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Family Caregiver Depressive Symptom and Grief Outcomes From the ENABLE III Randomized Controlled Trial

Open AccessPublished:June 02, 2016DOI:https://doi.org/10.1016/j.jpainsymman.2016.03.014

      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.

      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 (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 (CES-D) scale 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.

      Results

      For care recipients who died (n = 70), 44 CGs (early: n = 19; delayed: n = 25) completed after-death questionnaires. Mean depressive symptom scores (CES-D) for the early group was 14.6 (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 (SD = 6.9). Adjusted between-group differences were not statistically significant (CES-D: 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.

      Key Words

      Introduction

      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.
      Family Caregiver Alliance
      Selected caregiver assessment measures: a resource inventory for practitioners.
      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.
      • Ornstein K.A.
      • Aldridge M.D.
      • Garrido M.M.
      • et al.
      Association between hospice use and depressive symptoms in surviving spouses.
      • Allen J.Y.
      • Haley W.E.
      • Small B.J.
      • Schonwetter R.S.
      • McMillan S.C.
      Bereavement among hospice caregivers of cancer patients one year following loss: predictors of grief, complicated grief, and symptoms of depression.
      • Ghesquiere A.
      • Haidar Y.M.
      • Shear M.K.
      Risks for complicated grief in family caregivers.
      In one respect, bereaved caregivers are often relieved of burdensome tasks, such as assisting care recipients with activities of daily living and care coordination,
      • Schulz R.
      • Mendelsohn A.B.
      • Haley W.E.
      • et al.
      End-of-life care and the effects of bereavement on family caregivers of persons with dementia.
      that can consume over eight hours a day.
      • Yabroff K.R.
      • Kim Y.
      Time costs associated with informal caregiving for cancer survivors.
      However, they are also susceptible to a range of potentially longlasting, negative emotions, including profound loss and emptiness at the absence of a loved one;
      • Schulz R.
      • Hebert R.
      • Boerner K.
      Bereavement after caregiving.
      regret about unresolved issues or unsaid goodbyes;
      • Garrido M.M.
      • Prigerson H.G.
      The end-of-life experience: modifiable predictors of caregivers' bereavement adjustment.
      anger or shock at the manner in which a person died (e.g., extreme pain, gasping for breath);
      • Dionne-Odom J.N.
      • Willis D.G.
      • Bakitas M.
      • Crandall B.
      • Grace P.J.
      Conceptualizing surrogate decision making at end of life in the intensive care unit using cognitive task analysis.
      guilt about whether decisions they may have made as a surrogate decision-maker were the “right” ones (e.g., withdrawal of life-sustaining treatments);
      • Wendler D.
      • Rid A.
      Systematic review: the effect on surrogates of making treatment decisions for others.
      and distress at acclimating to a new lifestyle and daily routine.
      • Naef R.
      • Ward R.
      • Mahrer-Imhof R.
      • Grande G.
      Characteristics of the bereavement experience of older persons after spousal loss: an integrative review.
      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 et al.
      • Abernethy A.P.
      • Currow D.C.
      • Fazekas B.S.
      • et al.
      Specialized palliative care services are associated with improved short- and long-term caregiver outcomes.
      found that when care recipients received palliative care before death, decedent caregivers were significantly more likely to be able to move on with their lives. Similarly, a study by Ornstein et al.
      • Ornstein K.A.
      • Aldridge M.D.
      • Garrido M.M.
      • et al.
      Association between hospice use and depressive symptoms in surviving spouses.
      of 1016 family caregivers of hospice patients found significantly lower caregiver depressive symptoms at one-year postloss compared to caregivers of nonhospice care recipients. Palliative care, especially as delivered by hospice,
      Centers for Medicare and Medicaid Services
      Medicare benefit policy manual: Chapter 9: Coverage of hospice services under hospital insurance.
      provides specific support to caregivers before a care recipient's death and during bereavement period. Although hospice regulations allow for services to be offered for up to six months before death; on average hospice care is initiated only 23 days before death.
      Dartmouth Atlas of Health Care
      Hospice days per decedent during the last 6 months of life.
      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”
      • Farquhar M.
      • Higginson I.J.
      • Booth S.
      Fast-track trials in palliative care: an alternative randomized controlled trial design.
      Phase III randomized controlled trial 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 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

      The ENABLE III study design, methods, and patient and caregiver outcomes have been described elsewhere.
      • Bakitas M.A.
      • Tosteson T.D.
      • Li Z.
      • et al.
      Early versus delayed initiation of concurrent palliative oncology care: patient outcomes in the ENABLE III randomized controlled trial.
      • Dionne-Odom J.N.
      • Azuero A.
      • Lyons K.D.
      • 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.
      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.

      Setting and Sample

      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 Veterans Affairs Medical Center (White River Junction, VT). Patients were identified by research coordinators who reviewed weekly outpatient clinic schedules and tumor board lists. Patient inclusion criteria were as follows: 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 article),
      • Bakitas M.A.
      • Tosteson T.D.
      • Li Z.
      • et al.
      Early versus delayed initiation of concurrent palliative oncology care: patient outcomes in the ENABLE III randomized controlled trial.
      4) completion of baseline questionnaires. Patient exclusion criteria included 1) impaired cognition (Callahan score ≤4),
      • Callahan C.M.
      • Unverzagt F.W.
      • Hui S.L.
      • Perkins A.J.
      • Hendrie H.C.
      Six-item screener to identify cognitive impairment among potential subjects for clinical research.
      2) active Axis I psychiatric (schizophrenia, bipolar disorder) or substance use disorder, 3) uncorrectable hearing loss, 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

      The ENABLE III patient
      • Bakitas M.A.
      • Tosteson T.D.
      • Li Z.
      • et al.
      Early versus delayed initiation of concurrent palliative oncology care: patient outcomes in the ENABLE III randomized controlled trial.
      • Bakitas M.
      • Stevens M.
      • Ahles T.
      • et al.
      Project ENABLE: a palliative care demonstration project for advanced cancer patients in three settings.
      • 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.
      and caregiver
      • Dionne-Odom J.N.
      • Azuero A.
      • Lyons K.D.
      • 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.
      • Dionne-Odom J.N.
      • Lyons K.
      • Akyar I.
      • Bakitas M.
      Coaching family caregivers to become better problem solvers when caring for persons with advanced cancer.
      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 geography
      and long travel distances to DHMC, ENABLE pilot work
      • Bakitas M.
      • Stevens M.
      • Ahles T.
      • et al.
      Project ENABLE: a palliative care demonstration project for advanced cancer patients in three settings.
      demonstrated feasibility and patient preference for a telephone vs. 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.
      • Hilty D.M.
      • Ferrer D.C.
      • Parish M.B.
      • et al.
      The effectiveness of telemental health: a 2013 review.
      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;
      • McMillan S.
      • Small B.
      • Weitzner M.
      • et al.
      Impact of coping skills intervention with family caregivers of hospice patients with cancer.
      and a stepwise framework for engaging in problem-solving coping (derived from the conceptual foundations of problem-solving treatment).
      • McMillan S.
      • Small B.
      • Weitzner M.
      • et al.
      Impact of coping skills intervention with family caregivers of hospice patients with cancer.
      • Loscalzo M.
      • Bucher J.
      The COPE model: its clinical usefulness in solving pain-related problems.
      • McMillan S.
      • Small B.
      Using the COPE intervention for family caregivers to improve symptoms of hospice homecare patients: a clinical trial.
      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 two to four 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.
      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 principal investigator (M. A. B) provided one-on-one constructive feedback during training. After training, the principal investigator 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.
      • Dionne-Odom J.N.
      • Azuero A.
      • Lyons K.D.
      • 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.
      Eight to 12 weeks after death, participating caregivers of decedents were asked to complete a measure of depressive symptoms and grief.
      Depressive symptoms were measured using the Centers for Epidemiological Studies–Depression (CES-D) scale.
      • Radloff L.
      The CES-D scale: a self-report depression scale for research in the general population.
      This 20-item measure has demonstrated very good internal consistency reliability (Cronbach 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 [<1 day]; 1 = some or a little of the time [1–2 days]; 2 = occasionally or a moderate amount of time [3–4 days]; 3 = most of all of the time [5–7 days]). Total scores range from 0 to 60, with higher scores indicating higher depressed mood and scores >16 suggestive of clinical depression.
      • Lewinsohn P.M.
      • Seeley J.R.
      • Roberts R.E.
      • Allen N.B.
      Center for Epidemiologic Studies Depression Scale (CES-D) as a screening instrument for depression among community-residing older adults.
      Grief was measured using the Prigerson Inventory of Complicated Grief-Short Form (PG13).
      • Prigerson H.G.
      • Maciejewski P.K.
      • Reynolds C.F.
      • et al.
      Inventory of Complicated Grief: a scale to measure maladaptive symptoms of loss.
      This 13-item short form measure has demonstrated very good internal consistency reliability (Cronbach 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

      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 before 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 after-death between-group difference (early minus delayed) in CES-D score and the between-group difference in PG13 score. Within-person change in CES-D scores was 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.
      • Firth D.
      Bias reduction of maximum likelihood estimates.
      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 version 9.4 (SAS Institute Inc., Cary, NC).

      Results

      Sample Characteristics

      As shown in Figure 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 CES-D were associated with completion of the questionnaires. Protestants were more likely to complete (22/26, 84.6%), whereas 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 values (fewer depressive symptoms) of baseline CES-D (M [SD] = 15 [9.3]) compared to those who did not complete (M [SD] = 19.4 [12.5]; d = 0.40, P = 0.18).
      Figure thumbnail gr1
      Fig. 1CONSORT diagram of family caregiver enrollment.
      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 before death (59.1%, n = 26).
      Table 1Family Caregiver Characteristics of Decedent Care Recipients
      CharacteristicAll Caregivers (N = 44)Early Group (N = 19)Delayed Group (N = 25)P
      Fisher exact or Pearson chi-square test for categorical variables and t-test for continuous variables.
      Effect Size
      Cohen's d for continuous variables and Cramer's V for categorical variables.
      No.%No.%No.%
      Age, yrs
       Mean61.662.161.20.770.09
       SD10.111.98.6
      Female gender3784.11578.92288.00.420.12
      Race
       White4193.21895.02392.00.870.03
       Black000000
       Other24.615.314.0
       Missing12.30014.0
      Marital status
       Never married24.515.314.00.670.14
       Married or living with partner4193.21895.02392.0
       Divorced or separated000000
       Widowed12.30014.0
      Education
       High school or GED, some college or technical school1943.2947.41040.00.630.07
       College graduate or above2556.81052.61560.0
      Religion
       Protestant2250.01157.91144.00.200.33
       Catholic818.215.3728.0
       None818.2526.3312.0
       Other511.4210.5312.0
       Missing12.30014.0
      Employment status
       Full- or part-time2556.8947.41664.00.510.18
       Retired1431.8736.8728.0
       Not employed511.4315.828.0
      Relationship to patient
       Spouse/partner3681.81578.92184.00.810.17
       Other immediate relative (i.e., parent, child)715.9315.8416.0
       Other relative or friend12.315.200
      Decedent cancer diagnosis
       Lung2045.5736.81352.00.600.26
       Gastrointestinal1431.8842.1624.0
       Genitourinary36.8210.514.0
       Hematologic36.815.328.0
       Other solid tumor49.115.3312.0
      Patient hospice use before death
       Yes2659.11473.71248.00.060.30
       No1738.6421.11352.0
       Missing12.315.300
      GED = general equivalency diploma.
      a Fisher exact or Pearson chi-square test for categorical variables and t-test for continuous variables.
      b Cohen's d for continuous variables and Cramer's V for categorical variables.

      Depressive Symptoms and Complicated Grief

      Table 2 summarizes the CES-D 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 CES-D 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 CES-D change was of trivial magnitude (d = 0.08) even after adjusting for religious preference (d = 0.10) or patient hospice use (d = 0.07).
      Table 2Comparison of Change Over Time in Depression (CES-D) Scores, Early Versus Delayed Group
      Depression ScoreAll Caregivers (N = 44)Early Group (N = 19)Delayed Group (N = 25)Between-Group Difference
      MeanSDMeanSDMeanSDMeanSEPd
      Baseline CES-D13.28.811.28.214.89.2−3.62.70.19−0.41
      After care recipient death16.311.314.610.717.611.8−33.50.39−0.34
      Change from baseline CES-D
       Unadjusted310.93.49.52.612.10.73.40.830.08
       Adjusted for religious preference0.93.60.810.10
       Adjusted for hospice utilization0.63.60.880.07
      CES-D = Center for Epidemiological Study-Depression.
      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.
      Table 3 summarizes 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 CES-D 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).
      Table 3Comparison of Grief Scores After Patient Death, Early Versus Delayed Group
      GroupRaw Scores, Mean (SD)Between-Group Differences
      Crude EstimatesAdj. for Religious PreferenceAdjusted for Baseline CES-DAdj. for Patient Hospice Use
      Mean (SE)PdMean (SE)PdMean (SE)PdMean (SE)Pd
      Early22.7 (4.9)−2.2 (1.9)0.21−0.35−1.7 (2)0.40−0.27−1.21 (1.8)0.51−0.20−1.33 (2)0.51−0.21
      Delayed24.9 (6.9)
      CES-D = Center for Epidemiological Study–Depression.
      Between-group difference is early minus delayed. P is from general linear models. Cohen's d uses pooled SD.

      Discussion

      This trial represents the first attempt to test the effect of early palliative care telehealth support on bereaved family caregivers. We conducted an early vs. delayed “fast track” randomized controlled trial 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,
      • Dionne-Odom J.N.
      • Azuero A.
      • Lyons K.D.
      • 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.
      a terminal decline analysis of CG outcomes looking backward in time 36 weeks from care recipient death showed significantly lower depressive symptom scores in early compared to delayed group caregivers. Given that preloss caregiver distress has been associated with postloss outcomes,
      • Allen J.Y.
      • Haley W.E.
      • Small B.J.
      • Schonwetter R.S.
      • McMillan S.C.
      Bereavement among hospice caregivers of cancer patients one year following loss: predictors of grief, complicated grief, and symptoms of depression.
      • Garrido M.M.
      • Prigerson H.G.
      The end-of-life experience: modifiable predictors of caregivers' bereavement adjustment.
      • Kapari M.
      • Addington-Hall J.
      • Hotopf M.
      Risk factors for common mental disorder in caregiving and bereavement.
      • Ling S.F.
      • Chen M.L.
      • Li C.Y.
      • et al.
      Trajectory and influencing factors of depressive symptoms in family caregivers before and after the death of terminally ill patients with cancer.
      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 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.
      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.
      • Hebert R.S.
      • Prigerson H.G.
      • Schulz R.
      • Arnold R.M.
      Preparing caregivers for the death of a loved one: a theoretical framework and suggestions for future research.
      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 life-sustaining 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.
      • Hebert R.S.
      • Prigerson H.G.
      • Schulz R.
      • Arnold R.M.
      Preparing caregivers for the death of a loved one: a theoretical framework and suggestions for future research.
      Hence, future early palliative care for family caregivers might consider exploring nonthreatening ways to integrate end-of-life preparedness topics.
      Second, depressed mood and grief scores were collected eight to 12 weeks after the death of the care recipient. This time frame falls within the period when normal grief is expected, which is typically up to one year.
      • Schulz R.
      • Hebert R.
      • Boerner K.
      Bereavement after caregiving.
      Evidence suggests that significant differences between normal and prolonged grief are not evident until one to two years after an individual's death.
      • Ornstein K.A.
      • Aldridge M.D.
      • Garrido M.M.
      • et al.
      Association between hospice use and depressive symptoms in surviving spouses.
      • Abernethy A.P.
      • Currow D.C.
      • Fazekas B.S.
      • et al.
      Specialized palliative care services are associated with improved short- and long-term caregiver outcomes.
      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 after death. Hence, future studies of early palliative care for caregivers may need to protract the timeline of data collection for up to two years after a care recipient's death to capture meaningful differences. Although it will be important to control for CGs' use of bereavement services which are covered under Medicare's hospice benefit.
      Centers for Medicare and Medicaid Services
      Medicare benefit policy manual: Chapter 9: Coverage of hospice services under hospital insurance.
      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,
      • Ornstein K.A.
      • Aldridge M.D.
      • Garrido M.M.
      • et al.
      Association between hospice use and depressive symptoms in surviving spouses.
      • Abernethy A.P.
      • Currow D.C.
      • Fazekas B.S.
      • et al.
      Specialized palliative care services are associated with improved short- and long-term caregiver outcomes.
      • Higgins P.C.
      • Garrido M.M.
      • Prigerson H.G.
      Factors predicting bereaved caregiver perception of quality of care in the final week of life: implications for health care providers.
      avoidance of high intensity end-of-life care,
      • Wright A.A.
      • Zhang B.
      • Ray A.
      • et al.
      Associations between end-of-life discussions, patient mental health, medical care near death, and caregiver bereavement adjustment.
      • Wright A.A.
      • Keating N.L.
      • Balboni T.A.
      • et al.
      Place of death: correlations with quality of life of patients with cancer and predictors of bereaved caregivers' mental health.
      care recipient's quality of death and dying,
      • Wright A.A.
      • Zhang B.
      • Ray A.
      • et al.
      Associations between end-of-life discussions, patient mental health, medical care near death, and caregiver bereavement adjustment.
      and the leveraging of social support networks.
      • Allen J.Y.
      • Haley W.E.
      • Small B.J.
      • Schonwetter R.S.
      • McMillan S.C.
      Bereavement among hospice caregivers of cancer patients one year following loss: predictors of grief, complicated grief, and symptoms of depression.
      • Burton A.M.
      • Haley W.E.
      • Small B.J.
      • et al.
      Predictors of well-being in bereaved former hospice caregivers: the role of caregiving stressors, appraisals, and social resources.
      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 postloss bereavement services,
      • Lichtenthal W.G.
      • Nilsson M.
      • Kissane D.W.
      • et al.
      Underutilization of mental health services among bereaved caregivers with prolonged grief disorder.
      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.

      Limitations

      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 vs. 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 preloss may predict postloss 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 nonwhite caregivers may have higher rates of grief disorders.
      • Goldsmith B.
      • Morrison R.S.
      • Vanderwerker L.C.
      • Prigerson H.G.
      Elevated rates of prolonged grief disorder in African Americans.

      Conclusion

      Our study did not find statistical differences in depression and grief scores of family caregivers of decedents who received early vs. 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.

      Disclosures and Acknowledgments

      The parent study was supported by the National Institute of 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. Bakitas is a recipient of a National Palliative Care Research Center Junior Career Development Award. All authors declare no conflicts of interest.

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