Role Of Real-world Evidence Research Articles

Evaluating biosimilars: safety, efficacy, and regulatory considerations in clinical studies.

Biosimilars are a rapidly growing area of clinical research, yet they encounter significant challenges, especially in emerging markets where regulatory and clinical hurdles differ markedly from those in established regions like Europe and the US. This commentary addresses these unique challenges and offers new perspectives on the global adoption of biosimilars. It emphasizes the crucial role of real world evidence in supporting biosimilar approvals, an aspect often underrepresented in current literature. The commentary also provides a comparative analysis of the regulatory frameworks in China and Europe, highlighting how these differences shape biosimilar development and market approval processes. By focusing on the issues of indication extrapolation and immunogenicity, this commentary highlights the necessity of continuous real-world data collection to ensure the safety and efficacy of biosimilars across multiple indications. Our analysis enhances the understanding of biosimilar research and supports their broader adoption as safe, effective, and accessible healthcare solutions globally.

Real-world evidence for coverage determination of treatments for rare diseases

Health technology assessment (HTA) decisions for pharmaceuticals are complex and evolving. New rare disease treatments are often approved more quickly through accelerated approval schemes, creating more uncertainties about clinical evidence and budget impact at the time of market entry. The use of real-world evidence (RWE), including early coverage with evidence development, has been suggested as a means to support HTA decisions for rare disease treatments. However, the collection and use of RWE poses substantial challenges. These challenges are compounded when considered in the context of treatments for rare diseases. In this paper, we describe the methodological challenges to developing and using prospective and retrospective RWE for HTA decisions, for rare diseases in particular. We focus attention on key elements of study design and analyses, including patient selection and recruitment, appropriate adjustment for confounding and other sources of bias, outcome selection, and data quality monitoring. We conclude by offering suggestions to help address some of the most vexing challenges. The role of RWE in coverage and pricing determination will grow. It is, therefore, necessary for researchers, manufacturers, HTA agencies, and payers to ensure that rigorous and appropriate scientific principles are followed when using RWE as part of decision-making.

The Role of Real-World Evidence in Treatment Decision-Making, Regulatory Assessment, and Understanding the Perspectives of People with Type2 Diabetes: Examples with Gliclazide MR.

Real-world evidence (RWE) plays an important role in the management of type2 diabetes (T2D). It provides data about the effectiveness and safety of an intervention from outside the randomised controlled trial (RCT) setting and allows healthcare professionals (HCPs) to determine if RCT data are applicable to their patients in routine clinical practice. This review provides a discussion of the value of RWE in T2D management in day-to-day clinical practice, with a focus on RWE with sulfonylureas (SUs), and presents two examples of a new generation of international real-world studies in people with T2D managed in routine clinical practice. RWE plays a valuable role in advising HCPs in the day-to-day management of T2D, informing regulatory authorities with regard to pharmacovigilance and post-approval updates, and providing insights with regard to patients' treatment adherence and preference. RWE should be used alongside RCTs to increase HCP awareness and understanding of their patients' perspectives, potentially allowing for improvements in treatment adherence, glycaemic control and health-related quality of life (HRQoL). In addition, real-world studies must be conducted in a way that generates robust RWE by limiting the risks of bias and confounding as much as possible. A growing body of RWE is emerging from Asia. For example, in a preliminary HRQoL analysis of the Joint Asia Diabetes Evaluation (JADE) Register, Asian people with T2D had better HRQoL with gliclazide-based treatment than with other SU agents, despite being older and having more diabetes-related complications.

PD20 Real-World Evidence To Support Single Arm Trials Of Oncology Interventions: Necessity or ‘NICE’ (National Institute for Health and Care Excellence) to Have?

IntroductionThe recent National Institute for Health and Care Excellence (NICE) consultation on methods for health technology evaluation (HTE) outlined plans to include guidance on the role of real-world evidence (RWE) in HTE. This is particularly pertinent for interventions where the evidence base consists of a single arm trial (SAT) design, which is more frequently observed in oncology. This study reviewed the influence of RWE submitted as part of the evidence base for NICE oncology appraisals.MethodsA search for NICE HTEs was conducted for interventions supported by SATs from January 2017-November 2021. Evidence was stratified by submission packages with SAT evidence alone or in combination with randomized controlled trial (RCT) evidence, with or without RWE.ResultsThirty-two decisions for interventions supported by SATs were made by NICE between 2017-2021, all in oncology indications. Fifty percent were supported by SAT evidence and fifty percent by RCT plus SAT evidence, both with or without RWE. A lower proportion of RCT/ SAT HTEs submitted RWE compared to SAT HTEs (fifty vs ninety four percent). Seventy five percent and nineteen percent of SAT HTEs received a positive recommendation, with and without restrictions, irrespective of submitting RWE. One negative decision was observed for SATs supported by RWE. Sixty three percent and thirty eight percent of RCT/ SAT HTEs received a positive recommendation, with and without restrictions. Overall, the proportion of positive recommendations were lower for HTEs submitting RWE (ninety six percent) compared to HTEs not submitting RWE (one hundred percent), which is in contrast to recent findings specific to orphan oncology HTEs (one hundred versus seventy eight percent).ConclusionsRWE was more commonly submitted to support SAT HTEs, than RCT HTEs. The use of RWE seems to be established as a necessity to supplement a SAT evidence base, whereas RWE is more generally a nice to have in RCT HTEs. However, RWE appears to positively influence decision-making for orphan oncology indications with a more neutral influence for non-orphan indications.

Impact of Regulatory Approval Status on CADTH Reimbursement of Oncology Drugs and Role of Real-World Evidence on Conditional Approvals from 2019 to 2021.

Real-world evidence (RWE) is health and outcomes data generated from a patient's journey through the health care system or disease process (i.e., real-world data). RWE is now having an increasingly important role in regulatory/reimbursement decisions. This article examines reimbursement recommendations by the Canadian Agency for Drugs and Technology in Health (CADTH) on oncology drugs approved between 2019 and 2021. Oncology drugs with a Summary Basis of Decision (SBD) for original marketing approvals were used to generate a corresponding list of CADTH final clinical recommendations for review. Of the 45 oncology drugs approved by Health Canada, CADTH granted positive funding recommendations to all 11 drugs that had priority review approvals. Two of the 17 drugs with standard reviews did not file to CADTH and 3 received a negative recommendation. Of the 17 drugs with Notice of Compliance with Conditions (NOCc) status, three were not filed to CADTH and four were under active reviews. Of the ten completed NOCc reviews, all contained RWE from sponsors and six received a negative decision on their first review. No significant differences in review times were found between the three approval statuses. Regulatory approval status appeared to influence reimbursement outcomes in Canada and evaluation of 10 NOCc approvals provided little insight regarding robustness of RWE required for more favorable considerations.

How do cancer clinicians perceive real-world data and the evidence derived therefrom? Findings from an international survey of the European Organisation for Research and Treatment of Cancer.

Background: The role of real-world evidence (RWE) in the development of anticancer therapies has been gradually growing over time. Regulators, payers and health technology assessment agencies, spurred by the rise of the precision medicine model, are increasingly incorporating RWE into their decision-making regarding the authorization and reimbursement of novel antineoplastic treatments. However, it remains unclear how this trend is viewed by clinicians in the field. This study aimed to investigate the opinions of these stakeholders with respect to RWE and its suitability for informing regulatory, reimbursement-related and clinical decisions in oncology. Methods: An online survey was disseminated to clinicians belonging to the network of the European Organisation for Research and Treatment of Cancer between May and July 2021. Results: In total, 557 clinicians across 30 different countries participated in the survey, representing 13 distinct cancer domains. Despite seeing the methodological challenges associated with its interpretation as difficult to overcome, the respondents mostly (75.0%) perceived RWE positively, and believed such evidence could be relatively strong, depending on the designs and data sources of the studies from which it is produced. Few (4.6%) saw a future expansion of its influence on decision-makers as a negative evolution. Furthermore, nearly all (94.0%) participants were open to the idea of sharing anonymized or pseudonymized electronic health data of their patients with external parties for research purposes. Nevertheless, most clinicians (77.0%) still considered randomized controlled trials (RCTs) to be the gold standard for generating clinical evidence in oncology, and a plurality (49.2%) thought that RWE cannot fully address the knowledge gaps that remain after a new antitumor intervention has entered the market. Moreover, a majority of respondents (50.7%) expressed that they relied more heavily on RCT-derived evidence than on RWE for their own decision-making. Conclusion: While cancer clinicians have positive opinions about RWE and want to contribute to its generation, they also continue to hold RCTs in high regard as sources of actionable evidence.

Biologics in severe asthma: the role of real-world evidence from registries.

Asthma is one of the most common noncommunicable diseases; in the majority of patients it is well controlled with inhaled bronchodilators and inhaled corticosteroids, but the management of severe asthma has been a significant challenge historically. The introduction of novel biologic drugs in the past few decades has revolutionised the field, presenting physicians with a variety of biologic drugs with different mechanisms for the treatment of severe asthma.It is of crucial importance to evaluate the effectiveness of these drugs by following their "real-life" effectiveness rather than relying solely on their efficacy, established in carefully designed clinical trials, which therefore do not necessarily match the profile of the real-life patient. Understanding the actual effectiveness of the specific drugs in real-life patients is a crucial part of tailoring the right drugs to the right patients. Registries serve as an important tool in obtaining real-life evidence, since they are in effect observational studies, following the entire patient population.

The role of real-world evidence (RWE) registries using NGS testing to address cancer health disparities (CHD) in small community oncology practices.

e18519 Background: CHD may result from multiple factors, including access to care, screening, and clinical trials; limited uptake of biomarker and next-generation sequencing (NGS) testing; and unfavorable social determinants of health. CHD may contribute to almost 34% of deaths among adult cancer patients and additional spending of $230 billion. Addressing CHD could result in an indirect savings of as much as $1 trillion over 3 years (AACR, CDR, 2020). Biomarker testing enables the option of targeted treatment, providing better outcomes and reduced toxicity. The NGS testing rate is very low in some regions and among minority populations, and underuse worsens disparities. Carolina Blood and Cancer Care Associates (CBCCA) has created best practices to improve biomarker testing and provide standard-of-care treatment in advanced cancer. Methods: As a part of a pledge to decrease CHD, CBCCA partnered with 2 national NGS testing vendors to create a RWE registry to identify appropriate patients and provide access to NGS biomarker tests for somatic mutations, including whole exome sequencing (WES). Liquid biopsy was made available when tissue was unavailable. Results: CBCCA has 1 suburban and 1 rural location, with an ethnically diverse population. Regular care was provided for 1466 of the 1786 unique cancer patients seen in 2021, and 442 participated in a RWE registry. Nonparticipants were survivors having routine follow-up care (n = 512), patients with early-stage or noninvasive disease (510), or patients who refused testing because they were responding to ongoing treatment or had reservations. NGS testing was obtained for 354 patients, 31% of whom were members of ethnic minority groups. Liquid biopsy was used for 133 samples, and the remaining 221 were analyzed with somatic NGS panels or WES. Of the liquid biopsies, 24 patients had actionable mutations; an additional 52 had findings of germline implications. Actionable mutations that could be treated with an FDA-approved drug were identified using tissue-based NGS testing in 38 pt. In tissue-based testing, WES detected more results with germline implications, compared to somatic testing alone. Another 64 tests found mutations treatable with an approved drug in another tumor type. The NGS and biomarker testing rate (either tissue or liquid biopsy) was 84% of eligible pt. Of the patients tested with NGS, clinically actionable variants that could be treated with an approved agent were found in 23% (same tumor type) and 28% (another tumor type). Another 40% of patients had results with germline implications, of which P53 deletion was the most common finding. Conclusions: It is feasible to increase the NGS testing rate in appropriate situations. In this study, actionable mutations impacting treatment selection were found in up to 25% of patients where targeted therapy could be offered.

R WE ready for reimbursement? A round up of developments in real-world evidence relating to health technology assessment: part 7.

This month we focus on papers that provide insights into the potential for target trial emulation to be used in health technology assessment, the role of real-world evidence (RWE) in informing additional elements of value and the importance of RWE to European joint clinical assessments.

Editorial: The Role of Real World Evidence (RWE) for Digital Health

Editorial: The Role of Real World Evidence (RWE) for Digital Health

Health technology assessments and real-world evidence: tell us what you want, what you really, really want.

Health technology assessments and real-world evidence: tell us what you want, what you really, really want.

POSB267 Influence of Real-World Evidence to Support Single Arm Trials Submitted to NICE for Orphan Oncology Products

The recent NICE consultation on methods for health technology evaluation (HTE) outlined plans to include guidance on the role of real-world evidence (RWE) in HTE. This is particularly pertinent for indications where the evidence base consists of a single arm trial (SAT) design, such as orphan diseases. This study reviewed the influence of additional evidence submitted to NICE for orphan oncology products. A search for NICE HTEs was carried out using the IQVIA HTA Accelerator™. HTEs for orphan oncology products with a final decision in 2016-June 2021 were included, excluding resubmissions and extensions. Evidence was stratified by submission packages with randomised and non-randomised design, with or without RWE. Thirty-two decisions for orphan oncology products were made by NICE between 2016-2019. Of these, 25 (78%) submitted RCT evidence compared to 7 (22%) supported by SAT evidence. A lower proportion of RCT HTEs submitted RWE compared to SAT HTEs (32% vs 86%). All SAT HTEs received a positive recommendation with (57%) or without (43%) restrictions, irrespective of submitting RWE. All negative decisions were observed for RCT HTEs with no RWE (16%), with the remaining receiving a positive recommendation with (52%) or without (32%) restrictions. Overall, the proportion of positive recommendations were higher for HTEs submitting RWE (100%) compared to HTEs not submitting RWE (78%). HTEs submitting additional RWE are more likely to receive a positive recommendation, irrespective of the trial design for the core evidence base. The value of RWE seems to be established in HTEs relying on SAT evidence, whereas for RCT HTEs, there may be an opportunity to achieve higher rates of positive decisions by including additional RWE evidence. A closer examination of the role RWE played in the reviewed HTEs is ongoing.

The Role of Real-World Evidence in FDA-Approved New Drug and Biologics License Applications.

The US Food and Drug Administration (FDA) is open to accepting real‐world evidence (RWE) to support its assessment of medical products. However, RWE stakeholders lack a shared understanding of FDA’s evidentiary expectations for the use of RWE in applications for new drugs and biologics. We conducted a systematic review of publicly available FDA approval documents from January 2019 to June 2021. We sought to quantify, by year, how many approvals incorporated RWE in any form, and the intended use of RWE in those applications. Among approvals with RWE intended to support safety and/or effectiveness, we classified whether and how those studies impacted FDA’s benefit‐risk considerations, whether those studies were incorporated into the product label, and the therapeutic area of the medical product. Finally, we qualified FDA’s documented feedback where available. We found that 116 approvals incorporated RWE in any form, with the proportion of approvals incorporating RWE increasing each year. Of these approvals, 88 included an RWE study intended to provide evidence of safety or effectiveness. Among these 88 approvals, 65 of the studies influenced FDA’s final decision and 38 were included in product labels. The 88 approvals spanned 18 therapeutic areas. FDA’s feedback on RWE study quality included methodological issues, sample size concerns, omission of patient level data, and other limitations. Based on these findings, we would anticipate that future guidance on FDA’s evidentiary expectations of RWE use will incorporate fit‐for‐purpose real‐world data selection and careful attention to study design and analysis.

PNS153 The Role of Real World Evidence in Health Technology Assessment over Time: A Research on the French Situation

Real-World Evidence (RWE) is more and more recognized as a valuable source of evidence and has been a growing focus of Health Technology Assessment (HTA) in the past few years. This ongoing research aims at describing the role of post-registration studies in the HTA process and the evolution of those studies in France. Using the list published by the French HTA body (April 2020) on the commissioned and completed post-registration studies, the corresponding Transparency Committee recommendations were retrieved from the French HTA body website. A systematic review of these recommendations is underway. The types of outcomes expected from the post-registration studies, as well as the methodologies, are being studied. Where post-registration studies have been provided, the evolution of two indicators, the Actual Clinical Benefit (ACB) and Clinical Added Value (CAV), used to determine the reimbursement rate and price, is monitored. 253 Transparency Committee recommendations were retrieved, 122 concerning ongoing requests and 131 concerning completed studies. Studies were commissioned between 1997 and 2020. The most represented therapeutic areas for completed studies were cardiovascular diseases and rheumatology, while for ongoing studies they were oncology and endocrinology. Assessing effectiveness and Quality of Life were one of the objectives of 10% and 6% of completed studies, respectively, whereas this was the case for 84% and 25% of ongoing studies. Understanding the conditions of prescriptions or use of the medicines remained the most important study objective (>90%). First results show that the impact on ACB and CAV was limited. CONCLUSION: RWE is increasingly requested for HTA in France, while the shape of these studies has deeply evolved over the years. The lack of standardized methodologies to develop RWE has undercut its impact on regulators’ decision-making. It is now crucial to further define how collecting, analyzing, and reporting real-world data should be done.

OP184 Strengthening Patient Outcome Evidence In Health Technology Assessments: A Co-Production Approach

IntroductionInvolving patients is a core principle which governs the work of the National Institute for Health and Care Excellence (NICE). To improve how patient evidence is identified and considered in health technology assessments (HTAs), NICE worked with patient organizations to review existing HTA methods and co-designed proposals for change.MethodsA working group, including six patient organizations, oversaw the project, identifying and co-designing options for improvement. We held a stakeholder event with twenty-two patient organizations to identify themes for improving how we find and use patient evidence. We then ran an online quantitative and qualitative survey for targeted consultation with patient organizations to capture broader views.ResultsThe fifty-two people who responded to the consultation made the following suggestions: (i)Provide information about uncertainties that patient evidence might help to address;(ii)Explore the role of real-world evidence in patient involvement;(iii)Provide training and support to patient organizations;(iv)Create inclusive committee cultures; and(v)Include additional touchpoints during HTAs to incorporate patient evidence.ConclusionsThis work identified improvements in seeking and incorporating patient evidence into HTA processes. Precise guidance for patient organizations will help them to submit evidence that will make the most impact. This is particularly important when assessing disruptive technologies where there are likely to be greater uncertainties and cost pressures. The results of this work will be developed into formal options for NICE to consider when updating its methods guides.

Role of real-world evidence for oncology product registration in the United States: A review of approvals by the U.S. Food and Drug Administration from 2015 to 2019.

e14130 Background: There are few concrete examples of real world evidence (RWE) used to support clinical development in regulatory filings despite growing interest in this field. This study systematically reviewed FDA oncology approvals to identify use cases of RWE. Methods: FDA’s new drug application (NDA) and biologics license application (BLA) approvals for oncology products from 2015-2019 were systematically reviewed. Among cases with RWE, data characterizing the submission and RWE details (data source, study design, FDA comments) were synthesized. Results: 93 approved NDAs and BLAs were identified; 6 included RWE in support of efficacy (see Table), approved on or after 2017, and were largely retrospective studies that contextualized results to pivotal trial, with primary endpoints overall survival (OS), overall response rate (ORR), and time to treatment discontinuation (TTD). Flatiron data were used in 3 of these as database analyses, 1 was an expanded access program (EAP), 1 was a meta-analysis, and 1 was a retrospective chart review. Conclusions: In the past 5 years, few FDA decisions incorporated RWE in oncology drug approvals. When used, RWE has been a complement rather than a supplement for clinical trial data. Early engagement, a priori protocol development, and robust research design (adjusting for bias, comparability to clinical trial population) remain key determinants for successful use of RWE in FDA decision making. [Table: see text]

PCN506 MUTATION TESTING AND TREATMENT OF THE MOST COMMON ONCOLOGY DISEASES IN GERMANY: ANALYSIS OF AN ONCOLOGY EMR DATABASE

The role of real-world evidence (RWE) in healthcare decision-making is constantly growing, acknowledged by recent FDA and EMA communications. Especially in oncology, a better understanding of the real-world treatment of patients is needed, both to compare RWE with clinical trial results and to identify unmet needs in the real-world (RW) treatment of patients. However, there is a lack of reliable data in this respect. We aimed to describe the RW treatment of patients included in a new electronic medical record databank targeting German oncology patients (INGRESS-Indivumed Liquid Biopsy RWE oncology database). The databank is built based on German outpatient oncology cases, it currently includes 14,145 oncology patients. It provides data on patient and disease characteristics, treatments, diagnostics including mutation/immunohistochemistry testing, and clinical outcomes; furthermore, for each patient blood draws for an ex-post mutation testing are available. Most common cancer types in the database are breast cancer (BC), lung cancer (LC) and colon cancer (CC), with a proportion of 23.8%, 11.7% and 8.8%, respectively. The average age was 66.5 years in the overall sample (60.9/67.2/68.0 years in BC/LC/CC patients). Percentage of females was 56.3% (98.0%/40.6%/44.9%). A mutation/immunohistochemistry test was conducted in 98.9% of the patients with BC (54.6% of patients with HER2+). Proportion of tested patients was 66.0%/55.9% in LC/CC. Most common mutation types in LC were PD-L1 and EGFR+ (53.0%/12.1% of tested LC patients) and KRAS in CC (42.5%). The most frequently prescribed 1L treatment was paclitaxel in BC patients with/without HER2+, pembrolizumab in LC patients with PD-L1, carboplatin in non-PD-L1 LC patients, and irinotecan+folinic acid in KRAS+/non-KRAS CC patients. The Indivumed Liquid Biopsy RWE oncology database has the potential to provide valuable insights into RW data on the treatment and treatment-associated outcomes of German oncology patients.

Role of Real-World Evidence in Informing Cancer Care: Lessons from Colorectal Cancer

The term "real-world evidence" (rwe) describes the analysis of data that are collected beyond the context of clinical trials. The use and application of rwe have become increasingly common and relevant, especially in oncology, because there is growing recognition that randomized controlled trials (rcts) might not be sufficiently representative of the entire patient population that is affected by cancer, and that specific clinical research questions might be best addressed by real-world data. In this brief review, our main aim is to highlight the role of rwe in informing cancer care, particularly focusing on specific examples from colorectal cancer. Our hope is to illustrate the ways in which rwe can complement rcts in improving the understanding of cancer management and how rwe can facilitate cancer treatment decisions for real-world patients encountered in routine clinical care.

The Role of Real-World Evidence in UK Reimbursement: Case Study of Lenalidomide in Myelodysplastic Syndrome Deletion 5q.

BackgroundUncertainty within cost-effectiveness analysis, often driven by lack of mature data from large clinical trials, plays a key role in decisions made by the National Institute for Health and Care Excellence (NICE), particularly for early access medicines and orphan drugs.ObjectivesIn this case study, we used real-world evidence to address the uncertainty in the cost-effectiveness case for lenalidomide in transfusion-dependent low- and intermediate-1-risk myelodysplastic syndrome (MDS) deletion 5q [del(5q)], affecting a small but unique subpopulation with an orphan disease.MethodsAs part of a submission to NICE, we developed a cost-effectiveness model for lenalidomide, resulting in eventual recommendation.ResultsDue to data limitations within the trial evidence available, the model was based on surrogate outcomes supported by a disease-wide literature review. The validity of modelled estimates for critical long-term outcomes in terms of time on treatment (32% reaching 26 cycles when the patient access scheme applied in the model vs. 28% in the real-world data) and survival was confirmed using real-world evidence (projected median survival for best supportive care of 4.3 years vs. real-world evidence showing median survival with low- and intermediate-1-risk MDS of 5.7 and 3.5 years, respectively).ConclusionThis case study demonstrates the usefulness and relevance of the application of real-world data when trial data are limited.Electronic supplementary materialThe online version of this article (10.1007/s41669-018-0110-3) contains supplementary material, which is available to authorized users.

PHP330 - REAL-WORLD DATA COLLECTION ON MEDICAL DEVICES IN THE ERA OF VALUE-BASED HEALTHCARE: A LITERATURE REVIEW

To analyze the role of real world evidence in Value Based Health Care of medical devices. A literature search (research string released on 2nd April, 2018) was performed on PubMed including the following as main keywords: medical devices, real-world data and value-based healthcare. No restrictions on language, year of publications, and type of reference were imputed. Fifty-eight papers were identified and scrutinized. 2 additional references were identified through other sources. 27 were included. The records were published between 2004 and 2018. Once plotted against the year of publication, an upward trend was visible starting from 1 (4%) publications in 2004 up to 4 (15%) in 2016 and 5 (19%) in 2018. 81% of the records reported evidence in cardiology and cardiac surgery area; 7% in neurology. Most data came from registries (63%) and administrative databases (33%). The sponsors were healthcare industry (4%), academia (93%), health authorities (4%). Value based healthcare has become a hot topic both for policy makers and for the medical devices industry. The constantly increasing production of real world evidence and analyses based on observational data, registry and administrative databases confirms the increasing interest in this research area. The clinical practice may substantially differ from controlled trials; the use of real world data not only completes the body of evidence on a specific therapy, but also may drive the updates of clinical guidelines. Both the technological progress and the production of real world evidence have become so fast that an adequate way to timely develop guidelines should be sought. Alongside, the use of real world evidence may play a relevant role when policy makers need to measure the value of a medical technology.