Returning raw genomic data to research participants in a pediatric cancer precision medicine trial

Returning raw genomic data to research participants in a pediatric cancer precision medicine trial

Introduction

Sharing genomic data between research groups and other agencies is often mandated by funding bodies and promoted in ethical guidelines, as it is critical to the advancement of precision medicine1,2. Increasingly, attention is shifting to sharing data, on request, with parents/guardians of child research participants or adult participants (hereafter referred to collectively as parents/participants)3,4,5. Support for such requests is underscored by perceived legal duties4,6,7,8,9,10, and on ethical grounds, with some advocating that the policy to return is the “new normal”11. These data include raw genomic data defined as the sequence reads generated from biospecimens without filtering, annotation or interpretation. They also include the biospecimens themselves: both tumor and non-tumor fresh human tissue, fresh frozen tissue, formalin fixed tissue (prior to processing), formalin fixed paraffin embedded tissue, DNA or RNA isolated from tissue (e.g., blood or skin) or collected (e.g., urine).

Nevertheless, there is ethical and legal complexity, recognized concerns, and diverse perspectives on this issue. These include utility of the data, potential for harm arising from third party interpretation, and the possibility of unnecessary interventions5,12. Given this complexity, recommendations guiding ethical access to raw genomic data were developed in the USA, Europe, and Australia3,9,13. Despite these recommendations, large-scale sequencing studies have reached varying policy positions. For example, Genomics England returns genomic data to participants in its 100,000 Genomes Project if requested, informed by the requirements of the General Data Protection Regulation 201814. The Deciphering Developmental Disorders study in the UK and Ireland, however, declines requests from parents “on the basis of concerns about sample identity, a lack of resources to provide informatics-related support, and potential inability to mitigate against unintended consequences”15.

In Australia, National Health and Medical Research (NHMRC) ethical guidelines provide that researchers are not expected to return raw genomic data to participants, acknowledging the resource implications for such a stance16. However, requests for the return of raw genomic data and/or biospecimens to parents of children from four families participating in Australia’s first pediatric oncology precision medicine trial, PRISM (PRecISion Medicine for Children with Cancer, 2017–2023), were fulfilled17, [V. Tyrrell personal communication].

The PRISM trial, administered under the ZERO Program, aimed to enroll annually 100–150 children aged under 18 years and young adults aged 18–21 years with poor prognosis malignancies (expected survival likelihood less than 30%) at diagnosis or relapse. Upon enrollment, biospecimens (tumor and germline) were donated, a raw genomic sequence generated and subjected to molecular profiling analysis. Any potentially clinically relevant findings were discussed at a national molecular tumor board and reported to the recruiting clinician to be shared with the parents/participants18,19.

The PRISM trial was expanded in 2023 to ZERO2, which aims to enroll annually approximately 1000 children diagnosed with any type of cancer. In anticipation of an increased number of requests, a ZERO Program formal document delineating the Policy and Process for the return of raw data and/or biospecimens was considered critical, underpinned by a spirit of reciprocity between research participants and the research program.

This paper reports on the development of the document based on expert consensus that was further informed by feedback from parents whose children had or were participating in the ZERO Program.

Results

The Delphi expert panel

Overall, 21/54 invited experts completed the survey in Rounds 1 and/or 2 (Response rate, 39%). One expert in genomics/computational biology only participated in Round 1 and one pediatric oncologist only in Round 2 (Table 1). Eight invited experts in Round 1 only partially completed the survey and so their responses were not included in the analysis. All experts in Round 3 responded to the emailed V3.

Table 1 Delphi expert panel participants in Rounds 1 and/or 2
Full size table

Of the Delphi experts who provided consensus scores and comments, 71% were in the disciplines of pediatric oncology/hematology (7/21;33%), pediatric pathology (1/1; 100%) and clinical genetics/genetic counseling (7/8; 88%), representing those most likely to be caring for and working with parents/participants (Table 1). Their contribution to the Delphi demonstrates high engagement with the issue. Experts represented sites where ZERO2 is implemented: New South Wales (n = 11), Queensland (n = 2), Tasmania (n = 2), South Australia (n = 1), and Western Australia (n = 1) as well as New Zealand (n = 1). Females and males were equally represented.

The Delphi review rounds

Round 1: consensus ≥80% for both clarity and relevance was reached for the scope, premises under the policy, and ethical considerations in the V1 Policy and the first two of the eight steps in the Process) (Table 2). However, recommendations were received in the free-text boxes for amendments to the wording of statements under every heading.

Table 2 Consensus scores for clarity and relevance for statements, outcomes and actions Rounds 1 and 2
Full size table

Round 2: all statements in V2 reached consensus; edits suggested to the wording to improve clarification where appropriate were incorporated into V3.

Round 3: minor changes to the wording describing the format of the raw genomic data to be returned were incorporated into V4.

Comments and amendments over the Delphi consensus process included:

  • Concerns about the term ‘belongs’ in the statement that “the ZERO Program recognized that the biospecimens and generated raw data belongs to each participant”, resulted in replacement with “The research team are custodians of raw data generated through the research, but the participants have a recognized right of access to their raw data. For participants (and/or their families) the return of raw data might be of benefit or cause harm. While clinical expertize and counseling support form an integral part of minimizing any potential harm, these will not be provided as a routine part of the return of raw data”.

  • One expert suggested that returning biospecimens might devalue future research as it would limit availability of samples to re-test but this view was not supported in Round 2 and was not changed.

  • The statement that there was a “moral imperative underpinning the increasing [international] support for provision of raw data on request” was removed from V1.

  • The ethical issues were broadened: autonomy was expanded to reflect the importance of the child’s best interest and future autonomy; non-maleficence was named instead of simply ‘minimizing potential harm’ and also addressed the potential for a cascade of (possibly unnecessary) health interventions following a misinterpretation of the raw data, for example by a third-party service.

  • The process described in Part 2 should be limited to only parents/participants enrolled in ZERO2 who wish to have access to their child’s/their raw data.

  • Include in the ZERO2 Patient Information Sheet (PIS), but not in the consent form, that a process for potential return of raw genomic data or biospecimens is in place and requests should be discussed with the treating clinician or the ZERO2 Study team.

  • A meeting (online or in person) with a study team member and the treating clinician should be offered to gain understanding of the basis for their request, how they wish the raw data to be used and how to proceed. A leaflet outlining the issues to be considered would be provided to guide the discussion, streamline the process, and reduce barriers. The request should be fulfilled after they have been made aware of the possible outcomes, including benefits and harms, without having to justify the reason for their request. A pediatric oncology expert noted in Round 1 that “There should not be any requirements for participants to justify access to data if intrinsically we believe they have a right to the data. The reason they might want the data is irrelevant and should have no sway on the ability to provide the data”.

  • The request for release form should also articulate that as the data is research generated, it should not be used for clinical interpretation or decision-making without medical advice, a confirmatory testing in a clinically accredited laboratory is recommended. This aligns with the recommendation in the Australian National Statement on Ethical Conduct in Human Research20.

  • Where the parents/participants intend to share the data with another research organization for re-analysis purposes, applications for access should be managed through ZERO2’s Data Access Committee (DAC). While all efforts would be made to facilitate agreements to support such sharing, in the absence of formal agreements, there would be no barrier to parents who have the raw data independently providing the data to any organization.

  • The data as FASTQ files would be transferred, free of charge, on a hard drive. The FASTQ file format is a text file of the nucleotide sequence that is considered the standard format for raw genomic data which can then be processed in a pipeline to generate a variant list21.

Parent feedback—V4–5

Five representatives of the Australian Families for Genomics (AF4G) group who had been provided with V4 attended the online feedback session. The development of the document was viewed as a very welcome initiative to ensure the barriers that they had experienced with previous requests for data from the PRISM trial in which their children/families were enrolled will “not be repeated for other patients, and their families”. These included navigating tensions with treating clinicians and extended delays in finally meeting the request with no formal process in place.

Amendments proposed to V4 included:

  • Incorporate the return of biospecimens (with a definition) into the document.

  • Including anticipated turnaround times for the reporting of interpreted research findings was considered critical to inform planning for provision of the raw data to other researchers.

  • Recognize that while raw genomic data on its own cannot inform clinical decision-making nor answer questions in a research setting, its subsequent analysis and interpretation may be of great value to parents/participants.

  • As requests may be viewed by clinicians as questioning their expertize and that of the ZERO2 team the meeting to discuss a request and the outcomes that need to be considered should not include the treating clinician and rather than “a Study Team member”, it should specify that it be the ZERO2 site genetic counselor.

The initiative was also welcomed by the 2/5 invited parents from the ZERO Program Parents Consultation Group who provided feedback on V5 and as well as the content of a leaflet to be given when requests were received. They noted it provided the opportunity for parents to be able to take control of further research opportunities for their child if there were no reportable or actionable findings through ZERO2, or if treatments recommended by the findings were not effective. They reflected that it would be comforting to know if another group found something clinically actionable, or if not, that everything would have been tried. This was viewed as empowering parents/participants to make decisions that may have lifesaving outcomes and allow them to feel they explored all avenues. The benefits and risks were well described but ultimately the positives of being able to request the raw data outweighed the negatives.

Amendments to V5 included:

  • Emphasize in the PIS that deidentified data was shared by the ZERO Program with other research groups. For some parents, such data sharing may be seen as sufficient in advancing care for children with cancer and so may not feel the need to request the raw data to share.

  • Note that while the chance of identifying that the child has, or may develop in childhood, a genetic condition other than cancer is minimized by the ZERO2 analytic procedures, such minimization may not be in place when the raw data is analyzed by another research group.

  • While supporting the recommendation to have a genetic counselor conduct the discussion following a request, they suggested some parents may wish to also have their clinician present, and their preference should be facilitated.

  • The leaflet covering issues and potential outcomes from a request should be available for download on the ZERO Program website. It may be used to inform discussion that parents may wish to have with their child at a developmentally appropriate age that the child could make the request for return themselves when they turn 18 if they wished to do so.

Tables 3 and 4 summarize the final content of the Policy, Process. The content of the document and release form is available in Supplementary File 2.

Table 3 Summary points. Part 1 POLICY
Full size table
Table 4 Summary points. Part 2 APPLYING THE POLICY
Full size table

Discussion

The ZERO Program’s position is that the research team conducting the trials have a responsibility to safe-guard and maintain the biospecimens and the raw genomic data generated; that is, act as their custodian. It also supports the right of parents/participants to request access to both the biospecimens and a copy of the raw genomic data after receiving the research report regarding both the tumor and germline findings.

This position is in the context of an Australian setting where the Australian Federal Privacy Act 1988 (Cth)22 and State and Territory laws provide a right to access, upon request, personal data that identifies or reasonably identifies an individual. There may however be some uncertainty about whether raw genomic data falls into this category3,23. Adding to the lack of clarity, the NHMRC guidelines provide that researchers are not expected to return raw genomic data to participants.16. However, where findings are returned, the guidelines mandate that the policy and the process for return be described in the Ethically Defensible Plan (EDP) for genomic research24. Therefore, the return of raw genomic data has been included in ZERO2’s EDP.

The development of the ZERO2’s Policy and Process document described here, undertaken with both expert consensus and parent feedback, meets EDP requirements. The high engagement of the experts and their extensive contributions demonstrated the rigor of the reactive Delphi technique. The CREDES recommendations underpinned facilitating consensus over just three rounds of consultation25,26. The ethical complexities of respecting the autonomy of both the ZERO2 parents/participants and the child’s future autonomy is delineated. The potential benefits, including the option for further use and interpretation, are described, underpinned by recognition of the importance of providing hope to parents of children diagnosed with cancer. At the same time, awareness is raised of potential harms in returning raw data. It was equally important to reflect on the principle of reciprocity in that ZERO2 parents/participants and their families are partners in this clinical trial. In return for their data contributing to translational research in Australia and around the world, the Delphi experts supported that participants’ biospecimens and/or raw genomic data should be returned if requested.

Yet there were also significant additions to the document made after feedback from parents who had experienced the path of requesting and having their child’s raw genomic data returned and parents whose child had previously or were currently participating in ZERO Program trials. These included acknowledging in the final V7 that the raw genomic data is of value to parents for its potential but that on its own, cannot inform clinical decision-making nor answer questions in a research setting. Other issues, such as stating expected turnaround times of research result reporting was considered critical, as the lack of a reportable or actionable findings from ZERO2 may trigger interest in a request to seek answers from another source.

Families who had previous experience requesting the return of the raw data from the PRISM trial reported experiencing barriers and extended delays for eventual return in a setting where time is critical. Having a defined, streamlined Policy and Process, aligning the views and actions of data requesters and those responding to requests when they are received from ZERO2, may assist in addressing these friction-points. Acknowledging the needs and concerns of parents wanting to explore every avenue for their child may also prevent or alleviate such tensions in the future.

The approach to not involve parents initially in the Delphi consultation may be perceived as a limitation, given best practice is to involve consumers from the early stages of document development27. However, whilst recognizing that co-design is important, our aim in facilitating separate consultations and discussion of a document developed by clinicians and other experts was to sensitively address the views of those with previous and current lived experience, and the recognized potential for power dynamics influencing participation, particularly if there was a pre-existing relationship between the parent/guardian and oncologist who may have previously treated their child28. The potential was reinforced in that those with lived experience wished to have the discussion about their request for return with a genetic counselor and without their clinician. This underscores the critical importance of having genetic counselors embedded in precision medicine clinical trial programs such as ZERO2.

In response to the view that some parents may want to have their clinician present, the final policy ensured that parents had a choice in this matter. Importantly, broader consultation with other parent groups and reviewing the experiences of those requesting data sharing going forward as ZERO2 is implemented in Australia and New Zealand, will allow for opportunities to further refine the Policy and Process document.

As precision medicine is increasingly clinically implemented, requests by parents and patients for the return of their raw data may also be received, particularly if the report states that there are no reportable or actionable findings. The development of policy for return in such clinical settings, where standards of variant reporting in are high and quality controlled, require different considerations to policy developed for the research setting. While the experts participating in the Delphi included a pediatric pathologist and genetic clinicians with laboratory genetics experience, Board-certified laboratory geneticists or pathologists, responsible for clinical reporting, are not part of the ZERO Program and so did not participate, but their input will be integral in the development of policy for return in the clinical setting.

Acknowledging that parents/participants have a right of access to raw genomic data and biospecimens is fundamental in advancing a trusting, authentic partnership that hopes to advance knowledge and improve outcomes in this highly evolving research and clinical space. Translational precision medicine clinical trials are underpinned by partnership between data custodian researchers and participants. In the pediatric cancer setting, the ZERO Program demonstrated respect for this partnership by developing an ethical consensus pathway to return a child’s biospecimens and/or raw genomic data to parents/guardians, if requested.

The Policy and Process to guide response to such requests, informed by expert consensus and incorporating parent views, may guide considerations in ethical guidelines and serve as a model for other research groups taking this position in reciprocity for the donation of a child’s/participant’s biospecimen and the genomic data generated. Importantly, in this evolving space, learnings from patients/cancer-treating teams’ experiences will support further refinement of the process.

Methods

The development took place iteratively over four stages, comprising seven versions. As this was an internal process for the development of policy for the ZERO Program based on stakeholder consensus, ethics approval was not sought for its development. The final document was however approved for implementation in ZERO2 by the Sydney Children’s Hospital HREC in November 2023 (2022/ETH01232: ZERO Childhood Cancer Program).

Development of Version 1

Drafted by K.B.S., E.C., and C.J., based on the literature4,5,7,8,9,12,13,29, Version (V) 1 was in two parts: Policy (Part 1) and Process (Part 2) [Supplementary File 1]. Part 1 contained statements under the headings of Scope; Premises underpinning the policy; Background; Ethical considerations including respect for autonomy, beneficence/clinical utility, minimizing the potential for harm, responsibility to genetic relatives; reciprocity between research participants and the research program and, the Groups for whom the policy applied: (1) parents/guardians/participants; (2) clinicians who wish to provide a participant’s raw data for analysis to another research group; and (3) clinicians who wish to provide access to a participant’s raw data to another group to advise on treatment.

Part 2 described the eight steps to be undertaken in the release of raw data.

Toward expert consensus on the content and process—V2–4

A modified reactive Delphi survey methodology with experts affiliated with the ZERO2 trial was selected with the aim of reaching consensus over three rounds of consultation on the clarity and relevance of items in V130,31. Unlike the traditional Delphi technique, where the document is iteratively generated by experts, the reactive modification is applicable when a draft document is being reviewed32,33. The CREDES (Conducting and Reporting Delphi Studies) recommendations underpinned the study design and conduct including the choice of the Delphi technique utilized; study conduct; definition of consensus; data analysis; and reporting of the findings34.

Delphi participants

All members of the ZERO2 Study Committee, the Management team and the Ethical, Legal, and Social Issues Advisory Sub-Group of the ZERO2 Germline Working Group, collaborators with ZERO Program from the ZERO Program representatives from the Australian and New Zealand Children’s Hematology/Oncology Group (ANCHOG) were emailed an invitation to participate (n = 54) (Table 1).

The invitation included a link to the survey, allowing for response data to be collected and managed using REDCap electronic data capture tools hosted by the University of New South Wales25,26.

Delphi procedure and determination of consensus

Potential experts were asked to complete surveys over an anticipated three rounds. Participation was completely voluntary and participants could withdraw at any time without consequence.

The draft document at each round was available to download as a PDF version. All 54 invited participants were given the opportunity to comment in Rounds 1 and 2.

In each round, statements under the relevant headings in the version for comment were provided as a screenshot to prevent editing, with the option for free-text comments and suggested changes. Both the original and revised statements were presented as screenshots Experts were asked to state their level of agreement in terms of clarity and relevance for each statement on a 5-point Likert scale from strongly agree to strongly disagree. Statements that received ≥80% strongly agree/agree, for both relevance and clarity, and where no changes were suggested, were accepted. Where the support was <80% for either relevance or clarity, or where changes were proposed, the statement would be appropriately edited and included in the version assessed in the next round. The 80% level was chosen for additional rigor and followed King et al. (2021)31,35. The previous Round’s relevance and clarity results and feedback received were provided. Minor feedback was summarized; where too complex, experts’ comments were provided. The rationale was provided for any amendments.

Round 1: V1 was open for comment from mid-November 2021 until mid-January 2022 with two reminder emails (Supplementary File 1). To maintain anonymity, limited demographic data was collected including gender, field of expertize and years of experience in the field, and the Australian State or Territory where they were based (or if based in New Zealand). V 2 was open for comment for two weeks in June 2022 and a reminder sent after one week. Prior to completing the survey, experts were asked for their name, contact details and affiliation, if they would like to be a co-author in any publication arising and if they had participated in Round 1.

Round 3: V3 was emailed in September 2022 to experts who had contributed to Round 2. The email was also forwarded to a genomics/computational biology expert who had not participated in Round 2 for comments on technical issues in the Process document. Changes received as email responses were incorporated into V4 and provided to the ZERO Program National Steering Committee (NSC) for endorsement in November 2022.

Parent feedback—V5–6

In April 2023, V4 was provided for comment to representatives of the Australian Families for Genomics (AF4G) group, as some of their members were parents or relatives of children who had participated in PRISM and requested data return. An online meeting was held in May 2023 with K.B.S., E.C., and AF4G representatives to discuss their feedback. Following incorporation of their comments into V5, a leaflet for parents/participants requesting data access was developed to inform them of the issues that were important to consider.

Members of the ZERO Parents Consultation Group were invited by the group facilitators from the ZERO Program to provide feedback on V5 and the leaflet via an online meeting, facilitated by EC, held in July 2023.

Human Research Ethics Committee (HREC) ratification and implementation

Their feedback was incorporated into the final leaflet content (Fig. 1) and V6. Following review by the ZERO Program Management Committee for editing and formatting, V7, the leaflet content and a request form for the release of the data and/or biospecimen, adapted from the Ethical and Legal Aspects of Translational Medicine (EURAT) policy group12, received ethics approval for implementation in November 2023.

Fig. 1: Items to be discussed following request for return.
Returning raw genomic data to research participants in a pediatric cancer precision medicine trial

Content of leaflet.

Full size image

Related Articles

Targeting of TAMs: can we be more clever than cancer cells?

With increasing incidence and geography, cancer is one of the leading causes of death, reduced quality of life and disability worldwide. Principal progress in the development of new anticancer therapies, in improving the efficiency of immunotherapeutic tools, and in the personification of conventional therapies needs to consider cancer-specific and patient-specific programming of innate immunity. Intratumoral TAMs and their precursors, resident macrophages and monocytes, are principal regulators of tumor progression and therapy resistance. Our review summarizes the accumulated evidence for the subpopulations of TAMs and their increasing number of biomarkers, indicating their predictive value for the clinical parameters of carcinogenesis and therapy resistance, with a focus on solid cancers of non-infectious etiology. We present the state-of-the-art knowledge about the tumor-supporting functions of TAMs at all stages of tumor progression and highlight biomarkers, recently identified by single-cell and spatial analytical methods, that discriminate between tumor-promoting and tumor-inhibiting TAMs, where both subtypes express a combination of prototype M1 and M2 genes. Our review focuses on novel mechanisms involved in the crosstalk among epigenetic, signaling, transcriptional and metabolic pathways in TAMs. Particular attention has been given to the recently identified link between cancer cell metabolism and the epigenetic programming of TAMs by histone lactylation, which can be responsible for the unlimited protumoral programming of TAMs. Finally, we explain how TAMs interfere with currently used anticancer therapeutics and summarize the most advanced data from clinical trials, which we divide into four categories: inhibition of TAM survival and differentiation, inhibition of monocyte/TAM recruitment into tumors, functional reprogramming of TAMs, and genetic enhancement of macrophages.

Ethical considerations in AI for child health and recommendations for child-centered medical AI

There does not exist any previous comprehensive review on AI ethics in child health or any guidelines for management, unlike in adult medicine. This review describes ethical principles in AI for child health and provides recommendations for child-centered medical AI. We also introduce the Pediatrics EthicAl Recommendations List for AI (PEARL-AI) framework for clinicians and AI developers to ensure ethical AI enabled systems in healthcare for children.

Stromal architecture and fibroblast subpopulations with opposing effects on outcomes in hepatocellular carcinoma

Dissecting the spatial heterogeneity of cancer-associated fibroblasts (CAFs) is vital for understanding tumor biology and therapeutic design. By combining pathological image analysis with spatial proteomics, we revealed two stromal archetypes in hepatocellular carcinoma (HCC) with different biological functions and extracellular matrix compositions. Using paired single-cell RNA and epigenomic sequencing with Stereo-seq, we revealed two fibroblast subsets CAF-FAP and CAF-C7, whose spatial enrichment strongly correlated with the two stromal archetypes and opposing patient prognosis. We discovered two functional units, one is the intratumor inflammatory hub featured by CAF-FAP plus CD8_PDCD1 proximity and the other is the marginal wound-healing hub with CAF-C7 plus Macrophage_SPP1 co-localization. Inhibiting CAF-FAP combined with anti-PD-1 in orthotopic HCC models led to improved tumor regression than either monotherapy. Collectively, our findings suggest stroma-targeted strategies for HCC based on defined stromal archetypes, raising the concept that CAFs change their transcriptional program and intercellular crosstalk according to the spatial context.

Rapid brain tumor classification from sparse epigenomic data

Although the intraoperative molecular diagnosis of the approximately 100 known brain tumor entities described to date has been a goal of neuropathology for the past decade, achieving this within a clinically relevant timeframe of under 1 h after biopsy collection remains elusive. Advances in third-generation sequencing have brought this goal closer, but established machine learning techniques rely on computationally intensive methods, making them impractical for live diagnostic workflows in clinical applications. Here we present MethyLYZR, a naive Bayesian framework enabling fully tractable, live classification of cancer epigenomes. For evaluation, we used nanopore sequencing to classify over 200 brain tumor samples, including 10 sequenced in a clinical setting next to the operating room, achieving highly accurate results within 15 min of sequencing. MethyLYZR can be run in parallel with an ongoing nanopore experiment with negligible computational overhead. Therefore, the only limiting factors for even faster time to results are DNA extraction time and the nanopore sequencer’s maximum parallel throughput. Although more evidence from prospective studies is needed, our study suggests the potential applicability of MethyLYZR for live molecular classification of nervous system malignancies using nanopore sequencing not only for the neurosurgical intraoperative use case but also for other oncologic indications and the classification of tumors from cell-free DNA in liquid biopsies.

Why do travelers discontinue using integrated ride-hailing platforms? The role of perceived value and perceived risk

Despite integrated ride-hailing platforms have provided many benefits to travelers, there are also various potential risks. This study aims to examine travelers’ discontinuance behavioral intention toward integrated ride-hailing platforms. The research framework was established by extending the theory of planned behavior (TPB) with perceived value and perceived risk. Perceived value was classified into utilitarian, hedonic, and social values, while perceived risk was classified into privacy, performance, security, and financial risks. Additionally, the factors of switch cost and personal innovativeness were included. An empirical analysis was carried out using partial least-squares structural equation modeling (PLS-SEM) based on a survey conducted in Nanjing, China. Furthermore, a multi-group analysis (MGA) was performed to examine behavioral differences across demographic variables. The findings suggest that discontinuous behavioral intention is influenced by subjective norms, perceived behavioral control, and attitude. Among them, perceived behavioral control shows the strongest impact (−0.190). Perceived value, including utilitarian, hedonic, and social dimensions, negatively influences discontinuance intention, whereas the four variables of risk perception positively affect discontinuance intention. Notably, social value, performance risk, and privacy risk act higher total effects on discontinuance intention. Switch cost is negatively associated with attitude (−0.222), and positively affects discontinuance intention (0.189). Personal innovativeness has positive and stronger effects on perceived value (0.237), negative effects on perceived risk (−0.174), and negative effects on discontinuance intention. Regarding MGA results, older travelers demonstrate a stronger impact of social value on perceived value, higher-income groups exhibit greater sensitivity to security risks, and frequent travelers prioritize utilitarian value.

Responses

Your email address will not be published. Required fields are marked *