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Objectives To enhance the generalizability of the evidence it reviews, the US Food and Drug Administration (FDA) has encouraged manufacturers to expand the submission of real-world evidence (RWE). The extent to which this evidence, which is generated outside of research settings, can support decision making remains unclear. We described the current use of RWE for medical devices, assessed manufacturers’ challenges in generating and using it for regulatory and coverage decisions, and identified opportunities to expand its use. Methods We conducted 27 solo and group interviews with FDA officials and representatives of device manufacturers, payers, and health technology assessment organizations. All interviews used a semistructured protocol and were transcribed to allow thematic analysis. Results Accessing and linking real-world data sources, identifying unique devices, capturing longitudinal data, limited staff expertise, and uncertain return on investment have hampered efforts to use real-world data. Many companies in our sample were conducting research using real-world data, but none had submitted RWE as the primary evidence supporting a premarket approval. FDA guidance was helpful, but regulatory requirements remained ambiguous and examples of successful regulatory decisions based on RWE were limited. Payers mainly used RWE to supplement experimental evidence in coverage decisions, evaluated both types of evidence in similar ways, and had concerns about the rigor of RWE. Conclusions Technical challenges may slow efforts to generate and use RWE in the near term. Additional regulatory guidance and examples, greater use of rigorous study designs and analytic methods, and continued stakeholder engagement could accelerate the use of RWE.

Background: African Americans in the United States have worse end-of-life care and cancer outcomes than whites. Palliative care may improve this disparity. Community Health Workers may provide a means to improve palliative care disparities. Methods: Semistructured in-depth interviews (five) and stakeholder focus groups (four) were conducted with cancer patients, caregivers, health care administrators, oncologists, and community health workers (CHWs). Patients were recruited through snowball sampling. Three raters coded interviews independently. Data were analyzed using interpretative phenomenological analysis. Results: Seventy-one individuals were contacted to participate with 24 stakeholders (34%) participating in individual interviews or across 4 stakeholder engagements. Eleven constructs were identified and grouped in three broader themes: “hub of the wheel,” understanding palliative care, and patient–provider relationships. Participants felt that the role of a CHW should be central, bridging patients with their providers, information, and resources, including psychosocial support and advance care planning documents. They also placed an emphasis on the background of CHWs, saying individuals selected should be familiar with the history, culture, and norms of the communities from which they operate. Stakeholders reported that a CHW could activate a patient to contact their primary care physician or oncologist who may refer to or provide palliative care. Stakeholders reported that given the barriers to palliative care, a CHW could contribute to patient-centered multidisciplinary care while addressing palliative care domains with patients and families in a culturally sensitive manner. Conclusion: Based on feedback from patients, caregivers, and providers, a culturally adapted CHW intervention may improve palliative care use for African American patients with advanced malignancies.

The World Trade Center Health Program (WTCHP) has a research mission to identify physical and mental health conditions that may be related to the 9/11 terrorist attacks as well as effective diagnostic procedures and treatments for WTC-related health conditions. The ability of the WTCHP to serve its members and realize positive impacts on all of its stakeholders depends on effective translation of research findings. As part of an ongoing assessment of the translational impact of World Trade Center (WTC)-related research, we applied the National Institute of Environmental Health Sciences (NIEHS) translational framework to two case studies: WTC-related research on post-traumatic stress disorder (PTSD) and cancer. We conducted a review of 9/11 health-related research in the peer-reviewed literature through October 2017, grey literature, and WTCHP program documentation. We mapped peer-reviewed studies in the literature to the NIEHS framework and used WTCHP program documentation and grey literature to find evidence of translation of research into clinical practice and policy. Using the NIEHS framework, we identified numerous translational milestones and bridges, as well as areas of opportunity, within each case study. This application demonstrates the utility of the NIEHS framework for documenting progress toward public health impact and for setting future research goals.

IntroductionStakeholder engagement can play an important role in increasing public trust and the understanding of scientific research and its impact. Frameworks for stakeholder identification exist, but these frameworks may not apply well to basic science and early stage translational research.MethodsFour Clinical and Translational Science Award (CTSA) hubs led six focus groups and two semi-structured interviews using a semi-structured discussion guide to learn from basic science researchers about stakeholder engagement in their work. The 24 participants represented fourteen clinical and academic disciplines.ResultsEarly stage translational researchers reported engagement with a broad array of stakeholders. Those whose research has a clinical focus reported working with a more diverse range of stakeholders than those whose work did not. Common barriers to stakeholder engagement were grouped into three major themes: a poor definition of concepts, absence of guidance, and limited resources.DiscussionThe National Center for Advancing Translational Sciences (NCATS), the consortium of CTSAs, and the individual CTSA "hubs" are three actors that can help early stage translational researchers develop shared terms of reference, build the necessary skills, and assemble the appropriate resources for engaging stakeholders in Clinical and Translational Research. Getting this right will involve a coordinated push by all three entities.

With the increase in patient and consumer activism through the late twentieth century and into this century, patient roles in research evolved into a new model of research engagement, with patients serving as active advisors and co-leading or leading clinical research. By requiring active engagement of patients and other stakeholders, several government research funders have advanced this model, particularly in Canada, the United States (US), United Kingdom (UK), and Australia. A consortium of individuals from these countries formed a Multi-Stakeholder Engagement (MuSE) consortium to examine critical issues in engaged research, establish consensus on definitions, and provide guidance for the field, beginning with an overview of how to involve stakeholders in health research (Concannon et al. J Gen Intern Med. 2019;34(3):458-463) and continuing here with an examination of definitions of research engagement. The political and advocacy roots of engaged research are reflected in definitions. Engagement is conceptualized with reference to research project goals, from informing specific clinical decisions to informing health-system level decisions. Political and cultural differences across countries are evident. Some of these government funders focus on empirical rather than ethical rationales. In countries with centralized health technology assessment, the link between societal values and engaged research is explicit. Ethical rationales for engagement are explicit in most of the published literature on research engagement. Harmonization of definitions is recommended so that research engagement elements, methods, and outcomes and impacts can be clearly examined and understood, and so that the field of research engagement can proceed from a clear conceptual foundation. Specific recommendations for terminology definitions are provided. Placing engaged research on a continuum from specific clinical decisions to more global public and social justice concerns clarifies the type of engaged research, supports appropriate comparisons, and improves the rigor of engaged research methods. The results help identify knowledge gaps in this growing field. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s11606-019-05436-2) contains supplementary material, which is available to authorized users.

Emerging health care research paradigms such as comparative effectiveness research (CER), patient-centered outcome research (PCOR), and precision medicine (PM) share one ultimate goal: constructing evidence to provide the right treatment to the right patient at the right time. We argue that to succeed at this goal, it is crucial to have both timely access to individual-level data and fine geographic granularity in the data. Existing data will continue to be an important resource for observational studies as new data sources are developed. We examined widely used publicly funded health databases and population-based survey systems and found four ways they could be improved to better support the new research paradigms: (1) finer and more consistent geographic granularity, (2) more complete geographic coverage of the US population, (3) shorter time from data collection to data release, and (4) improved environments for restricted data access. We believe that existing data sources, if utilized optimally, and newly developed data infrastructures will both play a key role in expanding our insight into what treatments, at what time, work for each patient.

Stakeholder engagement is increasingly common in health research, with protocols for engaging multiple stakeholder groups becoming normative in patient-centered outcomes research. Previous work has focused on identifying relevant stakeholder groups with whom to work and on working with stakeholders in evidence implementation. This paper draws on the expertise of a team from four countries—Canada, Australia, the UK, and the USA—to provide researchers with practical guidance for carrying out multi-stakeholder–engaged projects: we present a list of questions to assist in selecting appropriate roles and modes of engagement; we introduce a matrix to help summarize engagement activities; and we provide a list of online resources. This guidance, matrix, and list of resources can assist researchers to consider more systematically which stakeholder groups to involve, in what study roles, and by what modes of engagement. By documenting how stakeholders are paired up with specific roles, the matrix also provides a potential structure for evaluating the impact of stakeholder engagement. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s11606-018-4738-6) contains supplementary material, which is available to authorized users.

To investigate the relationship between the framing of survival gains and the perceived value of cancer care.Through a population-based survey of 2040 US adults, respondents were randomized to one of the two sets of hypothetical scenarios, each of which described the survival benefit for a new treatment as either an increase in median survival time (median survival), or an increase in the probability of survival for a given length of time (landmark survival). Each respondent was presented with two randomly selected scenarios with different prognosis and survival improvements, and asked about their willingness to pay (WTP) for the new treatments.Predicted WTP increased with survival benefits and respondents' income, regardless of how survival benefits were described. Framing therapeutic benefits as improvements in landmark rather than median time survival increased the proportion of the population willing to pay for that gain by 11-35%, and the mean WTP amount by 42-72% in the scenarios we compared.How survival benefits are described may influence the value people place on cancer care.

Background— Evidence suggests that recent and projected future investments in percutaneous coronary intervention (PCI) programs at US hospitals fail to increase access to timely reperfusion for patients with ST-segment elevation myocardial infarction. Methods and Results— We set out to estimate the annual number and costs of new PCI programs in US hospitals from 2004 to 2008 and identify the characteristics of hospitals, neighborhoods, and states where new PCI programs have been introduced. We estimated a discrete-time hazard model to measure the influence of these characteristics on the decision of a hospital to introduce a new PCI program. In 2008, 1739 US hospitals were capable of performing PCI, a relative increase of 16.5% (251 hospitals) over 2004. The percentage of the US population with projected access to timely PCI grew by 1.8%. New PCI programs were more likely to be introduced in areas that already had a PCI program with more competition for market share, near populations with higher rates of private insurance, in states that had weak or no regulation of new cardiac catheterization laboratories, and in wealthier and larger hospitals. Conclusions— Our data show that new PCI programs were systematically duplicative of existing programs and did not help patients gain access to timely PCI. The total cost of recent US investments in new PCI programs is large and of questionable value for patients.

Background— In 2001, 1176 US hospitals were capable of performing primary percutaneous coronary intervention (PCI), and 79% of the population lived within 60-minute ground transport of these hospitals. We compared these estimates with data from 2006 to explore how hospital PCI capability and population access have changed over time. Methods and Results— We estimated the proportion of the population 18 years of age or older, living in 2006 within a 60-minute drive of a PCI-capable hospital, and we compared our estimate with a previously published report on 2001 data. Over the 5-year period, the number of PCI-capable hospitals grew from 1176 to 1695 hospitals, a relative increase of 44%; access to the procedure grew from 79.0% to 79.9% of the population, a relative increase of 1%. Conclusions— Our data indicate a large increase in the number of hospitals capable of performing PCI from 2001 to 2006, but this increase was not associated with an appreciable change in the proportion of the population with access to the procedure. In the future, more attention is needed on changes in PCI capacity over time and on the effects of these changes on outcomes of interest such as service utilization, expenditures, patient outcomes, and population health.

An important challenge in comparative effectiveness research is the lack of infrastructure to support pragmatic clinical trials, which compare interventions in usual practice settings and subjects. These trials present challenges that differ from those of classical efficacy trials, which are conducted under ideal circumstances, in patients selected for their suitability, and with highly controlled protocols. In 2012, we launched a 1‐year learning network to identify high‐priority pragmatic clinical trials and to deploy research infrastructure through the NIH Clinical and Translational Science Awards Consortium that could be used to launch and sustain them. The network and infrastructure were initiated as a learning ground and shared resource for investigators and communities interested in developing pragmatic clinical trials. We followed a three‐stage process of developing the network, prioritizing proposed trials, and implementing learning exercises that culminated in a 1‐day network meeting at the end of the year. The year‐long project resulted in five recommendations related to developing the network, enhancing community engagement, addressing regulatory challenges, advancing information technology, and developing research methods. The recommendations can be implemented within 24 months and are designed to lead toward a sustained national infrastructure for pragmatic trials.

Background: Medicare claims data sets have been used widely in outcomes research over the last decade. In 2010, the Centers for Medicare & Medicaid Services established a program to create de-identified basic standalone public use files (PUFs) from Medicare claims data, each one containing claims information from a 5% sample of beneficiaries. Methods: We conducted a series of structured key informant interviews with research stakeholders to compile recommendations that would guide the creation of these PUFs. In this paper, we describe the interview methodology and present our findings. Fifteen researchers, representing a range of clinical health services and health policy expertise, were interviewed. Results: All respondents supported the use of Medicare claims in comparative effectiveness research and responded favorably to the creation of PUFs for this purpose. The interviews resulted in administrative-, technical- and content-related recommendations, some of which led to important changes in the PUFs. Discussion: A primary trade-off in the development of the proposed PUFs involved assuring maximum research utility of the files while assuring security of beneficiaries’ protected health information. Protection of protected health information was considered a requirement. Given this constraint, the proposed PUFs may be most useful for two primary activities in comparative effectiveness research: first, working through the beginning stages of a research project; and second, examining high-level questions.

Aim: To identify ongoing practices and opportunities for improving national comparative effectiveness research (CER) translation through dissemination and implementation (D&I) via NIH-funded Clinical and Translational Science Award (CTSA) institutions. Materials & methods: Key informant interviews were conducted with 18 CTSA grantees sampled to represent a range of D&I efforts. Results & conclusions: The institutional representatives endorsed fostering CER translation nationally via the CTSA Consortium. However, five themes emerged from the interviews as barriers to CER D&I: lack of institutional awareness, insufficient capacity, lack of established D&I methods, confusion among stakeholders about what CER actually is and limited funding opportunities. Interviewees offered two key recommendations to improve CER translation: development of a centralized clearing house to facilitate the diffusion of CER D&I resources and methods across CTSA institutions; and formalization of the national CTSA network to leverage existing community engagement relationships and resources for the purpose of adapting and disseminating robust CER evidence locally with providers, patients and healthcare systems.

To identify and prioritize future research needs (FRN) topics for diagnosis and treatment of obstructive sleep apnea (OSA).Twenty-one panel members represented six stake-holder categories: patients and the public, providers; purchasers of health care, payers, policymakers, and principal investigators. Building on a recently completed comparative effectiveness review, stakeholders nominated and discussed potential FRN topics. Stakeholders then nominated their top priority FRN topics based on the Agency for Healthcare Research and Quality Effective Health Care Program Selection Criteria. From these nominations, the highest priority FRN topics were determined and were elaborated upon to include possible study designs to address the topics.Thirty-seven topics were discussed and prioritized. The nine highest priority FRN topics included: cost-effectiveness of management strategies, defining age- and sex-specific criteria for OSA, evaluating routine preoperative screening for OSA, evaluating involvement of a sleep medicine specialist in diagnosis of OSA, evaluating clinical prediction rules, assessing the effect of treating sleep disordered breathing and long-term clinical outcomes, comparing treatments for patients who do not tolerate positive airway pressure, evaluating strategies to improve treatment compliance, and evaluating the association between sleep apnea severity and long-term clinical outcomes.While there are numerous specific research questions with low or insufficient strength of evidence for OSA management, OSA patients, their healthcare providers, and society at large would benefit from refocusing research efforts into the prioritized research questions and away from simple comparisons of short-term outcomes between specific interventions.

We assessed how much, if anything, people would pay for a laboratory test that predicted their future disease status. A questionnaire was administered via an internet-based survey to a random sample of adult US respondents. Each respondent answered questions about two different scenarios, each of which specified: one of four randomly selected diseases (Alzheimer's, arthritis, breast cancer, or prostate cancer); an ex ante risk of developing the disease (randomly designated 10 or 25%); and test accuracy (randomly designated perfect or 'not perfectly accurate'). Willingness-to-pay (WTP) was elicited with a double-bounded, dichotomous-choice approach. Of 1463 respondents who completed the survey, most (70-88%, depending on the scenario) were inclined to take the test. Inclination to take the test was lower for Alzheimer's and higher for prostate cancer compared with arthritis, and rose somewhat with disease prevalence and for the perfect versus imperfect test [Correction made here after initial online publication.]. Median WTP varied from $109 for the imperfect arthritis test to $263 for the perfect prostate cancer test. Respondents' preferences for predictive testing, even in the absence of direct treatment consequences, reflected health and non-health related factors, and suggests that conventional cost-effectiveness analyses may underestimate the value of testing.

Summary Background Substantial geographical clustering of Clostridium difficile infection (CDI) outbreaks in hospitals in the USA have previously been demonstrated. Aim To test the hypothesis that hospital burden of CDI is associated with admission from and discharge to long-term care facilities (LTCFs). Methods Hospital discharge data from 19 states in the USA were used to identify all patients discharged with a diagnosis of CDI from 1 January 2002 to 31 December 2004. For every hospital, the proportion of discharges with a diagnosis of CDI was calculated, and those above the 90th percentile were classified as ‘high CDI' hospitals. We tested the association between this measure of hospital burden of CDI and the rates of admission from and discharges to LTCFs. We adjusted for other hospital level characteristics, case-complexity and local population characteristics. Findings We identified 38,372,951 discharges during the three-year study period. Of all discharges, 274,311 (0.71%) had a primary or secondary diagnosis of CDI. Hospitals had a mean CDI burden of 7.8 cases per 1000 discharges. High CDI hospitals ( N = 610; 10.0%) had a mean CDI burden of 34.8 cases per 1000 discharges. Compared to other hospitals, high CDI hospitals were more likely to have a high proportion of admissions from or discharges to LTCFs. This association persisted after adjustments for other hospital characteristics, case-complexity, and area population characteristics. Conclusion A high rate of admission from or discharge to LTCFs is associated with an increased hospital burden of CDI.

PURPOSE: A notable increase in-hospital admissions for Clostridium difficile colitis has occurred in the United States. In this paper we evaluate changes in the epidemiology of Clostridium difficile colitis in a subset of hospitalized patients with inflammatory bowel diseases. METHODS: A retrospective cohort analysis was conducted for all inflammatory bowel disease patients with Clostridium difficile colitis in the Nationwide Inpatient Sample, a 20 percent stratified random sample of national hospital discharge abstracts from 1993 through 2003. Using standard diagnostic codes, we identified yearly admissions for Clostridium difficile, other bacterial infections, and parasitic infections in inflammatory bowel disease patients. Next, we calculated prevalence, case fatality, and operative mortality for inflammatory bowel disease patients diagnosed with Clostridium difficile. RESULTS: We found that the prevalence of Clostridium difficile rose significantly in patients with ulcerative colitis and in those Crohn's disease patients with some component of large bowel involvement but not in patients with Crohn's disease limited to the small bowel alone. During the study period, case fatality also rose significantly in patients with ulcerative colitis and Clostridium difficile but not in patients with Crohn's disease and Clostridium difficile. Operative mortality for ulcerative colitis patients with Clostridium difficile reached 25.7 percent. CONCLUSIONS: The prevalence and case fatality of patients with inflammatory bowel disease and Clostridium difficile rose significantly during the study period. Changes in Clostridium difficile epidemiology were particularly noteworthy for those patients with ulcerative colitis, who experienced elevated rates of hospitalization and case fatality.

Context The delivery of burn care is a resource-intensive endeavor that requires specialized personnel and equipment. The optimal geographic distribution of burn centers has long been debated; however, the current distribution of centers relative to geographic area and population is unknown. Objective To estimate the proportion of the US population living within 1 and 2 hours by rotary air transport (helicopter) or ground transport of a burn care facility. Design and Setting A cross-sectional analysis of geographic access to US burn centers utilizing the 2000 US census, road and speed limit data, the Atlas and Database of Air Medical Services database, and the 2008 American Burn Association Directory. Main Outcome Measure The proportion of state, regional, and national population living within 1 and 2 hours by air transport or ground transport of a burn care facility. Results In 2008, there were 128 self-reported burn centers in the United States including 51 American Burn Association–verified centers. An estimated 25.1% and 46.3% of the US population live within 1 and 2 hours by ground transport, respectively, of a verified burn center. By air, 53.9% and 79.0% of the population live within 1 and 2 hours, respectively, of a verified center. There was significant regional variation in access to verified burn centers by both ground and rotary air transport. The greatest proportion of the population with access was highest in the northeast region and lowest in the southern United States. Conclusion Nearly 80% of the US population lives within 2 hours by ground or rotary air transport of a verified burn center; however, there is both state and regional variation in geographic access to these centers.