you a $5 gift card upon completion.” Patients will then click on the 
video, which will be physically hosted on the Qumu video platform. Patients will be asked to 
enter their initials and birthdate, which will facilitate linkage of individuals who watched the 
LTBI video with their electronic health records. After watching, patients will click to confirm 
they watched the video. 
Patients who click on the second link will be directed to their online Action Plan via KP.org. The 
video will be hosted in a tile with the following description, “Please watch this 3 minute Kaiser 
Permanente video about latent tuberculosis. Your opinions will help us evaluate this video. 
Evaluating the video is voluntary. Click here to answer a few questions about the video.” 
Patients will click on the video to play which the internal website will register as a watch. A 
patient who accesses the video through KP.org will not need to manually confirm they watched 
the video.  

Procedures 
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LTBI Video Intervention Trial 
KPSC Research & Evaluation 
 
 
Patients that have not watched the video will be sent a reminder via the same communication the 
initial outreach was sent, either text message or email. This reminder will be sent one week after 
they were sent the initial outreach. The reminder will also read, “KP: Your provider has an 
important 3 minute health video for you to view. Click bit.ly/34xmsvQ or sign into 
kp.org/actionplan. Reply STOP to unsubscribe.” 

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Follow-up survey 
 
Patients who watched the LTBI video via the REDCap page will be automatically navigated to a 
page which will offer them the ability to participate in a brief (4 short questions) survey about 
the accessibility of the video and their perceptions of the content. Patients will receive a $5.00 e-
gift card as renumeration for completing the survey. 
 
Patients who watched the LTBI video via the online Action Plan will be able to click on a link 
which will navigate them to the REDCap follow-up survey. 

Analysis 
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Description of intervention and control groups 
 
We will compare the distribution of demographic and clinical characteristics of patients in the 
two comparison groups with the t-test for continuous variables and the chi-square test for 
categorical variables. Among patients in the intervention group, we will describe the proportion 
who watched the video. 
Primary analyses 
 
The primary analyses will be based on intention-to-treat. The treatment completion rate will be 
compared between intervention and standard care groups. If necessary, we will use chart review 
to validate treatment completion based on pharmacy data for a sub-set of patients who received 
all doses in a single dispensing. The chart-confirmed rates by intervention group and control 
group can be accounted for in the analyses. To assess the effect of the intervention on treatment 
completion, we will estimate rate ratios (RR) and 95% confidence intervals using Poisson 
regression with robust variance, adjusting for covariates based on scientific relevance and/or 
significantly different distribution between groups. Missing data, which are expected to occur 
infrequently, will be handled using the missing data indicator approach. 
Secondary analyses 
 
Using similar methods as for the primary analyses, we will compare the initiation rate between 
intervention and standard care groups. Similarly, we will compare the initiation and completion 
rate between intervention and standard care groups by treatment type (if feasible, depending on 
the number of individuals receiving each type of LTBI treatment). We will also conduct per- 
protocol analyses to compare the initiation rate and the completion rate between those in the 
intervention group who watched the LTBI video and those in the standard care group. For the 
follow-up survey, we will report describe the distribution (number and percentage) for each 
response option. 
 
 
Analyses will be conducted in SAS (Version 9.4 for Unix; SAS Institute, Cary, NC). 

Sample size and power 
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LTBI Video Intervention Trial 
KPSC Research & Evaluation 
 
 
 
 
 
Based on data in recent years, we estimate that there are approximately 1,950 adult patients per 
year at KPSC with an LTBI treatment prescription. Using SAS 9.4 PROC Power test for two 
proportions, we calculated sample size estimates for a 1:2 randomized efficacy trial, given a 
range of completion rates based on other studies of 0.3, or 0.4, and a range of effect size (rate 
difference) of 0.05, 0.10, 0.15, and 0.2 to achieve 80% power, with type one error 0.05. If the 
completion rate in the control (standard care) group is 0.5, we need 918 patients (612 for 
intervention group and 306 for control group) to achieve 80% power to detect an intervention 
effect of 0.10 in the completion rate between two groups. As we will conduct the randomized 
efficacy trial over 1 year, this estimated sample size will be feasible. 
 
 
Table 2. Sample size calculation for a 1:2 randomized trial – completion 
 
Completion rate in 
control group 
Completion rate in 
intervention group 
Rate difference 
Sample size 
of control group 
Sample size 
of intervention 
group 
Sample size 
(total) 
0.4 
0.1 
282 
564 
846 
0.3 
0.45 
0.15 
132 
264 
396 
0.5 
0.2 
78 
156 
234 
0.5 
0.1 
306 
612 
918 
0.4 
0.55 
0.15 
140 
280 
420 
0.6 
0.2 
81 
162 
243 
0.6 
0.1 
306 
612 
918 
0.5 
0.65 
0.15 
137 
274 
411 
0.7 
0.2 
77 
154 
231 
0.7 
0.1 
281 
562 
843 
0.6 
0.75 
0.15 
124 
248 
372 
0.8 
0.2 
68 
136 
204 

Data management and quality assurance 
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LTBI Video Intervention Trial 
KPSC Research & Evaluation 
 
 
 
 
 
Data management and quality assurance activities will be performed by the study team. 
The algorithm for randomization will be piloted before beginning the trial to ensure that it 
accurately identifies all eligible patients and only eligible patients. Additionally, chart reviews 
will be conducted to confirm patients were correctly identified among those who watched the 
video and confirmed watching via REDCap. Validity and accuracy of REDCap survey data will 
be subject to range and consistency checks. 
Baseline characteristics and outcomes will be extracted from the KPSC electronic health records. 
KPSC programmers and/or biostatisticians will develop the study datasets and conduct data 
quality checks, which include data integrity control and program review. Data integrity control 
will include checks such as sample size, duplications, formatting, etc. All decisions made during 
data extraction and data quality checks will be documented. 

Ethical considerations 
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LTBI Video Intervention Trial 
KPSC Research & Evaluation 
 
 
 
 
 
The study has been reviewed and approved by the KPSC Institutional Review Board (IRB# 
12324). All study staff with access to protected health information (PHI) are trained in 
procedures to protect the confidentiality of subject data. Individuals who receive the intervention 
will provide agreement to participate in the research study. We will also obtain a waiver of 
informed consent, as all other aspects of the study are captured as part of routine clinical care. 
The HIPAA Privacy Rule governs the use and disclosure of personally identifiable information 
from covered entities. Throughout the course of this study, PHI will be accessed through the 
electronic health record by authorized study team members, but no PHI will be disclosed outside 
of the KPSC study team. As this access presents no more than minimal risk to individuals and 
the research could not be practically done if required to obtain written authorization for usage, 
we will obtain a waiver for written HIPAA authorization for research involving use of the EHR. 

References 
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