Targeting Self-regulatory Deficits Through Cognitive Remediation Intervention
Phase: NA
Conditions: Drug Use Disorders
Sponsor: Yale University

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Targeting Self-regulatory Deficits Through Cognitive Remediation Intervention 
NCT03373240 
March 22, 2019 
 
 

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HRP-503B – BIOMEDICAL RESEARCH PROTOCOL  
(2016-1) 
 
 
 
 
Protocol Title:  Targeting self-regulatory deficits through cognitive remediation intervention 
 
Principal Investigator: Arielle Baskin-Sommers, PhD 
 
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(If applicable) Clinicaltrials.gov Registration #: Click or tap here to enter text. 
 
 
INSTRUCTIONS 
 
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needed by the IRB to determine whether a study meets approval criteria. Read the following instructions 
before proceeding: 
 
1. Use this protocol template for a PI initiated study that includes direct interactions with research 
subjects. Additional templates for other types of research protocols are available in the system Library. 
 
2. If a section or question does not apply to your research study, type “Not Applicable” underneath. 
 
3. Once completed, upload your protocol in the “Basic Information” screen in IRES IRB system.  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
SECTION I: RESEARCH PLAN 
 
1. Statement of Purpose: State the scientific aim(s) of the study, or the hypotheses to be tested.  

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The overarching objective of this supplement application is to apply a behavioral medicine approach 
to validate a novel set of interventions that may be used to both study and treat cognitive-affective 
dysfunctions implicated in self-regulation. By systematically characterizing and addressing 
cognitive-affective processes, we aim to accelerate assessment and treatment efforts in disorders 
characterized by dysfunction in self-regulation, including substance use disorders (SUDs).  The 
proposed research will evaluate the possibility of modifying cognitive-affective deficits that hinder 
self-regulation using a focused skill-building approach targeting three domains demonstrated to be 
disrupted in SUDs: executive function, negative emotionality, and incentive salience.  
 
We are proposing a small randomized clinical trial in which 100 substance users will complete the 
existing Psychotherapy Development Center (PDC) pretreatment assessment battery as well as a 
novel battery of assays to evaluate cognitive-affective functioning.  These batteries will be 
administered before and after the intervention (cognitive training tasks) to help examine the 
generalizability of any training effects to related cognitive training tasks (tasks that the participant 
was not specifically trained on). These related tasks will also help quantify participants’ potential 
responsiveness to treatment and, as such, may help bridge the gap between behavior, mechanism, 
and treatment.  
 
After completing pretreatment assessments, participants will be randomized to either a (1) cognitive 
remediation program (training tasks) specifically designed to address cognitive-affective 
dysregulation or (2) control tasks (verbal fluency tasks).  Tasks will be completed twice per week for 
4 weeks, after which assessment batteries will be repeated.  Finally, we will evaluate real-world 
behavior and the durability of the training via a one-month follow-up, which will include assessment 
of substance use as well as the cognitive-affective battery.  Our primary Specific Aim will be to 
evaluate the efficacy of the cognitive-remediation program relative to the control condition control 
on the indicators of cognitive-affective functioning and substance use, testing the hypothesis that 
individuals randomized to the cognitive remediation program will demonstrate improved functioning 
on the cognitive-affective battery as well as reduced substance abuse.  We will also explore potential 
moderators of response to the training, including baseline measures of cognitive-affective function. 
 
Our long term goal is to enhance outcomes of effective ‘top down’ treatments like cognitive 
behavior therapy (CBT) and contingency management by combining them with brief ‘bottom up’ 
interventions that address, more directly, underlying mechanistic deficits that impact self-regulation 
and ultimately the maintenance of SUDs.  The proposed research will lay the foundation for a more 
thorough evaluation of ‘mechanism matched cognitive remediation’ (1). Translation of these 
findings is expected to eventually allow clinician to match cognitive remediation interventions to the 
respective core deficits of their patients. Targeted intervention strategies such as these are likely to 
improve outcomes for multiple externalizing disorders, including SUDs.  Moreover, as they are brief 
and administered via computer, the potential dissemination of these treatments could be more 
efficient, cost-effective, and implemented in a wider variety of settings (e.g., primary care, rural 
areas) than traditional behavior change interventions.  
 
2. Probable Duration of Project: State the expected duration of the project, including all follow-up and data 
analysis activities.   
 

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Two years 
 
3. Background: Describe the background information that led to the plan for this project. Provide references to 
support the expectation of obtaining useful scientific data. 
 
Cognitive-Affective factors and substance use disorders (SUDs): 
SUDs rank among the most widespread and costly illnesses in the US (17, 18).  Although multiple 
factors contribute to the development and maintenance of SUDs, core neurobiological and 
psychological processes are commonly implicated in the development and maintenance of SUDs and 
other externalizing disorders (e.g., antisocial personality, attention deficit-hyperactivity, conduct).  In 
particular, these disorders are characterized by marked dysfunction in self-regulation, subserved by 
impairments in executive function and hyper-reactivity of negative emotionality and incentive 
salience (19, 20).  Dysfunctions in these domains are mirrored in the tendency for individuals with 
SUDs to demonstrate strong attentional orienting to motivationally salient cues (21), failure to 
inhibit reward seeking responses (22), difficulty classifying rare or unexpected stimuli in the oddball 
task (23), deficits in distress tolerance (24), and poor delay discounting during gambling tasks (25). 
In these instances, individuals with SUDs react strongly to motivationally salient information (e.g., 
unexpected information, goal-relevant reward, punishment, threat), particularly when they are 
prepared to make a practiced, dominant response. Accordingly, reactivity to affective information 
(incentive or negative emotion) and deficiencies in executive function may disinhibit individuals 
with SUDs to engage in pleasure-seeking (e.g., substance use), display extraverted interpersonal 
tendencies, and to act in an impulsive manner, particularly when in an affectively charged situation.  
Thus, interventions that directly target these underlying cognitive-affective deficits are a novel and 
promising strategy to enhance intervention effectiveness.   
 
Translating mechanism into intervention:   
Cognitive-affective impairments are a persistent and functionally relevant feature of multiple 
disorders, including SUDs (26-30). Such impairments span multiple domains and are more closely 
linked to functional outcomes than severity of clinical symptomatology, making them a priority for 
treatment development (27, 28, 31, 32). Increasingly, there is strong interest in understanding the 
mechanisms of behavior change and developing effective interventions that capitalize on this 
understanding (3). One promising and innovative intervention strategy is cognitive remediation. 
Cognitive remediation encompasses a diverse array of “interventions that aim to improve 
(neuro)cognitive functions (attention, memory, executive function, social cognition, or 
metacognition) with the goal of durability and generalization” (33).  Some evidence suggests the 
promise of this approach for SUDs (34, 35), although early efforts to use this treatment approach for 
SUDs has failed to assess the translation of specific skills to generalizable skills. Additionally, most 
of this early work has either provided non-specific training (e.g., general executive functioning or 
attention bias modification) or training on a single dysfunction (e.g., distress tolerance) that did not 
necessarily capitalize on our understanding of the multifaceted cognitive-affective deficits affecting 
individuals with SUDs. Recent research suggests it is possible to identify cognitive-affective 
processes that are dysfunctional in SUDs and related disorders, target those cognitive-affective 
processes, and bring about change in those processes using a systematic approach to cognitive 
remediation tailored to specific self-regulatory deficits: Co-investigator Dr. Baskin-Sommers (1) 
designed a cognitive remediation program for incarcerated individuals with SUDs (see Preliminary 
Studies). This program was developed to target specific cognitive-affective deficits in two antisocial 

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subtypes (psychopathic and externalizing) with co-morbid SUDs. There is a large body of evidence 
suggesting that individuals with psychopathy + SUDs are characterized by impairments in 
modulating attention to accommodate multiple streams of information, whereas individuals with 
externalizing/antisocial personality disorder + SUDs demonstrate exaggerated responses to affective 
information and various kinds of motivational cues, in combination with reduced regulatory capacity 
(36).  Training that used a multi-task package designed to target the specific cognitive-affective 
deficits associated with either subtype (psychopathic versus externalizing) led to improvement on 
both trained and non-trained tasks, with improved outcomes for individuals who received the type of 
training tailored to the deficits associated with their subtype.  This SOBC supplement would extend 
this work by testing the cognitive remediation strategy used for the externalizing subtype in a 
heterogeneous sample of individuals with substance use disorders.     
 
Dr. Baskin-Sommers’ recently published cognitive remediation study in offenders (1) represents a 
proof of concept study for the proposed SOBC supplement (see Figure 1). Training designed to 
target affective self-regulation and remedy the distinct deficits associated with SUD-offender 
subtypes resulted in specific and differential improvement on trained and non-trained tasks. 
Moreover, analyses demonstrated that using three tasks to tap cognitive-affective dysfunction from 
multiple angles was a stronger predictor of change than any single task. Finally, unpublished 
analysis showed that individuals who received training that matched their cognitive-affective deficits 
had fewer disciplinary reports in prison two months following the training. Together, these tasks 
highlight the utility of targeting cognitive-affective functions through targeted computerized tasks 
and the generalizability of change to other tasks and to real-world behavior.  
 
 
Figure 1.  Overview of study design, 
Baskin-Sommers et al (2105).   Proposed 
SOBC project uses cognitive 
remediation tasks targeted for improved 
affective-cognitive control (boxed area) 
 
 
 
 
 
 
 
 
 
4. Research Plan: Summarize the study design and research procedures using non-technical language that can 
be readily understood by someone outside the discipline. Be sure to distinguish between standard of care vs. 
research procedures when applicable, and include any flowcharts of visits specifying their individual times 
and lengths. Describe the setting in which the research will take place. 
 
Overview:   
The proposed SOBC supplement project will be conducted at the Substance Abuse Treatment Unit 
(SATU) and Adult Outpatient Psychiatric Services (IOP) in New Haven.  One hundred substance 

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users will be randomized, via a computerized urn randomization program (55) we have used in 
multiple previous trials (9, 10, 37, 56, 57) to either the cognitive remediation package or a control 
condition (computerized verbal fluency tasks), with trainings conducted twice per week for 4 weeks.  
Training will be conducted as an add-on to the participants’ ongoing standard treatment at the clinic.   
 
Several variables will be assessed. Demographic variables will include gender, race, and level of 
education. Person-specific variables will include type and severity of substance use disorder, 
personality characteristics, and treatment readiness.  Pre- and post-training testing will evaluate 
change in cognitive-affective targets, with a one-month follow-up period to evaluate both the 
durability of training effects as well as impact on real-world behaviors (substance use).   
 
This project will benefit the Parent award (P50 DA 0009241) by enabling us to evaluate how 
individuals with varying levels of these cognitive-affective deficits respond to study interventions 
and hence inform future projects which could address whether addressing these deficits via cognitive 
remediation improves response to empirically validated therapies via ‘mechanism-matched’ 
cognitive remediation. 
 
Diagnostic and Baseline Assessments:   
After providing written informed consent (see Human Subjects), participants will complete the 
following components of the Parent award (Psychotherapy Development Center, PDC) Core 
assessment battery to facilitate comparison with ongoing/previous Center studies:    
• Structured Clinical Interview for DSM-5 (SCID) (58) (59), including antisocial personality 
disorder. 
• The Brief Symptom Index (BSI) (60) is a widely used 53-item inventory of psychiatric 
symptoms.    
• Substance Use Calendar. Self-reports of substance use (cocaine, alcohol, opioids, marijuana, 
other illicit drugs, and nicotine) are documented at each contact via the Substance Use Calendar.  
Similar to the Time Line Follow-Back (61), the Substance Use Calendar assesses substance use 
on a daily basis.  
• State-Trait Anxiety Inventory (STAI) is a widely-used measure of consistent and transient stress 
and anxiety (62). 
• Distress Tolerance. (24, 63, 64) is commonly measured using the Mirror Tracing Persistence 
Task (65). 
• Shipley Institute of Living Scale (66) is included as a widely used measure of general 
intelligence. 
• Balloon Analog Risk Task (BART) is a computerized measure of risk-taking (67). 
• Five-trial adjusting delay discounting task is a brief computerized measure of delay discounting 
(Koffarnus & Bickel, 2014). 
 
Baseline Cognitive-Affective Assessments:  
This battery includes three tasks that have been previously used to tap the cognitive-affective processes 
associated with SUDs and other externalizing disorders.  
• Incentivized n-Back task includes manipulations of working memory load, response prepotency, and 
incentivized performance (trial-by-trial feedback using monetary reward and punishment) to 
examine the integrity of cognitive control functions necessary for successful regulation of behavior. 
In this task, participants view a series of letters. Participants are instructed to monitor the letters and 

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respond with a button press if the preceding letter in the n-back position is different from the current 
letter (e.g., a mismatch trial). Participants are instructed to withhold their response when the 
preceding letter matched the current stimulus (e.g., a match trial). The majority of trials are 
mismatch trials (80%), whereas match trials are infrequent (20%). The task also includes a 
manipulation of working memory load. In the low load (1-back) condition, participants are 
instructed to determine whether the currently presented letter matched the immediately preceding 
letter in the sequence. In the high load (2-back) condition, participants are required to monitor and 
maintain the stimulus information in working memory in order to determine whether the letter 
stimulus 2 positions earlier matched the current letter. Finally, the task manipulates incentives on a 
subset of trials; in separate blocks participants received reward (sound of a coin drop and the 
addition of 5 cents) following a correct response or punishment following an incorrect response 
(aversive .5s 100dB noise blast and the loss of 5 cents). The primary dependent variable will be task 
performance. The Incentivized n-Back task is thus used to assess relevant processes because deficits 
because it evaluates a person’s tendency to over-allocate attention to motivationally-salient 
information (22, 74).   
 
Post-Treatment Follow- Assessments: 
At the end of the 4 weeks, the participant will be asked to fill out more questionnaires (see table below), 
provide a urine and breath specimen for drug and alcohol testing, and be interviewed again. This 
assessment session will take about 1 hour.   
 
Study assessments schedule: 
Instrument/task 
Rater 
Screen 
Week 0 
Training 
 
Week 4 
Follow-up 
Informed consent quiz 
P 
x 
 
 
 
 
Demographics and 
medical history 
P 
x 
 
 
 
 
Locator form 
RA 
 
 
 
 
 
SCID for DSM-5 
RA 
x 
 
 
 
 
Shipley 
P 
x 
 
 
 
 
Inclusion/exclusion 
RA 
x 
 
 
 
 
Urn randomization 
RA 
x 
 
 
 
 
Utox and BAC 
RA 
x 
x 
x 
x 
x 
BSI 
P 
 
x 
 
x 
x 
Substance Use Calendar 
RA 
 
x 
x 
x 
x 
State-Trait Anxiety 
P 
 
x 
 
X 
x 
Distress Tolerance 
RA 
 
X 
 
X 
x 
BART 
RA 
 
X 
 
X 
x 
5-Item Delay Discounting 
RA 
 
X 
 
X 
X 
Incentivized n-back 
RA 
 
X 
 
X 
X 
Externalizing Spectrum 
Inventory 
P 
 
x 
 
 
 
Perceived Stress Scale 
P 
 
x 
 
 
x 
Circumstance, 
Motivation, Readiness 
Scale for Treatment 
P 
 
x 
 
 
x 
 
Interventions:   

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Participants will be randomized to one of 2 training conditions, to be completed twice per week over 4 
weeks, in addition to standard treatment at SATU/IOP, which typically consists of weekly group 
meetings, case management and random urine toxicology screening. Each training session will be 30-45 
minutes (time variability depends on speed of reading instructions and choices made in the tasks).   
Across all weeks the participant will complete approximately six hours of training.      
            
         Control condition.  Participants randomized to this condition will complete a computerized verbal 
flexibility task (Text Twist).  An active computer-based control was selected as it provides a rigorous 
comparison to intervention and will help address concerns that any game-style activities will produce 
improvements by controlling for computer time and game experiences, as well as non-specific elements 
such as support, attention, study contact, activation, and motivation. It is possible an active and engaging 
control condition may produce modest neurocognitive change in some domains, but available data 
indicate the control condition is not likely to influence the target-specific processes associated with self-
regulation (75). 
 
              Cognitive Remediation tasks:  The target training focuses on providing individuals with 
practice inhibiting, learning, and making decisions within affective contexts. Well-validated tasks that 
have been reliably shown to tap these processes, and are amenable to repeated administration, were 
selected. Each of these tasks taps the underlying domains of self-regulatory dysfunction (executive 
function, negative emotionality, incentive salience).  Thus, this training package more directly builds on 
previous work that establishes the importance of dual demands on cognitive and affective processes 
associated with regulation of behavior. Moreover, it addresses the complex cognitive-affective 
dysfunctions in self-regulation from multiple angles rather than targeting or tapping a single process that 
is likely entrapped within a more multi-faceted dysfunction. The basic structure of this training has been 
successfully implemented in Dr. Baskin-Sommers’ previous work (1). The three tasks will address 
inhibition in the face of reward, cost-benefit decision-making in the face of uncertainty, and working 
memory in the face of distress.  These three tasks provide measures of the target processes of interest, 
but are distinct from the pre-post measures, so as to measure the transfer of skills from one setting to 
another (i.e., generalizability).   
Rewarded Stop Signal task (15 minutes). The Stop Signal task provides a measure of reward 
approach motivation (Go reaction time) and ability to inhibit motor behavior (Stop reaction time) under 
conditions of high motivation to approach. An interesting dissociation emerges, such that some people 
(high reward sensitivity) are faster at going and worse at stopping under higher reward (76), some 
people (impulsive) are faster at going but worse at stopping (77), and others are faster at going but show 
no reward effect on stopping (78). In order to measure these individual differences, we have developed a 
version of the task in which participants are given information on the reward value of each upcoming 
trial, with 75% of (standard) trials awarded 2 points for correct performance, and 25% high reward 
trials receiving 50 points for correct performance (1). All participants start with a neutral block and then 
enter the reward block where they view stimuli of circles (Go), but some circles will have a ton played 
which indicates that no response should be given (Stop). A dual staircase tracking procedure is used, 
with a separate mean calculated for both the standard and the high reward trials. We specifically 
selected a version utilizing a cue at the beginning of each trial, as pretrial cues can modulate Go reaction 
time on both simple reaction time and stop signal reaction time paradigms (79, 80). 
Decision-Making during Ambiguity (15 min).  This is a financial decision-making task in which the 
amounts of favorable and unfavorable information regarding an ambiguous financial prospect will be 
parametrically manipulated (81). On each trial, participants are presented with a (distinct) virtual "bag" 

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of exactly 100 poker chips, all of which were colored either red or blue. For this bag, 
participants receive partial information about the number of red and blue chips in the bag. 
Parametrically varying the number of red chips and blue chips shown to participants allows for a trial-
wise calibration of the availability of favorable or unfavorable information. Participants are asked 
to indicate whether they want to select a chip from the bag (giving them a chance to get a winning chip) 
or get 5 points for certain. The task consists of 56 trials. Each trial begins with a fixation cross, after 
which participants view the available information about the bag's contents versus the 5 point 
guarantee. Participants select which option they want for the current round by pressing the left or right 
key. Participants are not placed under time constraints for responding. 
 Paced Auditory Serial Addition Task (PASAT; 7 min) (82) The PASAT is a cognitive task purported 
to measure working memory, speed of information processing, and sustained and divided attention. It is 
a measure of many functional domains, but primarily relates to a participant’s ability to persist in the 
face of emotional reactions (i.e., distress tolerance) to the task’s demands.  For this task, numbers are 
sequentially flashed on a computer screen, and participants are asked to add the presented number to the 
one previously presented. For example, if the digits ‘3’, ‘6’ and ‘2’ were presented, the participant 
would respond with the correct sums, which are ‘9’ and then ‘8’. Participants provide answers by using 
the mouse to click on the correct answer on a number pad displayed on the screen. Participants are told 
that their score increases by one point with each correct answer and that incorrect answers or omissions 
would not affect their total score. However, if they provide an incorrect answer or omitted a response, 
participants would hear a loud noise blast presented over headphones. The task consists of three levels 
with varying latencies between number presentations. Specifically, the first level of the PASAT provides 
a 3-s latency between number presentations (i.e., low difficulty) for 2 minutes, the second level provides 
a 2-s latency for the first 2 minutes and a 1-s latency for the last minute (i.e., medium difficulty), and the 
third level provides a 1-s latency (i.e., high difficulty) until terminated, up to 7 minutes.  
 
Total Protocol Completion Time:  
From consent to the completion of the study, participants will complete approximately 10-12 hours of 
study-related activities.  
 
5. Genetic Testing    
N/A ☒ 
 
6. Subject Population: Provide a detailed description of the types of human subjects who will be recruited into 
this study. 
 
Participants will be 100 individuals (aged 18 and older) enrolled in outpatient (non- 
methadone/buprenorphine) treatment for any substance use disorder (other than PCP) at the Substance 
Abuse Treatment Unit in New Haven.  As the goal of this project is to develop interventions that address 
self-regulation across multiple disorders, we will recruit individuals who have a range of substance use 
disorders and levels of severity.  Otherwise, inclusion criteria are relatively broad and intended primarily 
to exclude individuals who are insufficiently stable to complete an outpatient trial of 4 weeks duration, 
who are highly unlikely to be located for assessment interviews, or who have a significant history of 
head injury or other condition that would confound interpretation of study findings.  Individuals who are 
currently physically dependent on opioids, alcohol, or other substances and who require detoxification 
will be referred appropriately and invited to be re-screened following detoxification and stabilization.  
Completion of assessment instruments requires a minimum of a 4th grade reading level.   
 

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7. Subject classification: Check off all classifications of subjects that will be specifically recruited for enrollment in 
the research project. Will subjects who may require additional safeguards or other considerations be enrolled 
in the study? If so, identify the population of subjects requiring special safeguards and provide a justification 
for their involvement. 
 
☐Children 
 
 
☐ Healthy  
 
 
☐Fetal material, placenta, or dead fetus 
☐Non-English Speaking  
☐ Prisoners 
 
 
☐Economically disadvantaged persons 
☐Decisionally Impaired  
☐ Employees 
 
 
☐Pregnant women and/or fetuses 
☐Yale Students  
 
☐ Females of childbearing potential 
 
NOTE: Is this research proposal designed to enroll children who are wards of the state as potential subjects? 
Yes ☐  No ☒  
 
8. Inclusion/Exclusion Criteria: What are the criteria used to determine subject inclusion or exclusion? 
 
Inclusion and exclusion criteria         
Participants will be included who: 
• 
Are between ages 18 and 50. 
• 
Meet current DSM-5 criteria for an alcohol, stimulant, cannabis, or opioid use disorder. 
• 
Are sufficiently stable for 4 weeks of outpatient treatment. 
• 
Are willing to provide locator information. 
• 
Are fluent in English and have a 4th grader or higher reading level  
 
Individuals will be excluded who: 
• 
Meet DSM-5 criteria for a bipolar or schizophrenic disorder. 
• 
Who have a legal case pending such that incarceration during the 4-week protocol is likely. 
• 
Are physically dependent on alcohol, opioids or benzodiazepines or who report recent PCP use. 
• 
Have a baseline Shipley estimated IQ less than 70 
• 
Have 3 or more head injuries with loss of consciousness for over 30 minutes or lasting effects 
• 
Have a history of chronic illness or neurological disorders (e.g., epilepsy or stroke) that would  
 
 complicate evaluation of effects of cognitive training 
 
9. How will eligibility be determined, and by whom? Write here 
 
Following provision of written informed consent, baseline assessments will be completed with the 
research assistants.  These will include demographic data, SCID interview for DSM-5, Shipley, and 
a brief medical history for determination of eligibility. 
 
10. Risks: Describe the reasonably foreseeable risks, including risks to subject privacy, discomforts, or 
inconveniences associated with subjects participating in the research.  
 
1. Cognitive remediation training and control condition.   
 
Cognitive remediation is safe, inexpensive, portable, and easy to administer. The cognitive training 
tasks proposed here have been used safely with similar populations in previous work (1, 85). Thus, 
the potential dissemination of these treatments could be more efficient, cost-effective, and 
implemented in a wider variety of settings than traditional behavior change interventions. The 

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computerized control condition is safe, consisting of simple verbal fluency tasks. Importantly, the 
skills needed to complete these games are non-specific and distinct from those required for the 
cognitive remediation training. Both the experimental and control condition will be administered in 
addition to standard treatment (TAU, treatment as usual) at the SATU/IOP clinic, which typically 
consists of weekly group meetings, urine toxicology screening, and case management.  Thus, 
psychological risks appear to be minimal and not different from those of equivalent non-study 
psychotherapeutic interventions.   
 
We believe that there are very few risks to participating in this treatment.  We would like 
participants to tell us about any times they use alcohol or illegal drugs while they are in the study.  It 
is not illegal to report past substance use.  Also, we know that stopping alcohol or substance use can 
be quite difficult.  In order to be helpful to participants, we simply need to know about their alcohol 
or substance use. The urine drug tests and the breathalyzer tests for alcohol enables us to be certain 
of our results.  The only way participants might be dismissed from the study is if they repeatedly do 
not come to treatment or violate the rules of this clinical program.  We would only ask that they do 
their best to stop using alcohol or drugs, be honest about themselves and their problems and to be 
available at their appointment times for both the research assistant and counselor. 
 
 
2. Urine and breath specimen collection 
Urine and breath specimens are collected primarily as safeguards to participants and should add no 
risks other than those normally associated with these procedures. 
 
3. Rating scale and questionnaires. 
 
These are all non-invasive, should add no risk, and have been used without difficulty or any adverse 
events in our previous studies with this population.  The major disadvantage is the time taken to 
complete them.  Our past experience with these measures indicates that they are acceptable to 
patients.  Careful efforts aimed at maintaining confidentiality have been effective in previous 
research, and only patients’ code numbers will be recorded on the forms themselves to protect 
confidentiality. 
 
11. Minimizing Risks: Describe the manner in which the above-mentioned risks will be minimized. 
 
Assessment of risks versus benefits requires some description of the individuals to be treated.  The  
study population is at high risk for a number of cognitive and psychiatric problems; this is also a 
population at high risk for treatment failure, either by treatment dropout or continued illicit 
substance use.  The behavioral therapies tested here carry minimal risk and will be implemented as 
adjuncts to standard outpatient treatment at this comprehensive treatment center.  We believe we 
have included adequate safeguards for participants to address the ethical questions, regular contacts 
with program staff and close monitoring of symptoms, and procedures to withdraw from study 
treatments participants who show significant deterioration or adverse events.  Thus, the potential 
benefits for individuals and society at large are high; and the risk/benefit ratio appears favorable 
toward the proposed study treatments. 
 
We will recruit participants via flyers distributed at the clinic and via direct referral from clinicians, 
following procedures we have worked out through multiple previous studies at this site (86-94).  The 

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screening of patients using the inclusion and exclusion criteria, and the urine toxicology screens and 
SCIDs, will minimize the risk of including participants who are not appropriate for this low-risk 
study.  On-site medical staff and frequent visits and monitoring by research staff will minimize the 
risks of adverse events and assure that they are managed quickly if they do occur.  Study physicians 
are available on call, including nights and weekends, to answer patient concerns.   
 
 
Participants will be withdrawn from the treatment arm if they show severe psychological or 
symptomatic deterioration, unacceptable levels of adverse events as determined by the SATU/IOP 
program director or if clinically necessary for ethical or safety purposes.  Participants dropped from 
the study for these reasons or because they wish to withdraw will be offered treatment as usual at 
SATU/IOP or be referred to a higher level of care, such as an inpatient facility, when appropriate.  
For all participants, if an emergent medical, psychiatric, or substance abuse issue emerges from any 
treatment or test given as part of the proposed study, these will be assessed through the SATU/IOP 
physician and appropriate referral or treatment will be delivered. Private referral and/or 
hospitalization may also be offered according to the participants’ needs and wishes. 
 
12. Data and Safety Monitoring Plan: Include an appropriate Data and Safety Monitoring Plan (DSMP) based on 
the investigator’s risk assessment stated below. (Note: the HIC will make the final determination of the risk to 
subjects.) 
 
a.  
What is the investigator’s assessment of the overall risk level for subjects participating in this 
study? Minimal risk 
b. 
If children are involved, what is the investigator’s assessment of the overall risk level for the 
children participating in this study? N/A 
c. 
Include an appropriate Data and Safety Monitoring Plan. Examples of DSMPs are   
available here http://your.yale.edu/policies-procedures/forms/420-fr-01-data-and-safety-
monitoring-plans-templates  
 
1. Procedures to ensure the validity and integrity of the data 
Multiple measures are in place to ensure the validity and integrity of the data.  First, all research staff 
receive Human Subjects Protection training, as well as training in Good Clinical Practice. Weekly 
research meetings for all research staff take place, in addition to weekly project-specific measures, as a 
forum for in-service training as well as to discuss questions regarding issues that arise in complex 
clinical research protocols.  Adherence to protocol procedures will be monitored using individual 
supervision conducted by the PI.  Multiple research staff are cross-trained to ‘cover’ for each other; 
thus, review by multiple staff with oversight by the PI facilitates early identification of errors and 
oversight. The Data Manager conducts weekly quality assurance checks of research charts and Case 
Report Form (CRFs).   
 
2. Procedures to guarantee the accuracy and completeness of the data during data collection, entry, 
transmission, and analysis. 
 
 
As CRFs are completed, they are scanned in and processed by the Data Manager.  The electronic 
images are verified by the Data Manager using Teleforms, and transferred to the database. The Data 
Manager processes the assessments on a daily basis, checks for missing data, logical inconsistencies, 
and reports any errors back to the Research Assistants.  Any necessary corrections are done by direct 
entry and documented in the system and on the CRF logs.  

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3.  Data and Safety Monitoring Board   
 
 
A Data and Safety Monitoring Board (DSMB) will monitor the proposed project because this 
population might be considered vulnerable due to their substance use. This board, already in place 
for all projects affiliated with the P50 Psychotherapy Development Center (PDC), is composed of 
Yale investigators who are independent of the parent trials and experienced in various aspects of the 
conduct of clinical trials for the treatment of addictive disorders (Drs. Sherry McKee, Declan Barry, 
and Jenifer Edelman).  Dr. Carroll has developed a standard DSMB report form that has been used in 
all PDC and PDC-related trials that summarizes on a quarterly basis: 
 
1.  Recruitment, retention, and follow-up rates for the study and compares them to target rates. 
2.  Rates of data completeness and availability of primary outcome data 
3.  Occurrence of AEs and SAEs 
4.  Report of study progress since the last report.   
5.  Rates of recruitment of women, minorities, and children with respect to targeted rates. 
 
These reports will be generated by the Data Managers each quarter, signed and reviewed by Dr. 
Baskin-Sommers prior to their submission to the DSMB.   
 
Because the projected effect sizes may not be large enough for detection during interim analyses, we 
are not proposing a preliminary analysis of accumulating efficacy and safety data by treatment 
assignment. Instead, we propose to submit a quarterly report of aggregate data to the DSMB 
members that contains screening data, baseline demographics, retention data, serious adverse events 
data, as well as accrual status including projections, times to milestones, and any other data that will 
help in the assessment of the clinical trial. Based on this report, each DSMB member will complete a 
form making one of two recommendations: 1) continue recruitment as planned; or 2) schedule 
formal DSMB meeting immediately. If any DSMB member recommends a meeting, this will be 
scheduled within one week, minutes will be kept, the report will be reviewed with the PI, and the 
committee will vote on whether the study should: 1) continue recruitment unchanged; 2) continue 
with a protocol amendment; 3) stop recruiting pending further investigation. If, after this meeting, 
any DSMB member votes to stop recruitment or requests a protocol modification, the Yale IRB will 
be informed. 
 
4. Reporting of Serious Adverse Events (SAEs) 
 
 
SAEs will be systematically assessed at each clinic visit. We have worked out these procedures in 
multiple clinical trials of behavioral interventions). The most common SAEs are expected to be 
overnight hospitalizations for reasons related to substance use, psychiatric, or medical problems. All 
events meeting FDA definition for SAEs (any medical occurrence that results in death; is life-
threatening; requires inpatient hospitalization or prolongation of existing hospitalization; creates 
persistent or significant disability/incapacity, or a congenital anomaly/birth defect will be reported) 
will result in immediate notification (within 1 hour of staff learning of SAE) to the study Principal 
Investigator (Dr. Baskin-Sommers), Psychotherapy Development Center (PDC) regulatory 
coordinator, and on-site SATU/IOP clinic director (or their designee). Within 24 hours, staff will 
complete the study SAE Form (without PHI) and send this to the same three individuals.  
 

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As part of this initial report, Dr. Baskin-Sommers will provide an evaluation of the SAE with regard 
to its: 1) grade of risk (none, mild, moderate, severe, life-threatening or disabling; fatal; 2) 
attribution of relatedness to study (unrelated/not, unlikely/remotely, possibly, probably, definitely); 
3) level of anticipation/expectedness given the risks of study population or protocol (anticipated, 
anticipated but at frequency greater than expected, unanticipated); 4) categorization (death, life 
threatening, hospitalization, disability, birth anomaly/defect, medical intervention required to 
prevent death/disability); 5) resolution (recovered/resolved, recovering/resolving, not 
recovered/resolved, fatal, lost to follow-up). This evaluation will be documented on study SAE 
Form. The PDC regulatory coordinator or designee will follow up with Dr. Baskin-Sommers or 
study staff until the SAE resolution (5) is considered resolved and any updates documented and 
reported appropriately.  
 
The Yale Human Investigations Committee (HIC) must be informed with 5 days of any SAE that Dr. 
Baskin-Sommers judges to be unanticipated (or anticipated but occurring greater than expected) and 
(possibly, probably, definitely) related to study participation. The HIC form must be completed 
either electronically through COEUS, faxed to the HIC office, or hand delivered. A copy of this HIC 
form will be forwarded to the PDC regulatory coordinator or designee. Yale’s File Transfer Facility 
or other secure system must be used if personal health information is included on this form. 
 
The NIDA Program Office must be informed of any SAE that results in death or which Dr. Baskin-
Sommers judges as sufficiently life threatening that death might have occurred if medical or 
psychiatric intervention were not provided. This report is made to NIDA regardless of whether the 
SAE was study related or unanticipated. Dr. Baskin-Sommers and study staff will provide a follow-
up report to the PDC regulatory coordinator or designee with 48 hours of the event so that NIDA’s 
SAE form can be completed and submitted. Copies of this form will be distributed to the PDC PI 
(Dr. Carroll), study co-investigators, all DSMB members, and the on-site program director. Yale’s 
File Transfer Facility or other secure system must be used if personal health information is included 
on this form. Within one week, the PDC PI or Scientific Director will confer with DSMB members 
to determine if a meeting should occur. 
 
In addition to the SAE forms completed, a progress note in the study clinical chart must be made that 
provides a detailed narrative description of the event with a co-signature by supervisory personnel.  
 
All SAEs regardless of grade, relatedness, anticipation, categorization, or resolution will be 
summarized in quarterly DSMB reports and annual reports to the Yale HIC.  
 
We will report all major protocol amendments or changes in the informed consent form to the NIDA 
Project Officer as well as any temporary or permanent suspension of patient accrual 
 
d. For multi-site studies for which the Yale PI serves as the lead investigator:  N/A 
i. How will adverse events and unanticipated problems involving risks to subjects or others be 
reported, reviewed and managed? Write here 
ii. What provisions are in place for management of interim results? Write here 
iii. What will the multi-site process be for protocol modifications? Write here 
 
13. Statistical Considerations: Describe the statistical analyses that support the study design.  

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Data will be collected, managed and analyzed through the standard procedures of the PDC as 
described in detail in the parent grant.  Regarding statistical power, Dr. Baskin-Sommers’ previous 
study using a similar cognitive remediation battery (1) with 55 participants revealed an effect size of 
d =.42 for the malleability of performance on the training, with 92% power.  A sample size of 100 
will allow us to evaluate the effect of ongoing substance use as a moderator of treatment response at 
80% power.  We have established that we can recruit and treat a sample of this size in the one-year 
time allotment of the SOBC supplement.  Our rates of end of treatment assessment and follow-up in 
Center trials is 90% or above, enabling us to conduct true intention to treat analyses with minimal 
statistical imputation (48, 49, 83). General Linear Modeling will be used to examine change in 
performance on these tasks over time. Using General Linear Modeling as we have in previous 
Center-supported studies (10, 37, 49, 57, 84), we will evaluate the extent to which participants who 
receive cognitive remediation show significantly greater improvement across time in the cognitive-
affective assessment battery than those who receive the control training. Additionally, structural 
equation modeling (SEM) and latent profile analysis (LPA) will be used to examine variable-
centered (correlation between measures) versus person-centered (profiles of individuals) alternatives. 
SEM with maximum-likelihood estimation will be used to test the association between pre-post 
measures and SUD-related behaviors. LPA, whereby each individual is assigned to a mutually 
exclusive assay class (i.e. profile) based on a data-driven analytic strategy, will be used to test the 
association between each individual’s pre-post profile and treatment response. Moreover, we will 
use regression discontinuity analyses compare observations clustered closely on either side of a 
process-level threshold around a particular intervention. This analysis would allow us to examine the 
local average treatment effects on pre-post measures in a non-parametric data-driven manner.  
 
Timeline 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
11 
12 
Recruit 3 
participants/week  
x 
x 
x 
x 
x 
x 
x 
x 
x 
 
 
 
Participant 100 
completes 4 week 
treatment 
 
 
 
 
 
 
 
 
 
 
x 
 
Participant 100 
completes 1 
month follow-up 
 
 
 
 
 
 
 
 
 
 
 
x 
Data analysis and 
preparation of 
reports 
 
 
 
 
 
 
 
 
 
 
 
x 
 
 
 
 
 

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SECTION II: RESEARCH INVOLVING DRUGS, BIOLOGICS, RADIOTRACERS, PLACEBOS AND DEVICES 
 
If this section (or one of its parts, A or B) is not applicable, check off N/A and delete the rest of the section. 
A.  RADIOTRACERS 
☒N/A 
 
 
If NO, an FDA issued IND is required for the investigational use unless RDRC assumes oversight.  
 
 
B.  DRUGS/BIOLOGICS    ☒N/A 
 
 
Note: If the YNHH IDS (or comparable service at CMHC or WHVA) will not be utilized, explain in detail how the PI 
will oversee these aspects of drug accountability, storage, and preparation.   
4. Use of Placebo:  
☒Not applicable to this research project 
 
B.  DEVICES 
 ☒N/A 
 
 
 
 
SECTION III: RECRUITMENT/CONSENT AND ASSENT PROCEDURES  
1. Targeted Enrollment: Give the number of subjects:  
a. Targeted for enrollment at Yale for this protocol: 100 
b. If this is a multi-site study, give the total number of subjects targeted across all sites: N/A 
 
2. Indicate recruitment methods below.  Attach copies of any recruitment materials that will be used. 
☒ Flyers 
☒ Internet/web postings (Criagslist) 
☐ Radio 
☐ Posters 
☐ Mass email solicitation 
☐ Telephone 
☐ Letter 
☒ Departmental/Center website 
☐ Television 
☐ Medical record review*  
☒ Departmental/Center research boards 
☒ Newspaper 
☐ Departmental/Center newsletters 
☐ Web-based clinical trial registries 
☐ Clinicaltrails.gov  
☒ YCCI Recruitment database 
☐ Social Media (Twitter/Facebook):  
 
☒ Other: Direct referral from 
clinicians to RA 
 
 
 
* Requests for medical records should be made through JDAT as described at 
http://medicine.yale.edu/ycci/oncore/availableservices/datarequests/datarequests.aspx 
 
3.  Recruitment Procedures:  
a. Describe how potential subjects will be identified. Flyers and direct clinician referral. Flyers will be posted 
throughout SATU, IOP, and on websites (Craigslist, Department/Center website). Additionally, all clinicians will 
be given a “Client Interest Sheet” that describes the basic study and asks clients to contact study personnel. 

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Clinicians will mention, in-person, that a study is being conducted at SATU/IOP. If a client expresses interest, 
the clinician will have the client fill out the “Client Interest Sheet.”  
b. Describe how potential subjects are contacted. Potential participants will be contacted via two options. One 
option will be that the client takes a flyer tab and calls the research staff via phone. That phone call will be 
used to set up an in person screen, where a consent form will be presented. The other option will be that a 
clinician provides the client with a “Client Contact Sheet” and then the client calls staff to set-up an initial in-
person screen.  
c. Who is recruiting potential subjects? Research staff and indirectly clinic staff who refer 
 
 
4. Assessment of Current Health Provider Relationship for HIPAA Consideration: 
Does the Investigator or any member of the research team have a direct existing clinical relationship with any 
potential subject?  
☐Yes, all subjects 
☐Yes, some of the subjects 
☒No 
 
If yes, describe the nature of this relationship. Write here 
 
5. Request for waiver of HIPAA authorization: (When requesting a waiver of HIPAA Authorization for either the 
entire study, or for recruitment purposes only.  Note: if you are collecting PHI as part of a phone or email 
screen, you must request a HIPAA waiver for recruitment purposes.)  N/A 
Choose one:  
☐ For entire study  
☐ For recruitment/screening purposes only  
☐ For inclusion of non-English speaking subject if short form is being used and there is no translated HIPAA 
research authorization form available on the University’s HIPAA website at hipaa.yale.edu. 
 
i. Describe why it would be impracticable to obtain the subject’s authorization for use/disclosure of this 
data: Write here 
 
ii. If requesting a waiver of signed authorization, describe why it would be impracticable to obtain the 
subject’s signed authorization for use/disclosure of this data: Write here 
 
The investigator assures that the protected health information for which a Waiver of Authorization has been 
requested will not be reused or disclosed to any person or entity other than those listed in this application, except 
as required by law, for authorized oversight of this research study, or as specifically approved for use in another 
study by an IRB. 
 
Researchers are reminded that unauthorized disclosures of PHI to individuals outside of the Yale HIPAA-Covered 
entity must be accounted for in the “accounting for disclosures log”, by subject name, purpose, date, recipients, 
and a description of information provided.  Logs are to be forwarded to the Deputy HIPAA Privacy Officer. 
 
6. Process of Consent/Assent: Describe the setting and conditions under which consent/assent will be obtained, 
including parental permission or surrogate permission and the steps taken to ensure subjects’ independent 
decision-making.  
 

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A trained research staff member will obtain written informed consent prior to any study related 
procedures.  The informed consent process will be conducted in a private, quiet setting.  The staff 
member and the participant will discuss the basic components described in the consent form.  These 
include: participation is voluntary and participants may withdraw without consequences to clinic 
services received, purpose, procedures, randomization, visit schedule, risks and benefits, potential 
compensation, alternatives to study participation, and confidentiality.  The consent form describing 
each of these components will be reviewed and approved by the Yale School of Medicine 
Institutional Review Board (Human Investigations Committee) prior to enrolling any participants.  
Potential participants will be provided an opportunity to ask questions and time to consider his/her 
decision to participate.  A comprehension quiz will be given to ensure the participant has an 
adequate understanding of study as we have done in multiple previous studies (87, 93, 95-97).  A 
copy of the consent form will be given to the participant.   
 
7. Evaluation of Subject(s) Capacity to Provide Informed Consent/Assent: Indicate how the personnel obtaining 
consent will assess the potential subject’s ability and capacity to consent to the research being proposed.  
 
We require participants to read and write in English, and we routinely use a multiple-choice test after 
review of the consent form to determine that participants understand the key points of the research.  
The research staff reviews the test with the participant and clarifies any question which was 
incorrectly answered. 
 
8. Non-English Speaking Subjects: Explain provisions in place to ensure comprehension for research involving 
non-English speaking subjects. If enrollment of these subjects is anticipated, translated copies of all consent 
materials must be submitted for approval prior to use.  
 
N/A 
 
As a limited alternative to the above requirement, will you use the short form* for consenting process if you 
unexpectedly encounter a non-English speaking individual interested in study participation and the 
translation of the long form is not possible prior to intended enrollment?  YES ☐  NO ☒ 
 
Note* If more than 2 study participants are enrolled using a short form translated into the same language, then 
the full consent form should be translated into that language for use the next time a subject speaking that 
language is to be enrolled. 
 
Several translated short form templates are available on the HRPP website (yale.edu/hrpp) and translated HIPAA 
Research Authorization Forms are available on the HIPAA website (hipaa.yale.edu). If the translation of the short 
form is not available on our website, then the translated short form needs to be submitted to the IRB office for 
approval via modification prior to enrolling the subject.   Please review the guidance and presentation on use of 
the short form available on the HRPP website. 
 
If using a short form without a translated HIPAA Research Authorization Form, please request a HIPAA waiver in 
the section above.  
 
9. 
Consent Waiver: In certain circumstances, the HIC may grant a waiver of signed consent, or a full waiver 
of consent, depending on the study. If you will request either a waiver of consent, or a waiver of signed consent 
for this study, complete the appropriate section below.   

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☒Not Requesting any consent waivers  
 
 
SECTION IV: PROTECTION OF RESEARCH SUBJECTS 
 
    Confidentiality & Security of Data: 
1. What protected health information (medical information along with the HIPAA identifiers) about subjects will 
be collected and used for the research?    
 
No PHI will be collected on study CRFs.  We only collect protocol session dates which are changed 
to “number of sessions completed” if data sets are released to other Yale investigators. 
 
2.   How will the research data be collected, recorded and stored? 
 
All research staff and clinicians receive annual Good Clinical Practice, Human Subjects 
Protection, and HIPAA training through the Yale School of Medicine. Our data collection and 
management procedures are fully compliant with HIPAA.  In addition:   
• Our study forms have been designed to avoid collecting identifiable information (e.g., no PHI 
is collected on CRFs).  We generally collect only protocol session dates.  These are changed 
to 'number of sessions completed' if data sets are released to other Yale investigators. 
• Research data are collected on CRFs, and sent to data managers in our research offices on a 
closed secure network.  All computers used by research staff are password protected.  No 
identifying information is on CRFs. 
• The screening of patients using the inclusion and exclusion criteria, and the comprehensive 
evaluations will minimize the risk of including subjects with insignificant substance use (or 
who are otherwise inappropriate for the study).   
• Confidentiality in regards to collected materials will be maintained via a numbered reference 
system maintained by the Project Director.  Participants' names will appear only on the consent 
form, HIPPA authorization form, and "key" form kept by the Project Director.   
• Limits to confidentiality include only disclosure of acute suicidality, homicidality, or abuse of 
a minor, as is standard in clinical practice. 
• Data are stored at our secure data management center; data sets do not include identifying 
information.  At the conclusion of the study, all locator data are destroyed.  Source data is 
generally destroyed 3 years after completion of the study at a secure location and destroyed by 
Shred-It.   
• 
The funding agency, NIDA, may access the data for routine audits. 
 
3. How will the digital data be stored? ☐CD  ☐DVD  ☐Flash Drive  ☐Portable Hard Drive   ☒Secured Server       
☐Laptop Computer  ☒Desktop Computer  ☐Other 
 
4. What methods and procedures will be used to safeguard the confidentiality and security of the identifiable 
study data and the storage media indicated above during and after the subject’s participation in the study?  
 
        See above 
 

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All portable devices must contain encryption software, per University Policy 5100.  If there is a technical reason a 
device cannot be encrypted please submit an exception request to the Information Security, Policy and Compliance 
Office by clicking on url http://its.yale.edu/egrc or email it.compliance@yale.edu 
 
5. What will be done with the data when the research is completed? Are there plans to destroy the identifiable 
data? If yes, describe how, by whom and when identifiers will be destroyed. If no, describe how the data and/or 
identifiers will be secured.  
 
Data are stored at our secure data management center; data sets do not include identifying information.  
At the conclusion of the study, all locator data are destroyed.  Source data is generally destroyed 3 
years after completion of the study at a secure location and destroyed by Shred-It. 
 
6. If appropriate, has a Certificate of Confidentiality been obtained?  
 
Will be applied for pending HIC approval. The Certificate of Confidentiality is being obtained to 
protect client’s omission of substance use and/or a toxicology screen. If the participant tests positive, 
results will be stored as a part of our research record on the secure server.  
 
SECTION V: POTENTIAL BENEFITS 
 
 
Potential Benefits: Identify any benefits that may be reasonably expected to result from the research, either to 
the subject(s) or to society at large. (Payment of subjects is not considered a benefit in this context of the risk 
benefit assessment.)  
 
The major potential benefit to participants is in potential reduction of substance use and improvements 
in cognitive affective functioning via the study treatments, which may, in turn, foster improvement in 
participants’ legal, medical, interpersonal, psychological and occupational functioning.   
 
         SECTION VI: RESEARCH ALTERNATIVES AND ECONOMIC CONSIDERATIONS 
 
1. Alternatives: What other alternatives are available to the study subjects outside of the research?  
 
Individuals who do not wish to participate or who are ineligible for the trial will continue to receive 
standard treatment at SATU/IOP. 
 
2. Payments for Participation (Economic Considerations): Describe any payments that will be made to subjects, 
the amount and schedule of payments, and the conditions for receiving this compensation. 
 
All participants will be offered compensation for time spent completing study assessments including 
$35 for the pre-treatment assessment, $10 for each training session, $35 for posttreatment 
assessment, $50 bonus for completing all training sessions and scheduled assessments and $50 for 
the one-month follow-up. The possible total is $250 for completing all timepoints. Payments to the 
participants will be prorated for those who withdraw prematurely; that is, they will receive payment 
only for those assessments they complete.    
 

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3. Costs for Participation (Economic Considerations): Clearly describe the subject’s costs associated with 
participation in the research, and the interventions or procedures of the study that will be provided at no cost 
to subjects.  
 
Subjects will not be charged for ancillary treatments or evaluations they receive at the clinic.  
Subjects will be charged for treatment as usual at the clinic; where most patients receive treatment 
with no-out of pocket expenses or on a sliding scale. 
 
4. In Case of Injury: This section is required for any research involving more than minimal risk, and for minimal 
risk research that presents the potential for physical harm (e.g., research involving blood draws). 
 
This is a minimal risk trial with no foreseen injury risks. The participant’s insurance carrier will be 
expected to pay the costs of medical care.  No additional financial compensation for injury is 
available. 
 
a. Will medical treatment be available if research-related injury occurs? No 
b. Where and from whom may treatment be obtained? The emergency room or private provider 
c. Are there any limits to the treatment being provided? Yes 
d. Who will pay for this treatment? Patient insurance 
e. How will the medical treatment be accessed by subjects? By self- referral 
 
 
 
 
 
 
 
 

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IMPORTANT REMINDERS 
 
Will this study have a billable service?  Yes ☐  
 No☒ 
 
A billable service is defined as any service rendered to a study subject that, if he/she was not on a study, would 
normally generate a bill from either Yale-New Haven Hospital or Yale Medical Group to the patient or the patient’s 
insurer. The service may or may not be performed by the research staff on your study, but may be provided by 
professionals within either Yale-New Haven Hospital or Yale Medical Group (examples include x-rays, MRIs, CT 
scans, specimens sent to central labs, or specimens sent to pathology). Notes: 1. There is no distinction made 
whether the service is paid for by the subject or their insurance (Standard of Care) or by the study’s funding 
mechanism (Research Sponsored). 2. This generally includes new services or orders placed in EPIC for research 
subjects.  
 
If answered, “yes”, this study will need to be set up in OnCore, Yale’s clinical research management system, for 
Epic to appropriately route research related charges. Please contact oncore.support@yale.edu 
 
Are there any procedures involved in this protocol that will be performed at YNHH or one of its affiliated entities?  
Yes ☐  No ☒