The Project ENABLE II Randomized Controlled Trial to Improve Palliative Care for Patients with Advanced Cancer

Context—There are few randomized controlled trials of the effectiveness of palliative care. Objective—To determine the effect of a palliative care intervention on quality of life (QOL), symptom intensity, mood, and resource utilization. Design, Setting, and Participants—Randomized controlled trial (November 2003-May 2008) of 322 patients with advanced cancer and an identified caregiver in a rural, NCI-designated comprehensive cancer center (the Norris Cotton Cancer Center, Lebanon, NH) and affiliated outreach clinics and Veteran’s Affairs Medical Center (White River Junction, VT). Intervention—A multi-component, psycho-educational, palliative care intervention (Project ENABLE) conducted by an advanced practice nurse consisting of 4 weekly educational sessions and monthly follow-up until death or study completion. Financial Disclosures: None Reported Author Contributions: Dr. Bakitas had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: Bakitas, Seville, Ahles, Acquisition of data: Bakitas, Lyons, Hegel, Balan, Brokaw, Ahles, Analysis and interpretation of data: Bakitas, Lyons, Hegel, Brokaw, Hull, Li, Tosteson, Byock, Ahles Drafting of the manuscript: Bakitas, Lyons, Hegel, Brokaw, Hull, Tosteson, Ahles, Critical revision of the manuscript for important intellectual content: Bakitas, Lyons, Hegel, Balan, Brokaw, Seville, Hull, Li, Tosteson, Byock, Ahles Statistical analysis: Bakitas, Hull, Li, Tosteson, Obtained funding: Bakitas, Ahles Administrative, technical, or material support: Bakitas, Lyons, Hegel, Balan, Brokaw, Li, Tosteson, Byock Study supervision: Bakitas, Lyons, Seville, Tosteson, Ahles NIH Public Access Author Manuscript JAMA. Author manuscript; available in PMC 2013 May 20. Published in final edited form as: JAMA. 2009 August 19; 302(7): 741–749. doi:10.1001/jama.2009. 1198. N IH PA Athor M anscript N IH PA Athor M anscript N IH PA Athor M anscript Main Outcome Measures—(1) The Functional Assessment of Chronic Illness TherapyPalliative (range: 0 to 184; higher scores indicate better QOL), (2) Edmonton Symptom Assessment Scale (range: 0 to 900; higher scores indicate greater symptom intensity), (3) Center for Epidemiological Studies-Depression (range: 0 to 60; higher scores indicate more depressive symptoms), completed at baseline, 1 month and every 3 months until death or study completion, (4) days in hospital, intensive care unit (ICU), and emergency department visits recorded in the medical record. Results—322 participants with gastrointestinal (41%), lung (36%), genitourinary (12%), and breast (10%) cancer were randomized. Estimated treatment effects (intervention minus usual care) for all subjects were 4.6 (P = .02) for QOL, −27.8 (P = .06) for symptom intensity, and −1.8 (P = . 02) for depressed mood. Estimated average treatment effects in the sample of participants who died during the study were 8.6 (P = .02) for QOL, −24.2 (P = .24) for symptom intensity, and −2.7 (P = .03) for depressed mood. Days in hospital, intensive care unit, and emergency department visits were not different between groups. Conclusions—Compared to participants receiving usual oncology care, participants receiving a palliative care intervention addressing physical, psychosocial, and care coordination provided concurrently with oncology care had higher QOL and mood; comparisons of symptom intensity and days in hospital, ICU, and emergency department visits were not statistically significant. Trial Registration—clinicaltrials.gov Identifier: NCT00253383 Fifty percent of persons with cancer are not cured of their disease; 1 however, with improved treatment even patients with advanced disease may live for years. Providing palliative care concurrent with oncology treatment has been proposed to improve quality of life (QOL) for patients with advanced cancer. 2–8 The National Consensus Project Clinical Practice Guidelines for Quality Palliative Care recommends palliative care referral at the time of a life-threatening diagnosis and other core elements including: multidimensional assessment to identify, prevent, and alleviate suffering, interdisciplinary team evaluation and treatment in selected cases, effective communication skills and assistance with medical decisionmaking, skill in care of dying and bereaved, continuity of care, equitable access, and commitment to continued improvement and excellence.9 However the evidence supporting many of these recommendations is sparse.6 We translated effective strategies from the literature10, 11 and our prior work, including a 3 year palliative care demonstration project, Project ENABLE (Educate, Nurture, Advise, Before Life Ends), 12–17 into a palliative care multi-component intervention that was consistent with guideline9 essential core elements. Specifically, the intervention included a palliative care advanced practice nurse-administered, phone-based, intensive curriculum and on-going assessment and coaching in problem-solving, advance care planning, family and health care team communication strategies, symptom management and crisis prevention, and timely referral to palliative care and hospice resources. We hypothesized that patients exposed to this palliative care intervention soon after a new diagnosis of an advanced cancer would become informed, active participants in their care and would experience improved QOL, symptom relief, mood, and lower resource use over the illness including at the very end-of-life (EOL) compared to care as usual. Therefore the goals of this study were to determine whether a palliative care intervention, that was introduced at the time of a new diagnosis of an advanced stage cancer, could influence QOL, symptom intensity, mood, and resource utilization. We also examined caregiver outcomes (e.g. caregiver burden, perceptions of EOL care, and grief), but a full discussion of these results is beyond the scope of this paper. Bakitas et al. Page 2 JAMA. Author manuscript; available in PMC 2013 May 20. N IH PA Athor M anscript N IH PA Athor M anscript N IH PA Athor M anscript METHODS Study Design Project ENABLE II was a randomized controlled trial of a palliative care intervention compared to care as usual for persons newly diagnosed with advanced cancer. The primary endpoints were patient-reported QOL, symptom intensity, and resource utilization. Mood was a secondary outcome. Enrollment began in November 2003 and ended in May 2007. Data collection of patient-reported outcomes closed December 31, 2007; outcomes that could be monitored via chart review (e.g. resource utilization and vital status) were collected through May 1, 2008. The study protocol and data and safety monitoring plan were approved by the institutional review boards of the Norris Cotton Cancer Center (NCCC)/ Dartmouth College and the Veterans Administration Medical Center (VAMC), White River Junction, VT and registered in the National Cancer Institute’s (NCI) PDQ database (clinicaltrials.gov; Identifier: NCT00253383). All patient and caregiver participants signed a document confirming their informed consent.