Pilot Study of Motivational Interviewing for Loved Ones
Phase: NA
Conditions: Psychotic Disorders, Psychosis, Psychotic Episode
Sponsor: Boston Medical Center

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Pilot Study of Motivational Interviewing for Loved Ones (MILO) 
 
ClinicalTrials.gov number: NCT04010747 
Protocol Version Number: 1 
Protocol Version Date: 3 March 2021 
NCT04010747 
Funding Mechanism:  NIMH K23 MH118373 
Principal Investigator: Emily Kline 
 
Phone: 412-298-8839 (cell) 
 
E-mail: Emily.kline@bmc.org 
 
 
 
 
Statistical Analysis Plan pages 15-17 
 
 
 
 
 
CONFIDENTIAL 
 
This document is confidential and the property of Boston Medical Center / Boston University. No part 
of it may be transmitted, reproduced, published, or used by other persons without prior written 
authorization from the study sponsor. 
 
 

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TABLE OF CONTENTS 
1 List of Abbreviations .............................................................................................................. 3 
2 Protocol Summary .................................................................................................................. 3 
3 Background/Rationale & Purpose ....................................................................................... 3 
3.1 
Background Information .............................................................................................. 3 
3.2 
Rationale and Purpose ................................................................................................ 4 
4 Objectives ................................................................................................................................ 4 
4.1 
Study Objectives ........................................................................................................... 4 
4.2 
Study Outcome Measures ........................................................................................... 5 
4.2.1 
Primary Outcome Measures ......................................................................... 5 
4.2.2 
Secondary Outcome Measures ................................................................... 5 
5 Study Design ........................................................................................................................... 6 
6 Potential Risks and Benefits ................................................................................................. 7 
6.1 
Risks ............................................................................................................................... 7 
6.2 
Potential Benefits .......................................................................................................... 9 
6.3 
Analysis of Risks in Relation to Benefits ................................................................... 9 
7 Study Subject Selection ........................................................................................................ 9 
7.1 
Subject Inclusion Criteria ........................................................................................... 10 
7.2 
Subject Exclusion Criteria ......................................................................................... 10 
8 Study Intervention ................................................................................................................ 10 
9 Study Procedures ................................................................................................................. 11 
10 Assessment of Safety and Data Safety Monitoring Plan (DSMP) ................................ 12 
10.1 Definitions .................................................................................................................... 13 
10.2 Safety Review ............................................................................................................. 13 
10.3 Reporting Plans .......................................................................................................... 14 
10.4 Stopping Rules ............................................................................................................ 14 
11 Data Handling and Record Keeping .................................................................................. 14 
11.1 Confidentiality .............................................................................................................. 14 
11.2 Source Documents ..................................................................................................... 15 
11.3 Case Report Forms .................................................................................................... 15 
11.4 Study Records Retention .......................................................................................... 15 
12 Statistical Plan ...................................................................................................................... 15 
12.1 Study Hypotheses ...................................................................................................... 16 
12.2 Sample Size Determination ...................................................................................... 16 
12.3 Statistical Methods ..................................................................................................... 16 
13 Ethics/Protection of Human Subjects ................................................................................ 17 
14 Literature References .......................................................................................................... 17 

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1 
List of Abbreviations 
 
Abbreviation 
Abbreviation definition 
MILO 
Motivational Interviewing for Loved Ones 
IP 
Individual with Psychosis  
PCSO 
Parents and Concerned Significant Others 
 
2 
Protocol Summary 
Title: 
Pilot Study of Motivational Interviewing for Loved Ones 
(MILO) 
Population: 
Caregivers (age 18 or older) of individuals ages 15-35 experiencing 
early course psychotic disorders; N = 100 
Intervention: 
Motivational Interviewing for Loved Ones, “MILO” 
MILO consists of four 60-minute sessions of communication skills 
training delivered by a trained provider in person or via secure 
telehealth 
Objectives: 
Evaluate the effectiveness of MILO for (1) facilitating the 
engagement of IP with evidence-based treatments and (2) reducing 
distress among PCSO 
Design/Methodology: 
Participants will be randomly assigned to either receive MILO (50%) 
or the waitlist condition (50%) as a partial cross-over design. 
Total Study Duration: 
3/1/21-7/31/23 
Subject Participation Duration: 
Four to six months, depending on whether participant is assigned to 
immediate intervention vs. waitlist condition as well as the pace  
 
3 
Background/Rationale & Purpose 
 
3.1 
Background Information 
 
First Episode Psychosis (FEP) often represents a time of crisis for young people and their families. Since 
peak onset occurs during late adolescence and early adulthood, the onset of serious mental health 
challenges can disrupt plans for education, relationships, and other milestones of independence. 
Although some psychoses are brief and self-limiting, more often these symptoms portend a potentially 
chronic and disabling psychiatric disorder such as schizophrenia. FEP can also be acutely dangerous: 
youth with FEP are far more likely to die in the year following their diagnosis relative to the general 
population of 16-30-year old’s in the United States. Approximately 100,000 youth in the United States 
experience FEP every year. Young people identified by providers as experiencing FEP often slip through 
the cracks before they reach appropriate treatment. A review of privately insured adolescents and 
young adults in the US showed that 62% of young people in the US with FEP filled no outpatient 
prescriptions, and 41% received no outpatient psychotherapy, in the year following their index 
diagnosis. Among those who do have an initial encounter with specialized FEP outpatient care, high 

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attrition is a common problem, with 30% of individuals initially enrolled in first episode programs 
dropping out prior to completing treatment.  
 
Many individuals experiencing psychosis are reluctant to seek mental health treatment due to lack of 
insight and fear of psychiatric interventions. Young adults may be torn between distress and 
dissatisfaction relating to their symptoms and functioning, and mistrust of mental health providers and 
irritation with their parents’ concern. Motivational Interviewing (MI) techniques are designed to elicit 
this ambivalence through nonjudgmental listening, so that discrepancies between current behaviors and 
ideal outcomes can be explored. Clinician-delivered MI has been identified as effective for enhancing 
adherence once individuals with psychosis are involved in care, and MI may also be useful for engaging 
those who are not yet interested in treatment. Several studies have found positive results in training 
and deploying non-professionals to use MI to influence others’ health behaviors. MI training for parents 
and concerned significant others (PCSO) is a promising venue through which PCSO can specifically 
influence their loved one’s decision to seek care and adhere to treatment plans. 
 
The PI (Dr. Kline) has developed a brief 4-5 session training course for caregivers called “motivational 
interviewing for loved ones” (MILO). Each training session lasts 45-60 minutes and consists of teaching 
the participant an MI based communication skill, reviewing previously discussed skills, or offering 
referral information for treatment for their IP. The training can be done in-person or virtually. In a 
feasibility focused pilot, the intervention was found to be highly valued by participants, with 94% of 
consented participants completing at least three sessions. This application represents the continuation 
of a pilot efficacy trial that was initiated at Beth Israel Deaconess Medical Center and which the PI would 
like to continue at Boston Medical Center. 
 
This study will be conducted in compliance with the protocol, applicable regulatory requirements, and 
BMC/BU Medical Campus Human Research Protection policies and procedures. 
 
3.2 
Rationale and Purpose  
 
MILO aims to address the critical problem of delayed treatment and under-treatment in early course 
psychosis by offering a motivational interviewing (MI) based skills intervention for parents or other 
concerned significant others (PCSO) of individuals with psychosis (IP) who refuse treatment. This 
intervention will offer psychoeducation and concrete skills for communicating with the IP about the 
potential benefits of seeking care. The primary aim of the intervention is to increase the likelihood of IP 
engaging with evidence-based treatment. Secondary outcomes include reductions in PCSO distress and 
increases in PCSO well-being. 
 
4 
Objectives 
 
4.1 
Study Objectives 
 
The initial aim of this pilot study is to evaluate feasibility of the intervention. The secondary aims 
are to evaluate the effectiveness of MILO for (a) facilitating the engagement of IP with evidence-
based treatments and (b) reducing distress among PCSO. We hypothesize that the intervention 

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will be superior to control condition for both enhancing IP engagement with mental health 
services and reducing PCSO distress. 
 
 
4.2 
Study Outcome Measures 
 
4.2.1 Primary Outcome Measures 
 
Feasibility will be analyzed using the following descriptive metrics: # participants screened; # 
Eligible; # Enrolled; # not enrolled and corresponding reasoning; # Meeting DSM-5 Adjustment 
Disorder criteria; Percentage of study sessions completed; study Satisfaction; % assessments 
completed; Duration of assessments. A demographics questionnaire, a clinician-administered 
assessment containing information relevant to the DSM-5 diagnosis of adjustment disorder, and 
the Client Satisfaction Questionnaire will be used.  
 
4.2.2 Secondary Outcome Measures 
 
Measurement of secondary outcomes will occur using the instruments in the table below.  
 
Measure 
Study Objective 
Time Point 
Absolute Worth and Autonomy 
Scale 
Aim 2b: Reducing distress 
among PCSO 
Baseline, Waitlist Condition, 
Post Intervention, 8 Week FU, 
12 Week FU 
Perceived Stress Scale 
Aim 2b: Reducing distress 
among PCSO 
Baseline, Waitlist Condition, 
Post Intervention, 8 Week FU, 
12 Week FU 
Conflict Behavior Questionnaire 
Aim 2b: Reducing distress 
among PCSO 
Baseline, Waitlist Condition, 
Post Intervention, 8 Week FU, 
12 Week FU 
SCORE-15 Index of Family 
Functioning 
Aim 2b: Reducing distress 
among PCSO 
Baseline, Waitlist Condition, 
Post Intervention, 8 Week FU, 
12 Week FU 
Parenting Self Agency 
Aim 2b: Reducing distress 
among PCSO 
Baseline, Waitlist Condition, 
Post Intervention, 8 Week FU, 
12 Week FU 
Family Questionnaire 
Aim 2b: Reducing distress 
among PCSO 
Baseline, Waitlist Condition, 
Post Intervention, 8 Week FU, 
12 Week FU 
Motivational Interviewing Skills 
Questions 
Aim 2a: Feasibility 
Baseline, Post- Intervention 
Mental Health Service Use 
History 
Aim 2a: Facilitating engagement 
of IP in treatment  
Baseline 
Past Month Service Use History 
Aim 2a: Facilitating engagement 
of IP in treatment 
Baseline, Waitlist Condition, 
Post Intervention, 8 Week FU, 
12 Week FU 
Change Questionnaire 
Aim 2b: Reducing distress 
among PCSO 
Post Intervention, 12 Week FU 

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10 Minute Audio Recorded Role 
Play  
Aim 2a: Feasibility 
Baseline, Waitlist Condition, 
Post Intervention 
  
 
 
5 
Study Design 
 
The study population is parents and concerned significant others (PCSO) of individuals 
experiencing psychosis (IP) who are not currently engaged with treatment. The IP has to have a 
recent onset of psychosis within the past 5 years. MILO is a structured brief intervention that 
seeks to accomplish two aims. The primary aim is to facilitate the engagement of IP with evidence-
based treatments. The secondary aim is to reduce the distress and increase the wellbeing of 
PCSO. The intervention will be trialed for feasibility and then tested against a small waitlist 
condition control arm. Participants will be randomly assigned to either receive MILO (50%) or the 
waitlist condition (50%) in a cross over design.  
 
The study is designed to minimize participant burden. Concerns about the ethics of 
randomization are allayed by the fact MILO is untested (effectiveness is not proven), and that the 
control condition represents treatment as usual. Thus the risk benefit ratio, even for those 
assigned to “treatment as usual/waitlist”, is favorable given that typically no particular assistance 
is offered in the community for parents/significant others attempting to connect their loved one 
with care. Phase 1 of the study was completed at its initial site at Beth Israel Deaconess Medical 
Center. Phase 2 was also started at the previous sight and will be completed at Boston Medical 
Center. 
 
We will be collecting data through REDCap surveys administered via email link to the 
participants. Those assigned to the MILO treatment condition will be assessed at 4 time points 
(study entry, post intervention, 8 week follow up, 12 week follow up). Those in the waitlist condition 
will be assessed at 5 time points (study entry, end of waitlist, post intervention, 8 week follow up, 
12 week follow up). Please see the following measures:  
• 
Participants Contact Information 
• 
Demographics questionnaire  
• 
SCID-5 Adjustment disorder module  
• 
Absolute Worth and Autonomy Scale  
• 
Perceived Stress Scale 
• 
Conflict Behavior Questionnaire  
• 
SCORE-15 Index of Family Functioning 
• 
Parenting Self-Agency 
• 
Family Questionnaire  
• 
Motivational Interviewing Skills Questions 
• 
Mental Health Service Use History & Past month Service Use History Forms  
• 
Modified Client Satisfaction Questionnaire  
• 
Change Questionnaire 

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• 
10-minute audio-recorded standardized patient role play (at study entry and post-intervention 
and waitlist time points only; role-plays will be scored using the Motivational Interviewing for 
Loved Ones Skills Assessment.  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
6 
Potential Risks and Benefits 
 
6.1 
Risks 
 
Potential risks to PCSO participating in MILO include: 1) There is a potential risk that confidential 
health information collected during the course of the study may be disclosed to others. 2) 
Participating PCSO may at times feel inconvenienced by the time required to complete the 
sessions and/or research assessments. 3) Participants may experience frustration or anxiety in 
learning to use the motivational interviewing communication skills. They may experience sadness 
or discomfort when discussing personal problems or in interacting with a family member. 
Discussing or experiencing the IP’s psychiatric problems may be upsetting to the family. 4) There 
is a potential risk that participants will be subjected to stigma or undue anxiety from identification 
with the study. 5) The individuals with psychosis will be discussed in detail during study sessions. 
These individuals might find it distressing to know that their circumstances are the topic of their 
loved ones’ research participation.  
 
The PI and study staff will take the following steps to protect against risks:  
 

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1) Confidentiality will be maintained by assigning each participant a study number, and 
coding all data collected with that number. Identifying information and study data will be 
stored separately on secure BMC servers. To protect the confidentiality of the IP being 
discussed, his/her name will not be written down anywhere. All computer databases will 
be password protected, and hard copies of all data and records will be stored in locked 
filing cabinets. All study personnel will be certified to conduct research with human 
subjects and will be aware of the importance of maintaining strict confidentiality. Audio 
recordings of participants will be saved in digital files on a secure BMC server. Audio files 
will be destroyed at the conclusion of the study unless explicit consent to use audio files 
(e.g. 
for 
training 
purposes) 
is 
obtained 
from 
participants. 
 
2) The assessment battery has been designed to minimize participant burden. 
 
3) The study PI is a very experienced clinician and will provide ongoing supervision to each 
individual working on the protocol to ensure that they are equipped to provide appropriate 
support when necessary and to recognize signs of distress and discomfort. It is not 
expected that participants will feel any more sadness or discomfort talking about personal 
problems or interacting with a family member than they would at home or if they took part 
in psychotherapy in the community. If participants or family members experience 
frustration or distress, the PI, will offer participants emotional support and validation. She 
will also offer strategies for managing the situation and accompanying emotional 
responses. Participants will also be informed that they can receive and follow-up on 
outside referrals for counseling outside of the study at any time without being dropped 
from the protocol.  
 
 
4) The PI will review each participant carefully with study staff. Study participants who are 
judged by the PI to be in need of additional psychiatric or psychological 
evaluation/treatment or medical consultation will be referred as clinically indicated. This 
includes endorsement of self-harm and suicidality which will be addressed immediately. 
The participants will be frequently asked whether they desire additional referral or 
consultation for their own or their loved one’s safety. If imminent danger is reported, 
participants will develop a safety plan with Dr. Emily Kline as described below. 
 
5) The PI will meet with stuff staff and clinicians at least weekly for supervision. Staff will be 
trained to recognize signs of distress (for instance, hopeless statements) and will report 
to the PI both the content of interactions with participants as well as any concerns about 
their mood or concerning statements. If needed, study staff will provide crisis intervention, 
recommendations or referrals for adjunctive medical/pharmacological interventions, and 
when necessary, referral to emergency or inpatient treatment facilities. The PI will closely 
supervise or personally provide any crisis intervention. Staff will seek written release to 
coordinate care with other mental health providers prior to the start of treatment to avoid 
need for acute care when increased outpatient supports may be sufficiently garnered. 
Participants will be told they may decline to answer any questions or participate in any 
component. Staff will make the study assessments and MILO sessions as pleasant as 
possible by developing rapport and going at an appropriate pace so that participants do 
not become frustrated.  
6) The PI does not believe this study poses significant risks to participants and does not 
anticipate any serious adverse events as a result of the study. However, first episode 
psychosis is associated with increased mortality in the community. Any safety concerns 

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relating to either the PCSO’s or IP’s wellbeing will be carefully discussed with the 
participant. Whenever reason for concern arises, the PI or other licensed clinician will 
evaluate safety risks and create a plan in collaboration with the participating PCSO to 
address such risk. This could involve calling 911 in cases of imminent safety threats. There 
is no reason to suspect that rates of illness complications will be higher if the parents or 
significant others of IP participate in the study.  
7) Risks to subjects will be closely monitored as described in Section 6.1.  Adverse events will be 
documented and reported per BMC/BUMC HRPP policies.  Any event or set of events meeting the 
definition of Unanticipated Problem (UP) will be reported in an expedited timeframe (within 7 days) of the 
study team learning of the UP. 
8) Staff will maintain regular contact with the IRB regarding study protocol, consents, 
recruitment materials, and human subject protection plan.  
 
 
 
6.2 
Potential Benefits 
 
If it is effective, the intervention has tremendous upside to both participants and their loved ones 
with psychosis. The goals of the intervention are to shorten DUP, increase service utilization by 
the IP, and reduce caregiver distress. These parents and other loved ones are often desperate to 
seek help on behalf of the IP. Learning MI skills may benefit participants by reducing their stress, 
helping them to feel more confident in their caregiving role, and giving them information about 
how they can better facilitate the IP’s connection or adherence to treatment. 
 
Those randomized to the waitlist will be offered a 30-minute consultation during which the PCSO 
is provided with information about treatment options (e.g., community mental health and FEP 
coordinated specialty care programs) and contact information for an active NAMI chapter in in 
his/her area. This will be done in person or by telephone. This consultation represents the 
minimum standard of care for caregivers of individuals with recent-onset psychosis being treated 
at BMC. Additionally, waitlist participants will have the opportunity to receive MILO training after 
a six-week wait.  
 
Concerns about the ethics of randomization are allayed by the fact MILO is untested 
(effectiveness is not proven), and that waitlisted participants will also be offered the MILO 
intervention after a short waiting period.  
 
 
6.3 
Analysis of Risks in Relation to Benefits 
 
This study will be of minimal risk to participants. There is a relatively low risk of harm to individuals 
receiving family therapies. Prior studies of family therapies with this and similar populations have 
demonstrated tolerability and efficacy. There are no physical risks of participating in this study 
and the study is not expected to be harmful or dangerous in any way. There are no manipulations 
of drug treatments. Pharmacotherapy is not required and if participants opt for it, they will be 
referred to appropriate providers. Thus the risk benefit ratio, even for those assigned to “waitlist”, 
is favorable.  

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7 
Study Subject Selection 
 
7.1 
Subject Inclusion Criteria 
 
In order to be eligible to participate in this study, an individual must meet all of the following criteria: 
• 
PCSO is 18 years or older 
• 
PCSO is able to communicate in English 
• 
PCSO is a primary care giver or an individual who has ≥20 hours weekly contact 
with an IP 
• 
PCSO is able to provide informed consent by demonstrating that they understand 
the aims and structure of the study 
 
Although the individual with psychosis will not participate in MILO, study staff will establish via 
the participating PCSO that the individual with psychosis is: 
• Aged 15-35 
• Has been diagnosed with a DSM-5 psychotic disorder by a health 
professional, OR has clearly observable (by the PCSO) symptoms/behaviors 
indicating psychosis 
• Experienced onset of observed symptoms or first psychosis diagnosis 
occurred within past five years 
• 
Is not optimally engaged in outpatient treatment 
Identifiable information about the individual with psychosis is not kept in study records. The 
information gathered about the IP is based on participants’ reporting and perceptions.  
 
 
 
Subject Exclusion Criteria 
 
An individual who meets any of the following criteria will be excluded from participation in this study: 
• 
Current mental health crisis: if study staff determine that the potential participant is in serious 
emotional distress during the eligibility determination and consent process, staff will consult 
with the PI to determine whether the participant should be referred to psychiatric care to 
address their distress prior to participating in MILO 
 
8 
Study Intervention 
The active intervention includes four to five 45-60 minute sessions. Sessions will be conducted 
individually with the clinician, or if two or more PCSO (e.g., parents) wish to participate together, 
they will meet at the same time with the clinician. The first two sessions will focus primarily on 
teaching through concept review, demonstration, and role play. In the third and fourth sessions, 
the clinician will learn about PCSOs’ efforts to initiate a conversation about treatment with the IP 
using, and will provide feedback, problem-solving, and encouragement regarding the PCSO’s 

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efforts. A fifth session may be offered upon request to provide additional coaching, consultation, 
and psychoeducation relevant to MILO topics.  See Table 1 for details about session content.  
 
Session  
Content 
1 
Participants talk with a study clinician about the IP’s illness history and how the 
experience has impacted them and their family. Treatment and psychoeducational 
resources are offered (e.g. NAMI support groups). Study staff teach participants about 
the philosophy of motivational interviewing and the potential value of listening and 
asking questions instead of giving advice or solving the problem. 
2-3 
Study staff teach participants core MILO communication skills (reflections, questions, 
asking permission before offering advice) and practice the skills during the session.  
4-5 (5th 
session 
optional 
depending 
on 
participants’ 
preference) 
Participants review their attempts to use MILO skills with the IP and receive feedback 
and encouragement from MILO clinicians. Participants have the opportunity to role 
play with the clinician to obtain additional practice. 
 
 
The waitlist condition offers a one-time consultation session to participants while they are on a 6-week 
waitlist condition to receive MILO sessions. This involves a 30 minute consultation with a clinician 
experienced psychosis treatment with the goal of providing some psychoeducational resources. These 
resources include links to NAMI handouts, a directory of psychosis early intervention clinics, and 
information about psychiatric emergency services. This is similar to content addressed the first half of 
session 1 of MILO. Participants may decline this consultation and wait for the MILO intervention instead.  
 
 
9 
Study Procedures 
 
See the Appendix for the schedule of events.  
 
Event 
Protocol 
Contact 
Potential participant contacts study staff via 
email or phone communication. This is a 
dedicated study phone number. Study staff 
schedule a 10 minute phone call with potential 
participant to review study details and complete 
pre-screen. 
Pre-Screen 
Study Staff confirm that potential participant is 
interested in learning more, reads the Consent to 
Phone Screen, asks eligibility criteria questions   
Eligibility Determination  
Study staff review the answers to the eligibility 
questions, if any answer is unknown or needs 
clinical input, study staff contacts the Principal 

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Investigator. If contact is ineligible, they are told 
why and given other resources to consider.  
Consent 
If potential participant is eligible, they are offered 
a time to review the study consent with study 
staff. Once study details have been reviewed and 
study staff have made sure participants have no 
lasting questions, then study staff send the 
REDCap consent link to the participants. 
Participants are given study staff contact 
information if they have any more questions 
before signing the document via REDCap. If 
participants do not have access to necessary 
technology to complete a remote consent, they 
will be invited to Dr. Emily Kline’s office. All in 
person operations will follow BMC’s COVID 
procedures.  
Baseline Assessments  
Participants are sent a REDCap survey link after 
consent is complete via email and asked to 
schedule a 15 minute phone call with study staff 
to complete their baseline real play assessment  
Randomization 
Once baseline assessments are complete, study 
staff randomize participant into MILO or waitlist 
condition.  
IF Waitlist Condition 
Participants randomized to waitlist condition, are 
emailed the date that their waitlist period ends 
and offered a 30 minute treatment consultation 
with one of the MILO trainers before the 6 week 
waitlist period is complete. This treatment 
consultation can be completed over the phone, 
over a BMC Zoom, or in person at Dr. Emily 
Kline’s office. All in person visits will follow BMC’s 
COVID procedures. At the end of the waitlist 
period, they are sent REDCap surveys and asked 
to complete another real play assessment over 
the phone (first done at baseline). 
MILO Treatment 
Participants randomized to immediate MILO, as 
well as those who have already finished the 
waitlist period, are scheduled for their first MILO 
training session.  Sessions are offered via a 
secure telehealth platform, HIPAA compliant 
Zoom or in person if the participant does not 
have access to appropriate technology. All in 
person operations will follow BMC’s COVID 
procedures. Sessions are 45-60 minutes and 
participants are offered 4-5 sessions. All sessions 
are conducted by trained study staff. Study staff 
receive weekly individual supervision from the PI. 

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Study staff utilize detailed guides to ensure high 
fidelity to the MILO intervention. Details of the 
intervention are described in the table above in 
section 8.  
Post-Intervention Assessments  
Once participants have completed MILO 
intervention, they are emailed their post-
intervention REDCap survey and asked to 
schedule their last real play audio recorded 
exercise over the phone.  
8 Week Follow Up 
Participants are emailed a REDCap survey 8 
weeks after their last MILO session. 
12 Week Follow Up 
Participants are emailed their last REDCap survey 
12 weeks after their last MILO session. 
 
 
9.1 
Definitions 
The following definitions will be used in the assessment of safety: 
 
Adverse Event (AE) is any untoward or unfavorable medical occurrence in a human subject, including any 
abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, 
temporally associated with the subject’s participation in the research, whether or not considered 
related to the subject’s participation in the research. 
 
Serious Adverse Event (SAE) is any adverse event that  
(1) Invasion of privacy 
(2) Breach in confidentiality  
(3) Breach in the protection of participant data 
(4) Any abnormal or harmful behaviors  
 
Unanticipated Problem is defined as an event, experience or outcome that meets all three of the 
following criteria:  
• 
is unexpected; AND 
• 
is related or possibly related to participation in the research; AND 
• 
suggests that the research places subjects or others at a greater risk of harm (including physical, 
psychological, economic, or social harm) than was previously known or recognized.  
 
Possibly related means there is a reasonable possibility that the incident, experience, or outcome may 
have been caused by the procedures involved in the research 
 
Unexpected means the nature, severity, or frequency of the event is not consistent with either: 
• 
the known or foreseeable risk of adverse events associated with the procedures involved in the 
research that are described in (a) the protocol–related documents, such as the IRB-approved 
research protocol, any applicable investigator brochure, and the current IRB-approved informed 
consent document, and (b) other relevant sources of information, such as product labeling and 
package inserts; or 

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• 
the expected natural progression of any underlying disease, disorder, or condition of the 
subject(s) experiencing the adverse event and the subject’s predisposing risk factor profile for the 
adverse event. 
 
9.2 
Safety Review 
 
Both the risks listed in Section 4.1 and unknown risks will be monitored as follows:  
Study staff who are meeting with participants will participate in weekly supervision with the PI. Staff are 
trained to identify signs of acute participants’ distress and potential suicidality. Via direct observation or 
supervision, the PI will monitor participant distress and clinical state and address concerns at the time 
they are raised or observed. Any and all adverse events will be reported to the IRB. Any adverse events 
will be evaluated by the PI who is a licensed PHD psychologist in accordance to IRB requirements and 
changes will be made to the protocol to prevent future adverse events if deemed necessary by research 
staff and/or the IRB. The PI will seek consultation from the IRB and/or her department chair Dr. 
Henderson if she has any question about whether to report an event to the IRB immediately or during 
annual review.  
 
 
9.3 
Reporting Plans 
 
The Principal Investigator at BMC/BU Medical Campus will report Unanticipated Problems, safety 
monitors’ reports, and Adverse Events to the BMC/BU Medical Center IRB in accordance with IRB 
policies: 
• 
Unanticipated Problems occurring at BMC/BU Medical Campus will be reported to the IRB within 7 
days of the investigator learning of the event. 
• 
Reports from safety monitors with recommended changes will be reported to the IRB within 7 
days of the investigator receiving the report.  
• 
Adverse Events (including Serious Adverse Events) will be reported in summary at the time of 
continuing review, along with a statement that the pattern of adverse events, in total, does not 
suggest that the research places subjects or others at a greater risk of harm than was previously 
known. 
• 
Reports from safety monitors with no recommended changes will be reported to the IRB at the 
time of continuing review.  
 
 
9.4 
Stopping Rules 
 
A subject will be withdrawn from the study if adverse event(s) occur that per the PI’s judgment require 
subject withdrawal. Examples would be a participant who endorses suicidal ideation or reports a violent 
altercation with the IP.  
 
There are no specified stopping rules. 
 
10 Data Handling and Record Keeping 
 
10.1 Confidentiality 

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Confidentiality will be maintained by assigning each participant a study number, and coding all 
data collected with that number. Identifying information will be saved separately from study data. 
To protect the confidentiality of the IP being discussed, his/her name will not be written down 
anywhere.  Databases containing both PHI and non-PHI study data will be stored on securely on 
the BMC Network and REDCap. Any papers containing study notes or participant information will 
be stored in locked filing cabinets in the PI’s BMC office. All study personnel will stay updated on 
CITI-based human subjects’ research training and will be aware of the importance of maintaining 
strict confidentiality and data security. Audio recordings of participants will be saved in digital files 
on a secure BMC server. Transcriptions of audio files will be performed by BMC research staff 
and stored on secure BMC servers. Audio files will be destroyed at the conclusion of the study 
unless explicit consent to use audio files (e.g. for training purposes) is obtained from participants 
during the informed consent process.  
 
Study monitors or other authorized representatives of the sponsor (i.e. NIMH) may inspect all 
documents and records required to be maintained by the investigator, including but not limited to, 
medical records (office, clinic, or hospital) and pharmacy records for the subjects in this study. The 
clinical study site will permit access to such records. 
 
The study is registered and regularly updated on clinical trials.gov, NCT04010747. 
  
 
10.2 Source Documents 
 
Source data and source documents will be stored on BMC secure servers. They include study team 
administrative notes, study clinician notes and progress checklists, recorded data from automated 
instruments including REDCap, audio files and audio transcription documents. Data generated by the 
methods described in the protocol will be recorded in the subjects' study progress notes.  
 
10.3 Case Report Forms 
 
CRFs will not be used for this study. All data will be saved in REDCap, most of which will be inputted by 
participants themselves.  
 
10.4 Study Records Retention 
 
All records will be saved on BMC’s secure servers electronically and retained at least seven years after 
completion of the study. At the completion of the study, any paper notes will be scanned and uploaded 
as electronic documents to the BMC server. Within the informed consent process, participants indicate 
whether their audio recordings can be used for research and teaching purposes. Examples on how they 
may be used include during training new study staff on the measure or used as an example during a 
research presentation. Audio recordings of participants who say that their recordings can be used will be 
retained and others will be deleted at the end of the study. Any identifying information disclosed within 
the audio files will be removed by editing, the files themselves are de-identified. 
 
11 Statistical Plan 

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11.1 Study Hypotheses 
 
1. The MILO intervention will be feasible and acceptable for participants.  
 
2. The MILO intervention will impact outcomes of interest (e.g., proficiency using MILO skills, 
confidence, stress, caregiving attitudes, and caregiver-reported IP treatment engagement).  
 
3. Participants attending MILO sessions will show more improvement with regard to outcomes of 
interest within the first six weeks of study participation relative to those on the waitlist. 
 
4. After attending MILO sessions, waitlisted participants will “catch up” to those randomized to 
receive the intervention immediately with regard to changes on outcomes of interest.  
 
5. Gains in MI proficiency as demonstrated via scored audio recordings will mediate the impact of 
the intervention on other outcomes such as reduced conflict and stress and increased 
confidence and caregiver-reported IP treatment engagement.  
 
 
11.2 Sample Size Determination 
 
The overall target for recruitment is 100 participants. 52 participants will be recruited for the protocol 
once approved by BMC (48 participants were recruited at Beth Israel Deaconess Medical Center which 
was the original recipient of the K23 funding support). This study is a pilot intended to test feasibility 
and preliminary effectiveness of the MILO intervention. Although true “pilot” studies focus an on 
intervention’s feasibility, rather than effects per se, the current study reflects a two-phase hybrid of 
priorities balancing the need to focus on feasibility while also investigating whether the intervention 
impacts the hypothesized treatment targets (MI skills, self-efficacy) and whether it is more effective in 
achieving the primary outcome (IP engagement in FEP treatment) than a control condition representing 
“treatment as usual” and a waiting period. The control group will be small relative to the active 
treatment group, thus maximizing the feasibility-focused sample. Thus the study may be somewhat 
underpowered to detect statistically significant effects, but has been designed to yield high quality 
feasibility metrics, highlight important factors for implementation, and provide a rough estimate of 
effect size that will inform a later, fully powered RCT.  
 
11.3 Statistical Methods 
 
Feasibility will be analyzed using the following descriptive metrics: # participants screened; # 
Eligible; # Enrolled; # not enrolled and corresponding reasoning # Meeting DSM-5 Adjustment 
Disorder criteria; Percentage of Treatment sessions completed; Treatment Satisfaction; % 
assessments completed; Duration of assessments. 
 
The outcomes of interest will be compared between the intervention and waitlist groups, and 
also within the waitlist group (comparing the pre-post intervention changes to the pre-post 
waitlist time changes.  Prevalence of IP treatment seeking in each group will also be analyzed 
via odds ratios. Secondary outcomes, i.e. changes in PCSO distress and quality of life, will be 

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assessed via repeated measures ANOVAs examining group-by-time changes. Similarly, 
hypothesized mediators of effects (MI skill proficiency and self-efficacy) will be examined via 
repeated measures ANOVAs examining group-by-time changes. Analyses will be conducted 
using SPSS software. 
 
12 Ethics/Protection of Human Subjects 
 
This study is to be conducted according to applicable US federal regulations and institutional policies 
(which are based in federal regulations, guidance, and ICH Good Clinical Practice guidelines). 
 
This protocol and any amendments will be submitted to the Boston Medical Center and Boston 
University Medical Campus IRB, for formal approval of the study conduct. The decision of the IRB 
concerning the conduct of the study will be made in writing to the investigator. A copy of the initial IRB 
approval letter will be provided to the sponsor before commencement of this study.  
 
All subjects for this study will be provided a consent form describing this study and providing sufficient 
information for subjects to make an informed decision about their participation in this study. The 
consent form will be submitted with the protocol for review and approval by the IRB. The consent of a 
subject, using the IRB-approved consent form, must be obtained before that subject is submitted to any 
study procedure. Consent will be documented as required by the IRB.   
 
13 Literature References 
 
Brown, GW, Birley, JL, Wing, JK. Influence of family life on the course of schizophrenic disorders: A 
Replication. Br J Psychiatry. 1972;121(562):241-258. doi:10.1192/bjp.121.3.241 
Butzlaff RL, Hooley JM. Expressed emotion and psychiatric relapse: a meta-analysis. Arch Gen 
               Psychiatry. 1998 Jun 1;55(6):547-52. 
Gates, PJ, Sabioni, P, Copeland, J, Le Foll, B, Gowing, L. Psychosocial interventions for cannabis use 
disorder. Cochrane Database Syst Rev. 2016 May 5;(5). doi: 10.1002/14651858.CD005336.pub4 
Glynn, SM, Cather, C, Gingerich, S, Gottlieb, JD, Meyer, PS, Mueser, KT, Penn, DL. NAVIGATE Family 
              Education Program (FEP). 2014 April 1.  
Kreyenbuhl, J, Buchanan, RW, Dickerson, FB, Dixon, LB. The schizophrenia patient outcomes research  
Team (PORT): updated treatment recommendations 2009. 2010; 36(1): 94-103. 
Napa, W, Tungpunkom, P, Pothimas, N. Effectiveness of family interventions on psychological distress  
and expressed emotion in family members of individuals diagnosed with first episode psychosis: 
a systematic review. JBI Database System Rev Implement Rep. 2014;15(4):1057-1079. Doi: 
10.11124/JBISRIR-2017-003361. 
Palacio, A, Garay, D, Langer, B, Taylor, J, Barbara, AW, Tamariz, L. Motivational interviewing 
improves medication adherence: a systematic review and meta-analysis. J Gen Intern 
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Peris, TS, Miklowitz, DJ. Parental expressed emotion and youth psychopathology: New 
directions for an old construct. Child Psychiatry Hum Dev. 2015; 46(6): 863-873. doi: 
10.1007/s10578-014-0526-7 
Rienecke, RD. Expressed emotion and eating disroders; an updated review. Current Psychiatry 
Reviews. 2018; 14(2): 84-98. DOI: 10.2174/1573400514666180808115637 
Schoenthaler, AM, Lancaster, KJ, Chaplin, W, Butler, M, Forsyth, J, Ogedegbe, G. Cluster 
randomized clinical trial of FAITH (faith-bsed approaches in the treatment of 
hypertension) in blacks. 2018 Oct: 11(10). doi: 10.1161/CIRCOUTCOMES.118.004691 
Simoneau, TL, Miklowitz, DJ, Richards, JA, Saleem, R, George, EL.  Bipolar disorder and 
family communication: effects of a psychoeducational treatment program. J Abnorm 
Psychol. 1999;108(4):588. doi: 10.1037//0021-843x.108.4.588 
Smeerdijk, M, Keet, R, de Haan, L, Barrowclough, C, Linszen, D, Schippers, G. Feasibility of 
teaching motivational interviewing to parents of young adults with recent-onset 
schizophrenia and co-ocuurring cannabis use. 2013 Oct: 46(3): 340-345. DOI: 
10.1016/j.jsat.2013.09.006 
Sorsdahl, K, Myers, B, Ward, CL, Matzopoulos, R, Mtukushe, B, Nicol, A, Cuijpers, P, Stein, 
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