A Stepped-Care Intervention to Reduce Disparities in Mental Health Services Among Underserved Lung and Head and Neck Cancer Patients and Their Caregivers
Phase: NA
Conditions: Cancer, Lung, Cancer, Head and Neck
Sponsor: University of Colorado, Denver

 
 
 
 
Borrayo, Stepped-care intervention for LC and HNC Patients and Caregivers, COMIRB # 
1
 
COMIRB Protocol 
COLORADO MULTIPLE INSTITUTIONAL REVIEW BOARD 
CAMPUS BOX F-490        TELEPHONE:  303-724-1055 
  Fax:  303-724-0990 
 
 
COMIRB Record #: 16-2621 
Protocol #: PCORI (154219) AD-1511-33395  
Project Title:  A Stepped Care Intervention to Reduce Disparities in Mental Health Services among 
Underserved Lung and Head-and-Neck Cancer Patients and their Caregivers 
Principal Investigator:  Evelinn A. Borrayo, PhD 
Version Date: 11/30/18 
 
I. Hypotheses & Specific Aims:  Medically underserved (i.e., low-income, uninsured, underinsured) 
cancer patients and their caregivers generally experience disparities in accessing mental health services. 
We will adapt evidence-based strategies to a stepped-care intervention model to address the mental 
health needs of underserved lung cancer (LC) and head-and-neck cancer (HNC) patients and of their 
caregivers across levels of depression and anxiety symptoms (e.g., mild, moderate, severe symptoms). 
We will compare the stepped-care intervention to “usual care,” which will be enhanced usual care 
(standardized list of mental health resources) due to variability in usual care offered across hospitals. 
We aim to recruit 848 underserved patients and 848 of their caregivers (1,696 participants) who will be 
screened to be randomized to a clinical trial. We estimate that about 816 participants (47%-57%) will 
not meet randomization criteria, leaving about 222 LC and HNC patients and 222 of their caregivers to 
be randomized to 1-of-2 arms. A randomized controlled trial (RCT) will compare the effectiveness of the 
stepped care intervention versus an enhanced usual care condition on reducing emotional distress and 
improving coping skills among medically underserved LC and HNC patients and their caregivers.   
 
Specific Aim 1: To work collaboratively with our clinician, patient and caregiver stakeholders to develop 
and implement a study protocol to ensure standardization of methods, fidelity of the intervention and 
its integration with clinical care.  
 
Specific Aim 2: To adapt the stepped-care intervention and enhanced usual care to ensure strategies, 
delivery, and assessments are sensitive to participants’ characteristics and properly applied, monitored, 
and integrated with clinical care. 
 
Specific Aim 3: To conduct a randomized controlled trial to assess if the stepped care intervention 
improves the primary patient-centered outcomes (depression and anxiety symptoms; coping skills) 
compared to an enhanced usual care condition. 
 
Hypothesis 1 (patients): Patients in the intervention group will show improvements in distress 
(depression and anxiety) and on coping self-efficacy compared to those in the usual care group. 
However, we hypothesize that QoL and perceived stress will remain similar across groups, indicating the 
intervention mitigates distress and coping in spite of treatment-related stress and decreased QoL. 
 
Hypothesis 2 (caregivers): Caregivers in the intervention group will show improvements in distress 
(depression and anxiety) and on adaptive coping compared to those in the enhanced usual care group. 
However, we hypothesize that caregiver burden and perceived stress will remain similar across groups, 
indicating that the intervention mitigates distress and coping in spite of caregiving stress and burden.  

 
 
 
 
Borrayo, Stepped-care intervention for LC and HNC Patients and Caregivers, COMIRB # 
2
II. Background and Significance 
LC is the primary cause of cancer death among men and women in the United States. 1 A significant 
number of LC patients present also with a primary diagnosis of head-and-neck cancer (HNC) or due to 
heavy smoking are at risk of developing these cancers and vice versa.2, 3 LC and HNC are considered 
among the most “traumatic” forms of cancer. 6 Treatment via surgery, radiation, and chemotherapy 
affect the most basic functions of life (e.g., breathing, swallowing, speaking, smell, taste, and vision). 7 
Physical disfigurement, weight loss, and high levels of pain and discomfort 8-10 result in poor quality of 
life (QoL) 4, 8, 11-18 and high psychological distress related to high levels of pain, treatment side-effects, 
and self-image disturbances. 5, 18 LC and HNC patients tend to experience high levels of anxiety (about 
33% of LC patients), 19 which increases as side effects increase and physical functioning decreases.19-22 As 
a result, LC and HNC patients tend to experience higher suicidality than other cancer patients.15, 23  
 
Social support tends to be lower among LC and HNC patients due to stigmatization, 24-31 functional 
disability, and physical disfigurement, 32-35 which often results in greater psychological distress. 36-38 The 
main source of social support for LC and HNC patients is often their caregivers.39, 40 Unfortunately, 
caregivers’ needs and distress often goes unrecognized.41 Similar to LC and HNC patients, distress in 
caregivers has been found to diminish their functioning, and consequently the quantity of home care 
they provide to patients.42 Caregivers are also affected by higher physical morbidity and premature 
mortality. 43, 44 Additionally, caregiver burden has been significantly associated with higher anxiety and 
depressive symptoms 47-49 and with significantly lower QoL among caregivers. 45, 46, 50-52  
 
There is limited research on the use of psychological interventions tailored to caregivers of LC and HNC 
patients, as well as on psychological interventions that include both caregivers and patients. There is 
also a void in the research on psychological interventions with medically underserved LC and HNC 
patients. Medically underserved cancer patients are significantly more likely to experience worse 
distress, higher levels of clinical depression, and lower QoL compared to other cancer patients.55 There is 
a need for studies that assess whether underserved LC and HNC patients and their caregivers benefit 
from evidence-based treatment to decrease psychological distress and improve their functioning.  
 
III. Preliminary Studies/Progress Report:   
In a pilot study, the PI, Dr. Borrayo et al. (2016),56 explored the challenges that underserved LC and HNC 
Hispanic patients undergoing treatment and their caregivers encountered.  There were 40 medical 
charts reviewed and 29 participants were interviewed, including 4 LC patients, 5 HNC patients, 6 
caregivers, 7 health care providers, and 7 lay-health workers about the treatment challenges that low-
income patients and their caregivers experienced that contribute to treatment delays.  The mental 
health challenges (i.e., depression, anxiety, substance abuse, fear) were reported to be the most 
concerning and to have negatively affected patients’ QoL and their treatment adherence, further 
contributing to treatment delays.  Health care providers also expressed concern about patients’ lack of 
access to mental health care to address emotional and behavioral challenges.  
 
In a previous pilot study, Dr. Kilbourn et al. (2013) assessed the acceptability and feasibility of an 
evidence-based intervention [i.e., “Easing and Alleviating Symptoms during Treatment” (EASE)] with 24 
HNC patients (34% attrition) to improve symptom management, distress, coping, and QoL among HNC 
patients.57 The intervention delivered evidence-based CBT and stress management across eight 
telephone counseling sessions.58 The CBT intervention was found acceptable, feasible, and clinically 
relevant to HNC patients. Dr. Kilbourn et al (2011) administered the same EASE intervention to 
caregivers of hospice patients in the Caregiver Life Line project (N = 19). In this pilot study.59 The CBT 
intervention included up to 12 weekly telephone calls aimed at fostering adaptive coping skills in the 

 
 
 
 
Borrayo, Stepped-care intervention for LC and HNC Patients and Caregivers, COMIRB # 
3
caregivers.  Caregivers were assessed at baseline, 3 months and 6 months for depression, emotional 
QoL, perceived stress, social support and benefit finding. Results demonstrated a trend toward reduced 
symptoms of depression and increased emotional QoL (greater reduction at 6 months than at 3 months, 
suggesting that the benefits of participating in the intervention may become more apparent over time).  
Caregivers reported high levels of self-efficacy regarding their ability to implement the coping skills 
learned. These findings demonstrate that the EASE’s CBT stress-management intervention is acceptable, 
feasible and beneficial to caregivers. Based on this evidence, the next step is to conduct a rigorous RCTs 
to assess whether evidence-based CBT stress-management interventions are equally effective at 
improving mental health outcomes among underserved LC and HNC patients and caregivers.  
 
IV. Research Methods 
 
A. Outcome Measures: We will utilize patient-reported outcome (PRO) measures that have been found 
to be valid and reliable, including with Spanish-speaking populations (see Table 1). To ensure that the 
measures are appropriate for low-literacy populations, a pilot test was conducted with our patient and 
caregiver stakeholders and items that were difficult to understand or to answer were simplified. Thus, 
we will further assess their validity and reliability in our sample. All consented study participants will be 
compensated $25 to complete the measures at baseline (“baseline measures”), which will also include 
sociodemographic questions to determine “randomization inclusion and exclusion criteria.” Only 
participants who are randomized to condition will complete the measures at 6-weeks, 3-months and 6-
months from the date they completed the baseline measures and will be compensated $25 every time.  
The measures package takes about +/- 30 minutes to complete when it is self-administered online or via 
a hard copy but about 45 minutes when administered orally in person or over the phone. If a participant 
is unable to complete the measures online or express preference for a hard copy, they will be:  
(1) Mailed a copy of the measures and ask to return within 15 days of receipt. If after 15 days of the 
initial online request or if they expressed preference for an oral administration, they will: 
(2) Receive a phone call from a Graduate research assistants (GRA) who will administer the measure 
to participants by phone. If the GRAs are unable to locate the participants after 3 attempts 
(including leaving voice messages), they will  
(3) Alert the Site Research Coordinators who will approach the participants to administer the 
measures in person either electronically with an iPad or with a hard copy.  
 
The following outcomes will be measured at baseline, 6-weeks, 3-months and 6-months: 
 
Distress (depression and anxiety symptoms): We will use two measure of distress. First, the 14-item 
Hospital Anxiety and Depression Scale (HADS) will be administered at baseline to obtain a global 
measure of anxiety (HADS-A) and depression (HADS-D) to provide validity data for the primary outcomes 
Table 1. Patient-centered outcomes to be assessed at baseline, 6-weeks, 3-months, and 6-months 
 
Patients 
Caregivers 
PRIMARY OUTCOMES 
Depression & Anxiety 
Hospital Anxiety and Depression Scale (14 items) 
Hospital Anxiety and Depression Scale (14 items) 
Depression 
PROMIS-Ca Form v1.0 – Depression (30 items) 
PROMIS Form v1.0  – Depression (28 items) 
Anxiety 
PROMIS-Ca  Form v1.0– Anxiety (22 items) 
PROMIS  Form v1.0  – Anxiety (29 items) 
Coping 
Coping Self-Efficacy (26 items) 
Coping Self-Efficacy (26 items) 
SECONDARY OUTCOMES 
Health-Related 
Quality of Life 
FACT-Lung Cancer version 4 (36 items) 
 
FACT-Head-and-Neck Cancer (27 items) 
 
Perceived Stress 
Perceived Stress Scale (PSS) (10 items) 
Perceived Stress Scale (PSS) (10 items) 
Caregiving Burden 
 
Zarit Burden Interview (ZBI) (12 items) 

 
 
 
 
Borrayo, Stepped-care intervention for LC and HNC Patients and Caregivers, COMIRB # 
4
to use in the study. The Cronbach's alpha for HADS-A has been reported from .68 to .93 (mean .83) and 
for the HADS-D from .67 to .90 (mean .82).96 Second, we will use the Patient-Reported Outcomes 
Measurement Information System (PROMIS) measures will assess the primary outcomes of distress 
(depression and anxiety symptoms) in patients (PROMIS cancer version) and in caregivers (PROMIS adult 
version).63 PROMIS measures have calibrated items (well-defined and validated) that have been found to 
be reliable measures. 65-67 Depression and anxiety symptoms constitute the primary study outcomes and 
will be interpreted as: (1) asymptomatic, PROMIS score < 50; (2) mild distress, PROMIS score 50-59; (3) 
moderate distress, PROMIS score 60-69; and (2) severe distress, PROMIS score >70. A negative outcome 
will include (a) unchanged distress scores or (b) an increase in distress scores at assessment points. A 
positive outcome will be a clinically significant decrease in distress at assessment points. 
 
Coping Self-Efficacy: Coping Self-Efficacy (CSE) scale by Chesney et al. (2006)73 assesses patient’s 
confidence in their ability to choose and implement a successful coping strategy via 26 items rated from 
1 to 10. The CSE taps into problem-focused coping, stopping unpleasant emotions and thoughts, and 
getting support from friends and family, all similar to emotion-focused coping, problem-focused coping, 
and social support of the CBT intervention.  Internal consistency range from .80 to .9173 
 
Health-related Quality of Life: We will use the Functional Assessment of Cancer Therapy (FACT)76 to 
measure health related quality of life. The FACT has been found valid and reliable among lung cancer 
(FACT-L, a=0.68-89) 77,78  and head-and-neck (FACT-HN, a=0.74-86) patients. 83, 84 The FACT-L and FACT-
HN incorporate the FACT plus additional symptom-specific items for LC and HNC.  Items are rated on a 0 
to 4 Likert type scale, and then combined to produce subscale scores and a global QoL score.   
 
Perceived Stress: The Perceived Stress Scale (PSS) 81 will be used to measure perceived stress. This 10-
item scale is scored on a 5-point Likert type scale to assess the degree to which situations are appraised 
as stressful. The PSS’ internal consistency reliability range from 0.80 to 0.89 82 and has been used among 
cancer patients 83 and among caregivers of cancer patients.84  
 
Caregiver Burden: The Zarit Burden Interview (ZBI) will measure caregiving burden. The 12 items ask 
caregivers to rate the impact that the patient’s condition has had on the caregiver’s life on a 5-point 
Likert-type scale. It provides an overall caregiver burden score, with higher scores indicating greater 
burden. The ZBI has good internal consistency reliability, with a Cronbach’s alpha coefficient of .92. 
 
Sociodemographic Characteristics at Baseline (including randomization inclusion and exclusion criteria): 
Demographic characteristics (not in Table 1) will be assessed at baseline with a self-report survey that 
includes participants’ age, sex, place of birth, years living in the U.S., marital status, current and future 
employment status, education, and mental health history. For patients it will also include diagnosis and 
treatment questions, and for caregivers it will include questions about caregiving responsibilities. The 
survey will ask “randomization inclusion or exclusion criteria” questions to determine RCT eligibility: 
 
1. Questions related to inclusion criteria will ask participants to report (a) what language they 
speak and read; (b) monthly income (after taxes); (c) how many people live at home that 
depend on the income reported; (d) health insurance status, including insurance type; and (e) 
estimated health insurance copays and deductibles (to estimate out-of-pocket costs). 
2. Questions related to exclusion criteria will ask participants to self-report (a) current or past 
impairments (cognitive and affective disorders) that make participants vulnerable to decision-
challenges; (b) current suicidal ideation; and questions to assess if they belong to vulnerable 
populations (e.g., inmates, homeless, pregnant, deaf).  

 
 
 
 
Borrayo, Stepped-care intervention for LC and HNC Patients and Caregivers, COMIRB # 
5
B. Description of the Methods to Enroll Participants in the Study  
 
Participants will be recruited from four hospitals: the Denver Health and Hospital Authority (DHHA), 
University of Colorado Hospital and National Jewish Hospital (NJH) in Denver, and Saint Mary’s 
Hospital and Medical Center (St. Mary’s) in Grand Junction. Each hospital will hire as their employee a 
Site Research Coordinator who will be trained to recruit and consent study participants (hospitals will 
cede to COMIRB’s oversight of the research, including personnel training requirements). 
 
1. We will pre-screen all cancer patients to identify recently diagnosed LC and HNC patients 
through various methods: 
a. Monthly audit of electronic medical records from all hospitals to identified patients 
diagnosed with LC or HNC within 30 days prior to the audit. 
b. Weekly attendance to cancer tumor boards to identify recently diagnosed patients. 
c. Daily review of clinic visits to identify all LC and HNC patients in the oncology clinic, ear-
nose-and throat (ENT) clinic, and radiation oncology clinic/unit at each hospital. 
d. Recruitment flyers in English and Spanish will be used to advertise the study at each 
hospital site and via Social Media sites. The flyers instruct recently diagnosed LC or HNC 
patients and their caregivers to contact the Site Coordinator if interested in the study. 
e. All patients and caregivers who agree and consent to participate in the study will receive 
a follow-up letter. The letter will include information based on whether or not the 
participant is randomized to a study condition, and if the participant is randomized, then 
he/she will receive a letter based on the step to which he/she was randomized. The 
letters are as follows: a) Letter to participants not randomized to a study condition, b) 
Letter to participants in the control condition, c) Letter to participants randomized to 
Step 1 of the intervention, d) Letter to participants randomized to Step 2 of the 
intervention, e) Letter to participants randomized to Step 3 of the intervention, f) Letter 
to participants randomized to Step 4 of the intervention. 
f. Advertise the study via Social Media sites and instruct recently diagnosed LC or HNC 
patients and their caregivers to contact the Site Coordinator if interested in the study. 
  
2. All recently diagnosed LC and HNC patients and their caregivers will be informed and invited to 
participate in the study following a series of procedures: 
a. Site Coordinator will arrange an information meeting with the patient (e.g., scheduled 
medical visit) to introduce and invite patient (and caregiver if present) to participate. 
b. If the patient’s caregiver is not present, the Site Coordinator will ask for the patient’s 
agreement to contact their caregiver via phone to invite them to participate in the 
study. The patient will be informed that “dyad” participation is not required but that 
only one or both of them can participate if desired. 
c. For caregivers absent at the time of the patient’s recruitment, the Site Coordinator will 
arrange to meet the caregiver to inform and invite them to participate in the study. 
 
3. We will consent all recently diagnosed LC and HNC patients who agree to participate in the 
study 
a. For patients and caregivers who agree to participate, the Site Coordinator will arrange a 
time to explain and sign the informed consent (IC). The time to conduct the IC process 
and sign the IC form could be during the initial recruitment meeting or at another 
subsequent time if that is more convenient for the patient and/or the caregiver. 

 
 
 
 
Borrayo, Stepped-care intervention for LC and HNC Patients and Caregivers, COMIRB # 
6
b. Participants will be provided with an electronic IC form to sign and will receive a hard 
copy for their records. The IC form and the oral explanation will emphasize that 
participants will (1) provide baseline data to determine if they meet the inclusion 
criteria to be randomized to 1 of 2 study conditions; (2) be randomized based on the 
“randomization inclusion and exclusion criteria” to either condition; and (3) participants 
who do not meet the randomization inclusion criteria will consent to remain in the study 
for comparison purposes (using only their unidentified baseline data).   
c. Patients who do not agree or who are unsure about participating at the initial meeting 
will be instructed to contact the Site Coordinator (within a month of the initial meeting) 
if they change their mind and would like to participate in the study at a later date. 
d. All patients and caregivers who agree and consent to participate in the study will 
complete “baseline measures” and will receive a $25 incentive. Sociodemographic 
questions will also include assessment of participants “randomization inclusion and 
exclusion criteria” criteria status to be further randomized to study condition. 
 
  
Authorization Procedures 
The protocol will be compliant with current HIPAA regulations and guidelines as follows: 
A. Authorization (via informed consent) will be obtained by each of the hospital’s Site Research 
Coordinator in a private and comfortable medical consultation room per site. 
B. Potential participants will electronically sign the authorization form via an I-pad, but will 
receive a paper copy for their records that is unsigned (but they can request a signed copy). 
C. The collection and use of each participant’s protected health information (PHI) will be 
protected in REDCap™.  We will not keep any PHI from our participants in paper form.  
D. PHI for each participant will be kept unidentified in REDCap,™ to be identified by a numeric 
study code assigned to the participant upon being consented into the study (only the Site 
Coordinators as employees of the institutions will have access to identified information). 
The SRC will only record PHI on the diagnostic criteria (e.g., LC and HNC) from all pre-
screened individuals. The SRC will also record demographic data (e.g.. age, gender, ethnicity, 
patient) to log recruitment efforts and for the DSMB to evaluate bias in recruitment, and for 
final analysis to determine demographics of individuals who were not included in the study.  
E. Each participant will be asked to provide, if possible, two phone numbers to deliver to them 
information related to their participation in the study (e.g., appointment reminders). 
 
4. Using information collected from the “baseline measures” we will screen for “randomization 
inclusion and exclusion criteria,” which includes the following criteria: 
 
LC and HNC patients’ randomization criteria [information in brackets refers to the question 
numbers that assess inclusion and exclusion criteria in the sociodemographic survey, attached] 
 
Eligibility criteria: 
a) Recently diagnosed LC and/or HNC (within a month of recruitment date from the date of 
1st visit oncology, ENT, or radiation clinic visit/consultation upon pathologic tissue 
diagnosis [question #14] 
b) LC and/or HNC patients at any stage of diagnosis (Stages 0-IV) [question #15]; 
c) Over 18 years old; [question #1]; 
d) English and/or Spanish speaking [questions #4]; 
e) Medically underserved, as defined by at least one or several of the following: 
a. Low-income: Below 400% of the 2016 Federal poverty levels 85, 87 [question #10]; 

 
 
 
 
Borrayo, Stepped-care intervention for LC and HNC Patients and Caregivers, COMIRB # 
7
b. Uninsured: No health insurance (public or private insurance) [question #9]; 
c. Underinsured: 
(c.1) Public insurance (e.g., Medicaid, Medicare exclusive, VA) [question #9]; 
(c.2) 10% of annual income on out-of-pocket medical expenses86 for individuals 
below 200% of the 2016 Federal poverty levels [questions #9 and #10]. 
 
Exclusion criteria:  
a) Individuals who do not meet eligibility criteria, including individuals who do not speak 
English or Spanish [at the discretion of the Site Coordinators upon recruitment]; 
b) Those who refuse treatment at one of four hospital sites. 
c) Decisionally-challenged adults with cognitive or personality impairment [question #19 & 
#20a-c], suicidal ideation [question #30], or intoxication (alcohol or drugs) that might 
interfere with their ability to consent or participate in the study [at the discretion of the 
Site Coordinators upon recruitment or the Counselor during for the intervention]; 
d) Individuals from vulnerable populations (e.g., inmates [question #29], homeless 
[question #28], pregnant women [question #2], and those with auditory impairment [at 
the discretion of the Site Coordinators upon recruitment]). However, individuals who 
become pregnant or develop auditory impairments after they have been randomized to 
study condition may remain in the study until completion. Additionally, individuals on 
probation will be considered eligible and their participation in the study will not 
interfere with their requirements of probation. 
 
Caregivers of LC and/or HNC patients 
 
Eligibility criteria: 
a) Primary caregiver of a recently diagnosed LC and/or HNC patient (per criteria for 
patients) [question #13];   
b) Over 18 years old [question #1];  
c) English and/or Spanish speaking [questions #4 and #5]; 
d) Medically underserved, as defined by at least one or several of the following: 
a. Low-income: Below 400% of the 2016 Federal poverty levels85, 87 [question #10] 
b. Uninsured: No health insurance (public or private insurance) [question #9] 
c. Underinsured:    
(c.1) Public insurance (i.e., Medicaid, Medicare exclusive, VA) [question #9] 
(c.2) 10% of annual income spent on out-of-pocket medical expenses86 for 
individuals below 200% of the 2016 Federal poverty levels [question #9 and 10]. 
Exclusion criteria:  
a) Individuals who do not meet eligibility criteria, including individuals who do not speak 
English or Spanish [at the discretion of the Site Coordinators upon recruitment]; 
b) Caregivers of patients who refuse treatment at one of four hospital sites. 
c) Decisionally-challenged adults with cognitive or personality impairment [question #19 & 
#20a-c], suicidal ideation [question #30], or intoxication (alcohol or drugs) that might 
interfere with their ability to consent or participate in the study [at the discretion of the 
Site Coordinators upon recruitment or the Counselor during the intervention]; 
d) Individuals from vulnerable populations (e.g., inmates [question #29], homeless 
[question #28], pregnant women [question #2], and those with auditory impairment [at 
the discretion of the Site Coordinators upon recruitment]). However, individuals who 
become pregnant or develop auditory impairments after they have been randomized to 

 
 
 
 
Borrayo, Stepped-care intervention for LC and HNC Patients and Caregivers, COMIRB # 
8
study condition may remain in the study until completion. Additionally, individuals on 
probation will be considered eligible and their participation in the study will not 
interfere with their requirements of probation. 
 
5. We will randomize participants (patients and caregivers) who meet the “eligibility criteria” and 
exclude from randomization participants based on the “exclusion criteria.” 
 
C. Randomized Controlled Trial (RCT) Design  
 
Population: To estimate the population of participants, we obtained data on the number of patients 
who have been diagnosed with LC and HNC at DHHA, University of Colorado Hospital, NJH, and St. 
Mary’s in a 3-year period (2012-2014) prior to the grant submission. The 4 sites had a population of 
about 1,211 LC and HNC patients who would be invited to participate in the study to complete “baseline 
measures,” with about 70% of patients expected to meet criteria as being uninsured or underinsured 
patients. As Figure 1 displays, the estimated sample is 848 patients (and 848 of their caregivers) 
expected to be eligible for randomization. 
 
Participants who meet the “randomization inclusion criteria” will be randomized to condition by the 
database manager using the REDCap™ software at CU-Denver as follows: 
1. Block randomization, adjusting for imbalance in patients’ tumor site and stage of diagnosis in 
the analysis, will ensure an equal distribution of patients and caregivers across arms. 
2. For patients and caregivers who both agree to participate in the study, they will be randomized 
together to the same condition (either “enhanced usual care” or “stepped-care intervention”). 
Per “baseline measures” of distress, patients and caregivers randomized to the “stepped-care 
intervention” will be assign to an intervention step based on their individual distress scores. 
 
Randomization and sample size: Figure 1 shows the participants’ random assignment to study condition.  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Figure 1. The 444 participants expected to be randomized  
(222 LC and HNC patients and 222 caregivers) 
Of the 1,211 patients and 1,211 caregivers 
(2,422 participants) about 30% will refuse 
to participate, leaving 848 patients and 848 
caregivers (n=1,696) to be screened for 
randomization. Of these, about 816 
patients (47%-57%) will meet exclusion 
criteria) or refuse further participation 
(drop-out), based on average participation 
rates reported in other similar studies. 92 
Thus, we estimate that about 444 
participants (222 patients; 222 caregivers) 
will be randomized to one of 2-arms (or 
222 per arm). About 44 participants in each 
arm might drop out of the study, have a 
member of the couple die, or be lost to 
follow-up (20% attrition), with 178 
participants per arm to remain in the study 
for the analyses. Figure 1 shows a total of 
about 356 participants will be available for 
final analyses. This sample allows us to 
detect a 0.38 effect size with 90% power. 
Assessed for Randomization 
(n=1,696) 
Excluded (n=816) 
Do not meet criteria; 
Drop-out.
Randomized (n=444) 
Intervention Arm (n=222) 
Drop out of the study; die; 
or lost-to-follow-up 
(n=150) 
Enhanced Usual Care Arm 
(n=222) 
Drop out of the study; die; 
or lost-to-follow-up (n=150) 
Analyzed (n=178) 
Analyzed (n=178) 
Population of Participants 
(n=2,422) 

 
 
 
 
Borrayo, Stepped-care intervention for LC and HNC Patients and Caregivers, COMIRB # 
9
RCT Conditions/Arms 
 
Arm 1: Enhanced Usual Care:  DHHA, St. Mary’s, University of Colorado Hospital, and NJH hospitals 
provide supportive mental health care for patients such as printed materials, support groups, 
crisis counseling, and specialized care (e.g., psychiatric medication). Because the amount of usual 
mental health care that each patient receives varies at each site, we will standardize and monitor 
the usual care arm across the four sites with an enhanced usual care condition.  All participants 
will receive upon enrollment a “Mental Health Resource Guide” with, (a) web links with mental 
health resources available at the national and local level, and (b) a list of support groups and 
mental health care providers to access if they encounter challenges. Participants in the baseline 
group and enhanced usual care, per usual care practices, with high levels of distress, suicidal 
ideation and needing specialized care (e.g., psychiatric medication, crisis counseling), will be 
referred to specialized mental health care following the established protocol at the hospital 
rather than provided access to the intervention.  
 
Arm 2: Stepped-Care Intervention:  Our intervention strategies are grounded in evidence-based CBT, that 
include stress management and relaxation treatment strategies and coping skills training.53, 58 Our 
treatment strategies have been adapted from the Transactional Model of Stress and Coping 
(TMSC), a theoretical model that predicts that individuals who are able to cope and adapt to the 
stress related to cancer treatment or caregiving will report less psychological distress than those 
unable to cope. 62 The TMSC will guide the progressive intensity of the treatment steps. The goal is 
to equip participants to identify and disaggregate the stress associated with treatment and 
caregiving related challenges (primary appraisal) while providing skills to manage stress, leading 
to increased adaptive coping (secondary appraisal), and reducing the emotional distress related to 
maladaptive coping.58 We hypothesize that applying the CBT strategies57, 59 in a stepped-care 
intervention format is likely to bring about the desired positive outcomes in distress levels.  
 
Stepped-Care Intervention Steps: A Master’s level Counselor will be hired as a hospital employee to only 
administer the intervention to participants (will not be involved in data collection).  Figure 1 describes 
the treatment steps that participants will be assigned to, based on their personal level of distress: 63 
 
Step 1: Watchful Waiting: (PROMIS score < 50).63 A face-to-face Orientation Session will be conducted 
with all intervention participants with to establish therapeutic alliance and explain the purpose, 
design, and content of the intervention.  Participants with no symptoms or with scores that fall 
below mild levels of distress will be followed by watchful waiting (active monitoring) only.  
 
Step 2: Self-Help Guide: (PROMIS score 50-59).63 Participants with mild levels of distress will receive the 
Orientation Session and a Self-Help Guide.  The Guide will contain self-administered evidence-
based stress-management and coping skills techniques 64, 54 that they can practice on their own. 
The Counselor will be available via telephone to answer questions about the Guide.  
 
Step 3: Coping Skills Training: (PROMIS score 60-69). 63 Participants experiencing moderate levels of 
distress will receive the Orientation Session, the Self-Help Guide, and two Coping Skills Training 
sessions with the Counselor.  Participants will learn problem-focused and emotion-focused 
coping strategies,54 and to identify controllable and uncontrollable stressors and how to match 
them to the appropriate strategy. Participants will practice the strategies between sessions.  
 

 
 
 
 
Borrayo, Stepped-care intervention for LC and HNC Patients and Caregivers, COMIRB # 
10
Step 4: Cognitive-Behavioral Therapy (CBT): (PROMIS score >70).63  Participants reporting high levels of 
distress, will receive the Orientation Session, the Self-Help Guide, two Coping Skills Training 
sessions, and four CBT sessions. The Counselor will introduce evidence-based CBT techniques, 
which focus on modifying the impact of stress via the interpretation of and reactions to stressors 
(cognitive and emotional reactions) and by correcting cognitive distortions. Participants who are 
not helped by the intervention or who require specialized treatment will be referred for services 
at the hospital, although they will continue to be included in the final analyses. If a patient dies, 
the caregiver may continue participating and will be moved to Step 4 to receive a grief session.  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Referral Protocol: Participants (baseline group, enhanced usual care, and stepped-care intervention) will 
be referred to specialized mental health care if they endorse suicide ideation or substance abuse items 
during any of the assessment points (baseline, 6-weeks, 3-months and 6-months) or if they voice such 
issues to the Site Research Coordinator upon enrollment or to the Counselor during the intervention. If 
participants are not helped by the intervention or require psychiatric medication, they will be referred 
also to specialized mental health services per protocols already in place at the participating hospitals. 
During the study’s 12-hour training, the Site Coordinators and Counselors will be instructed to follow 
their institution’s protocol for suicidal ideation and other crisis (e.g., intoxication) to make referrals.   
 
D. Description, Risks and Justification of Procedures and Data Collection Tools 
 
Potential Risks  
a) Physical injury – No known risks, but if there are risks they are likely to be rare and the 
magnitude low.  
b) Psychological trauma or stress – Psychosocial stress may increase in some participants during 
the intervention.  Support will be given throughout the intervention or information about 
sources of support will be given in writing to ensure patient safety.  It’s magnitude, should it 
occur, would be minimal and likely to be short in duration.  
c) Social/economic harm – No social or economic harm is anticipated.  Time commitment to 
participate in the intervention and to answer the measures will be requested but not expected 
to result in social or economic harm.  
d) Legal risk – No known risks, but if so they would be rare and the magnitude low.  
Positive  
Outcome 
Positive  
Outcome 
Positive  
Outcome 
Negative Outcome 
Negative Outcome 
Negative Outcome 
Step 4: CBT Sessions 
 
Assessed & 
Matched to 
Treatment 
Step Based 
on Distress 
(Anxiety & 
Depression) 
Step 1: Watchful Waiting 
Step 2: Self-Help Guide 
Step 3: Coping Training 
 
 
Positive 
Outcome: 
Monitor 
(6-months 
from 
enrollment) 
 
 
Distress 
Increases at 
6 weeks,  
3 month, or 
6 months 
Negative Outcome 
Refer Out (or crisis & suicidality) 
Figure 1. Stepped-Care Intervention Conceptual Framework to Assign Participants to a Step. 95  

 
 
 
 
Borrayo, Stepped-care intervention for LC and HNC Patients and Caregivers, COMIRB # 
11
e) Loss of confidentiality – Every effort will be made to maintain the confidentiality of participants 
by adhering to requirements for their protection that is in place by the institutions in the study.  
 
Procedure for Protection against Risk  
 
All the investigators and staff will meet COMIRB’s human subjects and institutional review board 
requirements.   
 
To minimize potential risks, the PI will monitor for any unanticipated problems while conducting 
the study and will report them to COMIRB.   
 
Research team meetings will be held once a month by the project’s leaders with the research 
project’s staff (e.g., Project Manager, Site Research Coordinators, Graduate Research Assistants) 
to closely monitor the study’s implementation fidelity, progress, and proper and ethical conduct 
of the trial with human subjects. 
 
Investigators/Institutions 
No risk to investigators and study staff is expected. 
 
Data Safety and Monitoring Board (DSMB): The DSMB will consist of four members who will have no 
direct involvement in the proposed project.  The DSMB will meet twice a year with the research project 
investigators and with stakeholders during key points in the study’s development, implementation, and 
evaluation to review its progress and provide feedback.  If an adverse event (AE) occurs, the DSMB will 
be called for an emergency meeting and the AE will be reported to COMIRB, which oversees the project 
across institutions.  Second, Dr. Borrayo and Dr. Kilbourn will hold monthly meetings with the research 
project’s staff (e.g., Project Manager, Site Research Coordinators, Counselors, Research Assistants) to 
review and closely monitor the study’s implementation fidelity and progress, including participants’ 
recruitment and drop-out and any difficulties in collecting and processing the data.  Minutes from the 
meetings will be used to record and track issues that need attention.  Dr. Borrayo (PI) and Dr. Juárez-
Colunga (biostatistician) will monitor the data monthly for consistency of collection.  Upon enrollment of 
the first 15 dyads of patients and caregivers (5 from each site) and their subsequent completion of 6-
months of participation, Dr. Juárez-Colunga will examine the data collected to assess if any problems 
exist.  
 
Established mechanisms to ensure data safety: Study data will be stored in a database located on a 
secure password-protected, HIPAA compliant University server. The data will be entered electronically 
using wireless touch screen tablets into a coded database in REDCap™ that can only be accessed via 
password by authorized research personnel. The database is hosted at UCD|AMC Development and 
Informatics Service Center (DISC) and will be used as a central location for data processing and 
management.  Access to the data will be based upon a unique username and password given to each 
user and stored within the REDCap authentication table. Users will need to be given rights to access the 
specific REDCap project database.  Rights within the project will be given based upon the user's role in 
the project.  For example, the SRC and Graduate Research Assistants (GRAs) would have rights to enter 
data, but will not have rights to electronically sign forms. A PI may be given rights to view data and 
electronically sign forms, but would not have rights to enter data. Users will be expected to comply with 
all applicable institutional policies regarding collection, storage, and analysis of data, including all 
applicable IRB and HIPAA regulations. Restricted access to the data will be handled via REDCap and only 
three team members will have access to the fill database: Dr. Elizabeth Juárez-Colunga (Co-I and 
statistician), 2) Data Manager (who will manage the database), 3) the Project Manager, and 4) Dr. 
Evelinn Borrayo (PI). Electronic communication about the data with outside research collaborators (e.g. 
Co-Investigators) and funding agency personnel (i.e. PCORI) will involve only unidentifiable information.  

 
 
 
 
Borrayo, Stepped-care intervention for LC and HNC Patients and Caregivers, COMIRB # 
12
 
Intervention Counseling Sessions: Digital auto recordings containing confidential information about the 
participants will also be collected for protocol quality control and participants’ safety monitoring. 
Counselors, employed by each of the hospitals, will deliver the intervention via in-person or over the 
phone and will audio record their counseling sessions with participants. Audio-recordings will be saved 
electronically with the numeric code used as the only identifier of the participant. The audio-recorded 
sessions will be reviewed by Dr. Kristin Kilbourn, Dr. Evelinn Borrayo, and Dr. Jeanette Waxmonsky, 
licensed clinical supervisors and IRB trained. The participants’ names, last names, numeric study code, 
and contact information will be kept in our password-protected  REDCap database. Audio-recordings will 
be shared electronically with the clinical supervisors, and with the PI and DSMB members HIPPA 
Compliant, University MS ONE Drive for Business account where they will be made accessible upon 
request.   
E. Potential Benefits of the Proposed Research to Human Subjects and Others  
 
To LC and HNC patients and their caregivers: Patients and caregivers who will receive the stepped-care 
intervention would benefit from receiving services that are targeted to their distress (i.e., mild, 
moderate, severe), which has the potential to improve their mental health wellbeing, along with 
potential gains in coping self-efficacy and decreased stress among other gains. Any risk involved in the 
study, such as temporary distress, may be outweighed by improvements to mental health needs.  
 
To society:  There is a dire need to provide underserved LC and HNC patients and their caregivers with 
mental health support. If successful, the intervention could improve mental health outcomes, patients 
and caregivers’ satisfaction with care, QoL, and caregiver burden. It may also provide other institutions 
with a cost-effective method to help underserved cancer patients receive mental health treatment. 
Thus, information gained is likely to outweigh any minimal risks (e.g., temporary psychological distress).  
 
Funding 
PCORI (154219) AD-1511-33395. Funding of this study will not pay for medical or mental health 
treatment for the participants.  Participants are responsible for their own standard medical or mental 
health care.  Participants will be given a $25.00 compensation for taking the time to answer the 
measures during the four total assessment points, thus, each participant randomized to condition will be 
paid a total of $100. Participants who are not randomized will only answer the “baseline measures” and 
will only receive $25.00 for that assessment point. Participants will not be paid for participating in the 
study, the RCT, or the Counseling sessions provided through the stepped-care intervention. 
 
Special Consent Issues 
There are no consent issues involving special populations such as prison inmates, persons with cognitive 
disabilities, homeless, or minors.  
 
Examinations, laboratory tests, and procedures 
Not applicable 
 
Biological Specimens/Genetic Testing 
This study does not involve collection of specimens or genetic testing. 
 
F. Potential Scientific Problems 
Potential limitations to this study include: researcher bias, participants bias, and generalizability. 
However, the oversight of the development, implementation, and evaluation of the study protocol, 

 
 
 
 
Borrayo, Stepped-care intervention for LC and HNC Patients and Caregivers, COMIRB # 
13
intervention, and conduct of RCT by a group of “Patient and Caregiver Stakeholders (PCS),” Clinician 
Stakeholders, and the DSMB will ensure that any bias introduce by the research team leadership and 
staff are minimized. The researchers will ensure that they standardize the interpretation of results 
during data analysis in order to reduce the impact of researcher bias. Some of our participants are 
cancer patients under distress and in need of services who might perceive the intervention to be more 
beneficial than under ordinary circumstances. Self-report measures might also lead to recall bias in 
reporting. Finally, we cannot generalize our findings to the overall LC and HNC patient and caregiver 
population because the focus is on medically underserved LC and HNC cancer patients and caregivers. 
 
G. Data Analysis Plan: An individual-level RCT design will assess the effects of the stepped care 
intervention condition compared to enhanced usual care condition on distress and adaptive coping skills.  
 
Sample size and power analysis: We estimated minimum effect sizes detectable for different power 
specifications for various sample sizes. Our target sample size for analyses is 290 patients and 290 
caregivers (145 per arm) but we will recruit an initial sample of 222 patients and 222 caregivers (222 per 
arm) to allow for variability due to 24-34% attrition, based on attrition rates in meta-analyses 88 and in 
our studies.57, 59 If we had a smaller number of participants or if attrition was higher, we would need a 
minimum of 110 dyads per arm to still be able to detect small to moderate effect sizes. Power is 
assumed to detect a time by treatment interaction within the proposed repeated measures design. 
Correlation of measures across time points (rho) was specified as moderate (.4), although sensitivity 
analyses examined the minimum detectable effect size at alternative specifications of rho and still allow 
small to moderate effects. Power calculations are for 3 outcomes through a Bonferroni reduction of the 
significance level to alpha = 0.05/3 = 0.0167. The study is designed to minimize contamination between 
intervention and control groups (e.g., randomizing both patients and their caregivers to the same group, 
referrals based on usual care practices). Nevertheless, based on Torgerson, we conservatively powered 
the study to detect a smaller effect than anticipated in the event of potential contamination. 89 
 
Analysis approach: Using an intent-to-treat (ITT) approach, primary and secondary outcomes will be 
analyzed with linear mixed models comparing the two groups (stepped care intervention, usual care) in 
patients and caregivers separately.  
 
Data aggregation, distributional assumptions, missing data, and attrition:  Maximum likelihood 
techniques will include participants with incomplete data without need for imputation. This technique is 
robust under certain conditions such that group comparisons will not be biased as long as missing data is 
ignorable. 90, 91  In addition, we will conduct sensitivity analyses to examine the effect of departures from 
key assumptions (e.g., similarity between groups) made in the main analysis and to help determine 
effects of missing data.92, 93  This approach will allow us to determine whether the significance of the 
main analysis was maintained in all sensitivity analyses or was changed in a limited or large number of 
sensitivity analyses. If this is the case, then separate analyses of only those participants who complete 
the study will be conducted.  To prevent missing data, participants will be administered the measures by 
research assistants trained on their proper administration.  Such an approach is more appropriate for 
low-literacy populations and maximizes the completion of the measures.  During the course of the trial, 
monthly reports will be generated summarizing recruitment/accrual and completeness of follow-up to 
allow collaborating sites to proactively follow-up with participants in a timely manner.  
 
Verification of Randomization, Inclusion of Covariates, and Stratification: Preliminary analyses will check 
for baseline differences between groups. By using a RCT, we seek to have groups that will be as similar 
as possible, even in terms of unknown covariates, allowing us to isolate the effect of the intervention. 

 
 
 
 
Borrayo, Stepped-care intervention for LC and HNC Patients and Caregivers, COMIRB # 
14
Should differences remain, we will co-vary variables that are correlated with the outcome and that differ 
by group. Because we are recruiting from four sites, we will verify that site has no impact on outcomes, 
either as a main effect or through interactions with treatment. Given block randomization, no 
differences are expected, particularly no differences in treatment response by site, though we are 
powered to detect differences between the four sites as low as f=.18 (Cohen’s d = .36).  In addition to 
site, responses to the intervention may be further stratified by tumor site (LC vs. HNC) or stage of 
diagnosis; thus, we will use a block randomization and adjust for imbalance by these variables. We will 
introduce fixed effects to account for stratified randomization in our primary analysis. 
 
Analytic Strategy: Primary and secondary outcomes will be analyzed with linear mixed models 
comparing the two groups (stepped care intervention, enhanced usual care) in patients and caregivers 
separately. An alpha level of 0.05 (alpha = 0.05/3 for primary outcomes) will be used to evaluate the a 
priori planned comparisons. Two-tailed tests will help to detect differences between groups. The study 
is powered for testing the hypothesis of no group differences in change over the four time points. The 
software SAS PROC MIXED will be used. 94 For hypotheses addressing group differences for patients and 
separately for caregivers, outcomes will be evaluated with the same design: 2 groups (stepped care 
intervention, enhanced usual care) over 4 times (prior to randomization, 6 weeks, 3 months, 6 months). 
Mixed models will specify group and time and their interaction as fixed effects and subject as a random 
effect, where subject is assumed independently normally distributed with mean 0 and variance 
independent of the random errors. A significant group by time interaction is hypothesized, where those 
in the stepped care intervention are expected to improve to a greater degree than those in the 
enhanced usual care group.  Planned comparisons of group differences at each time point will be 
conducted in the event of a significant interaction effect.  In analyses of caregivers, the model of distress 
will include the caregiver’s age and gender as covariates, as they have been found to be related to their 
distress; we will also investigate inclusion of patient distress, physical and QoL as covariates. The patient 
model of distress will include no a priori covariates, but we will explore inclusion of caregiver distress.  
 
Heterogeneous Treatment Effects: To assess how the heterogeneity of the sample may impact treatment 
effects, a descriptive analysis will be conducted to estimate treatment effects with standard errors for 
important subgroups determined by levels of sex, ethnicity, tumor site (LC vs. HNC), stage (I-II vs. III-IV), 
hospital site and primary language (English vs. Spanish). Analyses will be based on mixed models for 
each subgroup. A second analysis will add each factor separately to mixed models for the entire sample. 
We plan to report on the pre-specified analyses and any post-hoc analyses of subgroups and outcomes 
analyzed to contribute to the trial’s utility and interpretability for implementation and dissemination. 
 
H. Summary of Knowledge to be Gained  
Participating in an intervention that improves symptoms of distress (depression and anxiety) may help 
patients and their caregivers benefit from much needed assistance compared to not receiving support.  
By comparing the stepped-care intervention to usual care practices, the information gleaned from the 
results would demonstrate whether or not an evidence-based intervention targeted to patients’ and 
caregivers’ mental health needs would produce better patient-centered outcomes than usual care.  Any 
temporary discomfort or time spent during the intervention is considered minimal compared to how the 
information gained from the study could affect future underserved LC and HNC patients.  If successful 
and scalable, the study would not only improve access and services for underserved LC and HNC 
patients, but it would contribute information on effective interventions to reduce health disparities.  

 
 
 
 
Borrayo, Stepped-care intervention for LC and HNC Patients and Caregivers, COMIRB # 
15
 
REFERENCES CITED
 
1. American Cancer Society. Cancer Facts & Figures. Atlanta, GA: American Cancer Society; 2015. 
Access March 2, 2015. 
2. Siegel R, DeSantis C, Virgo K, et al. Cancer treatment and survivorship statistics, 2012. CA Cancer J 
Clin. 2012; 62(4):220-241. 
3. Kuriakose MA, Loree TR, Rubenfeld A, et al. Simultaneously presenting head and neck and lung 
cancer: a diagnostic and treatment dilemma. Laringoscope. 2002;112(1):120-3.  
4. Singh, B. Rehabilitation and Quality of Life Assessment in Head and Neck Cancer. In: Shah JP, Patel 
SG, eds. Cancer of the Head and Neck. Hamilton, Ontario: BC Decker Inc; 2001:467-77.  
5. Pozo CLP, Morgan MAA, Gray JE. Survivorship issues for patients with lung cancer. Cancer Control 
2014;21(1): 40-50. 
6. Frampton M. Psychological distress in patients with head and neck cancer: review. Br J Oral 
Maxillofac Surg. 2001;39(1):67-70. 
7. Carper E, Fleishman SB, McGuire M. Symptom management and supportive care for Head and Neck 
Cancer patients.  In: Harrison LB, Sessions RB, Hong WK, eds. Head and Neck Cancer: A 
Multidisciplinary Approach, Third Edition. Philadelphia, PA: Lippincott Williams & Wilkins; 2004:136-
149. 
8. Rogers LQ, Rao K, Malone J, et al. Factors associated with quality of life in outpatients with head and 
neck cancer 6 months after diagnosis. Head Neck. 2009;31(9):1207–14. doi: 10.1002/hed.21084 
9. De Boer MF, Van den Borne B, Pruyn JF, et al. Psychosocial and physical correlates of survival and 
recurrence in patients with head and neck carcinoma: results of a 6-year longitudinal study. Cancer. 
1998;83(12):2567-79. 
10. Fialka-Moser V, Crevenna R, Korpan M, Quittan M. Cancer rehabilitation: particularly with aspects 
on physical impairments. J Rehabil Med. 2003;35(4):153–162. 
11. Sugimura H, Yang P. Long-term survivorship in lung cancer: a review. Chest. 2006;129(4):1088-1097. 
12. van den Beuken-van Everdingen, MH, de Rijke JM, Kessels AG, Schouten HC, van Kleef M,  Patijn J. 
Prevalence of pain in patients with cancer: a systematic review of the past 40 years. Ann Oncol. 
2007;18(9):1437-49.  
13. Bjordal K, Freng A, Thorvik J, Kaasa S. Patients self-reported and clinician-rated quality of life in head 
and neck cancer patients: a cross-sectional study. Eur J Cancer B Oral Oncol. 1995;31B(4):235-41. 
14. Morton RP, Izzard ME. Quality of life outcomes in head and neck cancer patients. World J Surg. 
2003; 27(7):884-9. 
15. Hammerlid E, Silander E, Hornestam L, Sullivan M. Health-related quality of life three years after 
diagnosis of head and neck cancer-a longitudinal study. Head Neck. 2001;23(2):113-25. 
16. Gritz ER, Carmack CL, de Moore C, et al. First year after head and neck cancer: quality of life. J Clin 
Oncol. 1999; 17(1):352-360. 
17. Huguenin PU, Taussky D, Moe K, et al. Quality of life in patients cured from a carcinoma of the head 
and neck by radiotherapy: the importance of the target volume. Int J Radiot Oncol Biol 
Phys.1999;45(1):47-52. 
18. Fritz DJ. Life experiences of head and neck cancer survivors: a pilot study. ORL Head Neck Nurs. 
2001;19:99-102. 
19. Hopwood P, Stephens RJ. Depression in patients with lung cancer: prevalence and risk factors 
derived from quality-of-life data. J Clin Oncol. 2000;18(4):893–903. 

 
 
 
 
Borrayo, Stepped-care intervention for LC and HNC Patients and Caregivers, COMIRB # 
16
20. Buchanan D, Milroy R, Baker L, Thompson AM, Levack PA. Perceptions of anxiety in lung cancer 
patients and their support network. Support Care Cancer. 2010;18(1),29-36. doi: 10.1007/s00520-
009-0626-2. 
21. Davies AD, Davies C, Delpo MC. Depression and anxiety in patients undergoing diagnostic 
investigations for head and neck cancers. Br J Psychiatry. 1986;149:491-3. 
22. Zabora J, BrintzenhofeSzoc K, Curbow B, Hooker C, Piantadosi S. The prevalence of psychological 
distress by cancer site. Psychooncology. 2001;10(1):19-28. 
23. Zeller JL. High suicide risk found for patients with head and neck cancer. JAMA. 2006;296(14):1716–
7. 
24. Holland JC, Kelly BJ, Weinberger MI. Why psychosocial care is difficult to integrate into routine 
cancer care: stigma is the elephant in the room. J Natl Compr Canc Netw. 2010;8(4):362-6. 
25. Clarke A. Psychosocial aspects of facial disfigurement: problems, management and the role of a lay-
led organization. Psychology, Health &Medicine. 1999;4(2):127-42. doi: 10.1080/135485099106270. 
26. Gamba A, Romano M, Grosso IM, et al. Psychosocial adjustment of patients surgically treated for 
head and neck cancer. Head Neck. 1992;14(3): 218-23. 
27. Conlon A, Gilbert D, Jones B, Aldredge P. Stacked stigma: oncology social workers’ perceptions of the 
lung cancer experience. J Psychosoc Oncol. 2010;28(1):98-115. doi: 10.1080/07347330903438982. 
28. Chapple A, Ziebland S, McPherson A. Stigma, shame, and blame experienced by patients with lung 
cancer: qualitative study. BMJ (Clinical research ed.). 2004;328(7454):1470. doi: 
10.1136/bmj.38111.639734.7C. 
29. Gonzalez BD, Jacobsen PB. Depression in lung cancer patients: the role of perceived stigma. 
Psychooncology. 2012;21(3):239-46. doi: 10.1002/pon.1882. 
30. Henoch I, Bergman B, Gustafsson M, Gaston-Johansson F, Danielson E. The impact of symptoms, 
coping capacity, and social support on quality of life experience over time in patients with lung 
cancer. J Pain Symptom Manage. 2007;34(4):370-9.  
31. Lebel S. Castonquay M, Mackness G, Irish J, Bezjak A, Devins GM. The psychosocial impact of stigma 
in people with head and neck or lung cancer. Psychooncology. 22(1): 140-152. doi: 
10.1002/pon.2063. 
32. Ostroff J, Ross S, Steinglass P, Ronis-Tobin V, Singh B. Interest and barriers to participation in 
multiple family groups among head and neck cancer survivors and primary family caregivers. Fam 
Process. 2004;43(2):195-208. 
33. Watt-Wattson J, Graydon J.  Impact of surgery on head and neck cancer patients and their 
caregivers.  Nurs Clin North Am. 1995;30(4):659-71. 
34. Schwartz S, Plawecki HM. Consequences of chemotherapy on the sexuality of patients with lung 
cancer. Clin J Oncol Nurs. 2002;6(4):212–6. 
35. Shell JA, Carolan M, Zhang Y, Meneses KD. The longitudinal effects of cancer treatment on sexuality 
in individuals with lung cancer. Oncol Nurs Forum. 2008;35(1):73-9. doi: 10.1188/08.ONF.73-79.  
36. Maliski SL, Sarna L, Evangelista L, Padilla G. The aftermath of lung cancer: balancing the good and 
bad. Cancer Nurs. 2003;26(3):237-44. 
37. Karnell LH, Christensen AJ, Rosenthal EL, Magnuson JS, Funk GF. Influence of social support on 
health-related quality of life outcomes in head and neck cancer. Head Neck. 2007;29(2):143–6. 
38. Eom CS, Shin DW, Kim SY, et al. Impact of perceived social support on the mental health and health‐
related quality of life in cancer patients: results from a nationwide, multicenter survey in South 
Korea. Psychooncology. 2013;22(6): 1283-90. doi: 10.1002/pon.3133. 
39. Precious E, Haran S, Lowe D, Rogers SN.  Head and neck cancer patients’ perspective of carer 
burden. Br J Oral Maxillofac Surg. 2012;50(3):202-7. doi: 10.1016/j.bjoms.2011.04.072. 
40. Bakas T, Lewis RR, Parsons JE.  Caregiving tasks among family caregivers of patients with lung cancer. 
Oncol Nurs Forum. 2001;28(5):847-54.  

 
 
 
 
Borrayo, Stepped-care intervention for LC and HNC Patients and Caregivers, COMIRB # 
17
41. Roche V. The hidden patient: addressing the caregiver. Am J Med Sci. 2009;337(3):199-204. doi: 
10.1097/MAJ.0b013e31818b114d. 
42. Williamson GM, Shaffer DR. Relationship quality and potentially harmful behaviors by spousal 
caregivers: how we were then, how we are now. The Family Relationships in Late Life Project. 
Psychol Aging. 2001;16(2):217–26. 
43. Lebowitz BD, Pearson JL, Schneider LS, et al. Diagnosis and treatment of depression in late life. 
Consensus statement update. JAMA. 1997;278(14):1186–90. 
44. Schulz R, Newsom J, Mittelmark M, Burton L, Hirsch C, Jackson S. Health effects of caregiving: the 
caregiver health effects study: an ancillary study of the Cardiovascular Health Study. Ann Behav 
Med. 1997;19(2):110–6. 
45. Van Houtven CH, Ramsey SD, Hornbrook MC, Atienza AA, van Ryn M.  Economic burden for informal 
caregivers of lung and colorectal cancer patients. Oncologist. 2010;15(8):883-93. doi: 
10.1634/theoncologist.2010.0005. 
46. Chen SC, Tsai MC, Liu CL, Yu WP, Liao CT, Chang JT. Support needs of patients with oral cancer and 
burden to their family caregivers. Cancer Nurs. 2009;32(6):473–81. doi: 
10.1097/NCC.0b013e3181b14e94. 
47. Verdonck‐de Leeuw IM, Eerenstein SE, Van der Linden MH, Kuik DJ, de Bree R, Leemans CR.  Distress 
in spouses and patients after treatment for head and neck cancer. Laryngoscope. 2007;117(2): 238-
41. 
48. Fujinami R, Sun V, Zachariah F, Uman G, Grant M,  Ferrell B. Family caregivers' distress levels related 
to quality of life, burden, and preparedness. Psychooncology. 2015;24(1):54-62. doi: 
10.1002/pon.3562. 
49. Kim Y, Duberstein PR, Sorensen S, Larson MR. Levels of depressive symptoms of spouses of people 
with lung cancer: Effects of personality, social support, and caregiving burden. Psychosomatics. 
2005;46(2):123–30. 
50. Murray SA, Kendall M, Boyd K, Grant L, Highet G, Sheikh A.  Archetypal trajectories of social, 
psychological, and spiritual wellbeing and distress in family care givers of patients with lung cancer: 
Secondary analysis of serial qualitative interviews. BMJ. 2010;340:c2581. doi:10.1136/bmj.c2581. 
51. Persson C, Ostlund U, Wennman-Larsen A, Wengstrom Y, Gustavsson P.  Health-related quality of 
life in significant others of patients dying from lung cancer. Palliat Med. 2008;22(3):239-47. 
doi:10.1177/0269216307085339 
52. Zwahlen RA, Dannemann C, Grätz KW, et al. Quality of life and psychiatric morbidity in patients 
successfully treated for oral cavity squamous cell cancer and their wives. J Oral Maxillofac Surg. 
2008;66(6):1125-32. doi: 10.1016/j.joms.2007.09.003. 
53. Osborn RL, Demoncada AC, Feuerstein M. Psychosocial interventions for depression, anxiety, and 
quality of life in cancer survivors: meta-analyses. Int J Psychiatry Med. 2006;36(1):13-34. 
54. Northouse LL, Katapodi MC, Song L, Zhang L, Mood DW.  Interventions with family caregivers of 
cancer patients: meta‐analysis of randomized trials. CA Cancer J Clin. 2010;60(5):317-39. doi: 
10.3322/caac.20081. 
55. Luckett T, Goldstein D, Butow PN, et al. Psychological morbidity and quality of life of ethnic minority 
patients with cancer: a systematic review and meta-analysis. Lancet Oncol. 2011;12(13):1240–8. doi: 
10.1016/S1470-2045(11)70212-1. 
56. Borrayo, E.A., Scott, K., Drennen, A., MacDonald, T., Nguyen, J. (2016). Determinants of Treatment 
Delay among Underserved Hispanic Patients Diagnosed with Lung Cancer and Head-and-Neck 
Cancer. Cancer Control Journal, 23(4), 390-400. Epub 2016 Nov 1. 
57. Kilbourn KM, Anderson D, Costenaro A, Luzczakoski K, Borrayo E, Raben D. Feasibility of EASE: a 
psychosocial program to improve symptom management in head and neck cancer patients. Support 
Care Cancer. 2013;21(1): 191-200. doi: 10.1007/s00520-012-1510-z. 

 
 
 
 
Borrayo, Stepped-care intervention for LC and HNC Patients and Caregivers, COMIRB # 
18
58. Antoni MH. Stress management intervention for women with breast cancer: participant’s workbook. 
Washington, DC: American Psychological Association Press; 2003. 
59. Kilbourn KM, Costenaro A, Madore S, et al. Feasibility of a telephone-based counseling program for 
informal caregivers of hospice patients. J Palliat Med. 2011;14(11):1200-1205. 
60. Common mental health disorders. Identification and pathways to care. Agency for Healthcare 
Research and Quality and National Guideline Clearinghouse Web site. 
http://www.guideline.gov/content.aspx?id=34828. Published March 16, 2012. Accessed April 4, 
2015. 
61. National Collaborating Centre for Mental Health. Common Mental Health Disorders. Identification 
and Pathways to Care. London (UK): National Institute for Health and Clinical Excellence (NICE); 
2011. 
62. Lazarus RS, Folkman S. Stress, Appraisal, and Coping. New York: Springer Publishing Company;1984. 
63. Cella D, Choi S, Garcia S, et al. Setting standards for severity of common symptoms in oncology using 
the PROMIS item banks and expert judgment. Qual Life Res. 2014;23(10):2651-61. doi: 
10.1007/s11136-014-0732-6. 
64. Jacobsen PB, Meade CD, Stein KD, Chirikos TN, Small BJ, Ruckdeschel JC. Efficacy and costs of two 
forms of stress management training for cancer patients undergoing chemotherapy. J Clin Oncol. 
2002;20(12):2851-62. 
65. Cella D, Riley W, Stone A, 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. J Clin Epidemiol. 2010;63(11):1179–94. doi:10.1016/j.jc.linepi.2010.01.011. 
66. Schalet BD, Cook KF, Choi SW, Cella D. Establishing a common metric for self-reported anxiety: 
linking the MASQ, PANAS, and GAD-7 to PROMIS Anxiety. J Anxiety Disord. 2014;28(1):88-96. doi: 
10.1016/j.janxdis.2013.11.006. 
67. Choi SW, Schalet B, Cook KF, Cella D. Establishing a common metric for depressive symptoms: 
Linking the BDI-II, CES-D, and PHQ-9 to PROMIS Depression. Psychol Assess. 2014;26(2):513-27. doi: 
10.1037/a0035768. 
68. Marshall JA, Scarbro S, Shetterly SM, Jones RH. Improving power with repeated measures: diet and 
serum lipids. Am J Clin Nutr. 1998;67(5):934-9. 
69. Laird NM. Missing data in longitudinal studies. Stat Med.1988;7(1-2):305-15. doi: 
10.1002/sim.4780070131. 
70. White IR, Horton NJ, Carpenter J, Pocock SJ. Strategy for intention to treat analysis in randomized 
trials with missing outcome data. BMJ. 2011:342:d40. doi: 10.1136/bmj.d40. 
71. Thabane L, Mbuagbaw L, Zhang S, et al. A tutorial on sensitivity analyses in clinical trials: the what, 
why, when, and how. BMC Med Res Methodol. 2013;13:92. doi:10.1186/1471-2288-13-92. 
72. The NLMIXED Procedure. 9.3 ed. Cary, NC: SAS Institute, Inc.; 2011. 
73. Chesney, M. A., Neilands, T. B., Chambers, D. B., Taylor, J. M., & Folkman, S. (2006). A validity and 
reliability study of the coping self‐efficacy scale. British journal of health psychology, 11(3), 421-437 
74. Zarit, S. H., Reever, K. E., Back-Peterson, J. (1980). Relatives of the impaired elderly: correlates of 
feelings of burden. The Gerontologist, 20, 649-655 
75. Hérbert, R., Bravo, G., & Préville, M. (2000). Reliability, validity, and reference values of the Zarit 
Burden Interview for assessing informal caregivers of community-dwelling older persons with 
dementia. Canadian Journal on Aging, 19, 494-507. 
76. Cella DF, Tulsky DS. Quality of life in cancer: definition, purpose, and method of measurement. 
Cancer Invest. 1993;11(3):327-36. 
77. Cella DF, Bonomi AE, Lloyd SR, Tulsky DS, Kaplan E, Bonomi P. Reliability  and  validity  of  the  
functional  assessment  of  cancer therapy-lung  (FACT-L) quality of life instrument. Lung Cancer. 
1995;12(3):199-220. 

 
 
 
 
Borrayo, Stepped-care intervention for LC and HNC Patients and Caregivers, COMIRB # 
19
78. Browning KK, Ferketich AK, Otterson GA, Reynolds NR, Wewers ME. A psychometric analysis of 
quality of life tools in lung cancer patients who smoke. Lung Cancer. 2009;66(1):134-139. doi: 
10.1016/j.lungcan.2008.12.018. 
79. D'Antonio LL, Zimmerman GJ, Cella DF, Long SA. Quality of life and functional status measures in 
patients with head and neck cancer. Arch Otolaryngol Head Neck Surg. 1996;122(5);482-7. 
80. List MA, D'Antonio LL, Cella DF, et al. The Performance Status Scale for Head and Neck Cancer 
Patients and the Functional Assessment of Cancer Therapy-Head and Neck Scale. A study of utility 
and validity. Cancer. 1996; 77(11):2294-301. 
81. Cohen S, Kamarck T, Mermelstein R. A global measure of perceived stress. J Health Soc Behav. 
1983;24(4):385-396. 
82. Lee E-H. Review of the psychometric evidence of the perceived stress scale. Asian Nursing Research. 
2012;6(4): 121-7. doi: http://dx.doi.org/10.1016/j.anr.2012.08.004. 
83. Golden-Kreutz DM, Browne MW, Frierson GM, Andersen BL. Assessing stress in cancer patients: a 
second-order factor analysis model for the Perceived Stress Scale. Assessment. 2004;11(3):216-23. 
84. Kessler ER, Moss A, Eckhardt SG, et al. Distress among caregivers of phase I trial participants: a 
cross-sectional study. Support Care Cancer. 2014;22(12):3331-40. doi: 10.1007/s00520-014-2380-3.  
85. Calonge, N. The Affordable Care Act. The Colorado Trust. Retrieved from 
https://www.colorado.gov/pacific/sites/default/files/DC_Affordable-Care-Act-presentation-by-
Ned-Calonge.pdf. Published March 23, 2013. Accessed November 11, 2016. 
86. Health & Human Services Department. Annual Update of the HHS Poverty Guidelines. The Federal 
Register: The Daily Journal of the United States Government. Retrieved from 
https://www.federalregister.gov/documents/2016/01/25/2016-01450/annual-update-of-the-hhs-
poverty-guidelines. Published January 25, 2016. Accessed on November 11, 2016. 
87. Families USA. The Voice for Healthcare Consumers. Federal Poverty Guidelines. Retrieved from 
http://familiesusa.org/product/federal-poverty-guidelines. Published February 2016. Accessed on 
November 11, 2016. 
88. Badr H, Krebs P.  A systematic review and meta‐analysis of psychosocial interventions for couples 
coping with cancer. Psychooncology. 2013;22(8):1688-704. doi: 10.1002/pon.3200. 
89. Torgerson DJ. Contamination in trials: is cluster randomisation the answer? BMJ 2001;322:355-357. 
90. Marshall JA, Scarbro S, Shetterly SM, Jones RH. Improving power with repeated measures: diet and 
serum lipids. Am J Clin Nutr. 1998;67(5):934-9. 
91. Laird NM. Missing data in longitudinal studies. Stat Med.1988;7(1-2):305-15. doi: 
10.1002/sim.4780070131. 
92. White IR, Horton NJ, Carpenter J, Pocock SJ. Strategy for intention to treat analysis in randomized 
trials with missing outcome data. BMJ. 2011:342:d40. doi: 10.1136/bmj.d40. 
93. Thabane L, Mbuagbaw L, Zhang S, et al. A tutorial on sensitivity analyses in clinical trials: the what, 
why, when, and how. BMC Med Res Methodol. 2013;13:92. doi:10.1186/1471-2288-13-92. 
94. The NLMIXED Procedure. 9.3 ed. Cary, NC: SAS Institute, Inc.; 2011. 
95. Sobell MB, Sobell LC. Stepped care as a heuristic approach to the treatment of alcohol problems. J 
Consult Clin Psychol. 2000;68(4):573–9. 
96. Bjelland, I., Dahl, A. A., Haug, T. T., & Neckelmann, D. (2002). The validity of the Hospital Anxiety 
and Depression Scale: an updated literature review. Journal of psychosomatic research, 52(2), 69-
77.