Article Text

Early palliative care in newly diagnosed cancer in Ethiopia: feasibility randomised controlled trial and cost analysis
1. Eleanor Anderson Reid1,2,
2. Ephrem Abathun3,
3. Jilcha Diribi4,
4. Yoseph Mamo3,
5. Tigeneh Wondemagegnhu4,
6. Peter Hall5,
7. Marie Fallon6 and
8. Liz Grant7
1. 1Department of Emergency Medicine, Yale School of Medicine, New Haven, Connecticut, USA
2. 2Usher Institute, Center for Population Health Sciences, University of Edinburgh Division of Medical and Radiological Sciences, Edinburgh, UK
3. 3Hospice Ethiopia, Addis Ababa, Ethiopia
4. 4Department of Oncology, Addis Ababa College of Health Sciences School of Medicine, Addis Ababa, Ethiopia
5. 5Department of Oncology, University of Edinburgh Western General Hospital, Edinburgh, UK
6. 6Palliative Medicine, University of Edinburgh Western General Hospital, Edinburgh, UK
7. 7Programme Director Global Health: Non Communicable Diseases, University of Edinburgh Global Health Academy, Edinburgh, UK
1. Correspondence to Dr Eleanor Anderson Reid, Department of Emergency Medicine, Yale School of Medicine, New Haven, CT 06519, USA; eleanor.reid{at}yale.edu

## Abstract

Objectives Globally, cancer deaths are rising. In low-and-middle-income countries, there is a gap in access to palliative care (PC). We designed a feasibility trial to study the initiation of early PC in patients with cancer in Addis Ababa, Ethiopia.

Methods A randomised controlled trial (RCT) of standard cancer care versus standard cancer care plus in-home PC was conducted. Follow-up was at 8 and 12 weeks. Primary outcomes were: (1) feasibility, (2) patient-reported PC outcomes (African Palliative Care Association Palliative Outcome Scale (APCA POS)), and (3) costs.

Results Of 95 adults randomised (mean age 49.5 years; 66% female), 27 completed 3 study visits. Of these, 89% had stage III or IV disease. Recruitment was feasible, but attrition was high. APCA POS use was feasible, with significant within-arm improvements: 24% versus 18% reduction (p<0.0002, p<0.0025) in PC versus standard care, respectively. Standard care subjects reported higher out-of-pocket payments (5810 Ethiopian birr) (ETB) and lost wages of informal caregivers (74 900 ETB), multiple times an average Ethiopian salary (3696 ETB).

Conclusion It is feasible to conduct an RCT of early PC for patients with cancer in Ethiopia. Retention was the biggest challenge. This study revealed opportunities to improve care, and important feasibility results to inform future, larger scale PC research in Ethiopia and beyond.

• Cancer
• COVID-19

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#### WHAT IS ALREADY KNOWN ON THIS TOPIC

• PC adds value to medical care in developed countries.

• Similar health economic data are missing from low-and-middle-income countries.

• It is feasible to conduct a pilot randomised controlled trial of early palliative care (PC) in this fragile setting.

#### HOW THIS STUDY MIGHT AFFECT RESEARCH, PRACTICE OR POLICY

• Future, similarly designed but larger research is needed to define the value of PC in fragile settings.

## Introduction

Globally, non-communicable disease continue to rise, constituting more than 70% of deaths worldwide.1 As a result, people are living longer while accruing tremendous costs for seeking medical care.2 Palliative care (PC) aims to reduce pain and suffering for those with incurable disease.3 The benefits of early PC are numerous and well studied in high-income settings, including improved quality of life and increased value in healthcare spending.4–6 However, these outcomes are missing from low-and-middle-income countries (LMIC) and with it, the momentum to increase publicly available PC.7–9 We therefore designed a pilot, feasibility randomised controlled trial (RCT) of early PC in newly diagnosed cancer patients in Addis Ababa, Ethiopia.

## Methodology

### Study design

Our rationale and study design were previously published.10 Briefly, a feasibility, single-blinded RCT of early, in-home PC plus standard cancer care versus standard cancer care alone was conducted. All cancer care took place at Tikur Anbessa Hospital Oncology Clinic. Critically important is that treatments in both arms represent the standard of medical care in this resource-constrained location, including medication stock-outs, delays in diagnosis, and preferential oncological treatment given to ‘high priority’ patients, defined by a high likelihood of treatment response for example, oncologic emergency (spinal cord compression, space-occupying intracranial lesion, airway compromise) and certain cancers (germ-cell, testicular, lymphoma).

### Participants

Ninety-five adults with newly diagnosed, high-priority cancers were recruited and randomised in a 1:1 ratio to standard cancer care or standard cancer care plus PC. The web-based tool used to generate the randomisation scheme is open access and available at: www.randomization.com. Those randomised to early PC met with a PC provider at time of enrolment and at follow-up visits in their homes. All participants were assessed via questionnaire at enrolment and follow-up visits at 8±4 and 12±4 weeks, scheduled at the treating, blinded Oncologist’s discretion.

### Outcomes

#### Feasibility

Outcomes include (1) recruitment, retention, the intervention implementation and (2) the practicality of the study, including positive/negative effects on the target population.

#### Patient-reported outcomes

A composite survey contained demographic information, the APCA POS, and five questions assessing out-of-pocket payments for medical care and lost wages.

## Discussion

It is feasible in this fragile setting to conduct a pragmatic RCT, to recruit and randomise patients into a study examining outcomes of an integrated PC intervention. It was feasible to incorporate early, in-home PC at the time of a new cancer diagnosis. Patients were retained in the study, although attrition due to death and further complicated by limited death documentation in Ethiopia, made it difficult to obtain mortality data. Otherwise, the outcome measures chosen were acceptable and informative.

A caveat to the following discussion is that this was a feasibility study; however, the results are important in developing initial impressions and informing a larger, definitive study. Our results indicate that PC improves patient-reported outcomes in patients with late-stage cancers in this low-resource setting. We expected a greater improvement in APCA score in those receiving PC. There are potential explanations for why this was not observed: “high-priority” patients are preferentially given chemotherapy; thus, it is possible they responded to their treatment with improved symptoms. Second, analgesia is now regularly prescribed in this clinic, a hopeful and positive change from the time of our needs assessment (2017).9 Finally, the impact of COVID-19 adaptations to phone follow-up for our PC arm may have minimised differences between groups: PC is a holistic approach to physical and non-physical care which is likely less effective when reduced to a phone call.

The second important finding is that home delivery of PC is not only effective but also achievable in this resource-limited setting, at low cost. Due to small numbers in the cost analysis, our analysis was exploratory and between-group differences are interpreted with great caution. Despite randomisation and blinding, we report higher mortality in those receiving PC. This may be because those receiving PC decided to forgo aggressive, expensive treatments, resulting in lower costs and increased mortality. This finding in particular will be important to explore in a larger study, with longer follow-up.

## Conclusion

Despite the limitations and challenges of conducting an RCT in what became a particularly challenging environment and time, our results suggest that it is feasible to conduct an RCT of early PC with oncology care in Ethiopia. The study revealed opportunities to improve care for those with advanced cancers while informing future, larger research on the health economics of PC in Ethiopia and other similar settings.

## Ethics statements

### Ethics approval

Ethical approval was obtained from Addis Ababa University College of Health Sciences School of Medicine and Yale University School of Medicine. All subjects signed/thumb-printed informed consent. The study conformed to the principles embodied in the Declaration of Helsinki.

## Acknowledgments

We wish to thank our study participants, who despite their cancer diagnoses, showed profound humanity in their willingness to share their thoughts, fears and experience living with cancer within a fragile health system, in order to improve the care of future patients in Ethiopia. The study would not have been possible without the support of Addis-based research staff and nurses in the Department of Oncology at Tikur Anbessa Hospital. Finally, we wish to acknowledge the Yale Department of Emergency Medicine for funding the study and particularly Dr. Steve Bernstein, who believed enough in this project to continue funding despite significant budget cuts due to COVID-19.

• ## Supplementary Data

This web only file has been produced by the BMJ Publishing Group from an electronic file supplied by the author(s) and has not been edited for content.

## Footnotes

• Contributors EAR conceptualised the research, was awarded funding for the project, designed the methodology, supervised, conducted formal analysis and validation, wrote the original draft and edited subsequent drafts. EA was responsible for data curation, project administration, investigation, methodology and writing-review and editing. JD was responsible for data curation and writing-review and editing. YM and TW was responsible for conceptualisation, supervision and writing-review and editing. PH was responsible for methodology, formal analysis, writing-original draft and writing-review and editing. MF was responsible for conceptualisation, methodology, writing-original draft and writing-review and editing. LG was responsible for conceptualisation, writing-original draft and writing-review and editing.

• Funding This study was funded by Yale University School of Medicine, Department of Emergency Medicine, through a New Investigator mechanism awarded to Dr. EAR.

• Competing interests None declared.

• Provenance and peer review Not commissioned; internally peer reviewed.

• Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.