Living With Multimorbidity: Symptom Management Across the Illness Trajectory
Phase: NA
Conditions: Multimorbidity, Quality of Life, Symptom Management
Sponsor: Johns Hopkins University

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Living With Multimorbidity: CO-ORDINATE Program 
NCT05985044 
November 22, 2022 

 
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Table of Contents 
Study Protocol ................................................................................................................................. 3 
1. Abstract ................................................................................................................................................. 3 
2. Objectives .............................................................................................................................................. 3 
3. Background ........................................................................................................................................... 4 
4. Study Procedures ................................................................................................................................... 4 
Statistical Analysis Plan ................................................................................................................. 9 
 
 
 
 

 
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Study Protocol 
1. Abstract 
Background: In times of stress and critical illness, physical, social and psychological 
vulnerabilities for patients and their families are amplified and this fragility is most noted in 
older adults. This study is focused on adult aged 55 years and above, living with multimorbidity, 
admitted at or eligible to admitted to the intermediate care unit (IMCU). The IMCU is widely 
used to care for critically ill patients requiring more monitoring or nursing care than is provided 
on hospital acute care floors but who do not have intensive care needs. Half of the patients in 
these units present with multimorbidity and are hospitalized for a range of reasons. Further, these 
vulnerable patients are not often categorized in single disease specific categories such as, 
cardiac, respiratory and gastrointestinal because of multiple conditions and symptoms and have a 
greater potential to fall through the cracks. Additionally, the current pandemic, COVID-19 has 
primarily affected these adults with multimorbidity. There is a need to assess symptom trajectory 
and symptom burden and to develop an effective, and financially sustainable approach to meet 
the health needs of critically ill adults and families with multimorbidity. 
 
Aims: The study aims 1) to understand symptom trajectory and symptom burden from the 
perspectives of patients, family caregivers, health professionals and other key stakeholders and 
collectively develop a symptom management toolkit; 2) to refine and pilot test the nurse-driven 
symptom management toolkit/intervention among adults aged 55 years and above living with 
multimorbidity to improve symptom management and quality of life.  
 
Methods: The study will use mixed study design with 2 phases. The first phase will empirically 
describe the prevalence and burden of symptoms from the perspective of patients, family 
caregivers, health professionals and other key stakeholders. Using participatory, experience-
based co-design methodology, we will develop a symptom management toolkit. This approach 
will identify care delivery and care transitioning preferences and needs of patients with 
multimorbidity, family caregivers, healthcare providers, and other stakeholders. In the second 
phase, the data from phase one will inform the refinement and evaluation of a patient-centered 
symptom management intervention using a pre-post quasi-experimental design. 
 
2. Objectives  
 
The specific aims and goals of this study include:  
Aim 1 (Phase 1-Year 1): Describe the symptom trajectory and burden from the perspectives of 
patients, family caregivers, health professionals and other key stakeholders and collectively 
develop a symptom management toolkit. 
Goal 1: Develop symptom management toolkit 
Aim 2 (Phase 2-Year 2): Refine and pilot test the nurse-driven symptom management 
toolkit/intervention to decrease the symptom burden and increase the QOL of critically ill adults 
with multimorbidity. 
Goal 2: Toolkit refinement/Intervention development 
Goal 3: Intervention pilot test 

 
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Goal 4: Intervention evaluation 
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Primary outcomes: Symptom burden, Quality of life 
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Secondary outcomes: Pain, Fatigue, Social support, Resilience, Health-care utilization  
3. Background  
Multimorbidity is common and is the coexistence of two or more chronic conditions in the same 
individual. The prevalence estimate of multimorbidity is 50% for individuals aged under 65, 
62% aged 65-74, 75.5% aged 75-84, and 81.5% aged 85 and older in the US 1,2. Multimorbidity 
is higher among older adults and is expected to increase due to the aging population, advanced 
medical care and improved longevity 3. Multimorbidity adversely affects health status and 
wellbeing and is closely related to increased healthcare utilization, costs and mortality 2,4,5. 
Additionally, in the current COVID-19 pandemic, the higher mortality has been predicted by the 
older age and the presence of multimorbidity 6. People with multimorbidity suffer from a high 
symptom burden such as pain, fatigue, difficulty in breathing, difficulty sleeping, lack of energy 
and such symptom directly affecting quality of life (QOL) 1,7,8. Symptom burden related to 
multimorbidity is also associated with increased functional decline and higher risk for caregiver 
strain and burden 9. Adults with multimorbidity often experience hospitalization and are admitted 
to critical care units because of multiple organ dysfunction 10. Hospitalization can be a window 
of opportunity to initiate interventions to promote recovery and resilience and enhance QOL. 
Interventions targeting the symptom trajectory and burden of patients with multimorbidity are 
lacking 11. Our preliminary work has identified that often patients in the medical Intermediate 
Care Unit (IMCU) do not necessarily access post discharge services because of the organ 
centered arrangement of programs (e.g. chronic heart failure, chronic obstructive airways 
disease, chronic renal failure, and ICU survivorship).  
 
The innovation in this study is embedded in the heterogeneity of the population, the locus of care 
and the need for transitional and supportive care strategies. The study aims to involve patients 
living with multimorbidity including those with COVID-19 to understand their symptoms and 
develop symptom management intervention, which will be a timely and valuable knowledge. 
Based on our review of the literature on multimorbidity symptom burden –key symptoms include 
difficulty breathing, fatigue, sleep disturbance, weakness, and pain 1,8. We envisage a nurse led 
pre-discharge intervention augmented by telephone support and engaging caregivers, focusing on 
addressing key symptoms originating from inactivity and deconditioning as well as 
recommended self-management interventions. This approach is anticipated to reduce symptom 
burden, improve QOL, promote resilience, enhance social support and decrease healthcare 
utilization of adults living with multimorbidity. We are conscious that the proposed Experience 
Based Co-design (EBCD) methodology will be formative in developing the intervention.  
4. Study Procedures  
 
The proposed mixed method study will be conducted in two phases using social (justice)/human 
centered design. The first phase (Year 1) will empirically describe the prevalence and burden of 
symptoms from the perspective of patients, family caregivers, health professionals and other 
stakeholders. Using participatory co-design methodology, EBCD, we will develop a symptom 

 
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management toolkit. This approach will identify care delivery and care transitioning preferences 
and needs of patients with multimorbidity, family caregivers, healthcare providers, and other 
stakeholders. In the second phase, (Year 2) the data from phase one will inform the refinement 
and evaluation of a patient-centered symptom management intervention using a pre-post quasi-
experimental design.  
 
 
 
Phase 1: A collaborative study will be implemented to describe the symptom trajectory and 
burden including pain and fatigue and develop symptom management toolkit for critically ill 
adults with multimorbidity.   
Year 1, Goal 1: Develop multimorbidity management (which includes symptom management) 
toolkit, using co-design, by understanding disease trajectories, symptom trajectory, burden, 
gender roles and needs of the patient and family caregivers and key stakeholders’ priorities  
To achieve goal 1 we will use the EBCD and follow its six-stage process (Table 1), using online 
EBCD toolkit12 for consistency in documentation and processes. We will work with patients, 
family caregivers, healthcare providers, and other stakeholders through iterative rounds of data 
collection, analysis, validation and development strategies to address symptom burden. EBCD 
takes typically 9-12 months to complete13 and is proven means for understanding how to make 
the best use of data about patient, family, and healthcare providers' experience to improve the 
quality of care and culture of health services. Table 1 details the activities required for each stage 
of the EBCD process.  
 
 
 

 
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Table 1: Phase 1 
Goal 1: Develop symptom management toolkit by understanding symptom trajectory, burden, and needs of the 
patient and family caregivers and key stakeholders’ preferences 
Stages/ 
Goals 
Goals and Activities 
Stage 1 
Project preparation and relationship building  
- IRB approval 
- Identify and gain support from the stakeholders to prepare for the stages of research 
Stage 2 
Collect data form patients and family caregivers’ experiences on symptom trajectories and 
burden via filmed narrative interviews and survey 
Approximately 12 participants identified and recruited who meet the inclusion criteria 
Conduct a baseline survey and filmed and/or narrative interviews (narrative in-person or virtual 
interviews) 
The baseline survey will include questions on demographics (age, gender, ethnicity, education, and 
postal code), caregiver type, clinical profiles (co-morbidities, diagnoses, healthcare utilization in the 
last 3 months), symptom burden, quality of life, pain, fatigue, social support, and resilience.  
Patient-family shared event to validate findings, agree on quotes from interviews to represent shared 
patient-family experiences to include in the experience film and identify 3-5 strategies for effective 
symptom management  
Stage 3 
Collect data from key-stakeholders (nurses, physicians, researchers, community partners, and 
other identified stakeholders) experiences and priorities 
Approximately 12 in-depth filmed and/or narrative interviews (semi-structured in-person or virtual 
interviews) 
Non-participants observations of critically ill patients admitted or eligible be admitted at the JHH-
IMCU 
Analysis of data followed by stakeholders’ workshops to validate findings and identify 3-5 
improvement priorities for symptom management 
Stage 4 
Co-design event 
- All participants will collaborate in a workshop-style event  
- Patients, family caregivers, and key-stakeholders experiences and improvement priorities shared via 
film and discussion  
- Symptom trajectory developed in a timeline chart with patients and family experiences since the 
diagnosis of multimorbidity 
Facilitated discussion supports the identification of 3-5 shared priorities for the toolkit to reduce 
symptom burden and improve QOL in multimorbidity 
Stage 5 
Co-design working groups 
- Small groups of patients, family caregivers, and key-stakeholders will work on identified priorities, 
developing and guiding the implementation of measurable goals and strategies 
- Likely focus on goals include symptom management including pain and fatigue, QOL, resilience, 
social support, healthcare utilization  
Stage 6 
Celebration and evaluation event 
- Final outcomes will be evaluated for agreement across participants 
- Outcomes measures will be evaluated for implementation  
- Dissemination of strategies and outcome measures will be published for academic dissemination  
- The evaluation will address toolkit development and confirm participant commitment  
- The celebration and evaluation event will provide an opportunity for reflection and refocusing of the 
intervention  
 
Phase 1 will be extended for longer period and additional participants specifically with heart 
failure and other chronic conditions will be recruited to understand multimorbidity disease 
trajectories, symptom trajectory, burden, gender roles and needs of the patient and family 
caregivers and key stakeholders’ priorities using EBCD design. Additional 60 participants will 
be recruited for this (30 health care providers and stakeholders and 30 patient and family 
members). Semi-structured interview guide for healthcare providers and caregivers have been 

 
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attached. Patients baseline data collection will include data on heart failure clinical profile, 
multimorbidity disease burden, symptom burden, quality of life, co-morbidity, self-efficacy, 
social support, resilience and healthcare utilization (no. of hospitalization, no. of readmission and 
mortality in 30 days and one year, admission to nursing homes/assisted living). Additionally, 
data on fear of COVID-19 will be collected to understand effect of Pandemic. Co-design event 
and working groups will be organized in-person/virtually considering CDC-guideline for 
COVID-pandemic. Final outcome data will be compiled and presented as multimorbidity 
management toolkit. Consent form for this extended phase has been attached for review.  
 
Phase 2:  Refinement, pilot test and evaluation of the toolkit/intervention focused on decreasing 
symptom burden and improving QOL among critically ill adults with multimorbidity. 
To achieve Goal 2-4 we will continue to draw on a collaborative co-design approach and 
implement the quasi-experimental design. Figure 2 outlines the study protocol and Table 2 
details the activities necessary for the completion of phase 2.  
 
Patient recruitment and 
assessment 
 
Care following 
discharge 
 
Study assessments 
 
Follow up 
 
Figure 2: Study protocol for Phase 2 
 
 
All IMCU eligible patients (aged 55 years and older) before discharge 
from JHH with multimorbidity (≥ 2 chronic conditions) 
Consent to study inclusion, 
medical record use  
Exclude: refused consent; 
documented cognitive 
impairment  
Gather data: Demographics- Age, Gender, Ethnicity, Education, Postal code; Clinical profile- Co-
morbidities (CCI), Diagnoses, Healthcare utilization in last 3 months (No. of Emergency visits, Critical 
care admissions, and other Hospitalization); Outcome measures- Symptom burden (ESAS), Quality of life 
(SF-36), Pain (PROMIS-Pain), Fatigue (PROMIS-Fatigue), Social support (ESSI), Self-efficacy, Fear of 
COVID-19 and Resilience (Brief Resilience Scale) 
Participants receive nurse-led symptom management intervention pre-discharge with telephone follow-up  
at 48 hrs, 1 week, 4 weeks and 6 weeks after discharge  
(ESAS at each follow-up) 
At 6 weeks: Repeat ESAS, SF-36, 
PROMIS-Pain, PROMIS-Fatigue, 
ESSI, Resilience, Self-efficacy, Fear 
of COVID-19 and Health-care 
utilization  
At 3 months after completion of intervention: Repeat ESAS, SF-36, PROMIS-Pain, PROMIS-Fatigue, 
ESSI, Resilience, Self-efficacy, Fear of COVID-19, Health-care utilization (No. of Emergency visits, 
Critical care admissions, and other Hospitalization) 
At 6 weeks: Intervention feasibility and acceptability data 
from participants completing intervention, not completing 
intervention and nurse delivering intervention; Survey items 
on satisfaction; % Recruitment; % Retention; No. of patient-
nurse interaction 

 
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Table 2: Phase 2 
Goal 2-4: Develop, pilot test and evaluate the toolkit/intervention 
Stages/Goals 
Goals and Activities 
Goal 2 
Toolkit refinement/Intervention development 
Co-designed strategies/toolkit from phase 1 will be compiled in the user-friendly intervention 
protocol for implementation  
Goal 3 
Intervention pilot test 
Recruitment of 25 participants meeting eligibility criteria 
Baseline survey data collection on the same measures used in Phase 1, Stage 2  
Initiation of co-designed symptom-management intervention pre-discharge with telephone 
follow-up (symptom burden will be assessed at each follow-up) 
Survey data collection, at the end of the intervention (i.e., 6 weeks) and at 3 months after 
completion of the intervention  
Goal 4 
Intervention evaluation  
Participants survey and interview on satisfaction, feasibility, and acceptability of the intervention 
Data analysis  
Dissemination 
Manuscripts and project summary  
Dissemination at professional organization  
R01 Randomized Control Trial planning for scalability of the intervention 
 
Year 2 Goal 2: The user-friendly intervention protocol will be developed by refining the 
symptom management toolkit established in Phase 1. The intervention will be nurse-driven 
person-centered pre-discharge intervention engaging caregivers followed by telephone support, 
which will focus on the management of symptoms such as difficulty breathing, pain, fatigue and 
sleep disturbances among critically ill patients with multimorbidity and as identified from the 
survey on symptom burden.  
 
Year 2 Goal 3: We will pilot test the intervention among 25 participants over 9 month’s local 
rollout period. The symptom management intervention will be delivered by a nurse pre-discharge 
with telephone follow up over a 6 weeks period (at 48 hrs, 1 week, 4 weeks and 6 weeks) after 
the discharge from JHH-IMCU.  
 
Year 2 Goal 4: We will evaluate the effectiveness of the intervention on primary outcomes (i.e., 
symptom burden and QOL) by comparing pre-post intervention data (i.e., baseline, 6 weeks and 
3 months). Additionally, the intervention is anticipated to improve secondary outcomes (i.e., 
pain, fatigue, social support, resilience, and healthcare utilization). To evaluate the acceptability 
and feasibility of the intervention both quantitative (survey items on satisfaction and 
acceptability, no. of nurse-patient contacts, recruitment rate and retention rate) and qualitative 
(unstructured interview with selected participants who attended the intervention and the nurse 
delivering the intervention) data will be examined.  
 
 
 

 
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Statistical Analysis Plan 
 
a. Primary outcome variable. 
 
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Symptom Burden: Edmonton Symptom Assessment System (ESAS) 
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Quality of Life: BRICS NINR Short Form Survey (SF-36) 
 
b. Secondary outcome variables. 
 
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Health-care Utilization: No. of emergency visit, Hospitalizations, Critical care admissions 
 
c. Statistical plan including sample size justification and interim data analysis. 
 
Data collection and analysis are iterative processes throughout Goal 1, Stages 1-6 of the EBCD 
process, and Goal 3 and Goal 4 for intervention evaluation. The majority of data collected in 
phase 1, except the baseline survey, are qualitative and will be analyzed using thematic analysis. 
14,15 The software Atlas ti. will support qualitative analysis.  
 
Quantitative data will be analyzed using descripting statistics followed by inferential statistics. 
As a pilot study, the analyses of Phase 2 data will likely not have adequate power to detect 
significant differences. Therefore, effect sizes, followed by statistical significance will be 
explored for evidence of the effectiveness of the intervention on outcomes. To compare 
quantitative data at different time points, we will use Wilcoxon signed rank test to evaluate 
changes from baseline to 6 weeks and baseline to 3 months post-intervention. Additionally, the 
changes across baseline, 6 weeks, and 3 months post-intervention will be analyzed using the 
Friedman test for repeated measures, with Kendall’s W employed to assess effect size. 
Quantitative analyses will be performed using the Statistical Package for the Social Sciences 
(SPSS) or equivalent software. We will evaluate the acceptability and feasibility of the 
intervention using qualitative analysis of interview data from selected participants who attended 
the intervention, left the intervention if agree to interviewed and the nurse delivering the 
intervention. The quantitative data from satisfaction and feasibility items will be descriptively 
analyzed (mean, range, percentages). Further, evaluation of participants’ recruitment rate, 
retention rate and no. of nurse patient interaction will be performed. 
 
 
 

 
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