Developing an early scientific advice framework for health technology assessment in Saudi Arabia: insights from global practices and expert consultations

Abstract

Background

Early Scientific Advice (ESA) is an independent, non-binding guidance from Health Technology Assessment (HTA) bodies or regulatory authorities to manufacturers before market entry. Unlike company sponsored advisory boards focused on commercial purposes. Saudi Arabia lacks a formal ESA framework representing a policy gap as the country adopts value-based care and evidence-driven reimbursement. This study address gap by proposing a Saudi ESA framework informed by global best practices and stakeholder input.

Methods

A narrative review literature review was conducted across PubMed, Embase, Scopus, and a grey literature to examine established ESA systems, followed by a roundtable with 15 experts representing policymakers, regulators, clinicians, HTA experts, industry, payers, and academia, ensuring multi-stakeholder input.

Results

Benchmarking ESA models implemented by National Institute for Health and Care Excellence (NICE), Canadian Agency for Drugs and Technologies in Health (CADTH), and European Medicines Agency (EMA) and integrated roundtable consensus, four key pillars for the Saudi ESA were identified: (1) scope covering both pharmaceuticals and medical devices to support local of new technologies; (2) timing varies for ESA pharmaceuticals, it can be positioned before drug registration during the late stages of clinical development, phase 2 and 3 for diseases of high local relevance, such as rare diseases to align evidence pre-submission while for medical devices ESA would occur primarily in the post-marketing stage; (3) governance positioning the HTA centrally because of its role in value assessment and reimbursement; (4) patients’ involvement, facilitated through structured questionnaires, to ensure real-world perspective.

Conclusion

The four ESA pillars (scope, timing, governance, patients’ involvement) synthesize current international ESA practices and input from local experts, providing a structured foundation to support efficient evidence generation and alignment between regulatory and reimbursement requirements. Pilot evaluation is still required to validate anticipated benefits.

Background

Early Scientific Advice (ESA) is a structured and formal process enabling manufacturers to obtain confidential, nonbinding feedback from Health Technology Assessment (HTA) or regulatory bodies during the early stages of product or device development [1]. While ESA was initially associated primarily with regulatory bodies, authorities have also begun offering a parallel ESA to address both regulatory and HTA-related queries [2]. ESA can be pursued through one of three approaches: (a) regulatory or HTA advice from a single country, (b) parallel regulatory and HTA advice, and (c) multi-country advice, such as the Canadian Agency for Drugs and Technologies in Health (CADTH) parallel Scientific Advice (SA), United States Food and Drug Administration (FDA), European Medicines Agency (EMA) parallel SA, among others [2–4]. The primary objective of ESA is to align clinical development plans with HTA expectations, thereby increasing the likelihood of positive evaluations and reimbursement decisions. ESA involves proactive engagement with regulators and payers, enabling manufacturers to develop an evidence package that satisfies the requirements of key stakeholders. This process allows manufacturers to seek guidance on the suitability of their clinical trial design, evidence-generation strategies, and Real-World Evidence (RWE) activities to support both marketing authorization and reimbursement. It supports evidence-generation strategies for health technologies by: (1) optimising study designs prior to finalization of the pivotal trials, thereby minimising the need for costly amendments; (2) enabling early dialogue regarding the acceptability of RWE to complement, and in selected contexts potentially replace evidence from randomised controlled trials; (3) ensuring that the generated evidence fulfils both regulatory evidentiary requirements and the value-assessment expectations of HTA bodies; and (4) identifying potential evidence gaps during the planning phase, which may help reduce the likelihood of unfavourable reimbursement decisions at later stages. While regulatory and market access perspectives often differ, particularly regarding population coverage, comparators, and real-world outcomes, HTA agencies and payers across markets also employ varying evaluation criteria and methodologies to assess clinical and economic value based on their specific healthcare system needs. ESA may provide uniform guidance to achieve alignment on these aspects prior to the drug registration process [5–7].

ESA is particularly valuable for manufacturers developing innovative interventions when relevant details are unavailable or insufficient in existing guidelines, guidance documents, pharmacopoeia monographs, or draft documents. ESA is also beneficial when addressing emerging pathogens with unmet medical needs and no available guidance, or when manufacturers deviate from established guidelines or have limited knowledge of applicable regulations and requirements [5]. While ESA can help identify appropriate regulatory and HTA processes, it does not guarantee positive outcomes from the advising agency [8]. However, ESA offers significant potential benefits for all stakeholders in the drug approval and reimbursement process [7].

As drug development increasingly focuses on innovation, biotechnology, and orphan diseases, identifying suitable data for regulators and payers to make effective approval and reimbursement decisions has become more challenging. A pre-defined evidence generation plan can support the timely approval and reimbursement of innovative drugs and technologies [9]. During ESA interactions, the types of evidence most frequently discussed include pivotal clinical trial design elements, such as the selection of target populations, comparators, endpoints for reimbursement, and statistical consideration (stratification, subgroups); approaches to real-world evidence generation, including the validity of data sources and the design of external control studies; and economic topics such as population, choice of comparators, choice of economic model, data used to populate the model, time horizon and extrapolation hypothesis, utility values, resource utilization data, and cost effectiveness. Such interactions align development and evidence-generation plans with the specific context of the country where the advice is sought [10, 11]. Finally, as the end users of medicines, patients involved in scientific advice get an early opportunity to present perspectives different from those of the medical and scientific experts and raise issues that had not previously been considered, boosting the utility of the intervention in real-world settings later [12]. A published systematic review of early dialogue frameworks used in HTA found that ESA helps manufacturers better align product development and evidence generation with HTA and healthcare system requirements, potentially reducing uncertainties during downstream assessment and reimbursement evaluations [8].

In Saudi Arabia, the healthcare system is advanced, with universal healthcare funded by the government [13]. In 2016, Saudi Arabia announced Vision 2030, aiming to make public spending more efficient, use resources more effectively, and limit waste [14]. The population in Saudi Arabia is gradually increasing and aging, with Vision 2030 aiming to raise the average life expectancy to 80 years. At the same time, the country faces an increasing prevalence of non-communicable diseases, along with a heightened risk of communicable diseases. The Health Sector Transformation Program, launched in 2021 as part of Vision 2030, aims to restructure the healthcare system into a comprehensive, effective, and integrated model. This program focuses on transforming the healthcare sector into a value-based system, ensuring transparency and financial sustainability by prioritizing public health and disease prevention. Its specific goals include improving access to and the quality of healthcare services through optimal coverage and ensuring a comprehensive, equitable geographical distribution. This system focuses on the health of individuals and society, encompassing citizens, residents, and visitors [15, 16]. To achieve this mission, the HTA process was introduced in Saudi Arabia to allocate healthcare resources more efficiently and provide evidence-based recommendations for decisions regarding the approval and reimbursement of interventions [17]. In this context, strengthening structured evidence-informed decision-making frameworks is increasingly recognised as an important approach to enhance transparency, support effective health policy decisions, and guide the evaluation of emerging health technologies [18]. Given the purpose of ESA to enable the development of focused evidence for these decisions, it is important to establish a framework for the ESA process in Saudi Arabia. To achieve this goal, we invited a group of experts and key stakeholders from various ministries in Saudi Arabia to discuss and propose a framework for introducing ESA. This article discusses current global trends in ESA practice and proposes a framework for establishing the ESA process in Saudi Arabia.

Early scientific advice

In 2009, the United Kingdom’s National Institute for Health and Care Excellence (NICE) was the first agency to introduce an HTA-only single-country SA procedure [7]. Advice from a single HTA agency is usually sought to understand the national requirements to support jurisdictional access. Parallel regulatory plus HTA advice helps identify any discrepancies and/or gaps between regulatory and HTA requirements and the company’s development plan, helping to achieve alignment between the two. Simultaneous advice meetings with multiple HTA agencies provide a streamlined approach and may also present an opportunity to reconcile divergences between different agencies and confirm a single approach that may help satisfy the requirements of both agencies. The multi-country ESA process can also help optimize the allocation of development resources [2–4]. In 2010, EMA and several European HTA agencies launched a pilot program to provide parallel advice. This program was further refined through the European Network for Health Technology Assessment (EUnetHTA) and was formalized as EMA-EUnetHTA parallel consultation in 2017 [2, 4].

Global ESA practices

The ESA framework is built upon several key pillars, including the scope of services, the ESA process, the type of evidence, the nature of the technology, product eligibility, the involvement of experts and patients, and concerns related to confidentiality and conflict of interest. Further, the pillars for adopting ESA include stakeholder collaboration, clear regulatory pathways, robust data strategies, and adaptive planning. Enablers for successful adoption of ESA include transparency, flexibility, and iterative feedback loops to optimize drug development and align health technology assessment. A typical ESA process encompasses the following stages: defining objectives, preparing data, presenting to regulators, discussing findings, receiving feedback, and subsequently refining strategies based on the feedback.

Process of ESA

Initially, an application for an ESA is submitted to the relevant authority. Once the application is accepted and timelines are established, a briefing book is submitted to the authority. The manufacturer prepares a document that outlines the disease background, current treatment options, product details, and the proposed study design. Additionally, this document defines the specific questions the manufacturer seeks to address and the scope of engagement.

The materials for the briefing book are often required to be submitted in the local language. After the briefing book is submitted, clarifications from the authority are addressed, and the briefing book is finalized. Following the finalization, a scientific advice meeting is conducted. The meeting may last between one and three hours and is attended by internal and external experts, ESA officials, and company representatives. After the meeting, the ESA authority shares a detailed written summary of the advice [1, 5, 7, 19]. The entire process from application to finalization of ESA takes approximately 18 weeks; however, it may take as long as 6 to 8 months [11]. (Refer to Fig. 1 for Global ESA Process Overview)

Fig. 1.

Early scientific advice process overview

ESA can be incorporated into the planning process of the pivotal trial design. Although if pursued too early, there may be internal disagreements on major trial design aspects. Typically, the window of opportunity to seek ESA occurs after the conclusion of phase 2 trials, but before the initiation of phase 3 trials. This timing ensures sufficient data is available to address key uncertainties while allowing for necessary adjustments to the clinical development plan of pivotal trials. ESA sought at the phase 2 trial stage allows for refinement of the clinical development plan. In contrast, ESA sought to align the clinical development plan with the market access requirements at the phase 3/pivotal trial stage. Finally, ESA sought that the post-marketing authorisation phase may help refine the RWE plan [5–7].

Methods

Literature search

A structured narrative literature review was conducted to identify established ESA frameworks, without adherence to PRISMA or other systematic review reporting guidelines; therefore, no PRISMA flow diagram was generated. Searches were performed in PubMed, Embase, and Scopus without date restrictions and limited to English-language publications, using predefined terms related to ESA and HTA advisory processes.

Grey literature was identified through targeted searches of HTA organisation websites and supplementary purposive searches using Google, used to capture relevant policy and guidance documents not indexed in bibliographic databases. Google searches were conducted using predefined key terms related to ESA and HTA advisory processes (examples include early scientific advice, parallel scientific advice, and HTA early advice framework, and the first five pages of results were screened per search term to ensure a consistent and pragmatic approach to source identification. Eligibility criteria were defined a priori. Included sources comprised peer-reviewed studies, reports, and organisational documents describing ESA services, joint-parallel scientific advice, HTA advisory processes, or evidence-generation support frameworks. Opinion pieces, editorials, and news articles without methodological content, as well as sources not directly relevant to ESA were excluded. Titles and abstracts were screened for relevance, and full texts of potentially relevant records were retrieved for detailed assessment. Key information was extracted from included sources and synthesized narratively. Sources were included in the review based on the predefined eligibility criteria and are cited where they directly inform the findings and conclusions.

A total of 23 sources were included in this narrative review, all of which are cited in the reference list.

Roundtable meeting

A single‑day structured workshop was held in Riyadh, Saudi Arabia, on October 17, 2024, bringing together 15 participants to develop the proposed ESA framework. The group included 26% policymakers and regulators, 20% clinicians, 20% industry representatives, 13% HTA experts, 13% academics, and 6% payer representatives. The session was designed as a structured workshop rather than a formal Delphi or nominal group technique. A preliminary ESA framework was constructed based on the principal findings of the literature review, which encompassed processes, workflows, timings, challenges, and lessons learned. This framework was subsequently presented to the roundtable. Participants evaluated each component, benchmarked it against established international ESA frameworks (e.g., NICE, CADTH, EMA), assessed its applicability to the local context, and recommended either its retention or modification according to their domain expertise. Through facilitated discussion, the group integrated these roundtable contributions with the original evidence from the literature. The outcome was a refined framework, adapted to the local setting and informed equally by published evidence and stakeholder expertise. The roundtable was a physical meeting that was recorded with participant consent. The discussion followed a structured question-and-answer format, in which the facilitator posed questions on each ESA framework component and participants responded. Two independent scribes took detailed minutes. No formal qualitative analysis (e.g., thematic coding) was applied; instead, the minutes were reviewed and a descriptive summary of key points was prepared. To manage bias and conflicts of interest, all participants were asked verbally to disclose any relevant conflicts before the discussion; none were declared. No independent external review was conducted.

Results and discussion

Roadmap for Saudi Arabia

The roundtable, guided by the findings of the literature review and a structured, facilitator-led discussion, identified four pillars to underpin a national roadmap for implementing ESA: products for consideration, timing of ESA, governance of ESA, and the role and extent of patients’ involvement in ESA. The four pillars were derived from participant dialogue through structured group discussion and consensus during the session. They were identified as the key domains underpinning the development of a country-specific ESA framework. No formal thematic coding or quantitative consensus methods were applied. (Refer to Fig. 2 for Key Components of Saudi Arabia ESA Framework)

Fig. 2.

Key components of the Saudi Arabia ESA framework

Products for consideration under ESA

The scope of ESA varies across HTA agencies. While most agencies provide ESA primarily for pharmaceutical products, several have extended their scope to other technologies. For instance, NICE, Haute Autorité de Santé (HAS), and EUnetHTA-EMA offer scientific advice on both pharmaceutical products and MedTech devices. NICE also offers ESA for non-device technologies such as digital health interventions. Additionally, NICE provides advice for products related to topics from the Priority Lists. NICE further extends its scope to non-device technologies, as digital health interventions. Additionally, it provides advice for products related to topics from the Priority Lists. The differences in scope across agencies informed the roundtable discussions on which product categories should be prioritize for inclusion under a national ESA framework [5, 7, 11].

For the proposed Saudi Arabia’s ESA system, the initial suggestion was to include only pharmaceutical products. However, stakeholders reached consensus through facilitated discussion that the medical devices (including diagnostics) should be eligible alongside pharmaceuticals, aligning with international practices and national healthcare priorities.

Timing of ESA

Every regulatory or HTA agency applies eligibility criteria that are mostly dependent on the stage of development with specific data expected to be presented at that stage. Timing is therefore crucial to ensuring a successful advisory process, as the ESA process itself is lengthy. Identifying the optimal timing for the ESA process can help manufacturers ensure sufficient alignment in the clinical development plan, while still allowing enough time to incorporate recommendations before the product launch in cases of divergence between the proposed plan and the ESA [1].

Regulatory scientific advice and HTA advisory processes differ primarily in their timing and purpose. Regulatory advice, such as that from the EMA, is typically sought early in the development lifecycle. Manufacturers often request it prior to or during the design of pivotal clinical trials. The focus is on supporting evidence generation for marketing authorization and ensuring that study designs meet regulatory efficacy and safety requirements. In contrast, HTA advice, for example from NICE, may be sought at various stages of development, generally from early to late clinical development but prior to regulatory submission. The focus here is on ensuring that the generated evidence suits comparative effectiveness, health economic evaluation, and reimbursement decision making. As a result, regulatory advice tends to be earlier and development focused, whereas HTA advice aligns more closely with downstream assessment and access decision requirements.

NICE suggests that the best time to seek advice varies with the manufacturer and the intervention under development. Most manufacturers avail themselves of the ESA service before phase 3 or pivotal clinical trials; however, the service is available at any point during the development cycle. NICE also directs companies with technologies in the late stages of development to aim to finalize the scientific advice project no later than 38 weeks before the expected NICE Technology Appraisal committee meeting, so that the timing can be aligned with the opinion of other regulatory authorities, such as the Committee of Human Medicinal Products of EMA [7].

CADTH offers ESA prior to pivotal trials design and enables engagement at a stage where clinical protocols can still be refined. It also allows for follow-up advice on products that have received a “do not reimburse” recommendation due to shortcomings in clinical or real-world evidence [6]. Roundtable participants noted the CADTH framework as a comprehensive model due to its early engagement and revisited decisions after a non-reimbursement outcome. Saudi experts highlighted that the CADTH approach may inform a more flexible ESA framework in Saudi Arabia by supporting engagement at multiple stages of technology development and assessment.

EMA offers ESA during the initial development of a pharmaceutical product before the submission of a marketing authorization application. EMA also provides SA during the post-authorization phase [5]. EMA scientific advice is structured around specific questions submitted by medicine developers on key aspects of a product’s development plan, enabling targeted regulatory input at defined decision points. Key lessons from this process include the value of early and structured engagement during clinical development, as well as the importance of addressing critical study design element, such as endpoints, comparators, and target populations, at an early stage to ensure alignment with regulatory expectations. This approach informed the Saudi ESA framework by reinforcing the need for timely, question-driven interactions that support alignment between development strategies and future regulatory and HTA requirements, thereby reducing the risk of misalignment at the time of marketing authorisation [1].

Although the current clinical trials framework in Saudi Arabia may not be optimal for certain products at Phases 2 and 3, conducting ESA in therapeutic areas such as sickle cell disease and rare diseases is justified given their relevance to the local population. Some stakeholders emphasized the benefits of prioritizing post-authorization processes given the stability provided by the Saudi Food and Drug Authority (SFDA). However, with the establishment of the breakthrough committee for innovative medications, the ESA’s role in shaping the committee’s agenda before treatment registration was deemed significant.

The panel recommended the following timelines for ESA in Saudi Arabia:

• Saudi ESA can be positioned before drug registration during the late stages of clinical development.

• The Saudi ESA can be offered for phase 2 and phase 3 trials of drugs for specific specialty diseases with relevance to the local population, such as rare diseases. For medical devices, the proposed timing for ESA is post-marketing authorization.

From an operational perspective, the typical duration of the ESA procedure is approximately 4 months. The timeline for the EMA ESA process is 40 without a meeting discussion and up to 70 days with a meeting discussion, measured from initial submission. In contrast, for CADTH, the process takes 18 to 22 weeks. For NICE, the process lasts between 12 and 18 weeks. The actual ESA meeting typically lasts 3 h [1, 5–7, 11]. In the Saudi Arabian framework, the proposed timeline/duration is not yet defined.

Governance for ESA

In the Saudi Arabian ESA framework, the discussion regarding the authority for ESA highlighted that, although the ESA will be non-binding and not mandatory for registration or formulary inclusion, it is primarily expected to be adopted by the HTA body under the Council of National Health Insurance (CNHI) providing an institutional platform that can facilitate structured multi-stakeholder engagement within HTA and ESA processes.

Suggestions for oversight included establishing an independent body under the Ministry of Health (MoH), with other proposals considered the Saudi Health Holding Company or the Saudi Health Council to take responsibility for the ESA committee. Concerns were raised about potential conflicts of interest if the MoH conducted assessments, which could compromise confidentiality.

Patients’ involvement

Patients’ involvement is a key aspect of ESA, as patients’ contributions have been shown to have a tangible impact on the recommendations provided to manufacturers. Involving patients at early stages of development may lead to further discussions on relevant patient perspectives, thereby improving outcomes. Agencies such as NICE and HAS include patients as and when required, while EMA also has mechanisms in place to invite patients for ESA. Patient input is sought by identifying eligible patients or patient groups, carers, or consumers. Input is collected through tools such as surveys and questionnaires, in accordance with confidentiality procedures [11, 12]. In Saudi Arabia’s framework, the roundtable recommended collecting patient input through a questionnaire but did not discuss or recommend any specific validated patient-reported outcome measures (PROMs) to use. To achieve this, it is essential to establish eligibility criteria for participating patients and the questionnaire components. For instance, the questionnaire may include questions on out-of-pocket expenses, cost implications, and adverse events. The questionnaire should focus on short, closed-ended questions to facilitate clear responses. However, further deliberation is required to finalize the methodology for seeking patient input.

The proposed ESA framework serves as an upstream, non-binding advisory mechanism. It complements existing regulatory and reimbursement decision-making rather than replacing it. Under this structure, ESA recommendations support early evidence generation planning prior to regulatory submission, facilitate alignment with SFDA requirements during the marketing authorization process and help ensure that evidence from clinical development also addresses HTA and payer needs at the reimbursement stage. Importantly, ESA recommendations do not constitute regulatory or reimbursement decisions. Instead, they offer structured guidance to reduce uncertainty, improve evidence quality, and enable more efficient downstream assessment by regulatory and HTA bodies.

Further deliberation for Saudi ESA framework

Difference between ESA and advisory board meetings

The ESA process differs from the advisory board (Ad-board) meetings often held around the launch of a pharmaceutical product. Ad boards are company-sponsored meetings where key opinion leaders (KOLs) provide insights into a product’s clinical value for future marketing and sales purposes, and for treatment positioning within the guidelines, with a focus on commercial strategy. The participating experts must be specialists in the field and provide full disclosure of their involvement in these activities [20]. In contrast, ESA is an independent process led by HTA bodies and/or regulators, offering scientific advice either requested by companies or initiated by HTA following horizon scanning. ESA is patient-focused, adheres to regulatory standards, does not compensate advisors, and operates on a fee-for-service basis.

Horizon scanning

Organizations worldwide face the challenge of keeping pace with the rapid emergence of high-impact innovations. To address this, a systematic, comprehensive, and sustainable approach is being employed to identify future innovations and trends. This enables policymakers and stakeholders to respond effectively, facilitating the smooth market entry of innovations while minimizing developmental, procurement, legal, regulatory, and process barriers. Horizon scanning has emerged as a valuable and practical strategy to accelerate the realization of this goal [21]. Horizon scanning involves systematically reviewing information sources to identify early indicators of significant developments. This approach primarily focuses on the early lifecycle stages of a technology, during the initial adoption phase, before it enters the market. Still, it can also encompass broader trends, challenges, and opportunities. The service provides a comprehensive summary of the available evidence on technologies that are not yet widely adopted. These include technologies that are not yet licensed, approved, or marketed for use, as well as those that are not yet widely available or integrated into routine clinical practice [21]. The horizon scanning service is designed to assist decision-makers in planning and prioritization by enhancing their awareness of new and emerging health technologies. The service typically follows a structured signal-detection process, drawing on diverse sources such as scientific literature, clinical trials, patents, and industry pipelines. Detected signals are then filtered and prioritized using predefined criteria, and their relevance to healthcare objectives is assessed. Based on insights from horizon scanning, agencies can engage manufacturers to deliver well-informed, timely early scientific advice. This approach helps streamline the development of emerging technologies while strategically addressing regulatory and medical requirements at an early stage [22].

Fees for ESA service

The fees for these services vary widely. While certain countries, such as France and Norway, do not charge ESA fees, agency fees may vary widely (Italy: 10,000 to 40,000 €; United Kingdom: 29,000 to 91,051 £) [11, 23]. The specific details of the exact fees to be charged to the manufacturers were not discussed. The notion that ESA fees contribute to economic participation by facilitating local clinical trial requests and promoting local research and development was dismissed as a fundamental misunderstanding of the ESA’s purpose and process. The ESA is requested for inclusion in the formulary. The ESA aims to provide companies with guidance on what is needed to succeed in HTA appraisals. Moreover, while local clinical trials might drive economic contribution, ESA remains strictly a fee-for-service model, like the fees paid to the SFDA for product registration. Nonetheless, ESA fees could be considered an innovative source of funding for capacity-building efforts within the regulatory system.

Utilizing ESA for technical quality assessment

The potential use of ESA to guide technical quality assessments for products before filing or registration, particularly for Market Authorization Holders (MAH) located outside the territory or for biosimilars, was also explored. This approach could involve conducting trials to validate product quality before submitting them to the SFDA and ensuring the accuracy of documentation before forming local partnerships. While ESA typically does not provide technical or regulatory advice, the need for technical evaluations within the Saudi ESA may warrant assessment.

Inquiry regarding patient experience

The panel discussion sought to define patient experience, drawing on insights from both clinical trials and RWE. Patients contribute their perspectives through tools such as Patient-Reported Outcomes (PROs), which are essential for evaluating treatment effectiveness, particularly in terms of Quality of Life (QOL). QOL can be assessed during clinical trials through PRO questionnaires or measured post-marketing using RWE data. Patient experience evidence can influence HTA recommendations by revealing real-world disease burden and patient priorities not captured by clinical endpoints alone. This evidence also complements clinical and economic data. It aids in interpreting health-related quality of life outcomes. It also provides relevant context for benefit–risk assessments. As a result, the outcomes most meaningful to patients become more apparent. For reimbursement decisions, such evidence may justify coverage for specific subpopulations, inform value-based pricing, or support managed entry agreements. This approach follows international HTA practice, where patient input is increasingly integrated to reduce uncertainty and support more patient-centred coverage decisions.

Limitations

Several limitations should be acknowledged. This narrative review involved structured database searches supplemented with targeted grey literature from HTA websites and Google; however, it was restricted to English-language sources only, and the grey literature search was not designed to be fully reproducible. These factors may limit the comprehensiveness and reproducibility of the evidence synthesis.

The international ESA practices used as reference models reflect different regulatory and health system contexts and may not be fully directly transferable to Saudi Arabia. However, these models were not adopted directly; rather, they were reviewed and used as comparative benchmarks to identify core structural elements, which were adapted through expert input to ensure alignment with the Saudi regulatory and reimbursement context.

The study involved a purposively selected expert roundtable with a limited number of stakeholders, which may affect the transferability of findings beyond the study sample. In addition, as with all qualitative methodologies, potential selection and interpretation biases cannot be excluded, although steps such as multidisciplinary representation and structured facilitation were used to enhance the robustness of the findings.

From an implementation perspective, specific timelines for the Saudi ESA process remain undefined at this stage, unlike established benchmarks such as EMA (40–70 days), NICE (12–18 weeks) or CADTH (18–22 weeks). Defining appropriate timelines will be a key objective of the future pilot phase, informed by local regulatory capacity and stakeholder workflows.

Furthermore, the proposed ESA is informed by expert opinion and stakeholder consultation; however, further empirical testing and pilot implementation would help evaluate its effectiveness, feasibility, and operational impact in practice.

Finally, no specific fee model (e.g., fee-for-service versus government-funded) is proposed, leaving the financial sustainability of the program unclear and requiring further economic analysis prior to implementation.

Conclusion

ESA provides significant benefits to all stakeholders involved in the approval and reimbursement processes for pharmaceutical interventions, diagnostics, or medical devices. For an advanced healthcare system such as Saudi Arabia’s, it is important to provide ESA services to manufacturers to achieve optimal outcomes and improve access to these interventions. The discussion at the roundtable meeting revolved around four important pillars: products under consideration, timing of ESA, governance of ESA, and patients’ involvement. The panel proposed offering ESA for pharmaceuticals and medical devices (including diagnostics). Further, the panel suggested that ESA be considered before drug registration during the late stages of clinical development, and for phase 2 and phase 3 trials of drugs for specific specialty diseases relevant to the local population, such as rare diseases. For medical devices, the panel recommended the ESA process to be conducted post-marketing authorisation. The panel recommended that the HTA body in Saudi Arabia should be the governing body for ESA. Finally, the panel recommended seeking patient input through questionnaires administered to eligible patients and patient groups. Beyond these pillars, further deliberation on the operational timelines for the ESA process and the service fee is required.

The benefit of ESA, including but not limited to optimised study design prior to pivotal trials finalization, improved alignment of evidence generation with HTA and regulatory expectations, and reduced risk of rejections and reimbursement delays, are directly supported by findings from both literature review (NICE, CADTH, EMA) which highlighted the value of early engagement through structured frameworks and the round table discussion which identified key pillars deemed fundamental for establishing ESA in Saudi Arabia. With the absence of an ESA policy in Saudi Arabia, the proposed framework contributes to advancing HTA policy development in the country. It formalises ESA as a structured component of the decision-making ecosystem enabling earlier and more coordinated alignment between evidence generation and regulatory or HTA expectations while also bringing greater predictability and consistency to HTA informed policy decisions in line with the ongoing healthcare transformation towards value and evidence-based healthcare.

To operationalize this framework, a pilot implementation involving a limited number of innovative products is recommended. This phase would assess feasibility, refine procedures, and generate practical insights before national rollout. Successful implementation may position Saudi Arabia as a regional leader in structured early dialogue for health technology assessment.

Abbreviations

CADTH

Canadian Agency for Drugs and Technologies in Health

CNHI

Council of National Health Insurance

EMA

European Medicines Agency

ESA

Early Scientific Advice

EUnetHTA

European Network for Health Technology Assessment

FDA

Food and Drug Administration

HAS

Haute Autorité de Santé

HTA

Health Technology Assessment

KOLs

Key Opinion Leaders

MAH

Market Authorization Holders

MoH

Ministry of Health

NICE

National Institute for Health and Care Excellence

PROs

Patient-Reported Outcomes

PROMs

Patient-Reported Outcome Measures

QOL

Quality of Life

RWE

Real World Evidence

SA

Scientific Advice

SFDA

Saudi Food and Drug Authority

Author contributions

A.A. contributed to study conception and design, overall scientific leadership, critical intellectual oversight, interpretation of findings, critical revision of the manuscript, and final approval of the version to be published. H.A., H.H., and N.S.A. led the drafting of the original manuscript, contributed to data interpretation, and participated in manuscript review, revision, and final approval. M.K. contributed to study conceptualization, framing of the research objectives, interpretation of findings, critical review of the manuscript for intellectual content, and final approval. N.S.A. and H.H. additionally contributed to the study methodology, coordination and conduct of the work, and synthesis of evidence supporting the proposed framework. N.A., L.A., M.A., W.A., H.A., A.A., B.A., A.A., I.A., and N.A. contributed equally to the study through input into study design and scope, interpretation of results within their respective institutional and policy contexts, critical review and revision of the manuscript, and final approval of the submitted version.All authors made substantial contributions to the conception and/or design of the work, or the acquisition, analysis, or interpretation of data; drafting the work or revising it critically for important intellectual content; approving the final version to be published; and agreeing to be accountable for all aspects of the work.

Funding

Not applicable.

Data availability

No datasets were generated or analysed during the current study.

Declarations

Ethics approval and consent to participate

Not applicable.

Consent for publication

All authors consent to publish.

Competing interests

The authors declare no competing interests.