Use Of Real-world Evidence Research Articles

Mapping Canadian Data Assets to Generate Real-World Evidence: Lessons Learned from Canadian Real-World Evidence for Value of Cancer Drugs (CanREValue) Collaboration's RWE Data Working Group.

Canadian provinces routinely collect patient-level data for administrative purposes. These real-world data (RWD) can be used to generate real-world evidence (RWE) to inform clinical care and healthcare policy. The CanREValue Collaboration is developing a framework for the use of RWE in cancer drug funding decisions. A Data Working Group (WG) was established to identify data assets across Canada for generating RWE of oncology drugs. The mapping exercise was conducted using an iterative scan with informant surveys and teleconference. Data experts from ten provinces convened for a total of three teleconferences and two in-person meetings from March 2018 to September 2019. Following each meeting, surveys were developed and shared with the data experts which focused on identifying databases and data elements, as well as a feasibility assessment of conducting RWE studies using existing data elements and resources. Survey responses were compiled into an interim data report, which was used for public stakeholder consultation. The feedback from the public consultation was used to update the interim data report. We found that databases required to conduct real-world studies are often held by multiple different data custodians. Ninety-seven databases were identified across Canada. Provinces held on average 9 distinct databases (range: 8–11). An Essential RWD Table was compiled that contains data elements that are necessary, at a minimal, to conduct an RWE study. An Expanded RWD Table that contains a more comprehensive list of potentially relevant data elements was also compiled and the availabilities of these data elements were mapped. While most provinces have data on patient demographics (e.g., age, sex) and cancer-related variables (e.g., morphology, topography), the availability and linkability of data on cancer treatment, clinical characteristics (e.g., morphology and topography), and drug costs vary among provinces. Based on current resources, data availability, and access processes, data experts in most provinces noted that more than 12 months would be required to complete an RWE study. The CanREValue Collaboration’s Data WG identified key data holdings, access considerations, as well as gaps in oncology treatment-specific data. This data catalogue can be used to facilitate future oncology-specific RWE analyses across Canada.

Development and Pilot Test of the Registry Evaluation and Quality Standards Tool: An Information Technology–Based Tool to Support and Review Registries

ObjectivesHealth technology assessment (HTA) bodies are increasingly making use of real-world evidence and data. High-quality registries could be an asset for this; nevertheless, there is a lack of specified standards to assess the quality of data in the registry, or the registry itself. The European Network for Health Technology Assessment Joint Action 3 led the work to develop a tool for the evaluation of clinical registries: the “Registry Evaluation and Quality Standards Tool” (REQueST). MethodsREQueST was developed in 4 steps: (1) A partnership between HTA bodies across Europe drafted the assessment criteria. (2) Multiple rounds of consultation across HTA bodies and the public domain developed an Excel version of REQueST. (3) This version was transformed into a web-based application. (4) An external pilot tested this REQueST tool with SMArtCARE and NeuroTransData registries. ResultsHaute Autorité de Santé, the National Institute for Health and Care Excellence, and the Croatian Institute of Public Health led the development of REQueST. Another 4 HTA bodies contributed regularly to development meetings, and all European Network for Health Technology Assessment partners were invited to contribute. Eight methodological, 12 essential, and 3 supplementary criteria were identified. Both pilot registries scored well, fulfilling the requirements for >70% of criteria, with none failed. Feedback by registry holders led to streamlining of the process and clarification of the criteria. ConclusionsThe REQueST tool uses an iterative and collaborative methodology with registry holders. It has the potential to maximize the utility of registry data for decision making by regulatory and HTA bodies and provides a foundation for future research.

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.

Factors Affecting Citizen Trust and Public Engagement Relating to the Generation and Use of Real-World Evidence in Healthcare.

The potential for the use of real-world data (RWD) to generate real-world evidence (RWE) that can inform clinical decision-making and health policy is increasingly recognized, albeit with hesitancy in some circles. If used appropriately, the rapidly expanding wealth of health data could improve healthcare research, delivery of care, and patient outcomes. However, this depends on two key factors: (1) building structures that increase the confidence and willingness of European Union (EU) citizens to permit the collection and use of their data, and (2) development of EU health policy to support and shape data collection infrastructures, methodologies, transmission, and use. The great potential for use of RWE in healthcare improvement merits careful exploration of the drivers of, and challenges preventing, efficient RWD curation. Literature-based research was performed to identify relevant themes and discussion topics for two sets of expert panels, organized by the European Alliance for Personalised Medicine. These expert panels discussed steps that would enable a gradual but steady growth in the quantity, quality, and beneficial deployment of RWE. Participants were selected to provide insight based on their professional medical, economic, patient, industry, or governmental experience. Here, we propose a framework that addresses public trust and access to data, cross-border governance, alignment of evidence frameworks, and demonstrable improvements in healthcare decisions. We also discuss key case studies that support these recommendations, in accordance with the discussions at the expert panels.

POSB272 Use of Real-World Evidence for Reimbursement in Brazilian Public Sector: An Analysis of Submissions in Neurology and Rheumatology

Real world evidence (RWE) provides clinical insights and is also essential in the development of decision-analytic models to evaluate the cost-effectiveness of a technology. This information is often relevant for reimbursement decision-making. We aim to explore the current uses of RWE in the Brazilian public healthcare system for neurology and rheumatology areas, summarize key concerns raised by payers and identify opportunities for better use of RWE for coverage decisions.

POSA407 Perceptions of Clinicians on the Use of Real-World Evidence in Oncology: An EORTC Survey

Following the rise of precision medicine, real-world evidence (RWE) has been playing an increasingly important role in the development of anticancer therapies. Regulators, payers and health technology assessment agencies are more and more relying on RWE to inform and support their decision-making. However, it is unclear how cancer clinicians perceive this trend, and the value they attribute to such evidence has not been properly characterized before. The objective of this study is to gain insight into their views on the use of RWE in the field of oncology.

Digital Health Technologies for Medical Devices – Real World Evidence Collection – Challenges and Solutions Towards Clinical Evidence

The need for sufficient clinical evidence and the collection of real-world evidence (RWE) is at the forefront of medical device and drug regulations, however, the collection of clinical data can be a time consuming and costly process. The advancement of Digital Health Technologies (DHTs) is transforming the way health data can be collected, analysed, and shared, presenting an opportunity for the implementation of DHTs in clinical research to aid with obtaining clinical evidence, particularly RWE. DHTs can provide a more efficient and timely way of collecting numerous types of clinical data (e.g., physiological, and behavioural data) and can be beneficial with regards to participant recruitment, data management and cost reduction. Recent guidelines and regulations on the use of RWE within regulatory decision-making processes opens the door for the wider implementation of DHTs. However, challenges and concerns remain regarding the use of DHT (such as data security and privacy). Nevertheless, the implementation of DHT in clinical research presents a promising opportunity for providing meaningful and patient-centred data to aid with regulatory decisions.

"What's Keeping Me Up at Night?" Reflections on the COVID-19 Pandemic in Asia.

The 2021 Health Technology Assessment International (HTAi) Asia Policy Forum (APF) aimed to explore the challenges and opportunities presented by the global COVID-19 pandemic for health systems and industry in the Asia region, to discuss how HTA changed during the pandemic, and what its role may be moving forward into a postpandemic era. Discussions during the virtual 2021 APF, informed by a premeeting survey of HTA agencies and industry attendees from the region describing their experience during the pandemic, form the basis of this paper. During the pandemic, regulatory approval for COVID-related technologies was fast-tracked with fewer evidentiary requirements, and little or no HTA being conducted before these technologies were implemented in health systems in the region. "Living HTA" incorporating real-world evidence (RWE) as it was generated became part of the HTA landscape. In comparison, non-COVID technologies experienced regulatory approval and HTA delays. A major concern of APF members was future pandemic preparedness, and to ensure that lessons are learned from COVID-19. Governments need to continue to invest in innovation and allow early regulatory approvals with the increased use of RWE. Capacity building was identified as a key investment, including capacity in HTA, modeling, as well as local production of necessary supplies and equipment. Finally, collaboration at all levels of the health system was viewed as vital. Post-COVID, different forms of HTA must be embraced as part of the new HTA landscape in addition to increased intra- and intercountry collaboration across all sectors of the health system, including regulatory bodies.

Toward a better understanding about real-world evidence

BackgroundThere has been an interest in real-world evidence (RWE) in recent years. RWE is usually generated from data derived from routine healthcare, such as electronic healthcare records and disease registries....

PP205 The Use Of Real-World Evidence To Support National Institute For Health And Care Excellence Medical Technology Submissions

IntroductionAlthough randomized controlled trials (RCTs) are recognized as providing the highest level of clinical evidence, few medical device RCTs are available due to underfunding or inherent challenges associated with trial design. This study examines the extent to which real-world evidence (RWE) supports the recommendations made by the National Institute for Health and Care Excellence Medical Technologies Evaluation Programme (MTEP).MethodsAll MTEP guidance documents published online prior to October 2020 were reviewed. The “case for adoption” recommendation, type of clinical data, and clinical critiques for each MTEP submission were extracted and categorized. RWE was defined as studies with neither blinding nor prospective selection or control of patient characteristics.ResultsOf the MTEP submissions reviewed, 34 of 45 (76%) received a positive recommendation. Independent of outcome, all submissions included RWE, but only 19 (42%) utilized RCT evidence (15 were recommended and four were not). Meta-analyses of RWE were used whenever possible. The most common clinical critiques in unsuccessful submissions were the following: (i) not generalizable to the United Kingdom National Health Service (NHS); (ii) low quality; (iii) likelihood of bias; (iv) trial design faults; (v) uncertain benefit; and (vi) evidence unrelated to scope.ConclusionsThis study suggests that while the use of RCTs has not always led to a positive recommendation, RWE can be valuable in decision-making. Evidence that is generalizable to the NHS, is related to the scope, and shows clear indication of benefit is more likely to positively influence MTEP decision-making.

Real-World Anticoagulant Use and Incidence of Venous Thromboembolism and Major Bleeding in Children

Children generally have a lower risk of venous thromboembolism (VTE) than adults, but those with acute and chronic conditions requiring hospitalization and surgical procedures are at increased risk. Anticoagulant use in children has not been systematically studied, and limited data exist. This study aimed to provide data on the conditions associated with use of anticoagulants, the type of anticoagulant used in children, and the incidence of thromboembolism and major bleeding events reported in this population. To increase understanding of the use of anticoagulant therapies in children with at-risk conditions, 3 health claims databases in the United States were analyzed to describe the characteristics of use of heparins, warfarin, and direct oral anticoagulants (DOACs). Cumulative drug exposure was determined for continuous exposure, defined as >30 days. Unadjusted event rates of VTE and major bleeding after exposure to these therapies were reported. The data were presented descriptively and are not intended for comparison or to imply any causation. Anticoagulants were infrequently used in the pediatric population, including at any time point after Fontan surgery for congenital heart disease. Heparins were used most frequently in the population overall and especially for patients aged <12 years. DOACs were used least often and primarily for patients ages 12 to <18 years. Among pediatric patients exposed to anticoagulants, unadjusted incidence rates of VTE per 1000 person-years of exposure ranged from 30.8 to 34.0 for all DOACs, 21.6 to 46.2 for warfarin, and 6.0 to 7.3 for heparins. Rates per 1000 person-years for major bleeding ranged from 0 to 4.9 for all DOACs, 4.3 to 6.7 for warfarin, and 3.7 to 4.6 for heparins. With results from clinical trials evaluating DOACs in the pediatric population expected in the next 2 years, these descriptive real-world data may provide a baseline understanding of current prescribing patterns and outcomes associated with the use of DOACs and other anticoagulants in routine pediatric clinical practice. This information represents the use of real-world evidence and may function as the benchmark for evaluating changes in prescription practices and potential outcomes in the future.

OP188 Post-Launch Evidence Generation Studies For Medical Devices In Spain: Integrating Real World Evidence Into Decision-Making

IntroductionA national act (Order SSI/1356/2015) regulating Post-Launch Evidence Generation (PLEG) studies was set in Spain in 2015. These PLEG studies are to inform decisions about technologies already included in the Benefit Portfolio of the Spanish National Health System (SNHS) in order to confirm/exclude/modify their terms of use. Once a PLEG is established the selected hospitals provide the technology according to a common protocol and register outcomes until the required sample size is reached.MethodsThe PLEG studies are prospective, observational and single arm studies on safety, effectiveness and cost-effectiveness of a technology in real practice. The technology is selected because of the identification of an evidence gap, usually through a health technology assessment (HTA) report made by an agency of the Spanish Network of HTA Agencies (RedETS). The execution of a PLEG is assigned to one of the RedETS Agencies, which is responsible of delivering annual reports and a final report when the objectives are reached.ResultsThe following six PLEG studies, all of them on medical devices, have been launched in Spain so far, i) Endobronchial valve for patients with persistent air leak; ii) Biodegradable esophageal stent; iii) Percutaneous mitral valve repair system by clip; iv) Left Atrial Appendage Closure Device; v) Sensor-based glucose monitoring systems for children with type 1 diabetes mellitus; vi) Left ventricular assist devices for destination therapy. Five studies will finish their data collection by the end of 2020 or during 2021.ConclusionsA new national procedure using PLEG has been made available in Spain facilitating the use of real-world evidence to inform national decision-making on the financing of selected technologies due to uncertainties about their effectiveness, safety, cost-effectiveness and organizational impact. The studies are requiring a high amount of coordination tasks, as they are involving an average of 21 hospitals each. The usefulness and suitability of this procedure to achieve its objectives must be evaluated once their results are available.

Use of Real-World Evidence to Drive Drug Development Strategy and Inform Clinical Trial Design.

Interest in real‐world data (RWD) and real‐world evidence (RWE) to expedite and enrich the development of new biopharmaceutical products has proliferated in recent years, spurred by the 21st Century Cures Act in the United States and similar policy efforts in other countries, willingness by regulators to consider RWE in their decisions, demands from third‐party payers, and growing concerns about the limitations of traditional clinical trials. Although much of the recent literature on RWE has focused on potential regulatory uses (e.g., product approvals in oncology or rare diseases based on single‐arm trials with external control arms), this article reviews how biopharmaceutical companies can leverage RWE to inform internal decisions made throughout the product development process. Specifically, this article will review use of RWD to guide pipeline and portfolio strategy; use of novel sources of RWD to inform product development, use of RWD to inform clinical development, use of advanced analytics to harness “big” RWD, and considerations when using RWD to inform internal decisions. Topics discussed will include the use of molecular, clinicogenomic, medical imaging, radiomic, and patient‐derived xenograft data to augment traditional sources of RWE, the use of RWD to inform clinical trial eligibility criteria, enrich trial population based on predicted response, select endpoints, estimate sample size, understand disease progression, and enhance diversity of participants, the growing use of data tokenization and advanced analytical techniques based on artificial intelligence in RWE, as well as the importance of data quality and methodological transparency in RWE.

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.

How can real-world evidence aid decision making during the life cycle of nonprescription medicines?

Real‐world evidence (RWE) is an emerging scientific discipline which is being increasingly utilized for decision making on prescription‐only medicines. However, there has been little focus to date on the application of RWE within the nonprescription sector. This paper reviews the existing and potential applications of RWE for nonprescription medicines, using the nonprescription medicine life cycle as a framework for discussion. Relevant sources of real‐world data (RWD) are reviewed and compared with those available for prescribed medicines. Existing life‐cycle data gaps are identified where RWE is required or where use of RWE can complement data from randomized controlled trials. Published RWE examples relating to nonprescription medicines are summarized, and potential relevant future sources of RWD discussed. Challenges and limitations to the use of RWE on nonprescription medicines are discussed, and recommendations made to promote optimal and appropriate use of RWE in this sector. Overall, RWE currently plays a key role in specific phases of the nonprescription medicine life cycle, including reclassification and postmarketing safety surveillance. The increasing availability of patient‐generated health data is likely to further increase the utilization of RWE to aid decision making on nonprescription medicines.

Marketing Authorization Applications Made to the European Medicines Agency in 2018-2019: What was the Contribution of Real-World Evidence?

Information derived from routinely collected real‐world data has for a long time been used to support regulatory decision making on the safety of drugs and has more recently been used to support marketing authorization submissions to regulators. There is a lack of detailed information on the use and types of this real‐world evidence (RWE) as submitted to regulators. We used resources held by the European Medicines Agency (EMA) to describe the characteristics of RWE included in new marketing authorization applications (MAAs) and extensions of indication (EOIs) for already authorized products submitted to the EMA in 2018 and 2019. For MAAs, 63 of 158 products (39.9%) contained RWE with a total of 117 studies. For 31.7% of these products, the RWE submitted was derived from data collected before the planned authorization. The most common data sources were registries (60.3%) followed by hospital data (31.7%). RWE was mainly included to support safety (87.3%) and efficacy (49.2%) with cohort studies being the most frequently used study design (88.9%). For EOIs, 28 of 153 products (18.3%) contained RWE with a total of 36 studies. For 57.1% of these products, studies were conducted prior to the EOIs. RWE sources were mainly registries (35.6%) and hospital data (27.0%). RWE was typically used to support safety (82.1%) and efficacy (53.6%). Cohort studies were the most commonly used study design (87.6%). We conclude that there is widespread use of RWE to support evaluation of MAAs and EOIs submitted to the EMA and identify areas where further research is required.

Science, Innovation, and Society in the Age of Pandemics: Reflections From the Inaugural Sir Alasdair Breckenridge Lecture.

Science, Innovation, and Society in the Age of Pandemics: Reflections From the Inaugural Sir Alasdair Breckenridge Lecture.

A review on generation of real-world evidence

Real-world evidence can generate credible evidence to inform treatment decisions. Real-world evidence is in developmental stage and is fast evolving yet there are many unexplained attributes of real-world evidence. Real-world evidence informs benefit-risk decisions and is increasingly being used to support regulatory decision making. Potential benefits of real-world data include determination of extended outcomes including long-term outcomes, opportunities to partner with patients in innovative ways, and reduction in time and cost to generate dependable evidence. Limitations of real-world evidence include uncertainty in the quality of datasets and lack methodologic rigor in real-world studies. Use of real-world evidence for healthcare practices and policies is limited. Ensuring completeness, homogeneity, and linkage of datasets can enhance utility for epidemiological investigations and improvement in health outcomes. Research should be strengthened for real-world studies and technical standards should be reinforced. Collaborations of stakeholders is key to formulation and adoption of guidance for real-world evidence. Real-world data cannot be a substitute to randomized clinical studies but can possibly augment the generated evidence.

Use of real-world evidence in translational pharmacology research.

Real-world evidence (RWE) refers to observational data gathered outside the formalism of randomized controlled trials, in real life situations, on marketed drugs. While clinical trials are the gold standards to demonstrate the efficacy and tolerability of a medicinal product, the generalizability of their results to actual use in real-life is limited by the biases induced by the very nature of clinical trials; indeed, the patients included in the trials may differ from actual users because of their concomitant diseases or treatments, or other factors excluding them from the trials. Clinical researchers and pharmaceutical industries have hence become increasingly interested in expanding and integrating RWE into clinical research, by capitalizing on the exponential growth in access to data from electronic health records, claims databases, electronic devices, software or mobile applications, registries embedded in clinical practice and social media. Meanwhile, applications of RWE may also be used for drug discovery and repurposing, for clinical developments and post-marketing studies. The aim of this review is to provide our opinion regarding the use of RWE in translational research, including non-clinical and clinical pharmacology research, at the different step of drugs development use.

Use of RWE to Inform Regulatory, Public Health Policy, and Intervention Priorities for the Developing World.

For low‐ and middle‐income countries (LMICs) to benefit from real‐world evidence (RWE)/real‐world data (RWD) in both product registration (“regulatory”) decision making and in product utilization policy (“policy”) decision making, they need to overcome several challenges. They need to deploy more electronic health records systems (EHRs), adjust for confounder variables, build trust between stakeholders, and create laws and regulations for local generation of data that are assented for secondary use. The role of procurers and their use of RWE/RWD in the LMIC context likewise is in a state of ongoing development. Procurers of health products are strong players currently in the “access” chain as LMICs continue to work on strengthening governmental health technology assessment (HTA) bodies. Procurers’ use of RWE is presently at an early stage and is mostly indirect, leveraging RWE results that are produced by researchers in high‐income countries (HICs), often under considerably different regulatory and policy objectives and constraints compared to LMICs’ epidemiology and priorities. Pending wider deployment of EHRs and other RWE sources, stakeholders must realize that populations from HIC RWE (i) can be devised to closely resemble phenotypic patterns in LMIC populations and (ii) can be analyzed to align with LMICs’ unmet needs.