Palliative care is a service provided to patients with life-limiting illnesses, such as advanced cancer, focusing on improving quality of life and symptom management through the early identification, assessment, and treatment of pain and other ailments [1,2]. It can also enable patients to understand their choices for treatment while providing physical, psychological, social, and spiritual support to patients and their families or informal caregivers alike.

Prognostication is broadly defined as the process of making predictions about the future, such as the likely outcome or course of a disease and the chance of recovery or recurrence. This research is specifically concerned with prognostication of survival, or end-of-life (EOL) prognostication. Prognostication of EOL is a vital component of patient management and decision-making in palliative care [3,4]. An accurate prognosis of the EOL allows patients and their families or informal caregivers adequate time to prepare, such as making financial plans and identifying their preferences for place of death [5]. Medically, an accurate prognosis can allow clinicians to identify appropriate treatment strategies based on individual patients’ prognostic factors and symptoms [4].

Currently, there is no gold standard for prognostication of EOL. Many prognostic methods rely on clinician-estimated prognosis [5]. However, clinicians’ survival predictions are often inaccurate, inconsistent, and overoptimistic [6,7]. Various prognostic tools have been validated for use in palliative cancer care, and they may provide better accuracy, consistency, or other benefits in comparison with clinicians’ predictions [5]. However, the impact of such prognostic algorithms has yet to be established, and inconsistency in outcome reporting among prognostic studies makes it difficult to compare results.

The selection of appropriate primary and secondary outcome measures is an essential component of study design; a study is only as credible as its end points [8]. However, researchers may select outcomes that do not reflect meaningful end points for all stakeholders, namely patients and informal caregivers or clinicians [9,10]. Inconsistency in end points across a particular area of research can be a barrier to comparing study findings, reducing the feasibility of meta-analysis, and perpetuating outcome reporting biases [10]. Heterogeneity of outcomes has been noted in palliative care research. Previous studies have often focused on outcomes deemed important by experts, namely academics and clinicians, thereby overlooking patients’ and other stakeholders' opinions and experiences and hindering the translation of findings into clinical practice [11-14].

A core outcome set (COS) promotes consistency in outcome selection among studies within a particular population, such as palliative cancer care, by providing a consensus-based, agreed minimum set of clinically meaningful outcomes to be measured and reported in all clinical trials of a specific population [15]. The Core Outcome Measures in Effectiveness Trials (COMET) initiative provides guidance for COS developers planning to construct a COS [15]. First, it is recommended that outcomes in existing published and ongoing studies be identified. Interviews with patients, informal caregivers or family, and other stakeholders can then be performed to ascertain outcomes important to them and assist research teams in understanding why particular outcomes are important [16]. Next, a Delphi process is advised, where key stakeholders such as patients, informal caregivers, and those who design and use research rank all the outcomes identified in the previous 2 phases until consensus is reached on which ones are the most important. The result is an agreed set of core outcomes.

There is as yet no consensus on which outcomes should be used to assess the impact of EOL prognostication in palliative cancer care. This study will develop a COS to assess prognostic impact, which will assist in preparing for future impact studies.

Palliative care can be provided to people living with a variety of disease types and chronic illnesses, including but not limited to cancer, cardiovascular diseases, chronic respiratory disease, diabetes, and acquired immunodeficiency syndrome [1]. This study will focus on palliative care in patients with a life-limiting, advanced, or progressive cancer to avoid confounding outcomes that might arise from including all such a wide range of illnesses. This will be the first study to investigate and define a COS for prognostic research in palliative cancer care. For the purpose of this study, the term palliative cancer care will be defined as treatment, care, and support provided to those with a life-limiting, advanced, or progressive cancer that cannot be cured [1,2]. This is a working definition, in that this definition has been chosen for the purpose of this study, and we recognize that it may not fully conform with established or authoritative definitions of palliative cancer care. Informal caregivers will include family members, friends, or other individuals who provide a wide range of unpaid assistance for someone with whom they have a personal relationship, including but not limited to physical and psychological support [17,18].

The intervention of interest in our study is EOL prognostication, defined as any process of estimating and communicating the likelihood of survival (ie, how long an individual has left to live) [5].

This study aims to create a COS for measuring the impact of EOL prognostication in palliative cancer care.

The objectives for the whole study are as follows:

This study will adopt a multiphase, mixed methods approach suggested by the COMET guidelines [15] and will adhere to the Core Outcome Set—STAndards for Development (COS-STAD) recommendations to support the development, implementation, and evaluation of the COS [19]. This study protocol was written following the Core Outcome Set—STAndardized Protocol Items (COS-STAP) guidelines for reporting protocols of COS development [20].

The study will consist of three phases: (1) a systematic literature review of relevant outcomes reported in extant quantitative and qualitative literature to measure the impact of EOL prognostication in palliative cancer care; (2) semistructured, qualitative interviews to explore the views and experiences of patients, informal caregivers, and clinicians; and (3) a Delphi study to prioritize outcomes derived from phases I and II. Figure 1 shows a summary of the study design.

This study will involve four stakeholder groups: (1) patients with advanced cancer who are receiving palliative care, (2) informal caregivers, (3) clinicians, and (4) academics or researchers. We will recruit patients, informal caregivers, and clinicians through palliative care services from 3 sites in London, United Kingdom, including 2 National Health Service trusts and 1 hospice. We will begin recruitment to the study by placing posters advertising the study in public spaces of the participating sites to recruit patients (both inpatients and outpatients), informal caregivers, and clinicians simultaneously. These posters will include the researchers’ contact information so that interested individuals can contact them for further details regarding the study, to ask questions, or to express their interest in participating.

Where possible, a researcher (CS) will also attend weekly multidisciplinary team meetings within the sites and be available on site to encourage clinical staff to identify patients who are eligible to participate and who are physically and mentally capable. The researcher will only attend multidisciplinary team meetings at a time point agreed with the clinical team (ie, at the beginning or the end) to discuss the study and will leave before any confidential patient information is discussed. A member of the patient’s direct clinical care team (ie, someone who is currently treating them) will make the first approach to potential participants to ask them if they would be interested in participating in the study, and if so, whether they give permission for the clinical team to provide the minimum, necessary information (name and contact details) for the researcher to approach them. The researcher will only approach participants who have consented (ie, verbally) for them to do so. The researcher or clinical staff will provide such patients with a participant information sheet and the researchers’ contact information. If present at the time, informal caregivers will also be asked if they would be interested in participating in the study.

An invitation email, participant information sheet, and researcher contact information will be shared with palliative care clinicians at participating sites. We will also contact relevant organizations, such as the Association for Palliative Medicine of Great Britain and Ireland and the European Association for Palliative Care, to recruit national and international palliative care clinicians. We will ask the group or association chair to forward an email to group members that contains the participant information sheet and a link to the first round of the survey.

We will identify academics or researchers through opportunity sampling. We will ask colleagues and other contacts to suggest potential participants who have the relevant experience and are able to read and write in English. To encourage participation from a wide geographical area, we will screen academic profiles on UK and international university websites to identify individuals who have conducted relevant work. Heads of palliative care research departments may also be contacted and asked whether any members of their team have conducted research within the field of palliative care and would be willing to put us in contact. Additionally, the reference list of any relevant reviews will be searched to identify academics who have published research in the palliative care settings, and the authors who have cited relevant papers will also be screened for eligibility.

For phase II, we estimate that we will need to recruit 8 to 10 participants per group (patients, informal caregivers, and clinicians), making a total of 24 to 30 participants. This sample size is based on a previous COS study’s recommendations, as well as the research team’s experiences of qualitative research [21]. However, data collection will continue until data saturation is reached. Data saturation will be determined to have occurred when no new themes are being identified in analysis. Data collection will occur concurrently with recruitment to minimize attrition.

There is currently no consensus on how to determine the sample size for a Delphi survey. Balancing the sample size in a Delphi survey is crucial for achieving meaningful consensus; larger sample sizes may present challenges in terms of communication and follow-up, leading to lower response rates, whereas smaller sample sizes can restrict the scope and reliability of the survey results [22-24]. When considering sample size, it is also important to consider attrition that is likely to occur between each round. Therefore, based on previous studies’ recommendations [25,26], we took a pragmatic decision to recruit a minimum of 10 participants to represent each stakeholder group, with a minimum of 40 participants in total. For pragmatic reasons, and to ensure that we include a range of perspectives, we aim to recruit a minimum of 10 international experts. For the consensus meeting, we will recruit approximately 4 participants from each stakeholder group. Maintaining a balance between stakeholder groups is important to ensure that certain voices are not overpowered. This group size will be manageable for a web-based meeting, while still permitting a range of perspectives to be heard.

Phase I of the study was completed in June 2023. The complete protocol for this systematic literature review, including the search strategy and study selection criteria, was submitted for registration on PROSPERO (the International Prospective Register of Systematic Reviews) on March 29, 2022, and was subsequently published on the PROSPERO website on April 1, 2022 (CRD42022320117). This review was conducted according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) 2020 statement [27].

The aim of this systematic literature review was to identify existing outcomes to inform COS items and domains. Retrieved papers were analyzed in two subsets: (1) quantitative studies (clinical trials and observational studies), seeking to identify the outcomes used in previous research to measure the impact of EOL prognostication in palliative cancer care, and (2) a systematic review and thematic synthesis of qualitative studies exploring patients’ and informal caregivers’ experiences of EOL prognostication in palliative cancer care.

We carried out searches using the following electronic databases from inception to September 2022: Ovid MEDLINE, Ovid Embase, Ovid PsycINFO, CINAHL, and the Cochrane Library (both the Cochrane Controlled Register of Trials and the Central Register). We also extended searches to gray sources and adopted snowballing techniques to identify additional papers and ensure literature saturation. Search terms included keywords related to prognostication, palliative care, advanced cancer, and outcomes and cognate terms. Search limits were applied to restrict results to a human, adult population, and studies published in English language only due to limitations in resources. Eligibility criteria included (1) patients with advanced cancer, or their informal caregivers; (2) prognostication, defined as any process of estimating and communicating the length of survival of an individual’s disease; (3) quantitative studies that reported outcomes of prognostication; and (4) qualitative studies that explored experiences and perceptions of prognostication.

The search results from each database were imported and deduplicated in the Rayyan software [28]. The titles and abstracts of the studies were screened by 4 independent reviewers using the above-mentioned eligibility criteria. Those that met the inclusion criteria for either review question were read in full by at least 2 authors. Discrepancies were resolved through discussion between authors. If no consensus could be reached, a third author was consulted.

Methodological quality was assessed using the Mixed Methods Appraisal Tool [29]. A narrative approach was used to undertake the quantitative synthesis, along with tables of outcomes, their descriptions, and measures. Outcomes were categorized using the taxonomy for COS recommended by COMET [30]. For the qualitative analysis, the analysis was guided by Thomas and ’Harden’s [31] framework for thematic synthesis, with 3 stages. The COMET taxonomy was used as an external framework to support the development of analytical themes and facilitate the combination of the results of both the quantitative and qualitative studies. A narrative description of each theme in relation to the review question was provided.

The results of the review have been accepted for publication in an academic journal and will be taken forward for consideration for inclusion in the COS.

The second phase of this study will be a qualitative study using semistructured interviews to explore the perceptions and experiences of patients, informal caregivers, and clinicians regarding the potential outcomes and impact of EOL prognostication.

Once a list of core outcomes has been developed from phases I and II, we will carry out a Delphi survey and consensus meeting to achieve consensus between disparate stakeholders, including patients, informal caregivers, clinicians, and academics or researchers, about which of these outcomes are most important. An international sample of clinicians and academics or researchers will be sought to widen the generalizability of the final COS.

We advertised the opportunity to be involved in this research project as part of a patient and public involvement (PPI) advisory group through the National Institute for Health Research “People in Research” website and the Marie Curie Research Voices Group. Our advisory group included members of the public with experience of talking about prognosis, either as someone with advanced cancer or as one caring for someone with advanced cancer, who reviewed the protocol and all participant-facing documents. They advised on how the protocol could be adapted to ensure that the research study meets the needs and preferences of those taking part. They also made suggestions for how the documents might be made more suitable for participants, particularly for those receiving palliative care, to ensure that sensitive language was used.

In the future, we will consult this PPI advisory group regarding the format of the Delphi survey, before distributing it to participants, to ensure that it is easy to understand, access, and use. Specifically, the group will be requested to review and streamline the extensive list of outcomes intended for inclusion in the Delphi survey. We recognize that lengthy lists can be daunting for Delphi participants, potentially impacting their engagement. The PPI advisory group’s expertise will be invaluable in identifying and addressing this risk, guiding us in minimizing the occurrence of overly lengthy lists and ensuring that the Delphi survey is well received and productive. We will also ask the group to review and propose outcome names and plain-language descriptions for each outcome. This step aims to ensure that all participants interpret the concepts as intended, reducing the potential for misunderstandings and enhancing the overall clarity of the survey.

During the data analysis, we will ask members to comment on the plain-language presentation of findings to ensure that this is understandable and relevant. We will also seek input from members of the PPI advisory group when disseminating results of the study to ensure that we communicate the study in a way that is appropriate for the general public.

The involvement of the PPI advisory group in these crucial aspects of the study has already made, and will continue to make, a considerable contribution to the success and impact of our research. In particular, this facilitates more meaningful participation and the likelihood of gaining valuable insights from participants.

Ethical approval was obtained for this study from the London-Camberwell St. Giles Research Ethics Committee and the Health Research Authority on September 6, 2022 (reference 22/LO/0469).

Written, informed consent will be obtained from participants taking part in face-to-face interviews, the first round of the Delphi survey, and consensus meeting. Verbal, recorded consent will be obtained from participants being interviewed over the telephone or via a web platform. Participation in sequential rounds of the Delphi survey will be considered indicative of consent.

Promoting the uptake of the COS is paramount in preventing research waste and involves engaging key stakeholders, raising awareness, and demonstrating its value and relevance [38]. To achieve this, we will aim to disseminate findings to academic and research community audiences via publications in peer-reviewed journals and as presentations or posters at regional, national, and international palliative care conferences. After the finalization of the COS, further research will be necessary to identify the most suitable outcome measures or instruments for each core outcome. Subsequently, we will conduct a comprehensive evaluation of their quality and feasibility. To encourage adoption, we will collaborate with relevant journals and funding bodies, urging them to incorporate the COS in their guidelines for researchers and authors. Furthermore, we will actively seek feedback from researchers who pilot the COS in their studies. Being open to updates and revisions based on emerging evidence and feedback, we will continually improve the COS, ensuring its continued relevance and value over time.

The findings will be disseminated to participants in the form of plain-language summaries at the end of the study. To reach wider public audiences, plain-language newsletters, tweets, or blog posts will be published. Professional and clinical groups will also receive the findings as research summaries for participants and by engaging with palliative care representatives such as the palliative care team at the participating sites.

The final COS will be shared with the expert panel so they can verify the changes made and review what the project produced.

This study protocol presents what will be the first study that aims to develop a COS to measure the impact of EOL prognostication in palliative cancer care. The objective of this COS is to involve various stakeholders in its development and reach a consensus on the essential outcomes that hold significance for this population. Developing a COS for measuring the impact of EOL prognostication in palliative cancer care is an important step to improve patient care and communication of EOL prognoses. By addressing the inconsistent outcome measurement in existing studies and aligning the outcomes with those that are important to stakeholders, our COS has the potential to help standardize and improve prognostic research in palliative cancer care, such as the development of prognostic algorithms. Furthermore, the findings from this study have the potential to ensure that outcomes measured in future prognostic impact studies will reflect what is important to such stakeholders and ultimately facilitate the translation of the findings into clinical practice [39-41]. Once the COS is finalized, further research will be required to establish which outcome measures or instruments are most appropriate for each of the core outcomes, followed by an evaluation of their quality and feasibility.

Currently, research on the impact of EOL prognostication in palliative cancer care faces a significant challenge because of the measurement of different outcomes across various studies. Academic and clinical interests often dominate the selection of outcomes, potentially neglecting their meaningfulness to patients or informal caregivers [9,10]. Consequently, some studies might employ outcomes that do not resonate with those directly impacted by prognostic information. Moreover, the lack of uniformity in outcome measurement across studies hampers the ability to compare or combine results, leading to research wastage. A COS will address these issues. This COS aims to integrate the perspectives and experiences of patients and other personally affected stakeholders. By doing so, it is expected to enhance the translation of research findings into clinical practice and foster comparability in future prognostic research in palliative cancer care. Ultimately, this harmonized approach will optimize the use of research efforts and promote more effective advancements in the field.

This will be the first COS specifically focused on measuring the impact of EOL prognostication in palliative cancer care. The development of the COS will involve a rigorous and systematic search to gather the views and opinions of patients and other key stakeholders. Engaging with these groups will not only ensure that their perspectives are considered but will also enhance the overall relevance and applicability of the COS. By making the protocol for the COS publicly available, we will ensure the transparency and replicability of our study.

The inclusion of only adult English-speaking participants in this study might potentially limit the generalizability of the findings. Nevertheless, to mitigate this limitation, we will actively seek the involvement of international participants in the Delphi survey. Additionally, in phase I of the study, the systematic review considered international publications to minimize the risk of selection bias.

It is essential to acknowledge that conducting the Delphi survey using a web-based software may lead to underrepresentation of certain groups, particularly those who lack digital skills and access. To address this concern, we will explore alternative methods of data collection to ensure broader representation if it becomes apparent that our sample is significantly biased.

Recruiting and retaining participants may pose a challenge in our study, especially given the nature of the target population, who may face health deterioration or bereavement. To minimize attrition during phase II, we will conduct interviews concurrently with recruitment, aiming to interview participants shortly after enrollment to reduce dropouts. If a participant or caregiver cannot proceed with the interview, we will document their reasons for withdrawal and continue recruiting until reaching our desired number of interview participants or research data saturation, whichever occurs first. Attrition in Delphi surveys is a common challenge, resulting from both participant factors and reduced interest over time during multiple rounds [42]. Although we will send regular reminders and strive for timely rounds, it is challenging to minimize attrition resulting from external circumstances. Furthermore, the survey’s anonymity prevents us from knowing specific reasons for dropouts or withdrawals. Despite this limitation, we will openly acknowledge its impact in any published results.

Employing stakeholder meetings to determine the final COS carries the risk of bias based on the opinions expressed by those present. To counteract this, we will make diligent efforts to encourage participation from all stakeholder groups. Despite our efforts, there remains a possibility of underrepresentation for a particular stakeholder group, and we will be transparent about this potential limitation in our study.

The necessity for a COS to measure the impact of EOL prognostication within palliative cancer care arises from the need to enhance outcome measurement and reporting. This COS has the potential to make a substantial impact on the field by advancing prognostication practices and aligning outcome measures with the preferences and requirements of patients and other important stakeholders. As a result, it will enable more precise comparisons and better synthesis of evidence across various prognostic studies.

The overall promise of this study lies in its potential to elevate the quality of care and decision-making for patients facing EOL care in the context of palliative cancer care. By standardizing and improving the measurement and reporting of prognostic outcomes, the COS will play a vital role in optimizing patient outcomes and enhancing the overall care experience for those in need.