Augmenting Hospitalization for Serious Mental Illness by Targeting Interpretation Bias
Phase: NA
Conditions: Depression, Bipolar Disorder, Anxiety Disorders, Psychiatric Disorder
Sponsor: Mclean Hospital

 
 
Study Protocol 
 
 Study Title:  
Augmenting Hospitalization for Serious Mental Illness: Cognitive Bias Modification 
 
Document Date: 06/8/2021 
 
NCT#: NCT03509181 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Detailed Protocol 
 
PRINCIPAL/OVERALL INVESTIGATOR 
Courtney Beard (Legal last name: Elias), Ph.D. 
 
PROTOCOL TITLE 
Augmenting hospital care for SMI by targeting interpretation bias 
 
This study will be linked to an existing protocol entitled “Establishing the Effectiveness of 
Cognitive-Behavioral Partial Hospitalization for Anxiety, Depression, and Overall Functioning” (# 
2010-P-001047/6) 
 
VERSION DATE 
June 8th, 2021 
 
BACKGROUND AND SIGNIFICANCE 
There is an urgent unmet treatment need for individuals with Serious Mental Illness (SMI).  
NIMH Strategic Objective 4 states that the “chronic disability and early mortality of Serious 
Mental Illnesses (SMI)...demand a rapid response.” Over 4% of the adult US population has a 
SMI, defined as a mental disorder associated with significant functional impairment1. SMI spans 
diagnostic categories, including individuals with a range of mood and anxiety disorders, among 
others. Individuals with SMI die 10-32 years prematurely2, and are almost 13 times more likely 
to die by suicide3. Hospitalization is common among those with SMI, with 9% estimated to have 
received inpatient care in 20141, not including partial hospital and residential levels of care. 
Hospital stays are typically brief, and residual symptoms upon discharge predict relapse and re-
hospitalization4–7. Moreover, hospitalized patients often exhibit residual cognitive and functional 
impairments, despite symptom improvement8. The months following discharge from 
hospitalization are risky, as individuals transition from a highly structured and supportive 
environment to home, acute stressors, and uncertain aftercare. Interventions that efficiently 
accelerate improvement are urgently needed to reduce residual symptoms upon discharge and 
ultimately risk of rehospitalization. Ideally, augmentation strategies need to be reliably and 
easily delivered both in the hospital and continued during the transition to outpatient care.  
 
Interpretation bias is a crucial transdiagnostic target.  Daily life constantly requires the 
resolution of ambiguity. For example, not getting a job or a friend not returning a call can be 
interpreted in multiple ways. The way in which individuals automatically resolve the countless 
ambiguous situations encountered each day has a large impact on their affect and behavior. 
Interpretation bias, the tendency to resolve ambiguity negatively, is a crucial therapeutic target 
due to its causal maintaining role in emotional disorders9,10. Interpretations are made both “on-
line” the moment an individual encounters ambiguity and “off-line” during retrieval of a memory for 
the event. Theoretical models propose that interpretation bias maintains a vicious cycle in which 
an individual experiences the world as more hopeless or threatening, which heightens negative 
affect, increases behavioral avoidance and more biased cognition (e.g., 11,12). Interpretation bias 
maintains psychopathology not only due to its direct effect on affect, but also through cascading 
and interacting effects with other cognitive processes13,14, contributing to a pervasive maladaptive 
cognitive style. Individuals with this cognitive vulnerability have difficulty generating multiple 
interpretations for ambiguous situations, more easily get “stuck” in repetitive negative thinking, 
have poor emotion regulation, and more suicidal ideation (see 15). In a psychiatric hospital 
sample, interpretation bias was a better predictor of suicidal ideation at discharge than any other 
demographic or clinical variable available (see preliminary studies). Moreover, interpretation 
bias upon admission prospectively predicted treatment response.  

 
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Interpretation bias is an important mechanism across species and diagnoses.  
1)   Animals in stress and depression-like states exhibit interpretation bias16,17. 
2)   Self-report, reaction time, behavioral, and neurophysiological measures of interpretation 
bias correlate with psychopathology (Major Depressive Disorder (MDD)/dysphoria18–22; 
anxiety15,23,24; ruminators 21,22; Bipolar Disorder25; e.g., Interpretation bias explained 20% to 30% 
of symptom variance in individuals with MDD18).  
3)   Interpretation bias is a risk factor for developing psychopathology. 
• 
Children at familial risk for mood disorders exhibit interpretation bias26 . 
• 
Interpretation bias prospectively predicts depressive symptoms in adults27. 
• 
Inducing a negative bias in healthy individuals leads to impaired emotion regulation28.  
• 
Interpretation bias better predicts avoidance behavior than self-report symptom 
measures29. 
• 
Experimentally modifying interpretation affects other cognitive biases (attention14, 
memory30,31, imagery32), emotion regulation (attentional control and worry33, rumination34, 
intrusive memories35) and clinical symptoms when delivered over multiple sessions36,37. 
 4)   Interpretation bias influences treatment outcome. 
• 
Baseline level of interpretation bias predicts treatment response in SMI (see preliminary 
studies). 
• 
Change in interpretation bias mediates symptom improvement in treatment 38,39,40–42. 
• 
Rate of change in negative cognitions early in psychotherapy predicts overall symptom 
change43. 
• 
Successful reduction of interpretation bias leads to continued symptom improvement44.  
Given the wealth of data linking interpretation bias to psychopathology across diagnostic 
categories, engaging this target is consistent with the RDoC framework. Interpretation bias is 
linked to several RDoC constructs,45 primarily within the Negative Valence domain (rumination, 
worry, attentional bias, hopelessness, interpretation of facial expressions, risk assessment, 
avoidance behavior, memory retrieval). Interpretation bias has been validated as an important 
mechanism across multiple units of analysis and translationally across animal and human models. 
Targeting interpretation bias has positive effects on behavior, cognition, and clinical symptoms.  
 
CBM-I is a simple, efficient, and effective, method to engage interpretation bias. 
The current proposal aims to develop an efficient and scalable method for engaging 
interpretation bias to improve outcomes during and following hospitalization. Cognitive bias 
modification tasks targeting interpretation bias (CBM-I) are low-intensity, computerized 
interventions that facilitate a more adaptive interpretive style via repeated practice on a training 
task. Importantly, the CBM-I task proposed here aims to engage interpretation bias in an “on-
line” manner - the moment of encountering ambiguity - which more closely matches the manner 
that interpretation bias naturally operates and may not require as much insight as alternative 
methods. The proposed intervention, called HabitWorks, uses a Word-Sentence Association 
Paradigm (WSAP23,41) to reinforce 
an adaptive interpretation style. 
Specifically, this task presents a word 
representing either a negative or 
benign interpretation (“criticize” or 
“praise”) of an ambiguous sentence 
that follows (“Your boss wants to 
meet with you”). Individuals then 
indicate by button press if they think 
the word is related to the sentence. 
The feedback, “You are correct!” is 
displayed if they endorse benign 
interpretations or reject negative 
ones (Figure 1). This task taxes 
+
500 ms 
criticize 
500 ms 
Your boss wants to meet with you 
Participant presses button for (‘not related’) 
You are correct! 
TIME 
Feedback about accuracy 
CBM-I task 

 
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attentional control and working memory to remember the word that flashes and make the 
relatedness judgment. Participants complete the task as quickly and as accurately as possible, 
thereby prompting more automatic responding.  
 
Preliminary studies suggest that CBM-I is more efficient and effective at engaging interpretation 
bias than CBT55. Thus, CBM-I may be particularly useful in brief treatment settings, such as 
psychiatric hospitals. Meta-analyses suggest that CBM-I has large effects on its target 
(Hedges’s g = 0.81)37,48. For studies delivering multiple sessions of CBM-I, effects on clinical 
symptoms are also large. Most relevant to the current proposal, 10 studies support the ability 
of the WSAP CBM-I task to engage its target and improve clinical symptoms40–42,56–61. Of these, 
7 double-blind RCTs yielded medium to large between-group effect sizes (d’s = .48 to 1.05) 
for clinical symptoms that are comparable to existing evidence-based treatments. Of 
note, moderator analyses found that individuals with more biased cognition at baseline benefit 
more from CBM62,63. Thus, it is likely that effect sizes will be larger and more reliable in future 
studies that target this intervention to participants based on this dimension.  
 
To date, the available data is limited primarily by small sample sizes, but are rigorous in design 
with double-blind randomized controlled trials comparing CBM-I to a placebo task. Additionally, 
few studies have tested the long-term effects of CBM-I. Preliminary evidence suggests that 
cognitive and symptom changes may endure for at least two weeks and up to six months64–68. 
The proposed study will provide crucial follow-up data to determine whether changes endure at 
3 months post-discharge. 
 
CBM-I is an ideal hospital augmentation because it is brief (i.e., 10-minute sessions), 
standardized to ensure reliable delivery, requires minimal staff time, requires minimal language 
skills and does not require patients to apply complex theories on their own. Combining CBM-I 
with hospital care and continuing following discharge is consistent with recent guidelines for on-
line treatments recommending a standardized, concentrated dose followed by spaced out, 
booster sessions69. 
 
Pilot study in a partial hospital. Participants (n = 65) met criteria for a range of diagnoses, and 
70% met criteria for moderate or high suicide risk on the clinician-administered MINI75(specific 
suicide plans and suicidal gestures and attempts). The average number of prior hospitalizations 
was 2 (range 0 to 20). This pilot study did not include a measure of functional impairment; 
however, a prior sample from the same partial hospital reported significant disability on the 
Sheehan Disability Scale (M = 7 (out of 10) for each domain). 
Does interpretation bias matter in a hospital population? Almost all prior studies of interpretation 
bias have compared a healthy control group to a psychopathology group; thus, we first 
examined the clinical relevance of interpretation bias within a SMI sample. Even in a restricted 
range of high symptom severity in our partial hospital, robust associations were found with 
interpretation bias. Controlling for baseline symptom severity, patients who endorsed fewer 
benign interpretations at admission were less likely to respond to treatment (defined as 
“very much improved” on the self-reported Clinical Global Improvement Scale), and this model 
accounted for 28% of the variance in treatment response. Interpretation bias upon 
admission also prospectively predicted suicidal ideation at discharge better than any other 
demographic or clinical variable76.  
Randomized Controlled Trial. Patients were randomly assigned to CBM-I or a neutral control 
condition. All individuals received treatment as usual at the partial hospital. Patients completed 
the 10-minute task each day they attended the partial hospital on a laptop computer. 
Assessments of interpretation bias and symptoms occurred upon admission and discharge.  
Feasibility and acceptability: 99% of participants completed daily sessions of CBM-I. Attrition 
rate for the discharge assessment was low (11%), typically due to inpatient hospitalization or an 

 
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unexpected discharge. Patients easily fit the brief task into either their lunch break or between 
appointments. A bachelor’s level clinic staff member delivered CBM-I in this pilot study. Thus, 
the CBT treatment providers were not directly involved. Not requiring a mental health clinician 
substantially improved the scalability of the intervention. An exit questionnaire revealed 
moderate to high satisfaction. On a scale of 1 to 7, patients’ mean helpfulness rating was 5.2 
(SD=1.3). Qualitative feedback revealed that most patients found the intervention relevant and a 
helpful complement to CBT. Patients noted an increased awareness of negative thought 
patterns, a flexible interpretation style, and interruption of their automatic associations. Patients 
connected CBM-I with the CBT they received even without the CBT therapist being involved: “It 
helped me examine and challenge my Negative Automatic Thoughts” – a term presented in the 
CBT groups and “It helped solidify the program”.  
Target engagement: Following an average of 7 sessions, CBM-I decreased negative 
interpretations (d =2.59) and increased benign interpretations (d =2.28) of ambiguous situations, 
both of which significantly differed from a neutral comparison condition. In the CBM-I group, 
number of sessions correlated with change in negative interpretations (r = .37, p =.03), 
providing preliminary evidence for a dose-response relationship.  
Clinical outcomes: In patients who exhibited an interpretation bias upon admission (defined as 
endorsing ≥ 60% of negative interpretations), there was a significant treatment effect on the 
Clinical Global Improvement Scale: 36% of patients completing CBM-I were classified as 
responders (“very much improved”) compared to 0% in the control, χ2 = 4.41, p < .04. There 
was also a moderate between group effect size for improvement in well-being (d = 0.6).  
 
In sum, this pilot study revealed good acceptability and feasibility, target engagement, and 
preliminary evidence that CBM-I may augment partial hospital treatment effects on global 
improvement and well-being. However, this initial study did not include a comprehensive 
assessment of interpretation bias, nor any mid-point or follow-up assessments. Moreover, it only 
offered a basic, non-personalized, computer version of CBM-I during hospitalization (~7 
sessions). Given the preliminary evidence for a dose-response relationship, the proposed study 
will allow patients to continue treatment following discharge from the hospital to consolidate and 
generalize changes in cognition once individuals return to their daily lives. The proposed study 
will follow patients 3-months after discharge to evaluate the durability of cognitive changes, and 
the link to primary (clinical global improvement; psychosocial functioning) and secondary 
outcomes (e.g., suicidal ideation, rehospitalization).  
     
Rationale for Proposed Study.        
Individuals who require a hospital level of care are at risk for relapse, rehospitalization, and 
suicide, particularly during the months post-discharge. Augmentation strategies that can be 
reliably delivered both in the hospital and continued during the transition to outpatient care are 
urgently needed. Interpretation bias, a crucial mechanism underling many forms of 
psychopathology, is not sufficiently altered for all individuals by existing treatments. CBM-I, a 
low-intensity intervention, engages interpretation bias and leads to symptom improvement. 
However, apart from our pilot study, CBM-I hospital delivery procedures have not been 
developed or tested. Thus, we propose to develop a smart-phone delivered intervention, 
HabitWorks, to allow better accessibility, patient engagement, assessment, and a means to 
bridge the transition from partial hospitalization to outpatient care. Results will provide pilot data 
to support an R01 effectiveness trial.  
 
We will test HabitWorks as an augmentation to partial hospital (PH) treatment. Over 400 PHs in 
the US are used either as a step-down strategy or alternative to inpatient treatment. PHs 
provide intensive treatment during the day, allowing patients to return home in the evening. 
Results obtained from proposed study should generalize because the structure of the proposed 

 
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site is consistent with the structure of partial hospital and day programs across the US (e.g.,70). 
Acceptability data should also be relevant to individuals receiving inpatient hospitalization 
because half of patients attending the partial hospital are referred from inpatient care. 
 
I. 
SPECIFIC AIMS 
 
The primary goals of this R34 pilot effectiveness trial are to develop HabitWorks for partial 
hospital augmentation and transition to outpatient care and obtain pilot data to support a fully-
powered R01 effectiveness trial.  
 
Aim 1: Develop a smart-phone delivered intervention to augment hospital care  
Aim 2: Obtain pilot data to support a fully-powered RCT, including measures of:  
(a) Target engagement (improvement in interpretation bias)  
(b) Feasibility and acceptability of HabitWorks and procedures for hospital and home 
delivery 
(c) Clinical global improvement and functioning 
We hypothesize that the HabitWorks intervention and research procedures will meet a priori 
goals for feasibility, acceptability, and clinical utility (see data analysis section). 
 
 
Aim 3 : Obtain pilot data on CBM’s effect on suicidal ideation and behaviors.  
 
 
III. SUBJECT SELECTION 
 
Phase 1: Development (COMPLETED) 
In this first phase of this R34 pilot effectiveness trial, there will be no human subjects. The PI will 
meet with various stakeholders (e.g., clinicians at study site, clinic directors, BHP Patient 
Advisory Board) to obtain feedback about the HabitWorks app and research procedures. 
 
Phase 2: Open Trial (Enrollment COMPLETE) 
We will enroll 16 participants meeting the following inclusion criteria. 
 
Inclusion criteria: a) currently receiving partial hospital care at the study site; b) age ≥18; c) at 
least moderate symptom severity (PHQ-9 or GAD-7 score > 10); d) no current psychiatric 
symptoms that would prevent informed consent or understanding of research procedures (e.g., 
active symptoms of psychosis, mania), e) no current/active suicidal ideation (PHQ-9 item 9 > 1) 
and f) signing a release of information for treatment providers is an inclusionary requirement for 
study participation. Consistent with the RDoC, DSM-5 diagnosis will not affect eligibility. We 
anticipate a range of primary diagnoses, principally mood and anxiety disorders. Participants will 
be selected based on their baseline level of interpretation bias. Only patients who exhibit at 
least a minimal level of interpretation bias <80% accuracy on the WSAP) will be offered 
participation.  
 
Source of subjects. The Behavioral Health Partial Hospital Program (BHP) at McLean Hospital 
admits over 850 individuals per year. The PI is Assistant Director of Research and a staff 
psychologist at the BHP, and Dr. Bjorgvinsson (Co-I) is Director. The BHP delivers group and 
individual CBT to patients with a range of psychiatric disorders, primarily mood, anxiety, 
personality, and psychotic disorders. Treatment focuses on concepts such as self-monitoring, 
cognitive restructuring, and behavioral activation. The average length of stay is 8 days. Patients 
are assigned a case manager, psychiatrist, and skills coach. 
 

 
7 
Recruitment methods. Study staff will review partial hospital patients’ scores on the PHQ-9 
and GAD-7 to determine initial eligibility. On patients’ second day at the BHP, study staff will 
offer participation to those who score above the cut-offs. Interested patients will complete the 
interpretation bias assessment to determine eligibility. Patients may also express interest to 
study staff via flyers posted at the BHP.  
 
Phase 3: Randomized controlled trial. 
In this Randomized Control Trial, we will recruit 64 partial hospital patients. All inclusion and 
exclusion criteria, sources of subjects, and recruitment methods are the same as detailed in the 
Phase 2: Open Trial, except that current/active suicidal ideation criteria will be removed, such 
that individuals with all scores for phq9 item 9 are eligible. Further, after reaching our initial 
recruitment goal of 64, we will continue to recruit those participants that identify as BIPOC in 
order to achieve our proposed percentage of BIPOC participants. 
 
 
III. SUBJECT ENROLLMENT 
Procedures under existing BHP protocol: 
Upon arrival to the Behavioral Health Partial Program, all patients will be oriented by the 
Community Residence Counselors and/or Nurse Practitioner (all CITI certified staff members) to 
the program, building and set-up of the treatment.  Once oriented, patients will also be informed 
that as part of their treatment at the BHP they will be completing extensive self-report measures 
and a diagnostic interview. The Community Residence Counselors will explain to patients about 
our current research study examining the efficacy of CBT in naturalistic settings and ask 
whether or not they would like to consent to having their assessments be de-identified and 
included in our research database. It will also be explicitly instructed to patients, that if they were 
to refuse consent/participation, their treatment at the BHP will not be affected in any way.  
Patients will have the option to rescind their consent/participation at any point, and subsequently 
the Research Coordinator will take the appropriate measures to accommodate this decision. 
After obtaining informed consent from patients for the main effectiveness study, clinical staff will 
review a flyer about other studies being conducted in the program. Thus, clinical staff will inform 
patients of the research prior to staff approaching eligible participants. BHP clinical and 
research staff will reinforce that participation is voluntary and the decision not to participate will 
not affect their care at any time.  
 
Procedures under proposed protocol: 
The research coordinator or another member of the study staff will approach potentially eligible 
patients on their second day in the program and inform them about the study. During the Open 
Trial patients approached scored above a 9 on PHQ-9 or GAD-7, PHQ-9 item9 < 2 and they 
consented to main BHP study. During the RCT patients approached scored above a 9 on PHQ-
9 or GAD-7 and had no criteria for PHQ-9 item 9 and can consent to main study at any time 
prior to consenting to the current study. Interested patients will then receive a detailed 
description of the study procedures, risk, and benefits and will review a study fact sheet for 
remote consent with trained study staff. They will then complete the interpretation bias 
assessment to determine eligibility to participate in the trial. 
 
Randomization. We will use MINIMPY software to randomize participants to HabitWorks or 
Symptom Tracking. MinimPy is a desktop application program for sequential allocation of subjects to 
treatment groups in clinical trials by using the method of minimisation 
(https://sourceforge.net/p/minimpy/wiki/Home/).  
We will enter age and baseline level of interpretation bias as variables for which the program will 
balance group assignment. The PI will randomize all participants following their eligibility 
session. 

 
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V. STUDY PROCEDURES 
 
Phase 1: Development (COMPLETED) 
 
The team will develop the HabitWorks smartphone app:    
Harnessing the strength of smart-phone technology to enhance skill acquisition, HabitWorks will 
prompt patients to complete a practice session at set times to ensure adequate dosage and 
spacing of sessions. We will employ techniques known to enhance user engagement, such as 
progressing through levels, assigning points for correct responses, and tracking of progress. 
These reinforcing features may improve adherence, which may ultimately enhance effects on 
interpretation bias. We will develop the HabitWorks intervention to address common barriers to 
eventual implementation (e.g., customizability/personalization, ease of use)88. As part of a 
different project (MH097820), the PI developed an algorithm that creates a personalized CBM 
intervention for anxiety disorders based on demographic and clinical characteristics. We will 
develop a similar algorithm for a SMI population. Specifically, HabitWorks will use demographic 
questions, measures of symptom severity (see Measures), and questions about specific types 
of situations that are most relevant for the patient to create a personalized stimulus set (e.g., 
someone with financial worries will see trials related to this domain; a participant without 
children will not see stimuli related to parenting). We will create the stimulus pool from our 
previous trials, comprising a minimum of 600 word-sentence pairs. This large pool of stimuli will 
allow the intervention to present a mixture of new word-sentence pairs in each session. 
 
We will work with the software programmer to create a user-friendly and visually appealing 
smart-phone app, as well as the back-end infrastructure to access and manage the data 
through Partners RedCap. The app will use SSL encryption, and no HIPAA-defined personally 
identifiable information will be collected via the app. The app will be developed through Apple’s 
Research Kit and Android’s ResearchStack, both of which are open source frameworks that 
allow researchers and developers to create apps for medical research. 
 
 
Phase 2: Open Trial (Enrollment COMPLETE) 
We will conduct an open trial to obtain pilot data. In the open trial, we will enroll 16 patients with 
assessments at pre-, post-, 1-month, and 3-month follow-ups to pilot the measures we expect to 
use in the RCT. At the end of the 1st iteration (n=4), the PI will compare actual data to target 
feasibility and acceptability outcomes. Deviations from target outcomes will prompt investigation 
and discussion with the research team and advisory board, and possible revision of the 
intervention or research procedures. We will repeat this process in 3 more iterations of 4 
patients. The open trial will inform the design of the RCT. 
 
This is a sub-study under the existing protocol entitled “Establishing the Effectiveness of 
Cognitive-Behavioral Partial Hospitalization for Anxiety, Depression, and Overall Functioning” (# 
2010-P-001047/6). Data obtained under the existing BHP protocol will be shared with 
Investigators from this study. 
 
Procedures under existing BHP protocol: 
This research will be conducted with each patient who enters our program (up to 900 adult 
patients each year).  As the Behavioral Health Partial Program is an adult CBT-based program, 
all patients are at least 18 years of age and up.  Upon registration in our program, patients will 
receive the Mini-International Neuropsychiatric Interview (M.I.N.I.), a 20-45 minute non-invasive, 
structured diagnostic psychiatric interview to assess for psychiatric diagnostic criteria. Patients 
will also be asked to complete a self-report questionnaire assessing for demographic variables, 
symptom severity, functional impairment, and CBT skill acquisition upon registration, and upon 

 
9 
discharge. Information will be stored on-site, in a locked drawer, in a secure office. Patients’ 
original questionnaires will be maintained for no longer than five years.  Only the Principal 
Investigator (Courtney Beard), Research Coordinator, Nurse Director (Lynn Kopeski), and 
Program Director (Throstur Bjorgvinsson) will have access to PHI.  However, the majority of PHI 
will be stored electronically.  The proposed research will be using RedCap Database, an 
encrypted, electronic database that is both HIPPA compliant (Health Insurance Portability and 
Accountability Act) and approved by Partners IRB for the administration and storage of human 
subject information (for additional information on the RedCap Database feature see 
http://rc.partners.org).  To minimize inconvenience and provide maximum benefit to patients, 
data collection will be streamlined as a part of standard clinical care. Clinically salient 
information, including diagnostic output and patient's self report scores, will be highlighted and 
presented to clinical team managers and others involved in patient services. Non-BHP patients 
will not be able to participate in this research. 
 
Procedures for Proposed Protocol: 
Participants’ data collected as part of protocol (# 2010-P-001047/6) will be used to determine 
eligibility for this study, and to characterize the demographic and clinical characteristics of the 
sample and as outcome assessments. Thus, only participants who consent to the main BHP 
study protocol will be eligible for the current study. 
 
On patients’ second day at the BHP, staff will offer participation Interested patients will complete 
the eligibility assessment. Study staff will immediately review scores on the measure of 
interpretation bias (WSAP; see Measures) to determine eligibility. If eligible, they will complete 
the remaining pre-assessment measures. If ineligible, patients will be compensated and 
continue with treatment as usual at the BHP, 
 
The partial hospital employs a bachelor’s level progress monitoring coordinator who collects 
self-report data from patients and transmits this information to treatment teams. Identical to the 
pilot study, the PI will train this person to orient patients to HabitWorks and reinforce the 
rationale and instructions provided in the videos embedded within the app. The staff member 
will also conduct brief, in-person “check-ins” as often as desired by the patient, to answer 
questions about the intervention, provide accountability for the patient, and to provide 
encouragement. This extra support and human connection with the HabitWorks program should 
ensure adherence during the acute phase of treatment. On occasions when the progress 
monitoring coordinator is unavailable, a member of the study staff may provide the orientation 
and check-ins. 
 
Participants will complete a task designed to improve interpretation biases. Each session 
includes 150 trials of the previously validated word-sentence association paradigm during each 
session (~10 min). The task presents ambiguous sentences (“You failed an exam”) and 
provides positive feedback (“you are correct!”) when participants endorse benign 
interpretations/attributions (“difficult test”) and negative feedback (“you are incorrect!”) for 
negative interpretations/attributions (“stupid”). 
 
Once enrolled, participants will complete HabitWorks daily on their smart phones in a quiet room 
while attending the partial hospital, three times per week at home for 1-month following 
discharge, and as desired during the final 2 months. Sessions during the follow-up period will 
include approximately 75 trials and thus will only require 5 minutes to complete. 
 
During the 1-month post-acute period, participants will complete assessments of symptoms 
(PHQ-9 and GAD-7) as often as desired, including optional once weekly check-ins and daily 
assessment of affect (see EMA description in Measures). These surveys will be administered 

 
10
via Metricwire. The Metricwire app was designed to protect participants’ privacy, confidentiality, and data 
security. Only research personnel will have access to study information. Data collected by the Metricwire 
app is encrypted, and downloaded by the researcher to the local research server in a de-identified format 
(i.e., subject ID number). The local research server is only accessible by study staff. Study staff will 
provide orientation to the app and answer any questions regarding the assessments and data collected.  
 
 
 
Following Long-Term phase (post 3months from discharge) EPIC Research trained study staff 
will check every patients EMR, whether or not they completed the 3month assessment, for data 
on rehospitalization or ER visits and the reason why. This data will then be de-identified and 
kept in partners secure storage (Dropbox). 
 
Retention. Post-discharge, staff will monitor participants’ progress with the HabitWorks app 
daily and will call participants who have not completed any sessions in the past week. The 
purpose of these phone calls will be to help identify barriers and brainstorm potential solutions. 
To increase retention, we will: a) obtain contact information of individuals who will always know 
how to reach participants; b) pay participants for assessments; and c) provide transportation if 
needed, flexible scheduling for the assessments, and in rare individual cases conduct interviews 
via telephone.  
 
 
Measures. 
Participants will complete measures that are already administered as part of standard clinical 
care at the BHP. 
The Mini International Neuropsychiatric Interview (MINI) is a structured interview assessing for 
DSM-V Axis I disorders. The MINI will be administered by doctoral practicum students and 
interns in clinical psychology who will receive weekly supervision by the post-doctoral fellow. 
The PHQ-9 is a brief self-report questionnaire assessing symptoms of depression. Patients 
complete the PHQ-9 at daily. 
The GAD-7 is a brief self-report questionnaire assessing symptoms of anxiety. Patients 
complete the GAD-7 daily. 
The Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q97) will assess 
satisfaction and quality of life. 
To assess suicidal ideation and behaviors (lifetime, past month), we will use the interview 
administered Columbia Suicide Severity Rating Scale (CSSRS98). During remote assessments, 
when clinical interview is not possible, we will use an adapted form of the CSSRS as a self 
report measure. 
 
Participants in proposed study will complete the following additional measures: 
 
WSAP23,41. Word-sentence pairs representing benign or negative interpretations are presented, 
and patients decide if they are related or not. In the assessment version of this task, no 
feedback is given about the accuracy of participants’ responses. The task will record reaction 
times for 4 WSAP trial types (endorse benign, reject benign, endorse negative, reject negative), 
reflecting the relative speed or ease with which participants make interpretations. We will 
Treatment phase 
Location 
Frequency of sessions 
Session 
duration 
Acute (1 to 14 days) 
Hospital 
Daily to augment CBT-based hospital treatment 
10 min 
Transition (1-month) 
Home 
3x per week to transition from intensive hospital to outpatient care 
5 min 
Long-Term (2 mo) 
Home 
Sessions completed as desired by individual 
5 min 

 
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calculate reaction time bias scores for each trial type (negative vs. benign). The task will also 
record participants’ responses (yes/no) for each trial type (negative vs. benign) to allow 
calculation of the percentage of negative and benign interpretations endorsed.  In the case of 
remote recruitment in phase 2b and 3, the assessment version of the WSAP will be used as a 
screening tool prior to the Pre-treatment. 
 
The Scenario recognition 
task is the most widely 
used assessment of 
interpretation bias in CBM-
I91 and will ensure that 
effects are not solely 
attributable to practice or 
method effects. In brief, 
participants first read 10 
ambiguous scenarios and 
a comprehension question 
to ensure they actually 
read the scenario. In the 
second phase, 
participants read the title 
of the ambiguous scenario 
followed by four versions 
of the final sentence 
presented in a random 
order. Sentences 
represent a) a possible 
positive interpretation, b) a 
possible negative 
interpretation, c) a positive 
foil, and d) a negative foil. 
Participants rate each sentence for its similarity in meaning to the original story using a 4-point 
scale ranging from 1 (very different in meaning) to 4 (very similar in meaning). We will calculate 
the average similarity rating for negative and positive interpretations. 
 
 
Co-primary clinical outcomes will include stake-holder relevant measures of global improvement 
and functioning. The PI will train study staff to administer these brief scales and will monitor 
reliability using established procedures at the BHP. 
Clinician-administered Clinical Global Improvement Scale (CGIS93) to assess global 
improvement.  
Clinician-rated 5-item Work and Social Adjustment Scale (WSAS94) to assess interference 
caused by the patient’s symptoms in the domains of work, home management, leisure, and 
family relationships.  
 
Other self-report measures will include: 
 
Credibility Expectancy Questionnaire104 to assess patients’ beliefs about the treatment 
expectancy (affectively based) and treatment rationale credibility (cognitively based).  
 
Exit Questionnaire to assess patients’ satisfaction with the treatment provided.  
 
Beck Hopelessness Scale (BHS99)) to assess negative attitudes about the future.  
Schedule of Assessments 
Pre 
Daily 
Post 
1-mo 
3-mo 
Interviews 
MINI 
X 
 
 
 
 
CGIS 
 
 
X 
X 
X 
WSAS 
X 
 
X 
X 
X 
Longitudinal Interval Follow-Up Eval     
 
 
 
X 
X 
Qualitative Exit Interview (open trial 
and first 20 in RCT) 
 
 
 
X 
 
CSSRS 
X 
 
 
X 
X 
App or Computer Delivered 
*The HabitWorks app will deliver all daily surveys. Redcap will be used to 
deliver computerized surveys during in-person assessments. 
Demog. Form, CEQ 
X 
 
 
 
 
PHQ-9; GAD-7 
X 
X 
X 
X 
X 
Q-LES-Q, BHS, CFI, MPS, GSE 
X 
 
X 
X 
X 
Exit Questionnaire  
 
 
 
X 
 
WSAP  
X 
X 
X 
X 
X 
Scenario Recognition Task 
 
 
 
X 
 
EMA PANAS 
X 
X 
X 
X 
X 
CSSRS- Self Report 
X 
 
 
X 
X 
System Usability Scale- HW condition 
 
 
 
X 
 
TWEETS- HW condition 
 
 
 
X 
 

 
12
Cognitive Flexibility Inventory: The Cognitive Flexibility Inventory is a measure of mental 
flexibility and assesses the degree to which individuals are able replace maladaptive thoughts 
with adaptive ones and maintain a balanced mindset. 
 
15-Item Multidimensional Perfectionism Scale (short form): The MPS is a widely used self-report 
measure of perfectionism.  
 
10-item General Self Efficacy Scale: The GSE is a widely used self-report measure of self  
efficacy. 
 
Ecological Momentary Assessment (EMA) 
We will pilot the use of EMA to assess fluctuations in positive and negative affect using the 
PhenX Toolkit recommended measure PANAS-X 100. During the 1-month transition phase, 
participants will complete the PANAS-X 4 times every day via the smartphone app. The surveys 
will be administered at random times during each one of 4 stratified blocks of time (9am-12pm, 
12-3pm, 3-6pm, 6-9pm).  
 
Other interview measures will include: 
The Longitudinal Interval Follow-Up Evaluation (LIFE103) to assess psycho-pharmacotherapy 
use, including any medication or dosage changes. 
  
 
Study staff will conduct a qualitative exit interview with prompts about overall patient 
experiences, acceptability and feasibility, relevance of the stimuli, and user-experience of the 
app. 
 
Treatment adherence. Number of sessions completed will be recorded by the app and will be 
used as both a measure of feasibility/ acceptability, and as needed as a control variable in 
analyses.  
 
Compensation. Participants will receive compensation for their time to complete assessments. 
Participants will receive $20 for the eligibility assessment and pretreatment assessment, and an 
additional $20 for the post-treatment assessments. They will receive $30 for the 1-month and 3-
month follow-up assessments, $30 for completing at least 80% of the EMA surveys each week 
for 1 month, and $20 for the post-treatment qualitative interview (open trial only). 
 
 
Phase 3: Randomized Controlled Trial 
We will recruit 84 participants for the RCT with optional assessments at pre-, post-, 1-month and 
3month timepoints. Follow-up assessments at the 1-month and 3-month timepoints will be 
considered optional for participants. In this RCT we will randomize individuals to receive the 
experimental condition HabitWorks or a Symptom Tracking condition. Those in the HabitWorks 
group will complete the CBM task via smartphone application as an augmentation to treatment 
as usual(TAU), while those in the Symptom Tracking Group will complete weekly symptom 
monitoring surveys as an augmentation to TAU.  
 
Procedures under existing protocol: 
All procedures under existing BHP protocol are remaining the same as the Open Trial, except 
for the changes in the inclusion criteria that eliminates the PHQ-9 item 9 score <2 requirement 
and restricts additional recruitment to BIPOC participants with the goal of reaching our proposed 
percentage of BIPOC participants. 
 

 
13
Procedures for Proposed Protocol: 
The research coordinator or another member of the study staff will approach potentially eligible 
patients (scoring above a 9 on PHQ-9 or GAD-7) on their second day in the program and inform 
them about the study, and send them a brief screening survey to assess initial eligibility prior to 
study consent and enrollment (i.e., owns an iPhone, willing to sign a release of information for 
outpatient providers, willing to use the app per protocol and willing to complete follow-up 
assessments). If patients are eligible based on this initial screening questionnaire, they will then 
receive a detailed description of the study procedures, risk, and benefits and will review a study 
fact sheet for remote consent with trained study staff. Additionally, those patients who did not 
originally consent to the BHP main study, will have to consent to the main study in order to be 
eligible for the RCT. They will then complete the interpretation bias assessment to determine 
eligibility to participate in the trial. 
 
On patients’ second day at the BHP, staff will offer participation. Interested patients will 
complete the eligibility assessment. Study staff will immediately review scores on the measure 
of interpretation bias (WSAP; see Measures) to determine eligibility. If eligible, they will 
complete the remaining pre-assessment measures. If ineligible, patients will be compensated 
and continue with treatment as usual at the BHP.  After the eligibility session, patients will be 
randomized into either HabitWorks or Symptom Tracking groups by the PI. 
 
The PI will train research staff to orient patients to HabitWorks and Symptom Tracking 
conditions and reinforce the rationale and instructions provided in instructional videos.  
 
HabitWorks 
Participants assigned to HabitWorks will complete the same procedures as outlined in the Open 
Trial. Specifically, participants will complete a task designed to improve interpretation biases. 
During each session, participants complete the previously validated word-sentence association 
paradigm (~10 min). The task presents ambiguous sentences (“You failed an exam”) and 
provides positive feedback (“you are correct!”) when participants endorse benign 
interpretations/attributions (“difficult test”) and negative feedback (“you are incorrect!”) for 
negative interpretations/attributions (“stupid”). Sessions during the transition phase are shorter 
(~5 min). 
 
Once enrolled, participants will be asked to complete HabitWorks daily on their smart phones in 
a quiet room while attending the partial hospital, at least three times per week at home for 1-
month following discharge, and as desired during the final 2 months. During the 1-month post-
acute period, participants may complete assessments of symptoms (PHQ-9 and GAD-7) as 
often as desired, including optional once weekly check-ins for the study. For people in the 
HabitWorks condition, these surveys are administered via the HabitWorks app. 
 
During the 1-month post-discharge period, participants will also complete daily assessment of 
affect (see EMA description in Measures). These surveys will be administered via Metricwire. 
The HabitWorks and Metricwire app was designed to protect participants’ privacy, 
confidentiality, and data security. Only research personnel will have access to study information. 
Data collected by the Metricwire app is encrypted, and downloaded by the researcher to the 
local research server in a de-identified format (i.e., subject ID number). The local research 
server is only accessible by study staff. Study staff will provide orientation to the app and 
answer any questions regarding the assessments and data collected.  
 
HabitWorks 
Treatment phase 
Location 
Frequency of sessions 
Duration 

 
14
 
Symptom Tracking 
Participants assigned to the Symptom Tracking condition will be presented with a treatment 
rationale about the benefits of self-monitoring. They will complete daily symptoms surveys as 
part of routine clinical care while attending the BHP and will complete optional weekly symptom 
surveys, as well as the EMA, during the month post-discharge via the MetricWire app. 
Additionally during the Long Term phase, months 2 and 3 post discharge, participants can 
complete weekly symptom monitoring surveys as desired. 
 
 
If under any circumstance in-person assessments are not possible, all study assessments and 
procedures can be completed remotely via telephone, encrypted email, or video-call, depending 
on the preference of the participant (see Risks and Discomforts section). Additionally, in cases 
of remote recruitment, participants will be screened over the phone and will be sent the 
assessment version of the WSAP (see measures) to assess eligibility prior to consent. 
 
Retention. Post-discharge, staff will monitor participants’ progress with the HabitWorks app and 
MetricWire app and will call participants who have not completed any sessions in either app 
over the past week. They will monitor this each week for the month of transition phase. The 
purpose of these phone calls will be to help identify barriers and brainstorm potential solutions. 
To increase retention, we will: a) obtain contact information of individuals who will always know 
how to reach participants; b) pay participants for assessments; and c) provide transportation if 
needed, flexible scheduling for the assessments, and in rare individual cases conduct interviews 
via telephone. In the event that a participant is unable to attend follow-up assessments, or 
follow-up assessments are not occurring in person, we will conduct the entire assessment 
through remote methods such as encrypted email, phone call, and video call. We will follow 
these procedures for both treatment conditions.  
 
Measures: 
 
All measures from the Open Trial will remain the same. Additionally, the RCT will include the 
following new measures:  
 
Edinburgh Handedness Inventory- Short Form116 is a 4-item widely used validated measure of 
handedness. The EHI will be used to determine eligibility for the EEG Assessment. Participants 
rate how often they use their left or right hand in 4 different practical examples on a scale of 
+100 (“Always Right”) to -100 (“Always Left”). We will consider a score of +50 or above as right 
handed and eligible for EEG. 
Acute (1 to 14 days) 
Hospital 
Daily to augment CBT-based hospital treatment 
10 min 
Transition (1-month) Home 
3x per week to transition from intensive hospital to 
outpatient care, 4x daily affect surveys, weekly symptom 
monitoring survey 
15 
min/day 
Long-Term (2 mo) 
Home 
Sessions completed as desired by individual 
5 min 
Symptom Tracking 
Treatment phase 
Location 
Frequency of sessions 
Duration 
Acute (1 to 14 days) 
Hospital 
No additional treatment, self-monitoring as part of TAU 
na 
Transition (1-month) 
Home 
4x daily affect surveys as well as weekly symptom monitoring 
survey 
15 
min/day 
Long-Term (2 mo) 
Home 
Symptom monitoring surveys as desired 
2min/week 

 
15
 
 
The System Usability Scale(SUS117): The SUS is a 10-item assessment of the usability of a 
given product or service, and was intended to be used for all types of technological 
interventions. It collects the subjective self-report of usability and specifically relates to user 
experience of effectiveness, efficiency, and satisfaction. Participants will rate their agreement on 
a 5point likert scale ranging from 1(Strongly Disagree) to 5(Strongly Agree). This survey will be 
administered at the 1-Month Assessment, only for individuals in the HabitWorks condition. 
 
The Twente Engagement with Ehealth Technologies Scale (TWEETS118): The TWEETS is a 9-
item self-report measure used to assess user engagement with health apps. It will be used to 
assess the level of cognitive, affective, and behavioral engagement that participants have with 
the HabitWorks app. Participants will rate their agreement on a 4point likert scale ranging from 
0(strongly disagree) to 4(strongly agree). This survey will be administered at the 1-Month 
Assessment, only for individuals in the HabitWorks condition. 
 
 
Study staff will conduct a qualitative exit interview for the first 20 participants regarding 
questions similar to the Open Trial, but pertinent to either Symptom Tracking or HabitWorks 
treatment conditions. Additionally participants will be asked about their experience in relation to 
the EMA in transition phase.  
 
Finally, the Symptom Tracking condition will receive a different version of the Exit Questionnaire 
and the Credibility and Expectancy Questionnaire. 
 
Compensation. Participants will receive compensation for their time to complete assessments. 
Participants will receive $20 for the pretreatment assessment, and an additional $20 for the 
post-treatment assessments. They will receive $30 for the 1-month and 3-month follow-up 
assessments, and $20 for the post-treatment qualitative interview (first 20 participants only). 
Participants will also be compensated for completing EMA surveys- they will receive $10 each 
week they complete any surveys at all, and a bonus $30 for every week they complete 70% 
surveys (19/28).  
 
If, for whatever reason, a participant cannot or will not accept checks, the study will compensate 
with a one-time $50 giftcard. 
 
 
VII. RISKS AND DISCOMFORTS 
We believe that the risks of this study are minimal as most assessments used in this study are 
part and parcel of clinical care and are therefore no more invasive than treatment as usual in 
our program. The WSAP task and have been studied extensively by the PI and other 
researchers, with no adverse events reported. 
 
Common Risks include: transient negative emotional reactions to the computer task, EMA 
protocol or questionnaires. 
 
Uncommon Risks include: coercion, breach of confidentiality, and clinical deterioration,  
 
All treatments carry with them the risk of loss of confidentiality, increased distress due to 
assessment or intervention procedures, and risk of ineffective intervention. Pharmacotherapy 
carries with it the risk of associated physical problems, including both mild and severe side 

 
16
effects and interactions between medications. We note that pharmacotherapy is not proscribed 
for participants in this trial.  
 
All patients will be receiving partial hospital care. Following discharge from the hospital, patients 
are expected to continue with their outpatient treatment plan.  
 
 
Protection Against Risk. All aspects of the study will be conducted in accordance with HIPAA.  
 
 
The areas of risk outlined above will be minimized by the following procedures. 
 
1. The risk of potential coercion will be minimized by following standard procedures for 
obtaining informed consent.  Study personnel will fully explain the study procedures, 
risks, benefits, and alternatives to all potential participants.  It will be emphasized that 
their participation will have no impact on other services they receive at the partial 
hospital, or at other departments of McLean Hospital. Potential participants will not be 
recruited by their treatment team. All individuals will be reminded that there is no penalty 
for patients who choose not to participate or to withdraw from the study; they may refuse 
to participate or drop out of the study at any time without any negative repercussions 
from study staff, health care providers, or affiliated institutions. Consent will be 
documented through the individual’s signature on the consent form. In the case of 
remote assessment, we will waive the documentation of consent, and verbal consent will 
be obtained through Zoom or telephone call. We will maintain e-copies of these remote 
consents, which will indicate who obtained consent and by which medium (telephone or 
Zoom), on our Partners Dropbox. During remote consent, we will provide participant with 
a copy of the consent form, which we will send via email. We will also include the 
following Partners required language in the summary sheet that provided to participants, 
regarding HIPAA: We are required by the Health Insurance Portability and Accountability 
Act (HIPAA) to protect the privacy of health information obtained for research. This is an 
abbreviated notice, and does not describe all details of this requirement (see Partners 
Privacy Notice*). During this study, identifiable information about you or your health will 
be collected and shared with the researchers conducting the research. In general, under 
federal law, identifiable health information is private. However, there are exceptions to 
this rule. In some cases, others may see your identifiable health information for purposes 
of research oversight, quality control, public health and safety, or law enforcement. We 
share your health information only when we must, and we ask anyone who receives it 
from us to protect your privacy.  Dr. Beard has extensive experience supervising post-
doctoral fellows and research assistants in conducting informed consent processes. The 
PI will be available in person or over the phone to answer any questions or provide 
additional information regarding the study. Additionally, in the case of remote 
recruitment, verbal consent for release of information will be obtained instead of physical 
signatures. Electronic copies of release of information forms, explicitly stating who 
obtained consent and how (ie. Verbally), will be stored on Partners approved Dropbox. 
Participants who decline participation or who do not meet inclusion/exclusion criteria will 
continue with treatment as usual at the partial hospital.  
 
2. Potential risks due to loss of confidentiality will be minimized by having all information 
collected and handled by research staff trained to deal appropriately with sensitive 
clinical issues. All participants will be informed about the limits of confidentiality 
concerning suicidal intent, homicidal intent, suspected child abuse, and suspected elder 
abuse.  Moreover, all information will be treated as confidential material and will be 

 
17
available only to research and clinical staff. All self-report and interview data will be 
collected and stored in a Partners Hospital secure electronic database (using RedCap) 
which is stored on a secure server that is backed up on a daily basis. Cognitive bias data 
files will be available only to authorized personnel and no names or obvious identifying 
information will be stored in computer files containing study data. Patient identifying 
information will be stored in a separate database and will be password protected. Any 
paper files will be kept in a locked filing cabinet in a secured office. No subject will be 
identified in any report of the project.  Further, when contacting participants during 
treatment or for post-treatment or follow-up assessments, no identifying information 
other than the name of the study staff member and the name of the site will be used 
when leaving messages or speaking to anyone other than the participant. Participants 
will be asked to provide informed written consent for audio-recording at the time of study 
entry (except for participants in Phase 2b).  To assure the confidentiality and protection 
of participants with respect to audio recording, the following steps will be taken: a) audio 
-recordings will be labeled with the date and participant id number only; b) all recordings 
will be stored on a secure sever or in locked files in a secured office; c) access to the 
audio-recordings will be limited to individuals who will be rating the recordings for 
reliability and to the PI who will provide ongoing supervision; and d) all participants will 
have the right to revoke their consent for audio-recording or ask that any of the 
recordings be erased immediately or at any point during or after the study.  
 
To assure the confidentiality and protection of data collected through the smart-phone 
application, no identifying information will be collected. The survey/ intervention 
application is being developed using ResearchKit(TM) for Apple devices and 
ResearchStack for Android—now the standard open source frameworks for deploying 
clinical research applications. The app will reside on patients’ devices and only transmit 
data to the REDCap datastore. The survey app will transmit data to the REDCap 
datastore hosted by Partners. The app will only request data from the datastore in two 
circumstances: (1) to perform username/ password authentication, and (2) in the event 
that participant installs the app on a new or wiped phone, the app will retrieve responses 
to the customization portion of the intervention to personalize their instance of the app. 
Some remote assessments may be conducted through Partners Enterprise licensed 
Zoom accounts assigned to each staff. This version of Zoom is configured to be HIPAA 
compliant. Staff will send password protected links to individual participants at the time 
of assessment. Zoom implements a range of encryption technology to ensure all content 
remains between the intended recipients. Video, audio and screen sharing are protected 
across platforms with a combination of asymmetric and symmetric encryption using 
AES-256 and AES-128. Recordings through zoom are at the hosts discretion and there 
are preventative measures in place to ensure there will be no unauthorized access to 
these recordings. Additionally we will only be storing the audio-recordings from these 
assessments, and these will be stored within Partners approved Dropbox. 
As data are collected on the app, they are stored encrypted on the device until a 
connection is available for them to be pushed to the datastore using 128 bit SSL 
encryption, at which time the local copies are deleted. The app uses a unique ID 
assigned to the patient; no PII is generated or transmitted by the app. The Master Key 
(with subject ID and names) will only be accessible by research study staff, and located 
on our secure server. The server stores patient data using only the unique ID, no PII. 
The app requires a password for patient sign-in. All data obtained  via the smartphone 
app is for research only and will not be placed in medical records or shared with clinical 

 
18
staff.  
 
Metricwire was designed to ensure data security, privacy, and confidentiality. Data are 
encrypted on the phones and uploaded to a secure server (using HIPAA compliant 
software which has been reviewed and approved by Partners RISO in multiple other 
projects) and downloaded by the researcher to the local research server in a de-
identified format. All subject names will be coded. The master key (linking deidentified 
IDs to identifying information) will be stored securely on the Partners network and will 
only be accessible to study staff. No identifiable data will be stored on mobile devices.  
 
3. We also plan to make the de-identified data from this study available via the 
NIMH Data Archive (NDA) accordance with NIMH policy, to be stored in the 
National Database of Clinical Trials (excluding Phase 2b). 
 
4. The risks of possible distress due to the assessment and treatment procedures will be 
minimized by:  a) using assessments and procedures which have been widely used in 
previous clinical and research studies; b) conducting assessments at the clinic that the 
participant attends (and is familiar with); c) reminding all individuals that they do not have 
to answer assessment questions that they find too distressing, and that they can 
discontinue participation at anytime; and d) having licensed clinical psychologists (Drs. 
Beard, Björgvinsson, or McHugh) on call during all assessments, sessions, and daily 
throughout the course of the study to counsel participants and help facilitate the 
stabilization processes for participants who report experiencing distress. Patients who 
complete sessions at home will be given phone numbers of the PI and study staff, as 
well as hours that each individual may be reached via telephone. They will be instructed 
to call should they experience any distress while completing the smart phone app.  It is 
also possible that participants may become distressed should they experience technical 
difficulties at home. Prior to any home sessions, participants will have already completed 
daily sessions and will be fully competent to self-administer the program before 
attempting to complete at home. They will be instructed to call study staff should they 
experience any trouble with the program during regular work hours, and we will work 
with the patient to solve the problem. If they are accessing the program during non-
working hours, they will be instructed to leave a voicemail for study staff, who will return 
their call as soon as possible the next business day. Of note, in previous CBM protocols 
delivered at home, patients did not report experience any distress completing the 
computer programs.  
 
5. Minimization of risk of ineffective intervention 
 
The overall risk of possible ineffective intervention will be minimized by: 1) 
frequent monitoring (daily for all study participants); 2) allowing study 
participants to receive standard partial hospital level of care or outpatient care, 
including pharmacotherapy and psychotherapy; 3) reminding all participants at 
each contact of the emergency numbers they should call if they experience a 
significant worsening of symptoms and/or suicidal ideation; and 4) the study 
protocol specifying that, in the event of clinical deterioration of anxiety or 
depression symptoms, or increased suicidality, study subjects will be 
evaluated by a licensed clinician.  
 
To minimize risk of clinical deterioration of anxiety and/or depression, a 
protocol for close clinical monitoring has been established. 

 
19
See SOP. In brief, we will not be monitoring symptoms and suicide risk via 
app surveys AT ALL throughout the study. Patients will be reminded multiple 
ways that they should not use study surveys as a means to communicate a 
need for clinical attention (see Lab SOP). If they are in distress they may 
reach out to outpatient providers or emergency services. As part of TAU, 
patients will create a safety plan with their providers at the time of discharge 
from the program and research staff will go over this plan with them, as 
another reminder of what to do in cases of emergency, as we are not following 
them. Upon discharge from the BHP, we will also be providing participants 
with a contact list for local crisis services throughout the state, and helping 
participants identify a few resources they could use. Participants will be 
reminded before each survey that they may skip the survey or stop the survey 
at any time, and that they should reach out to outpatient providers, suicide 
crisis numbers, or 911 in case of emergencies. 
 
 
 
VIII. POTENTIAL BENEFITS 
Potential benefits to all participants include a detailed psychiatric evaluation and increased 
assessment and monitoring of their anxiety and depression symptoms. If a participant’s anxiety 
or depression worsens substantially, we will provide feedback to the partial hospital treatment 
team (acute phase). If the participant is at risk for a suicide attempt, we will take immediate 
action to safeguard that patient. All participants may also benefit from the opportunity to practice 
self-assessment skills (i.e., symptom tracking). We believe that serious risks (e.g., loss of 
confidentiality or major psychological distress due to study participation) to subjects are very 
unlikely. We have attempted to minimize these risks (as described above). While some risks 
may be more likely to occur (e.g., minor, transient psychological distress), these risks are much 
less serious. Therefore, the potential benefits of the proposed study seem to outweigh the 
potential risks of this study for the individual participants.  
 
The overall goal of this research project is to learn more about the development of efficacious 
and easily disseminated treatments for SMI, thus, indirectly, all participants may eventually 
benefit from furthering science in this field, as may other individuals who suffer from these 
disorders.  
 
Importance of the Knowledge to be Gained.  
 
The results of this study will provide important information about the feasibility and acceptability 
of HabitWorks as a personalized, augmentation intervention for SMI. Approximately 4.1% of the 
adult US population suffers from SMI, defined as a mental disorder associated with significant 
functional impairment. In addition to serious functional impairment, individuals with SMI die 10-
32 years prematurely, and are almost 13 times more likely to die by suicide. Hospitalization is 
common among those with SMI, and individuals requiring a hospital level of care are often 
treatment refractory and may benefit from the addition of a targeted augmentation strategy. 
Augmentation treatments that can be reliably delivered both in the hospital and during the 
transition to outpatient care are urgently needed.  
 
The knowledge gained concerning the modification of pathological information processing in 
SMI will advance our understanding of mechanisms underlying psychopathology. This line of 
research will also add to the growing evidence for smart-phone delivered interventions as 

 
20
potentially cost-effective and easily disseminated interventions. We believe that serious risks 
(e.g. loss of confidentiality or major psychological distress due to study participation) to subjects 
are very unlikely.  While some risks may be more likely to occur (e.g. minor, transient 
psychological distress), these are much less serious.  Thus, in relation to the importance of the 
knowledge to be gained, the minimal risk to participants is reasonable. 
 
IX. MONITORING AND QUALITY ASSURANCE 
Oversight of the participants’ safety will be conducted by the PI and by a Data Safety and 
Monitoring Board (DSMB) comprising Efrat Shavit, M.D., Eliza Menninger, M.D., and Marisa 
Silveri, PhD. Dr. Shavit is a psychiatrist at the BHP (study site). She has experience treating 
individuals with SMI, managing their safety, and training residents in these areas. Dr. Menninger 
is Medical Director of the BHP and has decades of experience managing suicide risk in acute 
treatment settings. Finally, Dr. Silveri is a Neuroscientist and Director of the 
Neurodevelopmental Laboratory on Addictions and Mental Health at McLean Hospital. Her NIH-
funded research examines cognitive ability and clinical indicators of mood, anxiety, and 
impulsivity, across healthy adolescent, emerging adult, and adult cohorts, and those with 
addictions and co-occurring psychiatric illnesses. Please see attached DSMB Charter. 
Efficacy plan.   
To ensure that valid, reliable, and accurate data are collected, we will audio-record all 
assessment interviews with the patient’s permission.  Self-report data will be obtained directly 
from the computer and stored in the secure database. Data collected from interviews will be 
entered into a secure database. All data will be reviewed and entered into the computer 
database a second time. Files from the two data entries will be compared in order to check for 
accuracy of data entry. Dr. Beard has extensive experience training research assistants and 
post-doctoral fellows in diagnostic and symptomatic assessments. Training involves a multi-
stage process in which study staff:  1) meet regularly with Dr. Beard to obtain education about 
DSM criteria for the disorders being assessed and general interviewing techniques; 2) view 
training videotapes on the MINI, CGI, and other assessments being utilized; 3) attend a half to 
full day meeting in which the administration of the interview measures are reviewed in detail and 
role-plays are conducted; 4) view a skilled interviewer conducting two or more interviews with 
actual participants (with consent of these participants) and conduct interviews with actual 
participants while Dr. Beard is present; 5) are scored by Dr. Beard on aspects of their skill in 
completing the assessments and are deemed fully trained to conduct interviews independently, 
after achieving a passing score.  Ongoing checks of assessment technique are conducted in a 
process to assure calibration and prevent rater drift, while also obtaining inter-rater reliability 
data.  Assessment staff and research assistants regularly independently listen to and rate a 
MINI assessment. This provides inter-rater reliability data. After each staff member rates a given 
interview, we discuss ratings as a group, a process that ensures calibration with an expert 
diagnosis, and helps to prevent rater drift. 
 
Safety Plan.   
See Lab SOP attached. 
 
The DSMB will review rates of adverse events to determine any changes in participant risk. A 
brief report will be generated quarterly for the study record and forwarded to the DSMB and 
annually to the Partners Healthcare Institutional Review Board. The DSMB members will be 
available to meet outside of the quarterly meetings, if necessary, to discuss concerns regarding 
a particular participant or research problem. If necessary, they will make appropriate 
recommendations for changes in protocol.  The PI will meet weekly with study staff to review 
experiences with participants.  All adverse events will be reported to the IRB per PHRC 

 
21
guidelines: https://partnershealthcare-public.sharepoint.com/ClinicalResearch 
/Reporting_Unanticipated_Problems_including_Adverse_Events.pdf. The DSMB will inform NIH 
of any significant action taken as a result of DSMB findings. This study will use the NIH’s 
Common Adverse Events (AEs) and Serious Adverse Events (SAEs) definitions for clinical 
research. Adverse events are defined as any event or outcome that has resulted in harm to the 
participant, has affected the participant detrimentally, has worsened as a result of participation 
in the study, or that has resulted in increased risk to the participant or others whether or not the 
risk actually results in harm. 
  
In the event that a participant either withdraws from the study or the investigator decides to 
discontinue a client due to SAE, the participant will be monitored by the PI via ongoing status 
assessment until 1) a resolution is reached i.e., the problem requiring hospitalization has 
resolved or stabilized with no further changes expected; 2) the SAE is determined to be clearly 
unrelated to the study intervention; or 3) the SAE results in death. Unexpected events are 
defined as any event or outcome that was not described as a risk of participation in the 
research, or though described as a risk, the event or outcome has occurred with unexpected 
severity or frequency.  
 
 
 
 
 
 

 
22
Lab Clinical Deterioration and Suicidality  
Standard Operating Procedure (SOP) 
Version date: January 20th, 2021 
 
Procedures during partial hospitalization (while patient attends BHP) 
All participants in this study will be receiving intensive partial hospital treatment during the acute phase of 
the study. Therefore, deterioration or suicide risk during this phase will be reported to the patient’s clinical 
team manager at the BHP. At that point, the treatment team will manage the safety of the patient and 
determine whether inpatient hospitalization is required.  
We will maintain regular communication with the patients’ treatment team throughout the 
course of their partial hospital stay. Dr. Beard’s office is in the same hallway as all of the BHP 
clinical team managers and psychiatrists. We will use the BHP’s confidential voicemail 
system for non-urgent information and pagers for urgent clinical information.  
 
Clinical Deterioration 
As part of standard clinical care, the BHP’s Progress Monitoring Coordinator (PMC) will monitor 
depression symptoms daily, via use of the PHQ-9 using RedCap. As part of standard clinical care, the 
PMC will notify the clinical team manager of any patient who experiences an increase of 5 or more points 
on the PHQ-9 from the baseline assessment. At that point, the treatment team will manage the safety of 
the patient and determine whether inpatient hospitalization is required. Each time the PHQ-9 total score 
increases by 5 or more points, the PMC will again notify the clinical team manager of the symptom 
increase. 
 
Suicidality 
As part of standard clinical care, the PMC will monitor suicidal ideation daily, via use of item 9 on the 
PHQ-9 using RedCap. As part of standard clinical care, the PMC will notify the clinical team manager of 
any patient whose experiences an increase from the baseline assessment (e.g., from a 0 to 1, from a 1 to 
2, etc.). At that point, the treatment team will manage the safety of the patient and determine whether 
inpatient hospitalization is required. Each time item 9 on the PHQ-9 increases by one or more points, the 
PMC will again notify the clinical team manager of the symptom increase.  
 
As part of standard clinical care, patients complete the Columbia Suicide Severity Rating Scale upon 
admission to the BHP. As part of this study, they will also complete it at post-BHP treatment. Answers of 
"Yes" to questions 4 or 5 on C-SSRS will result in emergent evaluation by licensed clinician (either BHP 
clinical team manager or Dr. Beard). During periods where the BHP is operating remotely, participants will 
complete the self-report version of the C-SSRS during study assessments. In these instances, study staff 
will monitor their responses in real-time, and will ensure that a licensed clinician is available at time of 
study assessment for emergent evaluation if necessary (Answers of “Yes” to questions 4 or 5). 
 
Procedures following partial hospitalization (post-discharge from BHP) 
At discharge as part of treatment as usual participants will create a safety aftercare plan with 
their BHP provider, and this plan will be gone over in their discharge session with research 
staff. In addition, staff will provide participants with a list of local crisis resources across the 
state, and ask participants to identify a few they could contact if needed. In this session we 
will reiterate that the research team will not be checking patients Weekly Check-Ins 
(PHQ/GAD) or the EMA surveys. Following discharge from the hospital, patients are 
expected to follow their aftercare plan with outpatient providers. During this time study staff 
will not be monitoring safety of any Mood Check ins completed by participants, nor will they 
be following the daily EMA surveys.  
 
The smart phone app will clearly remind patients as they complete these forms each day that study staff 
will not see the data and thus, if they feel that they need attention, they should call their outpatient 

 
23
providers, call 911, use the crisis text hotline, or go to their local Emergency Department. Additionally, if a 
patient indicates any level of suicidal ideation on the PHQ-9 (item 9 score ≥ 1), the app will generate a 
message urging the patient to call their outpatient providers, contact emergency services, or utilize the 
crisis text line if they are feeling unsafe. Additionally, the list of crisis resources provided to patients upon 
discharge will be available to view in the app FAQs. 
 
Additionally, any symptom monitoring surveys completed in the Long Term phase will not be monitored at 
all by staff. 
 
Suicidality 
 As part of this study, participants will complete the Columbia Suicide Severity Rating Scale at 1 and 3-
month follow-up assessments. Answers of "Yes" to questions 4 or 5 on C-SSRS will result in emergent 
evaluation by licensed clinician member of study staff (Dr. Beard) for appropriate assessment and triage 
(see risk assessment section below). In addition to clinical interview, as well as when clinical interview 
cannot be scheduled, participants will complete a self-report version of the C-SSRS. When this occurs, 
study staff will monitor their responses in real-time, and will ensure that a licensed clinician is available 
remotely at time of study assessment for emergent evaluation if necessary (Answers of “Yes” to questions 
4 or 5). If Dr. Beard is unavailable to conduct a risk assessment another pre-determined licensed clinical 
psychologist will reach evaluate the patient. If multiple risk assessments are required for the same 
participant, we will attempt to have the same clinician speak with the patient at all risk assessment 
timepoints 
 
 
Risk Assessment 
Risk assessments for suicidality (CSSRS) will be conducted by the close of business on the same day the 
notification was received. If the study participant has experienced significant deterioration but is not in 
immediate danger of hurting him or herself, we may take the following actions. First, we will inform the 
patient about procedures for contacting emergency services should they find themselves at risk for self-
harm. Second, we will urge the patient to make an appointment with their outpatient provider as well. 
Third, with the patient’s consent, we will speak with one of their family members so that he/she can be 
aware of the seriousness of the patient’s symptoms and the agreed-upon treatment plan. Fourth, if the 
patient wishes additional treatment referrals or other referrals, we will facilitate these referrals.  
Dr. Beard will conduct a suicide risk assessment to determine whether it is necessary to take immediate 
action to prevent the participant from causing harm to themselves. If Dr. Beard is unavailable to conduct a 
risk assessment another pre-determined licensed clinical psychologist will reach evaluate the patient. If 
multiple risk assessments are required for the same participant, we will attempt to have the same clinician 
speak with the patient at all risk assessment timepoints.  If needed, actions that Dr. Beard may take 
include having a family member bring the person to McLean Hospital or sending an ambulance so that 
the individual may be evaluated for inpatient psychiatric admission.  
Documentation 
Study staff will document each time a participant is identified for clinical deterioration or suicidality. 
Documentation will include the following: 
• 
Date of identification 
• 
Reason for identification (e.g., increase on GAD-7) 
• 
Date and time clinician contacted 
• 
Outcome  
 
 
 

 
24
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