Use Of Real-world Evidence Research Articles

PCN276 - MANAGED ACCESS AGREEMENTS UNDER THE CANCER DRUGS FUND (CDF): KEY METRICS AND DRIVERS

Since July 2016, the U.K.’s Cancer Drugs Fund (CDF) has been an avenue for the provisional reimbursement of drugs which do not demonstrate sufficiently robust evidence for a routine NICE guidance recommendation. 16% of current and prior CDF drugs have entered into a Managed Access Agreement (MAA), providing the metrics and drivers that will outline evidence collection, and potentially lead to baseline NHS commissioning for these therapies. Our research examined how the MAAs are structured, the key uncertainties which compel their use and what metrics drive the data collection. Sixteen MAAs across 10 indications, published between October 2016 and June 2018, were identified in the Context Matters data model. Estimated time for data collection; primary and secondary sources of data requested; Systematic Anti-Cancer Therapy Dataset (SACT) and Blueteq utilization rates; and the uncertainty drivers were analyzed. The average timeframe allotted for data collection was 25 months (median=24 months). All MAAs included patient eligibility requirements which were more stringent than the EMA label. The main uncertainty category was clinical efficacy (88%); followed by concerns over the applicability of trial results to the U.K. population (50%); concerns over clinical trial design (38%); and requiring subgroup analyses (19%). 63% of drugs with MAAs had more than one category of uncertainty driving the MAA. The majority of MAAs were awaiting ongoing phase III clinical trial results (69%). All MAAs specified the use of SACT data, and the majority indicated the use of Blueteq (75%). Only two MAAs outlined the anticipated use of Real World Evidence (RWE). MAAs allow therapies to access the CDF, which in turn, offers patients access to life-saving drugs. Pharmaceutical companies may rely on the commonalities among the drivers and metrics of these agreements to inform strategy in the future submission of oncology drugs.

Use of Real-world Evidence to Evaluate the Effectiveness of Herpes Zoster Vaccine.

This article reviews the use of real-world evidence (RWE) from observational studies to evaluate herpes zoster vaccine effectiveness and complement clinical trial data that have known limitations. The use of RWE with appropriate study designs and cautious interpretation can be informative in decision-making. Understanding the advantages and limitations of studies yielding RWE can facilitate the critical evaluation of findings from different studies. This is a timely issue, as regulatory agencies are considering how RWE can contribute to the assessment of effectiveness in regulatory decision-making.

PCP3 - Navigating the use of Real-World Evidence in Effectiveness Research and Patient Access Decisions

Reimbursement and patient access decisions for new medicines should be guided by relevant and good-quality evidence. Randomised controlled trial (RCT) data are used to support these decisions, however real-world evidence (RWE) could be considered too, especially in cases of accelerated regulatory access where RCT data is less mature, in orphan disease areas where randomised trials are difficult to conduct, or where RCTs do not reflect the patients or clinical practice outside of the trial setting. Stakeholders have different views of the acceptability of using RWE, therefore the GetReal Initiative’s (www.imi-getreal.eu) key aims are to educate and stimulate discussion on the appropriate use of RWE in medicines decision making. The Initiative has developed the "RWE Navigator" (rwe-navigator.eu) which explains key evidence challenges in relative effectiveness research and indicates potential uses for non-randomised evidence, accompanied by overviews of data sources, study designs, quality assessment and bias adjustment of RWE. The navigator also provides links to case studies that demonstrate the potential application of RWE to support regulatory and patient access decisions. It will continue to serve as a gateway to the ongoing work of the GetReal Initiative. The work of the GetReal Initiative indicates that further dialogue is needed to develop policies and perspectives on RWE. The RWE Navigator has been developed to stimulate and inform the debate on the use of RWE in effectiveness research, and it has created a platform for a dialogue between industry and decision-makers. It is a unique source of information on alternative study designs and analytical methods, informed by key decision makers’ views on the acceptability and usefulness of RWE, to inform health technology assessments andpatient access decisions in Asia and elsewhere.

The inclusion of real world evidence in clinical development planning

BackgroundWhen designing studies it is common to search the literature to investigate variability estimates to use in sample size calculations. Proprietary data of previously designed trials in a particular indication are also used to obtain estimates of variability. Estimates of treatment effects are typically obtained from randomised controlled clinical trials (RCTs). Based on the observed estimates of treatment effect, variability and the minimum clinical relevant difference to detect, the sample size for a subsequent trial is estimated. However, data from real world evidence (RWE) studies, such as observational studies and other interventional studies in patients in routine clinical practice, are not widely used in a systematic manner when designing studies. In this paper, we propose a framework for inclusion of RWE in planning of a clinical development programme.MethodsIn our proposed approach, all evidence, from both RCTs and RWE (i.e. from studies in routine clinical practice), available at the time of designing of a new clinical trial is combined in a Bayesian network meta-analysis (NMA). The results can be used to inform the design of the next clinical trial in the programme. The NMA was performed at key milestones, such as at the end of the phase II trial and prior to the design of key phase III studies. To illustrate the methods, we designed an alternative clinical development programme in multiple sclerosis using RWE through clinical trial simulations.ResultsInclusion of RWE in the NMA and the resulting trial simulations demonstrated that 284 patients per arm were needed to achieve 90% power to detect effects of predetermined size in the TRANSFORMS study. For the FREEDOMS and FREEDOMS II clinical trials, 189 patients per arm were required. Overall there was a reduction in sample size of at least 40% across the three phase III studies, which translated to a time savings of at least 6 months for the undertaking of the fingolimod phase III programme.ConclusionThe use of RWE resulted in a reduced sample size of the pivotal phase III studies, which led to substantial time savings compared to the approach of sample size calculations without RWE.

Real world evidence (RWE) - a disruptive innovation or the quiet evolution of medical evidence generation?

Stakeholders in healthcare are increasingly turning to real world evidence (RWE) to inform their decisions, alongside evidence from randomized controlled trials. RWE is generated by analysing data gathered from routine clinical practice, and can be used across the product lifecycle, providing insights into areas including disease epidemiology, treatment effectiveness and safety, and health economic value and impact. Recently, the US Food and Drug Administration and the European Medicines Agency have stated their ambition for greater use of RWE to support applications for new indications, and are now consulting with their stakeholders to formalize standards and expected methods for generating RWE. Pharmaceutical companies are responding to the increasing demands for RWE by developing standards and processes for each stage of the evidence generation pathway. Some conventions are already in place for assuring quality, whereas other processes are specific to the research question and data sources available. As evidence generation increasingly becomes a core role of medical affairs divisions in large pharmaceutical companies, standards of rigour will continue to evolve and improve. Senior pharmaceutical leaders can drive this change by making RWE a core element of their corporate strategy, providing top-level direction on how their respective companies should approach RWE for maximum quality. Here, we describe the current and future areas of RWE application within the pharmaceutical industry, necessary access to data to generate RWE, and the challenges in communicating RWE. Supporting and building on viewpoints from industry and publicly funded research, our perspective is that at each stage of RWE generation, quality will be critical to the impact that RWE has on healthcare decision-makers; not only where RWE is an established and evolving tool, but also in new areas that have the potential to disrupt and to improve drug development pathways.

Advancing Drug Safety Through Prospective Pharmacovigilance

Much has changed in a relatively short period of time. There is a raging debate over the level of evidence expected to first introduce a treatment to patients based on smaller, more adaptive data sets. Some argue for less data followed by postapproval follow-up, others for more adaptive clinical trial designs and end-point modification driven by patient-focused drug development and use of real-world evidence. The transition in both the review and postmarketing regulatory framework is happening in front of our eyes in real time. To improve the ability of patients to receive high-quality, safe, effective, and timely care, better information via pharmacovigilance must be a priority as the world's many regulatory systems build the capacity to harness electronic health information to improve health, care quality, and safety. Globally, the widely variable ability of nations to build reliable regulatory systems (from precise review to robust pharmacovigilance) is a dangerous source of health care inequality. Developing validated tools and techniques for "predictive pharmacovigilance" will assist all health systems in better understanding the risks and benefits of the medicines they regulate by understanding what should be happening once a new medicine moves from risk-benefit regulatory efficacy to real-world risk-effectiveness. This will be of particular utility for smaller regulatory agencies with fewer resources. By comparing preapproval predictive pharmacovigilance data, developing regulatory authorities will be able to better understand the potential gap between what was predicted and what was actually measured (via more traditional pharmacovigilance methodologies). Predictive pharmacovigilance recognizes the value of understanding the imperfect reporting of real-world clinical use and that the absence of reporting is, in itself, an important postmarketing signal.

Real-world evidence of the effectiveness of adjuvant chemotherapy for early stage breast cancer from Scottish routine data.

e12558Background: Real world evidence (RWE) has been proposed as a means to address the ‘efficacy-effectiveness gap’ in evidence-based oncology. A major barrier to use of RWE is the perceived lack ...

PRM124 - How is Real World Data Currently Used by Industry Professionals?

Randomized controlled trials may not provide enough information to resolve payer uncertainty around the benefit of an intervention in clinical practice and therefore the requirement for real-world evidence (RWE) to support healthcare decision making is growing. The objective of this survey was to understand pharmaceutical industry professionals’ views on the importance of and current use of RWE within their organisation. An electronic web-based survey was conducted at the 20th Annual European Congress of the International Society for Pharmacoeconomics and Outcomes Research (ISPOR) in November 2017. Industry professionals visiting the exhibit stand of the author organisation, a specialist RWE consultancy, were invited to complete a descriptive survey. A charity donation was offered for each completion. Data were anonymised, aggregated and reported following the conference. Twenty-three participants completed the survey with most (70%) employed by large or medium sized pharmaceutical companies. Almost two-thirds (61%) commissioned multi-country rather than single-country RWE studies to meet their evidence requirements. The most commonly reported markets requiring RWE studies included Europe (70%), America (30%) and the Nordic countries (22%). Participants reported the most important areas for using RWE to support brand value messages as: ‘the identification of unmet need’ (78%), ‘patient reported quality of life data’ (78%) and the ‘impact on healthcare resource utilisation’ (78%). Almost two thirds (65%) of participants stated that the use of RWE has changed the reimbursement of one or more of their brands. The results of this exploratory survey suggest that industry professionals recognise RWE as important in supporting brand value messages and report a direct positive impact of RWE on product reimbursement status. RWE should be considered as a key component of a product’s value proposition.

PCN229 - Use Of Real-World Evidence In Clinical Decision Making By Community Oncologists

PCN229 - Use Of Real-World Evidence In Clinical Decision Making By Community Oncologists

Practice-Based Research Networks and the Mandate for Real-World Evidence.

The 21st Century Cures Act encourages the Food and Drug Administration to consider "real-world evidence" in its regulation of the safety and efficacy of drugs and devices. Many have interpreted this mandate to focus on non-randomized observational research. However, we suggest that regulatory science must also move from rarefied academic hospitals to community-based settings, where the vast majority of patients in fact receive care in the fragmented U.S. healthcare system. This move is especially important if innovations are to reach, and be validated in, more diverse populations. A solution can be found in the 183 Practiced-Based Research Networks ("PBRN"), i.e., groups of primary care clinicians and practices in all 50 states working to improve clinical care and translate research findings into practice. This symposium contribution seeks to (1) describe some of the common shortcomings of clinical trials, (2) explore the opportunities and challenges posed by use of real-world evidence as a basis for drug and device regulation, (3) briefly describe the history and evolution of PBRNs, and (4) articulate the challenges and opportunities for using PBRNs to fulfill the 21st Century Cures Act mandate for real-world evidence.

Real-World Evidence for Regulatory Decisions: Concomitant Administration of Zoster Vaccine Live and Pneumococcal Polysaccharide Vaccine.

The US Food and Drug Administration is charged with expanding the use of real-world evidence for regulatory decisions. As a test case for real-world evidence to support regulatory decisions, we present the scenario of concomitant vaccination with zoster vaccine live (ZVL) and 23-valent pneumococcal polysaccharide vaccine (PPSV23). The prescribing information states that these vaccines should not be given concurrently, based on a small trial using varicella zoster virus antibody levels as a correlate of ZVL efficacy, even though ZVL protects against herpes zoster via cell-mediated immunity. We conducted an observational cohort study involving more than 35,000 members of Kaiser Permanente Southern California receiving concomitant ZVL and PPSV23 versus PPSV23 prior to ZVL. Occurrence of herpes zoster was assessed through electronic health records from January 1, 2007, to June 30, 2016. The adjusted hazard ratio comparing incidence rates of herpes zoster in the concomitant vaccination cohort and the prior vaccination cohort was 1.04 (95% confidence interval: 0.92, 1.16). This real-world evidence study provides direct evidence for a lack of vaccine interference, relying on herpes zoster occurrence rather than an intermediate marker of immunity. Real-world evidence is essential for regulators and policy makers in addressing evidentiary gaps regarding safety, effectiveness, compliance, and vaccine interactions for the new recombinant zoster vaccine.

Leveraging Real-World Evidence Derived from Patient Registries for Premarket Medical Device Regulatory Decision-Making

ABSTRACTIn this era of “Big Data,” there are many sources of real-world healthcare data that could be leveraged in clinical research in the regulatory environment. While such large quantities of data reflect real-world clinical practice and may potentially be used to reduce the cost or time of conducting clinical research, challenges arise concerning using real-world evidence derived from real-world data to inform or support premarket regulatory decision-making for medical devices. This article discusses such opportunities and challenges from statistical and regulatory perspectives with an emphasis on the use of real-world evidence derived from high-quality national and international patient registries.

443 - Use of Real-World Evidence to Characterize Clinical Outcomes in Patients Who Develop Acute Graft Versus Host Disease Undergoing Allogeneic Stem Cell Transplantation in the United States

443 - Use of Real-World Evidence to Characterize Clinical Outcomes in Patients Who Develop Acute Graft Versus Host Disease Undergoing Allogeneic Stem Cell Transplantation in the United States

Real world evidence (RWE) – a disruptive innovation or the quiet evolution of medical evidence generation?

Stakeholders in healthcare are increasingly turning to real world evidence (RWE) to inform their decisions, alongside evidence from randomized controlled trials. RWE is generated by analysing data gathered from routine clinical practice, and can be used across the product lifecycle, providing insights into areas including disease epidemiology, treatment effectiveness and safety, and health economic value and impact. Recently, the US Food and Drug Administration and the European Medicines Agency have stated their ambition for greater use of RWE to support applications for new indications, and are now consulting with their stakeholders to formalize standards and expected methods for generating RWE. Pharmaceutical companies are responding to the increasing demands for RWE by developing standards and processes for each stage of the evidence generation pathway. Some conventions are already in place for assuring quality, whereas other processes are specific to the research question and data sources available. As evidence generation increasingly becomes a core role of medical affairs divisions in large pharmaceutical companies, standards of rigour will continue to evolve and improve. Senior pharmaceutical leaders can drive this change by making RWE a core element of their corporate strategy, providing top-level direction on how their respective companies should approach RWE for maximum quality. Here, we describe the current and future areas of RWE application within the pharmaceutical industry, necessary access to data to generate RWE, and the challenges in communicating RWE. Supporting and building on viewpoints from industry and publicly funded research, our perspective is that at each stage of RWE generation, quality will be critical to the impact that RWE has on healthcare decision-makers; not only where RWE is an established and evolving tool, but also in new areas that have the potential to disrupt and to improve drug development pathways.

Real world evidence (RWE) - a disruptive innovation or the quiet evolution of medical evidence generation?

Stakeholders in healthcare are increasingly turning to real world evidence (RWE) to inform their decisions, alongside evidence from randomized controlled trials. RWE is generated by analysing data gathered from routine clinical practice, and can be used across the product lifecycle, providing insights into areas including disease epidemiology, treatment effectiveness and safety, and health economic value and impact. Recently, the US Food and Drug Administration and the European Medicines Agency have stated their ambition for greater use of RWE to support applications for new indications, and are now consulting with their stakeholders to formalize standards and expected methods for generating RWE. Pharmaceutical companies are responding to the increasing demands for RWE by developing standards and processes for each stage of the evidence generation pathway. Some conventions are already in place for assuring quality, whereas other processes are specific to the research question and data sources available. As evidence generation increasingly becomes a core role of medical affairs divisions in large pharmaceutical companies, standards of rigour will continue to evolve and improve. Senior pharmaceutical leaders can drive this change by making RWE a core element of their corporate strategy, providing top-level direction on how their respective companies should approach RWE for maximum quality. Here, we describe the current and future areas of RWE application within the pharmaceutical industry, necessary access to data to generate RWE, and the challenges in communicating RWE. Supporting and building on viewpoints from industry and publicly funded research, our perspective is that at each stage of RWE generation, quality will be critical to the impact that RWE has on healthcare decision-makers; not only where RWE is an established and evolving tool, but also in new areas that have the potential to disrupt and to improve drug development pathways.

OP03 Optimizing The Use Of RWE In HTA: Lessons From The ICER Summit

Introduction:Real world evidence (RWE) is changing the overall data landscape and it has potential to advance the evaluation of real world performance (comparative effectiveness) of healthcare technologies by providing a greater quantity and quality of evidence. However, many are concerned that non-randomized RWE may be substituted for RCT data and thus increase uncertainty about effectiveness. This presentation sets out the opportunities and challenges for use of RWE by payers and HTA bodies to evaluate health care technologies.Methods:Current uses, opportunities and challenges were identified via a literature review and interviews with nine experts. Interim results were discussed at the 2017 ICER Policy Summit, which brought together leaders from payer and life sciences organizations, to develop specific and actionable recommendations for the use of RWE in drug coverage and policy decision-making.Results:RWE is utilized for multiple purposes in the US and globally, including: aiding design of drug development pathways; supporting regulatory approval decisions; monitoring safety; and informing HTA assessments and payer coverage decisions. Some stakeholders see great value in RWE and want to make greater use of these data sources, including for: drug effectiveness evaluations (including supplementing network meta-analyses); innovative study designs (including pragmatic trials); real time patient monitoring; and adaptive pathways or coverage with evidence development. However, others see numerous challenges, many of which are related to the quality and reliability of RWE sources. Acceptance of an expanded future role for RWE is not universal, and payers and developers must work together to find mutually beneficial strategies for progressing the development and use of RWE.Conclusions:Specific and actionable recommendations will be presented which highlight the role that each stakeholder group can play in overcoming the challenges and realizing the potential for RWE.

Good Practices for Real-World Data Studies of Treatment and/or Comparative Effectiveness: Recommendations from the Joint ISPOR-ISPE Special Task Force on Real-World Evidence in Health Care Decision Making.

Real-world evidence (RWE) includes data from retrospective or prospective observational studies and observational registries and provides insights beyond those addressed by randomized controlled trials. RWE studies aim to improve health care decision making. The International Society for Pharmacoeconomics and Outcomes Research (ISPOR) and the International Society for Pharmacoepidemiology (ISPE) created a task force to make recommendations regarding good procedural practices that would enhance decision makers' confidence in evidence derived from RWD studies. Peer review by ISPOR/ISPE members and task force participants provided a consensus-building iterative process for the topics and framing of recommendations. The ISPOR/ISPE Task Force recommendations cover seven topics such as study registration, replicability, and stakeholder involvement in RWE studies. These recommendations, in concert with earlier recommendations about study methodology, provide a trustworthy foundation for the expanded use of RWE in health care decision making. The focus of these recommendations is good procedural practices for studies that test a specific hypothesis in a specific population. We recognize that some of the recommendations in this report may not be widely adopted without appropriate incentives from decision makers, journal editors, and other key stakeholders.

Practical implications of using real-world evidence (RWE) in comparative effectiveness research: learnings from IMI-GetReal.

In light of increasing attention towards the use of real-world evidence (RWE) in decision making in recent years, this commentary aims to reflect on the experiences gained in accessing and using RWE for comparative effectiveness research as a part of the Innovative Medicines Initiative GetReal Consortium and discuss their implications for RWE use in decision-making.

How can real-world evidence be used in practice to demonstrate drug value and improve patient care?

Evidence Europe 2017, Victoria Park Plaza, London, UK, 22-23 February 2017 The Evidence Europe 2017 meeting took place in February 2017 in London (UK). This year's event focused on the use of real-world evidence in practice, both before and after a product has been approved. Speakers and attendees represented a broad spread of stakeholders, including national bodies, industry and academia. The event involved expert presentations, lively panel discussions and networking opportunities, allowing everyone involved to improve their knowledge of how real-world evidence is being used and potential opportunities for the future.

PRIORITIES FOR HEALTH ECONOMIC METHODOLOGICAL RESEARCH: RESULTS OF AN EXPERT CONSULTATION.

The importance of economic evaluation in decision making is growing with increasing budgetary pressures on health systems. Diverse economic evidence is available for a range of interventions across national contexts within Europe, but little attention has been given to identifying evidence gaps that, if filled, could contribute to more efficient allocation of resources. One objective of the Research Agenda for Health Economic Evaluation project is to determine the most important methodological evidence gaps for the ten highest burden conditions in the European Union (EU), and to suggest ways of filling these gaps. The highest burden conditions in the EU by Disability Adjusted Life Years were determined using the Global Burden of Disease study. Clinical interventions were identified for each condition based on published guidelines, and economic evaluations indexed in MEDLINE were mapped to each intervention. A panel of public health and health economics experts discussed the evidence during a workshop and identified evidence gaps. The literature analysis contributed to identifying cross-cutting methodological and technical issues, which were considered by the expert panel to derive methodological research priorities. The panel suggests a research agenda for health economics which incorporates the use of real-world evidence in the assessment of new and existing interventions; increased understanding of cost-effectiveness according to patient characteristics beyond the "-omics" approach to inform both investment and disinvestment decisions; methods for assessment of complex interventions; improved cross-talk between economic evaluations from health and other sectors; early health technology assessment; and standardized, transferable approaches to economic modeling.