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Qol and Patients' Care

A randomized control trial of a psychosocial intervention for caregivers of allogeneic hematopoietic stem cell transplant patients: effects on distress

Abstract

Caregivers of patients receiving allogeneic hematopoietic stem cell transplants (allo-HSCT) serve a pivotal role in patient care but experience high stress, anxiety and depression as a result. We theorized that stress management adapted for allo-HSCT caregivers would reduce distress compared with treatment as usual (TAU). Of 267 consecutive caregivers of allo-HSCT patients approached, 148 (mean=53.5 years, 75.7% female) were randomized to either psychosocial intervention (i=74) or TAU (n=74). Eight one-on-one stress management sessions delivered across the 100-day post-transplant period focused on understanding stress, changing role(s) as caregiver, cognitive behavioral stress management, pacing respiration and identifying social support. Primary outcomes included perceived stress (psychological) and salivary cortisol awakening response (CAR) (physiological). Randomized groups were not statistically different at baseline. Mixed models analysis of covariance (intent-to-treat) showed that intervention was associated with significantly lower caregiver stress 3 months post transplant (mean=20.0, 95% confidence interval (95% CI)=17.9–22.0) compared with TAU (mean=23.0, 95% CI=21.0–25.0) with an effect size (ES) of 0.39 (P=0.039). Secondary psychological outcomes, including depression and anxiety, were significantly reduced with ESs of 0.46 and 0.66, respectively. Caregiver CAR did not differ from non-caregiving controls at baseline and was unchanged by intervention. Despite significant caregiving burden, this psychosocial intervention significantly mitigated distress in allo-HSCT caregivers.

Introduction

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is increasingly used for hematological malignancies.1 Allo-HSCT can be far more demanding than other cancer treatments for patients and families.2 Recipients require a full-time caregiver 24/7 for the first 100 days post transplant or longer. Post transplant, caregivers must monitor the recipient for numerous complications such as GvHD while providing social and practical support, for example, transportation.3 Programs often require that patients remain near the treating hospital thus requiring relocation so that emergent issues can be managed by staff trained in allo-HSCT. Multiple challenges take place while caregivers must additionally balance personal responsibilities (job and other family members). Thus allo-HSCT caregivers experience uncontrollable stressors associated with increased depression and anxiety, including a decline of their loved-one’s health, separation from their social support and uncertainty about patient prognoses.3, 4

Depression and anxiety are strikingly elevated in both cancer patients and their caregivers5 as well as in allo-HSCT caregivers.3 Allo-HSCT caregivers request help in meeting their patient needs, navigating care transitions and finding social and emotional support.6 The Surgeon General provided a prescription for caregivers for reducing stress, attending to depression and anxiety, identifying sources of support, maintaining physical health and receiving education regarding patient illness.7 In addition to the psychological toll of caregiving, there may be hidden biological costs to caring for cancer patients8 similar to those reported in other caregiver populations.9, 10 Although decrements in cancer caregiver well-being have been reported,11 physiological consequences in allo-HSCT caregivers have not been reported.

Psychosocial interventions targeting distress of cancer caregivers are needed,12 yet there are relatively few13 and trials of these interventions suffer from methodological problems.14 The present randomized clinical trial tested a psychosocial intervention for allo-HSCT caregiver’s unique needs that addressed the Surgeon General’s recommendations.7 We modified an efficacious cognitive-behavioral stress management intervention for cancer patients to meet the unique needs of allo-HSCT caregivers based on clinical experience, stakeholder input and a transactional stress and coping model.15, 16 We added a supplementary means for the participants to create a brief relaxing respite though the use of a biofeedback device approved for blood pressure reduction that paces and slows respiration,17 which we felt would facilitate relaxation. As the primary behavioral outcome, stress was assessed via the Perceived Stress Scale (PSS)18 owing to the scale measuring a sense of control. As the primary physiological outcome, the cortisol awakening response (CAR) represents the change, typically a rise, in salivary cortisol between awakening and 30 min later and is tied to anticipation of the upcoming day’s activities, high demands the preceding day or depression.19, 20 CAR is reduced in depression20, 21 as well as in caregivers22 and is negatively associated with the PSS.23 We hypothesized that the intervention would mitigate distress in caregivers such that, at the 3-month intervention completion point, caregivers randomized to stress management would have (1) reduced PSS, (2) increased CAR, (3) a decline in secondary psychological outcomes (for example, anxiety and depression) and (4) reduced markers of immune disturbance in comparison to those randomized to treatment as usual (TAU).

Methods

Eligibility criteria

Caregivers and their patients were recruited consecutively between November 2008 and April 2012 during pretransplant screening of all allo-HSCT patients (n=267) and their caregivers at a single site (Presbyterian St. Luke’s Medical Center, Denver, CO, USA). Caregiver inclusion criteria included caring for an allo-HSCT patient at least 50% of the time during the first 100 days post transplant, ability to speak/read English, 18 years and with telephone access; their patients must have received an allo-HSCT, be able to speak/read English and 18 years. Exclusion criteria included history of psychiatric illness (based on caregiver report) in the past 18 months (unrelated to patient illness) or diagnosis of medical condition or medications that might affect biomarkers. Caregivers and patients provided informed consent approved by the Colorado Multiple Institutional Review Board. Collecting demographics or information from those refusing consent was not permitted. Thirty-two non-caregiving controls were recruited from the university community to provide a comparison group for the biomarkers that did not have widely accepted norms (See Supplementary Information for description).

Study design

Consented participants (n=148 caregivers) were randomized with intent-to-treat by permuted block design to either PsychoEducation, Paced Respiration and Relaxation (PEPRR) or TAU as indicated in the CONSORT diagram24 in Figure 1 (also see additional comments in Footnote). The biostatistician (SKM-G) developed the randomization allocation, which was available only to the site coordinator (TLS).

Figure 1
figure1

CONSORT diagram24 representing subject flow and attrition through the study. From 267 patient–caregiver pairs approached, 149 were consented and 148 were randomized. Reasons for dropout are indicated as well as the numbers available for analysis. See Footnote.

Intervention

PEPRR consisted of eight semi-structured one-on-one sessions with a master’s level social worker beginning 16±10 days (Mean±SD) post transplant (transplantation day set as 0). Sessions were based on an intervention for cancer patients,16 which we modified to address allo-HSCT caregiver-specific needs. PEPRR utilized a Transactional Model of Stress and Coping, which predicts that those able to handle and adapt to the challenges of caregiving using tools taught in the program will show lower levels of stress.16 This approach has been the basis for numerous effective interventions and has been shown to improve coping and adaptation to stressful life events.25

Sessions began on average 2 weeks post transplant and continued weekly to complete all sessions before the 3-month assessment. Sessions lasted 60–75 min, were manualized and followed the same order with some flexibility in content as needed. To minimize caregiver burden, all sessions took place at the hospital when caregivers were visiting their patients during hospitalization or at the clinic during times when caregivers brought patients to appointments.

Sessions included in order: (1) program overview, instructions for biofeedback device (see below) and introduction to stress management; (2) impact of stress on physical and emotional health; (3) how thoughts and emotions lead to stress; (4) coping skills training; (5) management of fatigue, sleep and other health behaviors; (6) addressing lack of control, uncertainty and fear; (7) improving partner communication strategies and adapting to changing role(s); and (8) effective utilization of social support. A workbook including session topics was provided for use during sessions, with homework recommended but not assessed. Interventionist fidelity (>90%) to the manual was randomly checked by video for 20% of sessions. Details of this intervention are the subject of a subsequent report.

Caregivers randomized to PEPRR also received a biofeedback device, RESPeRATE (InterCure, Fort Luc, NJ, USA), with established efficacy for reducing hypertension.17 The RESPeRATE entrained respiration to specific tones, which increased in duration to slow and deepen respiration. Caregivers were asked to use this device for 15 min at least 4–5 times/week to facilitate relaxation. The device recorded participant’s use, and these data were uploaded to address adherence. Of the research participants randomized to PEPRR, only 12 caregivers (16%) showed consistent (weekly) use for the device throughout the intervention phase, with overall usage by others declining by the third week after beginning PEPRR. Adherence and satisfaction with this device was mixed and will be reported elsewhere.

All caregivers were encouraged to avail themselves of programs at the transplant clinic, including individual counseling, support groups and education classes. These voluntary programs focused on caregiving stress, taking care of oneself, identifying important community resources and specific problems raised by participants. Support in navigating the complex HSCT program (for example, arranging local housing following patient hospital discharge, insurance, diet restrictions and so on) was also available. Programs were free of charge to anyone who wanted assistance (family and/or caregivers) and were attended at least once by 16.1% of the TAU group and 7.2% of the PEPRR group during the 100-day post-transplant period. TAU caregivers received follow-up calls from research staff to sustain study retention, set up return appointments and encourage questionnaire completion.

Psychological outcomes

Questionnaires were completed prior to study randomization and patient transplant (M=−1 day relative to transplant which was treated as day zero, SD=10) reflecting baseline, and at Month 1 (M=37 days post transplant, SD=10) and Month 3 (M=93 days post transplant, SD=14). The Month 1 assessment was typically completed after 1–2 intervention sessions and the Month 3 assessment always occurred after completion of the full program. Instruments were anchored to the preceding month and included the primary psychological outcome, the 14-item PSS,18 a validated self-report of control over stress which we have shown to be elevated in allo-HSCT caregivers3 and other caregivers.26 Secondary psychological outcomes included depression (Center for Epidemiological Studies Depression scale (CESD) score)27 and state anxiety (State-Trait Anxiety Inventory (STAI) score),28 which show significant elevation in cancer patients and caregivers.5 The Caregiver Reaction Assessment (CRA)29 assessed post-transplant changes in burden. Total mood disturbance (Profile of Mood States (POMS-TMD)),30 sleep (Pittsburgh Sleep Quality Inventory (PSQI)),31 mental and physical health (Short Form Health Survey Version 2, (SF-36) summary scales)32 and trauma (Impact of Events Scale (IES))33 were evaluated. All instruments have excellent validity and reliability. Of caregivers enrolled at baseline and those remaining at 1 and 3 month collection times, 99, 93 and 90% returned their questionnaires, respectively. As the focus was on caregivers and to minimize burden, patients completed only demographic questionnaires and SF-36 at times corresponding to caregivers.

A caregiver composite distress score (CG-Distress) was created by principal component analysis (PCA) on five affective variables (PSS, POMS-TMD, CESD, STAI and IES) at each time and a composite measure of caregiver physical 'well-being' (CG-Well-being) summed standardized scores of CG-Distress, PSQI, CRA and SF-36 Physical score as described elsewhere.3

Physiological outcomes

The CAR19 was the primary physiological outcome. A comprehensive panel of physiological markers (Supplementary Information) reflecting neuroendocrine status (diurnal salivary cortisol and dehydroepiandrostenedione) and immune parameters (natural cytotoxicity and inflammation) was collected as the secondary physiological outcomes from caregivers at the time of questionnaire completion.

Statistical analysis

To allow sufficient (90%) statistical power based on existing literature34 to detect small-to-medium effect sizes (ES), 170 pairs of caregivers and their corresponding patients were initially targeted. Funding cut-backs lowered this to 148 caregivers with their corresponding patients, which still provided power to detect ESs >0.27, after allowing for planned attrition. Intent-to-treat analyses (including all randomized participants after removing one screen failure) used SPSS version 20.0 (IBM Corporation, Amock, NY, USA) and SAS version 9.3 (SAS Institute Inc, Cary, NC, USA) software. Baseline differences between PEPRR and TAU caregivers and patients on demographic and other key variables were assessed by chi-square and independent t-tests or non-parametric Mann–Whitney U and Fisher’s exact tests when data distributions were non-normal. Patient's and caregiver age was compared by paired t-test between TAU and PEPRR. Analyses of variance compared biomarker levels at baseline among PEPRR and TAU caregivers and non-caregiving controls. Patterns of missing data were evaluated with chi-square tests comparing PEPRR and TAU groups at each time.

Caregiver outcomes were analyzed by mixed models analyses of covariance using Satterthwaite approximation for degrees of freedom providing group estimates at each month with fixed effects of intervention (PEPRR, TAU), month (baseline, Month 1 and Month 3) and their interaction while co-varying for caregiver age, because older age is associated with greater resilience in response to challenge.35 Repeated measures were assumed to have unstructured covariance.36 To provide some protection for multiple comparisons,37 group effects were tested at Month 3 only if the omnibus test of the global null hypothesis (that is, means for each group by month combination were equal) was rejected. ESs at Month 3 were calculated as (MTAU−MPEPRR)/SD, where MTAU and MPEPRR represents adjusted means of TAU and PEPRR, respectively, at month 3 for outcomes and SD was computed as the square root of estimated variance of each outcome at Month 3. Comparisons utilized a two-tailed, 0.05 significance level. Outcomes collected at 6 and 12 months are not included here but are the subject of an ongoing secondary analysis.

Results

Sample characteristics

Neither caregiver nor patient characteristics differed by randomization group. Tests evaluating continuous outcomes indicated that variances were similar between groups. Caregivers averaged 53.5 years (range 21–80) and were predominately female (75.7%)/Caucasian (89.9%) consistent with caregiver demographics.38 During this recruiting period, the percentage of all males presenting for allo-HSCT at this clinic was 65.3%, and thus the consented sample was representative of this clinic’s patients. Fully employed caregivers declined from 48% pretransplant to 23.7% post transplant. Complete details are provided in Table 1.

Table 1 Baseline characteristics of caregivers and patients

Half of patients (54.1%) were diagnosed with leukemia. Patients’ illness demographics were similar across groups (Table 1) with one exception: time to neutrophil engraftment (ANC>500/μL for 3 consecutive days39) was 2.5 days earlier for TAU compared with PEPRR (P=0.04). As engraftment and first intervention session occurred around the same day (+16 days), this was unlikely related to group assignment. During the 100 days post transplant, a total of 11 patients died representing 6 in TAU and 5 in PEPRR. Although encouraged to continue completing questionnaires and the intervention, only two caregivers from PEPRR returned questionnaires while none completed the intervention. However, all available caregiver data are included in the intent-to-treat design.

Prior to randomization, perceived stress (PSS) exceeded population norms of 19.2 for this age range.40 Scores on the CESD for individual caregivers approached and occasionally exceeded published depression cutoffs of 16 (Table 2).27 Scores >16 triggered a clinical follow-up by staff regardless of group assignment (Table 2). Elevated anxiety and poor sleep based on national norms were also noted in caregivers prior to intervention. There was no difference between groups at baseline in psychological measures based on randomization as indicated in Table 2.

Table 2 Baseline assessment means and 95% CIs for caregivers

Efficacy outcomes

Chi-square tests confirmed no differences between groups in the pattern of missing data. Of the 148 participants, 18.9% and 17.9% were missing data, respectively, on primary psychological and physiological outcomes across months. Caregivers typically found the intervention acceptable, with 70% completing all eight sessions. Reasons for drop-out included inadequate time (n=10), patient becoming gravely ill (n=2) or patient death (n=11) and did not differ by group. Table 3 presents model estimates (mean, 95% confidence interval) by month for PEPRR and TAU for primary and secondary psychological outcomes based on analyses of covariance of outcomes by group, month and interaction. Caregiver age was a significant covariate (Ps<0.05); younger caregivers reported greater distress as predicted.35 All main effects and interaction test results are reported in Table 3 regardless of significance as well as post hoc comparisons and estimated ESs for the 3-month comparisons only when interactions were significant.

Table 3 Estimates and test results from mixed model analyses of covariance for primary and secondary psychological outcomes and composite scores

A reliable pattern of reduced distress at Month 3 across psychological measures was noted for participants receiving PEPRR (Table 3). Figure 2 shows model predictions for the primary outcome, PSS. At 3 months post transplant, PEPRR caregivers were significantly lower than TAU for PSS (t(117)=2.09; P=0.039), with an ES of 0.39 which declined below population norms at 3 months, whereas PSS in TAU increased. Similarly, anxiety and depression were significantly lower in PEPRR compared with TAU with ESs of 0.66 and 0.46, respectively. This overall pattern held for total mood disturbance (POMS-TMD) as well as the composite distress score. Graphic model predictions with confidence intervals for anxiety (Figure 3) and depression (Figure 4) are provided. Consistency across multiple psychological domains supports that PEPRR is efficacious in mitigating distress in spite of increasing caregiver burden (CRA) reflecting rising demand post transplant.

Figure 2
figure2

Primary psychological outcome of PSS.18 Model predictions at baseline and Months 1 and 3 post transplant for TAU (open symbols, broken line) and the intervention, PEPRR, (filled symbols, solid line) with 95% CI at each collection time are shown. The horizontal broken line indicates the population mean in a healthy comparably aged population.40

Figure 3
figure3

Secondary psychological outcome of anxiety based on the Spielberger State Anxiety Score.28 Model predictions at baseline and Months 1 and 3 posttransplant for TAU (open symbols, broken line) and the intervention, PEPRR, (filled symbols, solid line) with 95% CI at each collection time are shown for this secondary psychological outcome. The horizontal broken line indicates the population mean in a healthy comparably aged population.28

Figure 4
figure4

Secondary psychological outcome of depression based on the CESD.27 Model predictions at baseline and Months 1 and 3 posttransplant for TAU (open symbols, broken line) and the intervention, PEPRR, (filled symbols, solid line) with 95% CI at each collection time are shown for this secondary psychological outcome. The horizontal broken line indicates the clinical cutoff score for depression risk.27

Unlike reports of other caregiver populations,9, 10 caregivers’ biomarkers at baseline did not differ from non-caregiving controls (Supplementary Table SA). CAR and other caregivers’ biomarkers did not change as a function of intervention nor with regard to time (Supplementary Table SB). Consequently, detailed descriptions of methods, analysis and results of primary and secondary physiological outcomes are provided as Supplementary Information.

Discussion

Allo-HSCT caregivers are highly distressed during the transplant process. The present observations are significant, because they indicate that distress commonly reported in caregivers3, 41 can be mitigated by a semi-structured psychosocial intervention tailored to meet the needs of allo-HSCT caregivers. Comparable reductions in distress have also been reported for Alzheimer’s patient caregivers receiving a similar intervention.42

Visual inspection suggests a trend for a decline in caregiver distress in both groups 1 month post transplant (Table 3) during patient hospitalization. At discharge 2–5 weeks post transplant, allo-HSCT caregivers assume full burden of care. Increasing caregiver burden (see CRA, Table 3) post transplant indicated the realities of an allo-HSCT, for example, uncertainties, sudden changes in patient’s physical condition and, most of all, increased caregiver demands following discharge. Despite rising caregiver burden, the ability to attenuate key psychological markers through eight sessions of stress management training is significant in this challenging situation.

Reduced distress in caregivers are consistent with patient populations receiving a similar intervention. For example, breast cancer patients receiving this intervention showed reduced depression.25 Although HIV+ males receiving a similar intervention revealed changes in plasma cortisol and dehydroepiandrostenedione,43 the present study noted no changes. This difference may be due to the physiological disruption present in HIV+ participants unlike the present caregivers (see Supplementary Information) in spite of significant psychological distress. Caregiver’s self-reported physical health score also remained close to population norms32 throughout the first 100 days (see Table 3), suggesting participants were relatively healthy.

A lack of physiological disruption as measured by the CAR and other secondary biomarkers differs from reports of physiological disturbance in caregivers of other patient populations.8, 9, 10 This was unanticipated in light of signficant psychological distress. Reasons for this discrepancy may include duration of allo-HSCT caregiving, patient prognosis and/or a bias to select only healthy caregivers for allo-HSCT patients. Interestingly, duration of caregiving is rarely reported in caregiver research but when reported it often exceeds 4 years.4 For the present group, the average time since cancer diagnosis, and importantly not necessarily caregiving per se, was 26 months; full caregiving responsibilities may not begin until the patient is discharged from the hospital following transplant. It is likely the impact of the cancer diagnosis and/or caregiving stress on physiological functioning is not measurable during the current timeframe. Longitudinal studies of these caregivers are needed to address this question more fully and are presently underway.

Second, allo-HSCT is a relatively efficacious treatment option,1 with up to 70% long-term survival compared with the experiences of caring for progressive decline in cognitively impaired persons.44 Thus shorter caregiving duration and better prognosis for allo-HSCT patients may have contributed to the lack of differences in biomarkers in allo-HSCT caregivers compared with other caregiver groups. Longer-term caregiving represents a chronic stressor affecting allostatic load wherein regulation of the hypothalamic–pituitary–adrenal axis and other stress responsive systems are disrupted.45

Poor sleep is associated with increased inflammation.46 However self-reported caregiver sleep31 and inflammatory markers were not affected by PEPRR, which was also unrelated to the caregiver’s symptom experience in the immediate post-transplant period. That is, the composite physical well-being score from the SF-36 was stable and within population norms.32 We have observed a similar pattern of good physical health in caregivers of Phase 1 trial cancers patients in the presence of considerable psychological distress.41 Medically, healthy caregivers are necessary given the rigor of the allo-HSCT procedure. Caregivers undergo significant prescreening before approval raising a potential selection bias against disrupted physiological regulation.

The median 100-day cost for allo-HSCT is $203 206 (USD) covering all aspects of the treatment.47 Caregiver intervention delivered by a social worker represented about 12–14 care hours. Mean pay for a master’s level social worker is approximately $24.28/h (May 2011, United States Bureau of Labor Statistics), representing <$350. The biofeedback devices cost <$150 bringing the cost of this intervention to $500. An allogeneic transplant is impossible without a caregiver 24/7. This comes at a cost to the caregiver in terms of mental health consequences as well as lost wages. Similar coping training for Alzheimer’s caregivers was cost neutral and associated with improved caregiver quality of life.48 The burden of caregiving for a loved one with cancer clearly points to a need for a cost–benefit analysis of providing cancer caregiver intervention(s) as part of the standard of care for families experiencing an allo-HSCT. A future cost effectiveness analysis of the present approach is definitely warranted.

Several limitations were present. First, the demographics of this particular clinic limited the diversity of caregivers creating a relatively homogenous group as well as a relatively small sample size. Second, there was a single interventionist. Third, we did not address differences in the caregiver–patient dyadic relationships. Fourth, we did not assess patient's quality of life based on commonly accepted approaches. Finally, caregiver’s personal health and well-being may affect the quality of support caregivers provide their patients in significant and poorly understood ways, which we did not assess. These limitations are targets of a multisite trial currently underway utilizing this intervention.

In summary, in spite of increasing caregiver burden posttransplant, PEPRR proved to be efficacious in mitigating the corresponding psychological distress in allo-HSCT caregivers. Recuing distress has the potential benefit of improving caregiver well-being and thus may permit the caregiver to be more effective in fulfilling their caregiver task(s).

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Acknowledgements

The execution of this study was supported in full by the National Institutes of Health grant 1R01CA126971 while final preparation of this manuscript was supported partly by Patient Centered Outcomes Institute Contract CE-1304-6208. We are particularly grateful to the caregivers who not only give their time to the care of their patients but also accepted the added burden of participating in this study. We are also thankful to Dr Susan Lutgendorf in the development of the intervention. We also thank Africa Armendariz, Danielle Glenn, Robert Hill, Rita Ouseph and Maribel Perea for their contributions and support during the execution of this study.

Author Contributions

Dr Laudenslager and Dr Mikulich-Gilbertson had full access to all the data in blinded format and are responsible for its integrity, reporting to the DSMB and the accuracy of data analysis. Study concept and design: Kilbourn, Laudenslager, Mikulich-Gilbertson and Simoneau. Acquisition of data: Benitez, Natvig, Philips and Spradley. Analysis and interpretation of data: Laudenslager, Mikulich-Gilbertson, Kilbourn and McSweeney, Natvig, and Simoneau. Initial drafting of the manuscript: Laudenslager. Critical revision of the manuscript for important intellectual content: Benitez, Kilbourn, Laudenslager, McSweeney, Mikulich-Gilbertson, Philips, Simoneau and Spradley. Statistical analysis: Mikulich-Gilbertson. Obtained funding: Laudenslager and Simoneau. Administrative, technical or material support: Benitez, Laudenslager, McSweeney, Natvig and Simoneau.

Disclaimer

The funding sources had no role in the design and conduct of the study; in the collection, analysis and interpretation of the data; or in the preparation, review or approval of the manuscript.

Footnote

Regarding consistency of the information reported to ClinicalTrials.gov, a contract agency for the Protocol Coordinator for NCI's PDQ Cancer Clinical Trials Registry, Office of Communications and Education National Cancer Institute initially entered the trial information at ClinicalTrials.Gov using our approved IRB submission. We assumed this was the process for this new (2008) federal reporting requirement and believed we had performed our due diligence. We received a confirmation that the trial was recorded on 23 February 2009 although we had received a registration number prior to that date. We began recruitment only after that number was filed and we received approval by our IRB. When the responsibility for maintaining this information was shifted from NCI to the study site 3 years later, we realized that many errors were made by the contracting agency in the description of our protocol and we did our best to correct the errors. The first author takes full responsibility for errors in reporting at ClinicalTrials.gov. However, from a CONSORT perspective, a clear analysis plan was in place prior to breaking the blind. Although inadvertently omitted from the reported plan, we had planned two analysis stages: q(1) an intent-to-treat analysis of the 3-month intervention once all subjects had completed that assessment and the blind was broken and (2) a second analysis that would commence once all subjects completed their final 1-year evaluation time point.

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Correspondence to M L Laudenslager.

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A portion of this study was presented as a paper at the 10th Annual Meeting of the American Psychosocial Oncology Society, Huntington Beach, CA, USA by Simoneau TL, Kilbourn K, Mikulich-Gilbertson SK, Spradley J, Natvig C, McSweeney P, Laudenslager ML (February 2013). ‘Efficacy of a stress management intervention for allogeneic transplant caregivers’ and as a portion of the Norman Cousins Lectureship to the Psychoneuroimmunology Research Society, Stockholm Sweden by Mark L. Laudenslager, (June 2013), ‘Anatomy of an Illness: Control from a Caregiver’s perspective'.

Supplementary Information accompanies this paper on Bone Marrow Transplantation website

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Laudenslager, M., Simoneau, T., Kilbourn, K. et al. A randomized control trial of a psychosocial intervention for caregivers of allogeneic hematopoietic stem cell transplant patients: effects on distress. Bone Marrow Transplant 50, 1110–1118 (2015). https://doi.org/10.1038/bmt.2015.104

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