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J Pain Symptom Manage. Author manuscript; available in PMC 2017 September 01. Published in final edited form as: J Pain Symptom Manage. 2016 September ; 52(3): 378–385. doi:10.1016/j.jpainsymman.2016.03.014.
Family Caregiver Depressive Symptom and Grief Outcomes from the ENABLE III Randomized Controlled Trial
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J. Nicholas Dionne-Odom, PhD, RN, Andres Azuero, PhD, Kathleen D. Lyons, ScD, Jay G. Hull, PhD, Anna T. Prescott, Tor Tosteson, ScD, Jennifer Frost, MA, RN, Konstantin H. Dragnev, MD, and Marie A Bakitas, DNSc School of Nursing (J.N.D.-O., A.A., M.A.B.), and Division of Gerontology, Geriatrics, and Palliative Care (M.A.B.), Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama; Department of Psychiatry (K.D.L.), Geisel School of Medicine at Dartmouth, Hanover, New Hampshire; Department of Psychological and Brain Sciences (J.G.H., A.T. P.), Dartmouth College, Hanover, New Hampshire; Biostatistics Shared Resource (T.T.), Norris Cotton Cancer Center, Lebanon, New Hampshire; and Department of Medicine, Hematology/Oncology (J.F., K.H.D.), Geisel School of Medicine at Dartmouth and Norris Cotton Cancer Center, Lebanon, New Hampshire, USA
Abstract Context—Little is known about whether early palliative care (EPC) support for family caregivers (CGs) impacts depressive symptoms and grief after care recipients die.
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Objectives—To assess after-death CG depressive symptom and grief scores for early compared to delayed group CGs. Methods—We conducted a randomized controlled trial (RCT) (10/2010-9/2013) of an EPC telehealth intervention for CGs (n=123) initiated at the time of care recipients' advanced cancer diagnosis (early group) or 12 weeks later (delayed group) in a rural comprehensive cancer center, affiliated clinics, and a Veterans Administration medical center. The ENABLE [Educate, Nurture, Advise, Before Life Ends] CG intervention consisted of three weekly sessions, monthly follow-up, and a bereavement call. CGs completed the Center for Epidemiological Study-Depression scale (CESD) and the Prigerson Inventory of Complicated Grief-Short Form (PG13) 8-12 weeks after care recipients' deaths. Crude and covariate-adjusted between-group differences were estimated and tested using general linear models.
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Results—For care recipients who died (n=70), 44 CGs (early: n=19; delayed: n=25) completed after-death questionnaires. Mean depressive symptom scores (CESD) for the early group was 14.6 (standard deviation [SD]=10.7) and for the delayed group was 17.6 (SD=11.8). Mean complicated grief scores (PG13) for the early group was 22.7 (SD=4.9) and for the delayed group was 24.9 Address correspondence to: Marie Bakitas, DNSc, CRNP, School of Nursing, University of Alabama at Birmingham, 1720 2nd Ave South, 2M024, Birmingham, AL 35294-1210, USA, [email protected]. Disclosures: All authors declare no conflicts of interest. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
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(SD=6.9). Adjusted between-group differences were not statistically significant (CESD: d=0.07, P=0.88; PG13: d=-0.21, P=0.51). Conclusion—CGs' depressive symptom and complicated grief scores 8-12 weeks after care recipients' deaths were not statistically different based on the timing of EPC support. The impact of timing of CG EPC interventions on CGs bereavement outcomes requires further investigation. Keywords Family caregiving; palliative care; advanced cancer; telehealth
Introduction Author Manuscript
A family caregiver is an unpaid individual (a spouse, partner, family member, friend, or neighbor) involved in assisting others with activities of daily living and/or medical tasks.1 An estimated 20 to 50% of family caregivers experience negative psychological aftereffects, including depression and grief, from months to years after a care recipient's death from cancer.2-4 In one respect, bereaved caregivers are often relieved of burdensome tasks, such as assisting care recipients with activities of daily living and care coordination,5 that can consume over eight hours a day.6 However, they are also susceptible to a range of potentially long-lasting, negative emotions, including profound loss and emptiness at the absence of a loved one;7 regret about unresolved issues or unsaid goodbyes;8 anger or shock at the manner in which a person died (e.g., extreme pain, gasping for breath);9 guilt about whether decisions they may have made as a surrogate decision-maker were the “right” ones (e.g., withdrawal of life-sustaining treatments);10 and distress at acclimating to a new lifestyle and daily routine.11
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Emerging evidence suggests that specialty palliative and hospice care positively impacts family caregivers after their care recipients die. In a South Australian population-based survey of 9088 caregivers, Abernethy and colleagues12 found that when care recipients received palliative care prior to death, decedent caregivers were significantly more likely to be able to move on with their lives. Similarly, a study by Ornstein and colleagues2 of 1016 family caregivers of hospice patients found significantly lower caregiver depressive symptoms at 1 year post-loss compared to caregivers of non-hospice care recipients. Palliative care, especially as delivered by hospice,13 provides specific support to caregivers prior to a care recipient's death and during bereavement period. Though hospice regulations allow for services to be offered for up to 6 months prior to death; on average hospice care is initiated only 23 days before death.14
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Very little is known, about whether offering specialty palliative care to family caregivers soon after an advanced cancer diagnosis may impact caregiver bereavement outcomes. To test if initiating early vs. delayed palliative care support to family caregivers impacts depressive symptoms and grief, we conducted a “fast track”15 phase III randomized controlled trial (RCT) of a telehealth intervention called ENABLE III (Educate, Nurture, Advise, Before Life Ends). ENABLE III consists of a face-to-face palliative care consultation for patients (caregivers may attend) and manualized coaching sessions and monthly follow-up. Family caregivers of participants with newly diagnosed advanced or
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recurrent cancer received the intervention either early (within 60 days) of diagnosis or 12 weeks later (delayed group). For patients who died during the study, we hypothesized that bereaved caregiver depressive symptom and grief scores would be lower for early compared to delayed group caregivers.
Methods Study Design
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The ENABLE III study design, methods and patient and caregiver outcomes have been described elsewhere.16,17 Briefly, from October 11, 2010 to March 5, 2013, patients within 60 days of being newly diagnosed with advanced, recurrent, or progressive cancer with an oncologist-determined prognosis of six to 24 months and their family caregivers signed informed consent and were randomly assigned to receive the ENABLE III intervention either within 60 days of diagnosis (early group) or 12 weeks later (delayed group). Random one-to-one group assignment was computer-generated, stratified by six cancer types and four recruitment sites. Caregivers were assigned to the same group as the patient. The study was approved by the institutional review boards of Dartmouth College and the White River Junction Veterans Affairs Medical Center (VAMC). Setting and Sample
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Patient and caregiver participants were recruited from the Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center (DHMC) in Lebanon, New Hampshire, affiliated DHMC outreach clinics, and the VAMC (White River Junction, VT). Patients were identified by research coordinators who reviewed weekly outpatient clinic schedules and tumor board lists. Patient inclusion criteria were: 1) English-speaking; 2) ≥18 years of age; 3) advanced-stage solid tumor or hematologic malignancy (detailed diagnostic criteria included in supplement of patient outcomes paper);18 and 4) completion of baseline questionnaires. Patient exclusion criteria included: 1) impaired cognition (Callahan score≤4);19 2) active Axis I psychiatric (schizophrenia, bipolar disorder) or substance use disorder; 3) uncorrectable hearing loss; and 4) unreliable telephone service. Potential family caregiver participants were identified by asking patient participants to nominate a family member or friend “who knows you well and is involved in your medical care” to consider participation. There were no caregiver exclusion criteria and patient participants were not excluded if they did not have a participating caregiver. The ENABLE III Caregiver Intervention
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The ENABLE III patient18,20,21 and caregiver17,22 interventions have been described in detail elsewhere. Briefly, the ENABLE III caregiver intervention was a manualized intervention facilitated by advanced practice palliative care nurse coaches over the phone. Given the largely rural, mountainous Vermont and New Hampshire geography23 and long travel distances to DHMC, ENABLE pilot work20 demonstrated feasibility and patient preference for a telephone versus in-person approach. Moreover, numerous studies have reported successes of telehealth approaches, including a recent review of telehealth interventions reporting that phone-delivered psychoeducational support had comparable outcomes to in-person care, was cost effective, and improved access for rural populations.24
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After completing baseline questionnaires, caregivers were assigned a nurse coach (who was different than the patient nurse coach) and were mailed Charting Your Course-Caregiver (CYC-CG), an investigator-developed guidebook (manual available from authors) that contained resource material supporting the nurse coaching sessions. Caregivers participated in three weekly telephone coaching sessions using CYC-CG. Session 1 focused on “being a caregiver;” the goals of palliative care; an overview of the COPE (Creativity, Optimism, Planning, Expert guidance) attitude;25 and a step-wise framework for engaging in problemsolving coping (derived from the conceptual foundations of problem-solving treatment).25-27 Session 2 centered on caregiver self-care, addressing topics such as healthy eating and exercise, meditation, spirituality and partnering in a patient's symptom management. Session 3 reviewed communication, decision-making including decision aid tools (e.g., Ottawa Personal Decision Guide), and advance care planning. Caregiver participants then received monthly check-in calls to reinforce prior content and assist with new issues that arose. Follow up calls continued until study completion or care recipients death. Caregivers of care recipients who died, received a bereavement call from nurse coaches approximately 2-4 weeks after the date of death to offer condolences, inquire how they were doing, and ask permission for a data collector to contact them to administer a final survey. To enhance intervention fidelity, nurse coaches followed a script for all CYC-CG sessions, monthly check-in calls, and for the bereavement call.
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Seven advanced practice palliative care nurse coaches received approximately 30 hours of training that included self-study of all intervention protocols and scripts; one-on-one didactic education on problem-solving support and decision-aids; review of 12 recorded CYC practice sessions and role playing each session. The PI (MB) provided one-on-one constructive feedback during training. After training, the principal investigator (PI), blinded to group assignment, listened to all caregiver sessions and met weekly with the nurse coaches to discuss any protocol deviations or other issues. Measures Data collectors, blinded to group assignment, collected patient and caregiver measures by telephone at baseline, 6, 12, 18, and 24 weeks. After week 24, data collection was every 12 weeks until patients died or the study ended. Baseline family caregiver demographics included age, gender, race, ethnicity, religion, marital status, employment, education, and their relationship to the care recipient. Details of all other patient and caregiver measures are described elsewhere.17 Eight to 12 weeks after-death, participating caregivers of decedents were asked to complete a measure of depressive symptoms and grief.
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Depressive symptoms were measured using the Centers for Epidemiological StudiesDepression (CES-D) scale.28 This 20-item measure has demonstrated very good internal consistency reliability (Cronbach's alpha=0.85) and includes questions about how often one has had symptoms related to depression over the past week, such as appetite loss, feeling blue, restless sleep, loneliness, and crying spells. Response options range from 0 to 3 (0=rarely or none of the time [16 suggestive of clinical depression.29 Grief was measured using the Prigerson Inventory of Complicated Grief-Short Form (PG13).30 This 13-item short form measure has demonstrated very good internal consistency reliability (Cronbach's alpha=0.94) and includes questions to assess pathological grief over the past month, including yearning for the deceased, acceptance of the deceased death, and feelings of meaninglessness and being able to move on. Responses range from 1 (“never”) to 5 (“always”). Higher scores indicate higher grief and scores >25 indicate clinically significant complicated grief. Statistical Analysis
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Caregiver characteristics (study group, age, gender, race, marital status, education, religious preference, employment status, relationship to patient, patients' primary cancer site, patients' use of hospice prior to death, and baseline CES-D score) were tabulated by completion of after-death questionnaire status (and by study group) and then compared using effect sizes and significance tests. The objective of the analysis was to estimate the baseline to afterdeath between-group difference (early minus delayed) in CES-D score and the betweengroup difference in PG13 score. Within-person change in CES-D scores were computed and the between-group mean difference was estimated. The between-group difference in PG13 score was also estimated. These mean differences were compared using effect sizes (Cohen's d) and t-tests. Because the study groups differed on religious preference and patient use of hospice, between-group mean differences in outcomes, adjusted for the probability of group assignment given religious preference and for patient hospice use, were also estimated using general linear models (one covariate at a time because of the small sample size). The probability of group assignment given religious preference was estimated using a logistic regression model fitted with Firth's penalized likelihood method.31 The between group difference in PG13 score was also estimated after adjusting for baseline CES-D score. Because of the small sample size, we interpreted our results using both observed effect sizes and significance tests. Analyses were conducted in SAS software v. 9.4 (SAS Institute Inc., Cary, NC).
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Results Sample Characteristics
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As shown in Fig. 1, 207 patients were randomized into early and delayed intervention groups. One hundred twenty-four nominated a family caregiver to participate and 122 enrolled and provided data. A total of 70 patient participants with enrolled family caregivers died during the study (early: n=31; delayed: n=39) and 44 caregivers (early: n=19; delayed: n=25) completed after-death questionnaires. Approximately 37% (n=26) of decedents' caregivers did not complete after-death questionnaires. Religious preference and baseline CESD were associated with completion of the questionnaires. Protestants were more likely to complete (22/26, 84.6%), while Catholics were less likely to complete (8/20, 40%; Cramer's V= 0.38, P=0.02). Those who completed the questionnaires had, on average, lower
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values (fewer depressive symptoms) of baseline CESD (M(SD)=15 (9.3)) compared to those who did not complete (M(SD)=19.4 (12.5); d=0.40, P=0.18). There were no statistically significant differences between decedents' caregiver demographic characteristics by group (Table 1). On average, caregivers were age 62 years, female (84.1%; n=37), white (93.2%; n=41), and married or living with a partner (93.2%; n=41). Forty-three percent (n=19) had completed high school or some college or technical school and 56.8% (n=25) had a college or advanced degree. Approximately 68% (n=30) reported a Christian denomination (Protestant or Catholic), and 18.2% (n=8) reported no religious affiliation. Over half (n=25) were employed full- or part-time and approximately 43% (n=19) were retired or unemployed. Most caregivers (81.8%; n=36) were decedents' spouses or partners. Most cared for patients with lung (45.5%; n=20) and gastrointestinal cancers (31.8%; n=14) and a substantial proportion of patients used hospice prior to death (59.1%, n=26).
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Depressive Symptoms and Complicated Grief Table 2 shows the CESD between-group comparisons at baseline, after patient death, and the change from baseline to after-death. Adjusted between-group differences were not statistically significant (P=0.81). The CESD change from baseline for the early group was +3.4 (SD=9.5) and for the delayed group was +2.6 (SD=12.1). The between-group difference in CESD change was of trivial magnitude (d=0.08) even after adjusting for religious preference (d=0.10) or patient hospice use (d=0.07).
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Table 3 shows the PG13 between-group grief comparison scores. Again, the adjusted between-group differences were not statistically significant (P=0.51). The unadjusted effect size was moderate (early minus delayed, d=-0.35); however, the effect size decreased to d=-0.27 after adjusting for religious preference. Further adjustment for baseline CESD scores and patient hospice use resulted in a decrease of the effect size difference to d=-0.20 and d=-0.21, respectively (early minus delayed).
Discussion
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This trial represents the first attempt to test the effect of early palliative care telehealth support on bereaved family caregivers. We conducted an early versus delayed “fast track” RCT to determine if family caregivers who received the ENABLE III early palliative care telehealth intervention, within 60 days of their care recipients' advanced cancer diagnosis had lower depressive symptom scores and lower grief scores after care recipients' deaths than caregivers who received the intervention 12 weeks later. Our analysis detected no statistical differences on caregivers' after-death depression and grief scores relative to initiation of the intervention. In our prior report of this trial,17 a terminal decline analysis of CG outcomes looking backwards in time 36 weeks from care recipient death showed significantly lower depressive symptom scores in early compared to delayed group caregivers. Given that pre-loss caregiver distress has been associated with post-loss outcomes,3,8,32,33 we were surprised to find that the depressive symptom benefits for early group caregivers did not extend into the period after their care recipients' deaths. Because not all decedent caregivers completed
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after-death questionnaires, the sample of decedent caregivers was much smaller in this analysis compared to that in the terminal decline analysis, which greatly limited statistical power to detect differences between groups. Despite this limitation, it is worth highlighting that there was an observed small effect size difference in grief scores favoring the early group (early minus delayed; PG13: d=-0.20). We believe this signal of potential efficacy is sufficient to warrant future examination of the impact of early palliative care for caregivers on their after-death outcomes.
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There are several explanations for the lack of robust positive results. First, the ENABLE III caregiver intervention did not specifically address death preparedness and coping with the death of a loved one.34 Because ENABLE is an early palliative care intervention, topics were chosen that were most appropriate for the caregiving context while care recipients were still relatively high functioning and with potentially several years to live. Topics such as what to expect and how to care for the actively dying patient, withholding/withdrawing lifesustaining treatment, and funeral care were not discussed by nurse coaches unless the topics were broached by participants themselves. Discussing such topics before death may facilitate better bereavement adjustment.34 Hence, future early palliative care for family caregivers might consider exploring non-threatening ways to integrate end-of-life preparedness topics.
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Second, depressed mood and grief scores were collected 8 to 12 weeks after the death of the care recipient. This timeframe falls within the period when normal grief is expected, which is typically up to 1 year.7 Evidence suggests that significant differences between normal and prolonged grief are not evident until one to two years after an individual's death.2,12 For example, Ornstein et al. found that differences in spousal depression in those whose care recipients did and did not use hospice were most pronounced at one year following death. Hence, future studies of early palliative care for caregivers may need to protract the timeline of data collection for up to 2 years after a care recipient's death in order to capture meaningful differences. Though it will be important to control for CGs' use of bereavement services which are covered under Medicare's hospice benefit.13
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A number of factors have been associated with lower caregiver depression and grief scores that may be impacted by future models of caregiver early palliative care support. Examples include use of hospice,2,12,35 avoidance of high intensity end-of-life care,36,37 care recipient's quality of death and dying,36 and the leveraging of social support networks.3,38 These factors represent prospective mediators of early palliative care support for caregivers that impact after-death outcomes. In combination with evidence showing caregiver underutilization of post-loss bereavement services,39 a potential solution is to educate and encourage caregivers early on in the patient's disease trajectory to leverage these resources if needed in the future. Early palliative care supports family caregivers when they are less entrenched in day-to-day tasks because their care recipients are less ill and have fewer care needs. Hence, caregivers may be more capable during this period of relatively lower stress to obtain knowledge and skills that they will need in the future.
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Limitations
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Our study has important limitations. First, our trial did not have a usual care comparison group. Both caregiver groups received palliative care much earlier than would be provided through hospice. Therefore, we are unable to determine what after-death differences there might have been between caregivers receiving ENABLE versus those who did not. Second, because we did not collect data on caregivers' use of supportive services such as hospice bereavement programs and counseling, we are not able to account for the potentially mediating impact that use of these services may have had on caregiver after-death outcomes. Third, because data for this analysis could only be collected from caregivers of decedents, the sample size for this analysis was small, thus limiting statistical power and increasing the chances of failing to detect a true relevant effect (Type II error). Fourth, this analysis tested the “timing” of palliative care and did not account for the amount or “dosing” of palliative care one receives before death (e.g., as measured by the number of hours of one-on-one contact). It seems reasonable to hypothesize that the “dose” of palliative care support that caregivers receive pre-loss may predict post-loss depression and grief. However, it remains an unanswered and important research question about whether there are differences between “timing” and “dosing” of specialty palliative care. Finally, the caregiver sample was nearly all white, which is unsurprising given the population demographics of rural New England. Future work in this area would be strengthened by inclusion of racial and ethnic minorities, especially given evidence suggesting non-white caregivers may have higher rates of grief disorders.40
Conclusion Author Manuscript
Our study did not find statistical differences in depression and grief scores of family caregivers of decedents who received early versus delayed palliative care. However, our small sample size may have limited our ability to detect the impact of ENABLE on caregiver bereavement outcomes. Furthermore, after-death measures were collected within the time frame when normal grief is difficult to distinguish from complicated grief. Given that the observed effect size difference in grief scores favored early group caregivers, the possibility should not be ruled out that early palliative care may positively impact caregivers after patients die. Therefore the impact of early palliative care support for caregivers on bereavement outcomes is still an open and high priority research question.
Acknowledgments
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The parent study was supported by the National Institute for Nursing Research (R01NR011871-01), a Cancer and Leukemia Group B Foundation Clinical Scholar Award, the Foundation for Informed Medical Decision-Making, the Norris Cotton Cancer Center pilot funding, and the Dartmouth-Hitchcock, Section of Palliative Medicine. Dr. Dionne-Odom is a postdoctoral fellow supported by the University of Alabama at Birmingham Cancer Prevention and Control Training Program (5R25CA047888), by a National Palliative Care Research Center Career Development Award, and by the MSM/TU/UAB Comprehensive Cancer Center Partnership (U54CA118948). Dr. Lyons is supported by a Mentored Research Scholar Grant in Applied and Clinical Research (MRSG 12-113-01– CPPB) from the American Cancer Society. Dr. is a recipient of a National Palliative Care Research Center Junior Career Development Award.
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Fig. 1.
CONSORT Diagram of Family Caregiver Enrollment.
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Author Manuscript 10.1
0 2 1
Black
Other
Missing
41 0 1
Married or living with partner
Divorced or separated
Widowed
25
College graduate or above
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Catholic
None
Other
Missing
Employment Status
22
Protestant
Religion
19
High school or GED, some college or technical school
Education
2
Never married
Marital Status
41
White
Race
Female gender
61.6
SD 37
No.
Mean
Age, years
Characteristic
2.3
11.4
18.2
18.2
50.0
56.8
43.2
2.3
0
93.2
4.5
2.3
4.6
0
93.2
84.1
%
All Caregivers (N=44)
0
2
5
1
11
10
9
0
0
18
1
0
1
0
18
15
No.
11.9
62.1
0
10.5
26.3
5.3
57.9
52.6
47.4
0
0
95.0
5.3
0
5.3
0
95.0
78.9
%
Early Group (N=19)
1
3
3
7
11
15
10
1
0
23
1
1
1
0
23
22
No.
8.6
61.2
4.0
12.0
12.0
28.0
44.0
60.0
40.0
4.0
0
92.0
4.0
4.0
4.0
0
92.0
88.0
%
Delayed Group (N=25)
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.20
.63
.67
.87
.42
.77
P*
.33
.07
.14
.03
.12
.09
Effect size**
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Family Caregiver Characteristics of Decedent Care Recipients
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14 5
Retired Not Employed
7 1
Other immediate relative (i.e., parent, child) Other relative or friend
14 3 3 4
Gastrointestinal Genitourinary Hematologic Other Solid Tumor
26 17 1
Yes No Missing
Patient hospice use prior to death
20
Lung
Decedent cancer diagnosis
36
Spouse/partner
Relationship to patient
25
Full or part time
No.
2.3
38.6
59.1
9.1
6.8
6.8
31.8
45.5
2.3
15.9
81.8
11.4
31.8
56.8
%
1
4
14
1
1
2
8
7
1
3
15
3
7
9
No.
Cohen's D for continuous variables and Cramer's V for categorical variables
**
Fisher's exact or Pearson's Chi-square test for categorical variables and t-test for continuous variables
*
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Author Manuscript 5.3
21.1
73.7
5.3
5.3
10.5
42.1
36.8
5.2
15.8
78.9
15.8
36.8
47.4
%
Early Group (N=19)
0
13
12
3
2
1
6
13
0
4
21
2
7
16
No.
0
52.0
48.0
12.0
8.0
4.0
24.0
52.0
0
16.0
84.0
8.0
28.0
64.0
%
Delayed Group (N=25)
.06
.60
.81
.51
P*
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All Caregivers (N=44)
.30
.26
.17
.18
Effect size**
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Author Manuscript -
Adjusted for religious preference
Adjusted for hospice utilization
-
-
10.9
11.3
8.8
SD
-
-
3.4
14.6
11.2
Mean
-
-
9.5
10.7
8.2
SD
Early group (N=19)
-
-
2.6
17.6
14.8
Mean
-
-
12.1
11.8
9.2
SD
Delayed group (N=25)
0.6
0.9
0.7
-3
-3.6
Mean
3.6
3.6
3.4
3.5
2.7
SE
.88
.81
.83
.39
.19
P
.07
.10
.08
-.34
-.41
d
Notes: Change is follow-up minus baseline. Between group difference is Early minus delayed. P is from general linear models. Cohen's d uses the baseline pooled SD.
3
16.3
13.2
Unadjusted
Change from baseline
After care recipient death
Baseline
Mean
All caregivers (N=44)
Between-group difference
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Comparison of change over time in depression scores, Early vs. Delayed Group
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Author Manuscript Table 3
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24.9 (6.9)
Delayed
-2.2 (1.9)
Mean (SE) .21
P -.35
d -1.7 (2)
Mean (SE) .40
P -.27
d
Adj. for religious preference
-1.21 (1.8)
Mean (SE) .51
P -.20
d
Adjusted for baseline CES-D
Notes: Between-group difference is early minus delayed. P is from general linear models. Cohen's d uses pooled SD.
22.7 (4.9)
Raw scores, mean (SD)
Early
Group
Crude estimates
Between-group differences
-1.33 (2)
Mean (SE) .51
P -.21
D
Adj. for patient hospice use
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Comparison of grief scores after patient death, early vs. delayed group
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J Pain Symptom Manage. Author manuscript; available in PMC 2017 September 01. Published in final edited form as: J Pain Symptom Manage. 2016 September ; 52(3): 378–385. doi:10.1016/j.jpainsymman.2016.03.014.
Family Caregiver Depressive Symptom and Grief Outcomes from the ENABLE III Randomized Controlled Trial
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J. Nicholas Dionne-Odom, PhD, RN, Andres Azuero, PhD, Kathleen D. Lyons, ScD, Jay G. Hull, PhD, Anna T. Prescott, Tor Tosteson, ScD, Jennifer Frost, MA, RN, Konstantin H. Dragnev, MD, and Marie A Bakitas, DNSc School of Nursing (J.N.D.-O., A.A., M.A.B.), and Division of Gerontology, Geriatrics, and Palliative Care (M.A.B.), Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama; Department of Psychiatry (K.D.L.), Geisel School of Medicine at Dartmouth, Hanover, New Hampshire; Department of Psychological and Brain Sciences (J.G.H., A.T. P.), Dartmouth College, Hanover, New Hampshire; Biostatistics Shared Resource (T.T.), Norris Cotton Cancer Center, Lebanon, New Hampshire; and Department of Medicine, Hematology/Oncology (J.F., K.H.D.), Geisel School of Medicine at Dartmouth and Norris Cotton Cancer Center, Lebanon, New Hampshire, USA
Abstract Context—Little is known about whether early palliative care (EPC) support for family caregivers (CGs) impacts depressive symptoms and grief after care recipients die.
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Objectives—To assess after-death CG depressive symptom and grief scores for early compared to delayed group CGs. Methods—We conducted a randomized controlled trial (RCT) (10/2010-9/2013) of an EPC telehealth intervention for CGs (n=123) initiated at the time of care recipients' advanced cancer diagnosis (early group) or 12 weeks later (delayed group) in a rural comprehensive cancer center, affiliated clinics, and a Veterans Administration medical center. The ENABLE [Educate, Nurture, Advise, Before Life Ends] CG intervention consisted of three weekly sessions, monthly follow-up, and a bereavement call. CGs completed the Center for Epidemiological Study-Depression scale (CESD) and the Prigerson Inventory of Complicated Grief-Short Form (PG13) 8-12 weeks after care recipients' deaths. Crude and covariate-adjusted between-group differences were estimated and tested using general linear models.
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Results—For care recipients who died (n=70), 44 CGs (early: n=19; delayed: n=25) completed after-death questionnaires. Mean depressive symptom scores (CESD) for the early group was 14.6 (standard deviation [SD]=10.7) and for the delayed group was 17.6 (SD=11.8). Mean complicated grief scores (PG13) for the early group was 22.7 (SD=4.9) and for the delayed group was 24.9 Address correspondence to: Marie Bakitas, DNSc, CRNP, School of Nursing, University of Alabama at Birmingham, 1720 2nd Ave South, 2M024, Birmingham, AL 35294-1210, USA, [email protected]. Disclosures: All authors declare no conflicts of interest. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
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(SD=6.9). Adjusted between-group differences were not statistically significant (CESD: d=0.07, P=0.88; PG13: d=-0.21, P=0.51). Conclusion—CGs' depressive symptom and complicated grief scores 8-12 weeks after care recipients' deaths were not statistically different based on the timing of EPC support. The impact of timing of CG EPC interventions on CGs bereavement outcomes requires further investigation. Keywords Family caregiving; palliative care; advanced cancer; telehealth
Introduction Author Manuscript
A family caregiver is an unpaid individual (a spouse, partner, family member, friend, or neighbor) involved in assisting others with activities of daily living and/or medical tasks.1 An estimated 20 to 50% of family caregivers experience negative psychological aftereffects, including depression and grief, from months to years after a care recipient's death from cancer.2-4 In one respect, bereaved caregivers are often relieved of burdensome tasks, such as assisting care recipients with activities of daily living and care coordination,5 that can consume over eight hours a day.6 However, they are also susceptible to a range of potentially long-lasting, negative emotions, including profound loss and emptiness at the absence of a loved one;7 regret about unresolved issues or unsaid goodbyes;8 anger or shock at the manner in which a person died (e.g., extreme pain, gasping for breath);9 guilt about whether decisions they may have made as a surrogate decision-maker were the “right” ones (e.g., withdrawal of life-sustaining treatments);10 and distress at acclimating to a new lifestyle and daily routine.11
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Emerging evidence suggests that specialty palliative and hospice care positively impacts family caregivers after their care recipients die. In a South Australian population-based survey of 9088 caregivers, Abernethy and colleagues12 found that when care recipients received palliative care prior to death, decedent caregivers were significantly more likely to be able to move on with their lives. Similarly, a study by Ornstein and colleagues2 of 1016 family caregivers of hospice patients found significantly lower caregiver depressive symptoms at 1 year post-loss compared to caregivers of non-hospice care recipients. Palliative care, especially as delivered by hospice,13 provides specific support to caregivers prior to a care recipient's death and during bereavement period. Though hospice regulations allow for services to be offered for up to 6 months prior to death; on average hospice care is initiated only 23 days before death.14
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Very little is known, about whether offering specialty palliative care to family caregivers soon after an advanced cancer diagnosis may impact caregiver bereavement outcomes. To test if initiating early vs. delayed palliative care support to family caregivers impacts depressive symptoms and grief, we conducted a “fast track”15 phase III randomized controlled trial (RCT) of a telehealth intervention called ENABLE III (Educate, Nurture, Advise, Before Life Ends). ENABLE III consists of a face-to-face palliative care consultation for patients (caregivers may attend) and manualized coaching sessions and monthly follow-up. Family caregivers of participants with newly diagnosed advanced or
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recurrent cancer received the intervention either early (within 60 days) of diagnosis or 12 weeks later (delayed group). For patients who died during the study, we hypothesized that bereaved caregiver depressive symptom and grief scores would be lower for early compared to delayed group caregivers.
Methods Study Design
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The ENABLE III study design, methods and patient and caregiver outcomes have been described elsewhere.16,17 Briefly, from October 11, 2010 to March 5, 2013, patients within 60 days of being newly diagnosed with advanced, recurrent, or progressive cancer with an oncologist-determined prognosis of six to 24 months and their family caregivers signed informed consent and were randomly assigned to receive the ENABLE III intervention either within 60 days of diagnosis (early group) or 12 weeks later (delayed group). Random one-to-one group assignment was computer-generated, stratified by six cancer types and four recruitment sites. Caregivers were assigned to the same group as the patient. The study was approved by the institutional review boards of Dartmouth College and the White River Junction Veterans Affairs Medical Center (VAMC). Setting and Sample
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Patient and caregiver participants were recruited from the Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center (DHMC) in Lebanon, New Hampshire, affiliated DHMC outreach clinics, and the VAMC (White River Junction, VT). Patients were identified by research coordinators who reviewed weekly outpatient clinic schedules and tumor board lists. Patient inclusion criteria were: 1) English-speaking; 2) ≥18 years of age; 3) advanced-stage solid tumor or hematologic malignancy (detailed diagnostic criteria included in supplement of patient outcomes paper);18 and 4) completion of baseline questionnaires. Patient exclusion criteria included: 1) impaired cognition (Callahan score≤4);19 2) active Axis I psychiatric (schizophrenia, bipolar disorder) or substance use disorder; 3) uncorrectable hearing loss; and 4) unreliable telephone service. Potential family caregiver participants were identified by asking patient participants to nominate a family member or friend “who knows you well and is involved in your medical care” to consider participation. There were no caregiver exclusion criteria and patient participants were not excluded if they did not have a participating caregiver. The ENABLE III Caregiver Intervention
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The ENABLE III patient18,20,21 and caregiver17,22 interventions have been described in detail elsewhere. Briefly, the ENABLE III caregiver intervention was a manualized intervention facilitated by advanced practice palliative care nurse coaches over the phone. Given the largely rural, mountainous Vermont and New Hampshire geography23 and long travel distances to DHMC, ENABLE pilot work20 demonstrated feasibility and patient preference for a telephone versus in-person approach. Moreover, numerous studies have reported successes of telehealth approaches, including a recent review of telehealth interventions reporting that phone-delivered psychoeducational support had comparable outcomes to in-person care, was cost effective, and improved access for rural populations.24
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After completing baseline questionnaires, caregivers were assigned a nurse coach (who was different than the patient nurse coach) and were mailed Charting Your Course-Caregiver (CYC-CG), an investigator-developed guidebook (manual available from authors) that contained resource material supporting the nurse coaching sessions. Caregivers participated in three weekly telephone coaching sessions using CYC-CG. Session 1 focused on “being a caregiver;” the goals of palliative care; an overview of the COPE (Creativity, Optimism, Planning, Expert guidance) attitude;25 and a step-wise framework for engaging in problemsolving coping (derived from the conceptual foundations of problem-solving treatment).25-27 Session 2 centered on caregiver self-care, addressing topics such as healthy eating and exercise, meditation, spirituality and partnering in a patient's symptom management. Session 3 reviewed communication, decision-making including decision aid tools (e.g., Ottawa Personal Decision Guide), and advance care planning. Caregiver participants then received monthly check-in calls to reinforce prior content and assist with new issues that arose. Follow up calls continued until study completion or care recipients death. Caregivers of care recipients who died, received a bereavement call from nurse coaches approximately 2-4 weeks after the date of death to offer condolences, inquire how they were doing, and ask permission for a data collector to contact them to administer a final survey. To enhance intervention fidelity, nurse coaches followed a script for all CYC-CG sessions, monthly check-in calls, and for the bereavement call.
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Seven advanced practice palliative care nurse coaches received approximately 30 hours of training that included self-study of all intervention protocols and scripts; one-on-one didactic education on problem-solving support and decision-aids; review of 12 recorded CYC practice sessions and role playing each session. The PI (MB) provided one-on-one constructive feedback during training. After training, the principal investigator (PI), blinded to group assignment, listened to all caregiver sessions and met weekly with the nurse coaches to discuss any protocol deviations or other issues. Measures Data collectors, blinded to group assignment, collected patient and caregiver measures by telephone at baseline, 6, 12, 18, and 24 weeks. After week 24, data collection was every 12 weeks until patients died or the study ended. Baseline family caregiver demographics included age, gender, race, ethnicity, religion, marital status, employment, education, and their relationship to the care recipient. Details of all other patient and caregiver measures are described elsewhere.17 Eight to 12 weeks after-death, participating caregivers of decedents were asked to complete a measure of depressive symptoms and grief.
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Depressive symptoms were measured using the Centers for Epidemiological StudiesDepression (CES-D) scale.28 This 20-item measure has demonstrated very good internal consistency reliability (Cronbach's alpha=0.85) and includes questions about how often one has had symptoms related to depression over the past week, such as appetite loss, feeling blue, restless sleep, loneliness, and crying spells. Response options range from 0 to 3 (0=rarely or none of the time [16 suggestive of clinical depression.29 Grief was measured using the Prigerson Inventory of Complicated Grief-Short Form (PG13).30 This 13-item short form measure has demonstrated very good internal consistency reliability (Cronbach's alpha=0.94) and includes questions to assess pathological grief over the past month, including yearning for the deceased, acceptance of the deceased death, and feelings of meaninglessness and being able to move on. Responses range from 1 (“never”) to 5 (“always”). Higher scores indicate higher grief and scores >25 indicate clinically significant complicated grief. Statistical Analysis
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Caregiver characteristics (study group, age, gender, race, marital status, education, religious preference, employment status, relationship to patient, patients' primary cancer site, patients' use of hospice prior to death, and baseline CES-D score) were tabulated by completion of after-death questionnaire status (and by study group) and then compared using effect sizes and significance tests. The objective of the analysis was to estimate the baseline to afterdeath between-group difference (early minus delayed) in CES-D score and the betweengroup difference in PG13 score. Within-person change in CES-D scores were computed and the between-group mean difference was estimated. The between-group difference in PG13 score was also estimated. These mean differences were compared using effect sizes (Cohen's d) and t-tests. Because the study groups differed on religious preference and patient use of hospice, between-group mean differences in outcomes, adjusted for the probability of group assignment given religious preference and for patient hospice use, were also estimated using general linear models (one covariate at a time because of the small sample size). The probability of group assignment given religious preference was estimated using a logistic regression model fitted with Firth's penalized likelihood method.31 The between group difference in PG13 score was also estimated after adjusting for baseline CES-D score. Because of the small sample size, we interpreted our results using both observed effect sizes and significance tests. Analyses were conducted in SAS software v. 9.4 (SAS Institute Inc., Cary, NC).
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Results Sample Characteristics
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As shown in Fig. 1, 207 patients were randomized into early and delayed intervention groups. One hundred twenty-four nominated a family caregiver to participate and 122 enrolled and provided data. A total of 70 patient participants with enrolled family caregivers died during the study (early: n=31; delayed: n=39) and 44 caregivers (early: n=19; delayed: n=25) completed after-death questionnaires. Approximately 37% (n=26) of decedents' caregivers did not complete after-death questionnaires. Religious preference and baseline CESD were associated with completion of the questionnaires. Protestants were more likely to complete (22/26, 84.6%), while Catholics were less likely to complete (8/20, 40%; Cramer's V= 0.38, P=0.02). Those who completed the questionnaires had, on average, lower
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values (fewer depressive symptoms) of baseline CESD (M(SD)=15 (9.3)) compared to those who did not complete (M(SD)=19.4 (12.5); d=0.40, P=0.18). There were no statistically significant differences between decedents' caregiver demographic characteristics by group (Table 1). On average, caregivers were age 62 years, female (84.1%; n=37), white (93.2%; n=41), and married or living with a partner (93.2%; n=41). Forty-three percent (n=19) had completed high school or some college or technical school and 56.8% (n=25) had a college or advanced degree. Approximately 68% (n=30) reported a Christian denomination (Protestant or Catholic), and 18.2% (n=8) reported no religious affiliation. Over half (n=25) were employed full- or part-time and approximately 43% (n=19) were retired or unemployed. Most caregivers (81.8%; n=36) were decedents' spouses or partners. Most cared for patients with lung (45.5%; n=20) and gastrointestinal cancers (31.8%; n=14) and a substantial proportion of patients used hospice prior to death (59.1%, n=26).
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Depressive Symptoms and Complicated Grief Table 2 shows the CESD between-group comparisons at baseline, after patient death, and the change from baseline to after-death. Adjusted between-group differences were not statistically significant (P=0.81). The CESD change from baseline for the early group was +3.4 (SD=9.5) and for the delayed group was +2.6 (SD=12.1). The between-group difference in CESD change was of trivial magnitude (d=0.08) even after adjusting for religious preference (d=0.10) or patient hospice use (d=0.07).
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Table 3 shows the PG13 between-group grief comparison scores. Again, the adjusted between-group differences were not statistically significant (P=0.51). The unadjusted effect size was moderate (early minus delayed, d=-0.35); however, the effect size decreased to d=-0.27 after adjusting for religious preference. Further adjustment for baseline CESD scores and patient hospice use resulted in a decrease of the effect size difference to d=-0.20 and d=-0.21, respectively (early minus delayed).
Discussion
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This trial represents the first attempt to test the effect of early palliative care telehealth support on bereaved family caregivers. We conducted an early versus delayed “fast track” RCT to determine if family caregivers who received the ENABLE III early palliative care telehealth intervention, within 60 days of their care recipients' advanced cancer diagnosis had lower depressive symptom scores and lower grief scores after care recipients' deaths than caregivers who received the intervention 12 weeks later. Our analysis detected no statistical differences on caregivers' after-death depression and grief scores relative to initiation of the intervention. In our prior report of this trial,17 a terminal decline analysis of CG outcomes looking backwards in time 36 weeks from care recipient death showed significantly lower depressive symptom scores in early compared to delayed group caregivers. Given that pre-loss caregiver distress has been associated with post-loss outcomes,3,8,32,33 we were surprised to find that the depressive symptom benefits for early group caregivers did not extend into the period after their care recipients' deaths. Because not all decedent caregivers completed
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after-death questionnaires, the sample of decedent caregivers was much smaller in this analysis compared to that in the terminal decline analysis, which greatly limited statistical power to detect differences between groups. Despite this limitation, it is worth highlighting that there was an observed small effect size difference in grief scores favoring the early group (early minus delayed; PG13: d=-0.20). We believe this signal of potential efficacy is sufficient to warrant future examination of the impact of early palliative care for caregivers on their after-death outcomes.
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There are several explanations for the lack of robust positive results. First, the ENABLE III caregiver intervention did not specifically address death preparedness and coping with the death of a loved one.34 Because ENABLE is an early palliative care intervention, topics were chosen that were most appropriate for the caregiving context while care recipients were still relatively high functioning and with potentially several years to live. Topics such as what to expect and how to care for the actively dying patient, withholding/withdrawing lifesustaining treatment, and funeral care were not discussed by nurse coaches unless the topics were broached by participants themselves. Discussing such topics before death may facilitate better bereavement adjustment.34 Hence, future early palliative care for family caregivers might consider exploring non-threatening ways to integrate end-of-life preparedness topics.
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Second, depressed mood and grief scores were collected 8 to 12 weeks after the death of the care recipient. This timeframe falls within the period when normal grief is expected, which is typically up to 1 year.7 Evidence suggests that significant differences between normal and prolonged grief are not evident until one to two years after an individual's death.2,12 For example, Ornstein et al. found that differences in spousal depression in those whose care recipients did and did not use hospice were most pronounced at one year following death. Hence, future studies of early palliative care for caregivers may need to protract the timeline of data collection for up to 2 years after a care recipient's death in order to capture meaningful differences. Though it will be important to control for CGs' use of bereavement services which are covered under Medicare's hospice benefit.13
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A number of factors have been associated with lower caregiver depression and grief scores that may be impacted by future models of caregiver early palliative care support. Examples include use of hospice,2,12,35 avoidance of high intensity end-of-life care,36,37 care recipient's quality of death and dying,36 and the leveraging of social support networks.3,38 These factors represent prospective mediators of early palliative care support for caregivers that impact after-death outcomes. In combination with evidence showing caregiver underutilization of post-loss bereavement services,39 a potential solution is to educate and encourage caregivers early on in the patient's disease trajectory to leverage these resources if needed in the future. Early palliative care supports family caregivers when they are less entrenched in day-to-day tasks because their care recipients are less ill and have fewer care needs. Hence, caregivers may be more capable during this period of relatively lower stress to obtain knowledge and skills that they will need in the future.
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Limitations
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Our study has important limitations. First, our trial did not have a usual care comparison group. Both caregiver groups received palliative care much earlier than would be provided through hospice. Therefore, we are unable to determine what after-death differences there might have been between caregivers receiving ENABLE versus those who did not. Second, because we did not collect data on caregivers' use of supportive services such as hospice bereavement programs and counseling, we are not able to account for the potentially mediating impact that use of these services may have had on caregiver after-death outcomes. Third, because data for this analysis could only be collected from caregivers of decedents, the sample size for this analysis was small, thus limiting statistical power and increasing the chances of failing to detect a true relevant effect (Type II error). Fourth, this analysis tested the “timing” of palliative care and did not account for the amount or “dosing” of palliative care one receives before death (e.g., as measured by the number of hours of one-on-one contact). It seems reasonable to hypothesize that the “dose” of palliative care support that caregivers receive pre-loss may predict post-loss depression and grief. However, it remains an unanswered and important research question about whether there are differences between “timing” and “dosing” of specialty palliative care. Finally, the caregiver sample was nearly all white, which is unsurprising given the population demographics of rural New England. Future work in this area would be strengthened by inclusion of racial and ethnic minorities, especially given evidence suggesting non-white caregivers may have higher rates of grief disorders.40
Conclusion Author Manuscript
Our study did not find statistical differences in depression and grief scores of family caregivers of decedents who received early versus delayed palliative care. However, our small sample size may have limited our ability to detect the impact of ENABLE on caregiver bereavement outcomes. Furthermore, after-death measures were collected within the time frame when normal grief is difficult to distinguish from complicated grief. Given that the observed effect size difference in grief scores favored early group caregivers, the possibility should not be ruled out that early palliative care may positively impact caregivers after patients die. Therefore the impact of early palliative care support for caregivers on bereavement outcomes is still an open and high priority research question.
Acknowledgments
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The parent study was supported by the National Institute for Nursing Research (R01NR011871-01), a Cancer and Leukemia Group B Foundation Clinical Scholar Award, the Foundation for Informed Medical Decision-Making, the Norris Cotton Cancer Center pilot funding, and the Dartmouth-Hitchcock, Section of Palliative Medicine. Dr. Dionne-Odom is a postdoctoral fellow supported by the University of Alabama at Birmingham Cancer Prevention and Control Training Program (5R25CA047888), by a National Palliative Care Research Center Career Development Award, and by the MSM/TU/UAB Comprehensive Cancer Center Partnership (U54CA118948). Dr. Lyons is supported by a Mentored Research Scholar Grant in Applied and Clinical Research (MRSG 12-113-01– CPPB) from the American Cancer Society. Dr. is a recipient of a National Palliative Care Research Center Junior Career Development Award.
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1. Family Caregiver Alliance. Aging BRIo. 2nd. San Francisco, CA: Family Caregiver Alliance; 2012. Selected caregiver assessment measures: a resource inventory for practitioners. 2. Ornstein KA, Aldridge MD, Garrido MM, et al. Association between hospice use and depressive symptoms in surviving spouses. JAMA Intern Med. 2015; 175:1138–1146. [PubMed: 26009859] 3. Allen JY, Haley WE, Small BJ, Schonwetter RS, McMillan SC. Bereavement among hospice caregivers of cancer patients one year following loss: predictors of grief, complicated grief, and symptoms of depression. J Palliat Med. 2013; 16:745–751. [PubMed: 23697816] 4. Ghesquiere A, Haidar YM, Shear MK. Risks for complicated grief in family caregivers. J Soc Work End Life Palliat Care. 2011; 7:216–240. [PubMed: 21895438] 5. Schulz R, Mendelsohn AB, Haley WE, et al. End-of-life care and the effects of bereavement on family caregivers of persons with dementia. N Engl J Med. 2003; 349:1936–1942. [PubMed: 14614169] 6. Yabroff KR, Kim Y. Time costs associated with informal caregiving for cancer survivors. Cancer. 2009; 115(18 Suppl):4362–4373. [PubMed: 19731345] 7. Schulz R, Hebert R, Boerner K. Bereavement after caregiving. Geriatrics. 2008; 63:20–22. [PubMed: 18257616] 8. Garrido MM, Prigerson HG. The end-of-life experience: modifiable predictors of caregivers' bereavement adjustment. Cancer. 2014; 120:918–925. [PubMed: 24301644] 9. Dionne-Odom JN, Willis DG, Bakitas M, Crandall B, Grace PJ. Conceptualizing surrogate decision making at end of life in the intensive care unit using cognitive task analysis. Nurs Outlook. 2015; 63:331–340. [PubMed: 25982772] 10. Wendler D, Rid A. Systematic review: the effect on surrogates of making treatment decisions for others. Ann Intern Med. 2011; 154:336–346. [PubMed: 21357911] 11. Naef R, Ward R, Mahrer-Imhof R, Grande G. Characteristics of the bereavement experience of older persons after spousal loss: an integrative review. Int J Nurs Stud. 2013; 50:1108–1121. [PubMed: 23273923] 12. Abernethy AP, Currow DC, Fazekas BS, et al. Specialized palliative care services are associated with improved short- and long-term caregiver outcomes. Support Care Cancer. 2008; 16:585–597. [PubMed: 17960433] 13. Centers for Medicare and Medicaid Services. Medicare benefit policy manual: Chapter 9: Coverage of hospice services under hospital insurance. Baltimore, MD: CMS; 2015. 14. Dartmouth Atlas of Health Care. Hospice days per decedent during the last 6 months of life. Lebanon, NH: Dartmouth College; 2012. 15. Farquhar M, Higginson IJ, Booth S. Fast-track trials in palliative care: an alternative randomized controlled trial design. J Palliat Med. 2009; 12:213. [PubMed: 19254192] 16. Bakitas MA, Tosteson TD, Li Z, et al. Early versus delayed initiation of concurrent palliative oncology care: patient outcomes in the ENABLE III randomized controlled trial. J Clin Oncol. 2015; 33:1438–1445. [PubMed: 25800768] 17. Dionne-Odom JN, Azuero A, Lyons KD, et al. Benefits of early versus delayed palliative care to informal family caregivers of patients with advanced cancer: outcomes from the ENABLE III randomized controlled trial. J Clin Oncol. 2015; 33:1446–1452. [PubMed: 25800762] 18. Bakitas M, Tosteson T, Li Z, et al. Early Versus Delayed Initiation of Concurrent Palliative Oncology Care: Patient Outcomes in the ENABLE III Randomized Controlled Trial. J Clin Oncol. Mar.2015 19. Callahan CM, Unverzagt FW, Hui SL, Perkins AJ, Hendrie HC. Six-item screener to identify cognitive impairment among potential subjects for clinical research. Med Care. 2002; 40:771–781. [PubMed: 12218768] 20. Bakitas M, Stevens M, Ahles T, et al. Project ENABLE: a palliative care demonstration project for advanced cancer patients in three settings. J Palliat Med. 2004; 7:363–372. [PubMed: 15130218]
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21. Bakitas M, Lyons K, Hegel M, et al. Project ENABLE II randomized controlled trial to improve palliative care for rural patients with advanced cancer: baseline findings, methodological challenges, and solutions. Palliat Support Care. 2009; 7:75–86. [PubMed: 19619377] 22. Dionne-Odom JN, Lyons K, Akyar I, Bakitas M. Helping Family caregivers become better problem solvers when caring for persons with advanced cancer. J Soc Work End Life Palliat Care. in press. 23. 2010 Census Urban and Rural Classification and Urban Area Criteria. 2010 24. Hilty DM, Ferrer DC, Parish MB, et al. The effectiveness of telemental health: a 2013 review. Telemed J E Health. 2013; 19:444–454. [PubMed: 23697504] 25. McMillan S, Small B, Weitzner M, et al. Impact of coping skills intervention with family caregivers of hospice patients with cancer. Cancer. 2005; 106:214–222. [PubMed: 16329131] 26. Loscalzo M, Bucher J. The COPE model: its clinical usefulness in solving pain-related problems. J Psychosoc Oncol. 1999; 9:66–70. 27. McMillan S, Small B. Using the COPE intervention for family caregivers to improve symptoms of hospice homecare patients: a clinical trial. Oncol Nurs Forum. 2007; 34:313–321. [PubMed: 17573295] 28. Radloff L. The CES-D scale: a self-report depression scale for research in the general population. Applied Psychological Measurement. 1977; 1:385–401. 29. Lewinsohn PM, Seeley JR, Roberts RE, Allen NB. Center for Epidemiologic Studies Depression Scale (CES-D) as a screening instrument for depression among community-residing older adults. Psychol Aging. 1997; 12:277–287. [PubMed: 9189988] 30. Prigerson HG, Maciejewski PK, Reynolds CF, et al. Inventory of Complicated Grief: a scale to measure maladaptive symptoms of loss. Psychiatry Res. 1995; 59:65–79. [PubMed: 8771222] 31. Firth D. Bias reduction of maximum likelihood estimates. Biometrika. 1993; 80:27–38. 32. Kapari M, Addington-Hall J, Hotopf M. Risk factors for common mental disorder in caregiving and bereavement. J Pain Symptom Manage. 2010; 40:844–856. [PubMed: 20739140] 33. Ling SF, Chen ML, Li CY, et al. Trajectory and influencing factors of depressive symptoms in family caregivers before and after the death of terminally ill patients with cancer. Oncol Nurs Forum. 2013; 40:E32–40. [PubMed: 23269779] 34. Hebert RS, Prigerson HG, Schulz R, Arnold RM. Preparing caregivers for the death of a loved one: a theoretical framework and suggestions for future research. J Palliat Med. 2006; 9:1164–1171. [PubMed: 17040154] 35. Higgins PC, Garrido MM, Prigerson HG. Factors predicting bereaved caregiver perception of quality of care in the final week of life: implications for health care providers. J Palliat Med. 2015; 18:849–857. [PubMed: 26186021] 36. Wright AA, Zhang B, Ray A, et al. Associations between end-of-life discussions, patient mental health, medical care near death, and caregiver bereavement adjustment. JAMA. 2008; 300:1665– 1673. [PubMed: 18840840] 37. Wright AA, Keating NL, Balboni TA, et al. Place of death: correlations with quality of life of patients with cancer and predictors of bereaved caregivers' mental health. J Clin Oncol. 2010; 28:4457–4464. [PubMed: 20837950] 38. Burton AM, Haley WE, Small BJ, et al. Predictors of well-being in bereaved former hospice caregivers: the role of caregiving stressors, appraisals, and social resources. Palliat Support Care. 2008; 6:149–158. [PubMed: 18501050] 39. Lichtenthal WG, Nilsson M, Kissane DW, et al. Underutilization of mental health services among bereaved caregivers with prolonged grief disorder. Psychiatr Serv. 2011; 62:1225–1229. [PubMed: 21969652] 40. Goldsmith B, Morrison RS, Vanderwerker LC, Prigerson HG. Elevated rates of prolonged grief disorder in African Americans. Death Stud. 2008; 32:352–365. [PubMed: 18850684]
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Fig. 1.
CONSORT Diagram of Family Caregiver Enrollment.
Author Manuscript J Pain Symptom Manage. Author manuscript; available in PMC 2017 September 01.
Author Manuscript
Author Manuscript 10.1
0 2 1
Black
Other
Missing
41 0 1
Married or living with partner
Divorced or separated
Widowed
25
College graduate or above
J Pain Symptom Manage. Author manuscript; available in PMC 2017 September 01. 8 8 5 1
Catholic
None
Other
Missing
Employment Status
22
Protestant
Religion
19
High school or GED, some college or technical school
Education
2
Never married
Marital Status
41
White
Race
Female gender
61.6
SD 37
No.
Mean
Age, years
Characteristic
2.3
11.4
18.2
18.2
50.0
56.8
43.2
2.3
0
93.2
4.5
2.3
4.6
0
93.2
84.1
%
All Caregivers (N=44)
0
2
5
1
11
10
9
0
0
18
1
0
1
0
18
15
No.
11.9
62.1
0
10.5
26.3
5.3
57.9
52.6
47.4
0
0
95.0
5.3
0
5.3
0
95.0
78.9
%
Early Group (N=19)
1
3
3
7
11
15
10
1
0
23
1
1
1
0
23
22
No.
8.6
61.2
4.0
12.0
12.0
28.0
44.0
60.0
40.0
4.0
0
92.0
4.0
4.0
4.0
0
92.0
88.0
%
Delayed Group (N=25)
Author Manuscript Table 1
.20
.63
.67
.87
.42
.77
P*
.33
.07
.14
.03
.12
.09
Effect size**
Author Manuscript
Family Caregiver Characteristics of Decedent Care Recipients
Dionne-Odom et al. Page 12
14 5
Retired Not Employed
7 1
Other immediate relative (i.e., parent, child) Other relative or friend
14 3 3 4
Gastrointestinal Genitourinary Hematologic Other Solid Tumor
26 17 1
Yes No Missing
Patient hospice use prior to death
20
Lung
Decedent cancer diagnosis
36
Spouse/partner
Relationship to patient
25
Full or part time
No.
2.3
38.6
59.1
9.1
6.8
6.8
31.8
45.5
2.3
15.9
81.8
11.4
31.8
56.8
%
1
4
14
1
1
2
8
7
1
3
15
3
7
9
No.
Cohen's D for continuous variables and Cramer's V for categorical variables
**
Fisher's exact or Pearson's Chi-square test for categorical variables and t-test for continuous variables
*
Author Manuscript Characteristic
Author Manuscript 5.3
21.1
73.7
5.3
5.3
10.5
42.1
36.8
5.2
15.8
78.9
15.8
36.8
47.4
%
Early Group (N=19)
0
13
12
3
2
1
6
13
0
4
21
2
7
16
No.
0
52.0
48.0
12.0
8.0
4.0
24.0
52.0
0
16.0
84.0
8.0
28.0
64.0
%
Delayed Group (N=25)
.06
.60
.81
.51
P*
Author Manuscript
All Caregivers (N=44)
.30
.26
.17
.18
Effect size**
Dionne-Odom et al. Page 13
Author Manuscript
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Author Manuscript
Author Manuscript -
Adjusted for religious preference
Adjusted for hospice utilization
-
-
10.9
11.3
8.8
SD
-
-
3.4
14.6
11.2
Mean
-
-
9.5
10.7
8.2
SD
Early group (N=19)
-
-
2.6
17.6
14.8
Mean
-
-
12.1
11.8
9.2
SD
Delayed group (N=25)
0.6
0.9
0.7
-3
-3.6
Mean
3.6
3.6
3.4
3.5
2.7
SE
.88
.81
.83
.39
.19
P
.07
.10
.08
-.34
-.41
d
Notes: Change is follow-up minus baseline. Between group difference is Early minus delayed. P is from general linear models. Cohen's d uses the baseline pooled SD.
3
16.3
13.2
Unadjusted
Change from baseline
After care recipient death
Baseline
Mean
All caregivers (N=44)
Between-group difference
Author Manuscript Table 2
Author Manuscript
Comparison of change over time in depression scores, Early vs. Delayed Group
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Author Manuscript Table 3
Author Manuscript
Author Manuscript
24.9 (6.9)
Delayed
-2.2 (1.9)
Mean (SE) .21
P -.35
d -1.7 (2)
Mean (SE) .40
P -.27
d
Adj. for religious preference
-1.21 (1.8)
Mean (SE) .51
P -.20
d
Adjusted for baseline CES-D
Notes: Between-group difference is early minus delayed. P is from general linear models. Cohen's d uses pooled SD.
22.7 (4.9)
Raw scores, mean (SD)
Early
Group
Crude estimates
Between-group differences
-1.33 (2)
Mean (SE) .51
P -.21
D
Adj. for patient hospice use
Author Manuscript
Comparison of grief scores after patient death, early vs. delayed group
Dionne-Odom et al. Page 15
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