The methods for the EMPOWER study were developed in accordance with the SPIRIT guidelines(12).
Any prospective amendments to the protocol, eligibility, or outcomes will first be
approved by the institutional review boards of the study sites.
Develop EMPOWER for surrogate decision-makers of critically ill ICU patients who are
unable to make medical decisions. Key informants, including bereaved informal caregivers
of ICU patients and clinicians, will be asked to evaluate the EMPOWER intervention
manual to increase its potential tolerability, acceptability and efficacy.
Determine the feasibility, tolerability, acceptability, and preliminary effects of
EMPOWER on surrogate mental health. We hypothesize that revised EMPOWER will be feasible,
tolerable, and acceptable. The primary outcome will be symptoms of peritraumatic distress
measured following the intervention compared to enhanced usual care. Additional outcomes
at one-month and three-month follow-up from post-intervention assessment will be compared
to enhanced usual care as well.
Estimate the effects of EMPOWER on patient outcomes in the months following the post-intervention
assessment. Patients who receive EMPOWER are hypothesized to have higher rates of
engagement in advance care planning (e.g., a DNR order completed), better surrogate-reported
quality of life/quality of death, and more value-concordant care (measured by comparing
intensity of care at end-of-life to surrogate perception of patient treatment preferences)
compared to patients whose surrogates receive enhanced usual care.
Trial design:
The EMPOWER study is comprised of two phases conducted simultaneously in preparation
for the subsequent RCT. A timeline of the EMPOWER project is presented in Figure 1.
Phase 1 will first involve both an open trial, enrolling 10 surrogate decision-makers
who will receive the EMPOWER intervention and provide feedback about administration
of EMPOWER. The concurrent manual refinement activities will involve obtaining feedback
on the EMPOWER intervention manual itself from 15 stakeholders (bereaved informal
caregivers and ICU clinicians or mental health clinicians). Feedback from both the
open trial and stakeholder interviews will then be used to refine the EMPOWER intervention.
Phase 2 will involve a multicenter, open label, parallel group, exploratory RCT, which
aims to enroll up to 60 eligible surrogates of 60 incapacitated patients in the ICU.
This sample size ensures stable estimates of treatment effects and confidence intervals,
and, in case the effects of EMPOWER happen to be large, adequate (~80%) statistical
power to detect a minimum treatment effect size (Cohen’s d) of 0.75 (at alpha=0.05). Surrogates will be block-randomized to either the EMPOWER intervention or enhanced
usual care and will complete self-report measures (n = 30 in each group). A usual
care comparator will be enhanced with a packet providing general information and recommendations
on serving as an informal caregiver from the National Alliance for Caregiving (http://www.caregiving.org/pdf/resources/CFC.pdf) as well a handout documenting site-specific resources for caregivers at each hospital.
We will document the availability and use of social support services provided within
each of the three participating ICU sites (please see below) to control for inter-institutional
variability on the provision of supportive services as usual care.
Location and participants:
The study will take place at NewYork-Presbyterian Hospital/Weill Cornell Medical Center,
NewYork-Presbyterian Queens, and Memorial Sloan Kettering Cancer Center in New York
City. Research assistants will screen potential patient and informal caregiver dyads
and consent them as research participants following approval from ICU physicians and
guidance from allied health staff. This study will involve ICU clinicians, patients,
and patients’ surrogates as participants as well as stakeholders. Feedback from patients
and informal caregivers are integrated into several stages of the EMPOWER trial. Bereaved
informal caregivers of ICU patients and ICU clinicians will be consulted to improve
the EMPOWER intervention. Additionally, participants in the open trial will be consulted
through exit interviews to share their suggestions in improving the intervention,
assessments, and recruitment procedures of the trial. All research participants will
be compensated to promote retention and complete follow-up. Participating stakeholders
will receive compensation of a $50 gift card after reviewing the manual and providing
feedback. Participating surrogates in the open trial and RCT will receive $25 follow
the completion of each assessment and exit interview.
Inclusion criteria for open trial and RCT participants:
Patients (>21 years) in the ICU/step-down units who cannot communicate treatment preferences,
as determined by ICU physicians or fellows, and whose ICU physicians or fellows would
not be surprised if the patient did not survive more than 3 months
Informal caregivers of ICU patients whom ICU physicians or fellows indicate as the
decision-making surrogate for the patient, or who is listed as such in the patient’s
medical record
Surrogates must speak English
Surrogates must either meet the threshold for a high degree of dependence on the patient
(determined by the summed score of the overall dependence and emotional dependence
on the patient items of the Partner Dependency Scale(13) as greater than 8) or a high
degree of anxiety (determined by scoring greater than 5 on either anxiety item from
the McGill Quality of Life Scale(14))
Exclusion criteria for open trial and RCT participants:
Patients and surrogates who do not meet the eligibility criteria or surrogates who
endorse suicidal ideation in the past month based on responses to the Columbia Suicide
Severity Rating Scale(15)
Inclusion criteria for stakeholders:
Bereaved family caregivers of patients treated in the ICU identified by referring
clinicians and through support groups, clinics, and word of mouth
Clinicians with expertise in mental health care and/or critical care including but
not limited to nurses, nurse practitioners, social workers, psychologists, hospital
chaplains, psychiatrists and other physicians
Exclusion criteria for stakeholders:
Bereaved informal caregivers or clinicians who do not meet the eligibility criteria
The EMPOWER intervention will be administered by trained mental health professionals
such as psychologists or social workers. The EMPOWER intervention targets symptoms
of peritraumatic stress and anticipatory grief that may interfere with optimal decision-making
on the patient’s behalf or lead to adverse health outcomes such as prolonged grief
disorder or PTSD following the patient’s death or discharge from the ICU. The EMPOWER
intervention seeks to act on these symptoms through the reduction of “experiential
avoidance” (16, 17) and teaching of coping skills, empirically-supported techniques
from cognitive-behavioral therapy(18-20) and acceptance and commitment therapy(21-23)
that can be applied during the ICU stay and in the immediate aftermath of the ICU
stay. It consists of six discrete modules that take approximately 15 to 20 minutes
each to complete (for an approximate total of 1.5 to 2 hours) and can be delivered
flexibly to accommodate the numerous interruptions and unexpected crises typical in
an ICU setting. The EMPOWER modules include empathetic listening and alliance building,
breathing retraining, grounding exercises, guided mindfulness meditation, psychoeducation
about cognitive-behavioral and acceptance-based coping strategies, invoking of the
patient’s voice through an imaginal dialogue, and coping rehearsal to prepare for
potentially distressing scenarios. A brief summary of the structure of the intervention
is presented in Table 1. The six modules can be delivered in the ICU in a single session
or in multiple brief sessions based on the surrogate’s preference. Following the initial
EMPOWER session conducted in the ICU, two booster sessions will be delivered by phone
two weeks and four weeks after the end of the intervention. Booster sessions will
focus on issues relevant to the surrogate, such as bereavement, and reviewing the
skills taught in the original session to coping with new challenges. Each booster
session will last approximately 45 to 60 minutes. Of note, the content and format
of EMPOWER will be further developed through the input of surrogates in the open trial,
bereaved informal caregivers who have had relevant experiences in the ICU, and clinicians
with expertise in mental health and/or critical care.
EMPOWER will be delivered by at least Master’s level mental health clinician interventionist
who will receive intensive training prior to delivering the intervention and regular
supervision after each session. The interventionists will communicate with the medical
team as needed, but will provide a safe space separate from the ICU clinicians without
any agenda about the patient’s care. While a multidisciplinary approach in the ICU
is invaluable, anecdotal evidence suggests that interpersonal dynamics between the
surrogates and medical team sometimes complicate surrogates’ ability to independently
consider their and the patient’s wishes (e.g., surrogates have reported feeling pressured
by hospital staff to sign a DNR order while the patient is in the ICU and they feel
conflicted and/or defensive about this request). Sessions will be audio- recorded
(or video recorded if the surrogate provides permission) so that treatment fidelity
can be regularly monitored and independently rated by trained research assistants. We will monitor progress
of all participants and request their continued participation in the EMPOWER intervention.
If a participant has not completed a part of the intervention, we will contact that
participant to remind and encourage them to continue up to three times, with an upper
limit of contact in place to prevent bothering participants.
Enhanced usual care will consist of the various interactions a surrogate may have
with clinicians in the ICU, which may include social work and chaplaincy staff who
serve as providers of psychosocial support. Additionally, a packet providing information
about informal caregiving and resources will be provided to surrogates in the control
group by research staff. Lastly, a referral list of site-specific resources such as
caregiver support groups and hotlines will be provided. Use of the various components
of enhanced usual care will be monitored and extensively tracked through review of
notes in the patient’s medical record and surrogate self-report. Enhanced usual care
was chosen as the comparator in this study in order to determine whether the EMPOWER
intervention serves as an effective support for surrogates above and beyond standard
practice. Having three sites, each with unique practices for supporting informal caregivers
and surrogates, will allow the intervention to be compared to multiple smaller subsets
of standard treatment, and at the same time reflect general psychosocial informal
caregiver support as well.
Surrogate decision-makers will be permitted to continue to see any outside mental
health professionals during the trial. Mental health treatment they receive from outside
professionals, as reported to study clinicians by the subjects, will be documented
and controlled for during data analysis.
Assignment of Interventions:
Participants in the open trial will all be assigned to the EMPOWER intervention. Participants
in the RCT will be randomized to either EMPOWER or the control group with a block
randomization procedure in REDCap(24) using computer-generated random numbers generated
in R Studio(25). Research assistants will randomize a participant using REDCap following
the participant’s completion of the consent, eligibility screener, and baseline assessment.
Because a co-principal investigator will be conducting supervision for the interventionists,
and because different assessments will be administered depending on the intervention
assignment, the only person completely blinded to group assignment will be the data
analyst/statistician.
The first goal of this study is to determine the feasibility and acceptability of
the EMPOWER intervention. These outcomes will be measured quantitatively within the
week following the intervention (T2) through a post-intervention questionnaire and
at one-month (T3) and a three–month (T4) follow-up from post-intervention assessment
(including a qualitative exit interview at T4 of study participants who were assigned
to the EMPOWER intervention arm). More specifically, these assessments will measure
participant-perceived helpfulness/satisfaction to determine acceptability. Tolerability
will be measured in these assessments through participant reports of negative experiences,
emotional difficulties, and perceived costs and benefits of participating in the intervention.
Targets will include completion of 4/6 modules for feasibility and for acceptability
an average response score of at least 4 to items 1, 3, and 7 of the post-intervention
satisfaction questionnaire among at least 60% of intervention recipients. Rates of
recruitment, reasons for refusal, number of modules/booster calls completed, and study
attrition will also be examined. Drop-out post-intervention will not be considered
as a metric of tolerability due to the highly stressful and variable circumstances
(e.g., bereavement) of ICU caregiving, unless participants drop out of the study and
specifically express that they consider it to be too distressing.
The EMPOWER study also aims to improve surrogates’ symptoms of psychological distress.
This will be measured by comparing the EMPOWER group to the enhanced usual care group
at multiple time points. The primary outcome will be in peritraumatic distress at
post-intervention assessment (T2), administered within a week of the intervention.
Secondary outcomes will be differences in symptoms of PTSD, prolonged grief disorder,
and experiential avoidance, and exploratory outcomes will be anxiety, depression,
and decisional regret at one-month and three-month follow up from post-intervention
assessment (T3 and T4). </p>
Additionally, the EMPOWER study aims to improve patient outcomes through promoting
value-concordant care, quality of life, and quality of death. Rates of value-concordant
care will be measured through comparing surrogate perceptions of patient treatment
preferences assessed at baseline (e.g., a preference to prioritize care focused on
quality of life over quantity of life) with the intensity of care provided in the
indexed ICU stay (e.g., indication of cardiopulmonary resuscitation, dialysis, mechanical
ventilation, chemotherapy, or parenteral nutrition, and palliative care in the medical
record). We will compare surrogate-assessed patient quality of death (for patients
who died) using the CEQUEL (26) between groups, measured at either T3 or T4, depending
on which time point first follows the patient’s death. Surrogate-assessed patient
quality of life will be assessed as relevant to the most recent week (or week alive)
through Likert-type items previously published (27), as well as through a revised
version of the CEQUEL, and will be measured at one-month follow up (T3), three-month
follow up (T4), both, or neither, depending on patient status.
Surrogate decision-makers will be asked in a baseline assessment occurring either
in clinic or over the telephone their own and the patient’s age (years), gender, race,
education, mental health history, income, marital status, religious/spiritual beliefs,
advance care planning knowledge/understanding, treatment preferences, prognostic understanding,
and relationship with patient. Stakeholders will report on their own demographics.
Medical factors for patients:
We will abstract the medical chart to record patients’ primary hospital and ICU admitting
diagnoses (e.g., Stage IV pancreatic or NSCL cancer), do not resuscitate/do not intubate
order status, advance care planning items (e.g., Living Will, Health Care Proxy, Health
Care Power of Attorney), palliative care consultations, care plans obtained from the
medical chart or ICU physicians and fellows. This information will be compiled as
a medical chart abstraction and matched with surrogate-assessed patient treatment
preferences assessed at baseline to create a measure of rates of value-concordant
care. These medical factors, in addition to the CEQUEL(26), will serve to measure
the outcomes specified in Objective #3.
Psychosocial factors for surrogate decision-makers:
A description of each quantitative measure used at each assessment is provided in
Table 2, and a timeline of assessments is provided in Figure 2.
Screener: Consists of items from 4 items from McGill Quality of Life(14), two items from the
Partner Dependency Scale(13), and three items from the Columbia Suicide Severity Rating
Scale(15). We will also obtain the surrogate’s physician/healthcare provider information
at baseline should a medical or mental health emergency arise.
Pre-intervention/Baseline Assessment (T1): Psychiatric History, Demographics, and Treatment Preferences; Prolonged Grief Disorder
(PG-12) Caregiver Version(28-30); Fears of Losing Loved Ones Scale (FOLLOS); Peritraumatic
Distress Inventory (PDI)(31); Peritraumatic Dissociative Experiences Questionnaire
(PDEQ)(32); Impact of Events Scale-Revised (IES-R)(33); Brief Experiential Avoidance
Questionnaire (BEAQ)(34); State Trait Anxiety Questionnaire- Trait Scale (STAI-Y Trait)(35);
Patient Health Questionnaire (PHQ-9)(36); Distress Tolerance Scale (DTS)(37) revised
version; Caregiver Self-Efficacy in the ICU Scale; Decision Regret Scale (DRS) - EMPOWER(38).
Post-intervention Assessment (T2) Administered Within One Week of Intervention: PG-12 (if patient is alive); FOLLOS (if patient is alive); PG-13 (if patient is deceased)(28-30);
PDI; PDEQ; IES-R; BEAQ; STAI-Y Trait; DTS revised version; Caregiver Self-Efficacy
in the ICU Scale; DRS - EMPOWER; Post-Intervention Satisfaction Questionnaire (PISQ).
1 Month Follow-up from Post-intervention Assessment (T3): PG-12 (if patient is alive); FOLLOS (if patient is alive); PG-13 (if patient is deceased);
PDI; IES-R; BEAQ; STAI-Y Trait; DTS revised version; Critical Care Family Satisfaction
Survey- EMPOWER; CEQUEL-R (if patient is alive)(26); CEQUEL(26) (if patient is deceased);
Quality of Life (if patient is alive)(39); Quality of Death (if patient is deceased)(39);
DRS - EMPOWER; Medical Information Update
3 Month Follow-up from Post-intervention Assessment (T4): PG-12 (if patient is alive); FOLLOS (if patient is alive); PG-13 (if patient is deceased);
PDI; IES-R; BEAQ; STAI-Y Trait; PHQ-9; DTS revised version; Critical Care Family Satisfaction
Survey- EMPOWER; CEQUEL-R (if patient is alive); CEQUEL (if patient is now deceased,
but was alive at T3); Quality of Life (if patient is alive); Quality of Death (if
patient is deceased); DRS - EMPOWER; Medical Information Update; Qualitative Exit
Interview (for patients receiving the EMPOWER intervention only).
Surrogates will provide feedback on the intervention in a post-intervention satisfaction
questionnaire at T2 and a one-on-one semi-structured exit interview at T4 conducted
over the phone or in person solely for participants assigned to the experimental arm.
Stakeholders will provide feedback on the intervention manual in self-report questionnaires,
written form, and/or in-person interviews.
If participants drop out of the study, the investigative team will attempt to ask
them for their reasons for ceasing to participate, but no further data will be collected.
Data analysis plan
Below are descriptions of the statistical procedures performed to test each of the
hypotheses. Participant data will be stored in a locked file cabinet and using a secured
REDCap database. Missing data will be estimated using a multiple imputation procedure
described by Schafer and Olsen(40). There will not be a data monitoring committee
due to the trial’s relatively short duration and the minimal risks the intervention
poses. Trial data will not be independently audited. An interim analysis of the pilot
data will occur to inform the conduct of the RCT and edits to the EMPOWER manual.
Objective #1: Refine EMPOWER for surrogate decision-makers of critically ill patients who are unable
to communicate in the ICU.
We will use thematic content analysis, a well-established, systematic qualitative
analysis approach in health research, to identify themes from stakeholder participants’
narratives and exit interviews. We will follow Morse’s(41) guidelines for conducting
rigorous qualitative research (e.g., audit trail, saturation) using Atlas.ti software.
We will independently review each interview transcript as well as qualitative data
gathered from manual edits and Delphi survey responses and will synthesize and interpret
participants’ feedback about the content of the EMPOWER manual.
Objective #2: Determine the feasibility, acceptability, tolerability, and preliminary effects of
EMPOWER on surrogate mental health.
We will compute descriptive statistics to characterize the feasibility and acceptability
of EMPOWER by examining helpfulness/satisfaction ratings, rates of recruitment, reasons
for refusal, and number of modules/booster calls completed. These will be used to
determine whether the EMPOWER intervention meets the targets detailed in the above
outcomes. Qualitative data analysis will be used to analyze data from open-ended questions
to identify the most helpful components of EMPOWER.
To evaluate the preliminary effects of EMPOWER on peritraumatic stress at post-intervention
assessment (T2) in the RCT, we will use a hierarchical linear modeling (HLM) and an
intent-to-treat approach. HLM is statistically appropriate because it corrects for
clustering within interventionists and within surrogates by modeling them as random
effects. This will also provide a treatment assignment model coefficient and effect
size estimate for our future, larger study.
HLM modeling will determine differences between surrogates and patients assigned to
EMPOWER vs. enhanced usual care to examine the primary, secondary, and exploratory
outcomes described above. HLM models will include covariates, either as fixed-effect
or time-varying (e.g., patient death), if those variables are found to be significantly
statistically associated with both intervention assignment and the outcome examined.
Objective #3: Examine the effects of EMPOWER on patient outcomes in the month following the ICU
admission.
Logistic regression models will regress patient quality of life or quality of death
(depending on whether the patient survives or dies in the observation period) for
EMPOWER versus enhanced usual care condition. Logistic regression analyses will model
the effects of EMPOWER on the odds of patients receipt of value-concordant care (i.e.,
surrogate baseline assessment of patient preferences regarding quality of life versus
quantity of life matched with receipt of intensive life-prolonging procedures/palliative
care). Potential differences in assessment timing between groups will be adjusted
for.
Adverse reactions and events
We anticipate that there may be questions in the interview that some study participants
find upsetting. However, since study items and topics were chosen to reflect what
are likely to be existing concerns, the present study is not expected to markedly
increase participants’ psychological distress above their routine concerns. Topics
covered during the intervention sessions may be emotional, but related distress is
expected to be transient and will be supported by a mental health clinician. In addition,
experienced personnel trained in interviewing medically ill individuals and their
families will administer all instruments and will be supervised by the study principal
investigators (PIs). If a participant assigned to the EMPOWER intervention wishes
to stop participating in the intervention for any reason, we will request that they
inform the researchers, and, if willing and able, inform the research team of the
reason for ceasing participation. If a participant appears to be at risk for harming him/herself or others during the
course of the trial, the researchers will take immediate action to address this risk and the participant
would become ineligible for continuing with the study.
Potential adverse events for this project are expected to be all non-physical in nature.
The principal investigators will report unanticipated and serious adverse events to
the IRB in a timely manner on an ongoing basis. For the purpose of this study, a serious
adverse event is defined as an event that, as a direct result of the study, causes
serious harm to the participant (e.g., that involvement in the study caused the death
or serious injury to the participant). Adverse events are also reported as part of
the progress reports in the non-competitive and competitive renewals for the National
Institutes of Health. If at any point during the study period, the study intervention
is found to be associated with an undue risk for harm to subjects, the trial will
be stopped, such as if the research team determines, in good faith, that the intervention
appears to causing significant emotional distress or impairment for subjects beyond
what would be expectable, or leading to increased risk for harm to self or others.
All study staff involved in the research are educated on the protection of human research
participants and the proposed research will comply with the regulations set forth
in 45 CFR Part 46, Protection of Human Subjects. All personnel involved in the proposed
protocol have been educated regarding HIPAA regulations and fully understand their
responsibility to safeguard the personal health information of every participant involved
in the research. Any participant participating in the study may decline to continue
participation and may withdraw from the study at any time. Any participant who expresses
a desire for more intensive psychosocial support for issues such as PTSD or bereavement
following the intervention will receive a customized set of referrals from the study
team.
We will collect participants’ medical and mental health history, details about outside
clinicians, and emergency contact information. Participants will be screened for suicidality
with the Columbia Suicide Severity Rating Scale and in accord of our screening and
management guidelines (15). If research staff identify signs indicating a significant
and acute risk of harm to self or others, such information will immediately be shared
with the PIs of the study, so that a plan can be enacted for timely and appropriate
assessment and care, provided by a licensed/ board-certified mental health provider
or local clinicians (e.g., emergency rooms near the study participant).
Participant confidentiality will only be broken if information gathered during the
course of the study indicates that the participant poses a significant and acute risk
of harm to self or others. Prior to inclusion in the study, participants will be informed
of this exception. If a participant deemed to be at acute risk of self-harm or harm
to others cannot be reached by the study team within three hours (after at least two
telephone call attempts and an email requesting a call back), the participant’s emergency
contact(s) will be contacted. If an acutely distressed individual who has denied active
suicidality or homicidality, but for whom the study team has significant concern,
cannot be reached within 24 hours (after at least two phone call attempts and an email
requesting a call back), the participant’s emergency contact(s) will be contacted.
These details are outlined in the informed consent for study participation.