Dignity Therapy Led by Nurses or Chaplains for Elderly Cancer Palliative Care Outpatients: Protocol for a Randomized Controlled Trial

Background Our goal is to improve psychosocial and spiritual care outcomes for elderly patients with cancer by optimizing an intervention focused on dignity conservation tasks such as settling relationships, sharing words of love, and preparing a legacy document. These tasks are central needs for elderly patients with cancer. Dignity therapy (DT) has clear feasibility but inconsistent efficacy. DT could be led by nurses or chaplains, the 2 disciplines within palliative care that may be most available to provide this intervention; however, it remains unclear how best it can work in real-life settings. Objective We propose a randomized clinical trial whose aims are to (1) compare groups receiving usual palliative care for elderly patients with cancer or usual palliative care with DT for effects on (a) patient outcomes (dignity impact, existential tasks, and cancer prognosis awareness); and (b) processes of delivering palliative spiritual care services (satisfaction and unmet spiritual needs); and (2) explore the influence of physical symptoms and spiritual distress on the outcome effects (dignity impact and existential tasks) of usual palliative care and nurse- or chaplain-led DT. We hypothesize that, controlling for pretest scores, each of the DT groups will have higher scores on the dignity impact and existential task measures than the usual care group; each of the DT groups will have better peaceful awareness and treatment preference more consistent with their cancer prognosis than the usual care group. We also hypothesize that physical symptoms and spiritual distress will significantly affect intervention effects. Methods We are conducting a 3-arm, pre- and posttest, randomized, controlled 4-step, stepped-wedge design to compare the effects of usual outpatient palliative care and usual outpatient palliative care along with either nurse- or chaplain-led DT on patient outcomes (dignity impact, existential tasks, and cancer prognosis awareness). We will include 560 elderly patients with cancer from 6 outpatient palliative care services across the United States. Using multilevel analysis with site, provider (nurse, chaplain), and time (step) included in the model, we will compare usual care and DT groups for effects on patient outcomes and spiritual care processes and determine the moderating effects of physical symptoms and spiritual distress. Results The funding was obtained in 2016, with participant enrollment starting in 2017. Results are expected in 2021. Conclusions This rigorous trial of DT will constitute a landmark step in palliative care and spiritual health services research for elderly cancer patients. Trial Registration ClinicalTrials.gov NCT03209440; https://clinicaltrials.gov/ct2/show/NCT03209440 International Registered Report Identifier (IRRID) DERR1-10.2196/12213

ZCA1 RPRB-M (J1) EMANUEL, L; FITCHETT, G; et al PUBLIC HEALTH RELEVANCE: Our goal is to improve psychosocial and spiritual care outcomes for elderly patients with cancer by optimizing a nurse-led or chaplain-led intervention focused on dignity conservation tasks such as settling relationships, sharing words of love, and preparing a legacy manuscript. This dignity therapy is known to be well accepted by patients in studies, but it is not widely used and it remains unclear how best it can work in real life settings. We propose a rigorous study to evaluate the effects of usual outpatient palliative care compared with added nurse-led or chaplain-led dignity therapy, to assess dignity therapy's impact on patient dignity, preparation for death/life completion tasks, and spiritual well-being; rigorous evaluation of dignity therapy in real care settings would constitute a landmark step in health services research for elderly patients with cancer.

CRITIQUES:
The written critiques of individual reviewers are provided in essentially unedited form in this section. Please note that these critiques and criterion scores were prepared prior to the meeting and may not have been revised subsequent to the discussions at the review meeting. The "Resume and Summary of Discussion" section summarizes the final opinions of the review committee.

CRITIQUE 1:
Significance: 2 Investigator(s): 1 Innovation: 2 Approach: 3 Environment: 1 Overall Impact: The proposed study is a randomized trial of usual outpatient palliative care vs usual outpatient palliative care with either nurse-led or chaplain-led dignity therapy on patient outcomes (Primary: dignity impact; Secondary: existential tasks and cancer prognosis awareness). This is an important yet understudied area of gero-oncology palliative carethis study will advance the field through a rigorous test of a manualized program. Engagement of Dr. Chochinov [developer of the intervention] is an important strength. The research team is interdisciplinary with investigators who have worked together productively. While there are challenges in conducting a study across six sites, the team has the experience and expertise to do so successfully. The approach is well thought out and uses a novel step-wedge design to maximize what can be learned from a potentially difficult population to study. Many of the issues raised in the prior review have been clarified in this resubmission. A couple of minor weaknesses remain in terms of the approach but are easily addressed and do not significantly dampen enthusiasm for the project. Potential impact, overall, is expected to be high.

Significance: Strengths
The proposed study addresses a much understudied areaspiritual care interventions for elderly cancer patientsusing Dignity Therapy as the intervention. There is a major gap in the area of palliative care interventions, especially spiritual care interventions, for this population.
The findings from the proposed study will advance the field of gero-oncology palliative care by providing a manualized intervention that could be widely translated into clinical practice settings.

Weaknesses
None noted.

Investigator(s): Strengths
The Multiple Principal Investigator leadership team is an outstanding interdisciplinary group, and the plan is clearly articulated. Dr. Chochinov, who developed the Dignity Therapy intervention program, including the manual, is a consultant on the project. This is an important strength of the research team.

Weaknesses
None noted.

Innovation: Strengths
Use of the stepped wedge design, which requires few participants, is innovative.
Framing the Dignity Therapy intervention as a spiritual intervention and focusing on spiritual outcomes as a primary outcome is innovative.

Weaknesses
None noted.

Approach: Strengths
Clearly described conceptual framework that is linked to the aims and to the overall study design.
Well written description of the clinical trial of the intervention. Quota sampling with 50% demonstrating "low" spiritual distress and 50% demonstrating "high" distress at each site/step ensures variability. Use of six different sites from different geographic regions enhances generalizability. The intervention is manualized and has demonstrated feasibility. Plan to explore potential moderators as a precursor to future studies is a strength.

Weaknesses
Unclear if those who fall somewhere between "low" and "high" in spiritual distress will be included; if excluded, there needs to be a clear rationale for not including those persons, especially in a potentially difficult group to engage in the study.
Still not clear how variations in the type of usual palliative care that is delivered in each of the six sites will be documented.

Environment: Strengths
Primary sites which will support the multi-site coordination efforts are outstanding. The six different clinical sites from different geographic regions are all excellent in terms of the clinical and research resources to support the project.

Weaknesses
None noted.

Resubmission:
Very responsive to prior critiques.
Resource Sharing Plans: Acceptable.
Budget and Period of Support: Recommend as requested.

CRITIQUE 2:
Significance: 3 Investigator(s): 1 Innovation: 3 Approach: 3 Environment: 2 Overall Impact: This resubmitted application describes a 3-arm, pre/post-test, randomized controlled 4-step wedge designed efficacy trial that will compare the effects of usual outpatient palliative care and usual outpatient palliative care with either nurse-led or chaplain-led Dignity Therapy (DT) on pilot-tested dignity impact, existential tasks, and cancer prognosis awareness. Concerns raised in the prior review of this application are generally addressed. Strengths of the application include the innovation, investigators, and environments. Some of the weaknesses identified in the prior review of the application remain of concern, such as whether provider delivery of dignity therapy is the main issue, especially given the lack of availability of board certified chaplains. Also, whether the outcome measures of Aim 1 will be adequately sensitive to the intervention"s effect remains unclear. There is some concern that more preliminary data may be needed before conducting this large, multi-site randomized controlled trial. Overall, if successful, the project is expected to have a moderately high impact.

Significance: Strengths
Application addresses the need to advance the understudied scientific area of geriatric palliative care for cancer patients.
The study focuses on a spiritual intervention.
The study includes older adults in the home setting, not restricted to hospice settings.

Weaknesses
There is uncertainty as to whether Aim 1 outcome measures will be adequately sensitive to the intervention"s effect.

Investigator(s): Strengths
Principle Investigator has extensive knowledge and experience in conducting RCTs. The Principal Investigator has assembled an excellent team and six site directors to conduct this study; many have worked together on research and publications. Dr. Chochinov, developer of the Dignity Therapy program, is a consultant on the study, which is an important strength.

Innovation: Strengths
A rigorous trial of Dignity Therapy will be a landmark step in palliative care and spiritual health services research. Use of the stepped-wedge design has advantages for recruitment and smaller sample size in a palliative care context. Application proposes a novel method to impact spiritual care in a 4-6 week period.

Weaknesses
There is minor concern regarding capacity issues for delivery of this intervention by nurses and board-certified chaplains.

Approach: Strengths
The approach section has been modified in response to several concerns raised in the prior review of this application. Use of a manualized nurse-led or chaplain-led intervention to insure rigor at each site and with numerous research team members is a strength.

Weaknesses
The issue of sample variability on spiritual distress and how it impacts delivery of Dignity Therapy intervention is not sufficiently addressed. The revised accrual and withdrawal rates are more realistic but there is some concern that both estimates remain somewhat optimistic. There is remaining concern that additional preliminary data may be needed.

Environment: Strengths
The team has a history of excellence in palliative care research in elderly cancer patients. The study will use six strong research and clinical environments to conduct the study.

Weaknesses
Issue of coordination is a concern among sites where investigators are simultaneously recruiting palliative care patients for other studies.

Biohazards: Not Applicable (No Biohazards).
Resubmission: Responsive to many of the prior concerns.
Resource Sharing Plans: Acceptable. Overall Impact: The plan is to study an intervention delivered by nurses or chaplains to address patients" spiritual needs at end of life. The intervention is well-described, and, if successful, would have the potential to ameliorate suffering of both the patients and their survivors. The investigators are experienced and have worked together, and present preliminary data that the intervention is feasible and could have a positive effect on patients" spiritual outcomes. Studying patients" spiritual endpoints as a primary outcome in and of itself is quite innovative. The design of the study is well thought out. However, potential impact is somewhat tempered by concerns about the complexity of the study, the multiplicity of endpoints, the potential effect of informative missingness on the results, and variation in the delivery of the intervention.

Significance: Strengths
A systematic application of an intervention specifically designed to address patients" spiritual needs at end-of-life could have a significant positive effect both on those patients and on their survivors.

Weaknesses
The design of the experiment is complex, there is going to be significant variation in the delivery of the intervention both between and within sites and a large number of endpoints will be assessed. There is a concern that the results will therefore be a mixture of a large number of positive and negative results and the overall conclusion will be that more research is needed.

Investigator(s): Strengths
The Principal Investigator is highly experienced and well qualified to conduct the study. She is the Principal Investigator of an active PCORI grant and a recently completed R01. The research team includes experienced practitioners in palliative and end-of-life care, ministry, epidemiology, and psychiatry.

Weaknesses
There is minor concern regarding the minimal publication and/or grant support record of some of the co-investigators.

Innovation: Strengths
The use of Dignity Therapy and its analysis via a sophisticated RCT is quite innovative. Employing spiritual outcomes ("endpoints" may be more appropriate) as assessments of the effect of DT is novel.

Weaknesses
None noted.

Strengths
The step-wedge design is appropriate to the study. The power analysis is not overwhelmingly rigorous, but acceptable. There will almost certainly be inadequate power to compare nurse-and chaplain-led interventions, but that comparison should not be a focus of the study.

Weaknesses
The effect of the exclusion criteria on the analysis is unclear, as they are complicated and appear related to the study endpoints. There is concern that power analyses related to effect sizes, when the meaning of the effect size is unclear, are of little value. The nature of missingness could have a profound effect on the interpretation of the results from Aim 1, but this is not sufficiently addressed.
There is insufficient assessment of the quality of the intervention in the planned analysis of the results. Patients will be clustered not only within sites but within nurses and chaplains within sites, but the analysis model does not adequately deal with this.
There are a great many endpoints being studied and plans for multiplicity of testing are not adequately presented. Aim 2 analysis plan is superficial. It is unclear whether the effect on survivors will be adequately studied.

Environment: Strengths
The study is being conducted at major research institutions that should have the patient resources to recruit to the study. Conducting an efficacy, as opposed to an effectiveness study, is not a concern. Weaknesses The Environment section does not adequately describe the data collection and management systems to be implemented for this complex, multi-site study. Resubmission: Responsive to prior concerns.

Resource Sharing Plans: Acceptable.
Budget and Period of Support: Recommend as requested.