Behavioral Activation and Medication Optimization For Improving Perioperative Mental Health In Older Adults Undergoing Oncologic Surgery
Phase: NA
Conditions: Older Adults, Anxiety, Depression, Major Surgical Resection of a Thoracic Malignancy, Major Surgical Resection of an Abdominal Malignancy
Sponsor: Washington University School of Medicine

Title: 
Behavioral AcƟvaƟon and MedicaƟon OpƟmizaƟon For Improving PerioperaƟve 
Mental Health In Older Adults Undergoing Oncologic Surgery 
 
NCT#: 
NCT05685511 
 
Protocol #:   
202212097 

 
 
    
 
 
RESEARCH PROTOCOL 
 
 
Behavioral Activation and Medication Optimization For Improving Perioperative Mental 
Health In Older Adults Undergoing Oncologic Surgery 
 
 
 
Principal Investigator: 
 
Benjamin D Kozower MD, MPH 
Professor 
Department of Surgery 
Washington University School of Medicine  
660 S. Euclid Ave, Campus Box 8234 
Saint Louis, MO, 63110 
Tel: 314-362-8089 
Fax: 314-362-6288 
E-mail: kozower@wustl.edu 
 
 
Co-Investigators: 
 
 
Joanna Abraham, PhD 
Associate Professor, Department of Anesthesiology and Institute for Informatics 
Washington University School of Medicine  
660 S. Euclid Ave, Campus Box 8054-50-02 
Saint Louis, MO 63110 
Tel: 314-362-5129 
E-mail: joannaa@wustl.edu 
 
Simon Haroutounian, PhD, MSc 
Associate Professor and Division Chief, Department of Anesthesiology 
Washington University School of Medicine  
 
Katherine Clifton, MD  
Assistant Professor, Department of Medicine - Oncology  
Washington University School of Medicine  
 
Kenneth Freedland, PhD 
Professor, Department of Psychiatry 
Washington University School of Medicine 
 
Michael Avidan, MBBCh 
Professor and Chair, Department of Anesthesiology 
Washington University School of Medicine  
 
Eric Lenze, MD 
Professor and Chair, Department of Psychiatry 

 
 
    
 
 
Washington University School of Medicine 
 
 
Katherine Holzer, PhD 
Assistant Professor, Department of Anesthesiology 
Washington University School of Medicine 
 
Thomas Kannampallil, PhD 
Associate Professor, Department of Anesthesiology and Institute for Informatics 
Washington University School of Medicine 
 
J. Philip Miller, PhD 
Professor 
Division of Biostatistics 
Washington University School of Medicine 
 
Mary Politi, PhD 
Professor, Department of Surgery  
Washington University School of Medicine 
 
Ana Baumann, PhD 
Assistant Professor, Department of Surgery  
Washington University School of Medicine 
 
Bethany Pennington, PharmD 
Assistant Professor,  
Department of Anesthesiology  
Washington University School of Medicine 
 
Theresa Cordner 
Senior Research Coordinator 
Department of Anesthesiology  
Washington University School of Medicine 
 
 
 
 
 
202212097  
 
Version Date:  November 21, 2022 
Version 2 Date: March 6, 2023 
Version 3 Date: June 12, 2023 
Version 4 Date: October 30, 2023 

 
 
    
 
 
1.  SYNOPSIS 
 
Study Title 
Behavioral activation and medication optimization for perioperative 
mental health in oncologic surgery 
 
Abbreviated title 
CPMH Oncologic R34 RCT 
Objective 
Using a Hybrid Type 1 Effectiveness-Implementation RCT design, we 
will test the effectiveness of a bundled behavioral activation and 
medication optimization in reducing symptoms of depression and 
anxiety in older adults undergoing oncologic surgery (compared with 
usual care), while examining implementation outcomes. 
Study Period 
Planned enrollment duration: 12-15 weeks (an initial visit; follow-up 
survey at 1 and 3 months) 
 
Planned study duration: 2 years  
 
Number of Patients 
100 
 
 
Study Treatment  
Behavioral activation and medication optimization 
 
Study Design 
Hybrid Type 1 Effectiveness-Implementation prospective randomized 
controlled trial design. 
Inclusion and 
Exclusion Criteria 
Inclusion criteria: 
• Adults ≥ 60 years 
• Scheduled major thoracic, abdominal, or breast surgery for 
suspected or confirmed malignancy 
• PHQ-ADS ≥ 10, indicating clinically significant depression or 
anxiety symptoms 
Exclusion criteria: 
• Barrier to communication (Unable to read, speak, and 
understand English)   
• Severe cognitive impairment screened by the SBT (Short 
Blessed Test) >10 
• Acutely suicidal  
• Previous participation in this study or another CPMH study of 
the intervention bundle or its feasibility. 
Measurements 
 
Baseline 
PHQ-ADS 
Quality of Life (CDC HRQOL-14) 
Short Blessed Test (SBT) 
Presence and intensity of preoperative pain  
 
In-Hospital 
Delirium (extracted from electronic health record retrospectively) 

 
 
    
 
 
Medications of interest  
 
Postoperative 
PHQ-ADS 
Quality of life 
Rehospitalization 
Falls 
Presence and intensity of Persistent post-surgical pain (PPSP)   
Pain interference, using modified Brief Pain Inventory (BPI) 
Medications of interest  
 
 
Statistical 
Methodology 
The study will use a modified Intent To Treat (mITT) approach where 
randomized patients who did not have the surgery or procedure will not 
be included in the analyses.  We will compare the intra-group PHQ-ADS 
scores at 3 months after surgery as the primary outcome. 
 
As exploratory outcomes, we will compare each the following outcomes 
between the groups: (occurrence, or change from baseline to 1-month, 
and 3-month follow-ups, as appropriate): 
 
• Quality of life (CDC HRQOL-14) 
• Length of stay (ICU & hospital) 
• Delirium 
• Rehospitalization 
• Falls  
• Persistent post-surgical pain presence and pain interference 
• Medications of interest 
  
The following measures will be collected from patients allocated to the 
intervention arm for implementation assessment: 
 
• Reach 
• Implementation potential (i.e., Acceptability of intervention; 
Appropriateness of intervention; Feasibility of intervention) 
• Patient satisfaction and experiences with overall surgical 
experience and intervention bundle 
 
A combined measure including modified versions of the following  
scales will be collected only from patients allocated to the intervention 
arm to assess engagement with our intervention bundle approximately 2 
months  after surgery: 
• Sinclair Compassion Questionnaire-Short Form (SCQ-SF) 
• Behavioral Activation for Depression Scale (BADS) Activation 
subscale 

 
 
    
 
 
• MiPrep survey 
 

 
 
    
 
 
2.  STUDY PROTOCOL  
 
2.1 Background and Significance 
 
Inadequate management of preoperative mental health disorders often contributes to poor 
postoperative outcomes, including increased rates of readmission, delirium, falls, and mortality [1-5]. 
However, very little work has been done to improve perioperative mental health. In particular, there 
have not been any systematic efforts to identify evidence-based behavioral interventions that were 
originally developed for depression and anxiety in otherwise medically well psychiatric patients, 
adapt them for use in surgical populations, test their effectiveness in these patient populations, and 
study implementation strategies. 
Consequently, we currently lack conclusive evidence on effectiveness of interventions specifically 
focused on the delivery of perioperative mental health care in older surgical patients. To address this 
understudied research area, the proposed study will focus on comparing a bundled intervention of 
Behavioral Activation (BA) and Medication Optimization (MO) (compared to usual care) among 
older adults undergoing oncologic surgery. 
The mental health intervention bundle, (Surgical Wellness Program) composed of BA and MO, can 
mitigate anxiety and depression symptoms during the perioperative period [6]. Towards this end, we 
propose to test the effectiveness as well as the implementation potential of the intervention bundle in 
a Hybrid Type 1 Effectiveness-Implementation RCT Design. 
 
2.1.1 Preliminary Data 
 
In an IRB-approved study (IRB # 202101103), we enrolled 8 patients undergoing oncologic surgery 
to an open-label feasibility phase of the study, to establish recruitment feasibility, and finalize the 
details pertaining to the study protocol, participant screening, informed consent process, recruitment 
and follow-up, as well as finalize the workflow for medication optimization and behavioral 
activation. 
Given that these objectives were attained, and reflected in the finalized methodology proposed in this 
study protocol, we are ready to launch our clinical trial to evaluate the effectiveness and 
implementation-potential of our intervention bundle using a Hybrid Type 1 Effectiveness-
Implementation RCT design. 
 
2.2 Objective 
 
We will test the effectiveness of a bundled intervention comprised of behavioral activation and 
medication optimization in reducing symptoms of depression and anxiety in older adults undergoing 
oncologic surgery (compared with usual care), while examining implementation outcomes. The study 
will be conducted by the members of the newly established Center for Perioperative Mental Health 
(CPMH), supported by National Institute of Mental Health (NIMH).  
 
 
2.3 Patient Selection 
 
The study coordinators will screen the Thoracic, Breast, and Hepatobiliary Surgery clinic schedules, as 
well as the schedule for the Center for Preoperative Assessment and Planning (CPAP) at Barnes-Jewish 

 
 
    
 
 
Hospital for patients undergoing oncologic surgery. Prospective patients will also be identified by Epic 
workbench reports customized to limit results to those at least 60 years of age with an eligible surgery 
scheduled at BJH/WUSM.   In addition, study collaborators, along with thoracic, breast, and 
hepatobiliary surgery research support teams, will refer patients from their clinics who meet the 
inclusion criteria sought from the EHR. 
 
A member of the study team will obtain the patient's phone number, age and sex, as well as type of 
surgery, the surgeon’s name and planned surgery date through Epic. A member of the study team will 
contact potentially eligible patients to screen for inclusion criteria. 
 
2.3.1 Inclusion Criteria 
 
Pre-screening: 
 
To be considered for participation, patients will be screened using PHQ-4 questionnaire. Scores >3 
will indicate positive pre-screen (i.e. can be considered for participation and formal screening). 
Scores < 3 will indicate negative screen (i.e. patient not considered for formal screening due to low 
risk for anxiety or depression).  
 
Screening: 
 
Each participant must meet all of the following criteria: 
Inclusion 
• Adults age ≥ 60 years 
• Scheduled major thoracic, breast, or abdominal surgery for suspected or 
confirmed malignancy 
• PHQ-ADS (Patient Health Questionnaire Anxiety and Depression Scale) ≥10 
indicating clinically significant depression or anxiety symptoms.[7] 
 
2.3.2 Exclusion Criteria 
 
Participants will not be enrolled if any of the following criteria exist: 
Exclusion 
• Barrier to communication (Unable to read, speak, and understand English)   
• Severe cognitive impairment screened by the SBT (Short Blessed Test) >10 
• Acutely suicidal  
• Considered ineligible per the discretion of the oncologic surgeon or study PI 
• Previous participation in this study or another CPMH study of the intervention bundle 
or its feasibility. 
 
2.4. Study Design 
 
All eligible and consenting patients will be randomized in 1:1 ratio (with no stratifications) to receive 
either the intervention bundle or usual care. 
Consenting participants (in both arms) will undergo a standard battery of assessments at baseline (prior 
to the intervention in the intervention group) and will be followed until approximately 3 months 
postoperatively. In conjunction with the effectiveness outcomes data, implementation outcomes related 

 
 
    
 
 
to reach, and implementation feasibility, acceptability, and appropriateness of the intervention bundle 
will be collected. 
 
2.4.1 Study Procedures 
 
Consented subjects will be asked to participate in the study for approximately 3 months after surgery. 
All participants must sign a consent document (e-consent or paper), indicating their consent, 
approved by the Washington University School of Medicine Institutional Review Board, before they 
can participate in the study. 
 
All participants will be asked to complete the following questionnaires at baseline (in person, 
remotely via a web-based survey, or via telephone): 
• CDC HRQOL-14 Quality of Life survey 
• PHQ-ADS (Patient Health Questionnaire Anxiety and Depression Scale) 
• SBT (Short Blessed Test)  
• Presence and intensity of preoperative pain  
• Demographics survey  
• Patient-reported falls 
All participants will be followed for up to approximately 3 months after their scheduled procedure. 
They will complete follow-up surveys at approximately 1 month and 3 months after surgery by either 
web-based survey, mail, or via a telephone interview. 
At the end of the study, all participants in the intervention arm will be invited to take part in a semi-
structured telephone interview conducted by an experienced, qualitative researcher with whom they 
had no previous contact. The interviews will explore the participants’ perceptions, attitudes, and 
experiences of the intervention bundle.  
2.4.2 Minimization of Bias 
 
Enrollment will not be based on sex or ethnic background. Standard of care will not be affected for any 
of the participants due to study participation. Completion of the outcomes will be entirely patient-
reported, to minimize assessor’s bias in interpreting patient responses. 
 
2.4.3 Pre-Study Period 
 
Patients who are ≥ 60 years of age undergoing oncologic surgery will be approached for consent to this 
study. Eligible patients will be invited to participate in the study, which will be conducted remotely 
and in-person. Potential candidates for the study will be provided a written and oral description of the 
study procedures, benefits, and potential risks as well as the opportunity to ask questions regarding the 
study. Participants are informed that their participation is voluntary and that they may refuse to 
participate or withdraw from the study at any time without penalty. Patients will be required to give 
informed consent prior to participation. A study team member who is experienced with cognitive 
testing will recruit the subjects to the study, and perform the SBT assessment. 
 

 
 
    
 
 
Each subject who qualifies for entry into the study on the basis of inclusion/exclusion criteria and 
completion of informed consent will be assigned the next available patient number. This indicates 
enrollment in the study. Patients who are eligible but decline participation will be invited to complete 
an optional survey indicating reasons for decline.    
2.4.4. Randomization 
 
The randomization table will be generated by the study biostatistician, using a variable block 
sequence.  The assignment of the treatment condition for each individual participant will be done by 
the REDCap randomization module after they have been determined to be eligible for the trial. 
 
 2.4.5. Blinding 
Study staff responsible for administering ratings throughout the study are blinded. This blinding is 
kept throughout the study until data collection is complete. At the end of the follow-up, the study 
coordinator will complete a blinding question to try to guess the arm to which each participant was 
allocated. This will allow to determine whether the blinding procedures in the study were effective 
[8].  
 
2.4.6 Study Period 
 
Baseline Characterization of Participants: At enrollment, a battery of assessments will characterize 
participants. Anxiety and depression assessment will use the PHQ-ADS, as described above. The use 
of this tool for this population is supported by a recent meta-analysis suggesting that the PHQ9 (on 
which this tool is based) has good sensitivity and specificity in the diagnosis of depression in older 
adults [9]. Quality of Life (QoL) will be assessed using the CDC HRQOL-14 survey) [10]. The 
questions in this patient-reported survey correspond to the QoL domains of Healthy days (physical 
and mental), Activity Limitations, and Healthy Days Symptoms. Cognitive function assessment will 
be performed using the Short Blessed Test (SBT). SBT is a reliable test, with high inter-rater 
agreement, which is beneficial for characterizing cognitive functioning in the perioperative setting 
[11, 12]. Recognizing the uncertainty associated with face-to-face data collection due to the COVID-
19 pandemic, we selected tools such as the SBT because it can be delivered remotely [13].  
 
All patients in both arms will receive resources (see Handouts for CPMH RCT SOC Group and 
Handouts for CPMH RCT Intervention Group) either by mail or email if they prefer.  The resources 
include options for exploring brain health, supporting sleep and mental health, and introducing 
community resources for older adults.   
 
Intervention Bundle: This will be initiated prior to or soon after the surgery and will be continued 
until approximately 3 months postoperatively.  
The basic premise of behavioral activation is to help people with mental health problems to engage 
in activities that are reinforcing or meaningful and guided by their personal values [14]. Patients will 
be asked to check with their physicians if there is any question about the safety of any physical 
activities that are included in the behavioral activation plan. Behavioral activation as the core 

 
 
    
 
 
intervention allows for uniformity across participants from each cohort, yet enough flexibility for the 
actual components of behavioral activation to be individually adapted based on patient preferences. 
In a recent meta-analysis, behavioral activation programs improved depression and anxiety [15], as 
well as disability in older adults [16]. In addition, behavioral activation delivered by telehealth to 
older adults was cost-effective and lowered health care utilization costs over 1 year [17]. In addition 
to the core intervention of behavioral activation, study participants will tailor the intervention by 
choosing activities, per their preference, with demonstrated benefit in improving depression and 
anxiety symptoms in older adults [18, 19]. Behavioral activation will generally begin pre-operatively, 
with sessions approximately every two weeks. After discharge, the behavioral intervention will 
continue, for 10-12 sessions, or out to approximately 3 months postoperatively. Patients in the 
intervention arm will receive information (Handouts for CPMH RCT Intervention Group) by mail or 
email if they prefer. The handouts include tools to support behavioral activation and optional 
activities.    
Medications will be reviewed and optimized, as appropriate. In several clinical trials including 
thousands of older adults, we have developed and refined a process for this review and medication 
optimization, including adjusting suboptimal dosing for anti-depressants and discontinuing 
medications that are harmful for brain health (such as anticholinergics [20]). Medication optimization 
consists of a simple set of principles: reconcile patient’s medications, identify the patient’s likely 
need for, and interest in, a medication adjustment, make the adjustment, and assess the response to 
that adjustment. Benzodiazepines, and strong centrally acting anticholinergics and antihistamines, are 
the focus of deprescribing, as they increase the risk for falls and delirium. We will follow the 
principles of shared decision-making with patients for medication changes. While the participant is 
an inpatient, the study pharmacy team will coordinate with the inpatient team to ensure that 
medication changes that were introduced preoperatively are maintained in-house and that no new 
inappropriate medications are initiated. After discharge, and up to approximately 3 months 
postoperatively, the interventionist (also referred to as a perioperative wellness partner) and 
pharmacy team will ensure that targeted medication changes are reconciled during transitions of care.  
 
Methods 
 
2.4.6 Observations and Measurements 
 
2.4.6.3 Primary Outcome Measures 
 
Effectiveness outcomes will include the primary outcome measure of PHQ-ADS, a validated 
composite scale of depression and anxiety symptoms [7], measured at 1 and 3 months after surgery.  
Three months post-operatively is the primary endpoint. 
 
Process measure for target engagement  
As a process measure of target engagement at approximately 2 months  after surgery, we will use a 
combined measure including modified versions of the Sinclair Compassion Questionnaire-Short 
Form (SCQ-SF) [21], Behavioral Activation for Depression Scale (BADS) Activation subscale [22, 
23], the MiPrep survey [24], four questions specific to our Wellness Program, and one question to 
assess participants’ understanding of how the study’s target medications can affect their mental 
health, if applicable. The target engagement measure will be collected by survey, which participants 

 
 
    
 
 
in the intervention group can complete either online via REDCap link or by phone if they prefer, with 
an unblinded member of the study team. 
 
 
2.4.6.4 Exploratory Outcome Measures 
The exploratory outcomes will include QoL measured via the CDC HRQOL-14 survey, and other 
perioperative outcomes of interest, nominated by our stakeholders as key outcomes of interest, 
including:  
(1) In-hospital: (i) Delirium incidence,[20],  (ii) Length of Stay (hospital and ICU),(iii) information 
on the use of common medications for chronic pain, such as opioids, gabapentin and pregabalin. 
 (2) Post-discharge: (i) Falls, (ii) All-cause rehospitalization out to 90 days postoperative, (iii) 
persistent post-surgical pain (PPSP), (iv) information on the use of common medications for chronic 
pain, such as opioids, gabapentin and pregabalin.  
(3) Process outcomes: For patients on the intervention arm, CAHPS modified survey will be 
administered after the intervention is complete. 
(4)  Implementation-potential surveys: Acceptability of Intervention Measure, Intervention 
Appropriateness Measure, Feasibility of Intervention Measure. 
 
 
Table 2. Details on Study Outcomes  
 
Effectiveness Outcomes 
Data Source 
Description 
Data Collection 
Mechanism  
 
Time points   
(Baseline, 1, 
2, 3 month-
post-op or 
EOS) 
Primary 
(Clinical) 
Anxiety and 
Depression 
Patient Health 
Questionnaire 
Anxiety and 
Depression Scale 
(PHQ-ADS)  
A validated 
composite of 
symptoms of 
depression and 
anxiety 
Patient Self-Report 
Baseline; 
1 mo and 3 mo 
Exploratory 
(Clinical) 
Quality of Life 
The Health-
Related Quality 
of Life CDC 
HRQOL-14 
survey [10] 
A patient-reported 
global health 
measure. The 
questions in this 
survey correspond 
to the QOL domains 
of Healthy days 
(physical and 
mental), Activity 
Limitations, and 
Healthy Days 
Symptoms 
Patient Self-Report 
Baseline; 
1 mo and 3 mo 

 
 
    
 
 
In-hospital delirium 
incidence  
 
Retrospective 
EHR chart 
review  
  
. 
EHR report, and 
Research Team 
Member review 
EHR for delirium-
related information 
from the time of 
post-op inpatient 
stay.  
  
In-hospital: at 
ICU and 
hospital floor 
 
 
Post-discharge falls 
Patient 
Reported Falls  
A Patent Reported 
Falls survey will 
be collected at 1 
month and 3 
months either by 
phone or REDCap 
link, at follow-up 
clinic 
appointments. 
Patient Self-Report 
Baseline; 1mo 
and 3mo 
Pain 
Pain presence 
and severity at 
the site of 
surgery, and 
Brief Pain 
Inventory (BPI) 
pain 
interference 
scale 
BPI is a well 
validated measure 
of pain severity 
and pain 
interference items.  
Patient self-report 
Baseline, 1 
mo, 3 mo 
Medications of 
Interest 
EHR  
Review of CPMH 
targeted 
medicationsand 
common 
medications for 
chronic pain, such 
as opioids, 
gabapentin and 
pregabalin 
Patient Self-Report/ 
study team member 
verifies targeted 
meds and/or  EHR 
review 
Baseline, at 
transitions of 
care, and up 
to 3mo post-
op.   
Length of stay (both 
hospital and ICU) 
Research Data 
Core 
Standardized 
reports on RDC 
warehouse will 
generate statistics 
of enrolled patients 
regarding the 
length of stay, 
rehospitalization, 
and related clinical 
metrics.  
EHR report 
In-hospital: at 
ICU and 
hospital 
discharge 
All-cause 
rehospitalization  
EHR and 
patient 
EHR, patient 
Post-op: 1 mo 
and 3 mo 
Implementation and Process 
Outcomes 
 
Data Source 
Description 
Data Collection 
Mechanism 
 
Time points 
Reach 
Enrollment Log 
Reach of the study: 
patients who agreed 
to participate in the 
study out of total 
eligible to 
participate 
Electronic Health 
Record 
End of Study 

 
 
    
 
 
Reach of the 
intervention bundle: 
patients who 
completed the 
interventions out of 
patients who agreed 
to participate 
Implementation-Potential (I) 
Acceptability of 
Intervention 
Measure,  
Intervention 
Appropriateness 
Measure, 
Feasibility of 
Intervention 
Measure  
Acceptability, 
Feasibility and 
Appropriateness 4-
item Likert scale 
survey 
Patient Self-Report 
Post-EOS 
Patient satisfaction and experience 
Modified-
Consumer 
Assessment of 
Healthcare 
Providers and 
Systems 
(CAHPS)[26] 
The modified 
CAHPS asks 
patients about their 
experience with the 
intervention bundle 
before surgery, 
during surgery, and 
after surgery. 
Patient Self-Report 
Post-EOS  
Process measure for target 
engagement 
Data Source 
Description 
Data Collection 
Mechanism 
Time points 
Target engagement measure 
Combined 
measure of 
modified 
versions of the 
following scales: 
Sinclair 
Compassion 
Questionnaire-
Short Form 
(SCQ-SF)[21], 
Behavioral 
Activation for 
Depression Scale 
(BADS) 
Activation 
subscale [22], the 
MiPrep 
survey[24] 
The SCQ-SF is a 5-
item patient-
reported measure 
modified to assess 
compassion of the 
Wellness Provider; 
the BADS 
Activation Subscale 
(7 items) measures 
target engagement 
of BA in studies of 
geriatric depression 
[23]; and the 
MiPrep survey (3 
items) assesses 
patients’ preparation 
for medical 
interventions. 
Patient Self-Report 
Approximately 
2 mo post-op  
In addition to these outcomes, we will assess fidelity to our intervention bundle to ascertain the extent 
to which an intervention bundle is carried out, as intended and consistently across different settings, 
and patients. If the patient agrees to audio/video recording, the intervention sessions will be audio 
recorded (or audio/video if the patient prefers to meet by Zoom teleconference). To track this, we will 
use the recordings of these discussions between the patient and the perioperative wellness partner 
during the behavioral intervention and medication optimization sessions. We will capture data on 
patient interactions with the wellness partner, their delivery of the intervention bundle, any observed 
barriers and facilitators to the intervention adherence, acceptance and fit within the perioperative 

 
 
    
 
 
workflow. 10% of these sessions of patients and their wellness partners will be selected based on a 
convenience sample for evaluating fidelity of the bundle.     
Lastly, we will also obtain stakeholder perspectives on the intervention bundle after the intervention 
period has been completed using semi-structured interviews. We will conduct interviews with 
patients who participated in the intervention, and the topics of discussions will be guided by an 
implementation science framework referred to as CFIR (Consolidated Framework of Implementation 
Research). The interviews will explore the participants’ perceptions, attitudes, and experiences with 
the intervention bundle, intervention bundle acceptability and detailed accounts of participants' 
experiences after the intervention has been stopped with regards to intervention sustainability and 
maintenance. Interviews will be conducted via Zoom or telephone and will be digitally recorded and 
transcribed verbatim.  
 
Study Calendar  
 
 
Time 0 
Baseline/ 
Time 1 
1 mo 
follow up 
2 mo 
follow up 
3 mo 
follow up 
Post-
EOS 
Patient Consent 
X 
 
 
 
 
 
Patient Screening   
X 
 
 
 
 
 
Patient Baseline surveys  
 
X 
 
 
 
 
Patient Follow-up 1 & 3 mo Surveys 
 
 
X 
 
X 
 
For Patients on the Intervention Arm: 
Process Target Engagement Measure 
 
 
 
X 
 
 
For Patients on the Intervention Arm: 
Intervention-Patient Interviews and  
Implementation, Patient Satisfaction and 
Experience surveys 
 
 
 
 
 
X 
For Patients on the Intervention Arm:   
Behavioral Activation and Medication 
Review Intervention Sessions 
 
 
Approximately 8-12 sessions as needed 
(per Pt preference) from Baseline, 
continuing for up to approximately 3 
months post-op during study data 
collection, until EOS. 
 
 
2.4.6.5   Statistical Methods 
 
Primary Outcome Analysis: The primary outcome for the R34 is the change in PHQ-ADS from 
baseline to 3-month visit. The primary statistical model will be a mixed model repeated measures 
ANOVA with a treatment group by time point design. This model is ideal because it uses all 
available data and is robust even with some expected missing follow-up data. The primary statistical 
test is a contrast which compares the change in the treatment group to the change in the control 
group. The population used for the modified Intent to Treat analysis consists of those randomized 
patients who actually received the procedure or surgery. 
Analysis of Exploratory Endpoints: For exploratory endpoints which are measured on the same 
schedule as the PHQ-ADS, they will be analyzed utilizing the same mixed model. For the outcomes 
of length of stay (ICU & hospital), a simple analysis of covariance will compare the two groups 
where we will identify the relevant covariates during the planning phase. For the presence of delirium 
and rehospitalization we will use a corresponding generalized linear model with a logistic link 
function and appropriate covariates. For the presence of falls we will use the extension of the Cox 

 
 
    
 
 
model when there may be multiple events with appropriate covariates. [27] For all analyses, we will 
examine the potential moderating effect of sex.  
 
Descriptive data will be presented from the semi-structured interviews. The interviews will be 
conducted using an interview guide developed by study team members. These will either be audio-
recorded and transcribed verbatim or notes will be taken by a second researcher to capture the data. 
The transcriptions will be analyzed thematically using a pre-determined framework derived from the 
interview schedule and adapted and revised based on participant responses [45]. Semi-structured 
interviews will provide data on the acceptability of the intervention and detailed accounts of 
participants' experience after the intervention has been provided.  
2.4.6.6 Sample Size and Power of Primary Analysis:  
 
In order to estimate the power of the primary outcome analysis we examined the manuscript which 
provided the original validity and reliability studies for the PHQ-ADS [28] and one of the trials 
which provided data for that study (SCOPE) [29, 30]. At 3 months they observed a change from 
baseline divided by the standard deviation of the change of 0.43 which corresponds to a change of 3 
points on the PHQ-ADS. The PHQ-ADS authors estimate the minimal important clinical difference 
(MICD) from the standard error of measure (SEM) as 3-4 points. If we postulate a difference in the 
change scores of 2 points between the two groups, then with a power of 0.80 we would need 36 in 
each group. Since the SCOPE trial was a pain relief study without a requirement of anxiety or 
depression, we consider these estimates rough estimates.  This trial will having 100 mITT patients 
(50 per arm) in order to account for any incomplete data among recruited participants. Recruitment 
will continue until 100 randomized patients have had their procedure or surgery. 
 
2.5 Management of Intercurrent Events 
 
2.5.1 Adverse Experiences 
 
Based on the nature of this study, which involves surveys, a cognitive test, and a behavioral 
intervention, adverse events are exceedingly unlikely. 
 
2.5.2 Premature Withdrawal 
 
Subjects will be withdrawn if the investigator decides that discontinuation is in the best interest of the 
subject, or the subject requests withdrawal from the study. Additionally at PI discretion, they may be 
withdrawn if their surgery is cancelled or postponed (for clinical or non-clinical reasons) for more than 
approximately 3 months after baseline.   
 
Participants who choose to end study participation early, may be asked to complete early termination 
assessments.  Additionally, those in the intervention arm may choose to withdraw from that at any time, 
but will be allowed to continue with data collection follow-ups if they still want to participate. 
 
2.5.3 Potential Risks 
 

 
 
    
 
 
This study involves minimal risk to subjects. Unlikely but potential risks include increased risk of 
depression or anxiety, errors in medication recommendations or medication withdrawal symptoms, 
and breach of confidentiality. The risk of medication withdrawal (i.e., from benzodiazepines) is 
mitigated by slowly tapering rather than stopping these medications. Patients who are identified as 
being acutely suicidal will be excluded from the study. Nevertheless, since the rate of completed 
suicide in the USA remains high (i.e., about twice the rate of homicide) and most Americans who 
commit suicide suffer from depression, all participants eligible to participate in this study are 
statistically at a relatively higher risk for suicide than the general population. However, the 
participants’ absolute risk for completing suicide during this brief study remains very low (i.e., about 
1 in 3,000 to 10,000) and participation in the study does not create or increase the risk of completed 
suicide; rather, most experts believe that one of the most efficient ways to decrease suicidal risk in 
older depressed individuals is to treat their depression. Furthermore, all participants will be formally 
assessed frequently throughout the study. If the study personnel identify that a participant has become 
acutely suicidal, this participant will be referred to a mental health professional for further evaluation 
and treatment (see section: Procedures to Minimize Risks). This may lead to a clinical intervention 
that is lifesaving and may not have occurred had the participant not been participating in the study. 
 
2.5.4 Procedures to Minimize Potential Risks 
 
Medication Error Risk: Dr. Eric Lenze will supervise careful training and oversite of the intervention 
pharmacists making medication optimization recommendations to reduce the risk of medication error 
or medication withdrawal symptoms. Algorithms for tapering medications that should not be abruptly 
discontinued will be employed. We have carried out this deprescribing protocol in several large RCTs 
and have not seen any problems occur. 
 
Suicide risk management: As discussed above, at each assessment point, the research staff will assess 
for passive death wish, and suicidal ideation, intent or plan when they administer the PHQ-ADS. If a 
participant endorses suicidal ideation, intent, or plan, the rater will be trained to follow an 
operationalized protocol that has been developed to manage high-risk participants in other studies of 
depressed participants potentially at risk for suicide. This protocol has already been used successfully 
by Dr. Lenze’s team to manage acutely suicidal patients. Briefly, the protocol entails a specific 
determination of the suicidal risk and prescribes a set of actions. For instance, when a participant is 
determined to be at high and immediate risks, the rater is instructed to stay with the participant until 
he or she has contacted a study psychiatrist (Dr. Lenze) to discuss the situation and to devise a plan. 
For this reason, raters will have cell phones and Dr. Lenze will be reachable via email and cell phone. 
In case of extreme emergency, raters are instructed to call their hospital security team or 911 for 
immediate help and to initiate commitment proceedings. 
 
Patients will be asked to check with their clinician if there is any question about the safety of any 
physical activities that are included in the behavioral activation plan. 
 
The risk of breach of confidentiality will be minimized by ensuring that protected health information 
will only be shared with members of the research team. Only data necessary to complete the study 
will be collected. Electronic data will be kept in a password-protected electronic database only 
assessable via password protected departmental computers. Patients may choose to not participate in 
the study or withdraw at any time with no penalty in terms of the care they receive. 

 
 
    
 
 
 
2.5.5   Data and Safety Monitoring Plan 
 
The specific monitoring plan for this investigation is commensurate with the risks and the size and 
complexity of the studies planned. Given the nature of the protocol, the risks are likely limited to 
breach of confidentiality. The Principal Investigator will be responsible for monitoring the data and 
assuring protocol compliance. The PI will meet with the clinical research coordinator and Data 
Manager bi-weekly to review enrollment, eligibility, participant follow-up and outcome assessment. 
The PI and study coordinator will monitor for breaches of confidentiality on an ongoing basis. Study-
related adverse events will be reported per IRB guidelines. All serious adverse events (SAE) will be 
recorded and adjudicated by a CPMH Principal Investigator and reported per IRB guidelines. Any 
endorsement of suicidal ideation will be managed acutely as detailed in the section 2.5.4. If study 
staff becomes aware of a reportable adverse event, it will be reported to necessary stakeholders 
according to Washington University Human Protection Office guidelines. This type 1 hybrid 
randomized study does not require a Data and Safety Monitoring Board. 
 
3.  HUMAN SUBJECTS RESEARCH 
 
3.1 Protection of Human Subjects 
 
The study will be conducted under appropriate Washington University Institutional Review Board 
protocols and consent forms approvals. The study will be conducted under the supervision of the PI, 
who has extensive of experience in the conduct of human research studies. 
 
3.2 Sources of Materials 
 
Preoperative assessments along with preoperative and postoperative questionnaires regarding quality 
of life, depression, and anxiety will be obtained from all study participants. The results of follow-up 
questionnaires will be obtained via e-mail, mail, or telephone survey. Data will be collected at baseline, 
one, two, and 3 months following surgical procedure. 
3.2.1 List of Protected Health Information Collected for Study 
 
The HIPAA protected identifiers that will be collected for this study include: 
• Name 
• Dates 
o Date of birth 
o Date of services (surgical procedure) 
• Contact information 
o Mailing address 
o Phone number 
o Electronic mail address 
• Medical record number 
3.2.2 Data Management 

 
 
    
 
 
 
All paper data will be stored under lock and key (office, file cabinet) and all electronic data will be 
stored in REDCap, only accessible to the research team members. Surveys that are completed 
electronically will be administered via the REDCap server. All REDCap email correspondence will be 
sent using secure survey links. All survey information will be coded with the patient’s unique study ID 
number and no personal health information that may directly identify patients will be included. 
 
3.3 Recruitment and Informed Consent 
 
Participants will be recruited either from the oncologic surgery clinics at Washington University or the 
Center for Preoperative Assessment and Planning (CPAP) at Barnes-Jewish Hospital/Washington 
University. Participants with pre-screening scores of PHQ-4 ≥3 will be recruited, and eligibility 
confirmed if PHQ-ADS ≥10. Retention strategies will include flexibility in scheduling follow-up visits 
and coordination of research visits with any in-person clinical visits. Subjects will be given verbal and 
then written descriptions of the study aims, procedures, risks, and benefits, and will be required to give 
informed consent. A member of the research team will be available to present study descriptions, 
informed consent, and answer any questions. Subjects are informed verbally and in writing that 
participation is voluntary and they may refuse to participate and may withdraw from the study at any 
time without penalty. Remuneration for each data collection study visit will be provided to encourage 
retention as well. 
  
3.4 Potential Benefits of the Proposed Research to the Subjects and Others 
 
Although the study is designed to improve symptoms of depression and anxiety and other outcomes 
of care, there is no guarantee that the study participants will receive any clinical benefits by 
participating in the study. This may lead to a clinical intervention that is lifesaving and may not have 
occurred had the participant not been participating in the study. Given the undertreatment of 
depression and anxiety in older adults, the minimal risks are acceptable in comparison to the potential 
benefits in improving the mental health of older adults undergoing surgery. 
 
3.5 Remuneration 
 
Patients will receive remuneration by a reloadable debit card of $25 for completion of each data 
collection study visit.  Standard Care (control arm) participants will be compensated for their time at 
Baseline, 1, and 3 month post-op, up to $75 for completion of all data collection time points. 
Wellness Program (intervention arm) participants will be compensated for their time at Baseline, 1, 
and 3 month post-op, plus a post-EOS semi-structured interview, so up to $100 for completion of all 
data collection time points.   
 
3.6 Inclusion of Women 
 
Eligible individuals will be offered the opportunity to participate in the study regardless of gender or 
minority status. Thus, the sample composition will reflect the composition of community-living older 
adults in the St. Louis area. 
 
3.7 Inclusion of Minorities 

 
 
    
 
 
 
All of our studies actively encourage the participation of minorities in the research. Our minority 
recruiting typically matches the demographic composition of the Washington University community 
from which subjects will be recruited (78% white, 21% Black, <1 % Hispanic).  
 
3.8 Inclusion of Children 
 
We will not be including children in this study. 
 

 
 
    
 
 
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