PALLiON – PALLiative care Integrated in ONcology: study protocol for a Norwegian national cluster-randomized control trial with a complex intervention of early integration of palliative care
Authors: Hjermstad Marianne Jensen , Aass Nina , Andersen Sigve , Brunelli Cinzia , Dajani Olav , Garresori Herish , Hamre Hanne , Haukland Ellinor C. , Holmberg Mats , Jordal Frode , Krogstad Hilde , Lundeby Tonje , Løhre Erik Torbjørn , Mjåland Svein , Nordbø Arve , Paulsen Ørnulf , Schistad Staff Erik , Wester Torunn , Kaasa Stein , Loge Jon Håvard 
Published: April 2020

Abstract
Background
Several publications have addressed the need for a systematic integration of oncological care focused on the tumor and palliative care (PC) focused on the patient with cancer. The exponential increase in anticancer treatments and the high number of patients living longer with advanced disease have accentuated this. Internationally, there is now a persuasive argument that introducing PC early during anticancer treatment in patients with advanced disease has beneficial effects on symptoms, psychological distress, and survival.

Methods
This is a national cluster-randomized trial (C-RCT) in 12 Norwegian hospitals. The trial investigates effects of early, systematic integration of oncology and specialized PC in patients with advanced cancer in six intervention hospitals compared with conventional care in six. Hospitals are stratified on the size of local catchment areas before randomization. In the intervention hospitals, a three-part complex intervention will be implemented. The backbone of the intervention is the development and implementation of patient-centered care pathways that contain early, compulsory referral to PC and regular and systematic registrations of symptoms. An educational program must be completed before patient inclusion. A total of 680 patients with advanced cancer and one caregiver per patient are included when patients come for start of last line of chemotherapy, defined according to national treatment guidelines. Data registration, clinical variables, and patient- and caregiver-reported outcomes take place every 2 months for 1 year or until death. The primary outcome is use of chemotherapy in the last 3 months of life by comparing the proportion of patients who receive this in the intervention and control groups. Primary outcome is use of chemotherapy in the last 3 months before death, i.e. number of patients. Secondary outcomes are initiation, discontinuation and number of cycles, last 3 months of life, administration of other medical interventions in the last month of life, symptom burden, quality of life (QoL), satisfaction with information and follow-up, and caregiver health, QoL, and satisfaction with care.

Discussion
Results from this C-RCT will be used to raise the awareness about the positive outcomes of early provision of specialized palliative care using pathways for patients with advanced cancer receiving medical anticancer treatment. The long-term clinical objective is to integrate these patient-centered pathways in Norwegian cancer care. The specific focus on the patient and family and the organization of a predictable care trajectory is consistent with current Norwegian strategies for cancer care.

Trial registration
ClinicalTrials.gov, NCT03088202. Registered on 23 March 2017.