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Cochrane Database of Systematic Reviews

Cuidados paliativos tempranos en pacientes adultos con cáncer avanzado

Información

DOI:
https://doi.org/10.1002/14651858.CD011129.pub2Copiar DOI
Base de datos:
  1. Cochrane Database of Systematic Reviews
Versión publicada:
  1. 12 junio 2017see what's new
Tipo:
  1. Intervention
Etapa:
  1. Review
Grupo Editorial Cochrane:
  1. Grupo Cochrane de Dolor y cuidados paliativos

Copyright:
  1. Copyright © 2017 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

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Autores

  • Markus W Haun

    Correspondencia a: Department of General Internal Medicine and Psychosomatics, Im Neuenheimer Feld 410, Heidelberg University Hospital, Heidelberg, Germany

    [email protected]

  • Stephanie Estel

    Department of General Internal Medicine and Psychosomatics, Im Neuenheimer Feld 410, Heidelberg University Hospital, Heidelberg, Germany

  • Gerta Rücker

    Institute for Medical Biometry and Statistics, Faculty of Medicine and Medical Center – University of Freiburg, Freiburg, Germany

  • Hans‐Christoph Friederich

    Psychosomatic Medicine and Psychotherapy, University Hospital Düsseldorf, Düsseldorf, Germany

  • Matthias Villalobos

    Department of Thoracic Oncology, Thoraxklinik at Heidelberg University Hospital, Heidelberg, Germany

  • Michael Thomas

    Department of Thoracic Oncology, Thoraxklinik at Heidelberg University Hospital, Heidelberg, Germany

  • Mechthild Hartmann

    Department of General Internal Medicine and Psychosomatics, Im Neuenheimer Feld 410, Heidelberg University Hospital, Heidelberg, Germany

Contributions of authors

MWH drafted the protocol, developed and ran the search strategy, obtained copies of studies, selected studies for inclusion, extracted data from studies, entered data into RevMan, carried out and interpreted the analysis, and drafted the review. SE ran the search strategy, obtained copies of studies, selected studies for inclusion, extracted data from studies, and entered data into RevMan. GR drafted the protocol and assisted in carrying out and interpreting the analyses, and in drafting the final review. HCF and MT drafted the protocol, interpreted the analyses, and drafted the final review. MV interpreted the analyses from a clinical point of view and drafted the final review. MH drafted the protocol, developed the search strategy, selected studies for inclusion (as arbiter), supervised in carrying out and interpreting the analyses, and drafted the review.

Sources of support

Internal sources

  • Heidelberg University Hospital, Germany.

    Employer of MWH, SE, MV, MT, and MH

  • University Medical Center Freiburg, Germany.

    Employer of GR

  • University of Duesseldorf, Germany.

    Employer of HCF

External sources

  • No sources of support supplied

Declarations of interest

MWH: none known; MWH is an internal medicine physician (internist) and a junior research group leader in mental health services research.

SE: none known.

GR: none known.

HCF: none known; HCF is a specialist in psychosomatic medicine and internal medicine, and manages psychiatric comorbidity in patients with somatic illnesses.

MV: none known; MV is a specialist oncology and palliative care physician and manages patients with advanced cancer.

MT is a department head of thoracic oncology (Thoraxklinik, University of Heidelberg) and manages patients with malignant thoracic diseases and lung metastases. MT received personal consulting fees from Lilly, Novartis, Roche, AstraZeneca, Pfizer, Boehringer, and BMS in 2014; from Lilly, Novartis, Roche, AstraZeneca, BMS, MSD, Pfizer, Boehringer, and Celgene in 2015; and from Lilly, Novartis, Roche, AstraZeneca, BMS, MSD, Pfizer, Boehringer, and Celgene in 2016 for attending boards. MT received lecture fees from Lilly, Novartis, Roche, AstraZeneca, Pfizer, and Boehringer in 2014; from Lilly, Novartis, Roche, AstraZeneca, BMS, MSD, Pfizer, and Boehringer in 2015; and from Lilly, Novartis, AstraZeneca, BMS, MSD, Pfizer, Boehringer, and Celgene in 2016.

MH: none known.

Acknowledgements

We would like to thank Sabine Sommerfeldt for her contribution to development of this protocol. We would also like to thank Maria‐Inti Metzendorf of the Library for the Medical Faculty of Mannheim, Heidelberg University, for contributing to the search strategies, and Joanne Abbott, Information Specialist at the Cochrane PaPaS Group, for running database searches.

Cochrane Review Group funding acknowledgement: The National Institute for Health Research (NIHR) is the largest single funder of the Cochrane Pain, Palliative and Supportive Care Review Group (PaPaS).

Disclaimer: The views and opinions expressed therein are those of the review authors and do not necessarily reflect those of the NIHR, the National Health Service (NHS), or the Department of Health.

Version history

Published

Title

Stage

Authors

Version

2017 Jun 12

Early palliative care for adults with advanced cancer

Review

Markus W Haun, Stephanie Estel, Gerta Rücker, Hans‐Christoph Friederich, Matthias Villalobos, Michael Thomas, Mechthild Hartmann

https://doi.org/10.1002/14651858.CD011129.pub2

2014 May 26

Early palliative care for improving quality of life and survival time in adults with advanced cancer

Protocol

Markus W Haun, Stephanie Estel, Gerta Rücker, Hans‐Christoph Friederich, Michael Thomas, Mechthild Hartmann

https://doi.org/10.1002/14651858.CD011129

Differences between protocol and review

We updated and added references to the Background and Methods sections. In the Background section, we updated our definition of 'early palliative care' on the basis of current literature and introduced the recently conceptualised classification of models for early palliative care provided by Hui 2015a. In the Methods section, we documented our decision to conduct a subgroup analysis for two different models. In the 'Types of interventions' section, we specified as an additional inclusion criterion 'An early palliative care intent had to be stated explicitly or be reflected in the sample composition, i.e. most participants had to be enrolled shortly after diagnosis of advanced disease.' In the 'Assessment of risk of bias in included studies' section, we now state that we included blinding of participants and outcome assessment as sixth and seventh domains in the risk of bias assessment. Also in this section, we updated our justification for not excluding small studies from the review. We refrained from compiling funnel plots because of the small number of included studies. In light of new recommendations by the GRADE Working Group (Alonso‐Coello 2016), we have replaced the term "quality of the evidence", which we had used in the protocol, with the term "certainty of the evidence". For reasons of completeness, we reported results on outcomes in the review that had not been prespecified in the protocol (i.e. place of death, problems with medical interactions and satisfaction with care, and illness and prognosis understanding). Furthermore, we now explicitly state that we based survival analysis on unadjusted death hazard ratios. To enhance comprehensibility, we decided to refrain from additionally converting SMDs to odds ratios. We have explained in the Methods section all post‐protocol decisions concerning methods.

Keywords

MeSH

Medical Subject Headings Check Words

Humans;

PICO

Population
Intervention
Comparison
Outcome

El uso y la enseñanza del modelo PICO están muy extendidos en el ámbito de la atención sanitaria basada en la evidencia para formular preguntas y estrategias de búsqueda y para caracterizar estudios o metanálisis clínicos. PICO son las siglas en inglés de cuatro posibles componentes de una pregunta de investigación: paciente, población o problema; intervención; comparación; desenlace (outcome).

Para saber más sobre el uso del modelo PICO, puede consultar el Manual Cochrane.

Screening process diagram (as recommended by the PRISMA statement).
Figuras y tablas -
Figure 1

Screening process diagram (as recommended by the PRISMA statement).

Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
Figuras y tablas -
Figure 2

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

Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
Figuras y tablas -
Figure 3

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

Forest plot of comparison: 1 Health‐related quality of life, outcome: 1.1 Health‐related quality of life.
Figuras y tablas -
Figure 4

Forest plot of comparison: 1 Health‐related quality of life, outcome: 1.1 Health‐related quality of life.

Forest plot of comparison: 1 Early palliative care vs TAU, outcome: 1.2 Survival.
Figuras y tablas -
Figure 5

Forest plot of comparison: 1 Early palliative care vs TAU, outcome: 1.2 Survival.

Forest plot of comparison: 1 Early palliative care vs standard oncological care, outcome: 1.2 Depression.
Figuras y tablas -
Figure 6

Forest plot of comparison: 1 Early palliative care vs standard oncological care, outcome: 1.2 Depression.

Forest plot of comparison: 1 Early palliative care vs standard oncological care, outcome: 1.4 Symptom intensity.
Figuras y tablas -
Figure 7

Forest plot of comparison: 1 Early palliative care vs standard oncological care, outcome: 1.4 Symptom intensity.

Forest plot of comparison: 1 Early palliative care vs standard oncological care, outcome: 1.5 Health‐related quality of life (sensitivity analysis for study design including RCTs only).
Figuras y tablas -
Figure 8

Forest plot of comparison: 1 Early palliative care vs standard oncological care, outcome: 1.5 Health‐related quality of life (sensitivity analysis for study design including RCTs only).

Forest plot of comparison: 1 Early palliative care vs standard oncological care, outcome: 1.6 Symptom intensity (sensitivity analysis for study design including RCTs only).
Figuras y tablas -
Figure 9

Forest plot of comparison: 1 Early palliative care vs standard oncological care, outcome: 1.6 Symptom intensity (sensitivity analysis for study design including RCTs only).

Comparison 1 Early palliative care vs standard oncological care, Outcome 1 Health‐related quality of life.
Figuras y tablas -
Analysis 1.1

Comparison 1 Early palliative care vs standard oncological care, Outcome 1 Health‐related quality of life.

Comparison 1 Early palliative care vs standard oncological care, Outcome 2 Depression.
Figuras y tablas -
Analysis 1.2

Comparison 1 Early palliative care vs standard oncological care, Outcome 2 Depression.

Comparison 1 Early palliative care vs standard oncological care, Outcome 3 Survival.
Figuras y tablas -
Analysis 1.3

Comparison 1 Early palliative care vs standard oncological care, Outcome 3 Survival.

Comparison 1 Early palliative care vs standard oncological care, Outcome 4 Symptom intensity.
Figuras y tablas -
Analysis 1.4

Comparison 1 Early palliative care vs standard oncological care, Outcome 4 Symptom intensity.

Comparison 1 Early palliative care vs standard oncological care, Outcome 5 Health‐related quality of life (sensitivity analysis for study design including RCTs only).
Figuras y tablas -
Analysis 1.5

Comparison 1 Early palliative care vs standard oncological care, Outcome 5 Health‐related quality of life (sensitivity analysis for study design including RCTs only).

Comparison 1 Early palliative care vs standard oncological care, Outcome 6 Symptom intensity (sensitivity analysis for study design including RCTs only).
Figuras y tablas -
Analysis 1.6

Comparison 1 Early palliative care vs standard oncological care, Outcome 6 Symptom intensity (sensitivity analysis for study design including RCTs only).

Summary of findings for the main comparison. Early palliative care for adults with advanced cancer

Clinical question: Should early palliative care be preferred over treatment as usual for improving health‐related quality of life, depression, and symptom intensity in patients with advanced cancer?

Patient or population: patients with advanced cancer

Settings: mainly outpatient care in Australia, Canada, Italy, and the USA
Intervention: early palliative care

Comparison: treatment as usual

Follow‐up: at 12 weeks or mean difference in repeated measurement results for longitudinal designs

Outcomes

Anticipated absolute effects* (95% CI)

Relative effect
(95% CI)

Number of participants
(studies)

Certainty of the evidence
(GRADE)

Comments

Risk with treatment as usual

Risk with early palliative care

Health‐related quality of life (HRQOL), SD units: measured on FACIT‐Pal, TOI of FACT‐Hep, TOI of FACT‐L, FACT‐G, McGill Quality of Life, FACIT‐Sp. Higher scores indicate better HRQOL. Follow‐up: range 12 weeks to 52 weeks

HRQOL score improved on average 0.27 (95% CI 0.15 to 0.38) SDs more in early palliative care participants than in control participants

1028
(7 RCTs)

⊕⊕⊝⊝
LOW1,2,3

By conventional criteria, an SMD of 0.2 represents a small effect, 0.5 a moderate effect, and 0.8 a large effect (Cohen 1988)

Health‐related quality of life (HRQOL), natural units: measured on FACT‐G (from 0 to 108)

Baseline control group mean score at 70.5 pointsa

HRQOL score improved on average 4.59 (95% CI 2.55 to 6.46) points more in early palliative care participants than in control participants

1028
(7 RCTs)

⊕⊕⊝⊝
LOW1,2,3

Calculated by transforming all scales to the FACT‐G in which the minimal clinically important difference is approximately 5 and the SD in the cancer validation sample was 17.0 (Brucker 2005)

Survival: estimated with the unadjusted death hazard ratio

Study populationb

HR 0.85, 95% CI 0.56 to 1.28

800
(4 RCTs)

⊕⊝⊝⊝
VERY LOW1,4,5,6

61 per 100

56 per 100 (41‐71)

Depression, SD units: measured on CES‐D, HADS‐D, PHQ‐9. Higher scores indicate higher depressive symptom load. Follow‐up: range 12 weeks to 52 weeks

Depression score improved on average ‐0.11 (95% CI ‐0.26 to 0.03) SDs more in early palliative care participants than in control participants

762
(5 RCTs)

⊕⊝⊝⊝

VERY LOW1,2,4

By conventional criteria, an SMD of 0.2 represents a small effect, 0.5 a moderate effect, and 0.8 a large effect (Cohen 1988)

Depression, natural units: measured on CES‐D (from 0 to 60). Higher scores indicate higher depressive symptom load

Baseline control group mean score at 13.8 pointsc

Depressive symptoms score improved on average ‐0.98 (95% CI ‐2.31 to 0.27) points more in early palliative care participants than in control participants

762
(5 RCTs)

⊕⊝⊝⊝

VERY LOW1,2,4

Calculated by transforming all scales to CES‐D

and applying an SD of 8.9 from baseline control group score in Bakitas 2009

Symptom intensity, SD units: measured on ESAS, QUAL‐E Symptom Impact Subscale, SDS, RSC, LCS of FACT‐L, HCS of FACT‐Hep. Higher scores indicate higher symptom intensity. Follow‐up: range 12 weeks to 52 weeks

Symptom intensity score improved on average ‐0.23 (95% CI ‐0.35 to ‐0.1) SDs more in early palliative care participants than in control participants

1054
(7 RCTs)

⊕⊕⊝⊝
LOW1,2,3

By conventional criteria, an SMD of 0.2 represents a small effect, 0.5 a moderate effect, and 0.8 a large effect (Cohen 1988)

Symptom intensity, natural units: measured on ESAS (from 0 to 900). Follow‐up: range 12 weeks to 52 weeks

Baseline control group mean score at 286.3 pointsc

Symptom intensity symptoms score improved on average ‐35.4 (95% CI ‐53.9 to ‐15.4) points more in early palliative care participants than in control participants

1054
(7 RCTs)

⊕⊕⊝⊝
LOW1,2,3

Calculated by transforming all scales to the ESAS and applying an SD of 154.0 from baseline control group score in Bakitas 2009

Adverse events

See comment

See comment

Not estimable

1614
(7 RCTs)

See comment

Most often, study authors did not address assessment or findings on adverse events in their study publications. However, on request, authors of 6 studies described the tolerability of early palliative care as very good. A single study mentioned adverse events only in the early palliative care group, i.e. higher percentage of participants with severe scores for pain and poor appetite along with higher level of unmet needs (Tattersall 2014)

*Risk in the intervention group (and its 95% confidence interval) is based on assumed risk in the comparison group and relative effect of the intervention (and its 95% CI)

aApproximate average of baseline control group FACT‐G scores across 4 included studies (Bakitas 2009; Bakitas 2015; Maltoni 2016; Temel 2010)

b12‐Month follow‐up control group risk in the largest study reporting on survival (Bakitas 2009)

cBaseline control group CES‐D score in the largest study reporting on depression (Bakitas 2009)

CI: confidence interval; GRADE: Grading of Recommendations Assessment; HR: unadjusted death hazard ratio; SD: standard deviation; SMD: standardised mean difference

GRADE Working Group grades of evidence
High certainty: We are very confident that the true effect lies close to that of the estimate of the effect.
Moderate certainty: 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 certainty: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect.
Very low certainty: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect.

1We downgraded 2 points owing to very serious limitations in study quality (high risk of bias across studies)

2We decided against downgrading for indirectness, although 2 studies were conducted exclusively in patients with metastatic pancreatic and advanced lung cancer, respectively (Maltoni 2016; Temel 2010). We decided against downgrading for inconsistency, as we did not detect significant heterogeneity

3We decided against downgrading for imprecision, as the optimal information size (OIS) criterion was met, and the 95% confidence interval around the difference in effect between intervention and control excludes zero

4We downgraded 1 point for imprecision, as the optimal information size (OIS) criterion was met, but the 95% confidence interval around the difference in effect between intervention and control includes zero. The 95% confidence interval fails to exclude harm

5We decided against downgrading for important inconsistency (large I2) because we had downgraded by 3 points already

6We decided against downgrading for indirectness, as only a single study was conducted exclusively in patients with advanced lung cancer (Temel 2010)

Figuras y tablas -
Summary of findings for the main comparison. Early palliative care for adults with advanced cancer
Comparison 1. Early palliative care vs standard oncological care

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Health‐related quality of life Show forest plot

7

1028

Std. Mean Difference (Random, 95% CI)

0.27 [0.15, 0.38]

1.1 Co‐ordinated care model

3

485

Std. Mean Difference (Random, 95% CI)

0.21 [0.03, 0.39]

1.2 Integrated care model

4

543

Std. Mean Difference (Random, 95% CI)

0.31 [0.15, 0.46]

2 Depression Show forest plot

5

762

Std. Mean Difference (Random, 95% CI)

‐0.11 [‐0.26, 0.03]

2.1 Co‐ordinated care model

3

526

Std. Mean Difference (Random, 95% CI)

‐0.06 [‐0.23, 0.12]

2.2 Integrated care model

2

236

Std. Mean Difference (Random, 95% CI)

‐0.24 [‐0.50, 0.02]

3 Survival Show forest plot

4

800

Hazard Ratio (Random, 95% CI)

0.85 [0.56, 1.28]

4 Symptom intensity Show forest plot

7

1054

Std. Mean Difference (Random, 95% CI)

‐0.23 [‐0.35, ‐0.10]

4.1 Co‐ordinated care model

3

492

Std. Mean Difference (Random, 95% CI)

‐0.23 [‐0.41, ‐0.04]

4.2 Integrated care model

4

562

Std. Mean Difference (Random, 95% CI)

‐0.23 [‐0.43, ‐0.04]

5 Health‐related quality of life (sensitivity analysis for study design including RCTs only) Show forest plot

5

696

Std. Mean Difference (Random, 95% CI)

0.29 [0.14, 0.44]

6 Symptom intensity (sensitivity analysis for study design including RCTs only) Show forest plot

5

696

Std. Mean Difference (Random, 95% CI)

‐0.28 [‐0.43, ‐0.13]

Figuras y tablas -
Comparison 1. Early palliative care vs standard oncological care