Comprehensive vs. Assisted Management of Mood and Pain Symptoms (CAMMPS) Trial
Phase: NA
Conditions: Pain, Depression, Anxiety, Musculoskeletal, Fibromyalgia
Sponsor: VA Office of Research and Development

Page 1 of 56 
 
Study #1212010163 
 
 
 
 
 
Comprehensive vs. Assisted Management of Mood and Pain Symptoms (CAMMPS) 
NCT01757301 
November 30, 2015 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Page 2 of 56 
 
Study #1212010163 
 
SPECIFIC AIMS 
Comprehensive vs. Assisted Management of Mood and Pain Symptoms (CAMMPS) Trial 
A1. Introduction 
 
I am no better in mind than in body. Both alike are sick and I suffer double hurt.   [Ovid] 
 
Two millennia ago, the Greek poet Ovid recognized the “double hurt” caused by comorbid physical 
and psychological symptoms.  Pain is the most common presenting somatic symptom in medical 
outpatients, and depression and anxiety are the two most common mental disorders.  All three conditions 
are often inadequately treated and result in substantial disability, reduced health-related quality of life, and 
increased health care costs and utilization.  Moreover, they are often inextricably linked in a pain-anxiety-
depression (“PAD”) triad such that disentanglement is scientifically and clinically impractical.  Additionally, 
the PAD threesome has reciprocal negative effects on treatment response of one another, and additive 
adverse effects on health outcomes.  Although problematic in all practice settings, the PAD triad is 
especially burdensome in veterans. 
 
We propose to conduct a randomized comparative effectiveness trial – Comprehensive vs. Assisted 
Management of Mood and Pain Symptoms (CAMMPS) – to compare two pragmatic interventions (an 
intensive vs. a low-resource approach) for treating three of the most common, chronic, comorbid and 
disabling symptoms in veterans: pain, anxiety, and depression.  Indeed, CAMMPS will focus on patients 
with PAD comorbidity, i.e., those having pain plus anxiety and/or depression.  Whereas most previous 
studies have focused on the PAD symptoms individually, the high co-occurrence of these symptoms makes 
a mono-symptomatic approach impractical as well as suboptimally effective. Single-condition care 
management programs are not only costly but tend to provide fragmented disease-based care rather than 
integrated management of the complex patient with comorbidity. In particular, pain is viewed by clinicians 
and patients alike as primarily a “medical” condition whereas depression and anxiety are considered 
“mental” disorders.  As a consequence, the management of pain and depression/anxiety too often gets 
carved up between the medical and mental health components of the health care system, rather than being 
integrated and coordinated. 
 
Our trial will compare two levels of enhancement to usual care for the PAD triad:  1) assisted symptom 
management (ASM), consisting of automated symptom monitoring and prompted pain and mood self-
management;  2) comprehensive symptom management, combining ASM with optimized medication 
management and facilitated mental health care by a centralized nurse-physician team. The rationale for 
ASM is preliminary evidence of its effectiveness and its lower use of resources. The rationale for CSM is 
that the addition of care coordination, optimized medication management for the PAD symptoms, and 
facilitated mental health care should substantially enhance the benefits of ASM. 
A2. Specific Aims and Hypotheses 
 
 Our study has one primary aim (#1), two secondary aims (#2,3), and one exploratory aim (#4). 
 
 Aim 1.  To compare 12-month effectiveness of CSM vs. ASM in improving overall pain and mental 
health. Our hypothesis is that CSM will be superior to ASM in reducing a composite pain-anxiety-depression 
severity score. 
 
 Aim 2.  To compare 12-month effectiveness of CSM vs. ASM in improving specific PAD symptoms. 
Our hypothesis is that CSM will be superior to ASM in reducing pain, anxiety, and depression severity 
scores individually.  
 
 Aim 3. To compare the effects of CSM vs. ASM on secondary outcomes, including health-related 
quality of life, disability, health care utilization, treatment satisfaction, and patient and provider perceptions 
of barriers and facilitators to CSM and ASM. 
       Aim 4. To explore the relative contribution of each intervention component to overall symptom 
improvement. These 5 components are automated symptom monitoring, prompted self-management, nurse 
contacts, optimized medication changes, and facilitated mental health care. Our hypothesis is that each of 
these components will have a dose-response relationship with the degree of improvement in the primary 
outcome. 

Page 3 of 56 
 
Study #1212010163 
 
B. 
BACKGROUND 
“The mind may undoubtedly affect the body; but the body also affects the mind.  There is a re-action 
between them; and by lessening it on either side, you diminish the pain on both.” 
 
Leigh Hunt, a 19th century English poet and contemporary of Keats, realized that somatic and psychic 
pain are inextricably linked and exacerbate one another. This poetic insight portended what clinicians and 
scientists have repeatedly found, namely that disarticulating chronic physical and psychological symptoms 
is as hazardous as separating Siamese twins, and that an exclusive focus on treating one type of symptom 
while ignoring the other imperils the amelioration of both. 
B1. Pain is the most common physical symptom and a public health priority 
 
Pain is the most common symptom reported in both the general population and in primary care.1 
Pain complaints account for more than 40% of all symptom-related outpatient visits and over 100 million 
ambulatory encounters in the U.S. each year.2  In the United States alone, chronic pain conditions cost 
more than $500 billion annually in direct medical costs and lost productivity.1 Pain medications are the 
second most prescribed class of drugs (after cardiac-renal drugs), accounting for 12% of all medication 
prescribed during ambulatory office visits in the United States.3  Clinicians are being pressured to respond 
to pain as the “fifth vital sign”. In House Resolution 1863, the National Pain Care Policy Act of 2003, 
Congress declared this the “Decade of Pain Control and Research.”  Indeed, persistent pain is a major 
international health problem, prompting the World Health Organization to endorse a global campaign 
against pain.4  Persistent pain may lead to excessive surgery or other expensive or invasive procedures and 
is also the leading reason for use of complementary and alternative medicine.5  Pain is also among the most 
common reasons for temporary and permanent work disability.6   
 
Musculoskeletal pain is consistently the most common, disabling, and costly of all pain complaints.1,7  
Indeed, two-thirds of pain-related outpatient visits are due to musculoskeletal pain, accounting for nearly 70 
million outpatient visits in the U.S. each year.2  In a study assessing pain as the 5th vital sign in 9 VA clinics, 
more than 80% of all pain complaints expressed by Veterans were musculoskeletal in nature.8  Two Institute 
of Medicine reports have summarized the enormous functional and economic impact of musculoskeletal 
pain on both the working and the retired population.1,7  Back pain and joint pain alone result in an estimated 
200 million lost work days per year.  
B2. Depression and anxiety are the two most common psychological disorders in primary care, 
proving very disabling and costly. 
 
Depression and anxiety are the two most common mental health problems seen in the general 
medical setting,9,10 each being present in 10%-15% of primary care patients. They produce substantial 
disability and decrements in health-related quality of life, often exceeding the impairment seen in patients 
with chronic medical disorders.11,12  Depression has been the subject of considerable primary care and 
public health attention the past several decades. Depressive illness is projected to be the second leading 
cause of disability worldwide in 2020. The substantial public health and economic significance of depression 
is reflected by its considerable effect on health care utilization and great monetary costs: $83 billion 
annually, of which more than half represents lost work productivity.13 
 
Anxiety disorders are just as prevalent as depression and adversely affects patient functioning, work 
productivity, and health care costs.14  Over 30 million Americans have a lifetime history of anxiety, and 
anxiety disorders cost an estimated $42 billion dollars per year in the United States alone, counting direct 
and indirect costs.15  The four most common anxiety disorders (excluding simple phobias which seldom 
present clinically) are generalized anxiety, panic disorder, social anxiety disorder, and posttraumatic stress 
disorder (PTSD).16,17 Moreover, while PTSD is clearly the single most important anxiety disorder in 
Veterans, recent research shows that other anxiety disorders are also prevalent, undertreated, and 
disabling in Veterans (see section B3b below). However, despite the significant disability associated with 
each anxiety disorder and the availability of effective treatments, only a minority (15% to 36%) of patients 
with anxiety are recognized in primary care18 and often go untreated.16 Moreover, anxiety often co-occurs 
with depression and, when it does, the adverse effects on impairment and resource utilization are 
additive.19,20 
 

Page 4 of 56 
 
Study #1212010163 
 
B3. Anxiety is a large unmet need in primary care 
 
Depression has been a principal focus of research as well as quality improvement initiatives in primary 
care for the past 25 years, with chronic pain gaining increased attention the past decade. In contrast, 
anxiety has been understudied relative to its prevalence and impact summarized in B2 above.  Several 
recent studies highlight the importance of bringing anxiety into the fold.  
 
B3a.  Anxiety in Primary Care study.  We enrolled more than 2000 adult patients from 15 primary 
clinics in the United States.  A sample of 965 patients underwent a structured psychiatric interview for the 4 
most common clinically relevant anxiety disorders in primary care, revealing that posttraumatic stress, 
generalized anxiety, social anxiety, and panic disorder were present in 8.6%, 7.6%, 6.2%, and 6.2% of the 
patients, respectively.16 There was an incremental adverse effect of the number and severity of anxiety 
disorders on quality of life, disability, and health care use. Additionally, more than 40% of patients with an 
anxiety disorder reported no current treatment. In an editorial accompanying our paper, Katon and Roy-
Byrne wrote: “Anxiety disorders have been the neglected stepchild of primary care–based mental health 
care. Compared with the extensive research in primary care on the adverse effects of depression on 
somatic symptom burden, decrements in function, and medical utilization and costs, far less research has 
been completed on anxiety disorders. Yet, the National Comorbidity Survey has shown that anxiety 
disorders are the most frequent disorders in the general population and are associated with substantial 
social and vocational impairment.”21.  
    
There are 2 other findings from 
this study relevant to CAMMPS.22  First, 
of the patients with anxiety and/or 
depression, 42% had anxiety only, 29% 
had depression only, and 29% had both 
anxiety 
and 
depression. 
Thus, 
if 
screening programs focused only on 
depression, 2 out 5 patients with 
psychological comorbidity would be 
missed. Second, Figure 1 on the right 
shows the effects of anxiety and 
depression on 6 domains of health-
related quality of life (HRQL) as 
measured by the SF-20 where lower 
scores indicated worse HRQL. Notably, 
anxiety had an adverse impact on 
mental functioning and pain similar to 
depression, and an adverse effect on 
other 
health-related 
quality 
of 
life 
domains intermediate between depression and no anxiety/depression.  Also, for several domains of HRQL 
(e.g., mental and social functioning), the combination of anxiety and depression was worse than either 
condition alone.  
 
B3b.  Anxiety is a major problem in Veterans.  Magruder et al have demonstrated the high prevalence 
and impairment of untreated PTSD (including subthreshold PTSD) among Veterans receiving care in VA 
primary care clinics.23-25 A similar unmet need exists for Veterans in primary care with other anxiety 
disorders such as panic disorder and social anxiety disorder.26,27 
 
B3c.  Recent trials demonstrate the treatability of anxiety in primary care.  The Coordinated Anxiety 
Learning and Management (CALM) trial randomized 1004 primary care patients with anxiety disorders to 
either usual care or a flexibly delivered intervention that provided medication and/or cognitive-behavioral 
therapy based upon patient preferences and clinical response. The primary care-based intervention was 
superior to usual care, and was effective regardless of the type of anxiety disorder.17,28 A smaller trial 
demonstrated that telephone-based care management improved outcomes in primary care patients with 
generalized anxiety disorder and panic disorder.29 
20
30
40
50
60
70
80
90
100
Mental
Social
General
Role
Pain
Physical
20
30
40
50
60
70
80
90
100
Mental
Social
General
Role
Pain
Physical
Neither Anxiety Nor Depression
Anxiety only
Depression only
Both Anxiety and Depression
SF-20 Score

Page 5 of 56 
 
Study #1212010163 
 
 
B3d.  Adverse effect of comorbid anxiety on depression and pain outcomes.  In our SCAMP trial, we 
found that chronic pain patients with both depression and anxiety had more severe pain, greater disability, 
and worse quality of life than those with depression only.30  Longitudinally, baseline anxiety adversely 
influenced both depression and pain outcomes at 12 months, whereas early improvement in anxiety 
positively influenced outcomes.31 
B4. Pain-anxiety-depression (PAD) comorbidity is the norm, making single-condition disease  
management passé.  
A study of 965 primary care patients found 
high and overlapping levels of pain-anxiety-
depression (PAD) symptomatology (Table 
1).16  A survey of 2091 primary care patients 
in 15 U.S. clinics assessed the presence of 
high 
depressive, 
anxiety, 
and 
somatic 
symptom severity with the PHQ-9, GAD-7, 
and PHQ-15, respectively.20  Of note, pain 
symptoms 
accounted 
for 
a 
substantial 
proportion of somatic symptoms.  As shown in 
Figure 2 on the right, a “pure” form of any of the 
symptom 
types 
was 
less 
common 
than 
comorbidity.20 Similar results were found in a Swiss 
study where a survey of 917 general practice 
patients found that PAD comorbidity was present in 
60%, 71%, and 60% of individuals with depression, 
anxiety, and somatization, respectively.32 In a study 
of 
340 
OIF/OEF 
Veterans 
evaluated 
in 
a 
polytrauma clinic, 58.6% had both chronic pain and 
PTSD , 22.9% had chronic pain only, 9.7% had 
PTSD only, and 8.8% had neither.33  PTSD and 
depression frequently co-occur in Veterans.34 
Finally, our recent analysis of a large population-
based 
study 
of 
almost 
200,000 
individuals 
randomly sampled from the U.S. verified the high 
comorbidity and reciprocal adverse affects of 
depression, anxiety, and pain on each other and on HRQL and disability.35,36  
B5. Relative to depression, systems-based interventions for pain and anxiety care have been 
understudied, with a particular evidence gap for interventions targeting PAD comorbidity 
 
There have been more than 40 randomized controlled trials that have consistently demonstrated that 
collaborative care or other systems-based enhancements are superior to usual primary care for improving 
depression outcomes.37,38 Indeed, the VA has been among the leaders in such research and has developed 
a robust effort to support the implementation of evidence-based collaborative care for depression 
throughout its facilities nationwide.39  A national QUERI initiative (the TIDES model) has systematically 
disseminated evidence-based approaches.40 In contrast, there have been only a few published trials 
supporting collaborative care for chronic pain41,42 or anxiety28,29 in primary care. Moreover, only one trial has 
targeted two PAD symptoms42, whereas all the rest have focused on a single PAD symptom only. 
 
C. 
SIGNIFICANCE AND RELEVANCE 
C1. CAMMPS is responsive to two HSR&D priority areas 
 
CAMMPS is directly responsive to HSR&D Priority C – Healthcare Informatics, which is described in 
the Program Announcement:  “Healthcare informatics is the integration of biomedical knowledge systems 
with technology to improve decision-support systems, evidence-based practices, collaboration and 
continuity of care among providers, and Veteran and provider education.”  Specifically, sample research 
Table 1.  PAD Severity in 965 Primary Care Patients 
Severity * 
Pain 
Anxiety 
Depression 
None (0) 
12% 
35% 
35% 
Mild (1-3) 
36% 
30% 
31% 
Moderate (4-6) 
29% 
22% 
21% 
Severe (7-10) 
23% 
13% 
13% 
* 0-10 severity scale 

Page 6 of 56 
 
Study #1212010163 
 
topic #4 under this priority area is to “develop and evaluate decision support systems that incorporate 
Veteran preferences and enhance management of complex chronic conditions.”  There are several ways 
CAMMPS is responsive to this priority area.  First, automated symptom monitoring will play a key role in 
assessing pain, anxiety and depression severity, response to treatment, adherence, and side effects. This 
facilitates asynchronous data collection in a manner convenient to the patient’s schedule and minimizes the 
“telephone tag” that frequently occurs in standard nurse telecare management. In non-VA cancer 
populations, this automated approach has been shown to increase the efficiency of care manager time as 
well as enhance patient satisfaction.43  Second, prompted pain and mood self-management strategies will 
be built into the automated system, thereby allowing the technology to advance beyond simple data 
collection to enhanced treatment as well.44-46  Third, the system further enhances symptom management by 
facilitating communication between the Veteran and provider. This is accomplished by enabling the Veteran 
to request a nurse phone call as well as by flagging certain Veteran reports (e.g., symptom worsening, 
medication nonadherence or side effects, or a patient desire for treatment changes) and automatically 
alerting the nurse. 
 
CAMMPS is also responsive to HSR&D Priority Area E – Mental and Behavioral Health, which in the 
Program Announcement is “broadly defined to include issues ranging from substance use and depression 
to post-traumatic stress disorders and serious mental illness.” Specifically, sample research topic #2 under 
this priority area is to “evaluate methods to enhance the integration and coordination of mental health 
services with primary care and specialty services”, and sample research topic #3 is to “evaluate innovative 
strategies to improve earlier identification and treatment of posttraumatic stress disorders and related 
mental health disorders (substance use and depression).” There are several ways CAMMPS is responsive 
to this priority area.  First, it takes an important next step beyond traditional depression or pain care 
management programs by adding PTSD and other anxiety disorders. Second, it moves beyond typical care 
management programs which have supported and enhanced the care provided by primary care physicians 
to extending this same support to the care provided by psychologists embedded in VA primary care (see 
section C3 below). Specifically, automated monitoring of depression and anxiety treatment outcomes will 
facilitate treatment adjustments for patients seen by both primary care physicians and embedded 
psychologists.  Moreover, nurse care manager coordination will enhance both mental health referrals and 
appointment-keeping. 
C2. CAMMPS is highly relevant to the VHA patient care mission. 
 
CAMMPS addresses several issues of great significance and relevance to the VA.  First, it provides an 
integrated approach to three of the most prevalent and burdensome symptom-based disorders afflicting 
Veterans. While quality improvement initiatives for depression have been disseminated through the TIDES 
program, coordinated and outcome-based treatment for pain is in its infancy, and systems-based programs 
for PTSD and other anxiety disorders are likewise lacking.  Second, although the placement of 
psychologists in VA primary care clinics has great potential for improving outcomes, collaborative care that 
triangulates symptom-based care managers, primary care physicians, and embedded psychologists has not 
been tested.  Also, some of the key components that undergird the effectiveness of collaborative care for 
depression (e.g., measurement-based care to monitor and adjust treatment; disease registries; coordination 
of medication management by the physician and psychotherapeutic treatments and follow-up by the mental 
health professional) are often lacking. Third, the recent increase of mental health professionals in the VA 
may still be inadequate to meet the huge mental health needs of Veterans. A recent survey of 272 mental 
health (MH) providers throughout five VISNs found that 40% of MH caregivers cannot schedule an 
appointment in the desired two-week window (U.S. Medicine, Oct 11, 2011). Moreover, 70% of MH 
caregivers said they did not have adequate staff or space, and 26% said that the need to perform 
compensation and pension examinations pulled them away from patient care.  Thus, enhancing the first-line 
management of PAD comorbidity in primary care is an important strategy for optimizing the use of high-
demand mental health specialty services. 
C3. CAMMPS is an important advance that builds upon our completed and ongoing studies. 
 
Table 2 summarizes the key features of our clinical trials to date of pain and depression. Four 
innovative and significant features of CAMMPS highlighted in the table include: 1) the addition of anxiety 
conditions (including PTSD) to the care management program; 2) the comparison to a largely automated 

Page 7 of 56 
 
Study #1212010163 
 
active comparator intervention rather than simple usual care; 3) the collaboration with embedded 
psychologists in addition to primary care physicians; 4) the collaboration/integration of the intervention with 
the patient-aligned care teams (PACTs).  
 
The significance of these “next steps” has several additional implications.  First, not only is anxiety 
added (the critical third member of the PAD symptom triad), but CAMMPS focuses on the highly prevalent 
but much more difficult clinical population that has pain comorbid with depression and/or anxiety. Previous 
single-condition trials focusing only on pain or psychological conditions (depression, PTSD or other anxiety 
disorders) are not readily generalizable to the more common clinical scenario where the patient has PAD 
comorbidity. Second, CAMMPS is the first trial in primary care to simultaneously take on the monitoring and 
optimization of both analgesic and antidepressant management. Third, the use of outcomes monitoring 
using validated pain, depression and anxiety measures that are sensitive to change (i.e., measurement-
based care) will facilitate treatment adjustments in patients cared for by primary care physicians as well as 
by psychologists embedded in primary care.  Fourth, the comparison with a largely automated intervention 
will show the incremental benefit of adding nurse care management, optimized medication management, 
and facilitated mental health care.  
 
Regarding our two ongoing trials, SCOPE focuses only on pain (and not depression or anxiety); is 
compared to usual care rather than an active comparator; and partners only with primary care physicians 
and not psychologists.  CAMEO likewise focuses only on pain; targets only patients with low back pain 
receiving chronic opioid therapy; and compares pharmacological management of pain to structured 
cognitive-behavioral therapy. Neither trial collaborates with PACT. Thus, the 3 trials have distinct aims and 
interventions. 
Table 2.  Key Characteristics of Completed and Ongoing Trials 
 
 
 
 
 
 
Intervention 
Focus 
 
Partners† 
 
Trial   
(PI) 
N 
Prim 
Care 
Pain 
Site 
Prior 
Pain 
Rx 
% 
Vets 
Pain 
Dep 
Anx 
Compar-
ator   
Group 
PCP 
MH 
PACT 
Stat-
us 
ESCAPE 
(Bair) 
240 
Yes 
MS 
Any 
100% 
Yes 
No 
No 
Usual care 
Yes 
No 
No 
Com-
pleted 
SCOPE 
(Kroenke) 
250 
Yes 
MS 
Any  
100%  Yes 
No 
No 
Usual care 
Yes 
No 
No 
On-
going 
CAMEO 
(Bair) 
450 
Yes 
Back 
Opi-
oids 
100% 
Yes 
No 
No 
Behavioral 
intervention 
Yes 
Yes 
No 
On-
going 
SCAMP 
(Kroenke) 
250 
Yes 
MS 
Any 
40% 
Yes 
Yes 
No 
Usual care 
Yes 
No 
No 
Com-
pleted 
INCPAD 
(Kroenke) 
405 
No 
Any 
Any 
8% 
Yes 
Yes 
No 
Usual care 
Yes 
No 
No 
Com-
pleted 
CAMMPS 
(Kroenke) 
300 
Yes 
MS 
Any 
100% 
Yes 
Yes 
Yes 
Automated 
intervention 
Yes 
Yes 
Yes 
Pro-
posed 
† Partners denote clinicians with whom the intervention team collaborates during the trial.   
  PCP = primary/principal care provider.  MH = psychologist embedded in primary care.   
  PACT = patient-aligned care team 
C4. Overall Innovation and Significance of CAMMPS 
 
 CAMMPS compares a more resource-intensive intervention vs. a low-resource largely automated 
enhancement of usual care for the major symptom triad among Veterans in primary care. Innovations 
include an integrated approach to PAD symptom comorbidity rather than fragmented care of single 
symptoms; coordinated symptom management in partnership with both primary care clinicians and 
psychologists embedded in primary care; the efficient use of health information technology; attention to 

Page 8 of 56 
 
Study #1212010163 
 
physical and psychological symptom comorbidity; and the coupling of self-management with medication 
treatments. Significance is heightened not only by a comparative test of CSM vs. ASM but also by their 
potential future use in a tailored or stepped care (rather than either-or) approach, their application to 
symptom management in specialty as well as primary care settings, and their relevance in augmenting 
symptom management provided by VA telehealth services as well as patient-aligned care teams (PACTs).   
 
D. 
RESEARCH DESIGN AND METHODS 
D1. Conceptual Model 
 
 Figure 3 depicts the conceptual 
model underlying the CAMMPS trial. 
The assisted symptom management 
(ASM) arm has 2 components that 
enhance usual care:  automated PAD 
symptom monitoring and automated 
prompting of the patient to use pain 
and mood self-management strategies. 
The 
comprehensive 
symptom 
management (CSM) arm adds 3 
additional components to ASM:  nurse 
contacts; 
optimized 
medication 
regimens for PAD symptoms; and 
facilitated 
mental 
health 
care.  
Collectively, 
these 
5 
components 
constitute 
the 
active 
intervention 
ingredients 
which 
lead 
to 
an 
improvement in the primary (proximal) 
outcome, namely symptom burden as 
measured by the composite PAD 
symptom 
severity 
(i.e., 
PROMIS) 
score. Secondary (distal) outcomes postulated to benefit from reduced PAD symptom burden include 
health-related quality of life (HRQoL), disability, patient satisfaction, and health care use. 
 
D2a. Overall Design 
PAD 
(Pain with Anxiety/Depression Comorbidity)
(n = 300)
Assisted         
Symptom Management
(n = 150)
Outcome Assessment at baseline, 1, 3, 6, and 12 months
Comprehensive     
Symptom Management
(n = 150)
 
Automated contacts
Facilitated mental 
health care
Prompted pain self-
management
Optimized medications
Nurse contacts
C
S
M
A
S
M
INTERVENTION COMPONENTS
↓PAD 
Symptom 
Severity
OUTCOMES
Primary
Secondary
•HRQoL
•Disability
•Satisfaction
•Health care use

Page 9 of 56 
 
Study #1212010163 
 
 
Figure 4 above illustrates the CAMMPS 12-month trial design. Primary care Veterans with pain plus 
anxiety and/or depression that meet threshold levels of severity and persistence (see section D4a) and who 
are eligible and provide informed consent will be randomized to one of two treatment arms. One group will 
receive assisted symptom management (ASM) with automated monitoring by interactive voice recording or 
Internet with prompted pain and mood self-management. The second group will receive comprehensive 
symptom management (CSM) which combines ASM with care coordination by a nurse-physician specialist 
team that will optimize medication (analgesics/psychotropics) and facilitate mental health care. In short, 
CAMMPS compares: 1) usual care plus assisted symptom management (ASM) vs. 2) usual care plus ASM 
plus optimized medication management and facilitated mental health care.  Our primary hypothesis is that 
CSM is superior to ASM in improving both pain and mental health. Outcomes will be assessed at baseline, 
1, 3, 6, and 12 months. The primary outcome is a composite pain-anxiety-depression score. Secondary 
outcomes include individual pain, anxiety, and depression scores; functional status and health-related 
quality of life; health care utilization; and treatment satisfaction 
 
D2b. Key Questions Regarding CAMMPS Study Design 
There are several reasonable questions regarding the CAMMPS study design worth addressing: 
 
1)  Why is assisted symptom management (ASM) selected as an active comparator group? First, there 
is preliminary evidence from several trials that automated symptom monitoring with varying degrees of 
prompted self-management may improve pain and other symptoms in cancer46 and non-cancer44,45 
populations. Second, ASM uses substantially less resources than CSM so determining its relative 
effectiveness compared to the more intensive CSM is important from a VA policy and clinical practice 
standpoint. Indeed, ASM is principally an automated enhancement to usual care that requires a minimal 
amount of human/clinical resources and could be readily implemented with simple access to either a phone 
or a computer. In fact, where usual care has already been convincingly shown as inadequate (see #2 
below), effectiveness trials increasingly use simple enhancements to usual care as the comparator arm. 
Third, multiple agencies have called for comparative effectiveness trials: the U.S. Department of Health and 
Human Services, the Institute of Medicine, the Society for Clinical and Translational Sciences, and the 
Patient-Centered Outcomes Research Institute have all encouraged a paradigm shift in which head-to-head 
comparisons are conducted for two or more effective or potentially effective treatment strategies.47-50 Fourth, 
ASM will provide immediate symptom-specific self-management strategies to remind patients of the 
strategies as well as to reinforce potential adherence. Finally, even though CAMMPS is a head-to-head 
comparison of CSM vs. ASM, the two strategies to enhance usual care could be ultimately used in a 
stepped care rather than either-or approach.   
 
2) Why not include a usual care arm?  First, most collaborative care interventions for depression, pain, 
and anxiety have proven superior to usual care.28,37,38,41,42,51,52  Second, in these trials, the pre-post effect 
size within the usual care arm has been modest. Indeed, clinical trials are ethically justified only when there 
is therapeutic equipoise regarding the treatments being studied.53 Since patients assigned to the usual care 
arm in the multiple trials cited above have consistently experienced poor outcomes that are demonstrably 
inferior to patients assigned to systems-based interventions, the use of a usual care arm would be difficult to 
defend. Third, if usual care were added as a third arm to the trial, it would not only require a 50% increase in 
sample size but also mean that two-thirds of patients enrolled would be randomized to either a no-treatment 
(usual care) or low-resource (ASM) arm. Fourth, ASM is a relatively low-resource enhancement of usual 
care; our principal question is whether the more resource-intensive CSM strategy of enhancing usual care is 
superior to the primarily automated ASM approach. 
 
3) Why require PAD symptom comorbidity? Studies focusing on single conditions are numerous, with 
more than 40 trials for depression37,38, a few for pain41,42, and one large trial for anxiety.28 It is increasingly 
clear that enhanced primary care for a single condition is superior to usual care. However, since PAD 
comorbidity is more common than a single condition20, treating one condition to the exclusion of the others 
or merely adjusting for them as effect modifiers is neither patient-centered, practical, nor optimally effective. 
      4)  Why include other anxiety disorders besides PTSD? Several points noted in section B3 bear 
reiterating.  First, 4 anxiety disorders – PTSD, generalized anxiety disorder, panic disorder, and social 
anxiety disorder – are all prevalent, undertreated, and disabling in primary care patients.18 Moreover, a third 

Page 10 of 56 
 
Study #1212010163 
 
to half of primary care patients with an anxiety disorder have 2 or more anxiety disorders.18,19 Second, 
anxiety disorders other than PTSD are likewise prevalent and undertreated in Veterans.28,29  Third, the two 
trials for anxiety disorders in primary care patients showed that integrated treatment was effective 
regardless of the type of anxiety disorder.19,30,31 Additionally, our proposed approach using optimized 
antidepressant therapy and/or psychologist referral based upon patient preferences and clinical response is 
consistent with VA/DoD guidelines for PTSD (VA/DoD Clinical Practice Guideline: Management of Post-
Traumatic Stress, 2010, www.healthquality.va.gov) and likewise conforms evidence-based treatment of 
anxiety disorders other than PTSD.30 
 
5)  Why do we expect comprehensive symptom management (CSM) to be superior to ASM?  First, CSM 
will optimize medication (analgesic and antidepressant) management. Second, the nurse care manager will 
reinforce self-management strategies, enhance adherence, and overcome patient resistance to mental 
health referrals. Third, the nurse-physician team will enhance ASM by providing telecare management for 
more severe, non-responding, or multiple symptoms. Finally, CSM is a collaborative team-based approach 
that coordinates and triangulates the 3 key partners in PAD symptom management: the specialty team, 
primary care provider/PACT, and the embedded psychologist. 
 
D3. Enrollment and Randomization 
D3a. Eligibility   
 
 Individuals will be eligible if they have pain plus comorbid anxiety and/or depression.  
 
 Pain must:  (a) be musculoskeletal, either localized (in the arms, legs, back, or neck) or widespread 
(fibromyalgia); (b) have persisted 3 months or longer despite a trial of at least one analgesic medication; (c) 
at least moderate in severity, defined as a Brief Pain Inventory average severity score of 5 or greater.54  
Persistence for 3 months is a common definition of chronic pain.55  Musculoskeletal pain accounts for two-
thirds of pain-related outpatient visits, leading to nearly 70 million outpatient visits in the U.S. each year.2  
Likewise, musculoskeletal conditions account for more than 80% of pain complaints in Veterans.8 
 
 Depression must be of at least moderate severity, defined as a PHQ-8 score of 10 or greater with 
either depressed mood and/or anhedonia being endorsed.56,57  In previous studies,  more than 90% of 
patients fulfilling this PHQ-8 criterion had major depression and/or dysthymia, and the remaining patients 
had clinically significant depression with substantial functional impairment.56,57   
 
 Anxiety must be of at least moderate severity, defined as a GAD-7 score of 10 or greater.  In previous 
studies, the majority of patients fulfilling this GAD-7 criterion had one or more common DSM-IV anxiety 
disorders (generalized anxiety, panic, social anxiety, and/or posttraumatic stress disorder), and the 
remaining patients had clinically significant anxiety with substantial functional impairment.16,57  While the 
area under the curve is highest for generalized anxiety disorder (.91), it is also good for panic disorder (.85), 
social anxiety disorder (.83), and PTSD (.83). The positive likelihood ratio for a GAD-7 cutpoint of ≥ 10 for 
these 4 disorders is 5.1, 2.9, 3.6, and 3.5, respectively. 
 
 Composite Mood score must be of at least moderate severity, defined as PHQ-8 + GAD-7 scores of 
12 or greater. Because our primary outcome measure is a composite of pain-anxiety-depression scores, 
individuals with a score of 12 or greater will have sufficient anxiety and depressive symptoms to have 
mixed-anxiety depression which, combined with elevated pain, should still respond to our intervention.  
 
 Excluded will be individuals who: (a) have moderately severe cognitive impairment as defined by a 
validated 6-item cognitive screener58; (b) have schizophrenia, bipolar disorder or other psychosis; (c) are 
suffering from a severe or complex mental illness or are at high risk of suicide as their condition is 
unsuitable for a predominantly telecare intervention;(d) are pregnant; (e) have an anticipated life expectancy 
of less than 12 months. Patients who are on antidepressants but still meet the PHQ-8 and/or GAD-7 entry 
criterion for clinical depression and/or anxiety are still eligible since our aim is to work collaboratively with 
their treating clinician to optimize outcomes.  Such patients can be considered inadequate responders to 
their current antidepressant and could have dose titrations or be switched to a different antidepressant, 
presuming their primary physician (or mental health provider if prescribed by the latter) agrees. This 
approach has been used in our previous trials. 42,52,59,60 
D3b. Identifying Potential Subjects 

Page 11 of 56 
 
Study #1212010163 
 
Primary care physicians (PCPs) will be informed of the study in detail and provide written consent to 
approach their patients for participation in the trial.  Only patients from consenting PCPs will be enrolled. In 
our previous trials, over 90% of PCPs have agreed to participate. Electronic medical records will be used to 
create a master list of individuals who, within the preceding 36 months, have received an ICD diagnosis of a 
depressive disorder, an anxiety disorder, or a musculoskeletal pain condition. We have identified the 
relevant ICD codes in our previous studies. This patient list will be updated quarterly during the enrollment 
period. Individuals on this list will be mailed a letter describing the study and contacted within 2 weeks by 
telephone to determine potential interest in the study and, if willing, complete an eligibility interview.  A 
similar procedure has been used to enroll Veterans in our SCAMP42, INCPAD52, and SCOPE trials. 
D3c. Randomization 
 
 Eligible patients will be scheduled for an in-person research visit where, after providing informed 
consent/HIPPA authorization and completing the baseline assessment, study participants will be 
randomized to one of the two treatment groups.  Randomization will be computer-generated using 
randomly-varying block sizes of 4 or 8 (to assure allocation concealment). Similar randomization has been 
carried out successfully in our recent trials of pain and depression.42,52  Randomization will occur at the level 
of the patient rather than at the physician level for several reasons. First, physicians differ considerably in 
knowledge, attitudes, and prescribing practices regarding depression, anxiety and pain management, which 
in turn can serve as important confounders in intervention effectiveness. While multiple physicians will 
participate, the number will not be large enough to assure that a cluster design (i.e., randomization at the 
physician level) will result in a balanced distribution of physician-related treatment confounders among 
study arms. For this reason, patient-level randomization has been the most common design in collaborative 
care trials.37,38  Second, numerous trials by us42,52,61 and others37,38 have shown that for systems 
interventions like CSM, contamination of usual care patients is small. A principal ingredient for the 
effectiveness of collaborative care and other systems-based interventions for depression, pain, and anxiety 
is the regular monitoring of clinical response and adherence and, as a consequence, adjustments of 
treatment to optimize outcomes. This degree of regular monitoring and treatment adjustment cannot be 
readily replicated in usual primary care practice, thus minimizing contamination effects. Third, any spillover 
to control subjects that does occur will make our estimate of the intervention effect a conservative one.   
D3d. Feasibility   
 
 A search of the Roudebush VAMC CPRS found there were more than 7000 patients with the 
musculoskeletal pain conditions who had a primary care visit in the past 12 months. In prior studies, 40%-
50% of patients with chronic musculoskeletal pain have had clinically significant depression and/or anxiety. 
In our VA trials, we have successfully enrolled more than 50% of eligible subjects.   
D3e. Inclusion of Women and Minorities 
 
 Demographic data on 641 veterans we have enrolled in 3 pain trials at our Roudebush VAMC is 
summarized in Table 3 below. As shown, the proportion of women and black patients enrolled in our pain 
trials has increased over the past 7 years. Thus, we expect to enroll 15-20% women and 15-20% 
Black/African-American patients, while about 5% will be Hispanic. 
Table 3.  Sex and race distribution in recent primary care pain trials in Roudebush VAMC 
Trial 
N 
Enrollment Period 
Women 
Race 
White 
Black 
Other 
SCAMP 
200 
2005-2007 
5.5% 
81.0% 
16.0% 
3.0% 
ESCAPE 
241 
2008-2010 
11.6% 
76.7% 
12.9% 
10.4% 
SCOPE 
200 
2010-2012 
17.0% 
78.5% 
17.5% 
4.0% 
 
D4. Data Collection Protocol 
 
 Table 4 on the next page outlines the study measures and assessment schedule used to address our 
Specific Aims and detailed under Analysis. The primary outcome measure will be based upon a composite 
pain-anxiety-depression score (see D4a below). We will also measure clinical, quality of life and health care 

Page 12 of 56 
 
Study #1212010163 
 
use variables. The number of items assessed is similar to our prior trials, and has been well-tolerated with 
minimal missing data.42,52,62  
Table 4. CAMMPS Outcome Assessment:  Measures and Schedule of Administration 
Domain 
Text # 
Measure 
# 
Items 
 
  Schedule 
0 
mo 
1 
mo 
3 
Mo 
6 
mo 
12 
mo 
Sociodemographics 
1 
age, race, sex, education, 
marital, job status, income 
7 
 
X 
 
 
 
 
Medical comorbidity 
2 
Checklist of 9 conditions 
9 
 
X 
 
 
 
 
Primary PAD composite * 
 
 
 
 
 
 
 
 
 
• Pain severity/interference 
3 
Brief Pain Inventory 
11 
 
X 
X 
X 
X 
X 
• Depression severity 
4 
PHQ-9 depression scale 
9 
 
X 
X 
X 
X 
X 
• Anxiety severity 
5 
GAD-7 anxiety scale 
7 
 
X 
X 
X 
X 
X 
Secondary PAD composite * 
D4a 
PROMIS PAD measures 
24 
 
X 
 
X 
X 
X 
PTSD severity 
6 
PTSD Checklist 
17 
 
X 
 
X 
 
X 
Depression remission tool 
7 
REMIT depression scale 
5 
 
 
 
 
 
 
Clinical response 
8 
Global Rating of Change 
2 
 
 
X 
X 
X 
X 
Somatization 
9 
PHQ-somatic (12 items) 
12 
 
X 
 
 
 
X 
Functional status and health-
related quality of life 
10 
SF-20 (SF-12 + 8 SF items) 
20 
 
X 
 
X 
 
X 
11 
Sheehan Disability Scale 
3 
 
X 
 
X 
X 
X 
12 
Disability days 
2 
 
X 
 
X 
X 
X 
Pain catastrophizing 
13 
Pain catastrophizing scale 
6 
 
X 
 
 
X 
X 
Fatigue and insomnia 
14 
PROMIS fatigue & sleep 
8 
 
X 
 
X 
 
X 
Anxiety screeners --other 
15 
MINI-SPIN & OCD item 
4 
 
X 
 
 
 
 
Anxiety severity – other  
16 
SCL anxiety measure 
10 
 
X 
 
X 
 
X 
Somatization – other  
17 
SSS-8 
8 
 
X 
 
 
 
X 
Substance use 
18 
alcohol, tobacco, illicit drugs 
13 
 
X 
 
 
 
 
Health care & medication use 
19 
CPRS 
n/a 
 
 
 
 
 
X 
Treatment for PAD * 
20 
PAD-specific treatments 
15 
 
X 
 
 
X 
X 
Treatment satisfaction 
21 
PAD-specific satisfaction 
4 
 
 
 
X 
 
X 
Intervention satisfaction 
22 
Automated monitoring and 
care management 
9 
 
 
 
 
 
X 
* PAD = pain, anxiety, depression 
 
† SCID has screening questions and skip-outs; thus, number of items asked has wide range. 
D4a. Primary outcome measure 
 
 The primary outcome measure will be the composite z-score of the main pain, anxiety and depression 
scales in this trial: the BPI, GAD-7, and PHQ-9, respectively. These 3 symptom scales total 27 items: 11 
items for pain, 9 for depression, and 7 for anxiety. . Each of these measures has proven sensitive to change 
in treatment trials. The composite z-score reflects the 3 symptoms being targeted for treatment in CAMMPS 
and provides a standardized primary outcome that could not be derived from 3 disparate symptom 
measures. Calculation of this composite z-score is described in the Analysis section (D9a).  
 
As an important secondary outcome, a composite pain-anxiety-depression score from the PROMIS 
measures will be calculated. The PROMIS scales include 8 items each for depression and anxiety, and 9 for 
pain. Conversion tables allow direct conversion of simple summed raw scores from PROMIS symptom 
scales into T-score values. T-Score distributions are standardized such that a score of 50 represents the 
average (mean) for the US general population, and the standard deviation around that mean is 10 points. A 
high score represents greater symptom severity. For example, a person who has a T-score of 60 is one 

Page 13 of 56 
 
Study #1212010163 
 
standard deviation worse than the general population for the symptom being measured. The composite 
PROMIS score will be the mean of the 3 symptom scores; thus, a patient whose PROMIS pain, anxiety and 
depression scores are 66, 58, and 53 would have a composite score of 59. Although the PROMIS 
measures have had extensive validation in cross-sectional studies63,64, the evidence of their responsiveness 
(sensitivity to change) in clinical trials or other longitudinal studies is much less than the responsiveness 
data for the BPI, PHQ-9 and GAD-7. In fact, recent data from our SCOPE trial indicate the PROMIS pain 
scale may be less responsive than the BPI.  
 
D4b. Other measures 
D4b. Other measures 
 
  (1) Sociodemographics include age, sex, race, education, marital and job status, and income 
 
  (2) Medical comorbidity will be a checklist of 9 common medical disorders that we have shown 
predicts hospitalization and mortality.65  
 
  (3) The Brief Pain Inventory (BPI) rates the intensity of pain on 4 items (current, worst, least, and 
average pain in past week), and the interference in 7 areas (mood, physical activity, work, social activity, 
relations with others, sleep, enjoyment of life).66  
 
  (4) The PHQ-9 has been used in hundreds of research studies as a depression severity and outcome 
measure and, now translated into more than 80 languages, is among the most widely used depression 
measures in clinical practice.56,57 
 
  (5) The GAD-7 is an anxiety severity measure, validated in several thousand primary care patients 
and increasingly used in clinical research and practice.57,67  It is also a good first-line measure for estimating 
the probability of 4 common anxiety disorders in primary care – generalized anxiety disorder, panic disorder, 
post-traumatic stress disorder, and social anxiety disorder.16  
 
Of note, the BPI, PHQ-9 and GAD-7 have all proven sensitive to change as outcome measures in 
multiple studies.57,66  
 
  (6) The PTSD Checklist (PCL) is a 17-item validated measure68 that will be used to assess the 
presence and severity of posttraumatic stress disorder, a particularly important disorder in military Veterans 
and one that is commonly comorbid with chronic pain.  
 
  (7) The REMIT is a 5-item scale that is useful in predicting depression remission.69 
 
  (8) The Global Rating of Change assesses overall clinical response of pain and mood, consistent 
with the IMMPACT recommendations for a 7-item patient global change scale.70 This scale has been 
sensitive to change in our previous trials.42,52  
 
  (9) The PHQ-12 assesses the number and severity of common somatic symptoms and is adapted 
from the PHQ-15 commonly-used for assessing somatic symptom burden and somatization.57,71  
 
(10) The SF-20 will be used to assess generic health-related quality of life, which includes the SF-12 
(providing both Physical Component Summary and Mental Component Summary scores)72  
8 items from the SF-36 to provide the full mental health, social, bodily pain, and vitality scales. 
 
(11) The Sheehan Disability Scale (SDS) is a 3-item scale assessing how much an individual’s health 
condition has interfered with work, family life, and social life over the past month.73 It has proved responsive 
to treatment in studies of depression and pain.52  
 
(12) Disability days will be assessed with a 2-item measure that asks about the number of days in the 
past 4 weeks that the individual had to reduce activities by 50% or more for health-related reasons as well 
as the percent of effectiveness at work.54,74  
 
(13) Pain catastrophizing will be assessed with 6-item catastrophizing scale from the Coping 
Strategies Questionnaire, which has been shown to have strong reliability and validity.77,78 
 
 
(14) The PROMIS fatigue and insomnia 4-item scales will be used to assess these 2 symptoms that 
are frequently comorbid with pain, depression, and anxiety.63 
 
Because the relationship of anxiety with pain has been less well-studied than pain-depression 
comorbidity, additional scales will be included to increase our understanding of this relationship as well as to 
determine the operating characteristics and responsiveness of several anxiety scales. 
 
(15) Two anxiety screeners – the 3-item scale for social anxiety disorder and 1 item for obsessive-
compulsive disorder.79 
 
(16) The SCL-12 anxiety scale is a commonly-used 10-item measure of anxiety severity.80 

Page 14 of 56 
 
Study #1212010163 
 
 
(17)  The Somatic Symptom Scale (SSS-8) will be a secondary measure of somatization (Gierk et al, 
Arch Intern Med, in press). 
(18) Substance use with be assessed with the AUDIT-C for alcohol83 as well 
as questions about the use of tobacco, illicit drugs, and family history.79  
 
(19) Health care use and medication use (outpatient visits, emergency department visits, 
hospitalizations, analgesics, psychotropics) will be assessed by electronic medical record review.42,52  
 
(20) Treatments (i.e., medications and nonpharmacological treatments specific to pain and mental 
health) will be assessed using interview coupled with electronic medical review.42,52  
 
(21) Treatment satisfaction overall will be assessed with a 4-item scale used in previous trials.54  
 
(22) Satisfaction with the automated and nurse care manager components of the interventions will be 
assessed with an 9-item survey adapted from our INCPAD trial.43  
 
Finally, medications at baseline will be assessed using patient interview coupled with electronic 
medical record review, as conducted in our previous studies.42,52  
D4c. Distinction between Primary Research Outcome vs. Clinical Monitoring Symptom Measures 
 
While the composite z-score of the BPI, PHQ-9 and GAD-7 will be our primary outcome measure in 
CAMMPS, the PEG (a 3-item validated version of the Brief Pain Inventory)66, PHQ-8, and GAD-7, or a 
composite score from both the PHQ-8 and GAD-7 will be used to determine trial eligibility as well as to 
clinically monitor the intervention. It is advantageous for the nurse care manager to use tools to monitor and 
adjust treatment that are distinct from the outcome measures in order to remain blinded to the PROMIS 
scores as well as to avoid excessive subject “training” in the primary outcome measure. The PEG, PHQ-8 
and GAD-7 are used for study eligibility because these instruments are increasingly used in both practice as 
well as clinical research and cutpoints for clinically significant pain, anxiety, and depression are well-
established.57,66 For example, the majority of individuals who have a PHQ-8 or GAD-7 score ≥ 10 meet 
DSM-IV criteria for a depressive or anxiety disorder, respectively, while the remainder have depression or 
anxiety with at least moderately severe impairment across multiple domains of functional status and quality 
of life.57 Likewise, the PEG cutpoints and changes used in CAMMPS have been shown to represent 
clinically significant pain and pain response, respectively.66,84  
D4d. Participant burden and rationale for assessment intervals.   
 
 Our outcome assessment battery is similar in length to 5 previous trials where participant response 
and retention has been uniformly high.42,52,61,62,85  We have used the 4 follow-up assessment intervals in two 
prior 12-month symptom management trials42,52 for the following reasons. By month 1, effective treatments 
should show at least a partial response and, in fact, as much as 75% of the improvement that will ultimately 
occur does so by month 1.86  The first 3 months are typically the most active phase of symptom 
management, making month 3 an important time to assess for symptom remission or additional 
improvement. The next several months are the highest risk period for symptom relapse, thus justifying a 
month 6 assessment to determine maintenance of effect, decay or, for self-management strategies, even 
further benefits. Finally, our primary outcome point is 12 months.  
 
D5. Overview of Interventions 
 
 As highlighted in the Conceptual Model (Figure 3) previously and summarized in Table 5 below, there 
are 5 key components that constitute the interventions in CAMMPS:  two are the same in ASM and CSM, 
while three are unique to CSM. This choice of treatment arms allows for: 1) a low-resource principally 
automated arm to serve as an active comparator group; 2) testing the added value of the 3 more resource-
intense clinician-dependent components – nurse contacts, optimizing medications, and facilitating mental 
health visits; 3) conducting secondary analyses (see section D9c, Aim 4) to explore the dose-response 
relationship between each of the 5 components and improvement in the primary outcome. 
Table 5.  Comparison of Components in the Two Intervention Arms of CAMMPS Trial 
# 
Intervention component 
ASM 
CSM 
1 
Automated contacts (# and total minutes) 
 
 

Page 15 of 56 
 
Study #1212010163 
 
2 
Prompted pain and mood self-management strategies 
 
 
3 
Nurse contacts (# and total minutes) 
 
 
4 
Optimized medications (analgesic and psychotropic starts 
and dose changes) 
 
 
5 
Facilitated mental health care 
 
 
 
D6. Intervention Arm 1:  Assisted Symptom Management (ASM) 
 
 There will be 2 principal components to assisted symptom management (ASM):  automated symptom 
monitoring and prompted pain and mood self-management.  Automated symptom monitoring was effectively 
conducted in our INCPAD trial of telecare management of pain and depression43,52 as well as in our current 
SCOPE trial of pain management in Veterans.  The pain and mood self-management component was 
developed for our SCOPE trial, having evolved from previous versions in our SCAMP and ESCAPE trials. 
D6a. Component 1 – Automated Symptom Monitoring.   
 
 Similar to our INCPAD trial52 and our current SCOPE trial79, study participants will complete regular 
symptom surveys either by interactive voice recorded (IVR) telephone calls or Internet (based upon patient 
preference); both IVR and internet approaches will use push-technology (automated calls or e-mail 
reminders) to assure equal patient outreach. The schedule will be weekly for the first month, twice a month 
for months 2-6, and monthly for months 7-12. This “tapering dose” of automated monitoring corresponds: a) 
clinically to the acute phase of initial treatment and dose adjustment or adding/switching medications, 
followed by less frequent monitoring during the relapse prevention phase; and b) operationally to a similar 
approach used in our recent INCPAD and SCOPE trials.  Since all patients will have threshold levels of at 
least 2 PAD symptoms upon study enrollment, more up-front intensive monitoring with initiation and 
adjustment of symptom therapy followed by a tapering schedule is both rational and evidence-based.42,52 
The core survey will include 15 items: 10 selected pain and mood items from the PEG, GAD-7 and PHQ-9 
to assess severity of the PAD symptoms plus 5 items to prompt use of the pain and mood self-management 
units.  
D6b. Component 2 – Prompted Pain and Mood Self-Management.   
 
 A Pain and Mood Self-Management Program will include approximately 12 hours of web-based 
instruction divided into 9 units (coping with pain; pain medications; communicating with providers; 
depression; anxiety; sleep; anger management; moving forward; and problem-solving). These topics are 
partly derived from the nurse-administered self-management program in our SCAMP and ESCAPE trials 
and build upon several VA and non-VA website interactive self-management programs.. Subjects will be 
instructed in how to use the program by the nurse (CSM group) or project coordinator (ASM group). The 
web-based delivery of the program along with automated reminders to proceed through the 9 units 
increases the likelihood of delivery to the patient.  Also, the number of units a patient completes will serve 
as a measure of “dose”, which in turn can be examined as an explanatory variable of intervention efficacy. 
 
D7. Intervention Arm 2:  Comprehensive Symptom Management (CSM) 
D7a. Structured Protocol Overview. 
 
 This arm couples nurse care management with ASM, thus testing “combined” therapy vs. 
“monotherapy” (ASM only).  As illustrated in our conceptual model (Figure 3), the nurse provides several 
active components beyond ASM, including optimized medication management (analgesics and 
psychotropics) in conjunction with the supervising physician, facilitated mental health care, and enhanced 
coordination of care with the other key clinical partners – primary care physicians/PACTs and embedded 
psychologists.  CSM is intentionally tailored to each patient’s specific PAD symptoms, treatment 
preferences, and response to therapy; thus, frequency of nurse contacts as well as the specific content of 
nurse calls will necessarily vary with our “treat to target” approach.  However, similar to our INCPAD 
trial43,52,74, we will systematically document in detail the frequency, duration, and content of all nursing calls.  
The time spent on the call reinforcing self-management and discussing medication management will be 

Page 16 of 56 
 
Study #1212010163 
 
individually documented in order to explicitly capture the attention devoted to each component. This will 
allow us to secondarily examine the independent effect of the intensity (“dose”) and content of nurse 
contacts as a mediator of intervention outcomes. 
 
 In our previous and current pain effectiveness trials, virtually all patients desire some optimization of 
their pain treatment either through starting, adjusting, or switching analgesics or learning pain self-
management strategies. Regarding depression or anxiety, however, patients prefer different approaches. 
For those desiring active treatment, some patients prefer pharmacotherapy (typically antidepressants) while 
others opt for psychotherapy (talking with a psychologist, psychiatrist or other mental health professional). 
Since both types of treatment are effective, eliciting and honoring the patient’s choice is clinically 
appropriate. Still other patients are not interested in specific treatment for depression or anxiety initially, but 
may agree to treatment later once they are followed by the study team and regularly monitored for their 
symptoms. Thus, patients enrolled in the study will be encouraged to receive active treatment for their 
depression or anxiety, both initially and during follow-up contacts. However, as this is a real-world clinical 
trial, accepting active treatment will be optional for each study subject and not a requirement for enrollment. 
Notably, any patient with severe depression who is actively suicidal (a rare occurrence in our trials) with be 
managed by our suicidality protocol (section D7h). 
 
 The nurse will have scheduled telephone contacts with the patient at baseline, 1, 4, and 12 weeks, as 
well as symptom-triggered contacts based upon automated monitoring trend reports (see D7b below). The 
nurse will monitor trend reports weekly, respond to automated monitoring clinical alerts and patient calls 
daily, and serve as the coordinating linchpin between patient, supervising physician symptom specialist, 
primary care physician/PACT, and psychologist. A timely and innovative feature of this trial is the 
collaboration with not only the PCP but the entire primary care team, specifically the PACT (Patient-Aligned 
Care Team) and the embedded psychologist. Most prior collaborative care trials have focused on the nurse 
care manager triangulating treatment adjustments with the patient, PCP, and supervising physician 
specialist.37,38,87  PACTs in our VA facility have instituted daily “huddles” in which each PCP, his/her team 
nurse and other relevant PACT team members review key patient issues for the day.  Our nurse care 
manager will work with the most appropriate PACT team member for implementing and coordinating 
particular treatment recommendations. Also, the nurse care manager will coordinate care of depression and 
anxiety with the embedded psychologist, providing feedback on depression and anxiety scores to adjust 
therapy to optimize outcomes.  In essence, our CSM model is designed to optimize PAD symptom 
outcomes by integrating and coordinating management across all primary care team members involved in 
the veteran’s care. This integration of our intervention into our clinics and PACTs is strongly supported by 
our primary care leadership. 
 
The nurse will have weekly case management sessions with the supervising physician symptom 
specialist to review all new patients randomized to the CSM group to decide on a treatment plan, as well as 
enrolled patients not responding to therapy. Of note, the PAD symptoms are seldom urgent or life-
threatening but instead require treatment initiation, active monitoring, and treatment adjustments, all of 
which will typically occur in the CSM arm in a much more expedited fashion than in usual primary care. 
However, for any symptoms which are more urgent, the nurse care manager will have cell-phone/pager 
access to the supervising study physician at all times to address the symptoms in a timely fashion. This 
model of weekly staffing plus on-call physician availability has performed safely and effectively in our prior 
care management trials.42,52,59-61 
 
D7b. Assisted Symptom Management.   
 
 All patients randomized to the CSM group will receive ASM as described in Section D6 above.  
However, ASM will be enhanced in two ways for patients in the CSM group in order to take advantage of 
the “technology-human” partnership provided by the centralized nurse care manager-physician specialist 
symptom management team.  First, the 15-item ASMsurvey described above in D6a will be augmented by 5 
additional items used in our INCPAD and SCOPE trials: global change (i.e., degree of improvement or 
worsening), medication adherence, side effects, desire for treatment changes, and request for a nurse care 
manager call.43,52,74  Second, ASM responses will be tabulated in a trend report on a secure website 
accessible to the care management team. Trend reports will be reviewed weekly by the nurse care 
manager. Also, e-mail alerts will be sent to the nurse to trigger patient calls for side effects, a patient 
request for a treatment change or a nurse call, or missed ASM reports.  

Page 17 of 56 
 
Study #1212010163 
 
D7c. Analgesic Management for Pain. 
 
 The nurse care manager will obtain a detailed history of current and past pain medication use. The 
nurse care manager will then follow the pain medication algorithm developed for this study (Figure 5).  The 
pain medication algorithm is derived from our recent systematic review of the literature on pharmacotherapy 
for chronic pain.88  When available, VA guideline recommendations were prioritized over those developed 
for use in non-VA populations. Notably, this algorithm has worked well thus far in our SCOPE trial for the 90 
patients (72% of target sample) randomized to the optimized analgesic management arm.  
 
 This pain medication algorithm is a step-wise series of brief individual medication trials, and includes 
tailored steps for different types of chronic pain conditions. Multiple drug classes are included in the 
algorithm. Data from prior trials suggest that the majority of patients will already be using analgesics at 
baseline, including opioids in 30-40% of cases. However, the eligibility criteria for the trial require that, 
despite this, their pain control will be suboptimal. Thus, baseline pain medications may be discontinued, 
adjusted to achieve an adequate therapeutic trial, or continued with the addition of adjunctive drugs, 
depending on the patient’s history of medication use (e.g., dosing, scheduling, and adherence), therapeutic 
response, adverse effects, and preferences. 
 
D7c1   Rationale for the Analgesic Algorithm 
 
 The rationale and justification for the particular drugs, dosing, and sequencing used in CAMMPS is 
based upon several factors.  First, every recommended medication in the algorithm has demonstrated 
efficacy for the indications listed from at least 2 randomized clinical trials (RCTs) or, in many cases, from 
meta-analyses or systematic reviews of multiple RCTs.  This evidence has been summarized in our 
recently-published systematic review.88  Second, though many medications not listed in the algorithm have 
been used for treatment of pain, any treatment that does not meet our stringent evidence-based criterion is 
excluded from the algorithm. Third, for some conditions (e.g., neuropathic pain), treatment guidelines have 
been issued by more than one organization. In these cases, we determined areas of consensus among the 
several guidelines so that our algorithm reflects either the unanimous or “majority view” among evidence-
based guidelines. Fourth, since all medications in the guidelines have established efficacy in placebo-
controlled trials, fewer head-to-head comparisons of analgesics are available. Thus, sequencing is based 
upon other issues, such as cost, safety, and VA formulary availability.  For example, two classes of 
antidepressants (TCAs and SNRIs) have strong evidence of efficacy for several types of pain disorders.  
However, TCAs are less expensive and therefore listed first in the algorithm (unless contraindicated in 
certain groups such as the elderly or those with cardiovascular disease). Fifth, though evidence about the 
sequencing of analgesics in the algorithm is limited, this is not unlike guidelines we have for many chronic 
medical disorders. For example, the sequencing of different classes of hypoglycemic drugs in diabetes89, 
antihypertensive agents in hypertension90, and antidepressants in mood disorders91 is informed by issues of 
cost, convenience, side effect profiles, and comorbid conditions rather than superior efficacy of one 
treatment. Sixth, regular monitoring and adjustment of therapy is as important in achieving optimal 
outcomes as the specific treatment chosen, presuming a menu of equally effective treatments is available.91   
Figure 5.  Analgesic Algorithm* 
Step 1:   
Simple analgesics 
1. Acetaminophen 1000 mg q 6h (max 2000 mg if cirrhosis or ≥ 3 alcoholic drinks/day) 
2. NSAIDs: try at least 2; 
a. 1st line: naproxen 500 mg q 12h or 500 q am plus 250 bid (max 1000) 
b. 2nd line: (i) salsalate 1000 mg q 8h or 1500 q 12h (max 3000); (ii) etodolac 300-400 mg q 8h or 
500 q 12 h (max 1200); (iii) ibuprofen 600 mg q 6h (max 2400); (iv) meloxicam 7½-15 mg qd;   
(v) diclofenac 50 mg q 8h (max 150) 
3. Consider topical analgesic if neuropathic pain or localized pain (e.g. knee osteoarthritis).  For example,  
       capsaicin cream applied 4 times a day for at least 3-4 weeks 
Step 2:   
Does patient have: (1) neuropathic pain, (2) fibromyalgia/chronic widespread pain, or   (3) back pain? 
TCAs: try at least two 

Page 18 of 56 
 
Study #1212010163 
 
1. Amitriptyline, start at 10-25, titrate to 100 mg (max 50 mg if taking an SSRI/SNRI) 
2. Nortriptyline, start at 10-25, titrate to 100 mg (max 50 mg if taking an SSRI/SNRI) 
Step 3 
Tramadol 
  
1. Start 25 mg BID or TID and titrate to 100 mg QID (max 300 mg if age > 75; max 100 mg BID if CrCl < 30,  
       50 mg BID if CrCl <10; max 50 mg BID if cirrhosis) 
2. Use concurrent acetaminophen, 500-1000 mg dosed with tramadol TID-QID 
Step 4 
• 
Neuropathic pain 
1. Gabapentin, titrate up to 900-1200 mg tid 
2. Duloxetine (60 mg qd) and/or Pregabalin (300-450 mg qd, divided into bid doses)  
3. Consider topical analgesic if neuropathic pain or localized pain (e.g. knee osteoarthritis).  For example,  
       capsaicin cream applied 4 times a day for at least 3-4 weeks 
• 
Fibromyalgia/chronic widespread pain 
1. Cyclobenzaprine, titrate to 10 mg TID 
2. Pregabalin (300-450 mg qd, divided into BID doses) 
3. Duloxetine 60 mg qd or Milnacipran 100 mg qd. 
* Kroenke K, Krebs EE, Bair MJ.  Pharmacotherapy of chronic pain:  a synthesis of recommendations from  
  systematic reviews.  Gen Hosp Psychiatry 2009;31:206-219. 
 
 
D7c2   Opioid Management Strategy 
Although patients on chronic opioid therapy will be eligible to enroll, the study team will not start 
opioids or change opioid dosages during the trial without the primary care physician’s approval.  Instead, 
our opioid monitoring procedures will enhance the safety of patients already being prescribed opioids who 
will be monitored in accordance with the recently-updated 2010 VA/DoD Clinical Practice Guideline for the 
Management of Opioid Therapy for Chronic Pain (www.va.gov/pain_management).92 Indeed, our recent 
medical record review of Veterans receiving long-term opioids in primary care found infrequent use of 
guideline recommended opioid management practices; for example, opioid agreements, urine drug tests, 
assessment of alcohol or drug use, and assessment of medication adherence were all present in fewer than 
one in five records.93 Thus, our protocol will enhance the safety of opioids already being prescribed. The 
justification for this approach rather than a strategy which denies opioids to any patient is threefold: 
1) It is consistent with both VA and non-VA best-practice guidelines for treatment of chronic pain.  
Specifically, judicious use of opioids is recommended by the 2010 VA/DoD Clinical Practice Guideline for 
the Management of Opioid Therapy for Chronic Pain92 as well as the 2009 VHA Pain Management 
Directive.94 Additionally, guidelines from multiple organizations approve the use of opioids for selected 
patients who fail or do not tolerate nonopioid medications, including the American Pain Society, the 
American Academy of Pain Management, the American Geriatrics Society (AGS), and the 2011 Institute of 
Medicine report on “Relieving Pain in America.”95-97 Indeed, the AGS considers opioids as safe as or safer 
than NSAIDs in older patients with chronic pain. Thus, to exclude veterans from the trial who are already 
receiving opioids from their PCP would adversely affect generalizability of our trial results and furthermore 
deviate from VA and non-VA standard of care for chronic pain. 
2) Empirically, the selected use of opioids in our VA HSR&D funded trials of chronic pain (Table 2) has 
been IRB-approved and has not resulted in any serious adverse events.  This includes experience with 
nearly 500 veterans with chronic pain enrolled in our ESCAPE and SCOPE trials. These trials have had 
opioid use procedures in common with CAMMPS including the requirements for opioid pain care 
agreements, urine drug screens, regular monitoring, and close collaboration with the veteran’s primary care 
physician. Notably, most participants on opioids in these trials were receiving opioids from their PCP at the 
time of enrollment in the trial, and the small subset (< 10%) who were initiated on opioids during the trial 
typically required only low to moderate doses. 
 

Page 19 of 56 
 
Study #1212010163 
 
Procedures Regarding Opioid Use in CAMMPS 
• 
Opioids will not be initiated by the study team as part of the analgesic algorithm (Figure 5). 
• 
Patients already receiving opioids from their primary care physician (PCP) at the time of study 
enrollment will receive education about safe use of opioids by the study team, and be regularly 
monitored for side effects, other adverse events or aberrant drug behavior. 
• 
If pain persists despite proceeding through all 4 steps of the analgesic algorithm, the study team will 
discuss with the PCP/PACT whether a trial of opioids is warranted. An empiric trial may be considered if 
all of the following criteria are met: 
o Patient is not at high risk for opioid misuse as determined by an evidence-based classification 
algorithm we have used in our SCOPE trial (Appendix 1) 
o Patient agrees to an opioid pain care agreement, and regular monitoring for pain response, 
adverse events, and indicators of misuse 
o Opioid therapy will be considered as an empiric trial and will be discontinued in the event of 
inadequate pain response, adverse events, or opioid misuse 
• 
Patients receiving any opioids will be educated about adverse events and safety issues (including the 
use of lockboxes and other security measures to prevent access of others, especially children, to their 
opioid medications). 
D7d. Antidepressant Algorithm for Depression and Anxiety 
 
 Our antidepressant algorithm is informed by three recent trials:  the landmark multi-center STAR*D 
trial98, our SCAMP trial54, and the algorithm used for anxiety disorders in the CALM trial.99  STAR*D trial 
enrolled 4031 patients with major depression who were initiated on an SSRI, of whom 1439 had an 
inadequate response and proceeded to step 2.98  Of note, 41% were enrolled and treated in primary care 
clinics and these patients had outcomes equivalent to those enrolled and treated in psychiatry clinics.  Also 
of note, no specific antidepressant or combination proved superior, but instead the key to optimizing the 
proportion of patients achieving remission was regular depressive symptom monitoring coupled with dosage 
escalations or medication/other treatment changes. 
 
 Table 6 outlines our general prioritization of antidepressant selection and indications in special 
circumstances. An SSRI is the first choice because of wide usage, low cost, and well-established efficacy, 
safety and tolerability.62,98 Head-to-head trials and a systematic review suggest individual SSRI 
antidepressants are similar in efficacy and tolerability.62,100 Sertraline and citalopram are the first-line SSRIs 
in our algorithm because of their balance of efficacy and tolerability as demonstrated in a recent meta-
analysis of antidepressants101, their favorable profile in terms of drug-drug interactions, their cardiovascular 
safety in the SADHART and CREATE trials102,103, and their testing in both the STAR*D and SCAMP trials. In 
patients who are enrolled with anxiety as one of their PAD disorders, sertraline will be used first because of 
the greater clinical trial evidence and FDA indications across multiple anxiety disorders.  An SNRI will be 
used in those who fail an SSRI due to evidence from multiple clinical trials of SNRI efficacy in pain and 
anxiety disorders as well as depression.104,105 
 
 Should there be a suboptimal response to an SNRI or SSRI, steps 3 through 5 are summarized in 
Table 6 and adapted from STAR*D and SCAMP.  Four key points should be emphasized.  First, buproprion 
has neither strong evidence nor an FDA indication for treatment of anxiety; therefore, it will not be used in 
patients with anxiety only, and will only be used in combination with an SNRI or SSRI if patients have both 
depression and anxiety (step 6). Second, the sequence in Table 6 is also evidence-based for PTSD, with 
VA/DoD guidelines showing significant benefits for SSRIs and SNRIs and some benefit for mirtazapine 
(VA/DoD Clinical Practice Guideline: Management of Post-Traumatic Stress, Table I-6, p. 151, 2010, 
www.healthquality.va.gov). Third, combination therapy, when considered, will consist of an SSRI or SNRI 
coupled with one of 3 drugs: buproprion, mirtazapine, or buspirone (i.e., combinations used in STAR*D). 
Fourth, the CAMMPS algorithm provides a sequence of antidepressant selection that is both rational but at 
the same time flexible enough to allow appropriate tailoring based upon patient history (i.e., experience with 
prior antidepressants in terms of response, intolerance, etc.), medical comorbidity (e.g., demonstrated 
safety of sertraline and citalopram in patients with cardiovascular disease), psychiatric comorbidity (i.e., 
anxiety), and secondary drug effects that may lead to either preferential selection or avoidance of a 
particular drug (e.g., the sedation that may occur with mirtazapine may be beneficial in the depressed 

Page 20 of 56 
 
Study #1212010163 
 
patient with insomnia while the risk for weight gain may be undesirable in obese or diabetic patients).  See 
Appendix 2 for further details on the medication algorithms for depression and anxiety 
 
 While Table 6 provides a rational sequence of drug selection, we are not testing any particular 
antidepressant but, instead, optimal medication management that is both effective and tolerated in an 
individual patient.  Previous research has shown that fewer than half of patients started on a given 
antidepressant will achieve remission with the first drug.62,106  This was verified in our SCAMP trial where, of 
the 100 intervention subjects whose antidepressant status was known at 12 months, only 41% had 
remained on the antidepressant to which they were initially assigned, 43% had switched to a different 
antidepressant (n = 38) or combination pharmacotherapy (n = 5), and 16% were on no antidepressant.42  
Thus, our pragmatic, patient-specific approach approximates real-world in vivo depression management 
rather than an inflexible in vitro testing of a single drug.  At the same time, our algorithm provides a 
structured approach for the care manager, consistent with the STAR*D107, SCAMP54 and CALM99 
effectiveness trials. 
 
 For patients already on an antidepressant upon enrollment, adjustments or medication changes will be 
recommended if, despite antidepressant therapy, they remain clinically depressed and/or anxious.  This is a 
similar approach used in previous effectiveness trials by us and others which have shown that patients in 
primary care are frequently treated with antidepressants that are either inadequately dosed or ineffective for 
them. Subjects will be referred to mental health if they fail to achieve an adequate response after trials of 2 
different antidepressants, report suicidal ideation, or if they request a referral. 
Table 6.  Antidepressant Selection and Dosing Details for CAMMPS † 
Priority  
Indications 
Class 
Drug 
Dose (in mg) 
 
 
 
 
Initial 
Increases 
1 
1st-line (unless anxiety) including CV disease 
SSRI 
Citalopram 
20 
30, 40 
1 
If anxiety or cardiovascular (CV) disease 
SSRI 
Sertraline 
50 
100, 150 
2 
SSRI failure; refractory pain 
SNRI 
Venlafaxine 
75 
150, 225 
2 
SSRI failure, refractory pain 
SNRI 
Duloxetine 
30 
60 
3 
SSRI/SNRI  failure; weight gain; sexual side 
effects 
Other 
Bupropion 
200 
300, 400 
4 
SSRI/SNRI failure; insomnia 
Other 
Mirtazepine 
15 
30, 45 
5 
SSRI failure; refractory pain 
TCA 
Nortriptyline 
25 
50, 75 
 6¶ 
Partial response to antidep. Monotherapy 
 
Combination ¶ 
 
 
† Adapted from STAR*D, SCAMP and CALM trials.  Further details are provided in Appendix 2. 
¶ Acceptable combinations are those used in STAR*D, except lithium or thyroxine will not be used. 
D7e. Facilitated Mental Health Care 
 
 Patients will be offered an option of psychotropic medications, referral to psychologists embedded in 
primary care for psychotherapeutic treatment of their depression and/or anxiety, or combined therapy. 
Those with PTSD will be especially encouraged to accept a psychology referral. Moreover, patients not 
responding to one treatment will be encouraged to consider combined therapy. Depression (PHQ-9) and 
anxiety (GAD-7) scores that are obtained  by the nurse in response to elevated mood scores derived from 
automated symptom monitoring will be provided to the treating psychologist as one metric of treatment 
response and as additional information to determine if additional treatment sessions or modifications to 
treatment may be warranted. This collaboration between the nurse-physician study team and the embedded 
primary care psychologists in monitoring and adjusting treatment is one of the innovations of CAMMPS. 
D7f. Duration of Intervention 
 
 Our 12-month study is divided into 2 phases:  (1) acute phase (first 6 months) during which automated 
symptom monitoring will occur weekly (month 1) and then every other week (months 2 through 6) to allow 
careful follow-up of symptoms and treatment adjustments; (2) continuation phase (last 6 months) during 
which automated symptom monitoring will occur once a month for months 7-12 to allow further treatment 
adjustments in subjects who failed to achieve target clinical responses during the acute phase or to detect 

Page 21 of 56 
 
Study #1212010163 
 
relapse in subjects who did achieve target responses. Automated symptom monitoring will allow nurse care 
manager contacts to be selective, thereby making 12-month surveillance more efficient.43  
D7g. Sequencing PAD Symptom Treatment.   
 
 Unlike trials aimed at single symptoms, interventions encompassing multiple symptoms must consider 
whether to approach symptoms simultaneously or sequentially.  In general, a sequential approach is 
preferred for reasons of simplicity and efficiency. It must first be acknowledged there is no evidence-based 
approach to sequencing symptom treatment in the presence of multiple symptoms.  Thus, we provide an 
operational approach, based upon expected time to symptom improvement, strength of evidence for 
medications, and the likelihood certain symptoms are secondary to others.  
 
 Medication sequencing will be prioritized as:  pain  depression  anxiety. Pain will typically be 
targeted first since it is probably the most noxious of the 3 symptoms and tends to respond more quickly to 
medication. There are a number of analgesic options, both short- and long-acting, and some pain 
improvement is expected to occur in several days to a few weeks if a medication is effective in a particular 
patient.88,108  Finally, pain commonly may either trigger or aggravate psychological symptoms.109,110 
Depression and anxiety follow pain in the sequence since their response to treatment may take longer 
(weeks to several months), and may be moot in the event that pain is ameliorated. Depression is prioritized 
before anxiety because depression has larger and more pervasive effects on functional status and quality of 
life.20,111,112  Moreover, the evidence that primary care based collaborative approaches improve outcomes is 
much greater for depression than anxiety (35-40 vs. only 2 randomized clinical trials).28,29,37,38 The 12-month 
trial duration allows time for sequential treatment in patients. 
 
 Occasionally, clinical factors will dictate simultaneous treatment.  For example, the person with pain 
and severe depression might be started on both an analgesic and an antidepressant. Finally, it must be 
acknowledged that the large number of possible permutations of treatment sequences in a trial enrolling 
patients with several symptoms will mean CAAMPS is not powered to statistically compare different 
sequences of symptom treatment, much less specific types or doses of medication.  Indeed, this adheres to 
the principle of “treat to target” central to a number of symptom effectiveness trials, where the aim is to 
optimize the clinical outcome with evidence-based treatments rather than to test the efficacy of any 
particular medication or treatment, singly or in combination.42,52,113  
D7h. Defining a Clinical Response 
1. Symptom severity measure PEG (pain); PHQ-9 (depression); GAD-7 (anxiety) 
2. Global improvement 
    “Overall, would you say your pain recently is:  (1) Worse;  (2) About the same;  (3) A little  
     better;  (4) Somewhat better;  (5)  Moderately better;  (6) A lot better; (7) Completely better 
3. Treatment change desired:  
        “Would you like to make some changes in the treatment for your pain?”   (Yes or No) 
 
 The 3 criteria in Figure 6 assess the core outcome domains recommended by IMMPACT:  pain 
intensity/interference, patient-rated global improvement; and satisfaction with treatment.70,114  A ≥ 30% 
reduction of in pain is a commonly accepted threshold in pain treatment trials and is therefore defined as a 
partial response (Criterion 1). Criterion 2 represents the patient’s assessment of the direction and 
magnitude of symptom change.  A patient’s desire for treatment change (Criterion 3) typically represents a 
clinical action threshold signifying dissatisfaction with the current level of symptom control and a willingness 
to embrace the costs of and adjustment to increased or added treatments. 
 
 The decision to make treatment changes in symptom-based conditions like pain, depression and 
anxiety cannot be done in a formulaic (“cookbook”) fashion because, unlike conditions measured 
independent of patient-report (e.g., blood pressure, serum glucose, cholesterol), symptoms are self-rated 
and rely primarily on the patient’s internal weighting of symptom severity, interference with valued roles and 
activities, pros and cons of treatment changes, and other factors unique to the patient.  However, the 3 
clinical response criteria will be regularly assessed and applied by the nurse-MD symptom team in their 
weekly case management meetings. Clinical decision making will be guided by the algorithm in Figure 6 in 
accordance with 7 operating principles outlined in Appendix 3. 

Page 22 of 56 
 
Study #1212010163 
 
D7i. 
Suicidality 
Assessment Algorithm 
 
  
 
 
Subjects who endorse thoughts of self-harm (either spontaneously or by a positive response to item 9 of 
the PHQ-9) will be assessed with a standardized algorithm that we have used and validated in previous 
depression trials involving more than 3000 subjects.115 This validated algorithm (Appendix 4) provides a 
structured interview for the research assistants or nurse care manager that classifies the subject as low to 
minimal risk (Action Routine) or intermediate or higher risk (Action Today).  Although less than 5% of 
individuals who trigger the algorithm fall into the Action Today category, a physician-investigator is available 
24 hours a day 7 days a week to take over management of Action Today subjects. Those classified as 
Action Today during the eligibility interview will not be enrolled but instead immediately triaged for formal 
evaluation by a mental health professional in our VAMC. 
D7j. Other Safety Concerns and Adverse Events 
 
 Patients on an NSAID who are older than 70 or have a history of heart failure, liver disease, diabetes, 
or concurrent nephrotoxic drugs must have had a creatinine within the past year of initiation and may have a 
repeat creatinine 4-8 weeks afterwards if clinically indicated.  Acetaminophen will be limited to ≤ 2 gm/day in 
cirrhosis and chronic alcohol use (>3 drinks per day). Tramadol will not be used in patients with a history of 
seizures. Regarding antidepressants, patients started on and titrated to a dose of a tricyclic antidepressant 
(TCA) equivalent to 100 mg amitriptyline or 50 mg nortriptyline or 75 mg venlafaxine must have well-
controlled blood pressure at baseline, and at recheck within the first 2 weeks.   Other monitoring of adverse 
events is described in the Human Subjects section. 
D7k. Other treatments  
 
 Subjects will continue to be followed by their primary care physician (PCP) for all medical care not 
related to the study.  Specifically, use of all analgesic and psychotropic medications will be assessed, both 
to adjust for co-intervention differences between groups in the analyses and to assess as secondary 
outcomes.  For example, a decreased proportion of patients requiring opioids from their PCP would also be 
an important secondary outcome.   
 
D8. End-of Study Evaluation 
 
 
Since CAMMPS is a comparative effectiveness rather than implementation trial, the principal 
analyses will be quantitative rather than mixed-methods.  However, we will conduct an evaluation upon 
completion of the trial to inform subsequent implementation of the ASM and CSM interventions. We have 
conducted clinician surveys and qualitative interviews as described below in our previous trials which have 
Criterion 3 
Treatment change desired by patient? 
Criterion 3 
Treatment change desired by patient? 
Response? 
YES 
NO 
Probe reasons treatment 
change is desired 
Change  
treatment 
NO 
YES 
NO 
YES 
Figure 6.  Algorithm for Using Clinical Criteria to Decide on Treatment Changes 
Probe reasons treatment 
change is not desired 
Criterion 
Measure 
Partial response  
(4-11 weeks) 
Target response  
(≥ 12 weeks) 
1 
PEG (pain) 
PHQ-9 (depression) 
GAD-7 (anxiety) 
≥ 30% decrease 
≥ 50% decrease, or 
score of < 4 on PEG or  
< 5 on PHQ-9 or GAD-7 
2 
Global improvement 
4 or greater 
(“somewhat better”) 
6 or greater 
(“a lot better”) 
Response =  Both criteria met for ≥ 2 consecutive timepoints ≥ 2 weeks apart 
Continue same 
treatment 

Page 23 of 56 
 
Study #1212010163 
 
proven highly informative.43,116-119 This qualitative work has been critical to help us understand how patients 
believed they benefitted (or did not benefit) from an intervention by obtaining patients’ perspectives on the 
relative contribution of each intervention component, and giving us important information about how an 
intervention can be improved. Our provider surveys have likewise yielded important insights. This is 
especially critical given the innovative features of this trial. 
D8a. Survey of study patients and providers.  
 
 All study patients will complete a survey regarding the intervention as part of their 12-month interview. 
This survey will be a modified version of that used in our INCPAD trial which provided valuable feedback as 
reported in a recent publication.43 Similarly, we will develop a similar survey to be administered to 
participating PCPs and psychologists to elicit their perspectives regarding the interventions. 
D8b. Semi-structured interviews involving study participants.   
 
Methods similar to those used in our qualitative evaluations of our SCAMP trial will be used.116,117  
Briefly, those willing to participate will complete written informed consent. Participants will be purposively 
sampled to maximize diversity in age, gender, and race/ethnicity in an effort to increase the range of 
comments and perceptions elicited.. Based on previous experience, we anticipate conducting  up to 30 
semi-structured interviews with research participants. An experienced qualitative researcher and moderator, 
Dr. Matthias, will lead the study team in completing these interviews , combining open-ended questions with 
a series of probing questions to elicit perceived barriers and facilitators to key components of the 
interventions. Audio-tapes of the interviews will be transcribed and checked for accuracy.  
  
D9. Statistical Analysis 
D9a. Sample size determination.   
 
 Sample size is determined to ensure adequate power for our primary hypothesis in Specific Aim 1, i.e. 
CSM is superior to ASM in reducing composite PAD symptom severity. In our previous SCAMP and 
INCPAD effectiveness trials targeting depression and pain in primary care and cancer patients, respectively, 
the average intervention effect size, compared to a usual care control group, was 0.55 for pain and 0.54 for 
depression.42,52 Since CAMMPS will be comparing CSM to an active comparator ASM group rather than a 
usual care control group, we will conservatively estimate a smaller effect size of 0.35, which is half way 
between a small effect size of 0.2 and moderate effect size of 0.5.120  As noted previously, our primary 
outcome will be a composite pain-anxiety-depression score using the BPI, GAD-7, and PHQ-9 scores, 
respectively. A standard z-score will be calculated for each scale as follows:  subject’s scale score minus 
the sample mean divided by the sample standard deviation.124 A composite pain-anxiety-depression score 
will be the average of the standard z-scores for the 3 scales. Since the z-score already is equal to the 
number of standard deviations, a between-group composite z-score difference of 0.35 is equivalent to an 
effect size of 0.35. Having 128 participants per treatment arm, we will have 80% power to detect an 
between-group effect size difference of 0.35 using a two-sample t-test with a 5% Type I error rate. In our 
previous trials, 12-month attrition has been < 10%. Allowing for 15% attrition in our present trial, we would 
need 150 per treatment arm, or a total of 300 participants. Because of the use of repeated measurements 
(see D9b below) and adjustment for baseline characteristics, the error variance of the model is likely to be 
smaller as compared to unadjusted analyses. As a result, the power is likely to be greater than the nominal 
level of 80%. 
D9b. Analysis for primary aim. 
 
 Aim 1.  To compare 12-month effectiveness of CSM vs. ASM in improving overall pain and mental 
health. Our hypothesis is that CSM will be superior to ASM in reducing a composite pain-anxiety-depression 
severity score. 
 
All analyses will be based on intention-to-treat in all randomized participants. Before we perform the 
group comparisons of intervention effect, we will summarize the patients’ baseline characteristics by groups 
and compare between groups for any indication of systematic differences using two-sample t-tests for 
continuous variables and Chi-square tests for categorical variables. As the main test of our trial’s treatment 
effect, we will evaluate the overall between-group differences on the composite pain-anxiety-depression z-
score (calculated as described in section D9a) over the 12-month period of the trial using mixed effects 

Page 24 of 56 
 
Study #1212010163 
 
model repeated measures (MMRM) analysis in a similar way to Kroenke et al.42,52  Specifically, the 
composite z-score at 1, 3, 6, and 12 months will be used as the dependent variable in the model. 
Intervention group and dummy variables indicating the follow up time (1, 3, 6 months, and 12 months) will 
be included as the main predictors. Baseline composite score will be adjusted. The test of intervention 
group effect under this model will provide a comparison of the average difference in z-score over the 12 
months between the two groups which is our main goal.  A random intercept will be used to adjust for 
within-subject correlation. We will also evaluate the time-specific (1, 3, 6, and 12 months) between-group 
difference by using the MMRM model with additional interaction terms of time and intervention group. The 
group difference accompanied with 95% confidence interval will be provided. 
 
 Sensitivity analyses for primary outcome. We will use 4 secondary analytic strategies to test the 
robustness of our main composite z-score outcome. First, we will compare between-group differences on  
the PROMIS composite T score calculated as described in section D4a. Second, we will calculate a z-score 
and PROMIS T score for each subject using only their threshold-level symptoms, and compare groups on 
these patient-specific composite scores. Third, we will compare between-group differences in patient-rated 
global improvement, a measure that has proved sensitive to intervention effects in our previous trials.42,52 
Fourth, we will compare between-group differences in non-PROMIS symptom measure scores in the subset 
enrolled with that symptom (i.e., PHQ-9 differences in subset enrolled for depression; GAD-7 differences in 
subset enrolled for anxiety). 
 
 Moderator analyses. We will explore the role of potential baseline moderators (age, sex, race, medical 
comorbidity, disability index, sociodemographic disadvantage factors [low education, low income, 
unemployment]), and substance use risk. We will test for interactions between these potential moderators 
and treatment arm in separate models. A variable will be considered an effect moderator if the coefficient for 
the interaction term is significant (p ≤ .05).  Since our study is not specifically powered to detect moderator 
effects, only moderate to large moderator effects are likely to be detected. 
D9c. Analyses for Secondary Aims.   
 
 Since CAMMPS is not powered for the secondary aims, these results should be interpreted cautiously 
unless they are highly significant. 
 
 Aim 2.  To compare 12-month effectiveness of CSM vs. ASM in improving specific PAD symptoms. 
Our hypothesis is that CSM will be superior to ASM in reducing pain, anxiety, and depression severity 
scores individually.  
 
For these analyses, only the subgroup enrolled for each symptom will be compared.  Between-group 
differences for pain will be tested using all enrolled subjects since pain is a required eligibility criterion for 
this trial.  However, between-group differences for anxiety will only be tested for the enrolled subjects with 
threshold-level anxiety, and likewise for depression. Each symptom subgroup will be compared on the 
PROMIS and the non-PROMIS symptom measure. Specifically, between-group differences in pain will be 
compared on the PROMIS pain measure and the Brief Pain Inventory; between-group differences in the 
subgroup enrolled with threshold-level anxiety will be compared on the PROMIS anxiety measure and the 
GAD-7; and between-group differences in the subgroup enrolled with threshold-level depression will be 
compared on the PROMIS depression measure and the PHQ-9. Similar to the primary analysis, overall 
between-group differences over the 12-month trial period will be compared using MMRM.  The pain, 
anxiety, or depression score at 1, 3, 6, and 12 months will be used as the dependent variable. Intervention 
group and time (1, 3, 6, and 12) will be used as the predictors adjusting for the baseline symptom score. For 
each analysis focusing on a specific symptom subgroup, between-group differences analyses will be 
adjusted for the severity of each of the other two PAD symptoms. A random intercept will be used to adjust 
for within-subject correlation. We will also evaluate the time-specific between-group differences by using the 
MMRM model and provide the 95% confidence intervals. 
 
 Aim 3. To compare the effects of CSM vs. ASM on secondary outcomes, including health-related 
quality of life, health care utilization, treatment satisfaction, and patient and provider perceptions of barriers 
and facilitators to CSM and ASM. 
  
 Quantitative Analyses. Most secondary outcomes are continuous variables. For them analytic 
techniques will be similar to those described under Primary Analysis (section D9b) using MMRM, with the 
dependent variable in separate models being secondary outcomes that are both clinically important as well 

Page 25 of 56 
 
Study #1212010163 
 
as potentially modifiable by the intervention. These include the SF-12 PCS and MCS scores, Sheehan 
Disability score, disability days, global improvement, and treatment satisfaction. For the outcomes of health 
care use (outpatient visits, emergency department visits, and hospitalizations), we will evaluate the 
between-group differences using the negative binomial model which takes into account potential differences 
in  length of follow up due to early dropout and allows for overdispersion. Intervention group is the main 
predictor and other covariates will be adjusted as appropriate. For all secondary outcomes,the p-values will 
be adjusted for multiplicity using the Sidak method:62,121 where:  adjusted p-value = 1 – (1 – unadjusted p-
value)# tests   
 
 Qualitative Analysis of Semi-structured Interview Data. Three members of the research team led by 
Dr. Matthias will first read each transcript independently to orient to the data and begin grasping overall 
themes.  Second, the team will begin initial coding, in which each researcher independently labels each 
segment of data.  The team will meet weekly to compare and discuss these initial labels, resolving 
discrepancies iteratively by consensus. The team will use constant comparative methods throughout this 
process.  Once a set of codes is agreed upon and remains stable and consistent across transcripts, the 
team will move on to focused coding.  During focused coding the team will continue to evaluate the 
adequacy of each code and make any necessary changes by consensus.  The team will meet regularly to 
compare coding and ensure consistency.  Coding and analysis will be facilitated by the qualitative data 
software, ATLAS-ti. Finally, data will be summarized and grouped into conceptual themes and then 
analyzed using standard qualitative techniques.122,123  
       Aim 4. To explore the relative contribution of each intervention component to overall symptom 
improvement. These 5 components are automated symptom monitoring, prompted self-management, nurse 
contacts, optimized medication changes, and facilitated mental health care. Our hypothesis is that each of 
these components will have a dose-response relationship with the degree of improvement in the primary 
outcome. 
 
This exploratory aim is guided by our Conceptual Model shown previously in Figure 3 and is intended 
to examine the potential dose-response effect of each of the 5 components summarized in Table 5 (section 
D6). For this exploratory aim, we will use participants from the CSM arm only since they received all 5 
active components. We will quantify the 5 components as follows:  1) automated monitoring contacts (total 
number); 2) self-management strategies completed (number of self-management units completedby the 
patient as captured on the automated monitoring website); 3) medication changes (new analgesic and 
psychotropic starts, dose adjustments, and composite medication changes (summing medication starts and 
dose changes) with the latter as the principal measure;  4) nurse contacts (total number); 5) mental health 
visits (total number). The approach to capturing and quantifying these variables will be similar to previous 
trials by our team as well as others.46,52 We will run separate linear regression models for each of the 5 
components with the 12-month change in our primary outcome (PAD composite score) as the dependent 
variable and the specific component as the predictor variable adjusting for relevant covariates. A significant 
coefficient for a specific component will suggest a continuous association between that particular 
component and the primary outcome. These analyses will allow exploration of a dose-response effect of 
each component.   
D9d. Handling missing data.   
 
All outcome assessments will be interviewer-administered as in our previous trials totaling more than 
3000 patients, where missing data at the item level was <1% for individuals completing assessments.  Also, 
among participants alive at each assessment, interview completion rates were high (85-90%].  MMRM is 
our primary analytic approach and accommodates missing at random without imputations. To check 
whether the missing status depends on treatment assignment and/or other covariates, we will fit a logistic 
model with missing status as the outcome and treatment group and other baseline characteristics as 
covariates. Second, to test the robustness of our MMRM results, we will also run models using 2 imputation 
strategies (LOCF and multiple imputations). In our 2 recent trials, all 3 strategies yielded similar results.42,52  
 
E. 
PROJECT MANAGEMENT PLAN  
E1. Project Timeline   

Page 26 of 56 
 
Study #1212010163 
 
Table 7. CAMMPS Study Timeline 
 
Year 1 
Year 2 
Year 3 
Year 4 
Months 
 0- 
3 
 4- 
6 
 7- 
9 
10-
12 
13-
15 
16-
18 
19-
21 
22-
24 
25-
27 
28-
30 
31-
33 
34-
36 
37-
39 
40-
42 
43-
45 
46-
48 
Start-up 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Enrollment   
(10 per mo) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Intervention 
& Outcome 
Assessment 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Analysis 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Reports and 
Manuscripts 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Dissemin-
ation 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
As shown in the Study Timeline above (Table 7), this is a four-year project. The first 4 months will 
involve hiring and training personnel.  Important steps will include:  (1) finalizing the treatment manuals;  (2) 
training the research nurse care manager in assessing pain, depression and anxiety; managing analgesic 
and antidepressant medication; and delivering the pain and mood self-management program;  (3) training 
the research assistants in the procedures for screening, enrolling, and consenting study subjects, and 
conducting the telephone-based outcome assessments;  (4) working with Interactive Performance 
Technology (IPT) to set up the automated symptom monitoring program; (4) working with VA data 
managers to identify potential study subjects from CPRS;  (5) obtaining permission from primary care 
physicians to approach patients of theirs who might be eligible. 
 
During the next 26 months, we will enroll 300 subjects into the clinical trial, which will be approximately 
11-12 patients per month or an average of 3 patients per week.  Each subject will be followed for 12 
months, with outcome assessments at baseline, 1, 3, 6, and 12 months.  Thus, patient enrollment will be 
conducted from months 5-30, and the interventions and outcome assessments will occur during months 5-
42.  Data analysis will be conducted during the final 16 months of the study (separate baseline and end-of-
study analyses), and the main reports and manuscripts will be prepared during the final year.  Also, 
dissemination activities as outlined in the application will commence during the final 12 months. 
E2.   Overall Project Coordination and Facilities 
 
Overall project coordination will be led by Dr. Kroenke (PI) and Ms. Evans (Project Coordinator). Ms. 
Evans will coordinate all aspects of the project, trouble-shoot any problems, and provide regular updates on 
recruitment progress. Drs. Kroenke, Bair, and Matthias have office, meeting and research space within the 
HSR&D Center for Implementing Evidence-based Practice (CHIC) at the RVAMC. The CHIC includes 8500 
sq. ft. of recently-renovated space including 22 finished private offices, 2 large staff areas with modular 
offices, 2 conference rooms, dedicated research space, and computer resources. Dr. Yu’s office is within 
the Health Information Technology Services building, a 5-minute drive from the CHIC.   
E3. Investigator and Study Personnel Roles and Responsibilities 
 
Dr. Kroenke will serve as the Principal Investigator and be responsible for the overall conduct of the 
project and allocation of funds. He will train and oversee the Project Coordinator.  He will hire the nurse care 
manager and the research associates (RAs) and train them in care management duties and administering 
the outcome battery, respectively. He will serve as Medical Director for the study, supervising the nurse 
care manager in the weekly case management meetings as well as on an as-needed basis for more 
immediate decisions. He will oversee patient enrollment, meeting weekly with the RAs to monitor and 
modify recruitment procedures. He will head the outcome assessment team whose data collection will 

Page 27 of 56 
 
Study #1212010163 
 
remain blinded to the intervention.  
 
Dr. Bair will serve as Associate Medical Director, assisting Dr. Kroenke in his duties. Dr. Matthias will 
lead the qualitative interviewing team and qualitative data analysis. 
 
Dr. Yu will oversee all data analyses including the responsibilities of the masters-level biostatistician. 
He will direct the interim analyses for the generation of abstracts and will supervise the primary and 
secondary analyses for manuscripts. 
 
Sharon Weitlauf, BS, RN  will serve as the nurse care manager. She will provide medication 
management according to analgesic and antidepressant algorithms. She will contact patients at scheduled 
intervals or as triggered by automated symptom monitoring, monitor treatment response and adherence, 
and coordinate care between the study team, primary care physicians, and the psychologists embedded in 
primary care. Ms. Weitlauf is the nurse care manager on our VA-funded SCOPE trial. 
 
Jeffrey Barnd, MS, and Jingwei Wu, MS, will serve as the data manager and data analyst, 
respectively.  Together, they will program all study databases, retrieve information from the electronic 
medical records, assure data integrity and privacy, and conduct all analyses. 
 
 Erica Evans will serve as the Project Coordinator. She will oversee all aspects of patient enrollment, 
supervise the RAs, maintain study files, schedule meetings, manage budgets, and prepare all reports. She 
will work with the data managers to obtain patient lists, meet weekly with RAs and the investigators to 
monitor recruitment, retention, delivery of the intervention, and outcome assessment. 
 
Stephanie McCalley will serve as the principal Research Assistant (RA) and will be responsible for 
recruitment and blinded outcome assessment (baseline and 4 follow-up interviews) of the 300 study 
subjects. She will also coordinating patient travel and incentives, perform data entry, and other study tasks.  
She will be assisted in these activities by a student who will serve as a part-time RA.  Ms. McCalley has 
been the RA on our INCPAD and SCOPE trials. 
 
Interactive Performance Technology will:  (1) set up the home-based automated symptom monitoring; 
(2) design and program the IVR calls and voice record prompts; (3) train and support the research team in 
use of the system; (3) maintain the system for the duration of the study.  We have worked effectively with 
IPT in our INCPAD and SCOPE trials which enrolled Veterans. 
E4. Data Management 
 
Data management infrastructure will be provided by the CHIC.  All data will be stored in password-
protected folders on a secure VA shared drive that is backed up daily. Access to these folders will be limited 
to authorized study personnel. Outcome assessments will be programmed on a VA shared drive using 
Microsoft Access and research assistants will enter data into the database after conducting interviews. 
Algorithms will be created to check for inappropriate or missed data entry, to score the questionnaires and 
store the summary scales within the database, and to determine the appropriate date for follow-up 
interviews. Identifying information will be restricted to approved study personnel. A study identification 
number will be created and the document linking it to identifying information will be kept in a password-
protected access-limited folder on the secured drive. The study identification number will be used for data 
analysis and other purposes to protect patient confidentiality. Data will be backed up daily onto a secured 
server at Roudebush VAMC.  
 
F. 
DISSEMINATION PLAN 
      (1) The VHA National Pain Management Strategy Coordinating Committee, on which Dr. Bair is a core 
member, will serve as one primary channel for disseminating study findings to VA providers, administrators, 
researchers and policy makers.  Findings will be disseminated to the committee in the form of summary 
reports and presentations at their annual face-to-face meeting.  The Committee will advise and coordinate 
next steps for dissemination, including dissemination to other relevant entities such as VISN and hospital 
administrators; local Pain Management Committees; the VISN Pain Points of Contact, the Office of Quality 
and Performance; and the national working groups related to pain management education, guideline 
development, and performance measures.  Additionally, a summary of study findings and implications will 
be posted on the VHA Pain Management Committee’s website in a format readable to Veterans.    
 
(2) Findings will be disseminated to our research audiences through scientific presentations and 
publications, and HSR&D cyber seminars, as well as through conference calls with the Pain Research 

Page 28 of 56 
 
Study #1212010163 
 
Working Group, a subcommittee of the VHA National Pain Management Strategy Coordinating Committee.  
We also will seek synergistic opportunities with the Pain Research, Informatics, Medical comorbidities and 
Education (PRIME) Center and HSR&D-funded studies on pain management.   
 
(3) Other resources include a a widely subscribed VA pain list serve; a VA national pain management 
website (www.va.gov/PAINMANAGEMENT/index.asp); monthly national educational teleconferences 
targeting providers and administrators; a network of VISN Pain Points of Contact who hold monthly 
teleconferences and who serve an important liaison role between the National Pain Management 
Committee and facility level pain committees; and a network of VA and non-VA pain-relevant investigators 
(the Pain Research Working Group) who hold twice monthly teleconferences and yearly face-to-face 
meetings and who, among their goals, work to promote dissemination of research findings and to influence 
practice and policy related to pain care. In sum, an established network of resources is already in place to 
disseminate study findings.  
 
(4) In addition, to the local, regional, and national pain groups we are already tied into, we will 
disseminate study findings to the Mental Health and Substance Use Disorder QUERI groups, the National 
Serious Mental Illness Treatment Research and Evaluation Center (SMITREC), the Mental Illness 
Research, Education, and Clinical Center (MIRECC), and the HSR&D Center for Information Dissemination 
and Education Resources (CIDER). Our research group has disseminated study findings in the VA HSR&D 
Cyber-seminar forum sponsored by CIDER.  
 
(5) Papers published in peer-reviewed journals are an important source of disseminating research 
results.  Our productivity in this regard has been strong: our 2 recently-completed trials (SCAMP and 
INCPAD) have resulted in 15 and 12 publications to date, respectively.  Examples of some projected papers 
from CAMMPS are outlined in Table 8 below. 
Table 8.  Selected Proposed Paper from CAMMPS Trial 
1 CAMMPS trial design (methods) paper 
6 
Intervention mediators and moderators  
2 Pain-anxiety-depression triad (baseline data) 
7 
Provider and patient survey results 
3 Main trial results paper – 12 month outcomes 
8 
Patient semi-structured interview results 
(patients) 
4 Predictors of 12-mo pain outcomes 
9 
PROMIS vs. non-PROMIS symptom measures 
5 Predictors of 12-mo depression/anxiety outcomes 
10 
Somatization and stress 

Page 29 of 56 
 
Study #1212010163 
 
References 
1. Care and Education Committee on Advancing Pain Research IoM. Relieving Pain in 
America: A Blueprint for Transforming Prevention, Care, Education, and Research. 
Washington DC: National Academies Press; 2011. 
2. Schappert SM. National Ambulatory Medical Care Survey:  1989 summary. National 
Center for Health Statistics.  Vital Health Stat 13(110). 1992. 
3. Turk DC. Clinical effectiveness and cost-effectiveness of treatments for patients with 
chronic pain. Clin J Pain. 2002;18:355-365. 
4. Breivik H. International Association for the Study of Pain: update on WHO-IASP activities. 
J Pain Symptom Manage. 2002;24:97-101. 
5. Astin JA. Why patients use alternative medicine. Results of a national study. JAMA. 
1998;279:1548-1553. 
6. Smith BH, Elliott AM, Chambers WA, Smith WC, Hannaford PC, Penny K. The impact of 
chronic pain in the community. Fam Pract. 2001;18:292-299. 
7. Musculoskeletal Disorder and the Workplace: Low Back and Upper Extremities. National 
Academy Press; 2000. 
8. Lorenz KA, Sherbourne CD, Cohen AB et al. Evaluating a strategy to improve pain 
detection in routine outpatient care. Abstract submitted to 2007 VA HSR&D Annual 
Meeting. 2006. 
9. Spitzer RL, Williams JB, Kroenke K et al. Utility of a new procedure for diagnosing mental 
disorders in primary care. The PRIME-MD 1000 study. JAMA. 1994;272:1749-1756. 
10. Ansseau M, Dierick M, Buntinkx F et al. High prevalence of mental disorders in primary 
care. J Affect Disord. 2004;78:49-55. 
11. Spitzer RL, Kroenke K, Linzer M et al. Health-related quality of life in primary care patients 
with mental disorders:  results from the PRIME-MD 1000 study. JAMA. 1995;274:1511-
1517. 
12. Rapaport MH, Clary C, Fayyad R, Endicott J. Quality-of-life impairment in depressive and 
anxiety disorders. Am J Psychiatry. 2005;162:1171-1178. 
13. Stewart WF, Ricci JA, Chee E, Hahn SR, Morganstein D. Cost of lost productive work time 
among US workers with depression. JAMA. 2003;289:3135-3144. 
14. Stein MB, Roy-Byrne PP, Craske MG et al. Functional impact and health utility of anxiety 
disorders in primary care outpatients. Med Care. 2005;43:1164-1170. 
15. Greenberg PE, Sisitsky T, Kessler RC et al. The economic burden of anxiety disorders in 
the 1990s. J Clin Psychiatry. 1999;60:427-435. 
16. Kroenke K, Spitzer RL, Williams JBW, Monahan PO, Lowe B. Anxiety disorders in primary 
care: prevalence, impairment, comorbidity, and detection. Ann Intern Med. 2007;146:317-
325. 
17. Craske MG, Stein MB, Sullivan G et al. Disorder-specific impact of Coordinated Anxiety 
Learning and Management treatment for anxiety disorders in primary care. Arch Gen 
Psychiatry. 2011;68:378-388. 
18. Lowe B, Grafe K, Zipfel S et al. Detecting panic disorder in medical and psychosomatic 
outpatients - Comparative validation of the Hospital Anxiety and Depression Scale, the 

Page 30 of 56 
 
Study #1212010163 
 
Patient Health Questionnaire, a screening question, and physicians' diagnosis. Journal of 
Psychosomatic Research. 2003;55:515-519. 
19.  McLaughlin TP, Khandker RK, Kruzikas DT, Tummala R. Overlap of anxiety and 
depression in a managed care population: Prevalence and association with resource 
utilization. J Clin Psychiatry. 2006;67:1187-1193. 
20. Lowe B, Spitzer RL, Williams JB, Mussell M, Schellberg D, Kroenke K. Depression, 
anxiety and somatization in primary care: syndrome overlap and functional impairment. 
Gen Hosp Psychiatry. 2008;30:191-199. 
21. Katon W, Roy-Byrne P. Anxiety disorders: efficient screening is the first step in improving 
outcomes. Ann Intern Med. 2007;146:390-392. 
22. Kroenke K, Spitzer RL, Williams JBW, Lowe B. An Ultra-Brief Screening Scale for Anxiety 
and Depression: The PHQ-4. Psychosomatics. 2009;50:613-621. 
23. Magruder KM, Frueh BC, Knapp RG et al. Prevalence of posttraumatic stress disorder in 
Veterans Affairs primary care clinics. Gen Hosp Psychiatry. 2005;27:169-179. 
24. Magruder KM, Frueh BC, Knapp RG et al. PTSD symptoms, demographic characteristics, 
and functional status among veterans treated in VA primary care clinics. J Traumatic 
Stress. 2004;17:293-301. 
25. Grubaugh AL, Magruder KM, Waldrop AE, Elhai JD, Knapp RG, Frueh BC. Subthreshold 
PTSD in primary care: prevalence, psychiatric disorders, healthcare use, and functional 
status. J Nerv Ment Dis. 2005;193:658-664. 
26. Kashdan TB, Frueh BC, Knapp RG, Hebert R, Magruder KM. Social anxiety disorder in 
veterans affairs primary care clinics. Behav Res Ther. 2006;44:233-247. 
27. Gros DF, Frueh BC, Magruder KM. Prevalence and features of panic disorder and 
comparison to posttraumatic stress disorder in VA primary care. Gen Hosp Psychiatry. 
2011;33:482-488. 
28. Roy-Byrne P, Craske MG, Sullivan G et al. Delivery of evidence-based treatment for 
multiple anxiety disorders in primary care:  a randomized controlled trial. JAMA. 
2010;303:1921-1928. 
29. Rollman BL, Belnap BH, Mazumdar S et al. A randomized trial to improve the quality of 
treatment for panic and generalized anxiety disorders in primary care. Arch Gen 
Psychiatry. 2005;62:1332-1341. 
30. Bair MJ, Wu J, Damush TM, Sutherland JM, Kroenke K. Association of depression and 
anxiety alone and in combination with chronic musculoskeletal pain in primary care 
patients. Psychosom Med. 2008;70:890-897. 
31. Bair MJ, Poleshuck EL, Wu J et al. Anxiety but not social stressors predict 12-month 
depression and pain outcomes. Clin J Pain. 2011;(in press). 
32. Haftgoli N, Favrat B, Verdon F et al. Patients presenting with somatic complaints in 
general practice: depression, anxiety and somatoform disorders are frequent and 
associated with psychosocial stressors. BMC Fam Practice. 2010;11:67, 
http://www.biomedcentral.com/1471-2296/11/67. 
33. Lew HL, Otis JD, Tun C, Kerns RD, Clark ME, Cifu DX. Prevalence of chronic pain, 
posttraumatic stress disorder, and persistent postconcussive symptoms in OIF/OEF 
veterans: Polytrauma clinical triad. J Rehab Res Development. 2009;46:702. 

Page 31 of 56 
 
Study #1212010163 
 
34. Campbell DG, Felker BL, Liu CF et al. Prevalence of depression-PTSD comorbidity: 
implications for clinical practice guidelines and primary care-based interventions. J Gen 
Intern Med. 2007;22:711-718. 
35. Strine TW, Mokdad AH, Balluz LS et al. Depression and anxiety in the United States: 
findings from the 2006 Behavioral Risk Factor Surveillance System. Psychiatr Serv. 
2008;59:1383-1390. 
36. Strine TW, Kroenke K, Dhingra S et al. The associations between depression, health-
related quality of life, social support, life satisfaction, and disability in community-dwelling 
US adults. J Nerv Ment Dis. 2009;197:61-64. 
37. Gilbody S, Bower P, Fletcher J, Richards D, Sutton AJ. Collaborative care for depression: 
a cumulative meta-analysis and review of longer-term outcomes. Arch Intern Med. 
2006;166:2314-2321. 
38. Williams JW, Jr., Gerrity M, Holsinger T, Dobscha S, Gaynes B, Dietrich A. Systematic 
review of multifaceted interventions to improve depression care. Gen Hosp Psychiatry. 
2007;29:91-116. 
39. Post EP, Van Stone WW. Veterans Health Administration primary care-mental health 
integration initiative. N C Med J. 2008;69:49-52. 
40. Luck J, Hagigi F, Parker LE, Yano EM, Rubenstein LV, Kirchner JE. A social marketing 
approach to implementing evidence-based practice in VHA QUERI: the TIDES depression 
collaborative care model. Implementation Science. 2009;4:64 doi:10.1186/1748-5908-4-
64. 
41. Dobscha SK, Corson K, Perrin NA et al. Collaborative care for chronic pain in primary 
care:  a clustered randomized trial. JAMA. 2009;301:1242-1252. 
42. Kroenke K, Bair MJ, Damush TM et al. Optimized antidepressant therapy and pain self-
management in primary care patients with depression and musculoskeletal pain: a 
randomized controlled trial. JAMA. 2009;301:2099-2110. 
43. Johns SA, Kroenke K, Theobald D, Wu J, Tu W. Telecare management of pain and 
depression in patients with cancer: patient satisfaction and predictors of use. J Ambulatory 
Care Management. 2011;34:126-139. 
44. Naylor MR, Keefe FJ, Brigidi B, Naud S, Helzer JE. Therapeutic Interactive Voice 
Response for chronic pain reduction and relapse prevention. Pain. 2008;134:335-345. 
45. Williams DA, Kuper D, Segar M, Mohan N, Sheth M, Clauw DJ. Internet-enhanced 
management of fibromyalgia: A randomized controlled trial. Pain. 2010;151:694-702. 
46. Sikorskii A, Given CW, Given B et al. Symptom management for cancer patients: a trial 
comparing two multimodal interventions. J Pain Symptom Manage. 2007;34:253-264. 
47. Federal Coordinating Council for Comparative Effectiveness Research: Report to the 
President and Congress. Washington, DC: US Department of Health and Human 
Services; 2009. 
48. Committee on Comparative Effectiveness Research Prioritization IoMI. Initial National 
Priorities for Comparative Effectiveness Research. Washington, DC: National Academies 
Press; 2009. 
49. Selker, H. P., Strom, B. L., Ford, D. E., Meltzer, D. O., Pauker, S. G., Pincus, H. A., Rich, 
E. C., Tompkins, C., and Whitlock, E. P. White paper on CTSA Consortium role in 
facilitating comparative effectiveness research. Clin.Transl.Sci. 3, 29-37. 2010.  

Page 32 of 56 
 
Study #1212010163 
 
50. Methodology Committee of the Patient-Centered Outcomes Research Institute. 
Methodological standards and patient-centeredness in comparative effectiveness 
research: the PCORI perspective. JAMA 307, 1636-1640. 2012.  
51. Katon W, Unutzer J, Wells K, Jones L. Collaborative depression care: history, evolution 
and ways to enhance dissemination and sustainability. Gen Hosp Psychiatry. 
2010;32:456-464. 
52. Kroenke K, Theobald D, Wu J et al. Effect of telecare management on pain and 
depression in patients with cancer: a randomized trial. JAMA. 2010;304:163-171. 
53. Dawson, L, Zarin, D. A., Emanuel, E. J., Friedman, L. M., Chaudhari, B., and Goodman, S. 
N. Considering usual medical care in clinical trial design. PLoS.Med. 6, 
doi:10.1371/journal.pmed.1000111. 2009.  
54. Kroenke K, Bair M, Damush T et al. Stepped Care for Affective Disorders and 
Musculoskeletal Pain (SCAMP) study Design and practical implications of an intervention 
for comorbid pain and depression. Gen Hosp Psychiatry. 2007;29:506-517. 
55. Von Korff M, Jensen MP, Karoly P. Assessing global pain severity by self-report in clinical 
and health services research. Spine. 2000;25:3140-3151. 
56. Kroenke K, Spitzer RL, Williams JBW. The PHQ-9:  Validity of a brief depression severity 
measure. J Gen Intern Med. 2001;16:606-613. 
57. Kroenke K, Spitzer RL, Williams JB, Lowe B. The Patient Health Questionnaire Somatic, 
Anxiety, and Depressive Symptom Scales: a systematic review. Gen Hosp Psychiatry. 
2010;32:345-359. 
58. Callahan CM, Unverzagt FW, Hui SL, Perkins AJ, Hendrie HC. A six-item screener to 
identify cognitive impairment among potential subjects for clinical research. Med Care. 
2002;40:771-781. 
59. Dietrich AJ, Oxman TE, Williams JW, Jr. et al. Re-engineering systems for the treatment of 
depression in primary care: cluster randomised controlled trial. BMJ. 2004;329:602-605. 
60. Williams LS, Kroenke K, Bakas T et al. Care management of post-stroke depression: a 
randomized controlled trial. Stroke. 2007;38:998-1003. 
61. Hunkeler EM, Katon W, Tang L et al. Long term outcomes from the IMPACT randomised 
trial for depressed elderly patients in primary care. BMJ. 2006;332:259-263. 
62. Kroenke K, West SL, Swindle R et al. Similar effectiveness of paroxetine, fluoxetine, and 
sertraline in primary care: a randomized trial. JAMA. 2001;286:2947-2955. 
63. Cella D, Gershon R, Lai JS, Choi S. The future of outcomes measurement: item banking, 
tailored short-forms, and computerized adaptive assessment. Qual Life Res. 2007;16 
Suppl 1:133-141. 
64. Amtmann D, Cook KF, Jensen MP et al. Development of a PROMIS item bank to measure 
pain interference. Pain. 2010;150:173-182. 
65. Perkins AJ, Kroenke K, Unutzer J et al. Common comorbidity scales were similar in their 
ability to predict health care costs and mortality. J Clin Epidemiol. 2004;57:1040-1048. 
66. Krebs EE, Bair MJ, Wu J, Damush TM, Tu W, Kroenke K. Comparative responsiveness of 
pain outcome measures among primary care patients with musculoskeletal pain. Med 
Care. 2010;48:1007-1014. 
67. Spitzer RL, Kroenke K, Williams JB, Lowe B. A brief measure for assessing generalized 
anxiety disorder: the GAD-7. Arch Intern Med. 2006;166:1092-1097. 

Page 33 of 56 
 
Study #1212010163 
 
68. Weathers F, Ford J. Psychometric review of PTSD Checklist (PCL-C, PCL-S, PCL-M, 
PCL-PR). In: Stamm BH, ed.  Measurement of Stress, Trauma, and Adaptation. 
Lutherville: Sidran Press; 1996. 
69. 
Nease DE, Aikens JE, Klinkman MS, Kroenke K, Sen A.  Toward a more comprehensive 
assessment of depression remission: The Remission Evaluation and Mood Inventory Tool 
(REMIT).  Gen Hosp Psychiatry. 2011;33:279-286. 
70. Dworkin RH, Turk DC, Wyrwich KW et al. Interpreting the clinical importance of treatment 
outcomes in chronic pain clinical trials: IMMPACT recommendations. J Pain. 2008;9:105-
121. 
71. Kroenke K, Spitzer RL, Williams JBW. The PHQ-15:  Validity of a new measure for 
evaluating the severity of somatic symptoms. Psychosom Med. 2002;64:258-266. 
72. McHorney CA, Ware JE, Raczek AE. The MOS 36-Item Short-Form Health Survey (SF-
36):  II. Psychometric and clinical tests of validity in measuring physical and mental health 
constructs. Med Care. 1993;31:247-263. 
73. Sheehan KH, Sheehan DV. Assessing treatment effects in clinical trials with the Discan 
metric of the Sheehan Disability Scale. Int Clin Psychopharmacology. 2008;23:70-83. 
74. Kroenke K, Theobald D, Norton K et al. Indiana Cancer Pain and Depression (INCPAD) 
Trial: design of a telecare management intervention for cancer-related symptoms and 
baseline characteristics of enrolled participants. Gen Hosp Psychiatry. 2009;31:240-253. 
75. Cohen S, Kamarck T, Mermelstein R. A global measure of perceived stress. J Health Soc 
Behav. 1983;24:386-396. 
76. Lundberg O, Peck MN. A simplified way of measuring sense of coherence:  experiences 
from a population survey in Sweden. Eur J Pub Health. 1995;5:56-59. 
77. Robinson ME, Riley JL, III, Myers CD, Sadler IJ, Kvaal SA, Geisser ME et al. The coping 
strategies questionnaire: A large sample, item level factor analysis. Clin J Pain. 
1997;13:43-49. 
78. Harland NJ, Georgieff K. Development of the coping strategies questionnaire: a clinically 
utilitarian version of  the coping strategies questionnaire. Rehab Psychol. 2003;48:296-
300. 
79. 
Kroenke K, Krebs E, Wu et al. Stepped Care to Optimize Pain Care Effectiveness 
(SCOPE) Trial:  study design and sample characteristics. Contemporary Clin Trials. 
2013;34:270-281. 
80. 
Derogatis LR, Lipman RS, Rickels K, Uhlenhuth EH, Covi L. The Hopkins Symptom 
Checklist (HSCL): a measure of primary symptom dimensions. Mod Problems 
Pharmacopsychiatry. 1974;7:79-110. 
81. Bjellands I, Dahl AA, Haug TT, Neckelmann D. The validity of the Hospital Anxiety and 
Depression Scale: an updated literature review.  J Psychosom Res. 2002;52:69-77. 
82. First MB, Spitzer RL, Gibbon M, Williams JB. Structured Clinical Interview for DSM-IV Axis 
I Disorders (SCID). American Psychiatric Press Inc.; 1996. 
83. Fiellin DA, Reid MC, O'Connor PG. Screening for alcohol problems in primary care: a 
systematic review. Arch Intern Med. 2000;160:1977-1989. 
84. Krebs EE, Lorenz KA, Bair MJ et al. Development and initial validation of the PEG, a 
three-item scale assessing pain intensity and interference. J Gen Intern Med. 
2009;24:733-738. 

Page 34 of 56 
 
Study #1212010163 
 
85. Williams LS, Kroenke K, Plue L, Bakas T, Hendrie H, Biller J. AIM: A randomized trial of 
treatment for post-stroke depression. Am Heart J. 2002. 
86. Aikens JE, Kroenke K, Nease DE, Jr., Klinkman MS, Sen A. Trajectories of improvement 
for six depression-related outcomes. Gen Hosp Psychiatry. 2008;30:26-31. 
87. Oxman TE, Dietrich AJ, Williams JW, Jr., Kroenke K. A three-component model for 
reengineering systems for the treatment of depression in primary care. Psychosomatics. 
2002;43:441-450. 
88. Kroenke K, Krebs EE, Bair MJ. Pharmacotherapy of chronic pain: a synthesis of 
recommendations from systematic reviews. Gen Hosp Psychiatry. 2009;31:206-219. 
89. American Diabetes Association. Standards of medical care in diabetes - 2008. Diabetes 
Care. 2008;31:S12-S54. 
90. Chobanian AV, Bakris GL, Black HR et al. The Seventh Report of the Joint National 
Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: 
the JNC 7 report. JAMA. 2003;289:2560-2572. 
91. Adli M, Bauer M, Rush AJ. Algorithms and collaborative-care systems for depression: are 
they effective and why? A systematic review. Biol Psychiatry. 2006;59:1029-1038. 
92. VA/DoD Clinical Practice Guideline for Management of Opioid Therapy for Chronic Pain, 
Version 2.0. Washington,D.C.: Department of Veteran Affairs and Department of Defense; 
2010. 
93. Krebs, E. E., Ramsey, D. C., Miloshoff, J. M., and Bair, M. J. Primary care monitoring of 
long-term opioid therapy among Veterans with chronic pain. Pain Med. 12, 740-746. 2011.  
94. VHA Directive 2009-053 on Pain Management. Washington DC: Department of Veteran 
Affairs; 2009. 
95. Chou, R., Fanciullo, G. J., Fine, P. G., Adler, J. A., Ballantyne, J. C., Davies, P., Donovan, 
M. I., Fishbain, D. A., Foley, K. M., and Fudin, J. Clinical guidelines for the use of chronic 
opioid therapy in chronic noncancer pain (APS/AAPM). J Pain 2009;10:113-230. J.Pain 
10, 113-130. 2009.  
96. American Geriatrics Society Panel on Pharmacological Management of Persistent Pain in 
Older Persons. Pharmacological management of persistent pain in older persons. 
J.Am.Geriatr.Soc. 57, 1331-1346. 2009.  
97. Institute of Medicine. Relieving Pain in America: A Blueprint for Transforming Prevention, 
Care, Education, and Research. Washington, DC: National Academies Press; 2011. 
98. Rush AJ, Trivedi MH, Wisniewski SR et al. Acute and longer-term outcomes in depressed 
outpatients requiring one or several treatment steps: a STAR*D report. Am J Psychiatry. 
2006;163:1905-1917. 
99. Roy-Byrne P, Veitengruber JP, Bystritsky A et al. Brief intervention for anxiety in primary 
care patients. J Am Board Fam Med. 2009;22:175-186. 
100. Williams JW, Jr., Mulrow CD, Chiquette E, Noel PH, Aguilar C, Cornell J. A systematic 
review of newer pharmacotherapies for depression in adults: evidence report summary. 
Ann Intern Med. 2000;132:743-756. 
101. Cipriani A, Furukawa TA, Salanti G et al. Comparative efficacy and acceptability of 12 
new-generation antidepressants: a multiple-treatments meta-analysis. Lancet. 2009;(in 
press). 

Page 35 of 56 
 
Study #1212010163 
 
102. Glassman AH, O'Connor CM, Califf RM et al. Sertraline treatment of major depression in 
patients with acute MI or unstable angina. JAMA. 2002;288:701-709. 
103. Lesperance F, Frasure-Smith N, Koszycki D et al. Effects of citalopram and interpersonal 
psychotherapy on depression in patients with coronary artery disease: the Canadian 
Cardiac Randomized Evaluation of Antidepressant and Psychotherapy Efficacy 
(CREATE) trial. JAMA. 2007;297:367-379. 
104. Briley M, Moret C. Treatment of comorbid pain with serotonin norepinephrine reuptake 
inhibitors. CNS Spectr. 2008;13:7(Suppl 11):22-26. CNS Spectr. 2008;13:22-26. 
105. Marks DM, Shah MJ, Patkar AA, Masand PS, Park GY, Pae CU. Serotonin-norepinephrine 
reuptake inhibitors for pain control: premise and promise. Curr Neuropharmacol. 
2009;7:331-336. 
106. Simon G. Choosing a first-line antidepressant: equal on average does not mean equal for 
everyone. JAMA. 2001;286:3003-3004. 
107. Rush AJ, Trivedi MH, Wisniewski SR et al. Bupropion-SR, sertraline, or venlafaxine-XR 
after failure of SSRIs for depression. N Engl J Med. 2006;354:1231-1242. 
108. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology: 
Adult Cancer Pain, 2010. www.nccn.org. .  2010.  
109. Bair MJ, Robinson RL, Katon W, Kroenke K. Depression and pain comorbidity: a literature 
review. Arch Intern Med. 2003;163:2433-2445. 
110. Kroenke K, Wu J, Bair MJ, Krebs EE, Damush TM, Tu W. Reciprocal relationship between 
pain and depression: a 12-month longitudinal analysis in primary care 12:964-973. J Pain. 
2011;12:964-973. 
111. Spitzer RL, Kroenke K, Linzer M et al. Health-related quality-of-life in primary-care patients 
with mental disorders - Results from the PRIME-MD 1000 Study. JAMA. 1995;274:1511-
1517. 
112. Brown LF, Kroenke K, Theobald DE, Wu J, Tu W. The association of depression and 
anxiety with health-related quality of life in cancer patients with depression and/or pain. 
Psychooncology. 2010;19:734-741. 
113. Katon W, Lin EH, Von KM et al. Integrating depression and chronic disease care among 
patients with diabetes and/or coronary heart disease: the design of the TEAMcare study. 
Contemp Clin Trials. 2010;31:312-322. 
114. Dworkin RH, Turk DC, Farrar JT et al. Core outcome measures for chronic pain clinical 
trials: IMMPACT recommendations. Pain. 2005;113:9-19. 
115. Dube, P., Kroenke, K, Bair, M. J., Theobald, D., and Williams, L. S. The P4 screener:  
evaluation of a brief measure for assessing potential suicidal risk in 2 randomized 
effectiveness trials of primary care and oncology patients. Prim.Care Companion.J Clin 
Psychiatry 12[6], e1-e8. 2010.  
116. Bair MJ, Matthias MS, Nyland K et al. Barriers and facilitators to chronic pain self-
management: a qualitative study of primary care patients with comorbid musculoskeletal 
pain and depression. Pain Med. 2009;10:1280-1290. 
117. Matthias, M. S., Bair, M. J., Nyland, K A., Huffman, M. A., Stubbs, D. L., Damush, T. M., 
and Kroenke, K. Self-management support and communication from nurse care managers 
compared to primary care physicians: a focus group study of patients with chronic 
musculoskeletal pain. Pain Manag.Nurs. 2010;11:26-34.  

Page 36 of 56 
 
Study #1212010163 
 
118. Matthias, M. S., Parpart, A. L., Nyland, K. A., Huffman, M. A., Stubbs, D. L., Sargent, C., 
and Bair, M. J. The patient–provider relationship in chronic pain care: providers' 
perspectives. Pain Med. 2010;11:1688-1697.  
119. Matthias MS, Miech EJ, Myers LJ, Sargent C, Bair MJ. "There's more to this pain than just 
pain": How patients' understanding of pain evolved during a randomized controlled trial for 
chronic pain. J Pain. 2012;(in press). 
120. Kazis LE, Anderson JJ, Meenan RF. Effect sizes for interpreting changes in health status. 
Med Care. 1989;27:S178-S189. 
121. Sidak Z. Rectangular confidence regions for the means of multivariate normal 
distributions. J Am Stat Assoc. 1967;62:626-633. 
122. Miles MB, Huberman AM. Qualitative Data Analysis. Thousand Oaks, CA: Sage; 1994. 
123. Crabtree BF, Miller WL. Doing Qualitative Research. 2nd ed. Thousand Oaks, CA: Sage; 
1999. 
124. Von Ah D, Carpenter JS, Saykin A, et al. Advanced cognitive training for breast cancer 
survivors: a randomized controlled trial.  Breast Cancer Res Treat. 2012;135:799–809 
 
 
 

Page 37 of 56 
 
Study #1212010163 
 
 
HUMAN SUBJECTS PROTECTION 
 
1. 
Overview 
 
The target population for this Comprehensive vs. Assisted Management of Mood and 
Pain Symptoms (CAMMPS) study will be veterans receiving care at one of the Roudebush 
VAMC primary care clinics or VA Community-Based Outreach Clinics (CBOCs) and who suffer 
from clinically significant levels of chronic pain, anxiety, and/or depression (i.e., PAD 
conditions). Veteran patients in primary care who meet clinical severity levels of pain plus 
comorbid depression and/or anxiety as well as other eligibility criteria and who provide informed 
consent will be randomized to one of two treatment arms. One group will receive assisted 
symptom management (ASM) by interactive voice recording or Internet with prompted pain and 
mood self-management. The second group will receive comprehensive symptom management 
(CSM) which combines ASM with centralized medication management delivered by a nurse-
physician specialist team, care coordination, and facilitated mental health care. Both 
interventions will be enhancements to standard primary care. Research assessments, 
consisting of self-administered questionnaires and standardized interviews, will be conducted at 
baseline, 1, 3, 6, and 12 months. The evaluation instruments are validated measures to assess 
pain, anxiety, depression, health-related quality of life, and other patient-reported variables that 
can be effectively administered by trained research assistants. In short, CAMMPS compares: 1) 
usual care plus assisted symptom management (ASM) vs. 2) usual care plus ASM plus 
optimized medication management and facilitated mental health care(CSM).   
 
2. 
Risk to Subjects 
  2a. 
Human Subjects Involvement and Characteristics  
 
All Veterans 18 years and older will be potentially eligible. All subjects recruited for the 
study will be Veterans. A total of 300 subjects will enrolled.  Veterans receiving care in one of 
the Roudebush VAMC primary care clinics or VA CBOCs will be eligible if they have  comorbid 
pain plus anxiety and/or depression.   
 
Pain must:  (a) be musculoskeletal, either localized (in the arms, legs, back, or neck) or 
widespread (fibromyalgia); (b) have persisted 3 months or longer despite a trial of at least one 
analgesic medication; (c) be at least moderate in severity, defined as a Brief Pain Inventory 
average severity score of 5 or greater. Depression must be of at least moderate severity, 
defined as a PHQ-8 score ≥ 10 with either depressed mood and/or anhedonia being endorsed. 
Anxiety must be of at least moderate severity, defined as a GAD-7 score ≥ 10 or greater.   
 
Excluded will be individuals who: (a) do not speak English; (b) have moderately severe 
cognitive impairment as defined by a validated 6-item cognitive screener; (c) have 
schizophrenia, bipolar disorder or other psychosis; (d) are suffering from a complex or severe 
mental illness or are at high risk of suicide as their condition is unsuitable for a predominantly 
telecare intervention; (e) are pregnant; (f) have an anticipated life expectancy of less than 12 
months. 
 
 
This trial does not involve special vulnerable populations, such as fetuses, neonates, 
pregnant women, children less than 18 years old, prisoners, institutionalized individuals, or 
others who may be considered vulnerable populations. 
  2b. 
Sources of Materials 
 
The research material that will be obtained from study participants will be primarily data 
provided by them during research interviews or excerpted from their medical records (CPRS). 
Participants in the CSM arm in whom a nonsteroidal anti-inflammatory medication is started 

Page 38 of 56 
 
Study #1212010163 
 
during the study or in whom opioid medications are started or increased may be asked to 
provide a blood test (for serum creatinine) or a urine test (for drug testing) as part of clinical 
care.  All data gathered from participants will be with their approval as documented by written 
informed consent and HIPPA authorization. 
 
The data gathered will be obtained during research interviews and focus on the severity 
of pain, anxiety and depression as well as health-related quality of life, symptom-related 
treatments, health care use, and sociodemographic information. The exact patient-reported 
measures to be used are described in the Research Plan. 
 
Only study team members (study investigators, project coordinator, research assistants, 
nurse care managers, data managers, biostatisticians) who are IRB-approved will have access 
to individually identifiable private information.  Measures to assure privacy and confidentiality 
are described in Section 2dii(2) below. 
  2c. 
Potential Risks 
 
Potential risks primarily involve direct adverse effects of FDA-approved medications 
which are well-described and minimal in most patients.  Side effects of these medications 
typically resolve shortly after stopping them.  Since patients will also have depression and/or 
anxiety, another potential risk is emotional distress related to the discussion of psychological 
symptoms; this is typically a minor issue and well handled by trained research interviewers and 
study nurse care managers. Some patients may have a small amount (two teaspoons) of blood 
drawn before or starting a study medication which could result in some discomfort or bruising 
where the blood was drawn or the needle was placed. Suicide is an exceptionally rare event in 
medical patients enrolled in trials, and safeguards are discussed in section 5ciii below. 
 
Alternative treatments for potential study participants include receiving standard care 
from their primary care physician for their pain, anxiety and/or depression, receiving care from a 
mental health specialist, or receiving no treatment. The risks (failure of symptoms to improve) 
and benefits (symptomatic improvement) of these alternative treatments will be explained during 
the informed consent procedure. 
  2d. 
Adequacy of Protection against Risks 
    2di. Recruitment and Informed Consent 
 
 Primary care physicians (PCPs) will be informed of the study in detail and provide written 
consent to approach their patients for participation in the trial.  Only patients from consenting 
PCPs will be enrolled. Electronic medical records (CPRS) will be used to create a master list of 
individuals who, within the preceding 36 months, have received an ICD diagnosis of a 
depressive disorder, an anxiety disorder, or a musculoskeletal pain condition. This patient list 
will be updated quarterly during the enrollment period. Individuals on this list will be mailed a 
letter describing the study and contacted within 2 weeks by telephone to determine potential 
interest in the study and, if willing, complete an eligibility interview.   
 
Eligible patients will be scheduled for an in-person research visit where written informed 
consent and HIPPA authorization will be obtained by the project coordinator or trained research 
assistants. This consent will be obtained prior to any baseline assessment, randomization, or 
other study procedures. 
    2dii. Protection against Risk. 
 
 1)  Patient Safety. No experimental medications will be used in this trial.  Rather, we will 
use analgesics and antidepressants which are FDA-approved for treatment of pain, depression, 
and anxiety and widely-used in clinical practice. Clinical response to medications as well as any 
side effects will be monitored by the research nurse/supervising physician-investigator team. 
For patients who do not tolerate the side effects, the medication will be discontinued and an 
alternative medication begun in its place. We will use careful evaluation of all subjects at 

Page 39 of 56 
 
Study #1212010163 
 
baseline and close follow-up by a nurse specially trained for this study similar to nurse care 
managers we have used in our several previous trials. 
 
 Women of child-bearing age who are randomized to the comprehensive symptom 
management (CSM) group will be counseled about appropriate contraceptive measures to use 
during the time they are on antidepressant medication, consistent with standard clinical practice.  
Also, in these women, the initial drug of choice will be an SSRI (excluding paroxetine) since 
safety in the event of pregnancy has been established for SSRIs. 
           Patients enrolled in this study will have depression and/or anxiety. Also, the outcome 
assessments include the PHQ-9 depression measure which includes a question about thoughts 
of self-harm. The procedure for assessing risk of self-harm is discussed in section 5ciii below. 
 
 2) Participant Privacy and Confidentiality. We will assure the privacy of the content of all 
interviews and other data collected as part of this study by assigning patients unique identifiers 
to track their individual data (rather than using names or hospital or social security numbers) 
and keep all records under lock with access only by study personnel.  Additionally, our IRB 
consent forms include a HIPPA authorization form that subjects must read and sign prior to 
study enrollment. All data will be stored in password-protected folders on a secure VA shared 
drive that is backed up daily. Access to these folders will be limited to authorized study 
personnel. Identifying information will be restricted to approved study personnel. A study 
identification number will be created and the document linking it to identifying information will be 
kept in a password-protected access-limited folder on the secured drive. The study identification 
number will be used for data analysis and other purposes to protect patient confidentiality. Data 
will be backed up daily onto a secured server at Roudebush VAMC.  
 
 Automated symptom monitoring will be hosted by Interactive Performance Technologies 
(IPT) which has successfully set up and maintained similar automated monitoring for 202 cancer 
patients in our recently-completed NCI-funded Indiana Cancer Pain and Depression (INCPAD) 
trial.  IPT also has set up automated monitoring for telecare management of chronic pain in 
primary care as a component of our VA HSR&D-funded SCOPE clinical trial of collaborative 
care for chronic pain in Veterans.  The research team will access IPT’s hosted Symptom 
Monitor using standard PCs with an Internet connection.  IPT’s application is fully HIPAA 
compliant, using secure sockets layer (SSL) technology to authenticate users and encrypt 
information transmitted over the web.  In any instance where data is transferred via non-secure 
electronic networks, data will be encrypted at the source.  Data stored in IVR/CATI databases 
will be transferred in an encrypted fashion at regular intervals and loaded into a secured central 
database at IU.  Delivery of the intervention will include symptom monitoring via these secure 
mechanisms and, in the comprehensive symptom management group, involvement of the study 
participant’s primary care physician, psychologist, and the study team consisting of the nurse 
care manager and the supervising physician symptom specialist. Thus, all exchanges of clinical 
information will comply with HIPPA standards of patient privacy, and all data collected, 
transferred, and stored for research purposes will be done in a manner to assure confidentiality.  
 
3) Adverse Event Collection and Reporting.  See sections 5d, 5e, and 5f below. 
 
3. 
Potential Benefits of Research to Subjects and Others 
 
Both study arms are enhancements to the usual primary care provided to Veterans for 
pain, anxiety and depression. Thus, subjects randomized to either the comprehensive or 
assisted symptom management arms may experience improvement in their pain, anxiety and 
depression symptoms typically experience by patients only receiving usual primary care.  Given 
the prevalence of pain, anxiety and depression in Veterans, the benefits of developing and 
testing effective interventions are substantial. 
 
Study participants will not be charged for any of the study-related calls, including those 
from the nurse, research assistants, or project coordinator. Likewise, the automated home-

Page 40 of 56 
 
Study #1212010163 
 
based symptom monitoring done by IVR or Internet will be conducted at no cost. Furthermore, 
study participants will be compensated $25 for each of the five research assessments 
conducted at baseline, 1, 3, 6, and 12 months.  Participants will be financially responsible for all 
health care costs not directly associated with this study such as their routine clinic visits, 
medications, hospitalizations, and other health care. 
 
4. 
Importance of the Knowledge to be Gained. 
 
Pain, anxiety and depression afflict large numbers of Veterans (as well as non-Veteran 
primary care patients) and leads to huge individual and societal costs in terms of quality of life, 
social and work functioning, health care use, and lost productivity. Knowledge regarding the 
effectiveness of our two systems-based interventions has considerable potential for improving 
the health of Veterans and the public. 
  
5. 
Data and Safety Monitoring Plan 
 
 Core elements of the following multi-component Data and Safety Monitoring Plan have 
been successfully used in our 3 previous NIH-funded comparative effectiveness trials as well as 
our VA-funded ESCAPE and SCOPE trials of pain and depression.  
  5a. 
Determination of Level of Risk.  This study involves low to moderate risk: It is unlikely 
that serious adverse events will occur during the study.  
  5b. 
Data and Safety Monitoring Board.   
 
We will establish a local Data Safety Monitoring Board (DSMB) that meets every 6 
months during the study.  Members will consist of individuals not part of the study team and will 
include a pain specialist, a psychiatrist, a clinical psychologist, a nurse with expertise with care 
management, and a biostatistician. This DSMB will review adverse events, recruitment, and 
other data or study procedures as requested.  A copy of the DSMB minutes and recommend-
ations will be provided to the study PI and will be available to the IRB upon request. 
  5c. 
Study Monitoring.   
    5ci. Weekly Case Management Review. The study nurse care manager meets weekly with 
the supervising physician specialist to review all new patients enrolled in the comprehensive 
symptom management arm as well as previously enrolled patients who have clinical issues 
warranting discussion for potential treatment actions or study-related problems. Medication 
management as well as any side effects or patient concerns are reviewed and discussed.  The 
study PI or back-up physician is available by telephone and/or pager at all times. 
    5cii. Monthly Research Team Meetings. The PI, Project Coordinator, research assistants, 
nurse care manager, and relevant co-investigators meet monthly for study operations meetings.  
These meetings will focus on monitoring recruitment, enrollment and dropouts, eligibility, 
adherence to study protocols, data collection, and adverse events. Minutes of these meetings 
will be maintained by the Project Coordinator. Reporting of any unusual events or problematic 
issues will be done by the study PI and/or Project Coordinator. Decisions will be made jointly 
and recorded in the minutes. 
    5ciii. Suicidal risk assessment.  During nurse care manager contacts with subjects in the 
comprehensive symptom management arm, and outcome assessments by the research 
assistants with all subjects, the depression measure includes an item asking about “thoughts of 
death or harming yourself.”  If a subject endorses this item at any level, the research nurse or 
RA proceeds to a scripted interview. Based on the subject’s responses, they are characterized 
as: Action Routine (low to minimal suicidal risk) or Action Today (higher risk). For Action Today 
subjects, the investigator on call (PI, Co-PI, or backup physician) is contacted, notified of subject 

Page 41 of 56 
 
Study #1212010163 
 
responses, and directs study personnel how to proceed. Our approach is based upon an 
evidence-based algorithm that has been validated in our earlier depression effectiveness trials 
in medical patients (Appendix 4). By this algorithm patients are classified as minimal, lower, or 
higher risk.  The latter constitute < 2% of patients enrolled in depression trials, and we have a 
protocol for expedited evaluation by a study physician for the rare patient in the higher risk 
group. All research personnel will be trained by the PI (Dr. Kroenke) in this protocol.   
  5d, 
Adverse Event Grading. 
• The nature and severity of the adverse event as well as study team actions and follow-
up of the AE to its resolution will be documented in detail by the study nurse.  
• The relationship of the adverse event to the study intervention will be classified in a 
binary fashion as either probably or possibly study-related or unlikely to be study-
related:  
• The relationship of the adverse event to the therapy/study will be determined based 
upon clinical review of all data and subsequent clinical judgment.  
  5e. 
Explicit Definition of a Serious Adverse Event (SAE).  SAEs include the following:     
o 
Death 
o 
A life-threatening experience 
o 
Inpatient hospitalization 
o 
Prolongation of hospitalization 
o 
Persistent or significant disability or incapacity 
o 
Congenital anomaly 
o 
Birth defect 
o 
May require medical, surgical, behavioral, social or other intervention to 
prevent one of the above outcomes. 
  5f. 
Adverse Event Reporting.  
• All Serious Adverse Events will be evaluated to see if they meet the 4 criteria that 
mandate prompt reporting to the IRB (unexpected; related to the study intervention; 
causing harm or increased risk of harm; and requiring a change to the informed 
consent statement). Because this is a VA study, however, all SAEs will be reported to 
the IRB within5 working days using their Prompt Reporting Form, regardless of 
whether they meet these 4 prompt-reporting criteria.  
• All other adverse events will be reported annually with the continuing review. 
• All adverse events will be reviewed and evaluated by the Principal investigator. 
  5g. 
Specific information evaluated at the time of each DSMB review. 
• Recruitment, accrual and dropout statistics, number and description of any AE or SAE, 
any other additional concerns. 
• Data collection – key issues  
• A table with the number of adverse events and their severity will be used in the DSMB 
reports to assess the level of risk/toxicity that occurred. 
• The content and format of reporting may be modified as requested by the DSMB 
members. Since this is an effectiveness trial using treatments proven safe, there are 
no preplanned interim analyses. However, such analyses including testing of AE rates 
between groups will be done if requested by the DSMB. 

Page 42 of 56 
 
Study #1212010163 
 
 
CAMMPS Appendices 
 
Appendix 
 
Item 
 
     1 
 
 
Opioid Risk Stratification Algorithm 
 
     2 
 
 
Medication Algorithms for Depression and Anxietey 
 
     3 
 
 
Key Operating Principles Regarding Analgesic Management 
 
     4 
 
 
Suicidal Ideation Assessment Algorithm 
 
 

Page 43 of 56 
 
Study #1212010163 
 
Opioids being 
Initiated or 
Increased 
• No past or current 
SUD 
• No h/o ADRB 
•Low risk UDS
• Past SUD or risk for 
SUD 
• Level 1 ADRB 
• Intermediate risk 
• Current SUD 
• Level 2-3 ADRB 
• High risk UDS 
• Do not prescribe 
opioids  
• Consider specialty 
pain or mental 
• Opioid agreement 
• Collaborate with PCP 
• Periodic urine 
screening 
• Opioid agreement 
• Collaborate with PCP 
Low Risk 
Intermediate Risk 
High Risk 
 
Algorithm for Opioid Misuse Risk Stratification and Clinical Management 
 
Risk assessment for opioid prescribing in CAMMPS will be based on three sources of 
information, the substance use interview, medical history review, and baseline urine drug 
testing. Positive screens (interview, history, or urine) will be followed by additional data 
collection, including a structured substance use interview, to clarify risk categorization.  The 
algorithm is illustrated in the Figure below and described in the subsequent text. 
 
A.  Substance use interview 
Risk assessment is based on the AUDIT-C and drug history questions, as follows: 
1. AUDIT-C score 
a. Low risk: 0-3 (negative)  
b. ≥ 4 is a “positive screen” that should be followed with additional questions 
i. Low risk: No heavy drinking (defined as >14 drinks per week or ≥ 5 
drinks/day at least monthly) or abuse/dependence 
ii. Intermediate risk: Heavy drinking without abuse/dependence 
iii. High risk: Probable alcohol abuse/dependence 
2. Drug history questions  
a. Low risk: SUB8-10=0-1 and SUB12-13=0 
b. Intermediate risk: SUB8 or SUB10=2 or SUB 9=2-4 or SUB12=1 or SUB13=1 
c. High risk: SUB8 or SUB10=3-4  
 
 
APPENDIX 1 

Page 44 of 56 
 
Study #1212010163 
 
 
 
B.  Medical history review 
Risk assessment is based on review of CPRS and communication with the patient’s PCP. 
1. Substance use disorder 
a. Low risk: No past or current known or suspected SUD 
b. Intermediate risk: Remote personal history of SUD or recent (within 2 years) 
personal history of SUD in remission 
c. High risk:  Known or suspected active SUD 
2. Aberrant drug related behaviors (ADRB) 
a. Low risk: No history of non-adherence to pain management plans 
b. Intermediate risk: Level 1 behaviors (infrequent minor variations from pain 
treatment plan, such as requests for early refills, misplacing medications, or 
minor lending or borrowing of medications from family members) 
c. High risk: Level 2 (frequent, persistent deviations from the treatment agreement 
or behaviors that are manifestations of addiction or psychiatric or cognitive 
dysfunction) or Level 3 (serious illegal, criminal, or dangerous behaviors such as 
diversion or intentional overdose) ADRB. 
 
C.  Baseline urine drug testing 
Risk assessment is based on urine drug screen (UDS) alone if patient has no current opioid 
prescription or UDS + opiate confirmation if patient is already receiving opioid medications. 
Unexpected UDS results will be evaluated with consideration of potential causes for false 
positives/negatives, repeat testing or confirmation, or toxicology consultation as indicated.  
1. If no current opioid medication 
a. Low risk: Negative UDS 
b. Intermediate risk: UDS positive for cannabinoids only 
c. High risk: UDS positive for non-prescribed medication or illicit drugs other than 
cannabinoids  
2. If current prescribed opioid medication 
a. Low risk: Negative for non-prescribed medication or illicit drugs other than 
cannabinoids AND positive for prescribed medication 
b. Intermediate risk: Negative for non-prescribed medication or illicit drugs other 
than cannabinoids and negative for prescribed medication (especially in setting 
of intermittent or low dose opioids that may not be detected) 
c. High risk: Positive for non-prescribed medication or illicit drugs other than 
cannabinoids, repeated or confirmed negative for prescribed medication 
(especially round-the-clock or high dose opioids that should be detected) 

Page 45 of 56 
 
Study #1212010163 
 
 
 
Medication Guidelines for Depression and Anxiety in CAMMPS 
 
Condition/Medication 
Evidence 
Depression/Antidepressants INCPAD trialA,B, SCAMP trialC,D, and STAR*D trialE 
Anxiety/Anxiolytics 
CALM trialF,G, NICE guidelinesH 
 
A. Kroenke K, Theobald D, Norton K, Sanders R, Schlundt S, McCalley S, Harvey P, Iseminger 
K, Morrison G, Carpenter JS, Stubbs D, Jacks R, Carney-Doebbeling C, Wu J, Tu W. 
Indiana Cancer Pain and Depression (INCPAD) Trial: design of a telecare management 
intervention for cancer-related symptoms and baseline characteristics of enrolled 
participants. Gen Hosp Psychiatry. 2009;31:240-253. 
B. Kroenke K, Theobald D, Wu J, Norton K, Morrison G, Carpenter J, Tu W. Effect of telecare 
management on pain and depression in patients with cancer: a randomized trial. JAMA. 
2010;304:163-171. 
C. Kroenke K, Bair M, Damush T, Hoke S, Nicholas G, Kempf C, Huffman M, Wu J, Sutherland 
J. Stepped Care for Affective Disorders and Musculoskeletal Pain (SCAMP) study Design 
and practical implications of an intervention for comorbid pain and depression. Gen Hosp 
Psychiatry. 2007;29:506-517. 
D. Kroenke K, Bair MJ, Damush TM, Wu J, Hoke S, Sutherland J, Tu W. Optimized 
antidepressant therapy and pain self-management in primary care patients with depression 
and musculoskeletal pain: a randomized controlled trial. JAMA. 2009;301:2099-2110. 
E. Rush AJ, Trivedi MH, Wisniewski SR, Nierenberg AA, Stewart JW, Warden D, Niederehe G, 
Thase ME, Lavori PW, Lebowitz BD, McGrath PJ, Rosenbaum JF, Sackeim HA, Kupfer DJ, 
Luther J, Fava M. Acute and longer-term outcomes in depressed outpatients requiring one 
or several treatment steps: a STAR*D report. Am J Psychiatry. 2006;163:1905-1917. 
F. Roy-Byrne P, Veitengruber JP, Bystritsky A, Edlund MJ, Sullivan G, Craske MG, Welch SS, 
Rose R, Stein MB. Brief intervention for anxiety in primary care patients. J Am Board Fam 
Med. 2009;22:175-186. 
G. Roy-Byrne P, Craske MG, Sullivan G, Rose RD, Edlund MJ, Lang AJ, Bystritsky A, Welch 
SS, Chavira DA, Golinelli D, Campbell-Sills L, Sherbourne CD, Stein MB. Delivery of 
evidence-based treatment for multiple anxiety disorders in primary care:  a randomized 
controlled trial. JAMA. 2010;303(19):1921-1928 
H. McIntosh A, Cohen A, Turnbull N, Esmonde L, Dennis P, Eatock J, Feetam C, Hague J, 
Hughes I, Kelly J, Kosky N, Lear G, Owens L, Ratcliffe J, Salkovskis P (2004) Clinical 
Guidelines and Evidence Review for Panic Disorder and Generalised Anxiety Disorder 
Sheffield: University of Sheffield/London: National Collaborating Centre for Primary Care 
APPENDIX 2 

Page 46 of 56 
 
Study #1212010163 
 
Antidepressant Guidelines 
OVERVIEW 
 
Mandatory Care Manager Phone calls or contacts 
Baseline:  
Discuss depressive/anxiety symptoms, past treatment history, and treatment options 
 
 
Initiate treatment incorporating patient preferences and treatment algorithms 
Week 1:  
Scheduled phone call 
(assess side effects and adherence) 
Week 4:  
Scheduled phone call  (assess response, adjust dose, possibly change med) 
Week 12:  
Scheduled phone call  (assess response, adjust does, possibly change med) 
 
Triggered Care Manager Phone calls 
Care manager calls will be triggered based upon automated symptom monitoring (ASM), either: 
• 
Worsening in depressive or anxiety score (or failure to improve according to guidelines) 
• 
Nonadherence reported on ASM call 
• 
Side effects reported on ASM call 
• 
Patient requests care manager phone contact on ASM call 
• 
Missed ASM reports 
 
 
GENERAL PRINCIPLES 
• 
Pre-existing antidepressants.   
o If patient is already on an antidepressant at baseline and recently started (past 8 weeks), we 
may consider increasing the dose of that antidepressant, but discuss with MD investigator first. 
o If patient is on a low-dose antidepressant for a condition other than depression (e.g., peripheral 
neuropathic pain, fibromyalgia, insomnia, etc.), we may consider continuing that medication 
while still starting a study antidepressant.  The most common examples of this would be low 
dose amitriptyline or nortriptyline (e.g., 25 mg hs), or trazodone (e.g., 25-100 mg hs). 
• 
If significant side effects limit increasing any study antidepressant  and the patient has not had an 
adequate response, consult study physician for a recommendation. 
• 
PHQ-9 or GAD-7 Targets:  General guidelines. 
o Week 4 
5 points or greater decrease 
o Week 8 
Either a 50% decrease from baseline PHQ-9 (or GAD-7), or an absolute PHQ-9  
                      (or GAD-7) score < 10. 
o Week 12 
Either a 50% decrease from baseline PHQ-9 (or GAD-7), or an absolute PHQ-9  
                      (or GAD-7) score <  5 
• 
Antidepressant selection. 
o On first phone call, determine past treatment history for depression. 
o Follow algorithm order, skipping over antidepressants that have failed for the patient 
o Antidepressants will typically be prescribed by the primary care physician or psychiatrist 
caring for the patient, and guidelines on next pages apply to recommendations we may provide. 
 
• 
Mental health referral.  If monotherapy options exhausted in this set of algorithms – due to past or 
current antidepressant failures, side effects, or contraindications, facilitate mental health referral. 

Page 47 of 56 
 
Study #1212010163 
 
 
Antidepressant Selection and Dosing Details for CAMMPS † 
Priority  
Indications 
Class 
Drug 
Dose (in mg) 
 
 
 
 
Initial 
Increases 
1 
1st-line (unless anxiety) including CV disease 
SSRI 
Citalopram 
20 
30, 40 
1 
If anxiety or cardiovascular (CV) disease 
SSRI 
Sertraline 
50 
100, 150 
2 
SSRI failure; refractory pain 
SNRI 
Venlafaxine 
75 
150, 225 
2 
SSRI failure, refractory pain 
SNRI 
Duloxetine 
30 
60 
3 
SSRI/SNRI  failure; weight gain; sexual side 
effects 
Other 
Bupropion 
200 
300, 400 
4 
SSRI/SNRI failure; insomnia 
Other 
Mirtazepine 
15 
30, 45 
5 
SSRI failure; refractory pain 
TCA 
Nortriptyline 
25 
50, 75 
 6¶ 
Partial response to antidep. Monotherapy 
 
Combination ¶ 
 
 
† Adapted from STAR*D, SCAMP and CALM trials.  Further details are provided in Appendix 4. 
¶ Acceptable combinations are those used in STAR*D, except will not use lithium or thyroxine. 
 
ALGORITHM 1. CITALOPRAM  
 
1. Day 0:       Start citalopram, 20mg per day. 
2. Week 1:    Call patient, assess for adherence and side effects. 
3. Week 4:    Assess PHQ-9, side effects. If inadequate response, increase to 40 mg per day. 
4. Week 8:    Assess PHQ-9, side effects. If inadequate response, consider increase to 60mg per day 
or switch to different antidepressant. 
5. Week 12:  Assess PHQ-9, side effects; if inadequate response, consider alternative antidepressant. 
6. Month 6:  Assess PHQ-9.  If relapse, consider adjusting or changing antidepressants 
7. Month 9:  Assess PHQ-9.  If relapse, consider adjusting or changing antidepressants 
8. Weaning off citalopram. If a medication change is needed do not stop citalopram abruptly. 
Decrease to half the patient’s usual dose for 5 days, then discontinue. You may start the new 
medication while weaning the citalopram. 
 
ALGORITHM 1. SERTRALINE 
 
1. Day 0:       Start sertraline, 50 mg per day. 
2. Week 1:    Call patient, assess for adherence and side effects. 
3. Week 4:    Assess PHQ-9, side effects. If inadequate response, increase to 100 mg per day. 
4. Week 8:    Assess PHQ-9, side effects. If inadequate response, increase to 150 mg per day 
5. Week 12:  Assess PHQ-9, side effects; if no decrease or patient subjectively reports no 
improvement, consider alternative antidepressant. 
6. Month 6:  Assess PHQ-9.  If relapse, consider adjusting or changing antidepressants 
7. Month 9:  Assess PHQ-9.  If relapse, consider adjusting or changing antidepressants 

Page 48 of 56 
 
Study #1212010163 
 
8. Weaning off sertraline. If a medication change is needed do not stop sertraline abruptly. Decrease 
to half the patient’s usual dose for 5 days then discontinue. You may start the new medication 
while weaning the sertraline. 
ALGORITHM 2A.  VENLAFAXINE SA   
 
Screening and Monitoring Considerations for venlafaxine SA 
1. Does the patient have poorly controlled blood pressure (systolic ≥ 170 or diastolic ≥ 100) at baseline; 
if so consider another agent.   
2. Does the patient have cardiac disease (history of myocardial infarction, angina, congestive heart 
failure, arrhythmia, or other heart disease).  If so, consider sertraline or another agent. 
3. BP assessment. BP assessed and recorded at study entry (baseline). BP rechecked within the first 1-2 
weeks.  If systolic BP increases ≥ 20 above baseline (or diastolic increases ≥ 10 above baseline), 
notify RN who in turn will discuss with physician. 
 
Venlafaxine SA algorithm 
1. Day 0:     Start venlafaxine SA 37.5 mg qd. 
2. Week 1:   Assess side effects and adherence.  Increase to 75 mg qd.  Ask patient to get blood pressure 
checked by week 4 call (e.g., at pharmacy, supermarket, at home, doctor’s office, etc.).  Have patient 
call RN back if blood pressure is elevated (> 170 systolic or > 100 diastolic) 
3. Week 4:   Assess PHQ-9, side effects; if inadequate response, increase to 150 mg qd.  If patient has 
not had BP checked by week 4 call, ask if there are any barriers to having it checked, and do a follow-
up call 1 week later to ask about blood pressure.  If patient has still not had blood pressure check, 
consider bringing patient in for BP check if history of hypertension or if having symptoms (e.g., 
headache, dizziness, etc.).  Otherwise, make sure there is a BP check by week 8. 
4. Week 8:   Assess PHQ-9, side effects; if inadequate response, increase to 225 mg qd.  Also, 
recommend follow-up blood pressure, if dose increased to 225 mg. 
5. Week 12:  Assess PHQ-9, side effects; if inadequate response, consider alternative antidepressant. 
6. Month 6:  Assess PHQ-9.  If relapse, consider adjusting or changing antidepressants 
7. Month 9:  Assess PHQ-9.  If relapse, consider adjusting or changing antidepressants 
8. Weaning off venlafaxine. If a medication change is needed do not stop venlafaxine abruptly. 
Decrease to half the patient’s usual dose every 2 days until total daily dose is 75 mg or less, then 
discontinue. You may start the new antidepressant while weaning the venlafaxine. 
 
ALGORITHM 2A.  DULOXETINE 
 
Screening considerations for duloxetine 
1. Does the patient have liver disease?  If so, choose another antidepressant. 
Duloxetine algorithm 
1. Day 0:       Start duloxetine, 30 mg per day. 
2. Week 1:    Call patient, assess for adherence and side effects. 
3. Week 6:    Assess PHQ-9, side effects. If inadequate response, increase to 60 mg per day. 

Page 49 of 56 
 
Study #1212010163 
 
4. Week 12:    Assess PHQ-9, side effects. If inadequate response, consider switch to different 
antidepressant. 
5. Month 6:  Assess PHQ-9.  If relapse, consider adjusting or changing antidepressants 
6. Month 9:  Assess PHQ-9.  If relapse, consider adjusting or changing antidepressants 
7. Weaning off duloxetine. If a medication change is needed do not stop duloxetine abruptly. 
Decrease to half the patient’s usual dose for 5 days, then discontinue. You may start the new 
medication while weaning the duloxetine 
 
ALGORITHM 3.  BUPROPION SA 
 
Screening considerations for bupropion SA 
1. Does the patient have a history of seizures or an eating disorder?  If so, choose another 
antidepressant. 
Buproprion algorithm 
1. Day 0:  Start bupropion, 150 mg qd. 
2. Week 1:   Call patient, assess for adherence and side effects 
3. Week 4:  Assess PHQ-9, side effects. If inadequate response, increase to 150 mg BID. 
4. Week 8:  Assess PHQ-9, side effects. If inadequate response, increase to 200 mg BID or consider 
alternative antidepressant. 
5. Week 12:  Assess PHQ-9, side effects; if inadequate response, consider alternative antidepressant. 
6. Month 6:  Assess PHQ-9.  If relapse, consider adjusting or changing antidepressants 
7. Month 9:  Assess PHQ-9.  If relapse, consider adjusting or changing antidepressants 
8. Weaning off buproprion. If a medication change is needed do not stop bupropion abruptly. 
Decrease to half the patient’s usual dose for 5 days then discontinue. You may start the new 
medication while weaning the bupropion. 
 
ALGORITHM 4.  MIRTAZAPINE 
1. Day 0:       Start mirtazapine, 15 mg per day at bedtime. 
2. Week 1:    Call patient, assess for adherence and side effects.. 
3. Week 4:    Assess PHQ-9, side effects. If inadequate response, increase to 30 mg per day. 
4. Week 8:    Assess PHQ-9, side effects. If inadequate response, increase to 45 mg per day or 
consider alternative antidepressant. 
5. Week 12:  Assess PHQ-9, side effects; if inadequate response, consider alternative antidepressant. 
6. Month 6:  Assess PHQ-9.  If relapse, consider adjusting or changing antidepressants 
7. Month 9:  Assess PHQ-9.  If relapse, consider adjusting or changing antidepressants 
8. Weaning off mirtazapine. If a medication change is needed do not stop mirtazapine abruptly. 
Decrease to half the patient’s usual dose for 5 days then discontinue. You may start the new 
medication while weaning the mirtazapine. 

Page 50 of 56 
 
Study #1212010163 
 
 
ALGORITHM 5.  NORTRIPTYLINE 
Screening Considerations for nortriptyline 
1. Does patient have prior history (either documented in medical records or by the patient) of non-
response or significant adverse effects with nortriptyline? If so, move to different antidepressant. 
2. Does the patient have poorly controlled blood pressure (systolic ≥ 170 or diastolic ≥ 100) at baseline; 
if so consider fluoxetine or another agent.   
3. Does the patient have cardiac disease (history of myocardial infarction, angina, congestive heart 
failure, arrhythmia, or other heart disease).  If so, consider sertraline, citalopram, or another agent. 
4. Is an electrocardiogram (ECG) required?  It is required in patients who have not had an ECG in the 
past 3 months.  Review an ECG completed in past 3 months with MD investigator. 
5. BP assessment. BP assessed and recorded at study entry (baseline). BP rechecked within the first 1-2 
weeks.  If systolic BP increases ≥ 20 above baseline (or diastolic increases ≥ 10 above baseline), 
notify nurse who in turn will discuss with physician. 
 
Nortriptyline algorithm 
1. Day 0:      Start nortriptyline 25 mg qd. 
2. Week 1:   Call patient; assess side effects and adherence.  Follow blood pressure protocol (with 
reminders if needed) similar to that used for venlafaxine. 
3. Week 4:   Assess PHQ-9, side effects; if inadequate response, increase to 50 mg qd. 
4. Week 8:   Assess PHQ-9, side effects; if inadequate response, consider nortriptyline blood level, 
as well as increase in dose to 75 mg qd.  
5. Week 12:  Assess PHQ-9, side effects; if inadequate response, consider alternative antidepressant. 
6. Month 6:  Assess PHQ-9.  If relapse, consider adjusting or changing antidepressants 
7. Month 9:  Assess PHQ-9.  If relapse, consider adjusting or changing antidepressants 
8. Weaning off nortriptyline. If a medication change is needed do not stop nortriptyline abruptly. 
Decrease to half the patient’s usual dose every 3 days until total daily dose is 25 mg, then 
discontinue. You may start the new antidepressant while weaning the nortriptyline. 
 
ALGORITHM 4.   COMBINATIONS 
1. When to combine:  When patient has had partial response to a given antidepressant, and is 
tolerating it well. 
2. Common combinations 
a. Bupropion:  added to SSRI (or possibly SNRI) 
b. Mirtazapine:  added to SSRI or SNRI 
c. Nortriptyline:  added to SSRI. 
 
REFERRALS TO MENTAL HEALTH 
Indicators for Mental Health Referral 

Page 51 of 56 
 
Study #1212010163 
 
1. Risk of harm to self (suicidal) or others (homicidal) will trigger urgent referral to primary care 
psychologist or suicide prevention coordinator. 
2. Psychiatric comorbidity (e.g., substance use disorder; complex anxiety disorder; etc.) 
3. Patient has many psychosocial issues that may benefit from psychotherapy or counseling 
4. Patient desires psychotherapy or counseling instead of (or in addition) to antidepressants. 
5. Patient requests or desires referral. 
6. Poor responder (see below) to several steps of medication algorithm. 
Poor responder 
1. Mental health referral if all of the following 3 poor responder criteria are met: 
a. PHQ-9 or GAD-7 change from baseline < 5 on 2 consecutive calls 
b. Global depression or anxiety improvement < 4 (“somewhat better”) 
c. Failed adequate trials of 2-3 different antidepressants, singly or in combination 
Study Close-Out 
1. Verify that the patient has an adequate amount of medication until he/she is able to follow-up 
with primary care physician (PCP).   
2. Provide treatment synopsis to primary care physician (with copy to patient), summarizing type 
and dose of medications that patient is on. 

Page 52 of 56 
 
Study #1212010163 
 
Pharmacotherapy for Anxiety 
 
At all stages of anxiety treatment, it is important to discuss a mental health referral,  
since specific types of psychotherapy (cognitive-behavioral therapy for some types of 
anxiety disorders or exposure therapy for other types) may be particularly helpful. 
 
 
Step 1.  SSRI or SNRI Antidepressant * 
Priority  Drug 
Class Efficacy † 
Dose (in mg) 
 
 
 
 
Initial 
Increases 
1 
Sertraline 
SSRI 
Panic, GAD, SAD, PTSD 
50 
100, 150 
1 
Paroxetine 
SSRI 
Panic, GAD, SAD, PTSD 
20 
30, 40 
2 
Venlafaxine 
SNRI 
Panic, GAD, SAD, PTSD 
75 
150, 225 
2 
Escitalopram 
 
Panic, GAD, SAD 
5 
10,20 
3 
Fluoxetine 
SSRI 
Panic, PTSD 
20 
30, 40 
3 
Citalopram 
SSRI 
Panic 
20 
30,40 
3 
Duloxetine 
SNRI 
GAD 
30 
60 
*  For dosing details, see Antidepressant Guidelines on previous pages. 
† Panic = panic disorder; GAD = generalized anxiety disorder;  SAD = social anxiety disorder;   
   PTSD = posttraumatic stress disorder 
 
Step 2.  Benzodiazepines [only if primary care provider and/or mental health concurs] 
Priority  Drug 
Comments † 
Daily 
Dose 
Freq-
uency 
1 
Clonazepam 
Long half-life reduces withdrawal symptoms 
from missed doses. Also, less risk of abuse. 
1-4 mg 
QD-BID 
2 
Lorazepam 
 
4-12 mg 
BID-TID 
3 
Alprazolam 
More risk of withdrawal and abuse. 
2-6 mg 
TID-QID 
• 
Evidence of anxiolytic efficacy for benzodiazepines (BZD) is less than for antidepressants 
• 
What evidence exists is mainly for panic disorder and social anxiety disorder 
• 
If BZD are used, short-term use (≤ 12 weeks) is preferred, while starting an antidepressant 
• 
If used episodically, < 4 days per week use may be associated with less dependence 
 
Step 3 (options) 
• 
Combine an SSRI or SNRI antidepressant with a benzodiazepine 
• 
Combine an SSRI with a tricyclic antidepressant (imipramine or nortriptyline) 
• 
Consider buspirone 15-60 mg qd (BID-TID dosing) – equivocal evidence in GAD 

Page 53 of 56 
 
Study #1212010163 
 
 
 
 
Operating Principles to Guide Clinical Decisions Regarding Treatment Changes for Pain 
 
Principle 
Operational application (including examples) 
1 Concordance 
of criteria 
Confidence in continuing the same treatment, or in making changes, is 
increased when clinical response criteria are concordant (i.e., all or most of 
the criteria show either a poor response or a good response) 
2 Consistency 
of ratings 
Ratings of chronic pain have an intrinsic variability (greater in some patients 
than in others), similar to variability in other chronic psychological 
(depression) and medical (hypertension, diabetes) conditions.  Thus, 
treatment changes are best made when a consistent pattern (e.g., 
repeatedly high pain over several weeks) is documented. 
3 Patient 
preferences 
A “yes” response to criterion 4 (i.e., treatment change desired) will usually 
be honored, particularly if it is concordant with poor response on other 
criteria, and a safe, effective treatment option is available 
4 Adverse 
effects 
Honoring patient preferences must be balanced against potential adverse 
effects (e.g., medication side effects, drug-drug interactions, premature or 
excessive opioid use, high treatment costs, etc.) 
5 Negotiated 
changes 
The pros and cons of treatment changes are ideally negotiated by 
communication between the clinical team and an informed patient.  In 
particular, when clinical response criteria are discordant (e.g., the patient 
desires a treatment change despite low pain interference ratings and/or 
global improvement, or the patient does not desire a treatment change 
despite persistently high pain interference and lack of global improvement), 
reasons for discordance should be probed. 
6 Gradual 
improvement 
Optimizing outcomes in a chronic condition like pain is often an incremental 
rather than immediate process, particularly when sequential treatment 
adjustments and behavioral interventions are required.   
7 Benchmarks 
A partial response in at least 2 of the first 3 clinical response criteria is the 
treatment goal by week 4, and a target response in at least 2 of 3 criteria is 
the goal by week 12. 
 
APPENDIX 3 

Page 54 of 56 
 
Study #1212010163 
 
SUICIDAL IDEATION ALGORITHM  
 
 
S1.  Over the past 2 weeks, have you had thoughts of hurting or harming yourself?   
 
 
0 
NO 
 Done with this section  Go back to remainder of interview 
 
1 
YES  [Continue with S2 below]  
 
99 
DON’T KNOW OR REFUSED TO ANSWER 
[Continue with S2 below] 
 
 
S2.  Have you thought about how you might actually hurt yourself? 
 
 
0  
NO 
 
1 
YES  [How? ________________________________] 
 
99  
DON’T KNOW OR REFUSED TO ANSWER 
 
 
S3.  There’s a big difference between having a thought and acting on a thought.   
       How likely do you think it is that you will act on these thoughts about hurting  
       yourself or ending your life sometime over the next month?” 
 
 
0 
Not at all likely 
 
 
1 
Somewhat likely 
 
2 
Very likely 
 
99  
DON’T KNOW OR REFUSED TO ANSWER 
 
 
S4.  Is there anything that would prevent or keep you from harming yourself?  
 
 
0  
NO 
 
1 
YES  [What? ________________________________] 
 
99  
DON’T KNOW OR REFUSED TO ANSWER 
 
 
S5.  INTERVIEWER: IS THERE ANY SHADED RESPONSE TO ITEMS S2, S3 OR S4? 
 
 
 
0 
NO 
 
1) Complete interview 
 
 
1 
YES   
1) Complete interview 
2) Follow steps on next page 
APPENDIX 4 

Page 55 of 56 
 
Study #1212010163 
 
Action Today 
 For patients with YES on S5 (i.e., a shaded response on prior page to S2, S3, or S4) 
1) Before getting off the phone with the subject: 
a. Ask if he/she has been seen in mental health (psychiatry, psychology, etc.) 
i. Currently (if so, do they have an appointment sometime soon?) 
ii. In the past but not currently 
iii. Never 
b. Note that you would like to review the information with study doctor, and that you 
will call the patient back within the next hour.  Verify the phone number he/she 
will be at for the next hour. 
 
2) Discuss with physician by phone, making calls in following order: 
Order Physician 
Cell 
Pager 
Office  
1 
Kurt Kroenke 
474-5753 
none 
630-7447 
2 
Matt Bair 
287-9469 
310-4058 
988-2058 
3 
Other HSR&D MD 
not applicable 
not applicable 
VA HSR&D 
4 
VA Suicide Resources  see next page 
 
3) Notify Project Coordinator (Erica Evans) who will 
a. Check to see if patient is a CSM intervention group patient.  If so, she will inform 
study nurse, Sharon Weitlauf. 
b. File a copy of this form in the subject’s study file and document the AE and 
follow-up in the the AE spreadsheet. 
c. Note this as either an: 
i. AE (if no same-day mental health referral) 
ii. SAE (if same day mental health referral) 
 
***** See next page for more urgent VA suicide prevention resources ***** 

Page 56 of 56 
 
Study #1212010163 
 
Roudebush VAMC Suicide Prevention Resources 
 
1. On-site  participant is present in our Roudebush VAMC 
a. Suicide prevention coordinators 
Name 
Role 
Office phone 
Pager 
Travis Field 
Suicide coordinator 
988-3213 
310-4202 
Judi Green 
Case manager 
988-3365 
310-4025 
Christina McNeely 
Case manager 
988-4327 
310-4177 
 
b. The current protocol at the VA is to escort the patient to the emergency room.  
 
2. On phone   
a. Ask where patient currently is (what address). 
b. Do warm phone transfer to Suicide Hotline if situation appears urgent (i.e., 
patient is contemplating suicide today). 
 
To Conference: 
• Do not put the caller on hold 
• Push Transfer 
• Dial the extension or outside phone number  
 This puts the caller on hold and they will hear hold music while you are 
able to speak to the person you are eventually transferring to 
• Push Conference 
 All three parties will be able to speak to each other 
• When ready to let the other two parties speak privately, hang up 
• Do not push transfer or conference again 
• If patient hangs up and does not answer when you call back, call 911. 
 
 
 
Phone number for Veteran Crisis Line is 1-800-273-TALK (8255)