Interest In Comparative Effectiveness Research Research Articles

Customised fetal growth charts.......do they measure up?

The growing interest in comparative effectiveness research (CER) based on data from routine clinical practice also extends towards lung oncology. Although CER studies using real world data (RWD) have the potential to assist clinical decision-making, concerns about the quality and validity of studies with observational data subsist. The primary objective of the present study is to assess the current status of observational CER in the field of lung oncology, both quantitatively as qualitatively.We performed a systematic electronic literature database search in MEDLINE and EMBASE (up to 1 July 2015). The quality of all selected studies was assessed according to the Good ReseArch for Comparative Effectiveness (GRACE) checklist.The first selection included 657 publications. After screening the corresponding abstracts and full-text papers, 38 studies remained. A total of 36 studies included patients with advanced NSCLC. The comparison of the effectiveness of gefitinib versus erlotinib was the main objective in 22% of the studies. The median number of patients per study was 202 (range 21–10064). The number of publications increased over the years whereas the quality score remained stable over the years with several common shortcomings (checklist items M5, D1, D4, D6).The growing interest in clinical oncology CER studies using RWD is reflected in an increasing number of publications in the recent years. The studies have several common methodological shortcomings possibly limiting their applicability in clinical decision-making. To fulfil the promise of RWD CER in lung oncology effort should be continued to overcome these shortcomings.

Alternative consent models for comparative effectiveness studies: Views of patients from two institutions

ABSTRACTBackground: Informed consent requirements generally require a lengthy process and signed documentation for patients to participate in clinical research. With growing interest in comparative effectiveness research (CER), whereby patients receive approved (nonexperimental) medicines for their medical condition, questions have been raised whether the same consent requirements should apply. Little input from patients has been part of these debates. Methods: We conducted two “deliberative engagement sessions” with patients from Johns Hopkins Community Physicians (JHCP) and Geisinger Health System (GHS). Full-day sessions introduced participants to two different CER designs (observational vs. randomized) comparing two antihypertensive medications and three disclosure or consent approaches: Opt-In, Opt-Out, and “General Approval.” Sessions consisted of presentations and extensive discussion at small group tables. Pre- and posttest surveys were completed by participants before and after all-day discussions measuring attitudes about research and about each of the three disclosure/consent options. Results: One hundred thirty-seven adults over age 40 years participated. Attitudes were similar between JHCP and GHS. Participants strongly preferred Opt-In or Opt-Out consent options to General Approval for both observational and randomized designs. For the randomized CER study, 70% liked Opt-In, 65% liked Opt-Out, and 40% liked General Approval. In discussing disclosure/consent options, patients cared most about choice, information, privacy and confidentiality, quality of the research, trust, respect, and impact of the study on patient care. Conclusions: The majority of participants from two different types of health systems liked both Opt-In and Opt-Out approaches for observational and randomized designs for low-risk CER. There were no posttest differences in the proportion liking Opt-In versus Opt-Out. Patients in this study wanted to be told about research and have a choice, but were very open to such disclosures being streamlined. Policymakers may find patients' views about what matters to them in the context of consent and CER relevant.

Unanticipated Insights into Biomedicine from the Study of Acupuncture

Research into acupuncture has had ripple effects beyond the field of acupuncture. This paper identifies five exemplars to illustrate that there is tangible evidence of the way insights gleaned from acupuncture research have informed biomedical research, practice, or policy. The first exemplar documents how early research into acupuncture analgesia has expanded into neuroimaging research, broadening physiologic understanding and treatment of chronic pain. The second describes how the acupuncture needle has become a tool to enhance biomedical knowledge of connective tissue. The third exemplar, which illustrates use of a modified acupuncture needle as a sham device, focuses on emergent understanding of placebo effects and, in turn, on insights into therapeutic encounters in treatments unrelated to acupuncture. The fourth exemplar documents that two medical devices now in widespread use were inspired by acupuncture: transcutaneous electrical nerve stimulators for pain control and antinausea wrist bands. The final exemplar describes how pragmatic clinical trial designs applied in acupuncture research have informed current general interest in comparative effectiveness research. In conclusion, these exemplars of unanticipated outcomes of acupuncture research comprise an additional rationale for continued support of basic and clinical research evaluating acupuncture and other under-researched therapies.

Stakeholders' Views of Alternatives to Prospective Informed Consent for Minimal-Risk Pragmatic Comparative Effectiveness Trials.

As interest in comparative effectiveness research grows, questions have emerged regarding whether it is ever acceptable to alter informed consent requirements for research when patients are randomly assigned to widely-used therapies. This paper reports on interviews with Institutional Review Board members and researchers and on focus groups with patients from Geisinger and Johns Hopkins health systems. The objective was to elicit participants' views of the acceptability of four different disclosure and authorization models for low-risk pragmatic comparative effectiveness trials of widely-used therapies. Results suggest that although participants valued autonomous choice, many also believed that it was acceptable to streamline information disclosure and to use an opt-out process for eligible individuals who would prefer not to participate. This provides some preliminary evidence that relevant stakeholders find alternatives to traditional informed consent acceptable for low-risk pragmatic comparative effectiveness trials of widely-used therapies as long as a sufficient amount of choice is preserved.

FDAMA Section 114: Why the Renewed Interest?

The FDA regulates the use of information by biopharmaceutical companies in their promotional activities. Section 114 of the Food and Drug Administration Modernization Act of 1997 (FDAMA) was specifically designed to allow companies to more readily disseminate health care economic information (HCEI) to those who need it for formulary decision making. However, very little HCEI has been distributed promotionally under this provision over the past 17 years. There are recent discussions by stakeholders regarding the need for updates, revisions, or guidance regarding Section 114.In light of recent renewed interest in Section 114 of the FDAMA, the purpose of this commentary is to equip managed care decision makers with the information they need to understand and respond to industry communications that are governed by Section 114. This commentary reviews and synthesizes the regulatory history and language of the statute and changes to the promotion regulation generated by Section 114. It explores the reasons for the section's limited use to date, for recent renewed interest, and why changes by various stakeholders are suggested at this time. Also discussed is what managed care pharmacists need to know about Section 114, and suggestions are included regarding the active role pharmacists can play in this change process.Renewed interest in FDAMA Section 114 appears to stem largely from the increasingly visible and growing interest in comparative effectiveness research, the emergence of "big data," the expanding range of data sources available for deriving HCEI, and recent court decisions that might indicate a change in the regulatory environment. Various stakeholders are proposing recommendations regarding changes to FDAMA Section 114. Managed care pharmacists should be aware that companies are restricted when communicating HCEI promotional messages; this may mean seeing the use of FDAMA Section 114 as the "competent and reliable" effectiveness standard in promotion. If the managed care pharmacy community communicates clearly about what information it needs and the format in which it wants to receive that information, companies, policymakers, and regulatory bodies can work collaboratively with managed care pharmacy to create a regulatory environment that supports transparent communication of desired information.

What can comparative effectiveness research contribute to integrative health in international perspective?

The interest in Comparative Effectiveness Research (CER) in the international community is growing. A panel titled "What Can Comparative Effectiveness Research Contribute to Integrative Health in International Perspective?" took place at the 3rd International Research Congress on Integrative Medicine and Health in Portland, Oregon, in 2012. The presentations at this panel highlighted different perspectives on CER, including the funders' and the stakeholders' perspectives from the United States, as well as experiences with economic evaluations from Australia and pragmatic trials in Europe. The funders' perspective emphasized the need for innovation and controlling costs in large-scale studies. The stakeholder's perspective stressed the need to gather the input of stakeholders in shaping the framework for more informative, more decision-maker-driven research. Several examples of cost-effectiveness analyses were offered from Australia. The importance of balancing rigor and pragmatism was also discussed in a presentation of the efficacy-effectiveness continuum. A wide-ranging discussion explored additional questions concerning the translation of evidence into practice; the effect of pragmatic trials on funding or policy; evidentiary distinctions between and among pragmatic trials and traditional randomized clinical trials; and the multiple roles of stakeholders, particularly in generating new information and knowledge. The presentations and discussions showed that more development of methods is needed. This includes developments on study design and statistical approaches, as well as methods for stakeholder involvement and mechanisms to bring these results into practice.

Comparative Effectiveness Research in Practice and Policy for Radiation Oncology

Interest in comparative effectiveness research (CER) has increased dramatically over the past decade, yet perceptions about what comprises CER varies. CER has several attributes relevant to practice and policy: (1) The goal of CER is to inform decisions about health care. (2) Literature synthesis is used in addition to primary research. (3) CER evaluates not only overall outcomes for the population but also evaluates subgroups that may have heterogeneous outcomes. (4) Research places an emphasis on outcomes in the "real-world" settings. (5) Outcomes studied should be relevant to patients. In radiation oncology, where many of the traditional clinical trials are comparative in nature, the line between CER and "traditional" research may be blurred, but an increased emphasis on CER can help to bridge the research enterprise and clinical practice, helping to inform decision making at the patient, clinician, and policy levels.

The Politics of Comparative Effectiveness Research: Lessons from Recent History

Efforts to support and use comparative effectiveness research (CER), some more successful than others, have been promulgated at various times over the last forty years. Following a resurgence of interest in CER, recent health care reforms provided substantial support to strengthen its role in US health care. While CER has generally captured bipartisan support, detractors have raised concerns that it will be used to ration services and heighten government control over health care. Such concerns almost derailed the initiative during passage of the health care reform legislation and are still present today. Given recent investments in CER and the debates surrounding its development, the time is ripe to reflect on past efforts to introduce CER in the United States. This article examines previous initiatives, highlighting their prescribed role in US health care, the reasons for their success or failure, and the political lessons learned. Current CER initiatives have corrected for many of the pitfalls experienced by previous efforts. However, past experiences point to a number of issues that must still be addressed to ensure the long-term success and sustainability of CER, including adopting realistic aims about its impact, demonstrating the impact of Patient-Centered Outcomes Research Institute (PCORI) and communicating the benefits of CER, and maintaining strong political and stakeholder support.

Comparative Effectiveness Research in Cancer: What Has Been Funded and What Knowledge Gaps Remain?

A recent explosion of interest in comparative effectiveness research (CER) has been accompanied by diverse attempts to define CER and specify CER research methods. We explore how CER is relevant across the cancer control continuum, including prevention, screening, diagnosis, treatment, and survivorship. We review cancer CER research funded by the National Cancer Institute by analyzing project characteristics along the dimensions of cancer type, stage of the cancer continuum, position on the T0 to T4 translational continuum, and the size and representativeness of both the settings and populations studied. We also provide an assessment of cost and resources considerations in CER. One hundred three relevant projects on CER were funded by the National Cancer Institute’s Division of Cancer Control and Population Science between 2009 and 2011. Prevention studies were most frequent (38.8%), and survivorship grants were least frequent (13.5%). Many projects included economic (35.0%) or simulation modeling (10.7%) approaches as well as multilevel behavioral (53.4%) and/or organizational change (54.4%) interventions. Most studies used convenience sampling (54.3%) and studied two or less settings (50.0%). Cancer CER is active and diverse but could be enhanced by a greater focus on knowledge integration, context, relevance to stakeholders, transparency, and population impact. Processes for generating and evaluating evidence in cancer and other areas of health care are often slow, costly, or too unrepresentative to provide useful evidence to decision makers (1). Given cancer burden, increasing concerns about cancer treatment costs, and projections about the anticipated number of cancer survivors, there is a clear need for cancer comparative effectiveness research (CER) (2). Recently, CER has been recommended as a practical approach to determining what works in health care (3). As defined by the Institute of Medicine, CER is “the generation and synthesis of evidence that compares the benefits and harms of alternative methods to prevent, diagnose, treat, and monitor a clinical condition or to improve the delivery of care” (3). Concerns about the effectiveness of health care have promoted interest in CER, culminating in the recently established Patient Centered Outcomes Research Institute (PCORI). PCORI responds to concerns that patients, providers, and caregivers do not have the types of comparative information they need to make choices aligned with their desired health outcomes. Thus, the concepts of personalization and patient-centeredness are embedded in the PCORI (4–6). For example, one of the tenets of this research includes answers to these questions: “Given my personal characteristics, conditions, and preferences, what should I expect will happen to me?” and “What are my options, and what are the benefits and harms of those options?” (7). These same questions apply to personalized or precision medicine that seeks to integrate “-omic” information into health care (7). Personalizing health care according to patient preferences will require incorporating social and behavioral information from the outset, not just when a new application is ready for clinical use. There has been an outpouring of recent articles on CER, including special issues of JAMA (April 18, 2012) and the Journal of Clinical Oncology (October 15, 2012) that included both conceptual papers and a series of large-scale observational studies, three of which addressed cancer. Given the vast amount of emerging information, it remains to be seen how much evidence will have to come from comparative randomized clinical trials, observational studies, natural experiments, adaptive trials, pragmatic intervention studies, and evidence synthesis and modeling, all of which are tools of CER (7). Regardless, three things are clear: 1) CER research should be relevant and broadly applicable; 2) it should include information on costs, resources required, and efficiency issues; and 3) it should address public health impact (8,9).

Evaluation of Treatment Benefit in Journal of Clinical Oncology

Evaluation of Treatment Benefit in <i>Journal of Clinical Oncology</i>

Further evaluation of a claims-based algorithm to determine the effectiveness of biologics for rheumatoid arthritis using commercial claims data

As more biologics are approved, there is increasing interest in comparative effectiveness research (CER). Health insurance claims databases have encounter data but seldom contain clinical outcomes. recently published algorithm assessed the clinical effectiveness of RA biologics using VA claims data and validated against the DAS28ESR[1] had a sensitivity, 72% (95% CI = 67- 77%) and specificity, 91% (95% CI = 89- 93%). The accompanying editorial [2] commented, A claims-based effectiveness algorithm with acceptable performance characteristics across different data settings will be a powerful and desired tool for CER of RA. Such an algorithm will enable large-scale, population-based studies comparing the effectiveness of different DMARD regimens. Such studies will facilitate head-to-head comparisons, supplementing typical randomized controlled trials and prospective registries that usually include disease activity...Whether the algorithm will have a similar performance in other claims databases therefore needs to be further examined. We performed an independent analysis to evaluate the algorithm's positive predictive value (PPV) in a commercial claims data source compared to a clinical gold standard.

Predictors of Improved Pain After Surgical Treatment of Lumbar Spinal Stenosis

Degenerative lumbar spinal stenosis is a common condition in adult patients and is frequently managed by surgical treatment after failure of non-operative measures to relieve pain. While operative management is a well-established treatment modality for lumbar stenosis, limited evidence-based information regarding optimal selection of patients for surgery exists. Current reform in health care policy has sparked significant interest in comparative effectiveness research with the goal of optimizing treatment strategies for common conditions such as degenerative lumbar stenosis.

Predictors of Quality of Life and Physical Function After Surgical Treatment of Lumbar Spinal Stenosis

Degenerative lumbar spinal stenosis is a common condition in adult patients and is frequently managed by surgical treatment after failure of non-operative measures to relieve pain. While operative management is a well-established treatment modality, limited evidence-based information regarding optimal selection of patients for surgery exists. Current reform in health care policy has sparked significant interest in comparative effectiveness research with the goal of optimizing treatment strategies for common conditions such as degenerative lumbar stenosis.

The role for pragmatic randomized controlled trials (pRCTs) in comparative effectiveness research

There is a growing appreciation that our current approach to clinical research leaves important gaps in evidence from the perspective of patients, clinicians, and payers wishing to make evidence-based clinical and health policy decisions. This has been a major driver in the rapid increase in interest in comparative effectiveness research (CER), which aims to compare the benefits, risks, and sometimes costs of alternative health-care interventions in 'the real world'. While a broad range of experimental and nonexperimental methods will be used in conducting CER studies, many important questions are likely to require experimental approaches - that is, randomized controlled trials (RCTs). Concerns about the generalizability, feasibility, and cost of RCTs have been frequently articulated in CER method discussions. Pragmatic RCTs (or 'pRCTs') are intended to maintain the internal validity of RCTs while being designed and implemented in ways that would better address the demand for evidence about real-world risks and benefits for informing clinical and health policy decisions. While the level of interest and activity in conducting pRCTs is increasing, many challenges remain for their routine use. This article discusses those challenges and offers some potential ways forward.

Comparative effectiveness research: what is it and why do we need it in nephrology?

The USA leads other industrialized countries in health care spending but lags behind in terms of health outcomes. There has been growing interest in comparative effectiveness research (CER) as a means to identify best practices to create a more efficient and effective health care system. Two key concepts of CER are that it should (i) compare two or more alternative tests, therapies or procedures and (ii) be conducted in persons, clinical settings and conditions that are representative of the real world. The goal of CER is to provide evidence for clinicians, patients, policy makers and others to make informed decisions that will ultimately improve the overall health of specific subgroups and of the population as a whole. In this narrative review, we first describe the strengths and limitations of various types of studies that constitute CER, including randomized clinical trials, observational studies and systematic reviews, providing examples from the nephrology literature. Because of the concerns regarding confounding in observational CER, we also provide an overview of methods to reduce confounding in these types of studies. Finally, we will discuss why CER pertaining to kidney disease care needs to be a top priority in order to move our field from a largely opinion-based specialty to an evidence-based specialty.

Methods for developing and analyzing clinically rich data for patient‐centered outcomes research: an overview

Methods for developing and analyzing clinically rich data for patient‐centered outcomes research: an overview

The Methods of Comparative Effectiveness Research

This review describes methods used in comparative effectiveness research (CER). The aim of CER is to improve decisions that affect medical care at the levels of both policy and the individual. The key elements of CER are (a) head-to-head comparisons of active treatments, (b) study populations typical of day-to-day clinical practice, and (c) a focus on evidence to inform care tailored to the characteristics of individual patients. These requirements will stress the principal methods of CER: observational research, randomized trials, and decision analysis. Observational studies are especially vulnerable because they use data that directly reflect the decisions made in usual practice. CER will challenge researchers and policy makers to think deeply about how to extract more actionable information from the vast enterprise of the daily practice of medicine. Fortunately, the methods are largely applicable to research in the public health system, which should therefore benefit from the intense interest in CER.

From Methods to Policy: The intended and unintended consequences of comparative effectiveness research

As funding and interest in comparative effectiveness research (CER) in the USA and around the world continues to grow, this first From Methods to Policy column will kick off an ongoing dialog about several intended and unintended consequences stemming from that growth. This column will briefly introduce these consequences, and expanded views will occur in future issues of the journal. By starting this dialog, we hope to inform everyone who will have a role in shaping what CER becomes and how it ultimately impacts healthcare. The aim of CER is to create evidence for providers, patients, payers and other healthcare decision-makers. To reach its full potential, this evidence should identify what works best for which patients and under what circumstances. Where feasible, the evidence should derive from real-world environments, utilize comparators that represent best care alternatives and address outcomes relevant to key stakeholders. Looking forward, both intended and unintended consequences will arise related to the creation and expansion of CER agencies, a sheer increase in the volume of available CER and the variety in approaches to implementation, among other issues. Although the examples in this current article reflect activities in the USA, future columns will explore similar themes from other countries.

Infrastructure requirements for secondary data sources in comparative effectiveness research.

The growing interest in comparative effectiveness research (CER) has re-ignited the debate about the inadequacy of data from randomized controlled trials (RCTs) to address patient-centered decision making. Despite their well-known internal validity and use as the gold standard for regulatory decision making, the limitations of RCTs are widely recognized. In addition to their lack of statistical power due to inadequate sample size to address certain research hypotheses, practical and ethical considerations may preclude their viability. A case in point is the ethical dilemma in conducting an RCT to establish whether a diet high in fat content may be a risk factor for dementia, which might produce useful public health information but would not be acceptable in terms of protection of human subjects. Frequently, RCTs provide substantial information regarding the efficacy of drugs and other medical interventions, yet leave large gaps in evidence that would be relevant for medical decision making. Even when RCTs are carried out with this intent, they may not necessarily reflect “real-world” experience and, therefore may not provide sufficient evidence to guide patient-centered care. The substantial investment in CER and the broad objective implied in the American Recovery and Reinvestment Act of 2009 have necessitated the need to seek alternative sources of data to meet the emerging health care questions. The stated requirements include an “.... assessment of a comprehensive array of health-related outcomes for diverse patient populations and sub-groups” as well as “... a wide range of interventions;” and “[d]evelopment, expansion, and use of a variety of data sources and methods to assess comparative effectiveness.”1-2 Contending with the changes in health care policy and delivery clearly requires doing things differently, as discussed at a recent workshop sponsored by the Institute of Medicine.3 The workshop summary highlighted the dependence on clinical trials as the “sole source of evidence on the constantly accelerating flow of diagnostic and treatment challenges is unfeasible.” The need for a “learning healthcare system” with “real-time learning from the clinical experience and seamless application of the lessons in the care process” was emphasized. Secondary data, such as registries and retrospective databases, can be used to complement RCTs, since they are less costly and can be used to incorporate real world experience to answer questions. Further, important questions, such as adherence, treatment patterns, and burden of disease, can be answered in retrospective analyses of databases. However, effective use of secondary data requires addressing major methodological and infrastructural issues that may be related to, but often go beyond, those encountered with most RCTbased work. Infrastructural issues, such as tools to efficiently access and correctly analyze the data, need to be developed for effective use of such data sources. Guidelines need to be formulated and data standards established using RCTs as a role model. Data warehouses are also required to be established that respect the privacy and confidentiality of patients. In this paper, we discuss the infrastructural requirements for secondary data utilization in CER, and identify gaps that must be filled to address the underlying issues, with emphasis on data standards, data quality assurance, data warehouses, computing environment, and protection of privacy and confidentiality.

The Patient-Centered Outcomes Research Institute — Promoting Better Information, Decisions, and Health

Within the 2000 pages of the 2010 Patient Protection and Affordable Care Act (ACA) is a short section authorizing the creation of the Patient-Centered Outcomes Research Institute (PCORI) — a research organization dedicated to the support and promotion of comparative clinical effectiveness research. The establishment of PCORI represents the culmination of long-standing interest in comparative effectiveness research, a lengthy legislative gestation, and compromise among varied congressional perspectives and priorities.1 PCORI responds to a widespread concern that, in many cases, patients and their health care providers, families, and caregivers do not have the information they need to make choices aligned with . . .