The effectiveness and cost‐effectiveness of hospital‐based specialist palliative care for adults with advanced illness and their caregivers

Sabrina Bajwah; Adejoke O Oluyase; Deokhee Yi; Wei Gao; Catherine J Evans; Gunn Grande; Chris Todd; Massimo Costantini; Fliss E Murtagh; Irene J Higginson

doi:10.1002/14651858.CD012780.pub2

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Figure 1

PRISMA flow diagram.

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Figure 2

A figure describing the power of included studies at recruitment and follow‐up

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Figure 3

A figure showing the domains of HSPC in the studies that either included certified experts in palliative care or those described as palliative care clinicians

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Figure 4

A figure showing the domains of HSPC in studies that were unclear about palliative care training

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Figure 5

Risk of bias summary: review authors' judgements about each risk of bias item for each included study.

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Figure 6

Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.

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Figure 7

Funnel plot of comparison: 1 Patient health‐related quality of life, outcome: 1.1 HSPC versus usual care on patient HRQoL: adjusted endpoint values.

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Analysis 1.1

Comparison 1: Patient health‐related quality of life, Outcome 1: HSPC versus usual care on patient HRQoL: adjusted endpoint values

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Analysis 1.2

Comparison 1: Patient health‐related quality of life, Outcome 2: HSPC versus usual care on patient HRQoL: adjusted endpoint values (excluding McCorkle 2015)

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Analysis 1.3

Comparison 1: Patient health‐related quality of life, Outcome 3: HSPC versus usual care on patient HRQoL: unadjusted endpoint values

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Analysis 1.4

Comparison 1: Patient health‐related quality of life, Outcome 4: HSPC versus usual care on patient HRQoL: unadjusted endpoint values (excluding McCorkle 2015)

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Analysis 1.5

Comparison 1: Patient health‐related quality of life, Outcome 5: HSPC versus usual care on patient HRQoL: unadjusted change values

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Analysis 2.1

Comparison 2: Patient symptom burden, Outcome 1: HSPC versus usual care on patient symptom burden: adjusted endpoint values

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Analysis 2.2

Comparison 2: Patient symptom burden, Outcome 2: HSPC versus usual care on patient symptom burden: unadjusted endpoint values

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Analysis 2.3

Comparison 2: Patient symptom burden, Outcome 3: HSPC versus usual care on patient symptom burden: unadjusted endpoint values (excluding McCorkle 2015)

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Analysis 2.4

Comparison 2: Patient symptom burden, Outcome 4: HSPC versus usual care on patient symptom burden: adjusted change values

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Analysis 2.5

Comparison 2: Patient symptom burden, Outcome 5: HSPC versus usual care on patient symptom burden: adjusted change values (excluding McCorkle 2015)

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Analysis 2.6

Comparison 2: Patient symptom burden, Outcome 6: HSPC versus usual care on patient symptom burden: unadjusted change values

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Analysis 3.1

Comparison 3: Patient satisfaction with care, Outcome 1: HSPC versus usual care on patient satisfaction with care: adjusted endpoint values

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Analysis 4.1

Comparison 4: Achieving patient preferred place of death, Outcome 1: HSPC versus usual care on home deaths

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Analysis 5.1

Comparison 5: Pain, Outcome 1: HSPC versus usual care on pain: adjusted endpoint values

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Analysis 5.2

Comparison 5: Pain, Outcome 2: HSPC versus usual care on pain: adjusted change values

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Analysis 5.3

Comparison 5: Pain, Outcome 3: HSPC versus usual care on pain: unadjusted change values

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Analysis 6.1

Comparison 6: Patient anxiety, Outcome 1: HSPC versus usual care on patient anxiety: adjusted endpoint values

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Analysis 6.2

Comparison 6: Patient anxiety, Outcome 2: HSPC versus usual care on patient anxiety: adjusted endpoint values (excluding McCorkle 2015)

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Analysis 6.3

Comparison 6: Patient anxiety, Outcome 3: HSPC versus usual care on patient anxiety: unadjusted endpoint values

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Analysis 6.4

Comparison 6: Patient anxiety, Outcome 4: HSPC versus usual care on patient anxiety: unadjusted endpoint values (excluding McCorkle 2015)

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Analysis 6.5

Comparison 6: Patient anxiety, Outcome 5: HSPC versus usual care on patient anxiety: unadjusted change values

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Analysis 6.6

Comparison 6: Patient anxiety, Outcome 6: HSPC versus usual care on patient anxiety in different populations: adjusted endpoint values

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Analysis 6.7

Comparison 6: Patient anxiety, Outcome 7: HSPC versus usual care on patient anxiety in different populations: adjusted endpoint values (excluding McCorkle 2015)

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Analysis 6.8

Comparison 6: Patient anxiety, Outcome 8: EPC vs LPC on patient anxiety: adjusted endpoint values

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Analysis 6.9

Comparison 6: Patient anxiety, Outcome 9: Effect of MDT‐led services on patient anxiety: adjusted endpoint values

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Analysis 6.10

Comparison 6: Patient anxiety, Outcome 10: Effect of MDT‐led services on patient anxiety: adjusted endpoint values (excluding McCorkle 2015)

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Analysis 6.11

Comparison 6: Patient anxiety, Outcome 11: HSPC versus usual care on patient anxiety in different countries: adjusted endpoint values

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Analysis 6.12

Comparison 6: Patient anxiety, Outcome 12: HSPC versus usual care on patient anxiety in different countries: adjusted endpoint values (excluding McCorkle 2015)

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Analysis 7.1

Comparison 7: Unpaid caregiver anxiety, Outcome 1: HSPC versus usual care on unpaid caregiver anxiety: unadjusted endpoint values

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Analysis 8.1

Comparison 8: Patient depression, Outcome 1: HSPC versus usual care on patient depression: adjusted endpoint values

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Analysis 8.2

Comparison 8: Patient depression, Outcome 2: HSPC versus usual care on patient depression: unadjusted endpoint values

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Analysis 8.3

Comparison 8: Patient depression, Outcome 3: HSPC versus usual care on patient depression: unadjusted endpoint values (excluding McCorkle 2015)

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Analysis 8.4

Comparison 8: Patient depression, Outcome 4: HSPC versus usual care on patient depression: adjusted change values

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Analysis 8.5

Comparison 8: Patient depression, Outcome 5: HSPC versus usual care on patient depression: unadjusted change values

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Analysis 8.6

Comparison 8: Patient depression, Outcome 6: HSPC versus usual care on patient depression as a binary outcome

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Analysis 9.1

Comparison 9: Unpaid caregiver depression, Outcome 1: HSPC versus usual care on unpaid caregiver depression: adjusted endpoint values

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Analysis 9.2

Comparison 9: Unpaid caregiver depression, Outcome 2: HSPC versus usual care on unpaid caregiver depression: unadjusted endpoint values

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Analysis 10.1

Comparison 10: Unpaid caregiver quality of life, Outcome 1: HSPC versus usual care on unpaid caregiver quality of life: unadjusted endpoint values

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Analysis 11.1

Comparison 11: Unpaid caregiver burden, Outcome 1: HSPC versus usual care on unpaid caregiver burden: adjusted change values

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Analysis 12.1

Comparison 12: Patient breathlessness, Outcome 1: HSPC versus usual care on patient breathlessness: adjusted endpoint values

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Analysis 12.2

Comparison 12: Patient breathlessness, Outcome 2: HSPC versus usual care on patient breathlessness: unadjusted endpoint values

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Analysis 12.3

Comparison 12: Patient breathlessness, Outcome 3: HSPC versus usual care on patient breathlessness: unadjusted change values

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Summary of findings 1. Hospital‐based specialist palliative care compared to usual care for adults with advanced illness and their caregivers/families

Outcomes	*Anticipated absolute effects^ (95% CI)**		Relative effect (95% CI)	№ of participants (studies)	Certainty of the evidence (GRADE)
Hospital‐based specialist palliative care compared to usual care for adults with advanced illness and their unpaid caregivers/families
Patient or population: adults with advanced illness and their unpaid caregivers/families Setting: hospital and home Intervention: hospital‐based specialist palliative care Comparison: usual care
Outcomes	Risk with usual care	Risk with hospital‐based specialist palliative care	Relative effect (95% CI)	№ of participants (studies)	Certainty of the evidence (GRADE)
Patient health‐related quality of life (HRQoL)ⁱ, SD units (higher scores indicate better quality of life) Follow‐up: range two weeks after hospitalisation to 13 months	Mean (SD) ranging from ‐45.4 (26.83) to 131.14 (26.62)	SMD 0.26 SDs higher (0.15 higher to 0.37 higher)	‐	1344 (10 RCTs)	⊕⊕⊝⊝ LOW^a
Patient symptom burden assessed with generalised measuresⁱⁱ, SD units (lower scores indicate lower symptom burden) Follow‐up: range two weeks after hospitalisation to 13 months	Mean (SD) ranging from ‐19.3 (4.2) to 268.59 (201.65)	SMD 0.26 SDs lower (0.41 lower to 0.12 lower)	‐	761 (6 RCTs)	⊕⊝⊝⊝ VERY LOW^a,b
Patient satisfaction with careⁱⁱⁱ, SD units (higher scores indicate better patient satisfaction) Follow‐up: range 3 months to 6 months	Mean (SD) ranging from 6.4 (1.1) to 68.37 (9.03)	SMD 0.36 SDs higher (0.41 higher to 0.57 higher)	‐	337 (2 RCTs)	⊕⊕⊝⊝ LOW^a
Achieving patient preferred place of death (measured by number of patients with home death) Follow‐up: range 1 month to 13 months	462 per 1000	583 per 1000 (513 to 649)	OR 1.63 higher (1.23 higher to 2.16 higher)	861 (7 RCTs)	⊕⊕⊝⊝ LOW^a
Pain^iv, SD units (lower scores indicate less pain) Follow‐up: range 8 weeks to 6 months	Mean (SD) ranging from 2.2 (3.7) to 28.19 (32.81)	SMD 0.16 SDs lower (0.33 lower to 0.01 higher)	‐	525 (4 RCTs)	⊕⊝⊝⊝ VERY LOW^a,b
Unpaid caregiver burden^v Follow‐up: 6 months	Only two studies reported adjusted endpoint values but we could not pool them in a meta‐analysis. They both found no between‐group difference between HSPC and usual care		‐	170 (2 RCTs)	⊕⊝⊝⊝ VERY LOW^a,c
Cost and cost‐effectiveness	Of 13 studies reporting costs of HSPC, nine studies found no difference between HSPC and usual care and two studies favoured HSPC over usual care. The difference in cost was unclear in one study, while another study reported mixed findings with lower cost of hospitalisation in favour of HSPC but no difference in the cost of emergency room visit. Four studies with full economic analysis were inconclusive on the cost‐effectiveness of HSPC.		‐	2103 (13 RCTs)	⊕⊝⊝⊝ VERY LOW^a,d
*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: Confidence interval; OR: Odds ratio; RCT: randomised controlled trial; RR: Risk Ratio; SMD: standardised mean difference ^i. Assessed with the European Organisation for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ‐C30), Functional Assessment of Cancer Therapy ‐ Bone Marrow Transplant (FACT‐BMT), Functional Assessment of Cancer Therapy ‐ General Measure (FACT‐G), Functional Assessment of Cancer Therapy – Lung scale (FACT‐L), Functional Assessment of Chronic Illness therapy for Palliative Care (FACIT‐Pal), Functional Assessment of Chronic Illness Therapy ‐ Spiritual Well‐being Scale (FACIT‐Sp), McGill Quality of Life Questionnaire (McGill QoL questionnaire) and Minnesota Living with Heart Failure Questionnaire (MLHF questionnaire). ^ii. Assessed with the Edmonton Symptom Assessment Scale (ESAS) or a modified form of it, severity subscale of the Memorial Symptom Assessment Scale (MSAS), symptom impact subscale of the Quality of Life at End of life (QUAL‐E), Rotterdam Symptom Checklist (RSC ‐ Physical Symptoms Score) and lung cancer subscale of the FACT‐L. ^iii. Assessed with 16‐item Family Satisfaction with Care ‐ Patient Version (FAMCARE‐P16) and Modified City of Hope Patient Questionnaires ‐ Place of Care Environment Scale (MCOHPQ ‐ Place of Care Environment Scale). ^iv. Assessed with pain item of EORTC QLQ‐C30 and Brief Pain Inventory (BPI). ^v. Assessed with Montgomery‐Borgatta Caregiver Burden Scale and Zarit Burden Inventory
GRADE Working Group grades of evidence High quality: We are very confident that the true effect lies close to that of the estimate of the effect Moderate quality: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different Low quality: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect Very low quality: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect
^a We downgraded by 2 levels for very serious study limitations due to a high risk of bias in studies. ^b We downgraded by 1 level due to inconsistency between our main meta‐analysis and sensitivity analyses. ^c We downgraded by 1 level for imprecision due to the small number of participants. ^d We downgraded by 1 level for inconsistency because the results were inconsistent across studies.

Summary of findings 1. Hospital‐based specialist palliative care compared to usual care for adults with advanced illness and their caregivers/families

Author	Symptom control (e.g. assess symptoms, prescribing of medications)	Decision‐making (e.g. enquire about goals of care)	Future planning (e.g. advance care planning)	Coping and support (e.g. emotional and practical support)	Care co‐ordination (e.g. helping with co‐ordinating care)
Bajwah 2015	Yes	Yes	Yes	Yes	Yes
Bakitas 2009	Yes	Yes	Yes	Yes	Yes
Bakitas 2015	Yes	Yes	Yes	Yes	Yes
Bekelman 2018	Yes	Yes	No	Yes	Yes
Brannstrom 2014	Yes	Yes	No	Yes	Yes
Brumley 2007	Yes	Yes	Yes	Yes	Yes
Carson 2016	No	Yes	No	Yes	No
Edmonds 2010	Yes	Yes	Yes	Yes	Yes
El‐Jawahri 2016	Yes	No	No	Yes	No
Farquhar 2014	Yes	Yes	Yes	Yes	No
Farquhar 2016	Yes	Yes	Yes	Yes	No
Franciosi 2019	Yes	Yes	No	Yes	Yes
Gade 2008	Yes	Yes	Yes	Yes	No
Higginson 2009	Yes	No	Yes	Yes	Yes
Higginson 2014	Yes	Yes	Yes	Yes	Yes
Janssens 2019	Yes	Yes	Yes	Yes	Yes
Kane 1984	Yes	No	Yes	Yes	No
Lowther 2015	Yes	Yes	Yes	Yes	No
Ma 2019	Yes	Yes	No	Yes	Yes
McCorkle 2015	Yes	Yes	No	Yes	Yes
McWhinney 1994	Unclear	Unclear	Unclear	Yes	Unclear
Nottelmann 2018	Yes	Yes	Yes	Yes	Yes
Rodin 2019	Yes	No	No	Yes	No
Rogers 2017	Yes	Yes	Yes	Yes	Yes
Sidebottom 2015	Yes	Yes	Yes	Yes	Yes
Solari 2018	Unclear	Unclear	Unclear	Yes	Unclear
Tattersall 2014	Yes	No	No	Yes	No
Temel 2010	Yes	Yes	No	Yes	Yes
Temel 2017	Yes	Yes	No	Yes	Yes
Vanbutsele 2018	Yes	Yes	No	Yes	Yes
Wallen 2012	Yes	No	No	Yes	No

Author	Symptom control (e.g. assess symptoms, prescribing of medications)	Decision‐making (e.g. enquire about goals of care)	Future planning (e.g. advance care planning)	Coping and support (e.g. emotional and practical support)	Care co‐ordination (e.g. helping with co‐ordinating care)
Ahronheim 2000	Yes	No	Yes	Yes	No
Cheung 2010	Unclear	Unclear	Unclear	Unclear	Unclear
Groenvold 2017	Unclear	Unclear	Unclear	Unclear	Unclear
Grudzen 2016	Yes	Yes	Yes	Yes	No
Hopp 2016	Yes	Yes	Yes	Yes	No
Jingfen 2017	Yes	Yes	No	Yes	No
McCaffrey 2013	Unclear	Unclear	Unclear	Unclear	Yes
Mendoza‐Galindo 2018 (abstract only)	Yes	No	No	Yes	No
O'Riordan 2019	Yes	No	Yes	Yes	No
Ozcelik 2014	Yes	No	Yes	Yes	No
Woo 2019	Yes	No	No	Yes	No

Studies, primary endpoint (PEP), disease group	Scales used	Dimensions covered in scales
Bajwah 2015 PEP: 4 weeks Advanced fibrotic lung disease	KBILD (used in meta‐analysis) SGRQ	KBILD is a 15‐item questionnaire consisting of three domains (breathlessness and activities, chest symptoms and psychological) ‐ secondary outcome SGRQ is a 50‐item instrument designed to measure impact on overall health, daily life, and perceived well‐being in patients with obstructive airways disease. Part 1 has a symptoms component (frequency and severity) with a 1, 3 or 12 month recall (several scales); Part 2 has an activities component looking at activities that cause or are limited by breathlessness and an impact component looking at social functioning, psychological disturbances resulting from airways disease and referring to current state as the recall (dichotomous (true/false) except last question (4‐point Likert scale) – secondary outcome
Bakitas 2009 PEP: 13 months Cancer	FACIT‐Pal	Measures physical, emotional, social, and functional well‐being in addition to concerns relevant to persons with life‐threatening illness (e.g. feeling peaceful, reconciling with others) – primary outcome
Bakitas 2015 PEP: 3 months Cancer	FACIT‐Pal (used in meta‐analysis) Treatment Outcome Index	Measures physical, emotional, social, and functional well‐being and additional concern subscales – study did not specify whether primary or secondary outcome TOI, composed of FACIT‐Pal physical, functional, and additional concern subscales
Bekelman 2018 PEP: 6 months Heart failure	KCCQ	KCCQ is a valid, reliable measure of heart failure–specific health status that is responsive to change. No further details provided in the study
Brannstrom 2014 PEP: 6 months Heart failure	EQ‐5D (used in meta‐analysis) KCCQ	A generic, single index that defines health in the five dimensions of mobility, self‐care, usual activities, pain/discomfort, and anxiety/depression ‐ did not specify primary or secondary outcomes Full data not shown in study
Edmonds 2010 PEP: 12 weeks Multiple sclerosis	MSIS	Multiple Sclerosis Impact Scale (MSIS) is a 29‐item measure of disease impact. It has two subscales: physical and psychological subscales.
El‐Jawahri 2016 PEP: 2 weeks Cancer	FACT‐BMT	The 47‐item Functional Assessment of Cancer Therapy–Bone Marrow Transplant which includes subscales assessing physical, functional, emotional, social well‐being, and bone marrow transplant–specific concerns during the past week, was used to assess patients’ QoL – primary outcome
Franciosi 2019 PEP: 12 weeks Cancer	FACT‐G	Functional Assessment of Cancer Therapy‐General (FACT‐G) scale. It is a 27‐item internationally validated questionnaire divided into four primary HRQoL domains: physical well‐being, social/family well‐being, emotional well‐being, and functional well‐being. The total FACT‐G score is the sum of the 4 subscale scores.
Gade 2008 PEP: at hospital discharge Mixed diseases comprising cancer and non‐cancer	MCOHPQ	MCOHPQ Physical Area scale, emotional/relationship area and spiritual area scales and MCOHPQ place of care environment scale. Physical Area scale addresses pain, fatigue, sleep changes, nausea, constipation, diarrhoea, dry mouth, change in appetite, and shortness of breath. Emotional support items included: anxiety, burden to family, support they received, isolation, opportunity to discuss illness and possible death, and treatment wishes/goals. Spiritual support included: the importance of participation in spiritual or religious experiences from the Spiritual Area scale, and two items developed by the investigators: ability to find meaning in one’s life, and support given by religion or spiritual belief. MCOHPQ Place of Care Environment scale addressed experiences receiving pain management and symptom relief, psychological and social support, discharge planning, and end‐of‐life planning – primary outcome.
Grudzen 2016 PEP: 12 weeks Cancer	FACT‐G	Functional Assessment of Cancer Therapy‐General Measure (not specified in study) – primary outcome
Higginson 2014 PEP: 6 weeks Mixed diseases comprising cancer and non‐cancer	CRQ HROL (presented in meta‐analysis) EQ‐5D	Measures breathlessness mastery, breathlessness, fatigue, and emotional function – secondary outcome A generic, single index that defines health in the five dimensions of mobility, self‐care, usual activities, pain/discomfort, and anxiety/depression
Janssens 2019 PEP: 12 months COPD	SF‐36	A generalised self‐assessment scale assessing different dimensions including vitality, mental health, general health, physical functioning, role physical, role emotional, bodily pain, social functioning and health transition
Jingfen 2017 PEP: 3 months Cancer	EORTC QLQ‐C30‐Chinese version	Not specified as primary or secondary outcome
McCorkle 2015 PEP: not stated but 3 months used in meta‐analysis Cancer	FACT‐G (presented in meta‐analysis) SF‐12 (not used in meta‐analysis because only its first item was used)	No information provided in study on dimensions covered by FACT‐G ‐ secondary outcome
Nottelmann 2018 PEP: 12 weeks Cancer	EORTC QLQ‐C30	The EORTC QLQ‐C30 consists of 30 items in 15 scales. In the present study additional items measuring role functioning, cognitive functioning, social functioning, dyspnoea, pain, fatigue, insomnia, appetite loss, nausea/vomiting and constipation were added to the questionnaire to expand these scales to at least four items in each scale.
O'Riordan 2019 PEP: not stated but appeared to be 6 months. 6 months was used in meta‐analysis Heart failure	MLHF questionnaire	MLHF questionnaire measures heart failure–specific health–related quality of life. No further information provided
Ozcelik 2014 PEP: on discharge Cancer	EORTC QLQ‐C30	The scale consists of the 2 subscales 'functional' and ‘symptom'. The functional section is divided into 6 subsections: physical, role, cognitive, emotional, social, and global quality of life. The symptom section includes the following symptoms: fatigue, nausea and vomiting, pain, dyspnoea, sleep disorders, loss of appetite, constipation, diarrhoea, and financial impact – primary outcome
Rodin 2019 PEP: 12 weeks Cancer	FACIT‐Sp	The scale covers physical, social/family, emotional, functional, and spiritual well‐being.
Rogers 2017 PEP: 6 months Heart failure	FACIT‐Pal (presented in meta‐analysis) KCCQ	Assesses quality of life in several domains, including physical well‐being, social/family well‐being, emotional well‐being, functional well‐being, and palliative care – primary outcome The overall summary score is derived from the physical function, symptom, social function, and quality‐of‐life domains.
Sidebottom 2015 PEP: not stated but data presented at 3 months used in meta‐analysis Heart failure	MLHF questionnaire	The MLHF Questionnaire was created to be representative of the ways HF and treatments can affect key physical, emotional, social, and mental dimensions of QoL. It assess how much a person’s HF has affected many aspects of their life during the prior month – primary outcome
Solari 2018 PEP: 6 months	SEIQoL‐DW questionnaire	Schedule for the Evaluation of Individual Quality of Life‐Direct Weighting (SEIQoL‐DW). The SEIQoL‐DW is administered in an interview in which respondents nominate the five areas of life that are most important in determining their QoL, and rate the satisfaction/functioning and weight/importance in each of these areas. The SEIQoL‐DW index can range from 0 to 100 (best).
Tattersall 2014 PEP: one year Cancer	McGill QoL Questionnaire	Physical symptoms, psychological symptoms, outlook on life, and meaningful existence – primary outcome
Temel 2010 PEP: 12 weeks Cancer	FACT‐L (presented in meta‐analysis) LCS TOI	Assesses multiple dimensions of the quality of life (physical, functional, emotional, and social well‐being) during the previous week. In addition, the lung cancer subscale (LCS) of the FACT‐L scale evaluates seven symptoms specific to lung cancer – primary outcome
Temel 2017 PEP: 12 weeks Cancer	FACT‐G	Assesses four dimensions of QoL (physical, functional, emotional, and social well‐being) – primary outcome
Vanbutsele 2018 PEP: 12 weeks Cancer	EORTC QLQ‐C30 (presented in meta‐analysis) McGill QoL questionnaire	Global health status/quality of life scale of the European Organisation for Research and Treatment of Cancer Quality‐of‐Life Questionnaire Core 30 items (EORTC QLQ‐C30; version 3) Single item scale and overall summary score of the McGill Quality of Life questionnaire (MQoL). The MQoL incorporates a single item scale of global quality of life and four subscales, measuring four relevant domains of quality of life (i.e. physical, psychological, existential/spiritual, and social).
Woo 2019 PEP: 4 weeks Cancer	EORTC QLQ‐C30 (Korean version)	EORTC QLQ‐C30 (Korean version) assesses multiple dimensions of QoL (physical, functional, emotional and social well‐being) during the previous week.
COPD: CRQ HROL: EORTC QLQ‐C30: EQ‐5D: FACIT‐Pal: Functional Assessment of Chronic Illness Therapy for Palliative Care FACIT‐Sp: Functional Assessment of Chronic Illness Therapy—Spiritual Well‐Being (FACIT‐Sp) FACT‐BMT: Functional Assessment of cancer Therapy – Bone Marrow Transplant FACT‐G: Functional Assessment of Cancer Therapy‐General Measure/Functional Assessment of Chronic Illness Therapy–General Measure FACT‐L: HF: HRQoL: KBILD: Kings Brief Interstitial Lung Disease KCCQ: Kansas City Cardiomyopathy Questionnaire LCS: MCOHPQ: Modified City of Hope Patient Questionnaires MLHF: Minnesota Living with Heart Failure Questionnaire MQoL: MSIS: PEP: QoL: QUAL‐E: Quality of Life at the End of Life (QUAL‐E) SEIQoL‐DW: SF‐12: SF‐36: SGRQ: St Georges Respiratory Questionnaire TOI:

Author	Results for Mortality/Survival	P value
Ahronheim 2000	Number of deaths in the sample Intervention: 12 (25%) Control: 12 (25%)	0.96
Bajwah 2015	Number of deaths in the sample Intervention: 8 (32%) Control: 13 (54%)	Not stated
Bakitas 2009	Number of deaths in the sample Intervention: 112 (69.6%) Control: 119 (73.9%) Survival time (median, 95% CI) Intervention: 14 months (10.6 to 18.4) Control: 8.5 months (7 to 11.1)	Cox proportional hazards model estimate demonstrated a reduced relative risk of death (HR, 0.67 (95% CI: 0.496 to 0.906) P = .009) in the HSPC group during the first year of the study and a greater relative risk after one year, (HR, 1.56 (95% CI: 0.908 to 2.655)). P for survival time = 0.14
Bakitas 2015	Number of deaths (authors stated that there were 109 deaths (52.7%) Intervention: numbers not provided Control: numbers not provided Survival time (median) Intervention: 18.3 months Control: 11.8 months	Kaplan‐Meier curves illustrated a 15% difference in survival at 1 year (HSPC, 63% vs control, 48%; P = 0.038). However, for the overall log‐rank test, P = 0.18), suggesting a convergence in overall survival after 12 months.
Bekelman 2018	Number of deaths in the sample Intervention: 10 (6.4%) Control: 13 (8.3%)	0.52
Brannstrom 2014	Number of deaths in the sample Intervention: 8 (22%) Control: 4 (11.1%)	0.34
Brumley 2007	Number of deaths (authors highlighted 75% deaths among participants) Intervention: numbers not provided Control: numbers not provided Survival time (mean (SD)) Intervention: 196 days (SD:164) Control: 242 days (SD:200)	P = 0.03 However, results of the Kaplan‐Meier survival analysis did not show differences in survival time between study groups (P = 0.08).
Carson 2016	Survival time (median, IQR) Intervention: 19 days (12 to 37) Control: 23 days (12 to 39)	P for survival time = 0.51 90‐day survival (HR, 0.95 (95% CI: 0.65 to 1.38), P = 0.96). Post hoc adjustment for baseline activities of daily living and study site did not alter the outcome (HR,1.01 (95% CI; 0.69 to 1.47), P = 0.96)
Cheung 2010	Number of deaths in the sample Intervention: 7 (70%) Control: 9 (90%)	P = 0.58
Edmonds 2010	Number of deaths in the sample Intervention: 1 (70%) Control: 3 (11.5%)	P value not stated
El‐Jawahri 2016	Number of deaths in the sample Intervention: 3 (3.7%) Control: 0	P value not stated
Farquhar 2014	Number of deaths in the sample Intervention: 2 (5.7%) Control: 0	P value not stated
Farquhar 2016	Number of deaths in the sample Intervention: 1 (2.3%) Control: 1 (2.3%)	P value not stated
Franciosi 2019	Number of deaths in the sample Intervention: 52 (37.4%) Control: 30 (36.6%)	P value not stated
Gade 2008	Number of deaths in the sample Intervention: 173 (63%) Control: 132 (56%) Survival time (median, IQR) Intervention: 30 days (6 to 104) Control: 36 days (13 to 106)	P (for difference in number of deaths) = 0.08 P (for difference in survival time) = 0.08
Groenvold 2017	Number of deaths in the sample Intervention: 25 (27%) Control: 22 (23%) Survival time (median) Intervention: 323 days Control: 364 days	P (for difference in survival time) = 0.16, but in the adjusted analysis P = 0.39
Grudzen 2016	Number of deaths in the sample Intervention: 41 (59.4%) Control: 44 (65.7%) Survival time (median, 95% CI) Intervention: 289 days (128 to 453) Control: 132 days (80 to 302)	The P value for difference in median survival was 0.20 (log‐rank test)
Higginson 2009	Number of deaths in the sample Intervention: 1 (3.8%) Control: 3 (11.5%)	P value not stated
Higginson 2014	Number of deaths in the sample Intervention: 3 (5.7%) Control: 13 (25%) Survival time (median, range) Intervention: 745 (338 to1075) Control: 711 (345 to1045)	P (for survival rate) was 0.048. In subgroup analysis, this pattern was not recorded for patients with cancer (P = 0·97); but it became more marked for patients with diseases other than cancer (P = 0·01).
Hopp 2016	Number of deaths in the sample (denominator unclear) Intervention: 11 Control: 8	P = 0.47
Janssens 2019	Number of deaths in the sample Intervention: 4 (15.4%) Control: 4 (17.4%) Survival time (unclear if mean or median reported) Intervention: 454 days (95% CI: 382 to 525) Control: 425 days (95% CI: 339 to 509)	Survival did not differ between groups (log‐rank test, P = 0.913).
Kane 1984	One‐third of the sample died within 45 days after enrollment, the second third within 120 days but numbers were not provided for the intervention and control groups	Authors reported no difference in the survival patterns of HSPC and control patients
Lowther 2015	Number of deaths in the sample Intervention: 3 (5%) Control: 0	P value not stated
Ma 2019	Number of deaths in the sample Intervention: 34 (35.1%) Control: 37 (36.3%)	P = 0.87
McCaffrey 2013	Number of deaths in the sample Intervention: 16 (69.6%) Control: 5 (62.5%)	Increment (95% CI) reported as 7 (‐45.1 to 30.4)
McCorkle 2015	Number of deaths in the sample Intervention: 7 (10.6%) Control: 3 (3.8%)	P value not stated
McWhinney 1994	Authors reported that 36 (24.7%) patients died before one month but did not provide numbers in the intervention and control group.
O'Riordan 2019	Number of deaths in the sample Intervention: 1 (4.5%) Control: 1 (5.6%)	P value not stated
Rogers 2017	Number of deaths in the sample Intervention: 23 (30.7%) Control: 20 (26.7%)	P value not stated
Sidebottom 2015	Number of deaths in the sample Intervention: 14 (12.1%) Control: 5 (4.3%)	Results of the survival analysis found no association between study group assignment and death within 6 months after adjustment for age, gender, and marital status.
Solari 2018	Number of deaths in the sample Intervention: 3 (3%) Control: 0	P value not stated
Tattersall 2014	Number of deaths in the sample Intervention: 39 (65%) Control: 31 (51.7%) Survival time (median, 95% CI) Intervention: 7 months (5.2 to 9.8) Control: 11.7 months (9.8 to 18.8)	P (log rank) = 0.014. The estimated HR was 1.6 (95% CI: 1.1 to 2.3; P = 0.015). This estimate changed to 1.5 (95% CI 0.99 to 2.2; P = 0.06) when adjusted for the oncologist’s baseline estimate of likely survival, diagnosis, months since diagnosis, and gender.
Temel 2010	Number of deaths (authors stated 105 participants (70%) had died by the time of analysis) Intervention: numbers not provided Control: numbers not provided Survival time (median, 95% CI) Intervention: 11.6 (6.4 to 16.9) months Control: 8.9 (6.3 to 11.4) months	Log‐rank P = 0.02 After adjustment for age, sex, and baseline Eastern Cooperative Oncology Group performance status, the group assignment remained a predictor of survival (HR for death in the standard care group, 1.70; 95% CI, 1.14 to 2.54; P = 0.01).
Temel 2017	Number of deaths in the sample Intervention: 33 (18.9%) Control: 41 (23.4%)	P value not stated
Vanbutsele 2018	Number of deaths (authors stated that 121 (65%) of participants had died by the end of the study) Intervention: numbers not provided Control: numbers not provided Survival time (median, 95% CI) Intervention: 312 days (190 to 434) Control: 343 days (253 to 433)	P = 0.97
Woo 2019		Authors reported that there was no difference in survival between HSPC and usual care but did not present any data
CI: HR: HSPC: IQR: vs:

Studies	Participants	Adverse effects in patients/caregivers
Bajwah 2015	Patients and caregivers	Authors reported no worsening of any outcome after receiving the intervention.
Bekelman 2018	Patients	There were no harmful adverse events attributed to the intervention.
Groenvold 2017	Patients	Authors did not observe any harmful effect of the intervention.
Higginson 2014	Patients (and caregivers if present)	Authors did not observe any harmful effect of the intervention.
Lowther 2015	Patients	Authors did not observe any harmful effect of the intervention.
Rodin 2019	Patients	Authors reported no adverse events during the study.
Solari 2018	Patients and caregivers	Authors reported 15 serious adverse events in 13 patients in the HSPC group and 7 in 7 patients in the control group. Serious adverse events reported included aspiration pneumonia, generalised anxiety, breathing difficulty, urine retention/infection, anarthria, contact dermatitis, dysphagia, vomiting, bladder catheter malfunctioning, fever, arrhythmia, necrotising fasciitis, traumatic wound, macrohaematuria, constipation, abdominalgia and bronchitis. Three patients in the HSPC group died but this was considered to be unrelated to the intervention.
Tattersall 2014	Patients	Authors reported that more patients in the HSPC group had poorer appetite compared to the control group (P = 0.04).
HSPC:

Study	Time horizon	Significance and direction	Details
Bakitas 2009	During study period	Wilcoxon rank sum test P = 0.53	Intervention: 0.86 visits Control: 0.63 visits Note: not clear if the figures were means or medians
Bakitas 2015	Total use covering period before and after enrollment	Poisson generalised linear model P = 0.32 for baseline (total sample of 207) P = 0.21 for total use in 109 decedents	Intervention for baseline sample (days, 95% CI): 0.16 (0.1 to 0.25) Control for baseline sample: 0.21 (0.15 to 0.31 Intervention (total use in 50 decedents): 0.14 (0.09 to 0.2) Control (total use in 59 decedents): 0.19 (0.14 to 0.26)
Brumley 2007	During study period	Reduced ED use in intervention group Cramer’s V 0.15; P = 0.01 linear regression adjusted for survival, age and severity of illness showed intervention reduced ED visits by 0.35 (P = 0.02)	Intervention: 20% had ED visits Control: 33% had ED visits
Janssens 2019	Admissions to the emergency ward in the year before study enrollment	There was no difference in admissions to the emergency ward in the intervention group compared to the control group (Incidence rate ratio 1.27, 95% CI: 0.72 to 2.26, P = 0.384).	Number of admissions to emergency ward Intervention: 33 Control: 23
Janssens 2019	During study period	Admission to the emergency ward was twice as often in the intervention group compared to the control group (incidence rate ratio 2.05, 95% CI: 1.11 to 3.94, P = 0.014). However, after the Benjamini and Hochberg correction for multiple testing, this difference was not significant.	Number of admissions to emergency ward Intervention: 37 Control: 16
Ma 2019	During study period and post‐discharge	Patients in the intervention group had fewer ED visits compared to usual care (P = 0.0067)	% of ED visits: Intervention: 1.3% Control: 12.5% P: 0.0067
Mendoza‐Galindo 2018 (abstract only)	Unclear	P = 0.074	Intervention: 39 Control: 50
Rogers 2017	During study period	P value not stated	Frequency of interactions occurring between patients and providers Emergency department/urgent care: Intervention, mean (SD): 0.4 (0.12) Control, mean (SD): 0.5 (0.11)
Temel 2010	During study period	P value not stated	Any emergency department visit from enrollment to death: Intervention: 53.1% Control: 57.1%
Temel 2010		P value not stated	Any emergency department visit within 30 days of death: Intervention: 22.4% Control: 30.4%
CI: confidence intervals ED: SD: standard deviation

Study	Time horizon	Significance and direction	Details
Bakitas 2009	During study period	Wilcoxon rank sum test P > 0.99	Intervention: 0.06 days Control: 0.06 days Note: not clear if the figures were means or medians
Bakitas 2015	Total use covering period before and after enrollment	Poisson generalised linear model P = 0.10 for baseline (total sample of 207) P = 0.49 for total use in 109 decedents	Intervention for baseline sample (days, 95% CI): 0.52 (0.28 to 0.95) Control for baseline sample: 0.22 (0.1 to 0.5) Intervention (total use in 50 decedents): 0.1 (0.04 to 0.24) Control (total use in 59 decedents): 0.15 (0.07 to 0.3)
Carson 2016	Interviewed surrogate decision‐makers immediately after the second support and information team meeting for the intervention group and 10 days after randomisation for the control group, unless the patient had died. All surrogate decision‐makers were interviewed again by telephone for follow‐up beginning 90 days after randomisation.	Differences between groups for other patient outcomes were analysed based on t tests, nonparametric tests, χ2 tests (including the Fisher exact test), or log‐rank tests as appropriate. For total ICU days, P = 0.51 P value for after randomisation, P = 0.72	ICU days Total: Intervention, median (IQR): 19 (15 to 26) Control, median (IQR): 20 (15 to 30) After randomisation: Intervention, median (IQR): 9 (6 to 15) Control, median (IQR): 10 (5 to 17)
Cheung 2010	Enrollment to ICU discharge	Fisher’s exact test and the Mann‐Whitney test P = 0.97	Intervention: median (IQR) ICU length of stay: 3 (7) days Control: median (IQR) ICU length of stay: 5 (8) days
Grudzen 2016	During study period	Index‐admission Fisher exact test P > 0.99 Up to 180 days Fisher exact test P > 0.99	Hospital days at 180 days Index‐admission: Since only 1 participant had more than 1 ICU admission, the authors treated the ICU admission as a binary outcome. During the index‐admission, there was no difference between the 2 groups. (Fisher exact test P > 0.99) Up to 180 days: There was no difference between the 2 groups (Fisher exact test, P > 0.99).
Gade 2008	6 months post‐index hospitalisation	P = 0.04 Continuous measures for intervention and usual care patients were compared using t tests for normally distributed measures and Wilcoxon two‐sample tests for measures with skewed distributions.	ICU admissions, median n: Intervention: 12 Control: 21
Janssens 2019	Admissions to ICU for respiratory failure in the year before study enrollment	There was no difference in ICU admissions for respiratory failure in the intervention group compared to the control group (Incidence rate ratio 0.88, 95% CI: 0.26 to 2.96, P = 0.82).	Number of ICU admissions for respiratory failure in the year before inclusion: Intervention: 7 Control: 7
Janssens 2019	During study period	There was no difference in ICU admissions for respiratory failure in the intervention group compared to the control group (Incidence rate ratio 4.42, 95% CI: 0.49 to 20.92, P = 0.16).	Number of ICU admissions for respiratory failure during the study period: Intervention: 5 Control: 1
Kane 1984	During study period	P value not stated	Mean number of ICU days per patient: Intervention, mean per patient: 0.2 Control, mean per patient: 0.3
Ma 2019	During study period	No difference in ICU duration between intervention and control group (P = 0.38)	ICU duration in days, median (IQR): Intervention: 5 (3 ‐ 8) Control: 5.5 (3 ‐ 10) P: 0.38
CI: confidence intervals ICU: IQR: interquartile range

Study	Time horizon	Significance and direction	Details
Ahronheim 2000	During study period	P = 0.92	Mean number of total admissions Intervention: 1.94 Control: 1.90
Bekelman 2018	During study period	P = 0.61	Number of hospitalisations Intervention: 18 patients had 1 hospitalisation 9 patients had 2 or more hospitalisations Control: 30 patients had 1 hospitalisation 6 patients had 2 or more hospitalisations
Brannstrom 2014	During study period	P = 0.009	Number of hospitalisations, mean (SD) Intervention: 0.42 ± 0.60 Control: 1.47 ± 1.81 Total number of hospitalisations: Intervention: 15 Control: 53
Brumley 2007	During study period	Reduced hospitalisation in intervention group Cramer’s V 0.23; P < 0.001	Intervention: 36% were admitted Control: 59% were admitted
Farquhar 2014	During study period	P value not stated	Inpatient: Intervention, n (%), mean (SD) contacts: 2 (7%), 3.0 (2.8) Control, n (%), mean (SD) contacts: 3 (12%), 6.3 (6.8)
Farquhar 2016	During study period	P value not stated	Inpatient: Intervention, n (%), mean (SD) contacts: 6 (15%), 11.5 (8.3) Control, n (%), mean (SD) contacts: 4 (11%), 6.0 (3.4)
Janssens 2019	Hospital admissions for respiratory failure in the year before study enrollment	There was no difference in hospital admissions for respiratory failure in the intervention group compared to the control group (incidence rate ratio 1.18, 95% CI: 0.61 to 2.31, P = 0.60).	Number of hospital admissions for respiratory failure in the year before inclusion: Intervention: 24 Control: 18
	During study period	Hospital admission for respiratory failure was almost twice as often in the intervention group compared to the control group (incidence rate ratio 1.87, 95% CI: 1.04 to 3.48, P = 0.026). However, after the Benjamini and Hochberg correction for multiple testing, this difference was not significant.	Number of hospital admissions for respiratory failure during study period: Intervention: 38 Control: 18
	Hospital admissions for respiratory failure in the year before study enrollment	There was no difference in hospital admissions for respiratory failure in the intervention group compared to the control group (incidence rate ratio 1.18, 95% CI: 0.36 to 4.12, P = 0.77).	Other hospitalisations in the year before inclusion: Intervention: 8 Control: 6
	During study period	There was no difference in hospital admissions for respiratory failure in the intervention group compared to the control group (incidence rate ratio 1.01, 95% CI: 0.32 to 3.28, P = 0.99).	Other hospitalisations during study period: Intervention: 8 Control: 7
Ma 2019	During study period and post‐discharge	Patients in the intervention group had fewer hospital readmissions compared to usual care (P = 0.024)	% of hospital readmissions: Intervention: 17.3% Control: 33.3% P: 0.024
Mendoza‐Galindo 2018 (abstract only)	Unclear	There was no difference in number of hospitalisations. P value not given	Intervention: 48% Control: 51%
Rogers 2017	During study period	During the 6‐month follow‐up, 30% of patients were hospitalised for HF. No differences were seen between the 2 treatment groups in this clinical endpoints through the 6‐month follow‐up point. For hospitalisation for non‐heart failure/cardiovascular and hospitalisation for non‐cardiovascular, P value was not stated	Hospitalisation for HF: Intervention: 30.7% Control: 29.3% Hospitalisation for non‐heart failure/cardiovascular: Intervention: 16% Control: 13% Hospitalisation for non‐cardiovascular: Intervention: 10.7% Control: 24%
Sidebottom 2015	Inpatient readmission for any cause within 30 days	Survival analysis using proportional hazards regression P = 0.50	There was no association between study group assignment and 30‐day inpatient readmission (adjusting for age, gender, and marital status).
Temel 2010	During study period	P value not stated	Any admission from enrollment to death: Intervention: 73.5% Control: 76.8%
Temel 2010		P value not stated	Any admission within 30 days of death: Intervention: 36.7% Control: 53.6%
CI: HF: n: number SD: standard deviation

Study	Time horizon	Significance and direction	Details
Ahronheim 2000	During study period	Student’s t‐test was used P = 0.46	Intervention (mean (range)): 8.8 (1 ‐ 93) Control (mean (range)): 9.7 (1 ‐ 63)
Bakitas 2009	During the study	Wilcoxon rank sum test P = 0.14	Number of hospital days (unclear if mean or median reported) Intervention: 6.6 days Control: 6.5 days
Bakitas 2015	Total use covering period before and after enrollment	Poisson generalised linear model P = 0.03 for baseline (total sample of 207) P = 0.26 for total use in 109 decedents	Intervention for baseline sample (days, 95% CI): 0.69 (0.4 to 1.18) Control for baseline sample: 1.39 (0.97 to 1.97) Intervention (total use in 50 decedents): 0.95 (0.61 to 1.46) Control (total use in 59 decedents): 1.3 (0.91 to 1.86)
Brannstrom 2014	During the study period	P value for total hospital days = 0.011. The number of days spent in hospital was also significantly lower in the intervention group at the Departments of Medicine‐Geriatrics (100, range 1–45 vs. 242, range 2–46 days) and Surgery (0 vs. 56, range 2–21 days). Days in other departments did not differ significantly.	Total hospital days, mean (SD) Intervention: 2.9 (8.3) Control: 8.5 (12.4) Days in Department of Medicine‐Geriatrics: Intervention: 100 (range 1 ‐ 45) Control: 242 (range 2 ‐ 46) Days in Department of Surgery: Intervention: 0 Control: 56 Days in other departments: Intervention: 3 (range 1 ‐ 2) Control: 7 (1 ‐ 6)
Brumley 2007	During the study	Fewer hospital days in intervention group. Linear regression adjusted for survival, age and severity of illness showed intervention reduced hospital days by 4.36 (P < 0.001)	No descriptive data provided
Carson 2016	Interviewed surrogate decision‐makers immediately after the second support and information team meeting for the intervention group and 10 days after randomisation for the control group, unless the patient had died. All surrogate decision‐makers were interviewed again by telephone for follow‐up beginning 90 days after randomisation.	Differences in the number of hospital days were analysed using nonparametric methods. P value for total hospital days, P = 0.78 P value for deceased patients, P = 0.60 P value for after randomisation, P = 0.51	Hospital days Total hospital days: Intervention, median (IQR): 35 (23 to 52) Control, median (IQR): 36 (23 to 54) For deceased patients: Intervention (49 deaths), median (IQR): 25 (18 to 36) Control (51 deaths), median (IQR): 24 (14 to 39) After randomisation: Intervention, median (IQR): 19 (12 to 37) Control, median (IQR): 23 (12 to 39)
Cheung 2010	During study period	Fisher’s exact test and the Mann‐Whitney test P = 0.44	Intervention: median (IQR) hospital length of stay: 5 (8) days Control: median (IQR) hospital length of stay: 11 (27) days
El‐Jawahri 2016	During study period	P value not stated	Duration of HCT hospitalisation, median (range): Intervention: 20 (12 – 102) days Control: 21 (13 – 40) days
Gade 2008	6 months post‐index hospitalisation	P value for admission to study enrollment (days), P = 0.36 P value for study enrollment to discharge or death in the hospital (days), P = 0.10 P‐value for index hospital length of stay (days), P = 0.57 Continuous measures for intervention and usual care patients were compared using t tests for normally distributed measures and Wilcoxon two‐sample tests for measures with skewed distributions.	Admission to study enrollment (days), median (IQR): Intervention: 3 (2, 7) Control: 4 (2, 7) Study enrollment to discharge or death in the hospital (days), median (IQR): Intervention: 3 (1, 6) Control: 2 (1, 5) Index hospital length of stay (days), median (IQR): Intervention: 7 (4, 12) Control: 7 (4, 12)
Grudzen 2016	During study period	Index‐admission Wilcoxon test P = 0.67 Up to 180 days Wilcoxon test P = 0.14	Hospital days at 180 days Index‐admission: The authors found no difference in hospital days between the intervention and usual care groups during the index‐admission (Wilcoxon test P = 0.67). Up to 180 days: The intervention group had slightly more hospital days at 180 days than the usual care group (Wilcoxon test P = 0.14).
Higginson 2009	12 weeks following enrollment	Authors stated increased institutional days in control group but P value was not stated. “The control care patients were more likely to be (...) admitted to or seen in hospital”.	Intervention: 4/26 (17%) were institutionalised for mean 19.0 days (SD 21.6) Control: 6/28 (29%) were institutionalised for mean 30.7 days (SD 32.1)
Higginson 2014	Three months before baseline interview	P value not stated	Hospital inpatient days Intervention, mean (SD): 4.5 (6.8) Control, mean (SD): 4.6 (7.6)
Kane 1984	During study period	P value for general medical inpatient days, P < 0.05 P value for intermediate care inpatient days P < 0.05	Total inpatient days: Intervention, mean per patient: 51 Control, mean per patient: 47.5 General medical: Intervention, mean per patient: 13.2 Control, mean per patient: 20.7 Intermediate care: Intervention, mean per patient: 8.3 Control, mean per patient: 26.5
Ma 2019	During study period	No difference in hospital duration between intervention and control group (P = 0.43)	Hospital duration in days, median (IQR) Intervention: 10 (6 ‐ 15) Control: 11 (6 ‐ 19) P: 0.43
Mendoza‐Galindo 2018 (abstract only)	Unclear	P = 0.808	Intervention: 78 days Control: 90 days
Ozcelik 2014	During study period	P = 0.07	Intervention, mean (SD): 9.4 (6.27) days Control, mean (SD): 13.9 (11.5) days
Temel 2010	During study period	P value not stated	Median inpatient days (range) from enrollment to death: Intervention: 5 (0 – 50) Control: 7 (0 – 45)
IQR: interquartile range SD: standard deviation

Study	Time horizon	Significance and direction	Details
Brannstrom 2014	During study period	P value for physician visit, P = 0.000 P value for physician, phone calls and prescriptions, P = 0.012 P value for nurse visits, P = 0.003 P value for nurse visits, phone calls and prescriptions P = 0.003	Hospital outpatient clinic Physician visit, n, median (range): Intervention: 27, 1 (4 – 30) Control: 133, 3 (2 ‐11) Physician, phone calls and prescriptions, n, median (range): Intervention: 42, 3 (0 – 8) Control: 86, 3 (0 ‐10) Nurse visits, n, median (range): Intervention: 4, 1 (0 – 4) Control: 60, 2 (0 ‐27) Nurse, phone calls and prescriptions, n, median (range): Intervention: 8, 1 (0 – 4) Control: 44, 2 (0 ‐ 8)
Groenvold 2017	During study period	P values not stated	Contact with the HSPC team, (numbers): Intervention: 138 patients had at least one face‐to‐face contact Control: 13 patients had at least one face‐to‐face contact
Higginson 2009	12 weeks following enrollment	Hospital specialist visits differences and P value not stated	Hospital specialist visits: Intervention: 8 patients (35%) received; mean 1.0 contacts (SD 0.0) Control: 16 patients (76%) received; mean 1.3 contacts (SD 0.7)
Rogers 2017	During study period	P value not stated	Frequency of interactions occurring between patients and providers Total number of clinic encounter records: Intervention, mean (SD): 21.9 (1.99) Control, mean (SD): 20.8 (1.92) Cardiology: Intervention, mean (SD): 2.3 (0.55) Control, mean (SD): 3.2 (1.0) Rehabilitation clinic: Intervention, mean (SD): 1.4 (0.68) Control, mean (SD): 0.9 (0.48)
Tattersall 2014	During study period	P values not stated	Contact with palliative care physician consultant: Intervention: 51 patients (85%) Control: 8 patients (13.3%) Contact with palliative care physician in the last month of life: Intervention: 16 patients (26.7%) Control: 6 patients (10%)
Temel 2010	During study period	P values not stated	PC visits: All the patients assigned to early palliative care, except for one patient who died within 2 weeks after enrollment, had at least one visit with the palliative care service by the 12th week. The average number of visits in the palliative care group was 4 (range, 0 to 8). Ten patients who received standard care (14%) had a palliative care consultation in the first 12 weeks of the study, primarily to address the management of symptoms, with seven patients having one visit and three having two visits.
Temel 2017	During study period	P value not stated	Mean number of palliative care visits: Intervention, mean (range): 6.54 (0 to 14) Control, mean (range): 0.89 (0 to 7) Number of palliative care visits split on lung and GI cancer: The authors stated that “we explored characteristics between patients with lung and GI cancer and found no differences in baseline measures or in the number of PC visits among those patients who received intervention. However, the GI cancer cohort had a higher proportion of male patients and a greater number of hospitalisations (P = 0.038) from baseline to week 24 compared with the lung cancer cohort".
Vanbutsele 2018	During study period	P value not stated for some of the comparisons. However, the authors reported a difference between intervention and control groups for number of consultations with a psychologist (P = 0.02)	Number of consultations from the palliative care team nurse at 18 weeks: Intervention, median (IQR): 3 (1 – 4). 82 patients (89%) had at least one consultation Control, median (IQR): 17 patients (18%) had at least one consultation PC physician at 18 weeks: Intervention: 25 patients (27%) Control: 1 patient (1%) Nurses at 24 weeks: Intervention, median (IQR): 3 (2 – 5). 55 patients (60%) had at least 3 consultations Control, median (IQR): 12 patients (13%) had at least 3 consultations PC physician at 24 weeks: Intervention: 32 patients (35%) had at least one consultation Control: 1 (1%) had one consultation Number of consultations with a psychologist: 18 weeks: Intervention: 34 patients (37%) had at least one consultation Control: 21 patients (22%) had at least one consultation 24 weeks: No difference was found between intervention and control groups. Number of consultations with other professionals: There were no differences between study groups in the number of consultations with a social care nurse (P = 0·87), dietician (P = 0·32), or specialist nurse (P = 0·28) between 18 weeks and baseline; or between 24 weeks and baseline with social care nurse (P = 0·07), dietician (P = 0·95), or specialist nurse (P = 0·99).
Woo 2019	During study period	Forwards from enrollment	Consultation with a psychiatrist: The proportions that consulted a psychiatrist (12% vs 12%) were similar in the intervention and control groups.
HSPC: hospital‐based specialist palliative care IQR: Interquartile range PC: palliative care SD: standard deviation

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Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
6.1 HSPC versus usual care on patient anxiety: adjusted endpoint values Show forest plot	5	384	Mean Difference (IV, Random, 95% CI)	‐0.63 [‐2.22, 0.96]

6.2 HSPC versus usual care on patient anxiety: adjusted endpoint values (excluding McCorkle 2015) Show forest plot	4	320	Mean Difference (IV, Random, 95% CI)	‐1.60 [‐2.56, ‐0.65]

6.3 HSPC versus usual care on patient anxiety: unadjusted endpoint values Show forest plot	4	273	Mean Difference (IV, Random, 95% CI)	‐0.90 [‐2.52, 0.71]

6.4 HSPC versus usual care on patient anxiety: unadjusted endpoint values (excluding McCorkle 2015) Show forest plot	3	209	Mean Difference (IV, Random, 95% CI)	‐1.48 [‐3.52, 0.56]

6.5 HSPC versus usual care on patient anxiety: unadjusted change values Show forest plot	4	496	Std. Mean Difference (IV, Random, 95% CI)	‐0.62 [‐1.02, ‐0.21]

6.6 HSPC versus usual care on patient anxiety in different populations: adjusted endpoint values Show forest plot	5	384	Mean Difference (IV, Random, 95% CI)	‐0.63 [‐2.22, 0.96]

6.6.1 Cancer populations	3	275	Mean Difference (IV, Random, 95% CI)	‐0.65 [‐3.03, 1.74]
6.6.2 Non‐cancer populations	2	109	Mean Difference (IV, Random, 95% CI)	‐0.82 [‐2.45, 0.80]
6.7 HSPC versus usual care on patient anxiety in different populations: adjusted endpoint values (excluding McCorkle 2015) Show forest plot	4	320	Mean Difference (IV, Random, 95% CI)	‐1.60 [‐2.56, ‐0.65]

6.7.1 Cancer populations	2	211	Mean Difference (IV, Random, 95% CI)	‐1.91 [‐3.12, ‐0.70]
6.7.2 Non‐cancer populations	2	109	Mean Difference (IV, Random, 95% CI)	‐0.82 [‐2.45, 0.80]
6.8 EPC vs LPC on patient anxiety: adjusted endpoint values Show forest plot	5	384	Mean Difference (IV, Random, 95% CI)	‐0.63 [‐2.22, 0.96]

6.8.1 Early palliative care (EPC)	2	221	Mean Difference (IV, Random, 95% CI)	‐0.57 [‐3.94, 2.79]
6.8.2 Late palliative care (LPC)	3	163	Mean Difference (IV, Random, 95% CI)	‐0.81 [‐2.14, 0.52]
6.9 Effect of MDT‐led services on patient anxiety: adjusted endpoint values Show forest plot	5	384	Mean Difference (IV, Random, 95% CI)	‐0.63 [‐2.22, 0.96]

6.9.1 MDT‐led services	5	384	Mean Difference (IV, Random, 95% CI)	‐0.63 [‐2.22, 0.96]
6.10 Effect of MDT‐led services on patient anxiety: adjusted endpoint values (excluding McCorkle 2015) Show forest plot	4	320	Mean Difference (IV, Random, 95% CI)	‐1.60 [‐2.56, ‐0.65]

6.10.1 MDT‐led services	4	320	Mean Difference (IV, Random, 95% CI)	‐1.60 [‐2.56, ‐0.65]
6.11 HSPC versus usual care on patient anxiety in different countries: adjusted endpoint values Show forest plot	5	384	Mean Difference (IV, Random, 95% CI)	‐0.63 [‐2.22, 0.96]

6.11.1 Studies from USA	3	251	Mean Difference (IV, Random, 95% CI)	‐0.32 [‐3.04, 2.39]
6.11.2 Studies from UK	2	133	Mean Difference (IV, Random, 95% CI)	‐1.02 [‐2.45, 0.42]
6.12 HSPC versus usual care on patient anxiety in different countries: adjusted endpoint values (excluding McCorkle 2015) Show forest plot	4	320	Mean Difference (IV, Random, 95% CI)	‐1.60 [‐2.56, ‐0.65]

6.12.1 Studies from USA	2	187	Mean Difference (IV, Random, 95% CI)	‐1.45 [‐3.90, 1.00]
6.12.2 Studies from UK	2	133	Mean Difference (IV, Random, 95% CI)	‐1.02 [‐2.45, 0.42]

Study	Time horizon	Significance and direction	Details
Ahronheim 2000	During study period	Pearson chi² test P = 0.79	New feeding tube Intervention: 22 (45.8%) Control: 22 (43.1%)
		Pearson chi² test P = 0.66	Total feeding tube Intervention: 34 (70.8%) Control: 34 (66.7%)
		Pearson chi² test P = 0.44	Mechanical ventilation Intervention: 2 (4.2%) Control: 4 (7.8%)
		Not calculated because expected frequencies < 5 in at least 2 cells	Tracheostomy Intervention: 0 Control: 1
		Not calculated because expected frequencies < 5 in at least 2 cells	CPR Intervention: 0 Control: 3 (5.9%)
		Pearson chi² test P = 0.16	Systemic antibiotics (unclear if mean or median presented) Intervention: 73 (79.3) Control: 69 (70.4)
			Interventions during 190 admissions
		Pearson chi² test P = 0.025	IV for entire admission (unclear if mean or median presented) Intervention: 61 (66) Control: 79 (81)
		Pearson chi² test P = 0.30	Indwelling urinary catheter (unclear if mean or median presented) Intervention: 41 (44.6) Control: 51 (52)
		Pearson chi² test P = 0.33	Mechanical restraints (unclear if mean or median presented) Intervention: 13 (54.2) Control: 11 (45.8)
		Student’s t‐test P = 0.14	Days with restraints (mean) Intervention: 5.18 Control: 6.56
		Pearson chi² test P = 0.089	Daily phlebotomy for at least 50% of admission (unclear if mean or median presented) Intervention: 32 (34.8) Control: 46 (46.9)
		Pearson chi² test P = 0.461	Daily sc/im injection for at least 50% of admission (unclear if mean or median presented) Intervention: 16 (17.4) Control: 21 (21.6)
		ns Pearson chi² test P = 0.12	>1 complex non‐invasive test (unclear if mean or median presented) Intervention: 10 (11) Control: 4 (4)
		ns Pearson chi² test P = 0.215	>1 invasive test (unclear if mean or median presented) Intervention: 5 (4.3) Control: 2 (2)
		Pearson chi² test P = 0.15	Number of fingersticks per day in patients receiving insulin (unclear if mean or median presented) Intervention: 1.56 Control: 2.01
			Decisions to forgo treatments
		Not calculated because expected frequencies < 5 in at least 2 cells	Enteral feeds Intervention: 3 (6.3%) Control: 4 (7.8%)
		Not calculated because expected frequencies < 5 in at least 2 cells	Mechanical ventilation Intervention: 3 (6.3%) Control: 0
		Not calculated because expected frequencies < 5 in at least 2 cells	Intravenous lines Intervention: 5 (10.4%) Control: 1 (2%)
		Not calculated because expected frequencies < 5 in at least 2 cells	Blood draws Intervention: 4 (8.3%) Control: 0
		Not calculated because expected frequencies < 5 in at least 2 cells	Antibiotics Intervention: 3 (6.3%) Control: 0
		Pearson chi² test P = 0.65	CPR in‐hospital (unclear if mean or median presented) Intervention: 62 (67.4) Control: 63 (64.3)
		Pearson chi² test P = 0.10	CPR nonhospital (unclear if mean or median presented) Intervention: 47 (51.1) Control: 38 (38.8)
Bakitas 2009	During study period	P = 0.34 Referral to hospice care Fisher exact test P = 0.75	Referral to palliative care Intervention: 34/145 (23.4%) Control: 39/134 (29.1%) Referral to hospice care Intervention: 6/161 (3.7%) Control: 4/161 (2.5%)
Bakitas 2015	Total use covering period before and after enrollment	Poisson generalised linear model P = 0.54	Chemotherapy in last 2 weeks of life Intervention, rate (95% CI): 0.08 (0.03 to 0.2) Control, rate (95% CI): 0.05 (0.02 to 0.15)
Brumley 2007	During study period	Referral to hospice care (1of 2 sites only) Chi² P = 0.15 Days in hospice care (1of 2 sites only) t 0.52 P = 0.60	Referral to hospice care (1 of 2 sites only) Intervention: 25% Control: 36% Days in hospice care (1 of 2 sites only) descriptive data not provided
Carson 2016	Interviewed surrogate decision‐makers immediately after the second support and information team meeting for the intervention group and 10 days after randomisation for the control group, unless the patient had died. All surrogate decision‐makers were interviewed again by telephone for follow‐up beginning 90 days after randomisation.	Total ventilator days, P = 0.59 After randomisation, P = 0.42	Ventilator days Total Intervention, median (IQR): 19 (15 to 31) Control, median (IQR): 21 (14 to 35) After randomisation Intervention, median (IQR): 10 (5 to 20) Control, median (IQR): 12 (5 to 27)
Carson 2016	Interviewed surrogate decision‐makers immediately after the second support and information team meeting for the intervention group and 10 days after randomisation for the control group, unless the patient had died. All surrogate decision‐makers were interviewed again by telephone for follow‐up beginning 90 days after randomisation.	P = 0.62	Hospital discharge disposition (81 patients discharged from the hospital in intervention group and 75 in control group). Home Intervention, median (IQR): 15 (19) Control, median (IQR): 18 (24) Home with paid assistance: Intervention, median (IQR): 10 (12) Control, median (IQR): 7 (9) Hospice Intervention, median (IQR): 3 (4) Control, median (IQR): 4 (5) Acute rehabilitation facility Intervention, median (IQR): 22 (27) Control, median (IQR): 15 (20) Long‐term acute care hospital Intervention, median (IQR): 12 (15) Control, median (IQR): 12 (16) Other acute care facility Intervention, median (IQR): 0 Control, median (IQR): 1 (1) Skilled nursing facility Intervention, median (IQR): 19 (23) Control, median (IQR): 16 (21) Other Intervention, median (IQR): 0 Control, median (IQR): 2 (3)
Farquhar 2014	During study period	P value not stated	Other hospital care Intervention, n (%), mean (SD) contacts: 15 (54%), 1.5 (0.8) Control, n (%), mean (SD) contacts: 14 (54%), 1.4 (0.6)
		P value not stated	Nurse Intervention, n (%), mean (SD) contacts: 11 (39%), 3.0 (3.8) Control, n (%), mean (SD) contacts: 12 (46%), 1.8 (1.6)
		P value not stated	Other health professionals Intervention, n (%), mean (SD) contacts: 5 (18%), 1.2 (0.4) Control, n (%), mean (SD) contacts: 3 (12%), 1.0 (0.0)
			Social care Intervention, n (%), mean (SD) contacts: 4 (14%), 4.3 (6.5) Control, n (%), mean (SD) contacts: 3 (12%), 15.7 (22.9)
Farquhar 2016	During study period	P value not stated	Other hospital services Intervention, n (%), mean (SD) contacts: 20 (49%), 1.7 (1.0) Control, n (%), mean (SD) contacts: 19 (50%), 2.5 (3.5)
		P value not stated	Nurse Intervention, n (%), mean (SD) contacts: 21 (51%), 2.7 (3.3) Control, n (%), mean (SD) contacts: 16 (42%), 2.5 (2.5)
		P value not stated	Other health services Intervention, n (%), mean (SD) contacts: 14 (34%), 1.5 (1.1) Control, n (%), mean (SD) contacts: 4 (11%), 1.0 (0.0)
		P value not stated	Social and other care Intervention, n (%), mean (SD) contacts: 8 (20%), 5.4 (4.6) Control, n (%), mean (SD) contacts: 9 (24%), 11.3 (22.8)
Groenvold 2017	During study period	P value not stated	Telephone contact with the HSPC team, n Intervention: 116 patients had at least one telephone contact Control: 9 patients had at least one telephone contact
Higginson 2009	12 weeks after enrollment	P value not stated	Palliative care nurse Intervention: 9 (39%) received; M 3.0 (SD 1.5) Control: 0 received Other nurse Intervention: 7 (30%) received; M 40.0 (SD 63.8) Control: 7 (33%) received; M 95.0 (SD 79.6) Specialist (ward) Intervention: 5 (22%) received; M 1.0 (SD 0.0) Control: 7 (33%) received; M 9.6 (SD 12.1) Specialist (other) Intervention: 4 (17%) received; M 1.1 (SD 0.3) Control: 5 (24%) received; M 1.0 (SD 0.0) Occupational therapist/physiotherapist Intervention: 16 (70%) received; M 10.6 (SD 9.9) Control: 14 (67%) received; M 22.5 (SD 47.7) Dietitian/chiropodist Intervention: 12 (52%) received; M 3.5 (SD 2.5) Control: 13 (62%) received; M 2.6 (SD 1.3) Day centre Intervention: 5 (22%) received;M 20.2(SD 21.0) Control: 5 (24%) received; M 20.4 (SD 15.9) Respite care Intervention: 2 (9%) received; M 9.5 (SD 0.7) Control: 5 (24%) received; M 10.0 (SD 5.9)
Janssens 2019	During study period	P = 0.819	Use of antibiotics The use of antibiotics (for exacerbations not leading to hospital admission) did not differ between groups during the observation period.
Kane 1984	During study period	Major surgical procedures P < 0.05	Major surgical procedures Intervention, mean per patient: 0.09 Control, mean per patient: 0.01 Minor surgical procedures Intervention, mean per patient: 0.42 Control, mean per patient: 0.30
		Over 80% of both hospice and control patients had no radiation treatments. However, those few who did had as many as 48 treatments, hence the large number.	Radiation treatments Intervention, mean per patient: 7.4 Control, mean per patient: 7.7
		P = 0.03	Chemotherapy treatments Intervention, mean per patient: 1.3 Control, mean per patient: 0.49
Markgren 2016 (linked to Brannstrom 2014)	During study period	Only the change in patients receiving full target doses of the ACEIs/angiotensin receptor blockers, BBs and MRAs were higher (P = 0.0009) in the intervention arm than in the control arm.	Prescribed medication use In the intervention arm, the percentages of angiotensin converting enzyme inhibitors (ACEIs) and mineralocorticoid receptor antagonists (MRAs) increased at the end of the study from baseline, while loop diuretics decreased. Beta‐receptor blockers (BBs) decreased somewhat in both groups. The number of patients treated with MRAs differed the most between groups, and increased from 10 (28%) to 15 (48%) in the PREFER arm compared with 13 (35%) vs 13 (39%) in the control group. The change in patients receiving full target doses (+8 vs. +1) of the ACEIs/angiotensin receptor blockers, BBs and MRAs were higher (P = 0.0009) in the intervention arm than in the control arm.
O'Riordan 2019	During study period	CRT device, P = 0.3 ACE1/ARB device, P = 0.2 Diuretics, P = 0.2 Spironolactone/eplerenone, P = 0.9 Beta‐blockers, P = 0.4	Medications (prescription and over‐the‐counter) in the medication list of patients Guideline‐driven HF therapies CRT device Intervention: 20% Control: 35.7% ACE1/ARB Intervention: 60% Control: 35.7% Diuretics Intervention: 86.7% Control: 64.3% Spironolactone/eplerenone Intervention: 26.7% Control: 28.6% Beta‐blockers Intervention: 66.7% Control: 50% Medications for other conditions Cholesterol‐lowering medication Intervention: 73.3% Control: 50% Anti‐anginal Intervention: 20% Control: 14.3% Diabetes medication Intervention: 13.3% Control: 14.3% Antidepressants Intervention: 20% Control: 28.6% Pain medication (NSAIDS and opioids) Intervention: 53.3% Control: 21.4% Anxiety medication Intervention: 0 Control: 7.1% Constipation Intervention: 26.7% Control: 28.6%
Rodin 2019	During study period	P value not stated	Referral to palliative care Intervention: 22 (100%) Control: 1 (5%) Referral to social work Intervention: 22 (100%) Control: 20 (100%) Referral to psychiatry Intervention: 1 (4.5%) Control: 1 (5%)
Rogers 2017	During study period	P value not stated	Frequency of interactions occurring between patients and providers Total number of hospital encounter records Intervention, mean (SD): 2.5 (0.45) Control, mean (SD): 2.4 (0.35) Telephone contact Intervention, mean (SD): 12.6 (1.2) Control, mean (SD): 10.6 (0.88)
Temel 2010	During study period	P = 0.05	Aggressive end‐of‐life care among 105 decedents (chemotherapy within 14 days before death, no hospice care, or admission to hospice 3 days or less before death) Intervention: 54% Control: 33%
Temel 2010			Chemotherapy within 30 days of death Intervention: 32.5% Control: 42%
ACEI: ARB: BB: CPR: Cardiopulmonary Resuscitation CRT: HF:IQR: interquartile range M: mean MRA: n: number ns: NSAID: PREFER: sc/im: subcutaneous/Intramuscuslar SD: standard deviation

Studies	Participants interviewed	Qualitative approach	Findings of the qualitative study	Findings of the quantitative component
Bajwah 2015 (patients with interstitial lung disease (ILD))	5 patients 5 carers 1 ILD consultant 1 ILD CNS 1 community matron 1 community palliative care nurse 1 GP	Semi‐structured interviews analysed using a constant comparison approach within framework analysis	Findings: Patients and carers interviewed valued the case conference as they felt that it "laid everything on the table" and importantly addressed concerns and anxieties that had been playing on patients’ and carers’ minds. The qualitative work also identified lack of early referral to palliative care by community health professionals, despite requests from patients and carers, and some gatekeeping by hospital health professionals. Themes from patients: Support in the community Crisis management Palliative care, psychological support Advance care planning Themes from health professionals: GPs ‐ collaboration of care and efficiency Community palliative care clinical nurse specialist – individual care plans and practical problems addressed ILD consultant – symptom control ILD CNS – empowering health professionals	Primary outcome: Symptom burden Mean (SD) POS scores at 4 weeks were ‐5.7 (7.5) fast‐track vs ‐0.4 (8.0) control, (mean change difference between the two arms was ‐5.3 (95% CI ‐9.8 to ‐0.7) independent t test P = 0.02); effect size (95% CI) ‐0.7 (‐1.2 to ‐0.1). Secondary outcomes: The secondary outcomes of quality of life, anxiety and depression were superior in the fast‐track arm, and none were worse.
Bakitas 2013 (linked to Bakitas 2009) (ENABLE II) (cancer patients)	35 oncology clinicians comprising 21 physicians and 14 nurse practitioner	Semi‐structured interviews analysed using thematic analysis	Findings: Oncologists believed that integrating palliative care at the time of an advanced cancer diagnosis enhanced patient care and complemented their practice. Five themes comprised oncologists' views on the complementary role of palliative care: (1) “refer early and often,” (2) referral challenges: “palliative” equals “hospice”; “Heme patients are different,” (3) palliative care as consultants or co‐managers, (4) palliative care “shares the load,” and (5) ENABLE II facilitated palliative care integration. Self‐assessment of their practice with advanced cancer patients comprised four themes: (1) treating the whole patient, (2) focussing on quality versus quantity of life, (3) “some patients just want to fight,” and (4) helping with transitions; timing is everything.	Primary outcomes: Quality of life: The estimated treatment effects (intervention minus usual care) for all participants were a mean (SE) of 4.6 (2) for quality of life (P = 0.02) Symptom intensity The estimated treatment effects (intervention minus usual care) for all participants were a mean (SE) of ‐27.8 (15) for symptom intensity (P = 0.06) Resource use: Intensity of service did not differ between the 2 groups. Secondary outcomes: The estimated treatment effects (intervention minus usual care) for all participants were a mean (SE) of ‐1.8 (0.81) for depressed mood (P = 0.02).
Maloney 2013 (linked to Bakitas 2009 ) (ENABLE II) (cancer patients)	53 patients (28 females included)	Semi‐structured interviews analysed using thematic analysis	Findings: Participants' perceptions of intervention benefits were represented by four themes: enhanced problem‐solving skills, better coping, feeling empowered, and feeling supported or reassured. Three themes related to trial participation: helping future patients and contributing to science, gaining insight through completion of questionnaires, and trial/intervention aspects to improve. Participants did not describe participation as burdensome but rather described some inconveniences or disappointments such as non‐attendance of meetings by other participants and disappointment at not being randomised to the intervention group.	Primary outcomes: Quality of life: The estimated treatment effects (intervention minus usual care) for all participants were a mean (SE) of 4.6 (2) for quality of life (P = 0.02) Symptom intensity The estimated treatment effects (intervention minus usual care) for all participants were a mean (SE) of ‐27.8 (15) for symptom intensity (P = 0.06) Intensity of service did not differ between the 2 groups. Secondary outcomes: The estimated treatment effects (intervention minus usual care) for all participants were a mean (SE) of ‐1.8 (0.81) for depressed mood (P = 0.02).
Talabani 2017 (linked to Brannstrom 2014) (heart failure (HF) patients)	12 patients from the intervention group (8 men included)	Semi‐structured interviews analysed using content analysis	Findings: Two themes and a total of five categories were identified. The first theme was feeling secure and safe through receiving care at home with the categories: having access to readily available care at home, being followed up continuously and having trust in the team members' ability to help. The second theme was being acknowledged as both a person and a patient, with the following two categories: being met as a person, participating in decisions about one's care and receiving help for symptoms of both HF and comorbidities. The team also offered relatives support, which patients appreciated.	Outcomes: Quality of life: Between‐group analysis revealed that patients receiving HSPC had improved HRQoL compared with controls (57.6 ± 19.2 vs. 48.5 ± 24.4, age‐adjusted P = 0.05). Within‐group analysis revealed a 26% improvement in the HSPC group for HRQoL (P = 0.046) compared with 3% (P = 0.82) in the control group. Quality of life improved by 24% (P = 0.047). Symptom burden: Total symptom burden improved by 18% (P = 0.035) Resource use: Fifteen rehospitalisations (103 days) occurred in the HSPC group, compared with 53 (305 days) in the control group.
Farquhar 2014 (cancer patients)	20 patients (and associated carers)	Semi‐structured interviews analysed using framework analysis	Findings: Breathlessness intervention service (BIS) reduced fear and worry, and increased confidence in managing breathlessness. Patients and carers consistently identified specific and repeatable aspects of the BIS model and interventions that helped. The multidisciplinary staff expertise was repeatedly noted. How interventions were delivered was important with a suggestion that the intervention was delivered through the provision of knowledge, with specialist expertise, which increased patients’ and carers’ confidence. BIS legitimised breathlessness and increased knowledge whilst making patients and carers feel ‘not alone’.	Primary outcome: BIS reduced patient distress due to breathlessness (primary outcome: −1.29; 95% CI −2.57 to −0.005; P = 0.049) significantly more than the control group; 94% of respondents reported a positive impact (51/53) Secondary outcomes: Mean CRQ mastery scores improved only negligibly in the intervention arm and remained stable for controls. No differences were found between trial arms on other CRQ domains (dyspnoea, fatigue or emotional function). Mean anxiety scores (HADS) remained fairly stable (both arms). Mean depression scores decreased slightly in the intervention arm, increasing slightly for controls. There was little change in other patient or carer outcomes. BIS had a 66% likelihood of better outcomes in terms of reduced distress due to breathlessness at lower health/social care costs than standard care (81% with informal care costs included).
Farquhar 2016 (Non‐cancer (mostly COPD)	20 patients (and associated carers)	Semi‐structured interviews analysed using framework analysis	Findings: Patients with non‐malignant conditions and their carers described a range of impacts including reduced fear, anxiety, worry, and feelings of panic, as well as feeling more confident about breathlessness. They valued the multidisciplinary staff expertise (their knowledge and understanding of life with breathlessness), the characteristics of the BIS staff (their approachability and attentiveness) and their reassuring and positive approach, and the time BIS gave them to talk about breathlessness with an expert. They reported that being seen at home was especially helpful. The findings suggest that it was not only the provision of these interventions that was important, but also that how they were delivered was key to their impact: delivery of interventions through the provision of knowledge (why and how interventions work or specific guidance on how and when to use a particular intervention) increased patients’ and carers’ confidence.	Primary outcome: There was no difference between groups in the primary outcome ("distress due to breathlessness"), when compared to standard care, of –0.24 (95 % CI: –1.30, 0.82). Secondary outcomes: Mean CRQ mastery scores improved slightly on both arms with greater improvement in the intervention arm. No differences were found between trial arms on other CRQ domains (dyspnoea, fatigue or emotional function). Mean patient anxiety scores decreased slightly for the intervention arm and increased slightly for the control arm and mean depression scores decreased slightly in the intervention arm and remained stable for controls; no between‐group difference was found. Mean anxiety scores for carers achieved a greater, 1.65‐point, reduction in the intervention arm compared with a 0.15‐point reduction for controls, adjusted difference of –1.22 (95 % CI: –2.84 to 0.40), P = 0.14. There was little change in other patient or carer secondary outcomes. Carers of patients randomised to the intervention arm achieved a greater, 1.03‐point, reduction in their distress due to their patient’s breathlessness compared with a 0.2‐point increase for controls, adjusted difference of –0.42 (95 % CI: –1.86 to 1.02), P = 0.56. BIS resulted in extra mean costs of GBP799, reducing to GBP100 when outliers were excluded.
Hopp 2016 (patients with heart failure)	85 patients	Unclear although the authors stated that clinical records were qualitatively reviewed	Findings: Patients expressed concerns about hospital palliative care as it might prevent them from receiving more aggressive treatment. Most patients did not engage with advanced care options.	Primary outcome: There was no difference between groups in the primary outcome (election vs non‐election of measure of comfort‐oriented care) (difference 9.3%, 95% CI ‐11.8% to 30%; P = 0.12).
Veron 2018 (linked to Janssens 2019) (COPD patients)	18 patients (44.4% females)	Semi‐structured interviews analysed using thematic content analysis	Findings: Patients described poor recollection of the RCT and difficulties understanding the palliative care intervention. No major differences were observed between patients who received the specialised intervention and those who did not. Content analysis emphasised that although they experienced disabling symptoms, participants tended to attribute their limitations to problems other than COPD and some declared that they were not sick. Patients reported restrictions due to oxygen therapy, and the burden of becoming dependent on it. This dependence resulted in intense anxiety, leading participants to focus on the present only. A strong feeling of perceived helplessness emerged from the patients' interviews.	Primary outcomes: Patients in the HSPC group were hospitalised for respiratory failure (incidence rate ratio (IRR) 1.87, 95% CI 1.04 to 3.48, P = 0.026) and admitted to the emergency ward (IRR 2.05, 95% CI 1.11 to 3.94, P = 0.014) twice as often during follow‐up than the control group. However, after the Benjamini and Hochberg correction for multiple testing, none of these differences was significant. Furthermore, median values were identical in both groups (hospitalisation: median (IQR): 0.0 (1 to 2) vs. 1.5 (1 to 4), P = 0.219; admissions to emergency wards: 1.0 (0; 3) vs. 1.0 (0; 4), P = 0.484). Secondary outcomes: There was no difference in HRQoL assessed using the SF‐36 between the HSPC and control group. There was no difference in anxiety and depression measured by the HADS‐anxiety and HADS‐depression between the intervention and control group. At inclusion, 3 patients in each group had completed their advanced care planning (ACP) directives (P = 1.00). At the end of the study, 9 patients (35%) of the intervention group versus 3 (13%) of the control group had completed ACP directives (P = 0.194). There was therefore a difference in the number of patients who wrote their ACP directives in favour of the intervention group (P = 0.023). Survival did not differ between the groups (P = 0.913). 8 deaths occurred, 4 in each group. In the intervention group, survival was 454 days (1.24 years; 95% CI: 382 to 525 vs. 425 days (1.16 years; 95% CI: 339 to 509) in the control group; P = 0.592.
Lowther 2018 (linked to Lowther 2015) (HIV patients)	20 patients (predominantly females (85%)) from the intervention group	Semi‐structured interviews analysed using thematic content analysis	Findings: Patients reported that having time to talk, appropriate pain medication and effective health education was of therapeutic value for their psychological well‐being. Integration of mixed method findings suggested that positive effect in quantitative measures of mental health and well‐being were attributable to the active ingredients of: appropriate medication, effective health education and counselling, and having time to talk in clinical encounters. Mechanisms of action included symptom relief, improved understanding of illness and treatment, and support focussed on articulated concerns. Participants whose quality of life remained static or deteriorated reported concurrent intractable physical or social problems which prevented them from fulfilling their social roles and led to financial difficulties. This in turn led to stress, which was a barrier to positive psychological well‐being.	Primary outcome: In the control group, median pain score on the pain item of the APOS (range: 0 to 5; 0 indicates worst pain) improved from 1.0 (IQR 0.0 to 2.0) at baseline to 5.0 (3.0 to 5.0) at 4 months; in the HSPC group, it improved from 1.0 (0.0 to 2.0) at baseline to 4.5 (3.0 to 5.0) at 4 months. There was no between‐group difference (coefficient ‐0.01, 95% CI ‐0.36 to 0.34, P = 0.95). Secondary outcomes: Person‐centred assessment and care delivered by staff who had received additional training had positive effects on self‐reported mental health‐related quality of life and psychosocial well‐being.
Giovannetti 2018 (linked to Solari 2018) (multiple sclerosis)	12 patients, 15 caregivers, 8 physicians and nine members of HSPC team	Semi‐structured interviews analysed using framework method	Findings: Three themes emerged from the interviews: 'expectations,' 'met and unmet needs', and 'barriers'. Participants described benefits from the intervention such as improved control of symptoms and reduced sense of isolation of the patient‐caregiver dyads. Patient‐caregiver dyads valued the expertise of the HSPC team. Limitations identified that included factors related to experimental design (difficulty of dyads in identifying examiner and team roles, additional burden for caregivers); team issues (insufficient team building/supervision, competing priorities); limitations of the intervention itself (insufficient length, lack of rehabilitation input); and external factors (resource limitations, under‐responsive services/professionals). The referring physician focus groups provided little experiential data.	Primary outcomes: There was greater reduction in symptom burden (POS‐S‐MS) in the HSPC group compared to usual care (P = 0.047). Effect size was 0.20 at 3 months and 0.32 at 6 months. Changes in quality of life (SEIQoL‐DW index) did not differ between the two groups. Secondary outcomes: There were no differences between the secondary patient (POS, HADS, FIM total score) and carer outcomes (ZBI) at three and six months. There were 22 serious adverse events in 20 patients, 15 events in 13 patients in the HSPC group (30%) and 7 events in 7 patients in the control group (27%; P = 0.78).
Slota 2014 (linked to Wallen 2012) (cancer patients)	In Wallen 2012, n was unclear while Slota 2014 had 34 participants	Open‐ended, qualitative questions on a questionnaire. Method of analysis stated in Wallen 2012 was transcript‐based analysis while thematic analysis was stated in Slota 2014	Findings: Patients identified consistent communication, emotional support, and pain and symptom management as positive contributions delivered by the intervention. Consistent communication was described in terms of the team as a whole and their focus on individualising patients’ pain and comfort needs. When describing emotional support or 'being there' participants emphasised the support and reassurance they felt knowing the Pain and Palliative Care Team was available across time. They saw team members as their advocates.	Primary outcomes and secondary outcomes: There was no difference between HSPC and control group. However, for those who remained on study for 12 months, the HSPC group performed better than their standard of care counterparts.
ACP: APOS: African Palliative Care Outcome Scale BIS: CI: CNS: Clinical Nurse Specialist COPD: CRQ: Chronic Respiratory Questionnaire ENABLE II: FIM: GBP: Great British Pounds GP: General Practitioner HADS: Hospital Anxiety and Depression Scale HF: HIV: HRQL: Health‐Related Quality of Life HRQoL: HSPC: n: number HSPC: Hospital‐based Specialist Palliative Care ILD: IQR: Interquartile range IRR: POS: Palliative Care Outcome Scale POS‐S‐MS: SD: SE: Standard Error SEIQoL‐DW index: Schedule for the Evaluation of Individual Quality of Life‐Direct Weighting index SF‐36: ZBI: Zarit Burden Inventory

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