Association Between Palliative Care and Patient and Caregiver Outcomes: A Systematic Review and Meta-analysis

Abstract

Importance: The use of palliative care programs and the number of trials assessing their effectiveness have increased.

Objective: To determine the association of palliative care with quality of life (QOL), symptom burden, survival, and other outcomes for people with life-limiting illness and for their caregivers.

Data sources: MEDLINE, EMBASE, CINAHL, and Cochrane CENTRAL to July 2016.

Study selection: Randomized clinical trials of palliative care interventions in adults with life-limiting illness.

Data extraction and synthesis: Two reviewers independently extracted data. Narrative synthesis was conducted for all trials. Quality of life, symptom burden, and survival were analyzed using random-effects meta-analysis, with estimates of QOL translated to units of the Functional Assessment of Chronic Illness Therapy-palliative care scale (FACIT-Pal) instrument (range, 0-184 [worst-best]; minimal clinically important difference [MCID], 9 points); and symptom burden translated to the Edmonton Symptom Assessment Scale (ESAS) (range, 0-90 [best-worst]; MCID, 5.7 points).

Main outcomes and measures: Quality of life, symptom burden, survival, mood, advance care planning, site of death, health care satisfaction, resource utilization, and health care expenditures.

Results: Forty-three RCTs provided data on 12 731 patients (mean age, 67 years) and 2479 caregivers. Thirty-five trials used usual care as the control, and 14 took place in the ambulatory setting. In the meta-analysis, palliative care was associated with statistically and clinically significant improvements in patient QOL at the 1- to 3-month follow-up (standardized mean difference, 0.46; 95% CI, 0.08 to 0.83; FACIT-Pal mean difference, 11.36] and symptom burden at the 1- to 3-month follow-up (standardized mean difference, -0.66; 95% CI, -1.25 to -0.07; ESAS mean difference, -10.30). When analyses were limited to trials at low risk of bias (n = 5), the association between palliative care and QOL was attenuated but remained statistically significant (standardized mean difference, 0.20; 95% CI, 0.06 to 0.34; FACIT-Pal mean difference, 4.94), whereas the association with symptom burden was not statistically significant (standardized mean difference, -0.21; 95% CI, -0.42 to 0.00; ESAS mean difference, -3.28). There was no association between palliative care and survival (hazard ratio, 0.90; 95% CI, 0.69 to 1.17). Palliative care was associated consistently with improvements in advance care planning, patient and caregiver satisfaction, and lower health care utilization. Evidence of associations with other outcomes was mixed.

Conclusions and relevance: In this meta-analysis, palliative care interventions were associated with improvements in patient QOL and symptom burden. Findings for caregiver outcomes were inconsistent. However, many associations were no longer significant when limited to trials at low risk of bias, and there was no significant association between palliative care and survival.

Figure 1. Results of Literature Searches to Identify Randomized Clinical Trials of Palliative Care Interventions

The specific reasons for exclusion of 5958 records at the title and abstract screening stage were not recorded.

Figure 2. Random-Effects Meta-analysis of Randomized Clinical Trials on the Association Between Palliative Care and Patient Quality of Life at 1- to 3-Month Follow-up

For all trials, the P value for the pooled standardized mean difference (SMD) was .02; τ², 0.52; and Q, 268.18. For trials at low risk of bias, the P value for the pooled the SMD was .01; τ², <0.0001; and Q, 3.36. For trials at high risk of bias, the P value for the pooled SMD was .05; τ², 1.52; and Q, 233.84. For trials at unclear risk of bias, the P value for the pooled SMD was .31; τ², 0.01; and Q, 3.00. Sample sizes in the figure are the number of patients analyzed at the specific time points. Error bars represent 95%CIs. The size of the shaded squares indicates study weight. Diamonds represent pooled SMDs and 95%CIs. The vertical dashed line indicates the pooled effect estimate, and the solid vertical line depicts a null effect. SF-36 indicates Short Form-36; EQ5D, EuroQol 5 Dimensions Questionnaire; FACIT-Pal, Functional Assessment of Chronic Illness Therapy–Palliative; FACT-L TOI, Functional Assessment of Cancer Therapy–Lung Treatment Outcome Index; FACT-G, Functional Assessment of Cancer Therapy- General; FACIT-Sp, Functional Assessment of Chronic Illness Therapy-Spirituality; KCCQ, Kansas City Cardiomyopathy Questionnaire; MLHFQ, Minnesota Living With Heart Failure Questionnaire; and MQOL-HK, McGill Quality of Life Questionnaire–Hong Kong adaptation. ^aSolid or hematological cancers. ^bBrain, gastrointestinal, head-neck, lung, and other cancers. ^cBreast, colon, lung, and gynecological cancers, and lymphoma. ^dNot further specified. ^eBreast cancer. ^fGastrointestinal, lung, genitourinary, and breast cancers. ^gCancer, chronic obstructive pulmonary disease, interstitial lung disease, and motor neuron disease. ^hNon–small cell lung cancer. ⁱLung, gastrointestinal, genitourinary, breast, and gynecological cancers. ^jBreast, colon, lung, and other cancers. ^kBreast, colon, lung, and prostate cancers.

Figure 3. Random-Effects Meta-analysis of Randomized Clinical Trials on the Association Between Palliative Care and Patient Quality of Life at 4- to 6-Month Follow-Up

For all trials, the P value for the pooled standardized mean difference (SMD) was .12; τ², 0.04; and Q, 28.51. For trials at high risk of bias, the P value for the pooled the SMD was .07; τ², <0.06; and Q, 9.15. For trials at low risk of bias, the P value for the pooled SMD was .01; τ² <0.0001; Q, 3.20. For trials at unclear risk of bias, the P value for the pooled SMD was .41; τ², 0.05; and Q, 4.86. Sample sizes in the figure are the number of patients analyzed at the specific time points. Error bars represent 95%CIs. The size of the shaded squares indicates study weight. Diamonds represent pooled SMDs and 95%CIs. The vertical dashed line indicates the pooled effect estimate, and the solid vertical line depicts a null effect. EQ-5D indicates EuroQol 5 Dimensions Questionnaire; FACT-G, Functional Assessment of Cancer Therapy-General; FACIT-Pal, Functional Assessment of Chronic Illness Therapy-Palliative; FACIT-Sp, Functional Assessment of Chronic Illness Therapy-Spirituality; HIV, human immunodeficiency virus; MOS-HIV, Medical Outcomes Study-HIV scale; KCCQ, Kansas City Cardiomyopathy Questionnaire; and SF-36, Short Form-36. ^aBrain, gastrointestinal, head-neck, lung, and other cancers. ^bBreast, colon, lung, and gynecological cancers, and lymphoma. ^cBreast cancer. ^dUpper gastrointestinal cancers. ^eGastrointestinal, lung, genitourinary, and breast cancers. ^fProstate cancer. ^gNot further specified. ^hLung, gastrointestinal, genitourinary, breast, and gynecological cancers. ⁱBreast, colon, lung, and prostate cancers.

Figure 4. Meta-analysis of Randomized Clinical Trials on the Association Between Palliative Care and Symptom Burden at 1- to 3-Month Follow-up

For all trials, the P value for the pooled standardized mean difference (SMD) was .03; τ², 0.86; and Q, 230.90. For trials at high risk of bias, the P value for the pooled the SMD was .14; τ², 2.34; and Q, 215.72. For trials at unclear risk of bias, the P value for the pooled SMD was .01; τ², <0.0001; and Q, 230.90. Sample sizes in the figure are the number of patients analyzed at the specific time points. Error bars represent 95%CIs. The size of the shaded squares indicates study weight. Diamonds represent pooled SMDs and 95%CIs. The vertical dashed line indicates the pooled effect estimate, and the solid vertical line depicts a null effect. CHFQ indicates Chronic Heart Failure Questionnaire; COPD, chronic obstructive pulmonary disease; ESAS, Edmonton Symptom Assessment Scale; FACT-L LCS, Functional Assessment of Cancer Therapy-Lung Lung Cancer Scale; NRS SOB, Numerical Rating Scale Shortness of Breath; POS, Palliative Outcomes Scale; QUAL-E, Quality of Life at the End of Life; and SES, Symptom Experience Scale. ^aSolid or hematological cancers. ^bCOPD or other source of dyspnea. ^cBreast, colon, lung, and gynecological cancers, and lymphoma. ^dGastrointestinal, lung, genitourinary, and breast cancers. ^eCancer, COPD, heart failure, interstitial lung disease, motor neuron disease. ^fNon–small cell lung cancer. ^gLung, gastrointestinal, genitourinary, breast, and gynecological cancers.

Figure 5. Meta-analysis of Randomized Clinical Trials on the Association Between Palliative Care and Symptom Burden at 4- to 6-Month Follow-up

For all trials, the P value for the pooled standardized mean difference (SMD) was .01; τ², <0.0001; and Q, 3.97. For trials at low risk of bias, the P value for the pooled the SMD was .06; τ², <0.0001; and Q, 0.62. For trials at high risk of bias, the P value for the pooled SMD was .01; τ², <0.0001; and Q, 0.31. Sample sizes in the figure are the number of patients analyzed at the specific time points. Error bars represent 95%CIs. The size of the shaded squares indicates study weight. Diamonds represent pooled SMDs and 95%CIs. The vertical dashed line indicates the pooled effect estimate, and the solid vertical line depicts a null effect. APOS indicates African Palliative Outcomes Scale; BPI, Brief Pain Inventory; ESAS, Edmonton Symptom Assessment Scale; HF, heart failure; HIV, human immunodeficiency virus; MS, multiple sclerosis; OSQ, Omega Symptom Questionnaire; and SES, Symptom Experience Scale. ^aBreast, colon, lung, and gynecological cancers and lymphoma. ^bUpper gastrointestinal cancers. ^cGastrointestinal, lung, genitourinary, and breast cancers. ^dProstate cancer. ^eLung, gastrointestinal, genitourinary, breast, and gynecological cancers.

Figure 6. Meta-analysis of Randomized Clinical Trials on the Association Between Palliative Care and Survival

For all trials, the P value for the pooled hazard ratio (HR) was .44; τ², 0.08; and Q, 24.29. For trials at low risk of bias, the P value for the pooled the HR was .14; τ², <0.0001; and for Q, <0.0001. For high risk of bias, the P value for the pooled HR was .99; τ², <0.59; and Q, 7.03. For unclear risk of risk of bias the P value for the pooled HR was .74; τ², 0.06; and Q, 10.98. Sample sizes in the figure are the number of patients analyzed at the specific time points. Error bars represent 95%CIs. The size of the shaded squares indicates study weight. Diamonds represent pooled HRs and 95%CIs. The vertical dashed line indicates the pooled effect estimate, and the solid vertical line depicts a null effect (ie, HR, 1). ^aNon–small cell lung cancer. ^bGastrointestinal, lung, genitourinary, and breast cancers. ^cCancer, heart failure, chronic obstructive pulmonary disease, end-stage renal disease, stroke, and dementia. ^dBreast, colon, lung, and other cancers. ^eGastrointestinal, lung, breast, gynecological, genitourinary, kidney, lymphoma, skin, and other cancers.