Scenario analysis and multi-criteria decision analysis to explore alternative reimbursement pathways for whole genome sequencing for blood cancer patients

A B S T R A C T Background: Whole genome sequencing (WGS) has transformative potential for blood cancer management, but reimbursement is hindered by uncertain benefits relative to added costs. This study employed scenario planning and multi-criteria decision analysis (MCDA) to evaluate stakeholders ’ preferences for alternative reimbursement pathways, informing future health technology assessment (HTA) submission of WGS in blood cancer. Methods: Key factors influencing WGS reimbursement in blood cancers were identified through a literature search. Hypothetical scenarios describing various evidential characteristics of WGS for HTA were developed using the morphological approach. An online survey, incorporating MCDA weights, was designed to gather stakeholder preferences (consumers/patients, clinicians/health professionals, industry representatives, health economists, and HTA committee members) for these scenarios. The survey assessed participants ’ approval of WGS

Conclusion: Payers commonly emphasize acceptable cost-effectiveness, but strong clinical evidence for many variants and comparable costs to standard tests are likely to drive positive reimbursement decisions for WGS.

Background
The clinical evaluation and treatment of patients with blood cancer increasingly relies on genomic testing.While the primary approach for many years depended on conventional cytogenetic methods focusing on specific candidate genes associated with blood cancer, recent advancements in whole genome sequencing (WGS) have presented an opportunity to redefine the use of molecular diagnostics in clinical practice [1][2][3].WGS allows for the simultaneous determination of a comprehensive spectrum of somatic alterations including single nucleotide variants (SNV), small insertions and deletions (indels), structural variants (SV), and copy number variations (CNV) [4,5].Current studies on the application of WGS in blood cancers demonstrate its potential to significantly improve the accuracy of disease risk assessment and the personalization of treatment decisions for individuals when compared to standard of care testing [3,[6][7][8].While WGS is just one of several next-generation sequencing (NGS) technologies, WGS offers the distinct advantage of detecting all types of genomic variants across the entire genome, rather than focusing on predefined sets of genes compared to other methods such as whole exome sequencing (WES) and targeted gene panels [9].This is particularly paramount because with an increasing number of clinically significant variants being reported, WGS as a single test has the potential to streamline the stepwise molecular process required to reach a molecular diagnosis for therapeutic and prognostic purposes in patients with blood cancer [10].
In 2023, the United States (US) National Comprehensive Cancer Network (NCCN) updated its testing guidelines for acute myeloid leukemia (AML) to include WGS in its diagnostic protocol.This is an important milestone because it marks the first instance of WGS being integrated into oncology NCCN diagnostic guidelines [11].Furthermore, it lays the foundation for the potential adoption of WGS in other subtypes of blood cancers, particularly in cases where there is strong evidence of superior diagnostic performance and clinical utility, such as acute lymphoblastic leukemia (ALL) [12,13].
Currently, there is a lack of reimbursement of WGS for people with blood cancer in Australia, and this is widely recognized as a major barrier to its broader implementation into the healthcare system [14,15].Although WGS may be accessible through different funding programs, instituting a standardized reimbursement item for WGS from national public healthcare system insurance scheme ensures that healthcare providers are reliably compensated for providing WGS as a genomic testing service where there is a clinical need for patients and the financial burden on patients are minimized.Generally, reimbursement of a new health intervention within a public healthcare system is supported through health technology assessment (HTA), in which the new intervention is systematically evaluated for its clinical effectiveness, safety, cost-effectiveness, affordability and its broader value to the healthcare system [16].However, it has been generally acknowledged that there are numerous challenges in the economic assessment of WGS which largely accounts for its lack of cost-effectiveness [17][18][19][20][21][22][23][24][25][26][27][28][29][30].To summarize, these challenges are particularly the result of the treatment complexity following the use of WGS (co-dependents) as well as methodological challenges related to the overall approach and framework for assessing WGS [17][18][19]22,29,30], the complexities of analysis and modeling [20,26,28], and the availability and quality of data [21,24,25,27].As a consequence, the reimbursement landscape for molecular testing can be very scattered and inefficient because of the cascade of tests being done.
These issues are particularly relevant to genomic technologies given the fragmentation of a disease population into smaller subpopulations from different genomic profiles and individualized care pathways.Consequently, this is a source of uncertainty on the overall evidence on the value of WGS, which can make it difficult for decision makers to endorse a positive reimbursement recommendation [31].Therefore, there is a research and policy need to examine the various elements that contribute to the evidence uncertainties in reimbursement decision-making and use this knowledge to explore feasible strategies for achieving WGS reimbursement in blood cancers.
Scenario planning is a strategic method to consider different potential futures for a given problem within a set timeframe [32].A scenario is not predictive, but rather a hypothetical representation of a particular future outcome supported by plausible, consistent and relevant assumptions.Scenario planning originated from military planning but since then, this methodology has been applied to various disciplines including public policy, environmental planning, and healthcare.Notably, ven de Ven et al. [33] used scenario planning to develop nine different scenarios that could impact the use of WGS in non-small cell lung cancer (NSCLC) and found that reduced cost, faster turnaround time and improved clinical utility were main drivers to the implementation of WGS.However, these findings are not directly generalizable to blood cancers because specific attributes distinguish the application of WGS from solid cancers, particularly in relation to the types of detectable genomic alterations and the availability of treatment choices between blood versus solid cancers [5,34,35].
Furthermore, the scenario planning methodology has been combined with multi-criteria decision analysis (MCDA) to assess stakeholder preferences regarding these scenarios [36,37].MCDA is a decision-making tool to help decision makers evaluate and prioritize health interventions based on multiple criteria [38,39].MCDA has been tested across various HTA agencies where the scientific and societal values and preferences of stakeholders (including consumers) are incorporated within a transparent decision-making framework [40][41][42][43][44].These studies can make significant contributions to the thorough evaluation of the value associated with precision medicine products that is not solely rooted in cost-effectiveness judgements.Importantly this can deliver a nuanced, context-specific information for decision makers to determine what healthcare systems are willing-to-pay for [45].
Leveraging both scenario planning and MCDA offers potential advantages in complex decision contexts to examine how the decision maker's values or preferences may change for other future scenarios in relation to a policy problem [36,37,[46][47][48].The current policy problem of WGS not routinely being reimbursed for people with blood cancer for countries, such as Australia, leads to inefficiencies and potentially inappropriate care delivery.The purpose of this study is to describe possible future scenarios of WGS in blood cancers specifically different HTA evidence aspects, and to identify stakeholder preferences for these scenarios.

Study overview
This study utilized MCDA for reimbursement scenarios involving WGS in blood cancers.These scenarios are defined as conceivable representations of various evidential characteristics or considerations concerning the clinical application of WGS in blood cancers created for the purpose of an HTA submission.
Fig. 1 summarizes the study methodology, which was structured in three main phases: assess the preferences of primary stakeholder groups (i.e., consumers or patients, clinicians or health professionals, industry representatives, health economists, and HTA committee members) by weighting the factors identified in Phase 1 using the analytical hierarchy process (AHP) of the MCDA.

Key factors identification and selection
A systematic literature search was conducted on five electronic databases (MEDLINE, Embase, Cochrane Library, Health Technology Assessment, and National Health Services Health Economic Evaluation Database).Additional grey literature of previous submissions of WGS for blood cancer from three HTA organizations (Canadian Agency for Drugs and Technologies in Health [CADTH], Medical Services Advisory Committee [MSAC], and National Institute for Health and Care Excellence [NICE]) were searched for relevant publications.The selection criteria encompassed publications examining the clinical use of WGS for individuals with blood cancer, with a focus on reporting significant factors related to reimbursement, as either primary research (quantitative or qualitative study design) or reviews.Data extraction and narrative synthesis were conducted by M.V., who listed and organized factors into analytical themes.The development of these themes was predominantly informed by HTA guidelines from CADTH, MSAC, and NICE, allowing each factor to be categorized into a specific methodological component or evidence request outlined in these guidelines.All authors had the opportunity to suggest additional factors so that the final list of factors was complete and exhaustive.Appendix 1 provides further details of the systematic literature review and the final list of the 25 factors identified.
Next, an online survey was developed using a two-stage constant sum scale approach to assess the relative importance for the 25 factors on the Qualtrics XM program (Qualtrics, UT, US).The first stage of the survey instructed participants to evaluate each factor and specify any factor that they considered important for an HTA evidence review.The second stage of the survey asked participants to distribute 100 points to the factors that they previously selected based on their relative importance.For instance, the participants were informed if they perceived one factor to be twice as important as another, it should be assigned twice as many points, and if they regarded two factors as equally important, both should receive an equivalent number of points.The survey was distributed to consumers, clinicians, industry representatives, health economists, and HTA committee members.The survey results were reviewed by the authors where the top six highly scored factors were selected, with careful consideration given to avoiding unnecessary increases in the complexity of the decision problem that could arise from including additional factors.Table 1 presents the definitions of these six factors.Appendix 2 provides the results of this online survey.

Scenario development
The second phase developed the scenarios following the morphological approach.This is a well-established method for representing a problem through a matrix that incorporates various states or value conditions.For each of the six key factors derived from Phase 1, an exhaustive and exclusive set of potential values for the subsequent fiveyear period was defined.The five-year timeframe is common in scenario planning and balances between being near enough for reasonable accurate HTA evidence assumptions about WGS for blood cancers while still allowing for exploration of a range of potential evidence.These values were determined using a combination of literature sources and assumptions [3,7,13].Estimates from literature sources were rounded to the nearest 5 % for the ease of scenario interpretation and preference evaluation.Table 2 outlines the conceivable values for the six key factors within a matrix referred to as the morphological box.Every value configuration across the factors in the morphological box were examined to form a potential scenario, and any inconsistent or conflicting configurations were excluded as a scenario.After excluding any   Note: In the morphological box, the top row corresponds to the six critical uncertainties, while the columns represent the various potential states, values, or parameters associated with each of those specific critical uncertainties.* Duncavage et al. [3] identified that 25 % of myeloid cancer patients could be stratified into a distinct risk category through WGS that was not possible to detect from standard molecular tests.† Leongamornlert et al. [13] identified that 88 % of B-other ALL patients could be stratified into an established genetic subtype through WGS that was not possible to detect from standard molecular tests.This percentage was rounded up to 90 %. ‡ Burd et al. [7] identified that 64 % of AML patients were assigned targeted or investigation therapies following from WGS.This percentage was rounded up to 65 % QALY, quality adjusted life-year; WGS, whole genome sequencing.
Fig. 2. Reimbursement scenarios for WGS in blood cancers, Note: The arrows illustrate the differences between two scenarios.WGS, whole genome sequencing.
inconsistent or conflicting configurations, the scenarios representing the least likely and most likely to be reimbursed under the current HTA guidance, as well as additional configurations in between those two boundaries deemed relevant for reimbursement decision-making, were considered.An assessment was conducted on each of these configurations to ensure logical consistency (i.e., values that did not contradict each other) and empirical consistency (i.e., values not founded on highly improbable assumptions) prior to their inclusion in the final set of scenarios.Finally, five scenarios were selected and ordered based on a trade-off between one or more factor.Fig. 2 illustrates the five future scenarios of WGS in blood cancers describing different evidence aspects of an HTA submission.These five scenarios are: Scenario 1: Supportive WGS clinical evidencelimited access to targeted treatmenteconomic challenges.In this scenario, WGS has the capability to uncover genetic variants that standard molecular tests fail to detect in 25 % of patients with blood cancer.Subsequently, 65 % of these patients qualify for targeted or investigational therapies after undergoing WGS.However, a reimbursed targeted treatment is accessible to only 15 % of patients, and they must have previously undergone at least two lines of therapy before becoming eligible.The cost-effectiveness analysis of WGS indicates that utilizing WGS to inform treatment decisions incurs an incremental cost-effectiveness ratio (ICER) exceeding $100,000 per quality-adjusted life year (QALY) gained.Moreover, the expenses associated with WGS surpass those of standard molecular tests that are presently reimbursed.
Scenario 2: Improved WGS clinical evidencelimited access to targeted treatmenteconomic challenges.In this scenario, the trade-off relative to the previous scenario focuses on the improvement in clinical evidence for WGS.Consequently, this scenario assumes that WGS can identify variants not previously detected by standard molecular tests in 90 % of patients and that 85 % of patients are suitable candidates for targeted or investigational therapies after WGS.All other assumptions remain unchanged from Scenario 1.
Scenario 3: Improved WGS clinical evidencemoderate access to targeted treatmentequal cost.This scenario aims to gain better access to targeted treatment and that the cost of WGS is on par with reimbursed molecular tests.It is assumed that 50 % of patients with a treatable variant can access reimbursed targeted treatment, even after having previously undergone one or more lines of therapy.With WGS at the same cost as reimbursed molecular tests, the ICER falls within the $50,000 to $100,000 range per QALY gained.All other assumptions remain unchanged from Scenario 2.
Scenario 4: Improved WGS clinical evidencecomprehensive access to targeted treatmentfinancial benefits.Scenario 4 extends from Scenario 3 by improving access to targeted treatment and reducing the cost of WGS even further.This scenario assumes that 85 % of patients with a treatable variant can access reimbursed targeted treatment at any stage of therapy.The cost of WGS is lower than the cost of reimbursed molecular tests.All other assumptions remain unchanged from Scenario 3.
Scenario 5: Improved WGS clinical evidencecomprehensive access to targeted treatment -economic benefits.The final scenario focuses on the economic benefits of WGS such that the ICER falls below the threshold of $50,000 per QALY gained.All else remains consistent with Scenario 4.

Scenario evaluation
The third phase evaluated the scenarios through a (second) online survey.This survey applied the AHP technique and included pairwise comparisons to capture preferences from decision-makers and stakeholders regarding various factors (criteria) and alternatives (collectively referred to as elements).Here, the six factors that were identified from Phase 1 of the study were considered as the criteria and the five scenarios developed from Phase 2 were regarded as the alternatives in this MCDA survey.
The weighting in the survey was obtained by pairwise comparisons of the factorsfirstly pairwise comparisons of the factor and secondly pairwise comparisons of alternatives for each criterion.Initially, a total of 90 pairwise comparisons were expected when evaluating six factors against each other, and the five scenarios against the six factors (i.e., 6 C 2 + 5 × 6 C 2 ).However, to streamline this approach and reduce the number of survey questions, the participants were instructed to evaluate their relative preference between the two values within a single factor, as represented by the cells in the columns of the morphological box developed during Phase 2 instead of the five scenarios against the six factors.This adjustment reduced the number of pairwise comparisons to 29.Further details are provided in Appendix 3.All pairwise comparisons were conducted using Saaty's double ninepoint scale, where participants quantified the degree of relative importance/preference for an element using specific scores ranging from 1 (equally important/preferred) to 9 (extremely important/preferred).The survey also included several demographic variables.Additionally, participants were presented with each scenario and asked to evaluate them individually, indicating whether they would approve the reimbursement of WGS for blood cancer based on each scenario.The survey was developed on Qualtrics XM program (Qualtrics, UT, US).
Key stakeholder groups included consumers or patients, clinicians, industry representatives, health economists, and HTA committee members.The survey was distributed using a purposive, convenience sampling technique through research institutions, consumer advocacy groups, professional societies, industry groups, and other social network organization.These included Australian Genomics, the Australian Health Economics Society, the Australasian Leukaemia & Lymphoma Group, the Haematology Society of Australia and New Zealand, Illumina, the Industry Genomics Network Alliance, the Leukaemia Foundation and the Victorian Comprehensive Cancer Centre Alliance.This sampling approach was chosen to facilitate a comprehensive representation of key stakeholders given that experience with WGS in blood cancer could be considered a specialized or niche topic coupled with low patient access to this service.
The factor weights and preferences for the reimbursement scenarios were derived using the geometric mean method (GMM) from the AHP [49].These factor weights and preferences were presented as the mean and standard deviation (SD).Global Consistency Indices (GCIs) were computed for each matrix individually to assess the reliability and precision of participants' responses and the quality of their decision-making preferences based on a consistency ratio (CR) of 0.15 [50].Rather than discarding inconsistent responses from participants, an algorithm by Pascoe [51] was applied to modify the stated preferences and mitigate the degree of inconsistencies.Appendix 3 provides additional information of the analytical approach to estimate the factor weights and overall preferences of the scenarios.The analysis was performed using the R Statistical Software version 4.3.1 (R Foundation for Statistical Computing, Vienna, Austria).

Survey participants
The survey received complete responses from 19 (36 %) out of the 52 participants surveyed.Of these participants, 6 (32 %) were clinicians or health professionals, 5 (26 %) were consumers or patients, 5 (26 %) were industry members, and there were 2 (10 %) each who were health economists and involved in policy-making, regulation, or HTA committees (Appendix 3).A majority of participants (n = 13; 68 %) indicated that they have over 5 years of experience, whether through lived or professional experience, with WGS for blood cancers.Fifteen (79 %) participants resided within Australia and four (22 %) participates resided from outside Australia.

Preference scores for the scenarios
Table 3 presents the criteria weights and the preferences associated with different reimbursement scenarios for WGS in blood cancers.
Upon comparing the six criteria, "clinical impact of WGS results on patient care" with a weight of 0.25 was considered to be most important, followed by "diagnostic accuracy of WGS" (0.21), "cost-effectiveness of WGS" (0.19), "availability of reimbursed treatment after WGS" (0.16), and then both "eligibility criteria for reimbursed treatment based on actionable WGS results" and "cost comparison of WGS" (each weight of 0.09).
Scenario 1 is defined by favorable WGS clinical evidence but limited access to targeted and economic challenges.Participants' preferences for reimbursement scenarios show a preference score of 0.10 for Scenario 1. Conversely, Scenario 2 introduces improved WGS clinical evidence and has a preference score of 0.17.Building upon Scenario 2, Scenario 3 has a preference score of 0.20.This enhanced scenario encompasses improved access, cost-effectiveness outcomes ranging from $50,000 to $100,000 per QALY gained, and equal cost with other standard molecular tests.Scenario 4 maintains a focus on enhanced access and lower costs compared to other standard molecular tests, with a preference score of 0.20.Finally, Scenario 5 further enhances costeffectiveness, with outcomes falling below $50,000 per QALY gained compared to other standard molecular tests, and a preference score of 0.29.Therefore, the AHP analysis demonstrate that Scenario 5 has the highest preference amongst participants.

Assessment of reimbursement for each individual scenario
Fig. 3 shows the results of participants' decisions about reimbursing WGS in blood cancers for each individual scenario.The majority of participants (58 %; n = 11) indicated their disapproval for reimbursement of Scenario 1.On the other hand, there was an equal response to approving and disapproving reimbursement of Scenario 2 (each n = 9; 48 %), with one (5 %) participant undecided.However, the majority (n = 16; 84 %) were in favor of reimbursing Scenario 3 and only 2 participants (11 %) opposed reimbursing.Scenario 4 garnered approval from most participants (n = 18; 95 %), and Scenario 5 would be reimbursed by all participants (n = 19; 100 %).

Discussion
Reimbursement of WGS in blood cancer is complicated by uncertainties about its benefits and lack of clarity on the pathway to reimbursement.This study utilized scenario planning to create scenarios that address uncertainties related to the technological, methodological, and evidentiary aspects of WGS, while projecting potential future evidence attributes.In doing so, five scenarios were developed to describe varying levels of information on the evidence and value of WGS in blood cancer, intended for an HTA submission.These scenarios were presented  and evaluated among stakeholders in a survey, considering trade-offs associated with critical uncertainties affecting reimbursement.A broad range of stakeholders with direct experience with WGS in blood cancer, whether through personal experiences receiving genomic testing or professional roles, were engaged.This approach integrated varied perspectives to offer valuable insights into the combined benefits and consequences, impact, and perceived value of WGS.
Stakeholders responded to the survey by emphasizing the importance of both diagnostic accuracy and clinical impact of WGS in their decision-making process regarding reimbursement.Stakeholders also strongly preferred a scenario that included superior clinical effectiveness, comprehensive access to reimbursed targeted therapies across the treatment continuum and economic and financial benefits.When individually presented to stakeholders, stakeholders were initially hesitant to approve reimbursement of WGS until specific conditions were met.These included ensuring that at least 50 % of patients with a targetable variant could access reimbursed targeted treatment at any stage of therapy, demonstrating cost-effectiveness results falling within the range of $50,000 to $100,000 per QALY gained, and aligning the cost of WGS with that of standard molecular tests.Therefore, the findings of this study suggest that for WGS reimbursement in blood cancers, strong clinical evidence, cost parity with standard molecular tests and broad treatment accessibility are crucial factors, even if the cost-effectiveness of WGS exceeds the common willingness-to-pay (WTP) threshold of $50,000 but remains below the $100,000 per QALY gained threshold.
These findings have several implications that together contribute to a potential future pathway for achieving WGS reimbursement in blood cancers, as they emphasize several crucial areas for the improvement evidence development.For example, the current evidence supporting the clinical impact of WGS in blood cancers, at least in AML, indicates that 64 % of AML patients who underwent WGS were subsequently assigned targeted or investigational therapies [7].Scenario 1 was based on this evidence (rounded up to 65 %), while Scenarios 2-5 assumed an increase to 85 %.However, there are challenges to these assumptions that warrant attention.One major challenge is the accurate interpretation of WGS data, particularly when dealing with variants of uncertain significance, which complicates treatment and prognostic assessments for blood cancer patients e.g., in the context of tumor-agnostic therapies and decisions regarding hematopoietic stem cell transplantation options based on molecular abnormalities [10,[52][53][54].Another challenge arises in certain blood cancer subtypes where the survival benefit of targeted therapies is uncertain, for instance, in IDH-mutated AML patients, treatment outcomes may not significantly differ with or without the use of targeted therapy [55].Importantly, interpreting genomic data for clinical decision-making must be contextualised with other relevant clinical information, such as blood and bone marrow morphology and flow cytometry (e.g., for prognostic markers in post-induction measurable residual disease) [10].Despite these assumptions, significant trends suggest potential advancements in the utility of WGS.These include an increasing number of genes identified through WGS becoming the focus of targeting and an increasing regulatory approval of treatment in blood cancers, which collectively contribute towards the overall clinical impact of WGS in blood cancers [56,57].Consequently, WGS offers distinct advantages over a more targeted NGS approach for a limited number of known actionable genes, as patients undergoing genomic testing are restricted to the genes included in the panel.
Another implication is that achieving a cost of WGS that is equal to the cost of standard molecular tests and ensuring extensive treatment accessibility may hold greater significance than cost-effectiveness.Typical HTA approaches may require WGS in blood cancers comply with the commonly accepted WTP threshold set at $50,000 per QALY gained [58].However, according to stakeholder input, the emphasis on achieving affordability and improved treatment access may supersede the significance of the WTP threshold.Further, lowering the cost of WGS to match standard molecular tests would make comprehensive genomic testing more accessible, particularly if it replaces certain multimodal diagnostics in blood cancer, thereby the financial burden on healthcare systems and patients.This shift in focus towards affordability could facilitate broader implementation of WGS, allowing more patients to benefit from genomic profiling and personalized treatment plans.Importantly, a notable trend has been the declining cost of sequencing and the potential for workflow automation in WGS, which are expected to reduce overall costs [59].
There are several limitations to this study.Firstly, a degree of subjectivity is involved in developing the scenarios.Sources of subjectivity include the selection of scenarios based on the morphological approach and the sequence of trade-offs presented to survey participants.This subjectivity may potentially introduce bias when seeking to elicit preferences.Nevertheless, the rationale for scenario selection is to delve into these trade-offs, and while there is an implicit order in their presentation, the underlying assumption is that clinical evidence should precede treatment access, followed by cost considerations, and ultimately cost-effectiveness.Furthermore, as more variants are implicated for their actionability, there is an increased likelihood of achieving costneutrality.However, this relationship could not be examined given the sequential nature of the scenario analysis, with one factor being altered at a time.Secondly, the sample size for the survey was relatively small.However, genomics in blood cancer is to some extent a specialized field, and the survey participants encompass a broad spectrum of perspectives where the majority possess more than five years of experience.Nevertheless, a greater sample size will increase the validity of these findings.Thirdly, participants' responses to pairwise comparisons demonstrated a considerable degree of inconsistency.Nevertheless, this study employed a simplified approach to adjust AHP stated preferences, with the purpose of reducing the inconsistency observed in the results.Lastly, while there may be a risk of double-counting and therefore bias with including both economic criteria "cost-effectiveness of WGS" and "cost comparison of WGS" in the MCDA survey, significant efforts were made to clearly differentiate these definitions and ensure that the range of possible ratings for one criterion remains independent of ratings on other criteria, even when they are correlated [60,61].The criterion "cost comparison of WGS" was specifically framed in terms of affordability, comparing the costs of WGS relative to standard molecular tests that are currently reimbursed, and therefore emphasizes the financial implications of the WGS technology itself.In contrast, the criterion "cost-effectiveness of WGS" was framed as WGS to guide treatment decisions and presented through a series of WTP thresholds.

Conclusion
While demonstrating the substantial value of WGS is the preferred approach to garner reimbursement support from stakeholders, robust clinical evidence pertaining to a substantial number of tested variants are the primary drivers for WGS reimbursement in blood cancers.When this is demonstrated, stakeholders are inclined to approve the reimbursement of WGS in scenarios where, at the very least, WGS costs the same as standard testing and there is broad treatment accessibility.

1. Phase 1 :
Identification of key factors that directly or indirectly influence reimbursement decisions of WGS for blood cancer within clinical practice, and the selection of a subset of these key factors as both the critical uncertainties (important uncertainties relevant to reimbursement) in the scenario planning and criteria (variables used to evaluate and compare alternative scenarios) in the MCDA.2. Phase 2: Development of hypothetical scenarios incorporating the potential HTA evaluation components for WGS in blood cancers using the morphological approach based on the key factors identified in Phase 1. 3. Phase 3: Evaluation of hypothetical scenarios developed in Phase 2 to

Table 1
Overview of criteria and definition.

Table 3
Mean (SD) weights for criteria weights and preferences to reimbursement scenarios for WGS in blood cancers.