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Overview of Systematic Reviews of Advance Care Planning: Summary of Evidence and Global Lessons

  • Geronimo Jimenez
    Correspondence
    Address correspondence to: Geronimo Jimenez, MA, Lee Kong Chian School of Medicine, Novena Campus, Nanyang Technological University, 11 Mandalay Road, Level 18 Clinical Sciences Building, Singapore, Singapore 308232.
    Affiliations
    Centre for Population Health Sciences (CePHaS), Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore
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  • Woan Shin Tan
    Affiliations
    Centre for Population Health Sciences (CePHaS), Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore

    NTU Institute of Health Technologies (HealthTech), Interdisciplinary Graduate School, Nanyang Technological University, Singapore, Singapore

    Health Services and Outcomes Research Department, National Healthcare Group, Singapore, Singapore
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  • Amrit K. Virk
    Affiliations
    Centre for Population Health Sciences (CePHaS), Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore
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  • Chan Kee Low
    Affiliations
    Economics Programme, School of Social Sciences, Nanyang Technological University, Singapore, Singapore
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  • Josip Car
    Affiliations
    Centre for Population Health Sciences (CePHaS), Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore

    Global eHealth Unit, Department of Primary Care and Public Health, School of Public Health, Imperial College London, London, UK
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  • Andy Hau Yan Ho
    Affiliations
    Centre for Population Health Sciences (CePHaS), Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore

    Psychology Programme, School of Social Sciences, Nanyang Technological University, Singapore, Singapore

    Palliative Care Centre for Excellence in Research and Education, Singapore, Singapore
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Open AccessPublished:May 25, 2018DOI:https://doi.org/10.1016/j.jpainsymman.2018.05.016

      Abstract

      Background

      Advance care planning (ACP) involves important decision making about future medical needs. The high-volume and disparate nature of ACP research makes it difficult to grasp the evidence and derive clear policy lessons for policymakers and clinicians.

      Aim

      The aim of this study was to synthesize ACP research evidence and identify relevant contextual elements, program features, implementation principles, and impacted outcomes to inform policy and practice.

      Design

      An overview of systematic reviews using the Cochrane Handbook of Systematic Reviews of Interventions was performed. Study quality was assessed using a modified version of the AMSTAR (A MeaSurement Tool to Assess Reviews) tool.

      Data Sources

      MEDLINE, EBM Reviews, Cochrane Reviews, CINAHL, Global Health, PsycINFO, and EMBASE were searched for ACP-related research from inception of each database to April 2017. Searches were supplemented with gray literature and manual searches. Eighty systematic reviews, covering over 1660 original articles, were included in the analysis.

      Results

      Legislations, institutional policies, and cultural factors influence ACP development. Positive perceptions toward ACP do not necessarily translate into more end-of-life conversations. Many factors related to patients' and providers' attitudes, and perceptions toward life and mortality influence ACP implementation, decision making, and completion. Limited, low-quality evidence points to several ACP benefits, such as improved end-of-life communication, documentation of care preferences, dying in preferred place, and health care savings. Recurring features that make ACP programs effective include repeated and interactive discussion sessions, decision aids, and interventions targeting multiple stakeholders.

      Conclusions

      Preliminary evidence highlights several elements that influence the ACP process and provides a variety of features that could support successful, effective, and sustainable ACP implementation. However, this evidence is compartmentalized and limited. Further studies evaluating ACP as a unified program and assessing the impact of ACP for different populations, settings, and contexts are needed to develop programs that are able to unleash ACP's full potential.

      Key Words

      Introduction

      Advance care planning (ACP) refers to an ongoing process in which patients, their families, and health care providers reflect on the patient's goals and values and discuss how these should inform their current and future medical care.
      • Detering K.M.
      • Silveira M.J.
      Advance care planning and advance directives: UpToDate 2016.
      • Sudore R.L.
      • Lum H.D.
      • You J.J.
      • et al.
      Defining advance care planning for adults: a consensus definition from a multidisciplinary Delphi panel.
      Ideally, these preferences should be documented, so that this information follows the patient across health care settings to be actioned when needed.
      • Hickman S.E.
      • Hammes B.J.
      • Moss A.H.
      • Tolle S.W.
      Hope for the future: achieving the original intent of advance directives.
      The Institute of Medicine, a U.S. nonprofit organization that provides guidance on issues related to biomedical science, medicine, and health, recommends ACP to better align individuals' health care goals and preferences with the services they will ultimately receive.
      • IOM (Institute of Medicine)
      Dying in America: Improving quality and honoring individual preferences near the end of life.
      When appropriately conducted, ACP may benefit patients (increased autonomy, dignity, peace, and intimacy at the moment of death), their families (less intense grieving, less likelihood of developing psychiatric conditions), and the health care system (decreased resource utilization and costs).
      • Lum H.D.
      • Sudore R.L.
      • Bekelman D.B.
      Advance care planning in the elderly.
      However, currently, there are no clear, widely accepted guidelines on how to implement ACP, so that it brings forth its full potential across all health systems and populations.
      Although there is substantial research on ACP, available studies and systematic reviews (SRs) usually focus on isolated aspects pertaining to ACP within wider end-of-life (EOL) and palliative care interventions,
      • Hall S.
      • Kolliakou A.
      • Petkova H.
      • Froggatt K.
      • Higginson I.J.
      Interventions for improving palliative care for older people living in nursing care homes.
      • Kavalieratos D.
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      • Zhang D.
      • et al.
      Association between palliative care and patient and caregiver outcomes: a systematic review and meta-analysis.
      • Lorenz K.A.
      • Lynn J.
      • Dy S.M.
      • et al.
      Evidence for improving palliative care at the end of life: a systematic review.
      on different processes within the ACP concept (such as use of decision aids
      • Aslakson R.A.
      • Schuster A.L.
      • Reardon J.
      • et al.
      Promoting perioperative advance care planning: a systematic review of advance care planning decision aids.
      • Austin C.A.
      • Mohottige D.
      • Sudore R.L.
      • Smith A.K.
      • Hanson L.C.
      Tools to promote shared decision making in serious illness: a systematic review.
      • Butler M.
      • Ratner E.
      • McCreedy E.
      • Shippee N.
      • Kane R.L.
      Decision aids for advance care planning: an overview of the state of the science.
      and EOL communication strategies
      • Walczak A.
      • Butow P.N.
      • Bu S.
      • Clayton J.M.
      A systematic review of evidence for end-of-life communication interventions: who do they target, how are they structured and do they work?.
      • Bernacki R.E.
      • Block S.D.
      American College of Physicians High Value Care Task F. Communication about serious illness care goals: a review and synthesis of best practices.
      • Parry R.
      • Land V.
      • Seymour J.
      How to communicate with patients about future illness progression and end of life: a systematic review.
      ), or on different outcome measures,
      • Mularski R.A.
      • Dy S.M.
      • Shugarman L.R.
      • et al.
      A systematic review of measures of end-of-life care and its outcomes.
      • Lorenz K.A.
      • Lynn J.
      • Dy S.
      • et al.
      Quality measures for symptoms and advance care planning in cancer: a systematic review.
      or looking at the application of ACP on specific diseases or patient groups.
      • Harrison Dening K.
      • Jones L.
      • Sampson E.L.
      Advance care planning for people with dementia: a review.
      • Luckett T.
      • Sellars M.
      • Tieman J.
      • et al.
      Advance care planning for adults with CKD: a systematic integrative review.
      • Song K.
      • Amatya B.
      • Voutier C.
      • Khan F.
      Advance care planning in patients with primary malignant brain tumors: a systematic review.
      The decision faced by policymakers or health system administrators when introducing an ACP program involves a comprehensive and overarching approach to elucidate where, to whom, and how ACP should be implemented. The compartmentalization in the available evidence makes it difficult for clinicians and policymakers to grasp all the elements that matter when developing an ACP program, and such a piecemeal approach to research may overlook important aspects or neglect critical contextual factors that influence ACP implementation.
      In sum, the field is missing a comprehensive overview of this evidence, bringing together all these disparate elements to understand the role they play within ACP. An overview of systematic reviews will provide policymakers and decision makers with the evidence they need, by compiling all this information into a single, accessible document, summarizing evidence to support policy, clinical, and research decision making.
      • Smith V.
      • Devane D.
      • Begley C.M.
      • Clarke M.
      Methodology in conducting a systematic review of systematic reviews of healthcare interventions.
      • Silva V.
      • Grande A.J.
      • Vlegas de Carvalho A.P.
      • Cabrera Martimbianco A.L.
      • Riera R.
      Overview of systematic reviews - new type of study. Part II.
      • Bravata D.M.
      • McDonald K.M.
      • Shojania K.G.
      • Sundaram V.
      • Owens D.K.
      Challenges in systematic reviews: synthesis of topics related to the delivery, organization, and financing of health care.
      A summary of evidence of all ACP-relevant studies—particularly in terms of organization, content, process, and outcomes—will better support the design and implementation of ACP. This will benefit countries and institutions contemplating the introduction of ACP.

      Research Aim

      The main objective of this overview of SRs is to identify and integrate the relevant evidence that has emerged from the literature to narrow the current translational gap from research to practice and update the current knowledge base on ACP. This study will provide insights about the elements that play a major role in ACP, so that they are taken into account when designing ACP programs. We synthesize evidence about the full spectrum of ACP-related research coming from both clinical practice and research, on ACP contextual elements, program features, and implementation principles to derive relevant lessons for ACP clinicians, health system administrators, and policymakers.

      Methods

      For this overview, we define ACP as the process involving discussions, usually close to the EOL, whereby patients state their preferences for future treatment (including proxy designation, preferred place of care, and place of death) before they can no longer make care decisions.
      • Sudore R.L.
      • Lum H.D.
      • You J.J.
      • et al.
      Defining advance care planning for adults: a consensus definition from a multidisciplinary Delphi panel.
      These discussions may or may not be documented, but it is essential that there is tangible proof that the discussions took place. Methods for this overview were developed based on criteria for conducting overviews of reviews in the Cochrane Handbook of Systematic Reviews of Interventions to ensure methodological rigor and minimize the risk of bias.
      • Becker L.A.
      • Oxman A.D.
      Chapter 22: overview of reviews.

      Search Strategies

      We searched for articles published from the inception of each database up to July 2016, in our first stage, through the following electronic databases: MEDLINE, EBM Reviews and Cochrane Reviews through OVID; CINAHL, Global Health, and PsycINFO through EBSCO; and EMBASE. We developed three search strategies (Appendix I) in collaboration with our medical librarian to maximize sensitivity and specificity for each search engine. Two main strings of terms were developed: one pertained to ACP and its related concepts and keywords and the second string to the methodological filter for SRs, derived from the guidelines described in the Canadian Agency for Drugs and Technologies' Database Search Filters and the Health Information Research Unit's Search Strategies.
      • Canadian Agency for Drugs and Technologies in Health (CADTH)
      Strings Attached: CADTH's Database Search Filters 2016.
      • Health Information Research Unit (HIRU)
      Search Filters for MEDLINE in Ovid Syntax and the PubMed translation: McMaster University; 2016.
      We also manually searched Google and Google Scholar to ensure the completeness of our overview. In addition, we searched three gray literature databases: base-search.net, Opengrey.org, and science.gov. Later, and to account for reviews published in the past 12 months, we performed an update of the search in April 2017. References were managed using EndNote X7, developed by Clarivate Analytics. (Clarivate Analytics, Philadelphia, PA).
      Clarivate Analytics
      EndNote X7.

      Eligibility Criteria

      As per our definition, we included reviews with a primary focus on ACP—those that examined ACP or any of its related aspects such as its effectiveness, barriers/facilitators, completion rates, types of ACP tools used, decision aids, communication strategies, and economic impact. We also included reviews that may not focus on ACP but may include ACP as one of the key outcomes or results.
      We developed an a priori exclusion and inclusion criteria scheme (Appendix II) and included SRs that mentioned Advance Medical Directives, Do-Not-Resuscitate (DNR), Do-Not-Hospitalize (DNH), and Lasting Power of Attorney as well as ACP, if they describe that a discussion between patient and medical professional took place in any setting. Furthermore, studies that covered concepts inherent in the definition of ACP such as EOL decision making, treatment preferences, and surrogate decision making are included.
      We excluded reviews if they 1) focused only on calculating completion rates of advance medical directives and did not mention any EOL care discussions or interventions; 2) included only pediatric patients (aged <18 years old); or 3) focused on advance treatment directives for psychiatric conditions, which are not related to EOL and involve different dynamics and aims (i.e., to improve recovery-oriented outcomes and be used for psychiatric crises)
      • Zelle H.
      • Kemp K.
      • Bonnie R.J.
      Advance directives in mental health care: evidence, challenges and promise.
      other than the ACP process addressed in this study.
      We included SRs that 1) are titled or expressly stated to be systematic reviews within the abstract, or text and/or 2) followed systematic review principles including at least a comprehensive search strategy and quality appraisal of included studies.
      • Black A.D.
      • Car J.
      • Pagliari C.
      • et al.
      The impact of eHealth on the quality and safety of health care: a systematic overview.
      To comprehensively cover the ACP literature, there were no restrictions on study designs, populations, or settings. No language, geographical, or publication date restrictions were applied.

      Screening and Selection of Studies

      Two authors (G. J. and W. S. T.) independently screened titles, abstracts, and keywords to identify relevant studies for full-text review. Three authors (G. J., W. S. T. and A. K. V.) independently screened full texts for final inclusion. Discrepancies were resolved through discussion and consensus.

      Data Extraction and Critical Appraisal of Included Studies

      We developed a data extraction table (Appendix III) that included general information, topic of paper, PICO (population, interest, context, outcomes), methodology, results, and conclusions and future research.
      Full data extraction of all the included studies was performed by the lead author (G. J.). A second author (A. K. V.) performed data extraction on a random sample of 20% of the included studies and results were compared for consistency. There were minimal discrepancies (10%) that were resolved by discussion and reappraisal. The second author also reviewed the data extraction performed by the lead author for the remaining studies.
      We assessed the quality of included SRs to evaluate their methodological rigor and strength of the evidence they provide, using a modified version of the AMSTAR tool, an 11-item checklist widely used to evaluate the methodological quality of mainly quantitative systematic reviews.
      • Shea B.J.
      • Grimshaw J.M.
      • Wells G.A.
      • et al.
      Development of AMSTAR: a measurement tool to assess the methodological quality of systematic reviews.
      We modified this tool as described in the study by Lou et al.,
      • Lou S.
      • Carstensen K.
      • Jorgensen C.R.
      • Nielsen C.P.
      Stroke patients' and informal carers' experiences with life after stroke: an overview of qualitative systematic reviews.
      where Items 9 and 10 were adapted and excluded, respectively, to evaluate SRs that followed a narrative approach, and used qualitative or mixed methodologies.
      Our adapted checklist contained 10 items (Appendix IV) for a maximum score of 10. A review that adequately met all the 10 criteria was considered to be of the highest quality. The quality rating was as follows: a score (out of 10 criteria) rating of 8 to 10 is considered as high quality, 4 to 7 as moderate quality and 3 or less as low quality.
      • Bashi N.
      • Karunanithi M.
      • Fatehi F.
      • Ding H.
      • Walters D.
      Remote monitoring of patients with heart failure: an overview of systematic reviews.
      The quality scores were not used to exclude articles from our overview but to inform about the quality of research and guide the interpretation of results. Similar to the data extraction process, G. J. performed quality assessment on all studies and A. K. V. performed the same process on a random sample of 20% of the studies. There were no discrepancies. The second author also reviewed the quality appraisal performed by the lead author for the remaining articles.

      Data Analysis, Synthesis, and Presentation

      Data analysis was informed by the Framework Method involving thematic analysis.
      • Mays N.
      • Pope C.
      Rigour and qualitative research.
      • Ritchie J.
      • Lewis J.
      Qualitative research practice: A guide for social science students and researchers.
      • Gale N.K.
      • Heath G.
      • Cameron E.
      • Rashid S.
      • Redwood S.
      Using the framework method for the analysis of qualitative data in multi-disciplinary health research.
      Two reviewers (G. J. and W. S. T.) identified recurrent themes in the literature to develop the standardized extraction form in Microsoft Excel (Appendix III), which was used to categorize information along predetermined categories. Through reflection and iteration, thematic categories were further refined to derive a final set of codes to interpret the results. The data are presented using a narrative, descriptive approach, typically used in cases where the research question dictates the inclusion of a wide range of research designs, including qualitative and/or quantitative findings.
      • Gilissen J.
      • Pivodic L.
      • Smets T.
      • et al.
      Preconditions for successful advance care planning in nursing homes: a systematic review.
      We follow the ACP process from its contextual factors, to the mechanisms involved in its implementation, and ultimately its outcomes (Table 1).
      • de Souza D.E.
      Elaborating the Context-Mechanism-Outcome configuration (CMOc) in realist evaluation: a critical realist perspective.
      Given the heterogeneity of the included studies, it was not possible to pool results or use meta-analytical approaches and to estimate the magnitude of each of the effects from the evidence.
      Table 1Analytical Framework (Context-Mechanism-Outcomes (CMO) Configuration
      • de Souza D.E.
      Elaborating the Context-Mechanism-Outcome configuration (CMOc) in realist evaluation: a critical realist perspective.
      ) and Corresponding ACP Aspects
      CMO ConstructDescriptionRelated ACP Aspect
      ContextAspects related to the structure, culture, agency, and relations and the interplay between themLegal environment, institutional policy; culture, race, and ethnic influences; patients' and providers' perceptions and receptivity to ACP, and factors influencing this receptivity
      MechanismMechanisms related to roles, practices, resources, processes; to ideas or propositional formulations about structure, culture, agency, or relations; to beliefs and reasons for action or nonaction; to duties, responsibilities, rights, powerFactors influencing ACP implementation; barriers and facilitators related to patients, family caregivers, and health care providers influencing ACP initiation, decision making, and completion of the process; operational/administrative barriers; surrogate designation-related aspects
      OutcomeTransformation, invariance, or reproduction obtained from the aspects related to the mechanism listed previouslyPreferences, general reported outcomes, types of ACP interventions, and corresponding outcomes
      CMO = context-mechanism-outcomes; ACP = advance care planning.
      This work was based on publicly available literature and did not require ethics approval.

      Results

      Search Results and General Studies' Characteristics

      Overall, after removing duplicates and performing title/abstract screening, a total of 146 articles were subjected to full-text screening, from which 80 SRs were deemed appropriate for inclusion and analysis, as shown in the PRISMA flowchart in Figure 1.
      Figure thumbnail gr1
      Fig. 1PRISMA diagram of search results. ACP = advance care planning; SR = systematic review.
      Sixty percent (n = 48) of the included SRs have been published since 2014, and the majority come from high-income Western countries such as the U.S. (represented in 79% of the SRs, n = 63), Canada (in 44% of the SRs, n = 35), Australia (in 38%, n = 30), and the U.K. (in 35%, n = 28). Over half of the SRs (59%, n = 47) used descriptive/narrative synthesis or thematic/content analysis, and 39% (n = 31) of SRs included only quantitative studies in their analyses. Thirteen percent of the SRs (n = 10) performed meta-analysis. In terms of the main topics explored, 15 SRs (19%) studied ACP as part of an EOL/palliative care intervention, 12 (15%) focused on EOL decision aids or decision making, and ACP research/implementation for specific patient groups, facilitators/barriers to ACP, and communication/discussion strategies were the main topics for 10 SRs (13%) each. Most of the included SRs (65%, n = 52) fall under the moderate-quality category, and 30% (n = 24) qualify as low-quality studies. Only 5% (n = 4) of them are of high quality.
      There is a great variability in the way the SRs approached or conceptualized ACP. Several SRs used the term ACP as a general concept and grouped all their analyzed interventions together, even if they differed in their objectives and methodologies. These use ACP as an umbrella term and discuss the impact of ACP as a whole. Other SRs, whose focus was to examine differences depending on types or characteristics of interventions, separated the interventions and provided their features and associated outcomes individually. These may be ACP interventions or other interventions (such as palliative care interventions or educational interventions) that impact ACP or ACP-related outcomes.
      For detailed characteristics of each included SR, see Appendix V.

      Evidence Summary From Included Studies

      ACP Context

      ACP context refers to the setting in which an ACP program is implemented involving local institutional structures, cultures, agency and relations, and the complex interplay between them.

      Legal and Policy Environment

      There is a diversity in policy approaches to ACP across, and even within, countries.
      • Smith C.
      • Jaffray L.
      • Ellis I.
      Electronic advance care planning in community: nurses' role. GSTF Digital Library.
      The lack of a clear legal framework creates confusion about the legal status of ACP and hinders ACP implementation,
      • Lovell A.
      • Yates P.
      Advance Care Planning in palliative care: a systematic literature review of the contextual factors influencing its uptake 2008-2012.
      causing patients and family members to question its utility. Hence, ACP needs to be supported by strong policy initiatives at the health system and at the institutional level, as reflected by positive changes in staff, family, and patient outcomes after EOL policy implementation through the likes of the Patient Self-Determination Act in the U.S. and the Golden Standard Framework for Care Homes in the U.K.
      • Oliver D.P.
      • Porock D.
      • Zweig S.
      End-of-life care in U.S. nursing homes: a review of the evidence.
      • Kinley J.
      • Froggatt K.
      • Bennett M.I.
      The effect of policy on end-of-life care practice within nursing care homes: a systematic review.
      On the one hand, health system policies need to be directed at the ground level of service provision, as best clinical practices without systemic support are unlikely to produce positive change.
      • Lovell A.
      • Yates P.
      Advance Care Planning in palliative care: a systematic literature review of the contextual factors influencing its uptake 2008-2012.
      Policy reforms that include incentives, advocate for a multidisciplinary approach (i.e., involving professionals from different disciplines who are additionally trained in palliative care), and enhance EOL communication will help overcome current, ground-level barriers.
      • Lovell A.
      • Yates P.
      Advance Care Planning in palliative care: a systematic literature review of the contextual factors influencing its uptake 2008-2012.
      • Siouta N.
      • van Beek K.
      • Preston N.
      • et al.
      Towards integration of palliative care in patients with chronic heart failure and chronic obstructive pulmonary disease: a systematic literature review of European guidelines and pathways.
      On the other hand, there needs to be a focus on developing competent educational policies and training programs to better equip health care professionals with the necessary skill set to work with patients in meeting their ACP needs and to promote best practices on the ground.
      • Gilissen J.
      • Pivodic L.
      • Smets T.
      • et al.
      Preconditions for successful advance care planning in nursing homes: a systematic review.
      At the institutional level, the lack of governance and management policy to create a supportive culture for EOL care negatively impacts the working environment that are conducive to interdisciplinary teamwork,
      • Johnson K.S.
      • Elbert-Avila K.I.
      • Tulsky J.A.
      The influence of spiritual beliefs and practices on the treatment preferences of African Americans: a review of the literature.
      thus impeding ACP implementation.

      Ethnic, Cultural, and Spiritual Influences

      Multiple streams of research explore the role of ethnicity or race on ACP because they impact EOL perceptions and receptivity toward EOL care. Cultural and racial values influence perceived burden on family members, preferences for life-sustaining treatments, understanding of living wills, and completion rates of advance directives (ADs) and ACP.
      • Frost D.W.
      • Cook D.J.
      • Heyland D.K.
      • Fowler R.A.
      Patient and healthcare professional factors influencing end-of-life decision-making during critical illness: a systematic review.
      For example, as compared to Caucasian Americans in the U.S., use of hospices progressively diminished among Hispanic Americans, African Americans, and Asian Americans.
      • LoPresti M.A.
      • Dement F.
      • Gold H.T.
      End-of-Life care for people with cancer from ethnic minority groups: a systematic review.
      • Wicher C.P.
      • Meeker M.A.
      What influences African American end-of-life preferences?.
      Similarly, documentation of ADs, living wills, durable powers of attorney, and/or DNR orders was lower in all these minorities compared to Caucasians.
      • Rahemi Z.
      • Williams C.L.
      Older adults of underrepresented populations and their end-of-life preferences: an integrative review.
      Although most research exploring racial and ethnic differences toward ACP has been conducted in the U.S. (specifically looking at minorities differing from Caucasian populations),
      • Johnson K.S.
      • Elbert-Avila K.I.
      • Tulsky J.A.
      The influence of spiritual beliefs and practices on the treatment preferences of African Americans: a review of the literature.
      • LoPresti M.A.
      • Dement F.
      • Gold H.T.
      End-of-Life care for people with cancer from ethnic minority groups: a systematic review.
      • Wicher C.P.
      • Meeker M.A.
      What influences African American end-of-life preferences?.
      • Sanders J.J.
      • Robinson M.T.
      • Block S.D.
      Factors impacting advance care planning among African Americans: results of a systematic integrated review.
      research from Asian populations demonstrates a strong reliance on physicians and family when making ACP-related decisions for EOL treatments.
      • Lee M.C.
      • Hinderer K.A.
      • Kehl K.A.
      A systematic review of advance directives and advance care planning in Chinese people from eastern and western culture.
      For example, instead of appealing to self-determination and autonomy, Chinese culture values collective, familial decision making and defers health care decisions to physicians' authority.
      • Lee M.C.
      • Hinderer K.A.
      • Kehl K.A.
      A systematic review of advance directives and advance care planning in Chinese people from eastern and western culture.
      Therefore, numerous studies advocate for cultural sensitivity and embracing different social and spiritual needs when devising ACP interventions.
      • Rahemi Z.
      • Williams C.L.
      Older adults of underrepresented populations and their end-of-life preferences: an integrative review.
      • Schofield P.
      • Carey M.
      • Love A.
      • Nehill C.
      • Wein S.
      'Would you like to talk about your future treatment options'? Discussing the transition from curative cancer treatment to palliative care.
      • Zager B.S.
      • Yancy M.
      A call to improve practice concerning cultural sensitivity in advance directives: a review of the literature.

      Perceptions and Receptivity to ACP

      There is overall a positive view toward ACP and AD discussions among both patients and health care professionals. Patients see ACP as a way of ensuring their wishes are known and respected and aiding their families to make decisions on their behalf.
      • Sessanna L.
      • Jezewski M.A.
      Advance directive decision making among independent community-dwelling older adults: a systematic review of health science literature.
      • Sharp T.
      • Moran E.
      • Kuhn I.
      • Barclay S.
      Do the elderly have a voice? Advance care planning discussions with frail and older individuals: a systematic literature review and narrative synthesis.
      Physicians see ACP and AD conversations as an important part of their professional responsibility,
      • Sharp T.
      • Moran E.
      • Kuhn I.
      • Barclay S.
      Do the elderly have a voice? Advance care planning discussions with frail and older individuals: a systematic literature review and narrative synthesis.
      whereas nurses consider ACP a safeguard for patient's autonomy and prepare them for future scenarios.
      • Ke L.S.
      • Huang X.
      • O'Connor M.
      • Lee S.
      Nurses' views regarding implementing advance care planning for older people: a systematic review and synthesis of qualitative studies.
      Despite positive perceptions, patients, caregivers, and health care professionals evidently avoid EOL discussions and documentation because these deal with an emotionally difficult topic.
      • Layson R.T.
      • Adelman H.M.
      • Wallach P.M.
      • Pfeifer M.P.
      • Johnston S.
      • McNutt R.A.
      Discussions about the use of life-sustaining treatments: a literature review of physicians' and patients' attitudes and practices. End of Life Study Group.
      • Murray L.
      • Butow P.N.
      Advance care planning in motor neuron disease: a systematic review.
      Yet, the level of comfort with these discussions depends on people's knowledge and previous experiences with the process of dying and death,
      • Johnson S.
      • Butow P.
      • Kerridge I.
      • Tattersall M.
      Advance care planning for cancer patients: a systematic review of perceptions and experiences of patients, families, and healthcare providers.
      as greater exposure to both makes people less avert to explore this topic.
      To improve ACP receptivity, the SRs recurrently mention the need for educating the public so that they are aware that ACP serves to empower patients by helping them to set goals for future care so as to better cope with uncertainty.
      • Zager B.S.
      • Yancy M.
      A call to improve practice concerning cultural sensitivity in advance directives: a review of the literature.
      • Tong A.
      • Cheung K.L.
      • Nair S.S.
      • Kurella Tamura M.
      • Craig J.C.
      • Winkelmayer W.C.
      Thematic synthesis of qualitative studies on patient and caregiver perspectives on end-of-life care in CKD.
      Equally important is educating family members of older/ill relatives to prepare them to make informed care decisions when the need arises.
      • Sessanna L.
      • Jezewski M.A.
      Advance directive decision making among independent community-dwelling older adults: a systematic review of health science literature.
      • Tong A.
      • Cheung K.L.
      • Nair S.S.
      • Kurella Tamura M.
      • Craig J.C.
      • Winkelmayer W.C.
      Thematic synthesis of qualitative studies on patient and caregiver perspectives on end-of-life care in CKD.
      In contrast with the collective values reflected in studies that involved Asian populations, SRs from Western countries emphasize individuals' autonomy and self-determination as completing ACP and ADs serves to ensure that patients' wishes and care decisions are protected and respected by health care staffs.
      • Luckett T.
      • Sellars M.
      • Tieman J.
      • et al.
      Advance care planning for adults with CKD: a systematic integrative review.
      • Ke L.S.
      • Huang X.
      • O'Connor M.
      • Lee S.
      Nurses' views regarding implementing advance care planning for older people: a systematic review and synthesis of qualitative studies.
      Similarly, SRs involving nurses in ACP provision reveal that knowledge about the practical and legal issues,
      • Gilissen J.
      • Pivodic L.
      • Smets T.
      • et al.
      Preconditions for successful advance care planning in nursing homes: a systematic review.
      as well as proficiency in communication skills,
      • Ke L.S.
      • Huang X.
      • O'Connor M.
      • Lee S.
      Nurses' views regarding implementing advance care planning for older people: a systematic review and synthesis of qualitative studies.
      plays important roles in health care professionals' willingness to engage in ACP. Studies of palliative care programs show that educational interventions are effective in improving the quality of ACP rendered by physicians,
      • Lorenz K.A.
      • Lynn J.
      • Dy S.M.
      • et al.
      Evidence for improving palliative care at the end of life: a systematic review.
      thus enhancing ACP outcomes such as increasing patient-surrogate wishes' congruence, and increased knowledge and communication with patients.
      • Walling A.
      • Lorenz K.A.
      • Dy S.M.
      • et al.
      Evidence-based recommendations for information and care planning in cancer care.
      There is also a need for improving skills and attitudes of health care professionals, so that they provide better quality ACP,
      • De Vleminck A.
      • Houttekier D.
      • Pardon K.
      • et al.
      Barriers and facilitators for general practitioners to engage in advance care planning: a systematic review.
      by conveying the right information, giving useful advice, and showing empathy.
      • Luckett T.
      • Sellars M.
      • Tieman J.
      • et al.
      Advance care planning for adults with CKD: a systematic integrative review.
      Improving providers' skills will facilitate ACP initiation, implementation, and meeting patients' wishes.
      • Lewis E.
      • Cardona-Morrell M.
      • Ong K.Y.
      • Trankle S.A.
      • Hillman K.
      Evidence still insufficient that advance care documentation leads to engagement of healthcare professionals in end-of-life discussions: a systematic review.
      Receptivity toward these discussions also depends on having good relationships between all involved stakeholders (i.e., between patient, family, and professional caregiver), in addition to good family dynamics.
      • Gilissen J.
      • Pivodic L.
      • Smets T.
      • et al.
      Preconditions for successful advance care planning in nursing homes: a systematic review.

      ACP Implementation

      ACP implementation refers to all the aspects influencing the introduction of ACP such as providing information to patients and carers, facilitating discussion, completing, recording, revising, and updating ACP-related documents, as well as the application of this information when needed.
      • Emanuel L.L.
      • Danis M.
      • Pearlman R.A.
      • Singer P.A.
      Advance care planning as a process: structuring the discussions in practice.
      Available evidence reveals multiple barriers and facilitators, for patients and health care professionals, for having ACP conversations.

      Barriers and Facilitators

      Patient and Family Caregiver Level

      At the patient and family caregiver level, there are several barriers for ACP implementation. Lack of preparedness among patients and carers makes it difficult to initiate ACP conversations.
      • Lund S.
      • Richardson A.
      • May C.
      Barriers to advance care planning at the end of life: an explanatory systematic review of implementation studies.
      In the context of dementia care, the unpredictable nature of the disease, the degree of patient's involvement, the emotional distress on the family, and discrepancies between family and health care professionals may also act as barriers to making care decisions.
      • Lord K.
      • Livingston G.
      • Cooper C.
      A systematic review of barriers and facilitators to and interventions for proxy decision-making by family carers of people with dementia.
      Family carers of patients with dementia, for instance, want practical support but often report unavailability from health care professionals.
      • Lord K.
      • Livingston G.
      • Cooper C.
      A systematic review of barriers and facilitators to and interventions for proxy decision-making by family carers of people with dementia.
      Other factors that hinder ACP decision making and completion include discrepancies about the amount of information patients and caregivers want to know, and patients deferring responsibility to family members or physicians.
      • Ramsaroop S.D.
      • Reid M.C.
      • Adelman R.D.
      Completing an advance directive in the primary care setting: what do we need for success?.
      Conversely, patient factors associated with higher rates of ACP include older age, higher education levels, and diagnosis of more severe health conditions.
      • Harrison Dening K.
      • Jones L.
      • Sampson E.L.
      Advance care planning for people with dementia: a review.
      For example, there are higher rates of ACP in cancer patients compared to noncancer patients.
      • Lovell A.
      • Yates P.
      Advance Care Planning in palliative care: a systematic literature review of the contextual factors influencing its uptake 2008-2012.
      Diagnosis of dementia, on the other hand, can either act as a barrier to ACP or prompt early planning before patients are more severely impaired.
      • Sharp T.
      • Moran E.
      • Kuhn I.
      • Barclay S.
      Do the elderly have a voice? Advance care planning discussions with frail and older individuals: a systematic literature review and narrative synthesis.
      Comorbidity and poor functional status were associated with less invasive and more stable EOL care preferences.
      • Frost D.W.
      • Cook D.J.
      • Heyland D.K.
      • Fowler R.A.
      Patient and healthcare professional factors influencing end-of-life decision-making during critical illness: a systematic review.
      • Auriemma C.L.
      • Nguyen C.A.
      • Bronheim R.
      • et al.
      Stability of end-of-life preferences: a systematic review of the evidence.

      Health Care Provider Level

      Research underscores the central role of health care professionals, particularly physicians,
      • Sharp T.
      • Moran E.
      • Kuhn I.
      • Barclay S.
      Do the elderly have a voice? Advance care planning discussions with frail and older individuals: a systematic literature review and narrative synthesis.
      • Johnson S.
      • Butow P.
      • Kerridge I.
      • Tattersall M.
      Advance care planning for cancer patients: a systematic review of perceptions and experiences of patients, families, and healthcare providers.
      • van der Steen J.T.
      • van Soest-Poortvliet M.C.
      • Hallie-Heierman M.
      • et al.
      Factors associated with initiation of advance care planning in dementia: a systematic review.
      in initiating EOL discussions.
      • Luckett T.
      • Sellars M.
      • Tieman J.
      • et al.
      Advance care planning for adults with CKD: a systematic integrative review.
      • Song M.K.
      Effects of end-of-life discussions on patients' affective outcomes.
      There is a mixed evidence on the appropriate timing for ACP conversations, with some studies recommending earlier initiation, while others finding discussions more useful at a later stage of patient care.
      • Sharp T.
      • Moran E.
      • Kuhn I.
      • Barclay S.
      Do the elderly have a voice? Advance care planning discussions with frail and older individuals: a systematic literature review and narrative synthesis.
      • Layson R.T.
      • Adelman H.M.
      • Wallach P.M.
      • Pfeifer M.P.
      • Johnston S.
      • McNutt R.A.
      Discussions about the use of life-sustaining treatments: a literature review of physicians' and patients' attitudes and practices. End of Life Study Group.
      Barriers to initiate ACP conversations include prognosis uncertainty.
      • Lovell A.
      • Yates P.
      Advance Care Planning in palliative care: a systematic literature review of the contextual factors influencing its uptake 2008-2012.
      For specific diseases such as congestive heart failure or chronic obstructive pulmonary disease, it is even more complicated to initiate EOL conversations as these diseases are not directly linked to dying and conversations may inflict negative reactions from patients.
      • Siouta N.
      • van Beek K.
      • Preston N.
      • et al.
      Towards integration of palliative care in patients with chronic heart failure and chronic obstructive pulmonary disease: a systematic literature review of European guidelines and pathways.
      In addition, there is a lack of information regarding the best setting for ACP discussions,
      • Johnson S.
      • Butow P.
      • Kerridge I.
      • Tattersall M.
      Advance care planning for cancer patients: a systematic review of perceptions and experiences of patients, families, and healthcare providers.
      and little research has examined the triggers for a referral from curative cancer treatment to palliative care services.
      • Schofield P.
      • Carey M.
      • Love A.
      • Nehill C.
      • Wein S.
      'Would you like to talk about your future treatment options'? Discussing the transition from curative cancer treatment to palliative care.
      Additional problems to communication exist,
      • Mpinga E.K.
      • Chastonay P.
      • Rapin C.H.
      [End of life conflicts in palliative care: a systematic review of the literature].
      such as the lack of communication skills and preparedness exhibited by medical residents when trying to support patients making decisions at the EOL.
      • Gorman T.E.
      • Ahern S.P.
      • Wiseman J.
      • Skrobik Y.
      Residents' end-of-life decision making with adult hospitalized patients: a review of the literature.
      Factors that support the initiation of ACP discussions include having a clearer picture of disease trajectory, physicians' skills for gauging patients' willingness to discuss ACP, ACP knowledge, and length of relationship with patient.
      • Sessanna L.
      • Jezewski M.A.
      Advance directive decision making among independent community-dwelling older adults: a systematic review of health science literature.
      • De Vleminck A.
      • Houttekier D.
      • Pardon K.
      • et al.
      Barriers and facilitators for general practitioners to engage in advance care planning: a systematic review.
      • van der Steen J.T.
      • van Soest-Poortvliet M.C.
      • Hallie-Heierman M.
      • et al.
      Factors associated with initiation of advance care planning in dementia: a systematic review.
      ACP and AD completion increased with disease progression, with disease severity (e.g., cancer), and with health care professionals initiating the discussions.
      • Murray L.
      • Butow P.N.
      Advance care planning in motor neuron disease: a systematic review.
      • De Vleminck A.
      • Houttekier D.
      • Pardon K.
      • et al.
      Barriers and facilitators for general practitioners to engage in advance care planning: a systematic review.
      • Song M.K.
      Effects of end-of-life discussions on patients' affective outcomes.
      Different conversation techniques like indirect talk may be useful when a clinician wishes to test whether it is “the right time” to pursue these issues and the use of hypothetical questions may encourage on-topic talk.
      • Parry R.
      • Land V.
      • Seymour J.
      How to communicate with patients about future illness progression and end of life: a systematic review.
      An SR points out the need to invest time in relationship building so that strategies for ACP implementation carefully consider timing and receptiveness and are family and patient centered.
      • van der Steen J.T.
      • van Soest-Poortvliet M.C.
      • Hallie-Heierman M.
      • et al.
      Factors associated with initiation of advance care planning in dementia: a systematic review.

      Institutional and Operational Level

      Other issues emerge at the institutional and operational level. Administrative barriers include issues related to legalistic paperwork, administrative systems for monitoring and accessing records, and lack of information flow.
      • Wicher C.P.
      • Meeker M.A.
      What influences African American end-of-life preferences?.
      • Sharp T.
      • Moran E.
      • Kuhn I.
      • Barclay S.
      Do the elderly have a voice? Advance care planning discussions with frail and older individuals: a systematic literature review and narrative synthesis.
      There is also a lack of resources and time devoted to ACP,
      • Wicher C.P.
      • Meeker M.A.
      What influences African American end-of-life preferences?.
      shortage of manpower and poor staff preparation,
      • Fosse A.
      • Schaufel M.A.
      • Ruths S.
      • Malterud K.
      End-of-life expectations and experiences among nursing home patients and their relatives–a synthesis of qualitative studies.
      and difficulties arising from the ACP process not being embedded in routine care,
      • Gilissen J.
      • Pivodic L.
      • Smets T.
      • et al.
      Preconditions for successful advance care planning in nursing homes: a systematic review.
      which hinder actualizing advance care plans.
      • Lund S.
      • Richardson A.
      • May C.
      Barriers to advance care planning at the end of life: an explanatory systematic review of implementation studies.
      Operational issues involving health care providers include prognosis being poorly documented or overestimated,
      • Walling A.
      • Lorenz K.A.
      • Dy S.M.
      • et al.
      Evidence-based recommendations for information and care planning in cancer care.
      difficulties explaining forms, getting clinicians' signatures, and transferring the information across settings.
      • Hickman S.E.
      • Keevern E.
      • Hammes B.
      Use of the Physician Orders for Life-Sustaining Treatment program in the clinical setting: a systematic review of the literature.
      Health care professionals also reported the pressure to see a large number of patients and difficulty of scheduling timely follow-up visits.
      • Sharp T.
      • Moran E.
      • Kuhn I.
      • Barclay S.
      Do the elderly have a voice? Advance care planning discussions with frail and older individuals: a systematic literature review and narrative synthesis.

      Surrogate Designation

      An essential aspect of ACP implementation involves incorporating and designating a surrogate decision maker, and several SRs focused on this topic.
      • Fosse A.
      • Schaufel M.A.
      • Ruths S.
      • Malterud K.
      End-of-life expectations and experiences among nursing home patients and their relatives–a synthesis of qualitative studies.
      • Meeker M.A.
      • Jezewski M.A.
      Family decision making at end of life.
      • Wendler D.
      • Rid A.
      Systematic review: the effect on surrogates of making treatment decisions for others.
      • Kim H.
      • Deatrick J.A.
      • Ulrich C.M.
      Ethical frameworks for surrogates' end-of-life planning experiences.
      It is important for the patient to appoint someone who knows them well, usually a family member or spouse, given that patients are more concerned with whom will make the decision than with the decision itself.
      • Meeker M.A.
      • Jezewski M.A.
      Family decision making at end of life.
      Although surrogates try to do the right thing by protecting and advocating for their family member,
      • Kim H.
      • Deatrick J.A.
      • Ulrich C.M.
      Ethical frameworks for surrogates' end-of-life planning experiences.
      being a proxy decision maker can be stressful and anxiety producing.
      • Meeker M.A.
      • Jezewski M.A.
      Family decision making at end of life.
      • Wendler D.
      • Rid A.
      Systematic review: the effect on surrogates of making treatment decisions for others.
      Focus should be placed on providing surrogates with appropriate information and supporting them emotionally.
      • Fosse A.
      • Schaufel M.A.
      • Ruths S.
      • Malterud K.
      End-of-life expectations and experiences among nursing home patients and their relatives–a synthesis of qualitative studies.
      • Meeker M.A.
      • Jezewski M.A.
      Family decision making at end of life.

      ACP Interventions and Outcomes

      The included SRs analyzed the impact of ACP against a diversity of outcomes. As mentioned previously, we found that the studies differed in the way they conceptualized ACP, and either looked at it as whole concept regardless of differences in interventions or tried to elucidate differences depending on the type of ACP interventions studied.

      Different Types of ACP Interventions and Corresponding Outcomes

      From the SRs, we were able to classify ACP interventions into five main categories: 1) interventions providing information or educational content (either for patients, caregivers, or professionals); 2) interventions testing decision aids or communication strategies; 3) interventions exploring a subtype of ACP (such as interventions to increase AD completion, or DNR/DNH orders); 4) ACP interventions per se (which include complex or extensive interventions) or specific forms of ACP (e.g., the physician orders for life-sustaining treatments [POLSTs] or others); and 5) those that sought to improve palliative or EOL care (and which either include ACP as part of the intervention, or impacted ACP as part of its outcomes). Details about the interventions as presented in the SRs are provided in Table 2.
      Table 2Interventions Studied in the Included SRs
      Reference (Number of Included Studies)PopulationInterventionContextOutcome Summary (ACP-Related, Values Included if Provided)
      1. Interventions providing information or education about ACP or EOL
      Durbin
      • Durbin C.R.
      • Fish A.F.
      • Bachman J.A.
      • Smith K.V.
      Systematic review of educational interventions for improving advance directive completion.
      (12 RCTs and four non-RCTs)
      PatientsOne computer educational intervention (against control)Varied
      • -
        Inconclusive
      Six combined written and verbal educational interventions (against control)
      • -
        One of five studies demonstrated effectiveness of combined written and verbal interventions in increasing percent of newly completed ADs
      One combined written and computer educational intervention (against control)
      • -
        Inconclusive
      Three combined written and verbal vs. written only (all RCTs)
      • -
        Combined written and verbal interventions were significantly (P < 0.05) more effective than single written interventions in increasing percent of newly completed ADs
      One combined written, verbal, and video vs. written only (RCT)
      • -
        A combined written, verbal, and video educational intervention was significantly (P < 0.05) more effective than a single written intervention in increasing percent of newly completed ADs
      Hanson
      • Hanson L.C.
      • Tulsky J.A.
      • Danis M.
      Can clinical interventions change care at the end of life?.
      (16 studies total)
      Patient (education interventions for changing EOL care) values represent % of patients before and after intervention (eight studies)
      Systematic reviews that include more than one type of intervention.
      Written materials and discussion with materialOutpatients
      • -
        Increased patients' preferences (AD), 0% compared to 15%
      Discussion with researcherOutpatients
      • -
        Patients' preferences unchanged (AD), 10% compared to 15%
      Written materials and educational meetingVolunteer
      • -
        Increased patients' preferences (AD), 31% compared to 46%
      Mailed written materialsInpatient
      • -
        Increased patients' preferences (proxy), 0% compared to 19%
      Several discussions with social workerOutpatients
      • -
        Increased patients preference' (new proxy), 68%; (new AD), 71%
      Written materials and discussion with physicianOutpatients
      • -
        Increased patients' preferences (AD), 3% compared to 23%
      Mailed written materialsInpatient
      • -
        Patients' preferences unchanged (proxy), 11% compared to 13%
      Discussion with patient representativeInpatient
      • -
        Increased patients' preferences (proxy), 6% compared to 48%
      Physician (education interventions for changing EOL care) values represent % of patients before and after intervention (five studies)
      Systematic reviews that include more than one type of intervention.
      Expert modeling, extra clinic timeHome care/nursing homes
      • -
        Increased patients' preferences (AD)
      Physician lecture chart reminders, “talking points”Outpatient
      • -
        Increased patients' preferences (proxy)
      Case conference, feedbackInpatient
      • -
        Decreased use of life-sustaining treatments (LSTs) (discussions beyond DNR), 68% compared to 86%
      Chart reminder, feedback, new AD formInpatient
      • -
        Increased patient discussion (AD), 33% compared with 51%; decreased use of LSTs (DNR, 22% compared with 19%; discussion will change treatment, 3% to 13%
      Case conference, mentoringICU
      • -
        Increased patient discussion, 83% had earlier discussion; decreased use of LSTs (days in ICU), 46% decrease
      Physicians and patients (education interventions for changing EOL care) values represent % of patients before and after intervention (three studies)
      Systematic reviews that include more than one type of intervention.
      Patient and family (proxy) education, chart formNursing home
      • -
        Increased patients' preferences (new AD), 100%; no change in LSTs (treatment)
      Brief physician education, patient form, chart forms, and stickerOutpatient
      • -
        Increase patients' preferences (new AD), 66%; no change in LSTs; no change in cost
      Research nurse, discussion of patients' preferences and prognosis, chart formsInpatients
      • -
        No difference for any outcome
      Jezewski
      • Jezewski M.A.
      • Meeker M.A.
      • Sessanna L.
      • Finnell D.S.
      The effectiveness of interventions to increase advance directive completion rates.
      (25 studies)
      PatientsDidactic interventions to increase AD completion (only present information, may include video components and written materials)N/A
      • -
        AD completion ranged from 0% to 34%
      Interactive interventions to increase AD completion (information plus discussion with a knowledgeable person)
      • -
        AD completion ranged from 23% to 71%
      Interactive, and group education vs. single individual education
      • -
        Twice as effective for group session
      Provision of information several days before admission and at the time of admission vs. only at the time of admission
      • -
        AD completion: 40% for information given twice vs. 4% for only at the time of admission
      Patel
      • Patel R.V.
      • Sinuff T.
      • Cook D.J.
      Influencing advance directive completion rates in non-terminally ill patients: a systematic review.
      (nine studies)
      PatientsIntervention, directed at the patient, included at least one of 1) written, audio, or video material vs. 2) direct counseling (face-to-face discussion with a clinician) about advance care directivesN/A
      • -
        The pooled odds ratio and 95% confidence interval, using a random-effects model was 3.71 [1.46–9.40] with P < 0.001 for the test of heterogeneity, indicating a clinically important and statistically significant effect.
      Ramsaroop
      • Ramsaroop S.D.
      • Reid M.C.
      • Adelman R.D.
      Completing an advance directive in the primary care setting: what do we need for success?.
      (18 studies)
      Patients and HC providersDirect patient–health care professional interactions, using iterative interactions over multiple visitsVarious
      • -
        Unadjusted pooled effect size of 0.50 (95% CI = 0.17–0.83), indicating moderate overall positive effect favoring AD interventions; after adjustment, pool effect 1.15.
      PatientsPassive education of patients with written materials and no direct counselingPrimary care
      • -
        Ineffective for increasing ADs completion in primary care
      Tamayo
      • Tamayo-Velazquez M.I.
      • Simon-Lorda P.
      • Villegas-Portero R.
      • et al.
      Interventions to promote the use of advance directives: an overview of systematic reviews.
      (seven studies total)
      VariousPassive informative material (posters, leaflets, or videos)Various
      • -
        No significant increase in AD completion rates
      VariousInteractive informative interventionsVarious
      • -
        Increases AD completion rate, especially when including multiple sessions
      Walczak
      • Walczak A.
      • Butow P.N.
      • Bu S.
      • Clayton J.M.
      A systematic review of evidence for end-of-life communication interventions: who do they target, how are they structured and do they work?.
      (45 studies total)
      Systematic reviews that include more than one type of intervention.
      PatientsEOL communication educational interventions (two studies)N/A
      • -
        More positive attitudes to, and comfort with, EOL planning, greater power of attorney completion, knowledge, and recall
      • -
        Lower hospital readmission
      CaregiversStructured EOL family conference with bereavement brochure (one study)N/A
      • -
        Significantly reduced the impact of patients' illness and death on caregivers, caregivers' psychological morbidity, expressions of guilt, and provision of nonbeneficial treatments to patients after deciding to withdraw life-sustaining treatment
      • -
        Increased patient and nursing staff input into EOL discussions
      • -
        Did not impact life-sustaining treatment decision (dialysis withdrawal, or time in ICU from treatment withdrawal to death)
      CaregiversStructured EOL family conference without bereavement brochure (one study)N/A
      • -
        Significant reduction in the impact of caregiving challenges including worry and life interference
      • -
        Increased confidence to manage caregiving challenges
      2. Interventions exploring decision aids/decision making or communication strategies
      Aslakson
      • Aslakson R.A.
      • Schuster A.L.
      • Reardon J.
      • et al.
      Promoting perioperative advance care planning: a systematic review of advance care planning decision aids.
      (39 studies evaluating 30 unique decision aids)
      PatientsVideo-based ACP decision aid formatsPerioperative (acute) settings
      • -
        Data supporting benefit (P < 0.001) for informed treatment choice, opinions regarding decision aid, and patient-centered outcomes
      PatientsPaper-based ACP decision aid formatsPerioperative (acute) settings
      • -
        Study findings suggest that there are more data supporting potential benefit (P < 0.001) for ACP status
      Chung
      • Chung H.O.
      • Oczkowski S.J.
      • Hanvey L.
      • Mbuagbaw L.
      • You J.J.
      Educational interventions to train healthcare professionals in end-of-life communication: a systematic review and meta-analysis.
      (20 studies)
      Health professionals (medical trainees, and nurse practitioners)EOL communication skills training (majority of interventions used combination of didactic lectures, small group discussions, and role-play with direct observation and feedback)Mostly teaching hospitals
      • -
        Eight studies (two RCTs) found training was associated with improved self-efficacy (SMD 0.57; P < 0.001; very low–quality evidence)
      • -
        Four studies (two RCTs) found training was associated with increase in knowledge scores (SMD 0.76; P < 0.001; low-quality evidence)
      • -
        Eight studies (three RCTs) found training was associated with improved communication scores (SMD 0.69; P < 0.001; very low–quality evidence)
      Jain
      • Jain A.
      • Corriveau S.
      • Quinn K.
      • Gardhouse A.
      • Vegas D.B.
      • You J.J.
      Video decision aids to assist with advance care planning: a systematic review and meta-analysis.
      (10 RCTs, seven reporting on patients' preferences, four about ACP knowledge and with poolable data, four trials on AD completion)
      PatientsAll interventions compared an ACP video decision aid to assist with choices about future use of life-sustaining treatments against a non-ACP video decision aid (verbal description, pamphlet, usual care, etc.)Outpatient primary care or oncology settings
      • -
        Patients were less likely to indicate a preference for CPR (risk ratio, 0.50 [95% CI 0.27–0.95]; I2 = 65%; heterogeneity P = 0.01)
      • -
        Video decision aids resulted in greater knowledge scores compared with control (standardized mean difference, 0.58 [95% CI 0.39–0.77]; I2 = 0%; heterogeneity P = 0.99)
      • -
        There may be a small effect of video decision aids on this outcome, but with a wide 95% CI including no effect (risk ratio, 1.11 [95% CI 0.85–1.46]; I2 = 44%; heterogeneity P = 0.15)
      O'Connor
      • O'Connor A.M.
      • Rostom A.
      • Fiset V.
      • et al.
      Decision aids for patients facing health treatment or screening decisions: systematic review.
      (17 studies)
      Patients facing health treatment or screening decisions“More complex” decision aids vs. no or “simpler” intervention. All aids included information on the clinical problem in addition to information on the options and outcomes.Varied (major surgery, circumcision of boys, testing for prostate antigens, and other screenings)
      • -
        Improved average knowledge scores for the options and outcomes by 13 to 25 points out of 100 (weighted mean difference = 19.95%; CI 14–25)
      • -
        Positive impact on decisional conflict in three of four studies, with reductions ranging from 0.2 to 0.4 out of 5 (weighted mean difference = 0.3; CI 0.1–0.4)
      • -
        All studies (studying this outcome) showed that decision aids were better than usual care or simpler aids in improving patients' perceptions of “feeling informed.”
      • -
        In three studies, decision aids increased proportion of participants assuming a more active role in decision making compared with usual case control (pooled relative risk = 2.27; CI 1.3–4)
      • -
        No significant results regarding decision aids improving satisfaction. Four studies showed that the use of decision aids did not affect patients' anxiety
      Sessana
      • Sessanna L.
      • Jezewski M.A.
      Advance directive decision making among independent community-dwelling older adults: a systematic review of health science literature.
      (17 studies, eight intervention studies)
      N/AMailed, written AD educational materials, including state-specific AD guidelines and forms

      Addition of a mailed AD educational video
      N/A
      • -
        Increased AD placement in medical records
      • -
        Did not add to the effect of written materials
      Older adultsModerate-level, well-written, easily understood AD educational materials, in addition to easily accessed assistance regarding AD document completionN/A
      • -
        May increase AD use, knowledge, and familiarity
      Elderly outpatientsBrief and prepared physician-initiated AD discussionsN/A
      • -
        Did not increase elderly outpatients' comprehension of ADs
      PatientsOne-time intervention consisting of AD educational information, the provision of AD documents, and encouragement to discuss and complete an ADN/A
      • -
        Did not significantly increase the number of patients obtaining, discussing, or completing an AD
      N/APhysician-initiated AD discussionN/A
      • -
        Discussion was found nondistressing, positively viewed by sample participants, and encouraged participants to continue thinking about and discussing AD issues with family members
      Health care proxyPhysicians using “Talking Points” (a guide summarizing key points in New York State proxy law) as a counseling guide to initiate HC proxy discussion with their patients, combined with copies of language-appropriate proxy forms being placed on patient charts for patients to take home, language-appropriate HC proxy counseling using translators, and chart flagging as a physician reminder to discuss ADsN/A
      • -
        Increased health care proxy appointment
      Health care proxy and patientThe STEP program to facilitate health care professional (HCP) discussion between older adults and their potential or designated health care agentN/A
      • -
        Significantly increased HC proxy communication scores, HC proxy knowledge, and HC proxy understanding of the role and responsibility of a health care agent
      Song 2016
      • Song K.
      • Amatya B.
      • Voutier C.
      • Khan F.
      Advance care planning in patients with primary malignant brain tumors: a systematic review.
      (19 studies reviewed, two interventions)
      Primary malignant brain tumor patientVideo of goals of care decision support tool to facilitate ACP in brain tumor patients. Video-complemented verbal descriptionsN/A
      • -
        No participants in the video tool group preferred life-prolonging care, 4.4% preferred basic care, 91.3% preferred comfort care, and only 4.4% were uncertain (P < 0.0001), while in participants in the verbal narrative group, 25.9% of participants preferred life-prolonging care, 51.9% basic care, and 22.2% comfort care
      Primary malignant brain tumor patientImpact of pilot program of comprehensive palliative care (including provision ACP) on place of death, rehospitalization, and cost-effectivenessHome care
      • -
        61% were assisted at home until the EOL, 22.2% died in hospital, and 16.8% died in inpatient hospice
      • -
        Hospitalization readmission rates and intensive care unit utilization in the last two months of life were significantly lower than the control group who did not receive home assistance (16.7 vs. 38%, respectively; P < 0.001)
      Oczkowski
      • Oczkowski S.J.
      • Chung H.O.
      • Hanvey L.
      • Mbuagbaw L.
      • You J.J.
      Communication tools for end-of-life decision-making in ambulatory care settings: a systematic review and meta-analysis.
      (67 studies)
      PatientsStructured communication tools for EOL decision making (i.e., traditional decision aid in any format (paper, video, computer, etc.), and other structured approaches to help with decision making, including organized meeting plans, patient education interventions on EOL care options, reminders, or mailing of ADs); interventions included verbal discussions alone (n = 9 studies), paper tools alone (n = 9 studies), verbal discussion with paper tool (n = 20 studies), videos (n = 12 studies), computer programs (n = 4 studies), complex multimodal interventions (n = 10 studies), and interventions directed at HCPs rather than patients or SDMs (n = 3)Ambulatory care settings
      • -
        12 RCTs at “low” or “uncertain” risk of bias that reported on the documentation of ADs: pooled estimate of effect was statistically significant (RR 1.92, 95% CI = 1.43–2.59 P < 0.001, low-quality evidence)
      • -
        Four RCTs at “low” or “uncertain” risk of bias reported on ACP discussions: associated with statistically significant increase in the frequency of advance care planning discussions (RR 2.31, 95% CI = 1.25–4.26, P = 0.007, low-quality evidence)
      • -
        Two studies, one “low” risk of bias, other “unclear” risk of bias, reported were associated with a statistically significant increase in concordance of care with care desired by patients (RR 1.17, 95% CI 1.05–1.30, P = 0.004, low-quality evidence)
      Walling
      • Walling A.
      • Lorenz K.A.
      • Dy S.M.
      • et al.
      Evidence-based recommendations for information and care planning in cancer care.
      (number of studies not reported)
      Systematic reviews that include more than one type of intervention.
      MultiplePatient-physician communication techniquesN/A
      • -
        Can increase documentation of ADs
      PhysiciansEducational interventions and communication and care planning interventionsN/A
      • -
        Increased the ability of physicians to elicit patients' preferences
      • -
        Increased patient-surrogate congruence in goals of care
      Walczak
      • Walczak A.
      • Butow P.N.
      • Bu S.
      • Clayton J.M.
      A systematic review of evidence for end-of-life communication interventions: who do they target, how are they structured and do they work?.
      (45 studies total)
      Systematic reviews that include more than one type of intervention.
      PatientPatient-held medical record intervention and provision of audio recording of consultation (two studies)N/A
      • -
        Unaffected outcomes
      CaregiversWeb-based communication intervention with automatic report of concerns to clinicians (one study)
      • -
        No impact on caregiver preparedness or burden of the caregiver role
      • -
        Significantly reduced caregiver negative mood
      Health care professionalsCommunication skills training interventions with (19 studies) and without (one study) role-play, one computer-based and two as part of quality improvement interventions
      • -
        Largely consistent in impacting changes in skill, comfort, self-efficacy, preparedness, and knowledge or attitude in relation to specific communication skills such as delivering bad news (n = 18, 90%)
      3. Subcomponents of ACP (e.g., interventions aimed at increasing AD completion or effects of DNR orders, etc.)
      Brinkman-Stoppelenburg
      • Brinkman-Stoppelenburg A.
      • Rietjens J.A.
      • van der Heide A.
      The effects of advance care planning on end-of-life care: a systematic review.
      (113 studies)
      Systematic reviews that include more than one type of intervention.
      N/ADNR ordersN/A
      • -
        Associated with a decreased use of CPR (four of five studies) and an increased use of hospice and palliative care (six out of six studies). A majority of studies showed a decrease in life-sustaining treatments (12 of 21 studies)
      DNH orders
      • -
        Decrease in hospitalization (eight of nine studies), a decrease in life-sustaining treatments (three of three studies), and an increase in hospice and/or palliative care (five of five studies)
      Advance directives (including living wills and durable powers of attorney)
      • -
        Associated with an increase in hospice and palliative care (five of seven studies). For other outcomes, the results were mixed
      Houben
      • Houben C.H.
      • Spruit M.A.
      • Groenen M.T.
      • Wouters E.F.
      • Janssen D.J.
      Efficacy of advance care planning: a systematic review and meta-analysis.
      (56 studies)
      N/AInterventions: 1) advance directives (focused on completion of ADs, including (durable powers of attorney, living wills, limitation of care forms, 26 studies) vs. 2) communication in addition to ADs (focused on communication about ACP, 30 studies).N/A
      • -
        Both interventions increased the likelihood of completion of ADs (OR 3.26; P < 0.00001) and the likelihood of occurrence of EOL care discussions between patients and health care professionals (OR 2.82; P < 0.00001). Effects of both interventions for these outcomes were comparable
      • -
        Interventions including the communication aspect improved concordance between patient's preferences and received care (OR 4.66; P = 0.03)
      Sumalinog
      • Sumalinog R.
      • Harrington K.
      • Dosani N.
      • Hwang S.W.
      Advance care planning, palliative care, and end-of-life care interventions for homeless people: a systematic review.
      (16 studies, two included in meta-analysis)
      Patients (homeless individuals)Interventions to assist homeless persons in the completion of ADs; self-guided (provided with ACP document and written materials) vs. counselor-guided (additionally meeting a counselor for one-on-one assistance)N/A
      • -
        Counselor-guided interventions resulted in statistically significant increased likelihood of completing AD compared to self-guided (RR 2.6; P < 0.00001)
      4. ACP complex interventions and specific ACP “brands”
      Austin
      • Austin C.A.
      • Mohottige D.
      • Sudore R.L.
      • Smith A.K.
      • Hanson L.C.
      Tools to promote shared decision making in serious illness: a systematic review.
      (38 studies, seven studies testing four decision tools for ACP)
      Moderately, chronically ill older patients52-page workbook Your Life, Your Choices on ACP and 30-minute visit with social worker, vs. packet of AD formsOutpatient settings
      • -
        Increased patient report of ACP discussions after index visit (64% vs. 28%; P < 0.001); increased ACP-related notes written by the clinicians (48% vs. 23% of the medical records, respectively; P = 0.001)
      Moderately ill older patients12-page advance directive document modified for low health literacy, available in English or Spanish, vs. standard ADOutpatient settings
      • -
        Improved ease of use and understanding (69.1% vs. 48.7%; P < 0.001); increased completion of advance directives in six months (18.5% vs. 7.7%; P = 0.03)
      Moderate to severely ill ovarian cancer patientsWeb site information on ovarian cancer, shared decision making, advance directive completion, and palliative care consultation, vs. usual care, clinical docs available on web siteOutpatient settings
      • -
        No effect on completion of advance directives (P = 0.220); no effect on palliative care consultation (P = 0.440)
      Moderately ill older patientsVerbal description followed by a two-minute video showing features of advanced dementia, vs. verbal description of advanced dementiaOutpatient and rural outpatient
      • -
        Increased choice of comfort care as primary goal (Group 1: 86% vs. 64%; P = 0.003; Group 2: 91% vs. 72%; P < 0.001); increased concordance between patients and surrogates (100% vs. 33%; P = 0.015); decreased choice of life-prolonging care as primary goal (0% vs. 16%; P = 0.047)
      Baidoobonso
      • Baidoobonso S.
      Patient care planning discussions for patients at the end of life: an evidence-based analysis.
      (evidence-based analysis used data from 30 studies)
      N/ASingle-provider planning discussions (compared to no discussions or only provision of information with no human interaction)N/A
      • -
        Improve families' satisfaction with EOL care and concordance between patients' and families' wishes
      • -
        Reduce the likelihood of receiving hospital care and the number of days spent in hospital
      • -
        Increase completion of ACP processes and documents, and the likelihood of receiving hospice care
      Team-based discussions (compared to no discussions or only provision of information with no human interaction)
      • -
        Increase patients' satisfaction and the completion of ACP documents and processes
      • -
        Reduce the number of days spent in intensive care and decrease the use of outpatient services
      Earlier planning care discussions (compared to no discussions or only provision of information with no human interaction)
      • -
        Associated with reduced hospital care and with increased hospice care
      Brinkman-Stoppelenburg
      • Brinkman-Stoppelenburg A.
      • Rietjens J.A.
      • van der Heide A.
      The effects of advance care planning on end-of-life care: a systematic review.
      (113 studies total)
      Systematic reviews that include more than one type of intervention.
      N/AAdvance care planning (including let me decide AD program, respecting choices program, physician orders for life-sustaining treatment (POLST) program, let me talk program, making advance care planning a priority (MAPP) program, and several self-developed interventions such as conversations with a trained care planning mediator, a social work intervention, an AD tool, and a pathway tool for present and advance directives)N/A
      • -
        Studies on complex ACP pertain to a range of outcomes and were associated with an increase in compliance with patients' end-of-life wishes (three of four studies), results for other outcomes were mixed
      Dixon
      • Dixon J.
      • Matosevic T.
      • Knapp M.
      The economic evidence for advance care planning: systematic review of evidence.
      (18 studies total)
      VariousSeveral ACP programs (project CARE, optimizing advanced complex illness support, advanced illness coordinated care program, let me decide, SUPPORT, among others)Various
      • -
        Half of the included studies on interventions report statistically significant associations between intervention and health care savings
      Hickman
      • Hickman S.E.
      • Keevern E.
      • Hammes B.
      Use of the Physician Orders for Life-Sustaining Treatment program in the clinical setting: a systematic review of the literature.
      (23 studies)
      VariousPOLSTVarious
      • -
        Decisions to withhold interventions are usually honored
      • -
        Orders for Sections A (resuscitation) and B (medical interventions) are largely consistent with treatments received
      • -
        Orders for comfort measures in Section B are associated with lower rates of hospitalization and hospital death
      Walczak
      • Walczak A.
      • Butow P.N.
      • Bu S.
      • Clayton J.M.
      A systematic review of evidence for end-of-life communication interventions: who do they target, how are they structured and do they work?.
      (45 studies total)
      Systematic reviews that include more than one type of intervention.
      MultifocalACP (three studies)N/A
      • -
        Improved treatment preference, congruence between patients and surrogates, and perceived quality of EOL communication
      • -
        Reduced decision conflict in one study, but not in a second study
      • -
        Comfort with decision making, psychospiritual well-being, anxiety, and knowledge of ACP were unaffected
      PatientsACP interventions (two studies)
      • -
        Significantly higher EOL preference stability and improved discussion and communication of preferences
      • -
        Significantly decreased satisfaction with health care services in one instance
      • -
        Quality of life, anxiety, and depression were unaffected
      Wickson
      • Wickson-Griffiths A.S.K.
      • Ploeag J.
      • McAiney C.
      A review of advance care planning programs in long-term care homes: are they dementia friendly?.
      (six studies total)
      Systematic reviews that include more than one type of intervention.
      PatientsLet me decideN/A
      • -
        Increased ACP documentation, fewer hospitalizations, and less resource use
      Let me talk
      • -
        Increased knowledge of residents' ACP for staff and families, improved quality of residents' life, and stability of health care choices
      Social work strategy to enhance ACP documentation
      • -
        Increased documentation of specific ACP and adherence to residents' and family members' preferences
      5. Interventions aimed at improving palliative or EOL care
      Hall
      • Hall S.
      • Kolliakou A.
      • Petkova H.
      • Froggatt K.
      • Higginson I.J.
      Interventions for improving palliative care for older people living in nursing care homes.
      (three studies)
      Residents of care homes for older peoplePalliative care service delivery interventions, which included referrals to external palliative care services and/or palliative care training for care home staff.Older people residential homes
      • -
        In two studies, higher referral to hospice services in their intervention group six months after intervention; one study, fewer hospital admissions and days in hospital in the intervention group; one study, higher proportion of residents in the intervention group had DNR orders, had these easily identifiable on their chart, and had advance care plan discussions documented
      Kavalieratos
      • Kavalieratos D.
      • Corbelli J.
      • Zhang D.
      • et al.
      Association between palliative care and patient and caregiver outcomes: a systematic review and meta-analysis.
      (for ACP, 10 trials assessed)
      Patients and caregiversPalliative care interventions (among the five trials that reported statistically significant improvements, three were at high risk of bias and two were at unclear risk of bias)Palliative care
      • -
        Of the outcomes narratively synthesized, palliative care was associated with improved advance care planning, greater patients' and caregivers' satisfaction with care, and lower health care utilization
      Patients with lung cancerOne trial at low risk of bias trial of early specialist palliative care in patients with lung cancerPalliative cancer care
      • -
        No association with documentation of resuscitation preferences (P = 0.05)
      Khandelwal
      • Khandelwal N.
      • Kross E.K.
      • Engelberg R.A.
      • Coe N.B.
      • Long A.C.
      • Curtis J.R.
      Estimating the effect of palliative care interventions and advance care planning on ICU utilization: a systematic review.
      (22 studies)
      PatientsPalliative care consultations on ICU admissions as an outcome (three studies)Hospitals
      • -
        The mean relative risk reduction for ICU admissions associated with interventions was 37% (SD, 23%)
      PatientsAdvance care planning intervention and palliative care consultations on ICU length of stay (two RCTs)Inpatient, outpatient
      • -
        No change or inconclusive
      Patients (10 trials)

      Hospital or ICU (four trials)
      Ethics or palliative care consultations/interventions (four RCTs, 10 non-RCTs) reporting on ICU LOSICU
      • -
        The mean relative risk reduction for ICU LOS associated with all palliative care interventions in the ICU setting was 26% (SD, 23%)
      • -
        When restricting to palliative care interventions in the ICU setting that were directly targeted at the level of individual patients, the mean relative risk reduction was 33% (SD, 23%)
      Lorenz 2008
      • Lorenz K.A.
      • Lynn J.
      • Dy S.M.
      • et al.
      Evidence for improving palliative care at the end of life: a systematic review.
      (for ACP, nine systematic reviews and 32 intervention studies)
      VariousMulticomponent (palliative care interventions) (those that engage values, involve skilled facilitators, and include patients, caregivers, and providers). Interventions include multidisciplinary decision making, ACP workbook, peer mentoring, ethics team consultation, preoperative structured care planning, nursing home quality improvement, effects of directives on mutual understandingVarious
      • -
        Increase advance directives
      • -
        Can increase the rates and effectiveness of communication about late-life goals and advance care planning
      Walling
      • Walling A.
      • Lorenz K.A.
      • Dy S.M.
      • et al.
      Evidence-based recommendations for information and care planning in cancer care.
      (number of studies not reported)
      Systematic reviews that include more than one type of intervention.
      N/AOther ACP interventions—many times as one component of a palliative care intervention to effect hospice enrollmentN/A
      • -
        Positive effects on patients' satisfaction, patients' knowledge, and psychological adjustment
      Palliative care/coordinated care interventions
      • -
        Can increase documentation of ADs
      Wickson
      • Wickson-Griffiths A.S.K.
      • Ploeag J.
      • McAiney C.
      A review of advance care planning programs in long-term care homes: are they dementia friendly?.
      (six studies total)
      Systematic reviews that include more than one type of intervention.
      PatientsPalliative care quality improvement programsN/A
      • -
        Increased ACP discussion documentation
      Intervention aiming to improve hospice service
      • -
        Appropriate palliation or EOL care services in accordance with ACP and health care preferences
      Martin
      • Martin R.S.
      • Hayes B.
      • Gregorevic K.
      • Lim W.K.
      The effects of advance care planning interventions on nursing home residents: a systematic review.
      (13 studies, results do not specify outcomes for each intervention)
      Review mentions the different interventions but groups all the outcomes together. Therefore, all the interventions are grouped together and not in their corresponding classification.
      VariousFive of the interventions were an educational program: two ACP education for health care staff and three ACP education for health care staff, residents, and families.Nursing homes
      • -
        ACP reduces hospitalization of nursing home residents. Interestingly, where studied, mortality was not decreased by hospitalization
      • -
        Actions are highly consistent with resident's wishes when their ACP is completed and lead to decreased usage of unwanted life-sustaining treatments.
      • -
        Residents with ACP have a high incidence of dying in their preferred place of death, which was more often, in the nursing home. ACP was found to lead to increased and earlier community palliative care referrals
      • -
        QOL and satisfaction with the dying process were rarely measured in the studies reviewed
      • -
        For DNR studies, one found no difference in medical treatments to residents with full code vs. DNR orders. The second found those with DNR orders less likely to be hospitalized than those without
      VariousFive studies involved introduction or evaluation of a new ACP form in the facility.Nursing homes
      VariousTwo studies involved an ACP program with a palliative care initiativeNursing homes
      Residents with lower respiratory infectionsOne study involved observation of the effect of DNR orders on medical treatmentsNursing homes
      SR = systematic review; ACP = advance care planning; EOL = end-of-life; ADs = advance directives; DNR = Do-Not-Resuscitate; N/A = not available or not applicable; HC = health care; DNH = Do-Not-Hospitalize; OR = odds ratio; LOS = length of stay; QOL = quality of life; RCT = randomized controlled trial; SMD = standardized mean difference; CPR = cardiopulmonary resuscitation; RR = risk ratio; SDMs = substitute decision makers.
      a Systematic reviews that include more than one type of intervention.
      b Review mentions the different interventions but groups all the outcomes together. Therefore, all the interventions are grouped together and not in their corresponding classification.
      In the first group, a large number of interventions were either informational or educational,
      • Walczak A.
      • Butow P.N.
      • Bu S.
      • Clayton J.M.
      A systematic review of evidence for end-of-life communication interventions: who do they target, how are they structured and do they work?.
      • Ramsaroop S.D.
      • Reid M.C.
      • Adelman R.D.
      Completing an advance directive in the primary care setting: what do we need for success?.
      • Durbin C.R.
      • Fish A.F.
      • Bachman J.A.
      • Smith K.V.
      Systematic review of educational interventions for improving advance directive completion.
      • Hanson L.C.
      • Tulsky J.A.
      • Danis M.
      Can clinical interventions change care at the end of life?.
      • Jezewski M.A.
      • Meeker M.A.
      • Sessanna L.
      • Finnell D.S.
      The effectiveness of interventions to increase advance directive completion rates.
      • Patel R.V.
      • Sinuff T.
      • Cook D.J.
      Influencing advance directive completion rates in non-terminally ill patients: a systematic review.
      • Tamayo-Velazquez M.I.
      • Simon-Lorda P.
      • Villegas-Portero R.
      • et al.
      Interventions to promote the use of advance directives: an overview of systematic reviews.
      • Martin R.S.
      • Hayes B.
      • Gregorevic K.
      • Lim W.K.
      The effects of advance care planning interventions on nursing home residents: a systematic review.
      many focusing on specific groups of patients and settings. This type of intervention facilitated documentation of preferences and enhanced communication between patients and surrogates,
      • Walczak A.
      • Butow P.N.
      • Bu S.
      • Clayton J.M.
      A systematic review of evidence for end-of-life communication interventions: who do they target, how are they structured and do they work?.
      and increased AD completion.
      • Ke L.S.
      • Huang X.
      • O'Connor M.
      • Lee S.
      Nurses' views regarding implementing advance care planning for older people: a systematic review and synthesis of qualitative studies.
      • De Vleminck A.
      • Houttekier D.
      • Pardon K.
      • et al.
      Barriers and facilitators for general practitioners to engage in advance care planning: a systematic review.
      • Ramsaroop S.D.
      • Reid M.C.
      • Adelman R.D.
      Completing an advance directive in the primary care setting: what do we need for success?.
      • Auriemma C.L.
      • Nguyen C.A.
      • Bronheim R.
      • et al.
      Stability of end-of-life preferences: a systematic review of the evidence.
      • Houben C.H.
      • Spruit M.A.
      • Groenen M.T.
      • Wouters E.F.
      • Janssen D.J.
      Efficacy of advance care planning: a systematic review and meta-analysis.
      • Sumalinog R.
      • Harrington K.
      • Dosani N.
      • Hwang S.W.
      Advance care planning, palliative care, and end-of-life care interventions for homeless people: a systematic review.
      • Weathers E.
      • O'Caoimh R.
      • Cornally N.
      • et al.
      Advance care planning: a systematic review of randomised controlled trials conducted with older adults.
      The most successful ones at increasing AD completion were those that combined computer, video, and discussion elements instead of only providing written material; those directed at both patients and providers instead of being directed to single stakeholders; and those providing group education and information multiple times as opposed to a one-off event.
      The second group includes interventions that focused on decision aids or on improving decision making and those that explored communication or discussion strategies. Decision aids improved knowledge about ADs, ACP, treatment options, and goals of care
      • Aslakson R.A.
      • Schuster A.L.
      • Reardon J.
      • et al.
      Promoting perioperative advance care planning: a systematic review of advance care planning decision aids.
      • Sessanna L.
      • Jezewski M.A.
      Advance directive decision making among independent community-dwelling older adults: a systematic review of health science literature.
      • Jain A.
      • Corriveau S.
      • Quinn K.
      • Gardhouse A.
      • Vegas D.B.
      • You J.J.
      Video decision aids to assist with advance care planning: a systematic review and meta-analysis.
      • O'Connor A.M.
      • Rostom A.
      • Fiset V.
      • et al.
      Decision aids for patients facing health treatment or screening decisions: systematic review.
      ; increased AD completion and ACP status and discussions
      • Aslakson R.A.
      • Schuster A.L.
      • Reardon J.
      • et al.
      Promoting perioperative advance care planning: a systematic review of advance care planning decision aids.
      • Jain A.
      • Corriveau S.
      • Quinn K.
      • Gardhouse A.
      • Vegas D.B.
      • You J.J.
      Video decision aids to assist with advance care planning: a systematic review and meta-analysis.
      ; and decreased decisional conflict.
      • Aslakson R.A.
      • Schuster A.L.
      • Reardon J.
      • et al.
      Promoting perioperative advance care planning: a systematic review of advance care planning decision aids.
      • Sessanna L.
      • Jezewski M.A.
      Advance directive decision making among independent community-dwelling older adults: a systematic review of health science literature.
      Decision aids in video format improved informed treatment choice and increased patient confidence in decision making, and patients were less likely to choose aggressive care interventions.
      • Aslakson R.A.
      • Schuster A.L.
      • Reardon J.
      • et al.
      Promoting perioperative advance care planning: a systematic review of advance care planning decision aids.
      • Song K.
      • Amatya B.
      • Voutier C.
      • Khan F.
      Advance care planning in patients with primary malignant brain tumors: a systematic review.
      • Jain A.
      • Corriveau S.
      • Quinn K.
      • Gardhouse A.
      • Vegas D.B.
      • You J.J.
      Video decision aids to assist with advance care planning: a systematic review and meta-analysis.
      There was, however, an unclear impact of decision aids on ADs being included in the medical record, on improving treatment agreement between patients and surrogates, and on improving satisfaction or decreasing anxiety.
      • Aslakson R.A.
      • Schuster A.L.
      • Reardon J.
      • et al.
      Promoting perioperative advance care planning: a systematic review of advance care planning decision aids.
      • O'Connor A.M.
      • Rostom A.
      • Fiset V.
      • et al.
      Decision aids for patients facing health treatment or screening decisions: systematic review.
      Communication interventions, which included communication skills training for health care professionals as well as communication guides/techniques for patients, showed mixed results. While some increased documentation of ADs and patient-surrogate congruence about goals of care,
      • Walling A.
      • Lorenz K.A.
      • Dy S.M.
      • et al.
      Evidence-based recommendations for information and care planning in cancer care.
      • Oczkowski S.J.
      • Chung H.O.
      • Hanvey L.
      • Mbuagbaw L.
      • You J.J.
      Communication tools for end-of-life decision-making in ambulatory care settings: a systematic review and meta-analysis.
      others did not have much impact (most commonly, those not including interaction with a provider).
      • Walczak A.
      • Butow P.N.
      • Bu S.
      • Clayton J.M.
      A systematic review of evidence for end-of-life communication interventions: who do they target, how are they structured and do they work?.
      Communication skills training for health care professionals improved skills, comfort, self-efficacy, preparedness, and knowledge or attitudes in relation to specific communication skills such as delivering bad news.
      • Walczak A.
      • Butow P.N.
      • Bu S.
      • Clayton J.M.
      A systematic review of evidence for end-of-life communication interventions: who do they target, how are they structured and do they work?.
      • Chung H.O.
      • Oczkowski S.J.
      • Hanvey L.
      • Mbuagbaw L.
      • You J.J.
      Educational interventions to train healthcare professionals in end-of-life communication: a systematic review and meta-analysis.
      In the third category, interventions that aimed to impact subcomponents of ACP (such as effects of DNR orders or ADs) increased the completion of ADs and the occurrence of EOL care discussions between patients and health care professionals,
      • Houben C.H.
      • Spruit M.A.
      • Groenen M.T.
      • Wouters E.F.
      • Janssen D.J.
      Efficacy of advance care planning: a systematic review and meta-analysis.
      especially if they had a counselor guiding the process.
      • Sumalinog R.
      • Harrington K.
      • Dosani N.
      • Hwang S.W.
      Advance care planning, palliative care, and end-of-life care interventions for homeless people: a systematic review.
      AD interventions with a focus on communication also improved concordance between patient's preferences and received EOL care.
      • Houben C.H.
      • Spruit M.A.
      • Groenen M.T.
      • Wouters E.F.
      • Janssen D.J.
      Efficacy of advance care planning: a systematic review and meta-analysis.
      The effects of DNR orders were associated with decreased use of cardiopulmonary resuscitation (CPR), increased use of hospice and palliative care, and a decrease in life-sustaining treatments. DNH orders showed a decrease in hospitalization, a decrease in life-sustaining treatments, and an increase in hospice and/or palliative care.
      • Brinkman-Stoppelenburg A.
      • Rietjens J.A.
      • van der Heide A.
      The effects of advance care planning on end-of-life care: a systematic review.
      In the fourth category, complex ACP interventions varied in format and the SRs differed in the amount of details provided on each intervention (Table 2). A two-minute video for ACP discussions, a modified ACP for lower health literacy, and an ACP workbook increased ACP discussions held, completion of ADs, and choice of comfort care as primary goal, whereas a web site had no effect on completion of ADs or on palliative care consultations.
      • Austin C.A.
      • Mohottige D.
      • Sudore R.L.
      • Smith A.K.
      • Hanson L.C.
      Tools to promote shared decision making in serious illness: a systematic review.
      Single-provider discussions, team-based discussions, and earlier planning care discussions were all associated with lower use of health services, and both single-provider and team-based discussions also increased the completion of ACP processes.
      • Baidoobonso S.
      Patient care planning discussions for patients at the end of life: an evidence-based analysis.
      ACP interventions aimed at more than one type of stakeholder (i.e., not only at patients, but also including surrogates or providers); improved treatment preference, congruence between patients and surrogates, and perceived quality of EOL communication; and reduced decisional conflict, while several other outcomes (quality of life, anxiety and depression, comfort with decision making, psychospiritual well-being, knowledge of ACP) were unaffected.
      • Walczak A.
      • Butow P.N.
      • Bu S.
      • Clayton J.M.
      A systematic review of evidence for end-of-life communication interventions: who do they target, how are they structured and do they work?.
      Extensive ACP programs (compared to providing written documents alone) may be more effective at increasing frequency of out-of-hospital and out-of-ICU care, increasing compliance with patients' wishes and satisfaction with care,
      • Brinkman-Stoppelenburg A.
      • Rietjens J.A.
      • van der Heide A.
      The effects of advance care planning on end-of-life care: a systematic review.
      and may drive health care savings.
      • Dixon J.
      • Matosevic T.
      • Knapp M.
      The economic evidence for advance care planning: systematic review of evidence.
      For specific “brands” of ACP, the POLST was associated with withheld treatments when requested and with lower rates of hospitalization and hospital deaths when orders for comfort measures were in place.
      • Hickman S.E.
      • Keevern E.
      • Hammes B.
      Use of the Physician Orders for Life-Sustaining Treatment program in the clinical setting: a systematic review of the literature.
      Other programs such as the “let me decide” program showed increased ACP documentation, fewer hospitalizations, and less resource use.
      • Wickson-Griffiths A.S.K.
      • Ploeag J.
      • McAiney C.
      A review of advance care planning programs in long-term care homes: are they dementia friendly?.
      The “let me talk” program increased ACP knowledge among care home residents, staffs, and families as well as improved quality of care and stability of health care choices.
      • Wickson-Griffiths A.S.K.
      • Ploeag J.
      • McAiney C.
      A review of advance care planning programs in long-term care homes: are they dementia friendly?.
      Social work strategies to enhance ACP documentation increased adherence to care home residents' and family members' preferences.
      • Wickson-Griffiths A.S.K.
      • Ploeag J.
      • McAiney C.
      A review of advance care planning programs in long-term care homes: are they dementia friendly?.
      For the fifth category, palliative care interventions (in several different configurations, see Table 2) seemed to result in care home residents and patients having higher proportions of DNR orders, more ACP discussions documented, and higher documentation of ADs.
      • Hall S.
      • Kolliakou A.
      • Petkova H.
      • Froggatt K.
      • Higginson I.J.
      Interventions for improving palliative care for older people living in nursing care homes.
      • Lorenz K.A.
      • Lynn J.
      • Dy S.M.
      • et al.
      Evidence for improving palliative care at the end of life: a systematic review.
      • Wickson-Griffiths A.S.K.
      • Ploeag J.
      • McAiney C.
      A review of advance care planning programs in long-term care homes: are they dementia friendly?.
      In addition, palliative care was associated with improved ACP and greater EOL care satisfaction for caregivers and patients,
      • Kavalieratos D.
      • Corbelli J.
      • Zhang D.
      • et al.
      Association between palliative care and patient and caregiver outcomes: a systematic review and meta-analysis.
      with improved communication about late-life goals,
      • Lorenz K.A.
      • Lynn J.
      • Dy S.M.
      • et al.
      Evidence for improving palliative care at the end of life: a systematic review.
      and lower health care utilization and ICU admissions and length of stay.
      • Kavalieratos D.
      • Corbelli J.
      • Zhang D.
      • et al.
      Association between palliative care and patient and caregiver outcomes: a systematic review and meta-analysis.
      • Khandelwal N.
      • Kross E.K.
      • Engelberg R.A.
      • Coe N.B.
      • Long A.C.
      • Curtis J.R.
      Estimating the effect of palliative care interventions and advance care planning on ICU utilization: a systematic review.
      However, some palliative care trials resulted in no association between intervention and the documentation of preferences.
      • Kavalieratos D.
      • Corbelli J.
      • Zhang D.
      • et al.
      Association between palliative care and patient and caregiver outcomes: a systematic review and meta-analysis.
      An ACP intervention that included a palliative care consultation had no change in ICU length of stay.
      • Khandelwal N.
      • Kross E.K.
      • Engelberg R.A.
      • Coe N.B.
      • Long A.C.
      • Curtis J.R.
      Estimating the effect of palliative care interventions and advance care planning on ICU utilization: a systematic review.

      Undifferentiated ACP Interventions and Corresponding Outcomes

      The SRs that did not differentiate between individual types of interventions reported that ACP that was broadly conceptualized was associated with increased documentation of EOL preferences, as well as increased use and completion rates of durable powers of attorneys or ADs,
      • Weathers E.
      • O'Caoimh R.
      • Cornally N.
      • et al.
      Advance care planning: a systematic review of randomised controlled trials conducted with older adults.
      which helped shift decision responsibility from health care teams to patients and their families.
      • Ke L.S.
      • Huang X.
      • O'Connor M.
      • Lee S.
      Nurses' views regarding implementing advance care planning for older people: a systematic review and synthesis of qualitative studies.
      ACP was also beneficial at increasing EOL discussions with patients, family members, and physicians,
      • Song K.
      • Amatya B.
      • Voutier C.
      • Khan F.
      Advance care planning in patients with primary malignant brain tumors: a systematic review.
      • Smith C.
      • Jaffray L.
      • Ellis I.
      Electronic advance care planning in community: nurses' role. GSTF Digital Library.
      • Murray L.
      • Butow P.N.
      Advance care planning in motor neuron disease: a systematic review.
      • Hickman S.E.
      • Keevern E.
      • Hammes B.
      Use of the Physician Orders for Life-Sustaining Treatment program in the clinical setting: a systematic review of the literature.
      • Weathers E.
      • O'Caoimh R.
      • Cornally N.
      • et al.
      Advance care planning: a systematic review of randomised controlled trials conducted with older adults.
      clarifying patients' choices and raising awareness,
      • Murray L.
      • Butow P.N.
      Advance care planning in motor neuron disease: a systematic review.
      and improving communication between patients and clinicians,
      • Song K.
      • Amatya B.
      • Voutier C.
      • Khan F.
      Advance care planning in patients with primary malignant brain tumors: a systematic review.
      and between nursing homes and hospitals.
      • Hickman S.E.
      • Keevern E.
      • Hammes B.
      Use of the Physician Orders for Life-Sustaining Treatment program in the clinical setting: a systematic review of the literature.
      ACP interventions were also found to increase patients' and families' satisfaction with care and giving patients stronger feelings of being “cared for” and “in control,” which provided a greater peace of mind and a sense of relief.
      • Murray L.
      • Butow P.N.
      Advance care planning in motor neuron disease: a systematic review.
      • Weathers E.
      • O'Caoimh R.
      • Cornally N.
      • et al.
      Advance care planning: a systematic review of randomised controlled trials conducted with older adults.
      ACP also had an effect on preventing or decreasing use of unwanted life-sustaining treatments.
      • Murray L.
      • Butow P.N.
      Advance care planning in motor neuron disease: a systematic review.
      • Martin R.S.
      • Hayes B.
      • Gregorevic K.
      • Lim W.K.
      The effects of advance care planning interventions on nursing home residents: a systematic review.
      Preparing ADs and earlier discussions of EOL issues improved surrogate accuracy with patients' wishes.
      • Ke L.S.
      • Huang X.
      • O'Connor M.
      • Lee S.
      Nurses' views regarding implementing advance care planning for older people: a systematic review and synthesis of qualitative studies.
      • Meeker M.A.
      • Jezewski M.A.
      Family decision making at end of life.
      However, surrogates' confidence in their choices was found to be higher than their measured accuracy,
      • Dixon J.
      • Matosevic T.
      • Knapp M.
      The economic evidence for advance care planning: systematic review of evidence.
      reflecting a disconnect between surrogates and patients. Some SRs found that when ACPs were completed, nursing home residents' and motor neuron disease patients' preferences were consistently honored in terms of the treatment they received, although this finding comes from low-quality evidence.
      • Murray L.
      • Butow P.N.
      Advance care planning in motor neuron disease: a systematic review.
      • Martin R.S.
      • Hayes B.
      • Gregorevic K.
      • Lim W.K.
      The effects of advance care planning interventions on nursing home residents: a systematic review.
      In addition, those that had completed an ACP had a higher incidence of dying at their preferred place of death: nursing home residents tended to die in their nursing homes,
      • Martin R.S.
      • Hayes B.
      • Gregorevic K.
      • Lim W.K.
      The effects of advance care planning interventions on nursing home residents: a systematic review.
      and patients with primary malignant brain tumor tended to die in their home or hospice.
      • Song K.
      • Amatya B.
      • Voutier C.
      • Khan F.
      Advance care planning in patients with primary malignant brain tumors: a systematic review.
      ACP was also found to improve the transition from acute to terminal care and was associated with earlier community palliative care referrals.
      • Oliver D.P.
      • Porock D.
      • Zweig S.
      End-of-life care in U.S. nursing homes: a review of the evidence.
      • Martin R.S.
      • Hayes B.
      • Gregorevic K.
      • Lim W.K.
      The effects of advance care planning interventions on nursing home residents: a systematic review.
      In terms of resource use or cost outcomes, ACP interventions, hospice use, and programs such as the POLST can lower hospitalization rates and use of resources,
      • Oliver D.P.
      • Porock D.
      • Zweig S.
      End-of-life care in U.S. nursing homes: a review of the evidence.
      • Weathers E.
      • O'Caoimh R.
      • Cornally N.
      • et al.
      Advance care planning: a systematic review of randomised controlled trials conducted with older adults.
      • Klingler C.
      • In der Schmitten J.
      • Marckmann G.
      Does facilitated Advance Care Planning reduce the costs of care near the end of life? Systematic review and ethical considerations.
      especially for nursing home residents.
      • Dixon J.
      • Matosevic T.
      • Knapp M.
      The economic evidence for advance care planning: systematic review of evidence.
      • Martin R.S.
      • Hayes B.
      • Gregorevic K.
      • Lim W.K.
      The effects of advance care planning interventions on nursing home residents: a systematic review.
      In addition, there were associations between ACP and reductions in ICU use and admissions, and ICU length of stay.
      • Dixon J.
      • Matosevic T.
      • Knapp M.
      The economic evidence for advance care planning: systematic review of evidence.
      • Khandelwal N.
      • Kross E.K.
      • Engelberg R.A.
      • Coe N.B.
      • Long A.C.
      • Curtis J.R.
      Estimating the effect of palliative care interventions and advance care planning on ICU utilization: a systematic review.
      However, all the studies exploring ACP and costs mention that the information regarding the source of cost savings is limited and that only preliminary conclusions can be made owing to poorly defined and heterogeneous interventions.
      • Dixon J.
      • Matosevic T.
      • Knapp M.
      The economic evidence for advance care planning: systematic review of evidence.
      • Khandelwal N.
      • Kross E.K.
      • Engelberg R.A.
      • Coe N.B.
      • Long A.C.
      • Curtis J.R.
      Estimating the effect of palliative care interventions and advance care planning on ICU utilization: a systematic review.
      • Klingler C.
      • In der Schmitten J.
      • Marckmann G.
      Does facilitated Advance Care Planning reduce the costs of care near the end of life? Systematic review and ethical considerations.
      • Taylor J.S.
      • Heyland D.K.
      • Taylor S.J.
      How advance directives affect hospital resource use. Systematic review of the literature.
      A summary of ACP interventions and outcomes can be seen in Table 3.
      Table 3ACP Interventions and Outcomes Summary
      Type of InterventionOutcomeRef. Examples
      ACP (broadly conceptualized), associated with:Improved surrogate and patient's wishes concordance
      • Ke L.S.
      • Huang X.
      • O'Connor M.
      • Lee S.
      Nurses' views regarding implementing advance care planning for older people: a systematic review and synthesis of qualitative studies.
      • Meeker M.A.
      • Jezewski M.A.
      Family decision making at end of life.
      Concordance between wishes and received care (for some groups of patients)
      • Murray L.
      • Butow P.N.
      Advance care planning in motor neuron disease: a systematic review.
      • Martin R.S.
      • Hayes B.
      • Gregorevic K.
      • Lim W.K.
      The effects of advance care planning interventions on nursing home residents: a systematic review.
      Higher incidence for preferred place of death (for some groups of patients)
      • Oliver D.P.
      • Porock D.
      • Zweig S.
      End-of-life care in U.S. nursing homes: a review of the evidence.
      • Martin R.S.
      • Hayes B.
      • Gregorevic K.
      • Lim W.K.
      The effects of advance care planning interventions on nursing home residents: a systematic review.
      Increased ACP-related documentation
      • Weathers E.
      • O'Caoimh R.
      • Cornally N.
      • et al.
      Advance care planning: a systematic review of randomised controlled trials conducted with older adults.
      Increased occurrence of discussions
      • Song K.
      • Amatya B.
      • Voutier C.
      • Khan F.
      Advance care planning in patients with primary malignant brain tumors: a systematic review.
      • Smith C.
      • Jaffray L.
      • Ellis I.
      Electronic advance care planning in community: nurses' role. GSTF Digital Library.
      • Murray L.
      • Butow P.N.
      Advance care planning in motor neuron disease: a systematic review.
      • Hickman S.E.
      • Keevern E.
      • Hammes B.
      Use of the Physician Orders for Life-Sustaining Treatment program in the clinical setting: a systematic review of the literature.
      • Weathers E.
      • O'Caoimh R.
      • Cornally N.
      • et al.
      Advance care planning: a systematic review of randomised controlled trials conducted with older adults.
      Decreased use of unwanted life-sustaining treatments
      • Murray L.
      • Butow P.N.
      Advance care planning in motor neuron disease: a systematic review.
      • Martin R.S.
      • Hayes B.
      • Gregorevic K.
      • Lim W.K.
      The effects of advance care planning interventions on nursing home residents: a systematic review.
      Lower use of resources and hospitalization rates
      • Oliver D.P.
      • Porock D.
      • Zweig S.
      End-of-life care in U.S. nursing homes: a review of the evidence.
      • Dixon J.
      • Matosevic T.
      • Knapp M.
      The economic evidence for advance care planning: systematic review of evidence.
      • Martin R.S.
      • Hayes B.
      • Gregorevic K.
      • Lim W.K.
      The effects of advance care planning interventions on nursing home residents: a systematic review.
      • Weathers E.
      • O'Caoimh R.
      • Cornally N.
      • et al.
      Advance care planning: a systematic review of randomised controlled trials conducted with older adults.
      Different types of ACP interventions/different interventions impacting ACP
       Information/educational interventionsFacilitated documentation of preferences; enhanced communication between patients and surrogates
      • Walczak A.
      • Butow P.N.
      • Bu S.
      • Clayton J.M.
      A systematic review of evidence for end-of-life communication interventions: who do they target, how are they structured and do they work?.
      Increased AD completion
      • Ramsaroop S.D.
      • Reid M.C.
      • Adelman R.D.
      Completing an advance directive in the primary care setting: what do we need for success?.
      • Durbin C.R.
      • Fish A.F.
      • Bachman J.A.
      • Smith K.V.
      Systematic review of educational interventions for improving advance directive completion.
      • Hanson L.C.
      • Tulsky J.A.
      • Danis M.
      Can clinical interventions change care at the end of life?.
       Decision aids/communication interventionsImproved knowledge about ADs, ACP treatment options and goals of care
      • Aslakson R.A.
      • Schuster A.L.
      • Reardon J.
      • et al.
      Promoting perioperative advance care planning: a systematic review of advance care planning decision aids.
      • Sessanna L.
      • Jezewski M.A.
      Advance directive decision making among independent community-dwelling older adults: a systematic review of health science literature.
      • Jain A.
      • Corriveau S.
      • Quinn K.
      • Gardhouse A.
      • Vegas D.B.
      • You J.J.
      Video decision aids to assist with advance care planning: a systematic review and meta-analysis.
      • O'Connor A.M.
      • Rostom A.
      • Fiset V.
      • et al.
      Decision aids for patients facing health treatment or screening decisions: systematic review.
      Increased AD completion and ACP status and discussions
      • Aslakson R.A.
      • Schuster A.L.
      • Reardon J.
      • et al.
      Promoting perioperative advance care planning: a systematic review of advance care planning decision aids.
      • O'Connor A.M.
      • Rostom A.
      • Fiset V.
      • et al.
      Decision aids for patients facing health treatment or screening decisions: systematic review.
      Decreased decisional conflict
      • Aslakson R.A.
      • Schuster A.L.
      • Reardon J.
      • et al.
      Promoting perioperative advance care planning: a systematic review of advance care planning decision aids.
      • Sessanna L.
      • Jezewski M.A.
      Advance directive decision making among independent community-dwelling older adults: a systematic review of health science literature.
      Improved skills, comfort, preparedness and knowledge about ACP for health professionals
      • Walczak A.
      • Butow P.N.
      • Bu S.
      • Clayton J.M.
      A systematic review of evidence for end-of-life communication interventions: who do they target, how are they structured and do they work?.
      • Chung H.O.
      • Oczkowski S.J.
      • Hanvey L.
      • Mbuagbaw L.
      • You J.J.
      Educational interventions to train healthcare professionals in end-of-life communication: a systematic review and meta-analysis.
       AD/DNR/DNH, and so on, interventionsIncreased AD completion and occurrence of EOL discussions
      • Houben C.H.
      • Spruit M.A.
      • Groenen M.T.
      • Wouters E.F.
      • Janssen D.J.
      Efficacy of advance care planning: a systematic review and meta-analysis.
      • Sumalinog R.
      • Harrington K.
      • Dosani N.
      • Hwang S.W.
      Advance care planning, palliative care, and end-of-life care interventions for homeless people: a systematic review.
      Associated with decreased use of CPR; increased use of hospice and palliative care
      • Brinkman-Stoppelenburg A.
      • Rietjens J.A.
      • van der Heide A.
      The effects of advance care planning on end-of-life care: a systematic review.
      Decrease in life-sustaining treatments
      • Brinkman-Stoppelenburg A.
      • Rietjens J.A.
      • van der Heide A.
      The effects of advance care planning on end-of-life care: a systematic review.
       ACP complex interventionsIncreased occurrence of ACP decisions, completion of ADs, and preferences for comfort care
      • Austin C.A.
      • Mohottige D.
      • Sudore R.L.
      • Smith A.K.
      • Hanson L.C.
      Tools to promote shared decision making in serious illness: a systematic review.
      Lower use of services and increased completion of ACP processes
      • Baidoobonso S.
      Patient care planning discussions for patients at the end of life: an evidence-based analysis.
      Improved preference congruence between patient and surrogate; reduced decisional conflict
      • Walczak A.
      • Butow P.N.
      • Bu S.
      • Clayton J.M.
      A systematic review of evidence for end-of-life communication interventions: who do they target, how are they structured and do they work?.
      Increased frequency of out-of-hospital and out-of-ICU care; health care savings
      • Brinkman-Stoppelenburg A.
      • Rietjens J.A.
      • van der Heide A.
      The effects of advance care planning on end-of-life care: a systematic review.
      • Dixon J.
      • Matosevic T.
      • Knapp M.
      The economic evidence for advance care planning: systematic review of evidence.
       Palliative care interventionsHigher documentation of ACP-related documents
      • Hall S.
      • Kolliakou A.
      • Petkova H.
      • Froggatt K.
      • Higginson I.J.
      Interventions for improving palliative care for older people living in nursing care homes.
      • Lorenz K.A.
      • Lynn J.
      • Dy S.M.
      • et al.
      Evidence for improving palliative care at the end of life: a systematic review.
      • Wickson-Griffiths A.S.K.
      • Ploeag J.
      • McAiney C.
      A review of advance care planning programs in long-term care homes: are they dementia friendly?.
      Higher EOL care satisfaction
      • Kavalieratos D.
      • Corbelli J.
      • Zhang D.
      • et al.
      Association between palliative care and patient and caregiver outcomes: a systematic review and meta-analysis.
      Improved communication about late-life goals
      • Lorenz K.A.
      • Lynn J.
      • Dy S.M.
      • et al.
      Evidence for improving palliative care at the end of life: a systematic review.
      ACP = advance care planning; AD = advance directive; CPR = cardiopulmonary resuscitation; DNR = Do-Not-Resuscitate; DNH = Do-Not-Hospitalize; EOL = end-of-life.

      Discussion

      This overview of systematic reviews synthesized available evidence on ACP, revealing key contextual elements, program features, types of interventions, and outcomes that influence its design and implementation. Overall, despite the large amount of research analyzed, the quality of current evidence is limited with mixed results and outcomes, and therefore should be interpreted with caution. It is clear that the SRs' divergent results are dependent on the interventions examined.
      The evidence derived from the analysis of available SRs provides different layers of information, which may be of use when thinking about implementing an ACP program. First, there should be an assessment of whether ACP is the most appropriate intervention in terms of what needs to be achieved, by identifying the outcomes that ACP is able to influence (Table 3). As seen in the results, ACP may increase EOL discussion rates, documentation of EOL preferences, and completion of several ACP-related documents (Lasting Powers of Attorney, ADs, etc.). In addition, it may increase incidence of dying in preferred place of death, be associated with earlier palliative care referrals, and improve communication between health care professionals and patients and their families. Although the evidence on ACP costs and resources is nondefinitive, there is a tendency to report associations between health care savings and decreased use of resources with ACP programs. A limited number of higher quality studies demonstrate ACP may be pragmatically beneficial for certain population groups, settings, and outcomes. For instance, ACP is associated with health care savings for people living in nursing homes and for those with dementia living in the community.
      • Dixon J.
      • Matosevic T.
      • Knapp M.
      The economic evidence for advance care planning: systematic review of evidence.
      There is also high-quality evidence about single-provider discussions improving concordance between patients' and families' wishes in EOL care decisions and outcomes.
      • Martin R.S.
      • Hayes B.
      • Gregorevic K.
      • Lim W.K.
      The effects of advance care planning interventions on nursing home residents: a systematic review.
      Once it has been established that ACP is the appropriate intervention based on its associated benefits, it is important to understand the country context and culture in which the ACP program is going to be implemented. Studies from Western countries, which provide the bulk of the evidence, emphasize the reliance on autonomy as a driver for ACP, while evidence from Asian countries reveals that patients prefer to incorporate family and community into their decisions and to rely on the opinion of physicians. Examples like this showcase that an ACP model developed, say, in the U.S. cannot just be transferred to China or Hong Kong as it is. It needs to be contextualized and adapted to the local realities for it to work.
      In addition, it is important to define the way to approach ACP. A key and constant message from the SRs is to use a “whole-system strategic approach.” This means to see ACP as an interconnected set of elements relying on each other, instead of focusing separately on its individual components. As such, there is a need to set up the structural basis from a systems perspective to include legislations and policy structures to positively influence health care institutions as well as the social aspects and cultural awareness promoting ACP.
      • Walczak A.
      • Butow P.N.
      • Bu S.
      • Clayton J.M.
      A systematic review of evidence for end-of-life communication interventions: who do they target, how are they structured and do they work?.
      • Gilissen J.
      • Pivodic L.
      • Smets T.
      • et al.
      Preconditions for successful advance care planning in nursing homes: a systematic review.
      • Lovell A.
      • Yates P.
      Advance Care Planning in palliative care: a systematic literature review of the contextual factors influencing its uptake 2008-2012.
      Its different components, such as organization, funding, and availability of skilled staff, should be set up concurrently.
      • Fosse A.
      • Schaufel M.A.
      • Ruths S.
      • Malterud K.
      End-of-life expectations and experiences among nursing home patients and their relatives–a synthesis of qualitative studies.
      In a similar manner, the evidence shows that interventions are more effective when they involve patients, caregivers, and providers, at the same time.
      • Walczak A.
      • Butow P.N.
      • Bu S.
      • Clayton J.M.
      A systematic review of evidence for end-of-life communication interventions: who do they target, how are they structured and do they work?.
      The next layer of information pertains to the design of the ACP program itself. There are several features of ACP programs that were consistently associated with improved outcomes. The provision of information should include interactive sessions with a knowledgeable person, capable of discussing and addressing concerns,
      • Jezewski M.A.
      • Meeker M.A.
      • Sessanna L.
      • Finnell D.S.
      The effectiveness of interventions to increase advance directive completion rates.
      • Tamayo-Velazquez M.I.
      • Simon-Lorda P.
      • Villegas-Portero R.
      • et al.
      Interventions to promote the use of advance directives: an overview of systematic reviews.
      given that providing materials, such as videos or pamphlets, on their own did not have meaningful effects. In addition, these sessions should be iterative and repeated so as to maximize ACP effectiveness.
      • Jezewski M.A.
      • Meeker M.A.
      • Sessanna L.
      • Finnell D.S.
      The effectiveness of interventions to increase advance directive completion rates.
      • Tamayo-Velazquez M.I.
      • Simon-Lorda P.
      • Villegas-Portero R.
      • et al.
      Interventions to promote the use of advance directives: an overview of systematic reviews.
      Another important factor relates to the implementation of ACP across different settings, so that the process follows the patients across their EOL journey (e.g., from the community to the general practitioner clinic, to the hospital, and then to the hospice).
      • Mularski R.A.
      • Dy S.M.
      • Shugarman L.R.
      • et al.
      A systematic review of measures of end-of-life care and its outcomes.
      • Biondo P.D.
      • Lee L.D.
      • Davison S.N.
      • Simon J.E.
      Advance Care Planning Collaborative R, Innovation Opportunities P. How healthcare systems evaluate their advance care planning initiatives: results from a systematic review.
      Finally, several SRs reinforced the need for new innovations to support ACP programs. For example, the use of Information and Communication Technologies to provide ACP information and education could reduce costs and make programs more easily scalable.
      • Ostherr K.
      • Killoran P.
      • Shegog R.
      • Bruera E.
      Death in the digital age: a systematic review of information and communication Technologies in end-of-life care.
      There is also a need to improve the storage and retrieval systems of ACP records, for example, through the use of electronic ADs,
      • Ke L.S.
      • Huang X.
      • O'Connor M.
      • Lee S.
      Nurses' views regarding implementing advance care planning for older people: a systematic review and synthesis of qualitative studies.
      so that they are readily available when needed. To have a more standardized and uniform program, the same ACP model should be implemented across entire regions or countries.
      • Ke L.S.
      • Huang X.
      • O'Connor M.
      • Lee S.
      Nurses' views regarding implementing advance care planning for older people: a systematic review and synthesis of qualitative studies.
      Finally, to reach the largest amount of people who need it, the implementation of ACP may need to expand beyond hospital or health care institution settings to a large community-shared model.
      • Wang C.W.
      • Chan C.L.
      End-of-life care research in Hong Kong: a systematic review of peer-reviewed publications.
      A summary of the elements supporting a successful ACP implementation is in Table 4.
      Table 4Elements Supporting Successful ACP Implementation
      Main FactorSpecific ElementsRef. Examples
      Whole-system strategic approachAddress social and cultural beliefs of people and health systems, and structural constraints of health and legal systems influencing ACP
      • Gilissen J.
      • Pivodic L.
      • Smets T.
      • et al.
      Preconditions for successful advance care planning in nursing homes: a systematic review.
      • Lovell A.
      • Yates P.
      Advance Care Planning in palliative care: a systematic literature review of the contextual factors influencing its uptake 2008-2012.
      Focus on all different components such as organization, funding, and skilled staff, including available doctors
      • Fosse A.
      • Schaufel M.A.
      • Ruths S.
      • Malterud K.
      End-of-life expectations and experiences among nursing home patients and their relatives–a synthesis of qualitative studies.
      Interventions targeting multiple stakeholders (patients, caregivers, providers) concurrently
      • Walczak A.
      • Butow P.N.
      • Bu S.
      • Clayton J.M.
      A systematic review of evidence for end-of-life communication interventions: who do they target, how are they structured and do they work?.
      Successful ACP program featuresInteractive information interventions with knowledgeable person, to discuss and address concerns
      • Jezewski M.A.
      • Meeker M.A.
      • Sessanna L.
      • Finnell D.S.
      The effectiveness of interventions to increase advance directive completion rates.
      • Tamayo-Velazquez M.I.
      • Simon-Lorda P.
      • Villegas-Portero R.
      • et al.
      Interventions to promote the use of advance directives: an overview of systematic reviews.
      Repeated conversations to increase ACP stimuli, effective for patient education and increasing AD completion
      • Jezewski M.A.
      • Meeker M.A.
      • Sessanna L.
      • Finnell D.S.
      The effectiveness of interventions to increase advance directive completion rates.
      • Tamayo-Velazquez M.I.
      • Simon-Lorda P.
      • Villegas-Portero R.
      • et al.
      Interventions to promote the use of advance directives: an overview of systematic reviews.
      Implement ACP and concurrent evaluations across different settings (patients use multiple sites for EOL care over time)
      • Mularski R.A.
      • Dy S.M.
      • Shugarman L.R.
      • et al.
      A systematic review of measures of end-of-life care and its outcomes.
      • Biondo P.D.
      • Lee L.D.
      • Davison S.N.
      • Simon J.E.
      Advance Care Planning Collaborative R, Innovation Opportunities P. How healthcare systems evaluate their advance care planning initiatives: results from a systematic review.
      Use strategies to solve EOL conflicts (e.g., use of ethics and mediations, improved communication, application of guidelines, and skills training)
      • Mpinga E.K.
      • Chastonay P.
      • Rapin C.H.
      [End of life conflicts in palliative care: a systematic review of the literature].
      Innovations for ACP supportScalable programs to improve quality of EOL and reduce costs (e.g., such as use of ICTs to provide ACP information and education)
      • Ostherr K.
      • Killoran P.
      • Shegog R.
      • Bruera E.
      Death in the digital age: a systematic review of information and communication Technologies in end-of-life care.
      Improving storage and retrieval system of ACP records (e.g., electronic ADs)
      • Ke L.S.
      • Huang X.
      • O'Connor M.
      • Lee S.
      Nurses' views regarding implementing advance care planning for older people: a systematic review and synthesis of qualitative studies.
      Implementation of same ACP model across entire regions
      Move ACP from a hospital-based to community-shared model
      • Wang C.W.
      • Chan C.L.
      End-of-life care research in Hong Kong: a systematic review of peer-reviewed publications.
      ACP = advance care planning; AD = advance directive; EOL = end-of-life; ICTs = Information and Communication Technologies.
      Given the differences in results and multiplicity of factors and caveats, it is difficult to determine at this point a gold-standard ACP that is suitable for most contexts (social, cultural, regional), population groups, and settings. However, conceptualizing ACP as a whole process (instead of as a collection of individual, disjointed steps), composed of many interconnected elements and stakeholders, may provide insight on how to evaluate it better and produce higher quality evidence to improve its implementation and potential.

      Strengths and Limitations of This Overview of SRs

      This overview is characterized by a number of strengths and limitations, which should be considered when interpreting this work. One of the strengths is the comprehensive definition of ACP we have adopted, which allowed us to include articles explicitly related to ACP, as well as research that may not be considered as ACP on its own but that is definitely part of the ACP process. In addition, by analyzing systematic reviews, we were able to incorporate research coming from over 1660 original articles, guidelines, and reports and thus provide as vast a picture as possible of the evidence regarding ACP.
      As with any SR, one potential limitation pertains to our search strategy not being able to capture all available evidence. However, our comprehensive definition and inclusion of aspects regardless of the presence of the “ACP” term should help include the relevant research to meet our objectives. The inclusion of only SRs might have excluded important research in other formats but provides a minimum standard of methodological and scientific quality.
      Our greatest cause for concern was the lack of quality of the available studies; therefore, the evidence at this point is preliminary and most of the recommendations are based on associations. In addition, the considerable heterogeneity in how ACP is defined and analyzed makes it difficult to distil which benefits or impacts come specifically from which type of intervention. Higher quality, more holistic approaches, and clearer definitions are needed to explore specific research questions and identify the effect of specific interventions. Finally, most of the current evidence comes from U.S., U.K., Australia, and a few other western European countries limiting the generalizability of these findings.

      Conclusions

      ACP is an essential tool to facilitate important decision making on future medical care preferences. The large body of studies exploring ACP in recent years reflects the importance it has gained. ACP is associated with positive patient, health care professional, and health system outcomes such as increased EOL discussions and documentation of preferences, as well as health care savings in some contexts for specific populations. This overview highlights several features for developing more effective, successful, and sustainable ACP. Such a program needs a supporting policy and cultural environment, backed by knowledgeable health care professionals willing to lead and embrace the process, so as to improve the life of patients at the end of life. The lack of high-quality research warrants further investigations evaluating ACP as a unified program and assessing the impact of ACP for different populations, settings, and contexts, to obtain solid evidence to support healthy and sustainable ACP development in the global context.

      Disclosures and Acknowledgments

      The authors would like to thank Caroline Pang, LKCMedicine medical librarian, for her support with the search process and development of strategies. The authors declare no conflict of interest with respect to the research, authorship, and/or publication of this article. The work for this overview was supported by a project commissioned by the Agency for Integrated Care (AIC) (grant number: RCA 16-099) and the Ministry of Health in Singapore to evaluate the local Advance Care Planning program (https://livingmatters.sg/).

      Appendix. Appendix I. Search Strategies

      For OVID

      • 1
        exp Advance Care Planning/
      • 2
        (Advance Healthcare planning or advance health#care plan*).mp.
      • 3
        (advance medical plan* or (advance medical adj3plan*).mp.
      • 4
        (Advance care plan* or (advance care adj3plan*)).mp.
      • 5
        (Advance care adj3 (directive* or statement* or decision*).mp.
      • 6
        (Advance adj3 (directive* or statement* or decision*)).mp.
      • 7
        (Advance medical adj3 (directive* or statement* or decision*)).mp.
      • 8
        (Disease specific plan* or (disease* specific adj3 plan*)).mp.
      • 9
        ((Chronic illness* or progressive illness*) adj3 plans).mp.
      • 10
        (Patient advance plan* or (patient advance adj3 plan*)).mp.
      • 11
        (Patient advance adj3 (directive* or statement* or decision*)).mp.
      • 12
        exp Living Wills/
      • 13
        Living will*.mp.
      • 14
        1 or 2 or 3 or 4 or 5 or 6 or 7 or 8 or 9 or 10 or 11 or 12 or 13
      • 15
        metaanalysis.pt.
      • 16
        metaanalysis/ or systematic review/ or metaanalysis as topic/ or “meta analysis (topic)”/ or “systematic review (topic)”/
      • 17
        ((systematic* adj3 (review* or overview*)) or (methodologic* adj3 (review* or overview*))).ti,ab,kf,kw.
      • 18
        ((integrative adj3 (review* or overview*)) or (collaborative adj3 (review* or overview*)) or (pool*adj3 analy*)).ti,ab,kf,kw.
      • 19
        ((quantitative adj3 (review* or overview* or synthes*)) or (research adj3 (integrati* or overview*))).ti,ab,kf,kw.
      • 20
        (data synthes* or data extraction* or data abstraction*).ti,ab,kf,kw.
      • 21
        (handsearch* or hand search*).ti,ab,kf,kw.
      • 22
        (meta regression* or metaregression*).ti,ab,kf,kw.
      • 23
        (metaanaly* or metaanaly* or systematic review*).mp,hw.
      • 24
        (medline or cochrane or pubmed or medlars or embase or cinahl).ti,ab,hw.
      • 25
        (comparative adj3 (efficacy or effectiveness)).ti,ab,kf,kw.
      • 26
        (outcomes research or relative effectiveness).ti,ab,kf,kw.
      • 27
        ((indirect or indirect treatment or mixedtreatment) adj comparison*).ti,ab,kf,kw.
      • 28
        or/
      • 29
        14 and 28 154 Advanced

      For EBSCO

      • S1 (MH “Advance Care Planning+”)
      • S2 Advance Care Planning
      • S3 (advance healthcare planning or advance health#care plan*)
      • S4 (advance medical plan* or (advance medical N3 plan*))
      • S5 (advance care plan* or (advance care N3 plan*))
      • S6 (advance care N3 (directive* or statement* or decision*))
      • S7 (advance N3 (directive* or statement* or decision*))
      • S8 (MH “Advance Directives+”) or (DE “Advance Directives+”)
      • S9 (disease-specific plan* or (disease* specific N3 plan*))
      • S10 ((chronic illness* or progressive illness*) N3 plans)
      • S11 (patient advance plan* or (patient advance N3 plan*))
      • S12 (patient advance N3 (directive* or statement* or decision*))
      • S13 (patient advance N3 (directive* or statement* or decision*))
      • S14 (MH “Living Wills+”)
      • S15 living N3 will*
      • S16 S1 OR S2 OR S3 OR S4 OR S5 OR S6 OR S7 OR S8 OR S9 OR S10 OR S11 OR S12 OR S13 OR S14 OR S15
      • S17 (TI (systematic* n3 review*)) or (AB (systematic* n3 review*)) or (TI (systematic* n3 bibliographic*)) or (AB (systematic* n3 bibliographic*)) or (TI (systematic* n3 literature)) or (AB (systematic* n3 literature)) or (TI (comprehensive* n3 literature))
      • S18 (AB (comprehensive* n3 literature)) or (TI (comprehensive* n3 bibliographic*)) or (AB (comprehensive* n3 bibliographic*))
      • S19 (TI (integrative n3 review)) or (AB (integrative n3 review)) or (JN “Cochrane Database of Systematic Reviews”) or (TI (information n2 synthesis)) or (TI (data n2 synthesis)) or (AB (information n2 synthesis)) or (AB (data n2 synthesis)) or (TI (data n2 extract*)) or (AB (data n2 extract*))
      • S20 (TI (medline or pubmed or psyclit or cinahl or (psycinfo not “psycinfo database”) or “web of science” or scopus or embase)) or (AB (medline or pubmed or psyclit or cinahl or (psycinfo not “psycinfo database”) or “web of science” or scopus or embase))
      • S21 MH “Systematic Review”) or (MH “Meta Analysis”) or (TI (meta-analy* or metaanaly*)) or (AB (meta- analy* or metaanaly*))
      • S22 S17 OR S18 OR S19 OR S20 OR S21
      • S23 S16 AND S22
      • S24 S23 Limiters—Exclude MEDLINE records
      • S25 S24 Limiters—Age Groups: All Adult; Age Groups: Adulthood (18 yrs & older)

      For EMBASE

      • 1
        exp patient care/
      • 2
        advance care planning.mp.
      • 3
        (advance healthcare planning or advance health#care plan*).mp.
      • 4
        (advance medical plan* or (advance medical adj3 plan*)).mp.
      • 5
        (advance care plan* or (advance care adj3 plan*)).mp.
      • 6
        (advance care adj3 (directive* or statement* or decision*)).mp.
      • 7
        (advance adj3 (directive* or statement* or decision*)).mp.
      • 8
        (advance medical adj3 (directive* or statement* or decision*)).mp.
      • 9
        (disease-specific plan* or (disease* specific adj3 plan*)).mp.
      • 10
        ((chronic illness* or progressive illness*) adj3 plans).mp. More
      • 11
        (patient advance plan* or (patient advance adj3 plan*)).mp.
      • 12
        (patient advance adj3 (directive* or statement* or decision*)).mp.
      • 13
        exp Living Will/
      • 14
        living will*.mp.
      • 15
        2 or 3 or 4 or 5 or 6 or 7 or 8 or 9 or 10 or 11 or 12 or 13 or 14 10314
      • 16
        1 and 15
      • 17
        meta-analysis.tw.
      • 18
        systematic review.tw.
      • 19
        17 or 18
      • 20
        16 and 19
      • 21
        limit 20 to exclude medline journals
      • 22
        lim it 21 to embase
      Appendix IIInclusion and Exclusion Criteria