Choosing Options for Insomnia in Cancer Effectively (CHOICE): A Comparative Effectiveness Trial of Acupuncture and Cognitive Behavior Therapy
Phase: NA
Conditions: Insomnia, Cancer
Sponsor: Memorial Sloan Kettering Cancer Center

Memorial Sloan Kettering Cancer Center
IRB Number: 16-947 A(5) 
Approval date: 05-Oct-2017 
 
 
 
 
 
PROTOCOL FACE PAGE FOR 
MS K THE RA P E UT IC /D IA GN OS T IC P RO T OC OL 
 
 
Principal Investigator/Department: 
Jun J. Mao, MD, MSCE 
Medic ine/Integrative 
Medic ine 
Co-Principal 
Investigator(s)/Department: 
Ting Bao, MD, DABMA, MS 
Medic ine/Integrative Medicine 
Investigator(s)/Department: 
Katherine Duhamel, PhD 
Allison Applebaum, PhD 
Gary Deng, MD, PhD 
Shelly Latte-Naor, MD 
K. Simon Yeung, PharmD, Lac 
Theresa Affuso, L.Ac Yi 
Chan, DPM, L.Ac 
Jonathan Siman, L.Ac 
Matthew Weitzman, L.Ac 
Yi Lily Zhang, L.Ac 
Irene Orlow, PhD 
Psychiatry & Beh. Sciences 
Psychiatry & Beh. Sciences 
Medic ine/Integrative Medicine 
Medic ine/Integrative Medicine 
Medic ine/Integrative Medicine 
Medic ine/Integrative Medicine 
Medic ine/Integrative Medicine 
Medic ine/Integrative Medicine 
Medic ine/Integrative Medicine 
Medic ine/Integrative Medicine 
Epidemiology/B iostatistics 
Consenting Professional(s)/Department: Jun J. Mao, MD, MSCE 
Ting Bao, MD, DABMA, MS 
Katherine Duhamel, PhD 
Gary Deng, MD, PhD 
K. Simon Yeung, PharmD, Lac 
Stephanie Pearson 
Marci Coleton, MA 
Janice DeRito 
Lauren Piulson 
Jamie Green 
Benjamin Search 
Medic ine/Integrative Medicine 
Medic ine/Integrative Medicine 
Medic ine/Integrative Medicine 
Medic ine/Integrative Medicine 
Medic ine/Integrative Medicine 
Medic ine/Integrative Medicine 
Medic ine/Integrative Medicine 
Medic ine/Integrative Medicine 
Medic ine/Integrative Medicine 
Medic ine/Integrative Medicine 
Medic ine/Integrative Medicine 
 
Participating Institution s 
PI's Name 
Site's Role 
University of Pennsylvania 
Philip Gehrman, PhD CBSM 
Data Collaborator 
Ple ase Note: A Consenting Professional must have completed the mandatory Human 
Subje cts Education and Ce rtification Program. 
 
 
 
Memorial Sloan Kettering Cancer Center 
1275 York Avenue 
New York, New York 10065 
 
 
 
 
 
 
Page 1 of 39 

Memorial Sloan Kettering Cancer Center
IRB Number: 16-947 A(5) 
Approval date: 05-Oct-2017 
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Table of Contents 
 
1.0 
PROTOCOL SUMMARY AND/OR SCHEMA........................................................................3 
 
2.0 
OBJECTIVES AND SCIENTIFIC AIMS .................................................................................4 
 
3.0 
BACKGROUND AND RATIONALE .......................................................................................5 
 
4.0 
OVERVIEW OF STUDY DESIGN/INTERVENTION .............................................................. 8 
 
4.1 
Design..................................................................................................................................8 
 
4.2 
Intervention ..........................................................................................................................9 
 
5.0 
THERAPEUTIC/DIAGNOSTIC AGENTS.............................................................................10 
 
6.0 
CRITERIA FOR SUBJECT ELIGIBILITY.............................................................................11 
 
6.1 
Subject Inclusion Criteria ...................................................................................................11 
 
6.2 
Subject Exclusion Criteria..................................................................................................11 
 
7.0 
RECRUITMENT PLAN .........................................................................................................11 
 
8.0 
PRETREATMENT EVALU ATION ........................................................................................13 
 
9.0 
TREATMENT/INTERVENTION  PLAN .................................................................................15 
 
10.0 EVALU ATION DURING TREATMENT/INTERVENTION....................................................15 
 
11.0 TOXICITIES/SIDE EFFECTS ............................................................................................... 18 
 
12.0 CRITERIA FOR THERAPEUTIC RESPONSE/OUTCOME ASSESSMENT ......................19 
 
13.0 CRITERIA FOR REMOVAL FROM STUDY ........................................................................20 
 
14.0 BIOSTATISTICS ...................................................................................................................20 
 
15.0 
RESEARCH PARTICIPANT REGISTRATION AND RANDOMIZATION PROCEDURES23 
 
15.1 Research Participant Registration .....................................................................................23 
 
15.2 Randomization...................................................................................................................24 
 
16.0 DAT A M AN AGEMENT ISSUES...........................................................................................24 
 
16.1 Quality Assurance..............................................................................................................25 
 
16.2 Data and Safety Monitoring ............................................................................................... 25 
 
17.0 PROTECTION OF HUMAN SUBJECTS..............................................................................26 
 
17.1 Privacy ............................................................................................................................... 27 
 
17.2 Serious Adverse Event (SAE) Reporting ..........................................................................28 
 
17.2.1.........................................................................................................................................29 
 
18.0 INFORMED CONSENT PROCEDURES..............................................................................29 
 
19.0 REFERENCES ......................................................................................................................30 
 
20.0 APPENDICES .......................................................................................................................38 

Memorial Sloan Kettering Cancer Center
IRB Number: 16-947 A(5) 
Approval date: 05-Oct-2017 
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1.0 
PROTOCOL SUMMARY AND/OR SCHEMA 
 
Table 1. Protocol Summary 
Study Title 
CHoosing Options for Insomnia in Cancer Effectively (CHOICE):  A 
Comparative Effectiveness Trial of Acupuncture and Cognitive Behavior 
Therapy 
Primary Objective 
To compare the effectiveness of acupuncture versus Cognitive Behavior 
Therapy for insomnia (CBT-I) and co-morbid symptoms. 
Secondary Objectives To identify patient-level demographic characteristics, clinical factors , and 
psychological attributes, that are associated with improved insomnia at 
post-intervention in acupuncture or CBT-I. 
To understand patients‟ experiences of acupuncture or CBT-I to better 
inform future decision-making, intervention refinement, and treatment 
dissemination. 
Patient Population 
Patients with a diagnosis of insomnia who have completed active 
treatment (surgery, chemotherapy, radiation) for cancer at least one 
month prior to study initiation with no restrictions placed on type of cancer 
or stage. 
Number of Subjects 
40 
Study Design 
Parallel-randomized controlled trial 
Treatment 
Acupuncture delivered by a licensed acupuncturist for a total of 10 
treatments over the course of 8 weeks. 
Cognitive Behavior Therapy for Insomnia delivered by a study therapist 
for a total of 7 sessions over the course of 8 weeks. 
Time to Completion 
Patients will receive 8 weeks of treatment and be followed for 3 months 
post-treatment. 
 
 
Figure 1. CHO ICE Study Schema 

Memorial Sloan Kettering Cancer Center
IRB Number: 16-947 A(5) 
Approval date: 05-Oct-2017 
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ACU (n=20) 
 
 
 
 
 
 
 
CBT-I (n=20) 
 
 
 
 
 
 
 
 
 
This project was initially opened at the University of Pennsylvania Health System (Penn) by the 
principal investigator (Jun Mao, MD, MSCE).  Dr. Mao has changed institutions as of December 7 th, 
2015; he is now at MSK.  As of June 30, 2016, ninety participants were enrolled at Penn.  The 
protocol currently open at Penn will remain open there and will continue to be administered by Penn. 
A separate and parallel protocol will be open at MSK upon MSK‟s IRB approval.  Target enrollment 
at MSK will be 40 patients.  Target enrollment at Penn will be 120 patients.  At the end of the study, 
Penn will send deidentified data and samples to MSK.  The appropriate material transfer and data 
transfer agreements will be executed for this transfer. The datasets will be combined for analysis. 
The funding agency (PCORI), Penn‟s IRB, and their Cancer Center support this plan. Upon MSK‟s 
IRB approval, we plan to enroll 20 patients at MSK in 2016 and another 20 in 2017. 
 
2.0 
OBJECTIVES AND SCIENTIFIC AIMS 
  
To determine which of the treatments (acupuncture or cognitive behavioral therapy for insomnia 
[CBT-I]) is more effective for insomnia (Primary outcome) and co-morbid symptoms (i.e. pain, fatigue, 
and psychological distress) in individuals with cancer. 
 
• Primar y Aim: To compare the effectiveness of acupuncture versus CBT for insomnia and 
co-morbid symptoms. 
 
• Se condary Aim 1: To identify patient-level demographic characteristics (e.g. gender), 
clinical factors (e.g. pain), and psychological attributes (e.g. outcome expectancy), that are 
associated with a better Insomnia Severity Index ( ISI) score at Week 8 (post-intervention) in 
acupuncture or CBT-I. 
 
• 
Se condary Aim 2: To understand patients‟ experiences of acupuncture or CBT-I to better 
inform future decision-making, intervention refinement, and treatment dissemination. 
 
• Exploratory Aim 1: To understand the potential impact of sleep disruption and insomnia 
treatment on memory, attention, and concentration. 

Memorial Sloan Kettering Cancer Center
IRB Number: 16-947 A(5) 
Approval date: 05-Oct-2017 
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• Exploratory Aim 2: To collect biological samples to examine potential biomarkers that are 
associated with sleep disturbance and/or response to insomnia treatment. 
 
3.0 
BACKGROUND AND RATIONALE 
 
Burden of Cancer and Insomnia: Cancer is one of the leading causes of global morbidity 
and mortality, second only to heart disease. 
1 Fortunately, with early detection and treatment 
advances a greater number of Americans will live longer with cancer and many will become 
cancer-free. 1 These improved survival rates mean that more people will require ongoing 
treatment for persistent side effects from cancer and its treatments. Compared with the 
general population, cancer survivors are at a greater risk for chronic physical and 
psychological symptoms. 2,3 Sleep disturbances, primarily in the form of insomnia, are an 
especially important, but frequently overlooked, consequence of cancer. 4,5 Several large- 
scale epidemiological studies demonstrate that close to 60% of people treated for cancer 
experience insomnia. 6,7 Unfortunately, once chronic, sleep disturbances are unrelenting if 
not appropriately treated, and can persist for years or even decades. 
7 Sleep difficulty is one 
of the most frequent reasons that cancer survivors visit their general practitioners and 
corresponds to 7.8 fewer workdays and $2,280 in lost income per person per year. 8,9 When 
patients were asked about the development of their insomnia, most reported that it began 
with, or followed, their cancer diagnosis and that the effects of poor sleep were more 
overwhelming than the effects of cancer treatment. 10 
 
Insomnia and Co-morbid Symptoms: Cancer-related sleep disturbances are particularly 
pernicious because of their negative relationship to psychological health and physical well- 
being. More often than not, insomnia co-exists with pain, fatigue, depression, and anxiety, 
creating a positive feedback loop in which all symptoms are amplified and overall symptom 
burden is increased. In a study exploring the relationships between patient-reported pain, 
fatigue, depressed mood, and difficulty sleeping in 11,445 cancer patients, depressed mood 
significantly increased trouble sleeping, pain, and fatigue levels. 11   Independent of mood, 
trouble sleeping also had a direct influence on pain and fatigue levels. A more recent study 
also investigated the relationships between self-reported sleep difficulty, pain, and emotional 
distress in a sample of 2,862 cancer outpatients. 12   Individuals reporting significant pain were 
2.7 times more likely to experience sleep difficulty than those without pain, whereas people 
with higher levels of emotional distress were 4.5 times more likely to report problems with 
sleep that those with low distress levels. In a prospective study of a heterogeneous sample 
of 828 cancer patients over an 18-month period, those patients with higher levels of insomnia, 
anxiety, depression, and fatigue had significant impairments in functioning and the lowest 
quality of life. 
13 This supports the relationship between disturbed sleep, perceived physical 
functioning, and psychological well-being. Based on these results the use of targeted 
interventions to treat difficulty sleeping and depressed mood would be expected to also 
positively impact pain and fatigue levels. 
 
Nee d for Non-pharmacological Tre atment: Considering the prevalence, significance, and 
impact of insomnia, cancer patients require information about treatment options in order to 

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Approval date: 05-Oct-2017 
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make timely and informed decisions. At present, the treatment for cancer patients with sleep 
difficulties is typically pharmacological. In a sample of 219 women with breast cancer, 46% 
received a prescription for sleeping medication during cancer treatment.14   Although sleep 
medication is only recommended for short-term use, 30% of the original sample was still 
using prescription sleep aids one year following treatment completion. Unfortunately, 
sedative medications can have substantial side effects. Long-term hypnotic use is associated 
with continued sleep difficulty and performance problems, memory disturbances, driving 
accidents, and falls in the general population.15  As such, many patients often prefer non- 
pharmacological interventions to treat insomnia. In a qualitative study conducted by Drs. Mao 
and Barg with White and African American cancer survivors, some patients indicated their 
desire for natural approaches to avoid adding another “toxin” to their body after 
chemotherapy. Others simply wanted to avoid poly-pharmacy given that their many co- 
morbid conditions often require ten or greater medications already.
16  These findings support 
the need for rigorously evaluating the effects of, and patient preferences for, non- 
pharmacological therapies for insomnia and co-morbid symptoms in cancer.Gap in 
Ev idence: Acupuncture and Cognitive Behavioral Therapy for Insomnia (CBT-I) are both 
widely available and commonly used non-pharmacological treatments for insomnia and other 
co-morbid symptoms. Despite a documented preference for non-pharmacological methods of 
treating insomnia, there is currently a gap in the evidence available as to the comparative 
effectiveness of these options. 
17 Some estimates suggest that up to one-third of cancer 
patients use acupuncture to help manage problematic cancer-related symptoms 18 and there 
is increasing evidence for the use and efficacy of acupuncture for the treatment of insomnia. 
19,20 Acupuncture has been shown to affect a number of neurotransmitters and hormonal 
factors known to be involved in sleep regulation, such as serotonin, melatonin, and gamma- 
aminobutyric acid (GABA). 21  A systematic review of 20 randomized controlled trials of 
acupuncture for insomnia suggested that traditional needle acupuncture was slightly more 
effective than benzodiazepines with response rates for acupuncture and benzodiazepines 
being 91% and 75%. 22 Similarly, acupuncture was found to be equally as effective as 
zolpidem for improving sleep in 33 patients with insomnia. 23 Evidence also suggests that 
acupuncture has the potential to repair fragmented sleep architecture and increase time 
spent in slow wave sleep. 
24 While the evidence for the use in insomnia and comorbid 
symptoms is compelling, acupuncture research has also been criticized for having 
substantial poor methodologies such as small sample size, questionable randomization, poor 
reporting, and inappropriate analyses. 25-27 Our study aims to address these methodological 
challenges and provide reliable evidence that patients and providers can rely on.Cognitive 
Behavior Therapy for Insomnia (CBT-I) is a form of CBT specifically for insomnia that 
combines principles from stimulus control therapy (developing a learned association between 
the bed and sleep) and sleep restriction therapy (consolidation of sleep periods through 
buildup of sleep drive) with formal cognitive restructuring (reducing misconceptions about 
sleep) in order to target hyperarousal, dysfunctional behaviors and maladaptive thoughts, 
beliefs, and attitudes associated with insomnia. CBT-I is recommended by the American 
Association of Sleep Medicine as a first line treatment for insomnia,28,29  is considered well 
established by the American Psychiatric Association,30    and has demonstrated efficacy in 
many randomized controlled trials.31-34  A review of studies with clinical samples of individuals 

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IRB Number: 16-947 A(5) 
Approval date: 05-Oct-2017 
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with primary insomnia concluded that CBT-I is a highly effective treatment for sleep 
disturbance and produces significant improvements in a variety of subjective sleep 
components.35  In preparation for this proposal, our team completed a systematic review of 
eight controlled and four uncontrolled trials of CBT-I in cancer patients and concluded that 
CBT-I is associated 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Figure 2. CHO ICE STUDY MODEL 
 
 
with clinically and statistically meani ngful sleep improvements in cancer patients.36 
Recent evidence also suggests that CBT-I is effective in reducing clinical levels of fatigue, 
anxiety, and depression related to cancer treatment. Despite the evidence that CBT- I is an 
effective intervention, there is still a significant proportion of individuals whose insomnia 
does not respond or remit after treatment. In a study comparing CBT-I alone or combined 
with medication, 40% of those randomized to CBT-I did not experience a treatment 
response and 61% still experienced residual insomnia symptoms.34  Considering that 32- 
89% of patients treated with CBT-I (including those with cancer) do not consistently follow 
treatment recommendations,38  poor adherence may be one factor accounting for these 
findings. Additionally, perhaps CBT-I does not adequately, or comprehensively, address 
the multitude of factors that contribute to the development and maintenance of insomnia 
(e.g. autonomic hyperarousal).
39  There is an increasing awareness that not all treatments 
are effective for every person and that treatment decisions should be guided by person- 
level factors such as personal preference. 
40 For behavioral interventions like CBT-I, which 
require a significant investment of time and active participation, patient preference for 
treatment is a particularly important contributor to patient adherence and outcomes. 41,42 
Clearly, there is a need to improve and/or expand the available insomnia treatment 
options. 
 
Rationale for the study: 
• 
We chose to compare acupuncture against CBT-I because CBT-I is the current gold 
standard non-pharmacological intervention for insomnia. 28,29 Our patient stakeholders 
were clear that they preferred non-pharmacological interventions. 
• 
We did not include a usual care or waitlist control because both acupuncture and 

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IRB Number: 16-947 A(5) 
Approval date: 05-Oct-2017 
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CBT-I have already demonstrated superiority over no-treatment control groups. 
Research demonstrating that insomnia is relatively stable once developed 
7 reduces 
the potential for change due to the passage of time alone (maturation) or statistical 
regression towards the mean. 
• 
We have chosen the Insomnia Severity Index 51 as the primary outcome measure 
because it has been validated in cancer populations with excellent reliability and 
validity. The ISI captures the daytime impairment and subjective distress associated 
with insomnia, has clinical cutoffs for symptom severity, and has established minimally 
important change values to ensure that the changes produced are not only significantly 
but also clinically significant to patients. When our patient stakeholders reviewed the 
available options they preferred the ISI because it is short, easy to complete, and has 
face validity. 
• 
We incorporated patient-centered secondary outcomes of pain, physical and mental 
fatigue, anxiety, and depression because these were the areas that our advisory panel 
told us were impacted the most by insomnia symptoms. We also included a measure 
of quality of life in order to capture the potential for insomnia treatment to improve 
overall well-being. 
 
In summary, the proposed study is highly significant in that it is the first rigorously designed 
comparative effectiveness study ever to examine the relative benefits of acupuncture and 
CBT-I. As summarized in the background section, with the help of our patient partners, we 
have built a conceptual model that is grounded in the current scientific understanding of 
acupuncture, CBT-I, and insomnia. It is also the first study to incorporate carefully selected 
social-demographic, clinical, and psychological factors to examine the predictors and 
moderators of treatment effect of both acupuncture and CBT-I. The results of the proposed 
study have the potential to improve healthcare and outcomes by helping cancer survivors 
and their caregivers make informed and evidenc e-based decisions and leading to patient-
centered and individualized care for cancer survivors with insomnia. 
 
 
Role of Patie nt and Stakeholder Adv isory Panel 
 
Our patient advisory panel consists of eight patients, one caregiver, and two representatives 
of cancer support organizations. The panel is diverse in terms of cancer type, stage, age, 
race, sex, educational level and occupational status. The panel helped generate the research 
question, choose the comparison groups, develop patient-centered inclusion and exclusion 
criteria, refine the research protocol, choose the most appropriate outcomes, and decide on 
specific measurement tools. Our patient partners will help to ensure that our research is able 
to engage participants from a diverse audience. W e have created four committees consisting 
of researchers and patient partners with oversight of key research components: recruitment, 
outcomes, interpretation, and dissemination. The research team and patient partners will 
attend bi-annual meetings to review the research progress, develop or revise recruitment and 
engagement strategies, and plan for dissemination efforts. 
 
4.0 
OVERVIEW OF STUDY DESIGN/INTERVENTION 
 
4.1 
Design 
  
We will conduct a parallel-randomized controlled trial to compare the effectiveness of 

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IRB Number: 16-947 A(5) 
Approval date: 05-Oct-2017 
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acupuncture and CBT-I for insomnia and co-morbid symptoms in a heterogeneous sample 
of cancer survivors who have finished primary treatment.  Forty patients will be enrolled in 
this study at MSK.  A parallel study is being conducted at Penn.  Deidentified data from 
the 120 patients enrolled at Penn will be combined with the MSK data for analysis. Eligible 
patients will be randomly assigned to acupuncture or CBT-I. In the acupuncture group, 
patients will receive ten treatments of acupuncture over eight weeks. In the CBT-I group, 
patients will receive seven sessions of CBT-I over eight weeks. Patients will complete 
validated patient-reported outcome (PRO) measures of sleep and co-morbid symptoms at 
baseline, mid-treatment, post-treatment, and at monthly intervals for 3 months to assess 
durability of effect. For the Penn study, to understand patient experience, semi-structured 
interviews will be conducted among 60 patients pre- and post-intervention to elicit their 
experience of their insomnia and cancer, their attitudes, beliefs, and preferences for a 
specific intervention prior to the intervention, as well as explore what influences their 
decision to choose a particular treatment. Structured interviews will not be done as part of 
the MSK protocol.  At the end of intervention, we will elicit both expected and unexpected 
benefits and side effects of treatments, assess changes in patient 
attitudes/beliefs/preferences, and gather recommendations for how to disseminate our 
findings. In keeping with standards for transparent reporting of clinical trials, we will follow 
the CONSORT guidelines for reporting of non-pharmacological treatment interventions  
43 
and the Standards for Reporting Interventions in Clinical Trials of Acupuncture (STRICTA). 
44   In designing the current study we relied heavily on the Effectiveness Guidance 
Document for conducting comparative effectiveness research of acupuncture interventions. 
45 
 
 
4.2 
Intervention 
 
Acupuncture: After the acupuncture evaluation, the acupuncture procedure will be carefully 
explained to each subject. The patient will be positioned in a comfortable position, either in a 
massage chair or lying on an exam table depending upon patient comfort and need for 
access to appropriate acupuncture points. Each acupuncture session lasts approximately 30 
minutes. Licensed acupuncturists will administer acupuncture following the acupuncture 
protocol and procedure (Appendix 1) twice per week for two weeks, then weekly for six more 
weeks, for a total of ten treatments over eight weeks. The first visit to an acupuncturist often 
involves a more detailed history and an examination that takes an additional 30 minutes so 
the total contact time is about 330 minutes. 
 
The FDA classifies acupuncture needles as a Class II medical device for “general acupuncture 
use” by licensed, registered or certified practitioners. The acupuncture groups at each site have 
performed many clinical trials in acupuncture without significant adverse events. 
 
Cognitive Be havior Therapy for Insomnia (CBT -I): CBT-I is a multi-component 
intervention that includes sleep restriction, stimulus control, cognitive restructuring, relaxation 
training, and sleep hygiene (See Appendix 2). Sleep restriction is designed to restrict time 
spent in bed to closely match the time actually spent sleeping. A sleep efficiency percentage 
(the amount of time spent sleeping divided by the amount of time spent in bed) is calculated 
and when the individual is able to achieve 90% sleep efficiency their sleep time is increased. 
This process continues until the person can achieve a restful night‟s sleep with few or no 

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disturbances. Stimulus control is based on the theory that the body eventually becomes 
conditioned to associate the sleep time and setting with arousal (e.g. only go to bed when 
sleepy and refrain from lying awake in bed). This technique is designed to break the 
perpetuating behaviors and re-associate the bed with positive sleep experiences. Cognitive 
restructuring addresses the dysfunctional thoughts and beliefs that serve to maintain and 
exacerbate insomnia. Individuals are taught to monitor these thoughts and beliefs, challenge 
their validity, and replace them with adaptive cognitions conducive to the sleep process. 
Relaxation training targets the physiological and cognitive arousal that accompanies 
insomnia and sleep hygiene promotes healthy sleep behaviors and environmental conditions. 
Study therapists will deliver six weekly sessions of CBT-I for six weeks followed by o ne 
session two weeks later, for a total of seven sessions over eight weeks. The first CBT-I 
session lasts 60 minutes and the remaining sessions last 30 minutes, bringing the total 
contact time to 240 minutes. 
 
Selection of study therapists and their intensive training and supervision have been carefully 
considered. The manualized research intervention for this protocol is highly structured, and 
the session interventionist is provided with an outline of content for all study modules. Study 
therapists will have received specialized training in CBT-I prior to delivery in this study. 
 
Study therapists will at minimum be a doctoral student in Clinical Psychology or have a 
Masters degree in Mental Health Counseling, Social Work, or Psychology to qualify for 
consideration as an interventionist on this study. Clinicians with greater experience and mor e 
advanced skills will also be considered for the interventionist role. We will largely draw from 
our existing pool of experienced therapists (mental health counselors, psychologists, 
psychiatrists, social workers, and advanced psychologist trainees) already trained for our 
ongoing trials. 
 
Supervision and training for CBT-I interventionists will be conducted by Dr. Katherine 
Duhamel and/or Dr. Allison Applebaum, both of whom have extensive training and 
supervision experience in these approaches, and will include both didactic and experiential 
training. At study start-up, intensive training workshops in the delivery of CBT-I will be 
provided, with a focus on the unique issues of cancer survivors. These trainings will focus on 
the acquisition of skills in the conduct of the sessions. All interventionists will be provided 
with a copy of the manual, describing in detail the philosophy, format, and techniques 
involved in the approach. Drs. Duhamel and Applebaum  will lead weekly supervision 
sessions for the different providers. Interventionists will receive intensive supervision, and 
their competency in the approach will be continually assessed. 
 
5.0 
THERAPEUTIC/DIAGNOSTIC AGENTS 
  
The FDA classifies acupuncture needles as a Class II medical device for “general hospital and 
personal use” by licensed, registered or certified practitioners. 
 
Acupuncture Needles Seirin acupuncture needles will be used in this study. The needles 
are purchased and distributed from Seirin® in the United States 

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(http://www.seirinamerica.com). Seirin acupuncture needles are approved by the FDA 
(http://www.accessdata.fda.gov/cdrh_docs/pdf/K962809.pdf). 
 
The acupuncture needles will be inserted 0.5 inch into the skin and will remain in the skin for 
30 minutes at the points noted in Appendix 1. 
 
6.0 
CRITERIA FOR SUBJECT ELIGIBILITY 
 
6.1 
Subject Inclusion Criteria 
 
• 
English-speaking, age ≥ 18 years old 
• 
A diagnosis of cancer with no restrictions placed on type of cancer or stage.  Eligibility 
criteria are not be restricted to MSK confirmed biopsy/diagnosis.  Participating 
institution‟s testing is sufficient for other study sites. 
• 
Completed active treatment (surgery, chemotherapy, and/or radiotherapy) at least one 
month prior to study initiation (patients on continued hormone treatment or maintenance 
targeted therapies will not be excluded). 
• 
A score >7 on our primary outcome (the Insomnia Severity Index) 
• 
A diagnosis of insomnia disorder as defined by the Diagnostic and Statistical Manual of 
Mental disorders, 5th Edition (DSM-5), per the diagnostic interview. According to this 
nosology, insomnia is defined as dissatisfaction with sleep quality or quantity 
characterized by difficulty initiating sleep, maintaining sleep, or early morning awakenings 
that cause significant distress or impairment in daytime functioning and occur at least 
three nights per week for at least three months despite adequate opportunity for sleep. 
• 
Patients using psychotropic medication (e.g. antidepressants) will remain eligible for 
study participation provided that the dose was not recently altered (stable over the 
previous 6-weeks). 
• 
Patients using hypnotics or sedatives will be eligible for study participation. Considering 
the high use of benzodiazepines within the oncology population, past research has 
included participants who met diagnostic criteria for insomnia, despite the use of 
benzodiazepines, and included monitoring of medication use. 
 
6.2 Subject Exclusion Criteria 
 
 
• 
Another sleep disorder, other than sleep apnea, that is not adequately treated. 
• 
Previous experience with CBT or acupuncture to treat insomnia 
• 
Currently participating in another acupuncture trial or a trial to treat insomnia 
• 
The presence of another Axis I disorder not in remission 
• 
Employment in a job requiring shift work that would impair the ability to establish a 
regular sleep schedule 
• 
Patients who are currently taking oral (not including oral sprays/inhalers) or intravenous 
corticosteroids as part of treatment for cancer or any other condition will be excluded 
because of the potential of these drugs to induce insomnia 
 
7.0 
RECRUITMENT PLAN 
 
 
Re cruitment Plan (with Limite d waiver of Authorization) 

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No restrictions are placed on cancer type or stage so all patients with a diagnosis of cancer, 
who completed active treatment, have a diagnosis of insomnia, and meet the remaining 
eligibility criteria will be eligible for participation in the study.  There will be no restrictions 
regarding Service or Clinic.  Potential patients who meet basic eligibility criteria will be 
identified via querying of Dataline at MSK and sent a recruitment letter (See Appendix 6). 
The recruitment letter introduces the study to patients and states that we are conducting a 
study to compare the effectiveness of two non-medication based insomnia treatments for 
individuals diagnosed with cancer and if interested in learning more about the study, the 
patient should contact the research study assistant.  The letter provides patients with an opt- 
out phone number and study e-mail address to contact if they do not wish to participate or be 
contacted further.  We have successfully used this recruitment method  for similar studies.  A 
Dataline query for MSK patients who meet basic eligibility criteria, including having an ICD-9 
coded diagnosis of insomnia after their last treatment date, yielded over 500 patients per 
year for each of the three years queried.  In addition to patients who have been formally 
diagnosed with insomnia, we expect that there will be patients who are experiencing 
insomnia that have not yet been diagnosed and that we will be able to meet our target 
accrual goal of 40 patients at MSK.  We will also be identifying patients that meet basic 
eligibility criteria and report sleep difficulties on the MSK Engage symptom questionnaire 
through a dataline query. 
 
In addition to sending recruitment letters, patients a ls o c an be identified and referred to 
the study RSA for accrual and consent by a member of the patient's treatment team or by 
protocol investigators. T he s t u dy P I a nd o t her m em be rs of t h e r es e arc h t eam 
w i ll r eac h o ut t o c o ll e ag ues a b ou t t he s t ud y a n d pr es e nt at S er vic e 
m eet i ngs , i nc l u di ng B re as t Me dic i ne , G I, Pr os t a te , H e ad a n d N ec k S er v ic es 
an d Ps yc hi a tr y a nd B eh a vi or a l Sc i enc es to in tr od uc e th e s tu d y . Colleagues in 
Survivorship will be informed about the study and recruitment materials will be provided to 
them.  In addition to Integrative Medicine physicians, other Integrative Medicine therapists 
can also refer patients to the study.  St u dy in v es t ig a to rs an d i nt er es t ed c o l l ea gu es 
w i ll b e p ro v id e d w i th s t ud y f l ye rs an d/ or r ac k c ar ds t o p ro v id e t o p at ie n ts 
(Se e Ap p en d ix 7 an d 8 f or a s t u dy f l y er a nd r ac k c a rd ).  Patients may also be 
self-referred or referred by a clinic ian from other hospitals. Information about the protocol 
will appear in lay language on MSK ‟s web site and on clinicaltrials.gov. Printed material 
w ill be posted in clinic areas w here w e have s uccess fully pos ted s tudy materials  for 
other Integrative Medic ine s tudies before (e.g., the Breas t and Imaging C enter, the 
Main Hos pital, Kimm el, and the R oc kefeller O utpatient Pavilion) .  Perm iss ion from 
the c linic sites w ill be obtained be fore pos ting in any loc ation.  Materials will also be 
distributed to potential referral sources who we have worked with on other research studies . 
All study recruitment materials will be submitted to, and approved, by the Institutional Review 
Board.  We have used these recruitment strategies successfully to recruit participants to 
similar studies. 
 
Participants will receive $20 at the first, second, and third evaluation time points with an 
additional $40 for completion of the final assessment (total of $100 per participant). 
Compensation will be in the form of gift cards. 
 
Initial contact with prospective subjects typically will be made by a member of the study 
team. The recruitment process presents no more than minimal risk to patient privacy, and 
minimal PHI will be maintained on screening logs. For these reasons, we seek a (partial) 
limited waiver of authorization to: (1) review medical records to identify potential research 
subjects and obtain information relevant to the enrollment process; (2) converse with 

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patients regarding possible enrollment; (3) handle PHI contained in those records and 
provided by potential subjects; and (4) maintain minimal PHI information in a screening 
log of patients approached. 
 
8.0 
PRETREATMENT EVALUATION 
 
 
Initial Screening: All potential participants will undergo an initial screening with a research 
study assistant (RSA) in person or over the telephone. At this initial contact, the study goals 
and procedures will be explained and the research study assistant will ensure that 
participants meet basic eligibility criteria, including having an insomnia severity score greater 
than 7. 
 
Diagnostic Phone Interview: Interested participants will be scheduled to be interviewed by 
telephone by a trained member of the research staff to complete a diagnostic interview for 
insomnia and confirm inclusion/exclusion requirements.  Research staff conducting the 
diagnostic interview will review with a study investigator, and the study investigator will 
approve the patient‟s insomnia diagnosis per the diagnostic interview conducted with 
research staff. 
 
Confirmed eligible patients will then be scheduled to meet with a trained member of the 
research staff to obtain informed consent and complete the baseline assessment. 
 
Sleep Apnea Screening Protocol: Interested patients will be screened for possible 
obstructive sleep apnea using the Multivariable Apnea Prediction (MAP) form (Appendix 3). 
The Multivariable Apnea Prediction (MAP) Index and computing tools were developed by the 
Human Assessment and Biostatistics Core of the Center for Sleep and Respiratory Biology, 
University of Pennsylvania Medical Center.  A cut off score of 0.50 or greater warrants a 
referral for formal assessment. 
 
Patients with scores of 0.50 or greater will be told that they have symptoms suggestive of 
sleep apnea. We will provide them with a copy of their answers and suggest that they 
discuss it with their family physician. We will recommend that they pursue this first to treat 
their sleep difficulty. If, after treatment, the patient continues to have residual insomnia 
symptoms they will be welcome to participate in the trial. Should the patient not want to 
speak with their doctor about their potential sleep apnea, they will still be able to enroll. We 
will use their MAP score to determine whether it is significantly related to treatment outcome. 
 
 
Base line Asse ssment: After consenting, the patients will complete the baseline assessment 
which includes questionnaires and a blood draw. Please refer to Table 2 for questionnaires 
collected at baseline. Patients who endorsed difficulties with attention, concentration and/or 
memory will also complete the supplementary cognitive measures. Identification of patients 
who have difficulties with attention, concentration and/or memory is by self report in response 
to the question “ Have you experienced any difficulty with attention, concentration and/or 
memory as a result of your cancer treatment and/or insomnia?” At this time, we will assess 
beliefs about insomnia and pre-randomization treatment expectancy using validated 

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measures. Treatment preference will be elicited using the Treatment Acceptance and 
Preference (TAP) instrument with two sequential questions. The first item asks participants to 
indicate whether they have a preference for one of the two treatment options (yes or no). The 
second question asks participants with a preference to indicate which option is the preferred 
choice. The participant will be informed that there are two treatment options under 
investigation and there is an interest in learning about his or her perception of each treatment. 
A verbal description of the ﬁrst treatment option will be read aloud in a slow, clear, and 
unbiased manner and the participant will be asked to respond to the TAP items measuring 
treatment acceptability and preference in relation to the option presented. This process will 
be repeated for the other treatment. The presentation of the treatment options will be 
alternated to prevent sequencing effects.  All participants will then receive the details of their 
treatment group allocation. The RSA will provide participants with two weeks of sleep diaries 
to complete at home. 
 
Blood Draw: In preparation of a future grant submission, blood samples will be collected at 
baseline, at the end of the intervention, and at the final follow up assessment to be banked 
for future correlative studies related to the intervention should we identify any literature 
during the conduct of the trial demonstrating that specific biomarkers are associated with 
symptoms or treatment responses. Patients will be able to opt out of the blood draw or 
provide a saliva sample if desired.  Saliva samples are collected once at baseline.  Samples 
will be stored at -80°C until ready for processing.  (See Appendix 5 for details).  If there is 
anything left over, it will be banked for future use under 06-107. 
 
Table 2. Schedule of Asse ssments and Outcome Measures 
 
 
Instrument 
Base li 
ne 
T0 
We ek 0 
Mid- 
tre atment 
T1 
We ek 44 
Post- 
tre atment 
T2 
We ek 84 
Follow-up 
T3 
1, 4 
We ek 12 
Follow-up 
T4 
1, 4 
We ek 16 
Follow-up 
T5 
We ek 204 
DEM
3
 
X3
 
X3
 
TAP 
X 
TES 
X 
CAM -I 
X 
HAS 
X 
BSR
2
 
X 
X 
X 
BADDS
2
 
X 
X 
X 
NYU-PR
2
 
X 
X 
X 
ISI 
X 
X 
X 
X 
X 
X 
Sleep Diaries 
X 
X 
X 
X 
PSQI 
X 
X 
X 
X 
BPI 
X 
X 
X 
X 
HADS 
X 
X 
X 
X 
MFSI-SF 
X 
X 
X 
X 
PROMIS 
X 
X 
X 
X 
X 
X 

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Blood Draw 
X 
X 
X 
Time to 
Comple te 
45-60 
min 
15-20 
min 
30-45 
min 
5-10 
min 
5-10 min 
30-45 
min 
 
(BADDS)-B rown Attention Deficit Disorder Scale; (BP I) -Brief Pain Inventory; (BSR)-B uschke Selecti ve Remi 
nding Task; (CAM-I)-Causal Attributions of my Insom nia questionnaire; (DEM )-P atient Demographics Form 
(HAS)-Hyperarousal Scale; (HA DS) -Hospital Anxiety and Depression Scale; (IS I) -Insomni a Severity Index; 
(MFSI-SF)-Multidim ensional Fatigue Symptom Inve ntory-S hort Form; (NYU -PR)- New York Uni versity 
Paragraph Recall Test; (PSQI)-Pittsburgh Sleep Quality Index; (PROMIS )-Pati ent Reported Outcomes 
Measurement Informati on System; (TAP) -Treatm ent Acceptability and Preference questionnai re; (TES)- 
Treatm ent Expectancy Scale 
 
1. Can be conducted over the phone 
2. These measures will only be administered with those patients who report difficulty with memory, 
attention, and/or concentration at baseline, and consent to cogniti ve testing. 
3. DEM form includes patient‟s height and weight.  At week 20 patient‟s weight will be re -assessed, 
patient will not be asked to repeat filling out the demographic form. 
4. (+/-) 3 day window 
  
9.0 
TREATMENT/INTERVENTION PLAN 
  
Acupuncture: Licensed acupuncturists will administer acupuncture twice per week for two weeks, 
then weekly for six more weeks, for a total of ten treatments over eight weeks. The first visit to an 
acupuncturist often involves a more detailed history and an examination that takes an additional 30 
minutes so the total contact time is about 330 minutes.  A window of +/- 3 days will be allowed for 
these treatment appointments.  Refer to Appendix 1 for acupuncture protocol. 
 
Cognitive Be havioral Therapy for Insomnia (CBT -I): Study therapists will deliver six weekly 
sessions of CBT-I for six weeks followed by one session two weeks later, for a total of seven 
sessions over eight weeks. The first CBT-I session lasts 60 minutes and the remaining sessions last 
30 minutes, bringing the total contact time to 240 minutes.  A window of +/- 3 days will be allowed for 
these treatment appointments.  Refer to Appendix 2 for CBT-I protocol. 
 
 
10.0 EVALUATION DURING TREATMENT/INTERVENTION 
  
The study schema and study schedule were presented in Section 1.0, Figure 1, and Section 8.0, 
Table 2, respectively. The following questionnaires (Appendix 4) will be collected according to the 
study schedule table. 
 
Primar y Outcome - Insomnia Se verity Index (ISI): We will use patient-reported insomnia severity 
as measured by the Insomnia Severity Index ( ISI) as the primary study outcome. The ISI is one of 
the few well-validated patient-reported outcome measures designed to specifically assess the 
impact on daytime functioning and the amount of associated distress. 47 The ISI includes 7 items that 
are scored on a five-point scale ranging from 0 to 4 with higher scores representing more severe 
insomnia symptoms. The optimal cutoff scores are 0-7 (no clinically significant sleep difficulties, 8-14 

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(sleep difficulties warrant further investigation) and 15+ (presence of clinically significant insomnia). 
47 The ISI has demonstrated internal consistency, reliability, construct validity, specificity and 
sensitivity in a representative sample of 1670 cancer patients. 46 The ISI has established minimally 
important change values to ensure that the change is not only statistically, but also clinically, 
meaningful to patients. 48 A reduction of eight points has been deemed to be clinically significant 
improvement. 48   The ISI has been used in several insomnia trials in cancer survivors and has 
demonstrated sensitivity to change in response to intervention as well as discriminating effects 
between interventions. 
 
Se condary Sleep Outcomes: The Pittsburgh Sleep Quality Index (PSQI) was specifically designed 
for use in clinical populations to assess seven component scores (subjective sleep quality, sleep 
latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of sleeping medication, 
and daytime dysfunction) and a global score. It consists of 19 self-rated questions that are scored on 
a 0 to 3 scale over a period of one month. It has sensitivity and specificity in distinguishing good and 
poor sleepers. Acceptable measures of internal homogeneity, consistency (test-retest reliability), and 
validity have been demonstrated. 50,51 
 
The Consensus Sleep Diary (CSD) provides a night-by-night, self-report of sleep duration, disruption, 
and perceived quality and will be used to capture more subtle variations in sleep. The sleep diary will 
be used to calculate sleep efficiency, sleep-onset latency, wake after sleep onset, total sleep time, 
time in bed, number of awakenings, sleep quality, and terminal wakefulness. Sleep diaries are 
considered a reliable and valid patient report of nightly insomnia symptoms. 
52   Participants will 
complete the sleep diary daily throughout treatment. 
 
Se condary Comorbid Symptom Outcomes: 
Brief Pain Inventory (BP I): An 11-item pain assessment tool for use with cancer patients. 
53 The BPI 
measures both the intensity of pain (sensory dimension) and interference of pain in the patient's life 
(reactive dimension). It also queries the patient about pain relief, pain quality, and patient perception 
of the cause of pain. The BPI has a total score and two subscales, pain severity and pain 
interference. The psychometrics of the BPI is well-established with Cronbach‟s alpha ranging from 
0.77 to 0.91. 
 
Hospital Anxiety and Depression Scale (HADS): A 14-item, self-rated instrument for anxiety (7 items) 
and depression (7 items) symptoms in the past week and has been extensively used in people with 
cancer. 54 Established cutoffs for the depression and anxiety scales are independent and are: 0–7 
not significant; 8–10 subclinical; and 11-21 clinically significant depression/anxiety. 
 
Multidimensional Fatigue Inventory-Short Form (MFS I-SF): A 30 item self-report measure comprised 
of five subscales (general, emotional, physical, mental, vigor) and a total fatigue score. Internal 
consistency ranges from 0.87 to 0.92 with test-retest reliabilities ranging from 0.51 to 0.70. The 
MFSI-SF has demonstrated appropriate convergent and discriminant validity. 55   We chose MFSI-SF 
over the Brief Fatigue Inventory 
56 based on feedback from our patient partner advisory panel that 
mental fatigue was a unique and important consequence on insomnia that was not adequately 
captured by the other measurement tools. 

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Patient Reported Outcomes Measurement Information S ystem – Global Health Scale (PROMIS- 
GHS): The 10-item Patient-Reported Outcomes Measurement Information System Global Health 
Scale (PROMIS® Global 10) was used to assess key HRQOL domains including pain, fatigue, 
mental health, physical health, social health, and overall health. Prior psychometric work suggests 
the presence of two 4-item factors: global physical health (overall physical health, physical 
functioning, pain, and fatigue) and g lobal mental health (quality of life, mental health, satisfaction 
with social activities, and emotional problems) 57. The physical and mental health summary scores 
will be scored according to PROMIS® instructions and transformed to T-score distributions with a 
mean of 50 and SD of 10. The PROMIS® T-score metric was set on the basis of a sample that is 
representative of the U.S. adult population. Higher PROMIS® scores represent better 58 
 
Asse ssment of Potential Mediators of Outcome 
Treatment Acceptability and Preference (TAP): This measures patient acceptability and preference 
for treatment and is based on the methodology used by Sidani et al. 59 The speciﬁc attributes 
included in the TAP are: (a) appropriateness (i.e. the treatment option seems logical for addressing 
insomnia); (b) suitability to individual lifestyle; (c) effectiveness in managing insomnia; and (d) 
convenience, operationalized as willingness to apply and adhere to the treatment. Each of the four 
attributes are rated on a 5-point scale ranging from „not at all‟ (0) to „very much‟ (5), with higher 
scores indicating that the treatment option is perceived as appropriate, suitable, and effective, and 
that the participant would be willing to adhere to it. A total score is computed as the mean of the four 
items‟ scores to reflect overall acceptability. This method of eliciting treatment acceptability and 
preferences was well received by patients and has established internal consistency reliability and 
factorial validity. 59  An outcomes panel of the patient advisory group has agreed to assist 
researchers to generate a brief description of the treatment‟s purpose, components and specific 
activities, role of provider, schedule (number of sessions, frequency, and mode of delivery), benefits, 
and risk of discomfort to ensure that the information is presented in a non-technical, clear and simple 
to understand manner at a 6th grade reading level. 
 
Causal Attributions of my Insomnia Questionnaire (C AM- I): This is a 12 item self-report measure that 
presents 12 domains often attributed to contribute to insomnia. 
60 These include: sleep related 
thoughts, hormonal factors, bodily arousal, genetic factors, lifestyle factors, thinking patterns, 
biochemical factors, environmental factors, scheduling, sleep-related emotions, other emotions, and 
developmental factors. The questions are rated on a 7-point Likert scale with three anchors, „very 
likely,‟ „neither likely nor unlikely,‟ and „very unlikely.‟ Responses on the CAM-I have been 
associated with preference for psychological or biological treatment options. This measure will be 
particularly important to determine the relative importance or impact of patient beliefs about 
insomnia on treatment outcome. Each item is assessed separately. 
 
Treatment Expectancy Scale (TES): A 4-item instrument developed by Mao (PI) et al. Outcome 
expectancy has long been considered an important predictor of treatment outcomes 61 and has 
gained important consideration in acupuncture in recent years. 
62   It has demonstrated reliability 
(Cronbach‟s α of 0.82) and validity and is positively c orrelated with patient self-reported efficacy and 
satisfaction. 
63 The TES has also been validated in breast cancer survivors and is sensitive to 
change over time in response to acupuncture treatment. 64  In our previous study, we found 
expectancy was stable overtime in the waitlist control group. 65 Baseline expectancy predicted 

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Approval date: 05-Oct-2017 
Page 18 of 39 
 
 
 
 
 
treatment outcomes of acupuncture. We will modify the TES for CBT by changing the word 
“acupuncture” to “Cognitive Behavioral Therapy.” A single total score is calculated. 
 
Hyperarousal Scale (HAS): A 26 item measure of self-reported behaviors commonly exhibited in 
individuals with insomnia and has been validated against objective measures of EEG arousal. 66 
Items are rated on a four point Likert scale ranging from „0-not at all‟ to „3-extremely.‟ Considering 
that insomnia is characterized by 24 hour hyperarousal in which perceived stress can initiate and 
maintain sleep difficulty in patients with pre-existing levels of elevated emotional, cognitive, and 
physiological arousal,6 7,68 it is relevant to determine how levels of hyperarousal may impact 
treatment outcomes. A single total score is provided. 
 
Cognitive Measures: 
Brown Attention Deficit Disorder Scale (BADDS): The BADDS is a 40-item scale that measures a 
range of symptoms related to attention. The items are scored on a 4-point scale (0 = never, 1 = once 
a week or less, 2 = twice a week, 3 = almost daily) and are grouped into five subscales: 1 
(Organizing and Activating to work), 2 (Sustaining Attention and Concentration), 3 (Sustaining 
Energy and Effort), 4 (Managing Affective Interference), and 5 (Utilizing Working Memory and 
Accessing Recall). A total score is also calculated. The BADDS has been used to assess attention in 
peri- and post-menopausal women and has demonstrated sensitivity to change. 
69
 
 
Buschke Selective Reminding Test (BSR): The BSR is a validated measure of memory retention and 
retrieval. Subjects are read a list of 16 words and asked to recall as many as possible in a total of 6 
trials immediate recall) and 20 minutes after completion of the sixth trial (delayed recall). Words are 
substituted from a standard set so that each word list is completely different each assessment time. 
The Total Recall is the sum of Short-term Recall and Long-term Recall. Performance on the 
Buschke was previously found to vary by age and impairment status. 
70,71 
 
New Yor k University Paragraph Recall (NYU-PR): The NYU-PR test is a verbal memory measure 
that is one component of the Guild Memory Test. 72 It consists of a short paragraph presented 
verbally and measures encoding of contextual information. Participants are asked to recall the 
paragraph verbatim following immediate and 30-minute delays. No credit is given for gist responses. 
Scores range from 0–21 on both immediate and delayed portions of the test. Alternate forms are 
used to avoid practice effects on re-testing. 73 
 
Blood Samples: Samples will be labeled with the subject‟s study ID, the date that the sample was 
drawn and type of the blood sample. The laboratory technicians will keep a log with the specimen 
information, conditions, processing, and storage information. 
 
11.0 TOXICITIES/SIDE EFFECTS 
 
Pote ntial Risks: Patients will be monitored for side effects at each visit. Adverse effects related to 
the administration of acupuncture or CBT-I will be collected each week before and after each 
treatment by the acupuncturist/therapist or research study assistant. 

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Although the risks associated with participation in the proposed study are minimal, all potential risks 
that might occur as a result of participation will be detailed in an informed consent form, and will also 
be fully discussed with each subject prior to enrollment. It will be further explained that while some 
risks are not predictable, every precaution consistent with the best medical practice to protect the 
health and safety of subjects will be taken. We will document all adverse events and report any 
related serious adverse events promptly to the IRB. 
 
Risk of Acupuncture and CBT-I: The risks associated with acupuncture and CBT-I are minor, and 
there are very few serious side effects. The most common side effects of acupuncture are mild pain 
on insertion of the needle, occurring at rates twice that of the placebo group. There is a possibility of 
a small amount of bleeding or bruising and very rarely infections at the site of insertion. Every effort 
will be made to ensure the safety and comfort of the research subjects, including wiping the needli ng 
site with alcohol before the procedure and wiping the needling site with sterile gauze. The most 
common side effects of CBT-I are short-term (less than 2 weeks) increases in daytime sleepiness 
and mood disturbance. The acupuncture and CBT-I will be delivered by experienced professionals 
under the supervision of senior faculty psychologists . Every effort will be made to ensure the safety 
and comfort of the research subjects. Adverse events will be recorded during each clinical visit.  Any 
SAEs will be reported to the IRB within 5 calendar days of the event. 
 
Risk of Blood Draw: A small number of people find blood draws very uncomfortable. Risks and 
discomforts involved in having blood drawn are pain and bruising where the needle enters the skin 
and the possibility of infection or fainting. Standard of care procedures will be followed to minimize 
these risks. 
 
Confidentiality Risks: Information about study subjects will be kept confidential and managed 
according to the requirements of the Health Information Portability and Accountability Act (HIPAA). 
The paper data files will be kept in locked cabinets and electronic files will be kept in password 
protected computers. The data will be disclosed to the IRB upon request for regulatory and data 
safety monitoring. Secondary use of the data will not be attempted after the study ends without 
subsequent IRB approval. 
 
Risk of psychological distress: It is possible that subjects may be upset to find out that they are 
randomized to their non-preferred arm of the study. With appropriate consent and the debriefing 
process, such risks are minimized. Subjects will be informed that they are participating in an 
experimental study to determine the comparative effectiveness of acupuncture or CBT for insomnia. 
They have the chance to be randomized to either intervention. At the end of the study, subjects will 
be offered the opportunity to discuss the findings with the PI. In addition, some of the questions in 
the questionnaire may elicit distress among subjects. At the baseline examination, patients will be 
screened for any elevated anxiety and depression or suicidal ideation/plan. If the subject 
demonstrates clinically significant distress, she/he will be referred to the psychosocial counseling 
services at each study site. During the study period, if the research staff identifies any patients who 
are psychologically distressed they will notify the study PI immediately to facilitate appropriate 
evaluation and treatment. 
 
12.0 CRITERIA FOR THERAPEUTIC RESPONSE/OUTCOME ASSESSMENT 

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Our primary outcome measure is the Insomnia Severity Index (ISI), which will be measured at 
baseline, mid-treatment, post-treatment, 1-month, 2-month and 3-month follow-up visits. Our 
hypothesis is that between Acupuncture and CBT, one treatment will result in greater overall 
reduction in insomnia measured by the ISI. Our secondary outcomes will be measured by Brief Pain 
Inventory (BPI), Brief Fatigue Inventory (BFI), Hospital Anxiety and Depression Scale (HADS) (see 
Section 10.0), etc. Our hypothesis is that between Acupuncture and CBT-I, one intervention will 
result in greater improvement in pain, fatigue, and psychological distress than the other intervention 
for patients reporting insomnia. 
 
13.0 
CRITERIA FOR REMOVAL FROM STUDY 
 
Any subjects experiencing a serious adverse event felt to be related to study intervention will be 
withdrawn from the study. Subjects will be withdrawn if they miss two consecutive acupuncture or 
CBT-I visits without notification of study staff, or if discontinuation from the study is deemed by the 
principal investigator to be in their best interest. Sometimes, cancer patients have unexpected 
medical visits or family events, if they miss two visits , but let study staff/PI know, we can 
reschedule their visits.  Based on our experience doing these types of interventions, as long as 
patients get adequate sessions of treatments, their therapeutic outcomes should be optimal.  Any 
subject withdrawing their consent to participate in the study or their authorization to use their 
protected health information will be withdrawn from the study. Subjects discontinued from the 
clinical trial will be scheduled for a final evaluation and given appropriate treatment referrals. For 
the final visit, subjects will receive all assessments that were scheduled for the end of study visit. 
 
 
Subjects will be informed at the consent session that treatment may be discontinued due to: 
 
1)  Intolerable side effects (side effects felt by the patient, therapist, acupuncturist or physician to 
be of greater severity than the potential benefit from treatment); 
2)  Failure to attend 2 consecutive acupuncture or CBT-I visits without notification of study staff; 
3)  Failure to complete questionnaires. 
 
 
If patients fail to attend sessions with notification, every effort will be made to reschedule the patient 
such that they can receive the maximum number of treatments. 
 
Reasons why subjects are discontinued from the clinical trial will be documented on the Study 
Termination Form, along with any referrals that are made.  Every effort will be made to continue to 
collect data on every subject for the entire study duration regardless of whether or not the subject 
continues to adhere to the study interventions, assuming the subject has not withdrawn his/her 
authorization to obtain such information. 
 
14.0 
BIOSTATISTICS 
Quantitative Data Analysis Plan 
De -Identified data and biospecimens from the University of Pe nnsylvania study will be 
submitted to MSKCC to combine databases for our final dataset. 

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Descriptive Statistics: Standard descriptive statistics will be used to report baseline participant 
characteristics. Summary statistics such as means, medians, standard deviations, and ranges will 
be produced for measured variables. Frequencies will be tabulated for categorical and ordinal 
variables. Graphical methods will be used extensively to examine distributions, identify potentially 
influential points, and guide data transformations if warranted. For continuous variables with 
markedly non-normal or skewed distributions, appropriate transformations may be required, such as 
natural logarithms, and will be applied as necessary and appropriate. In the sections below, we will 
assume, when discussing particular outcomes, that the appropriately transformed variables will be 
used. We will perform analysis according to the intention-to-treat (ITT) principle (i.e. participants will 
be analyzed according to the treatment group to which they will be randomly allocated regardless of 
drop-out or treatment adherence status). 
 
Primary Aim Hypothesis Testing: To evaluate the comparative effectiveness of acupuncture vs. 
CBT-I for insomnia and comorbid symptoms.  Primary Hypothesis: Between Acupuncture and CBT-I, 
one treatment will result in greater overall reduction in insomnia measured by the Insomnia Severity 
Index (ISI). The primary endpoint is ISI at week 8. The primary comparison will be ISA difference 
between groups at week 8. We will use mixed-effects models and will include ISI measures at all 
time points to address this primary hypothesis. Time by treatm ent interaction will be included in the 
mixed-effects models in order to obtain the between group difference of ISI at week 8.  Secondary 
Hypothesis: Between acupuncture and CBT, one intervention will result in greater improvement in 
pain, fatigue, and psychological distress than the other intervention for patients reporting insomnia. 
Since our primary outcome (ISI) will be repeated over time, we will use mixed-effects models to 
examine the primary hypothesis. 74 This statistical procedure takes into account within-subject 
correlations from repeated measurements in the same subjects and allows estimation of between- 
group difference without necessitating last observation carried forward or exclusion of participants 
with missing data. Tests of ITT differences between intervention arms with respect to change of ISI 
will be based on time-intervention interactions in the mixed-effects models. Although randomization 
theoretically balances the potential confounders between treatment groups, occasional unequal 
distribution can be seen. Should this happen, we will perform sensitivity analyses to evaluate the 
effect of confounding by including the potential confounders as co-variates in the models. 75 For 
secondary and exploratory hypotheses, we will use similar analytical strategies co-morbid symptoms 
(pain, fatigue, anxiety and depression), QOL, and cognitive dysfunction. 
 
 
Missing Data: As the only certain way to avoid biases from missing data is to collect complete 
data,76  our first line of defense will be to minimize the occurrence of missing observations, using 
well-constructed study design with patient input, well-trained research staff and acceptable subject 
burden,77  as demonstrated by our preliminary data. 78 We have and will continue to engage our 
patient partners to help us understand the clinical trial experience from the patient perspective and 
decrease the barriers to recruitment/retention by providing treatment at convenient time for the 
patient. Next, we will ask those who would potentially withdraw from intervention to continue to 
provide data and reimburse them for completing the evaluation. Lastly, for those who voluntarily 
withdraw from the study, we will record their reasons for withdrawing and use this information in the 
sensitivity analyses. Because missing data is inevitable in a prospective study like this, our second 
line of defense is to apply data analysis strategies that are as robust as possible to data losses. No 

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universal method exists for handling missing data in clinical trials. 76 We will perform sensitivity 
analyses to evaluate the robustness of our results. Initially, we will perform compete-case analysis 
(participants with missing data are simply excluded from the analysis). We will then apply single 
imputation methods such as last-observation and baseline carry forward analyses. Lastly, we will 
perform multiple imputation analyses. When estimating models by maximum likelihood, inferences 
retain their validity under the assumption of missing at random (MAR), which asserts that the 
probability an observation is missing, given all the observed data items, does not depend on the 
value of the potentially missing data item. This is a weaker assumption than missing completely at 
random (MCAR), which is the broadest general sufficient condition for validity of inferences in 
frequentist analysis methods. While it is generally impossible to test whether MAR is a valid 
assumption, one can readily assess the sensitivity of maximum likelihood estimates to departures 
from MAR using the Index of Sensitivity to Nonignorability (ISNI), a class of methods developed by 
Heitjan et al. 
79,80 These sensitivity analyses will not replace the primary findings of ITT, but will 
enhance the understanding/interpretation of our data. Patient partners will be engaged as we 
present our primary and secondary analyses to ensure our interpretation of data remains patient- 
centered. 
 
Secondary Aim: Heterogeneity of treatment effect (HTE): We will conduct HTE analyses to 
identify patient-level demographic characteristics (e.g. sex 81 ), clinical factors (e.g. pain, 82   time 
since diagnosis, time since cancer therapy completion), and psychological attributes (e.g. preference 
and expectancy 41 ) that are associated with improved ISI scores at Week 8 in acupuncture or CBT-I. 
To be specific, factors that predict better outcomes regardless of treatment assignments are 
considered predictive factors. Factors that predict outcomes for one treatment (e.g. acupuncture), 
but not the other (e.g. CBT- I) are considered prognostic factors. 83   In a clinical trial such as ours, 
continuous outcomes provide the greatest statistical power to detect an effect, especially potential 
effect modification between baseline characteristics and treatment groups; however, our patient 
partners suggested that this may not be as patient centered or as clinically meaningful as using a 
dichotomous outcome of treatment response. In reviewing the literature 34   and, consulting with 
patient partners, we will define treatment responders as those patients with an ISI change score 
compared to baseline of >8 points. We will consider participants to be remitted from their insomnia if 
their absolute ISI score is <8. We intend to approach the evaluation of HTE based on existing 
literature and patient/clinician input as well as important knowledge gained from the qualitative study. 
Our current focus of evaluating and reporting HTE will be based on the approach proposed by Kent 
et al.84 Based on the conceptual model, past literature, and patient input, we are going to select four 
actionable variables as primary subgroup analyses. These variables are gender, presence of pain at 
four or greater, outcome expectancy, and preference score. The rest of the sub-group analyses will 
be exploratory and these will include socio-demographic (e.g.  age, race/ethnicity, education, and 
marital/partner status), clinical (time since diagnosis, time since cancer therapy completion, 
insomnia severity, depression, anxiety, fatigue, and sleep apnea symptoms), and psychological 
(insomnia beliefs, hyperarousal) factors. 
 
We will carefully examine the data descriptively stratified by sub-groups using tables and appropriat e 
graphs. Logistic regression will be used to examine predictors of treatment response. We will initially 
examine the main effect of key patient characteristics associated with the dependent outcome. Then 
we will test whether specific characteristics will interact with treatment groups (acupuncture vs. CBT) 

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in impacting outcomes by adding an interaction term. Once we have done preliminary analyses, we 
will bring in patient partners for a data analyses and interpretation meetings to maximally incorporate 
their perspective as we interpret the statistical outputs. Subgroup analyses and HTE is an area of 
uncertainty in clinical research 85,86 without clear guidelines. 87 However, by pre-specifying primary 
subgroup analyses and using multivariate regression modeling with interaction terms, we w ill 
minimize the possibility of false positive results. 84,88,89  As we publish our results, we will caution 
readers/patients that these are exploratory and require caution in interpretation. With that 
acknowledged, the HTE is probably the most patient-centered given that patient will have a more 
nuanced perspective whether for his/her type of person, one treatment will be more effective than 
the other. As we conduct this research, we will learn together with our patient-partners to develop 
more matured methodologies to guide future patient-centered outcomes comparative effectiveness 
research. 
 
Sample Size Considerations: Our sample size is based on our primary hypothesis and primary 
outcome of Insomnia Severity Index (ISI). Since the ISI is a continuous outcome, we powered our 
trial using independent t-test for score at the end of Week 8. This is a conservative way to estimate 
sample size since the longitudinal analysis using the mixed-effects model specified in the analysis 
plan will provide higher power than a t-test. Based on our preliminary research with CBT-I in cancer, 
ISI score decreased from baseline 17.8 to 8.3 with SD of 3.7 at end of CBT-I treatment. 90 If we 
hypothesize that the post-treatment effect difference between acupuncture and CBT-I is 1.85 (0.5 
SD of observed ISI in CBT-I group), this will provide a Cohen‟s d of 0.5 (moderate effect size). We 
estimated that the difference between the two treatments would be half of the effect observed for 
CBT-I alone which would provide adequate strength to detect a difference between the two groups. 
Sample size was not based on what has been considered a clinically meaningful change within 
groups (e.g. and 8 point reduction).  With power of 0.8 and two-sided alpha of 0.05, we will need 64 
participants per treatment group and 128 in total to detect this effect size of 0.5. Accounting for a 20% 
potential attrition, we will need to enroll 160 participants to reach our recruitment target. We 
accounted for attrition in sample size calculations because our sample size calculation was based 
on complete data and was a conservative estimate. In the actual analysis, we will use all patient 
data including patients without complete data according to ITT principle. Based on discussion with 
our patient partners, insomnia and co-morbid symptoms are highly subjective and patient preference 
plays a key role in choosing what therapies they would like. We feel that a moderate effect would be 
required to influence patients‟ pre-treatment preference of acupuncture or CBT-I. If acupuncture is 
only slightly better than CBT-I with very small effect size, it is unlikely a patient would choose 
acupuncture over CBT-I even knowing that acupuncture will produce a small benefit if a patient‟s 
prior preference is CBT-I. With that stated, our research might miss detecting small effects between 
acupuncture and CBT-I. For our secondary aim, since the sample size is fixed, the effect size of sub- 
group analyses will be determined by the distribution of predictors and outcomes from the trial. 
Before approaching sub-group analyses, we will perform effect size estimations. These analyses will 
be conducted in conjunction with the stratified qualitative data interpretation to explore important 
sub-group differences that can guide future research, clinical innovation, and personalized care. 
 
15.0 
RESEARCH PARTICIPANT REGISTRATION AND RANDOMIZATION PROCEDURES 
 
15.1 
Re search Participant Re gistration 
 
Confirm eligibility as defined in the section entitled Criteria for Patient/Subject Eligibility. 

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Obtain informed consent, by following procedures defined in section entitled Informed 
Consent Procedures. 
 
During the registration process registering individuals will be required to complete a protocol 
specific Eligibility Checklist. 
 
All participants must be registered through the Protocol Participant Registration (PPR) Office 
at Memorial Sloan Kettering Cancer Center. PPR is available Monday through Friday from 
8:30am – 5:30pm at 646-735-8000. Registrations must be submitted via the PPR Electronic 
Registration System (http://ppr/).  The completed signature page of the written consent/RA or 
verbal script/RA, a completed Eligibility Checklist and other relevant documents must be 
uploaded via the PPR Electronic Registration System. 
 
 
 
15.2 
Randomization 
 
 
Randomization for the full sample size (n=160) was already prepared by the University of 
Pennsylvania with a randomization list for 200 treatment assignments if necessary.  MSKCC 
participants will be taking the 40 randomization slots (121-160) and will be allocated as per those 40 
slots (20 acupuncture slots and 20 CBT-I slots are identified in these randomizations).  Patients will 
be blinded to randomization until completion of baseline questionnaires. 
 
16.0 
DAT A M AN AGEMENT ISSUES 
 
The Research Study Assistant will be responsible for project compliance, data collection, 
abstraction and entry, data reporting, regulatory and quality control monitoring, problem 
identification and prioritization. Coordination of study team activities will be the responsibility 
of our Research Supervisor and/or Research Manager. 
 
All data and forms gathered for this study will be collected and stored in a secure location in 
the facilities of the Integrative Medicine Service. The data collected for this study will be 
entered into a secure database (CRDB), a study Excel database and into  study Access 
Databases. Source documentation will be available to support the computerized patient data. 
The confidentiality of patient information will be carefully protected. Following data entry by 
Integrative Medicine Service research staff, data will be maintained in a secure location in 
the Integrative Medicine offices. 
 
The questionnaires that patients fill out for this protocol will not be IRB stamped 
documents.  The questionnaires will not be changed from their IRB stamped counterparts, 
but in order to use these questionnaires, we need to have them in Microsoft Word 
format.  The software (AutoData Scannable Office) we will use takes these Microsoft Word 
documents, and prints them with a patient specific barcode at the bottom.  After the patient 
fills it out, the original questionnaire can be scanned into this software, and the software 
reads and records the patients answers in a Microsoft Access database, where the data will 
ultimately be stored. 

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16.1 
Quality Assurance 
 
Weekly registration reports will be generated to monitor patient accruals and completeness of 
registration data. Routine data quality reports will be generated to assess missing data and 
inconsistencies. Accrual rates and extent and accuracy of evaluations and follow-up will be 
monitored periodically throughout the study period and potential problems will be brought to the 
attention of the study team for discussion and action. Random -sample data quality and protocol 
compliance audits will be conducted by the study team, at a minimum of two times per year, more 
frequently if indicated. 
 
 
16.2 
Data and Safety Monitoring 
 
The Data and Safety Monitoring (DSM) Plans at Memorial Slo an-Kettering Cancer Center were 
approved by the National Cancer Institute in September 2001. The plans address the new policies 
set forth by the NCI in the document entitled "Policy of the National Cancer Institute for Data and 
Safety Monitoring of Clinical Trials" which can be found at: 
http://cancertrials.nci.nih.gov/researchers/dsm/index.html. The DSM Plans at MSK were established 
and are monitored by the Office of Clinical Research. The MSK Data and Safety Monitoring Plans 
can be found on the MSK Intranet at: http://mskweb2.mskcc.orglirb/index.htm 
 
There are several different mechanisms by which clinical trials are monitored for data, safety and 
quality. There are institutional processes in place for quality assuranc e (e.g., protocol monitoring, 
compliance and data verification audits, therapeutic response, and staff education on clinical 
research QA) and departmental procedures for quality control, plus there are two institutional 
committees that are responsible for monitoring the activities of our clinical trials programs. The 
committees: Data and Safety Monitoring Committee (DSMC) for Phase I and II clinical trials, and the 
Data and Safety Monitoring Board (DSMB) for Phase III clinical trials, report to the Center's 
Research Council and Institutional Review Board. 
 
During the protocol development and review process, each protocol will be assessed for its level of 
risk and degree of monitoring required. Every type of protocol (e.g., NIH sponsored, in-house 
sponsored, industrial sponsored, NCI cooperative group, etc.) will be addressed and the monitoring 
procedures will be established at the time of protocol activation. 
 
In addition to MSK‟s DSM, this study also has an independent Data and Safety Monitoring Board 
(DSMB) which was required by the funding agency PCORI. This DSM will monitor the Penn site.  In 
order to assess possible changes in risk/benefit ratio to study subjects and to obtain independent 
oversight of the study conduct (including review of the consent form , protocol, subject requirement 
and retention, AE reporting, SAE reporting, procedures for handling patients who have symptom 
worsening), external safety monitors will be invited to oversee the progress of the study: (1) Roger 
Cohen, MD, Professor of Medicine, Division of Hematology-Oncology, Department of Medicine, 
Perelman School of Medicine, University of Pennsylvania, (2) Tavis Campbell, PhD, Professor of 
Psychology, Department of Psychology, University of Calgary, and, (3) Sarah Ratcliffe, PhD, 
Associate Professor of Biostatistics, Center for Clinical Epidemiology & Biostatistics at the University 

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of Pennsylvania. These DSMB members will review and monitor the study procedures, study risks, 
risk/benefit ratio, patient enrollment, and any study-related SAEs. All SAEs will be reviewed by the 
DSMB members in order to determine whether additional safety measures should be initiated, or 
whether there is a change in the risk / benefit ratio for study subjects. External DSMB oversight and 
study review will be conducted at 6-month intervals between the PI and DSMB members by direct 
meetings or by regular teleconferencing and e-mail correspondence. It is expected that the DSMB 
experts will be available to the PI and other study personnel regarding emergency issues , changes 
in research design, and for other regulatory and clinical questions. 
 
 
 
17.0 
PROTECTION OF HUMAN SUBJECTS 
 
Pote ntial Risks and Protection against Risks (See Se ction 11.0 Toxicity/Side Effe cts): 
 
Although the risks associated with participation in the proposed study are minimal, all potential risks 
that might occur as a result of participation will be detailed in an informed consent form, and will also 
be fully discussed with each subject prior to enrollment. We will also explain to each subject that in 
the unlikely event of physical injury directly resulting from the research procedures, every effort will 
be made to make available the facilities and professional skills of MSK. It will be further explained 
that while some risks are not predictable, every precaution consistent with the best medical practice 
to protect the health and safety of subjects will be taken. We will document all adverse events and 
report any serious adverse event promptly to IRB and DSMB. 
 
Risk of Acupuncture and CBT-I: The risks associated with acupuncture and CBT-I are minor, and 
there are very few serious side effects. The most common side effects of acupuncture are mild pain 
on insertion of the needle, occurring at rates twice that of the placebo group. There is a pos sibility of 
a small amount of bleeding or bruising and very rarely infections at the site of insertion. Every effort 
will be made to ensure the safety and comfort of the research subjects, including wiping the needling 
site with alcohol before the procedure and wiping the needling site with sterile gauze. The most 
common side effects of CBT-I are short-term (less than 2 weeks) increases in daytime sleepiness 
and mood disturbance. The acupuncture and CBT-I will be delivered by licensed and experienced 
professionals. Every effort will be made to ensure the safety and comfort of the research subjects. 
Adverse events will be recorded during each clinical visit. Any related SAEs will be reported to the 
IRB. 
 
Confidentiality Risks: Every effort will be made to maintain confidentiality of the study subjects. 
Research and hospital records are confidential. Subject's names or any other personally identifying 
information will not be used in reports or publications resulting from this study. Authorized agencies 
(e.g., qualified monitors from PCORI etc.), and appropriate personnel may review subject's records 
as required. All forms are kept in a locked file cabinet when not in use. Clinical data will be kept in a 
centralized database with restricted access to study personnel. Data will be entered into MSK's 
clinical research database (CRDB), a study excel file, and study Access Databases on a secure 
MSK shared drive. Individual identifying information will be omitted from figures used in publications 
resulting from this research. 

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Risk of psychological distress: It is possible that subjects may be upset to find out that they are 
randomized to their non-preferred arm of the study. With appropriate consent and the debriefing 
process, such risks are minimized. Subjects will be informed that they are participating in an 
experimental study to determine the comparative effectiveness of acupuncture or CBT for insomnia. 
They have the chance to be randomized to either intervention. At the end of the study subjects will 
be offered the opportunity to discuss the findings with the PI. In addition, some of the questions in 
the questionnaire may elicit distress among subjects. At the baseline examination, patients will be 
screened for any elevated anxiety and depression or suicidal ideation/plan. If the subject 
demonstrates clinically significant distress, she/he will be referred to the psychosocial counseling. 
During the study period, if the research staff identifies any patients who are psychologically 
distressed they will notify the study PI immediately to facilitate appropriate evaluation and treatment. 
 
Costs: Study related procedures and visits will be provided to the subjects at no cost. To encourage 
adherence to the study procedures, we will provide $20 at the first, second, and third evaluation time 
points with an additional $40 for completion of the final assessment (total of $100 per participant). 
Compensation will be in the form of gift cards. 
 
Pote ntial Be nefits: 
 
 
Subjects who receive acupuncture or CBT-I may experience an improvement in their insomnia 
and/or other cancer-related co-morbidities (e.g. pain, fatigue, mood disturbance). Improving 
insomnia and other problematic symptoms often leads to an improvement in overall physical and 
emotional well-being. 
 
Alte rnatives to Participation: 
 
 
If patients do not enroll in this study, they may contact their personal physicians to discuss other 
treatments for insomnia. 
 
Risk/Benefit Ratio: 
 
 
The potential benefits of this study far outweigh the potential risks. Insomnia is a common and 
debilitating symptom that is experienced by many cancer survivors . The results of the proposed 
study will have an immediate impact to help cancer survivors and their caregivers make informed 
and evidence-based decisions about how to most effectively address cancer-related insomnia 
and co-occurring symptoms. Thus, this study has the potential to improve symptom burden and 
wellbeing for millions of individuals whose life is impacted by cancer. This research also has the 
potential to generalize to other chronic conditions and the population at large. We will carefully 
monitor any adverse events related to acupuncture and CBT-I, and minimize the risks for 
research subjects. 
 
17.1 
Priv acy 
 
MSK‟s Privacy Office may allow the use and disclosure of protected health information pursuant to a 
completed and signed Research Authorization form. The use and disclosure of protected health 

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information will be limited to the individuals described in the Research Authorization form. A 
Research Authorization form must be completed by the Principal Investigator and approved by the 
IRB and Privacy Board (IRB/PB). 
 
17.2 
Se rious Adverse Event (SAE) Re porting 
 
An adverse event is considered serious if it results in ANY of the following outcomes: 
• 
Death 
• 
A life-threatening adverse event 
• 
An adverse event that results in inpatient hospitalization or prolongation of existing 
hospitalization 
• 
A persistent or significant incapacity or substantial disruption of the ability to conduct 
normal life functions 
• 
A congenital anomaly/birth defect 
• 
Important Medical Events (IME) that may not result in death, be life threatening, or 
require hospitalization may be considered serious when, based upon medical judgment, 
they may jeopardize the patient or subject and may require medical or surgical 
intervention to prevent one of the outcomes listed in this definition 
Note: Hospital admission for a planned procedure/disease treatment is not considered an 
SAE. 
  
SAE reporting is required as soon as the participant signs consent.  SAE reporting is 
required for 30-days after the participant‟s last investigational treatment or intervention. Any 
events that occur after the 30-day period and that are at least possibly related to protocol 
treatment must be reported. 
 
If an SAE requires submission to the IRB office per IRB SOP RR-408 „Reporting of Serious 
Adverse Events‟, the SAE report must be sent to the IRB within 5 calendar days of the event. 
SAE‟s classified as unrelated to the study intervention (per section 11.0) will not be 
considered reportable to the IRB and will not have a corresponding Clinical Research 
Database (CRDB) SAE report generated.  The IRB requires a Clinical Research Database 
(CRDB) SAE report be submitted electronically to the SAE Office as follows: 
 
For IND/IDE trials: Reports that include a Grade 5 SAE should be sent to 
saegrade5@mskcc.org.  All other reports should be sent to saemskind@mskcc.org. 
 
 
For all other trials: Reports that include a Grade 5 SAE should be sent to 
saegrade5@mskcc.org.  All other reports should be sent to sae@mskcc.org. 
 
The report should contain the following information: 
Fields populated from CRDB: 
• 
Subject‟s initials 
• 
Medical record number 
• 
Disease/histology (if applicable) 

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• 
Protocol number and title 
 
Data needing to be entered: 
 
• 
The date the adverse event occurred 
• 
The adverse event 
• 
The grade of the event 
• 
Relationship of the adverse event to the treatment (drug, device, or intervention) 
• 
If the AE was expected 
• 
The severity of the AE 
• 
The intervention 
• 
Detailed text that includes the following 
o A explanation of how the AE was handled 
o A description of the subject‟s condition 
o Indication if the subject remains on the study 
• 
If an amendment will need to be made to the protocol and/or consent form 
• 
If the SAE is an Unanticipated Problem 
 
The PI‟s signature and the date it was signed are required on the completed report. 
 
For IND/IDE protocols: 
The CRDB SAE report should be completed as per above instructions.  If appropriate, t he 
report will be forwarded to the FD A by the SAE staff through the IND Office 
17.2.1  Not Applicable 
 
 
18.0 
INFORMED CONSENT PROCEDURES 
 
Before protocol-specified procedures are carried out, consenting professionals will explain full details 
of the protocol and study procedures as well as the risks involved to participants prior to their 
inclusion in the study. Participants will also be inf ormed that they are free to withdraw from the study 
at any time. All participants must sign an IRB/PB-approved consent form indicating their consent to 
participate. This consent form meets the requirements of the Code of Federal Regulations and the 
Institutional Review Board/Privacy Board of this Center. The consent form will include the following: 
 
1.  The nature and objectives, potential risks and benefits of the intended study. 
2.  The length of study and the likely follow-up required. 
3.  Alternatives to the proposed study. (This will include available standard and 
investigational therapies. In addition, patients will be offered an option of supportive 
care for therapeutic studies.) 
4.  The name of the investigator(s) responsible for the protocol. 
5.  The right of the participant to accept or refuse study interventions/interactions and to 
withdraw from participation at any time. 
 
Before any protocol-specific procedures can be carried out, the consenting professional will 
fully explain the aspects of patient privacy concerning research specific information.  In 

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addition to signing the IRB Informed Consent, all patients must agree to the Research 
Authorization component of the informed consent form. 
 
Each participant and consenting professional will sign the consent form. The participant must 
receive a copy of the signed informed consent form. 
 
 
 
 
 
19.0 
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20.0 APPENDICES 
Appendix 1:  Acupuncture protocol 
Appendix 2: CBT-I protocol 
Appendix 3: Multivariable Apnea Prediction (MAPS) Index 
Appendix 4: Patient Reported Outcome Measures 
Appendix 5: Blood Processing and Shipping 
Appendix 6: Recruitment Letter 
 
Appendix 7: Recruitment Flyer 
Appendix 8: Recruitment Rack Card 
Appendix 9: Tips for Healthy Sleep 

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