This paper describes our process to engage regional stakeholders for prioritizing comparative effectiveness research (CER) in cancer diagnostics. We also describe a novel methodology for incorporating stakeholder data and input to inform the objectives of selected CER studies.
Materials & methods
As an integrated component to establishing the infrastructure for community-based CER on diagnostic technologies, we have assembled a regional stakeholder group composed of local payers, clinicians and state healthcare representatives to not only identify and prioritize CER topics most important to the western Washington State region, but also to inform the study design of selected research areas. A landscape analysis process combining literature searches, expert consultations and stakeholder discussions was used to identify possible CER topics in cancer diagnostics. Stakeholders prioritized the top topics using a modified Delphi/group-nominal method and a standardized evaluation criteria framework to determine a final selected CER study area. Implementation of the selected study was immediate due to a unique American Recovery and Reinvestment Act funding structure involving the same researchers and stakeholders in both the prioritization and execution phases of the project. Stakeholder engagement was enhanced after study selection via a rapid analysis of a subset of payers’ internal claims, coordinated by the research team, to obtain summary data of imaging patterns of use. Results of this preliminary analysis, which we termed an ‘internal analysis,’ were used to determine with the stakeholders the most important and feasible study objectives.
Stakeholders identified PET and MRI in cancers including breast, lung, lymphoma and colorectal as top priorities. In an internal analysis of breast cancer imaging, summary data from three payers demonstrated utilization rates of advanced imaging increased between 2002 and 2009 in the study population, with a great deal of variability in use between different health plans. Assessing whether breast MRI affects treatment decisions was the top breast cancer study objective selected by the stakeholders. There were other high-priority research areas including whether MRI use improved survival that were not deemed feasible with the length of follow-up time following MRI adoption.
Continuous stakeholder engagement greatly enhanced their enthusiasm for the project. We believe CER implementation will be more successful when undertaken by regional stakeholders.
breast cancer; cancer imaging; comparative effectiveness research; research prioritization; stakeholder involvement
Stakeholder engagement is fundamental to comparative effectiveness research (CER), but lacks consistent terminology. This paper aims to define stakeholder engagement and present a conceptual model for involving stakeholders in CER.
Materials & methods
The definitions and model were developed from a literature search, expert input and experience with the Center for Comparative Effectiveness Research in Cancer Genomics, a proof-of-concept platform for stakeholder involvement in priority setting and CER study design.
Definitions for stakeholder and stakeholder engagement reflect the target constituencies and their role in CER. The ‘analytic-deliberative’ conceptual model for stakeholder engagement illustrates the inputs, methods and outputs relevant to CER. The model differentiates methods at each stage of the project; depicts the relationship between components; and identifies outcome measures for evaluation of the process.
While the definitions and model require testing before being broadly adopted, they are an important foundational step and will be useful for investigators, funders and stakeholder groups interested in contributing to CER.
cancer genomics; comparative effectiveness research; consumer participation; deliberative methods; public participation; stakeholder engagement; stakeholders
The increasing burden of chronic diseases presents not only challenges to the knowledge and expertise of the professional medical community, but also highlights the need to improve the quality and relevance of clinical research in this domain. Many patients now turn to complementary and integrative medicine (CIM) to treat their chronic illnesses; however, there is very little evidence to guide their decision-making in usual care. The following research recommendations were derived from a CIM Stakeholder Symposium on Comparative Effectiveness Research (CER): (1) CER studies should be made a priority in this field; (2) stakeholders should be engaged at every stage of the research; (3) CER study designs should highlight effectiveness over efficacy; (4) research questions should be well defined to enable the selection of an appropriate CER study design; (5) the CIM community should cultivate widely shared understandings, discourse, tools, and technologies to support the use and validity of CER methods; (6) Effectiveness Guidance Documents on methodological standards should be developed to shape future CER studies. CER is an emerging field and its development and impact must be reflected in future research strategies within CIM. This stakeholder symposium was a first step in providing systematic guidance for future CER in this field.
There is a need for more Comparative Effectiveness Research (CER) to strengthen the evidence base for clinical and policy decision-making. Effectiveness Guidance Documents (EGD) are targeted to clinical researchers. The aim of this EGD is to provide specific recommendations for the design of prospective acupuncture studies to support optimal use of resources for generating evidence that will inform stakeholder decision-making.
Document development based on multiple systematic consensus procedures (written Delphi rounds, interactive consensus workshop, international expert review). To balance aspects of internal and external validity, multiple stakeholders including patients, clinicians and payers were involved.
Recommendations focused mainly on randomized studies and were developed for the following areas: overall research strategy, treatment protocol, expertise and setting, outcomes, study design and statistical analyses, economic evaluation, and publication.
The present EGD, based on an international consensus developed with multiple stakeholder involvement, provides the first systematic methodological guidance for future CER on acupuncture.
Comparative effectiveness research; Effectiveness guidance document; Acupuncture
The Division of Lung Diseases of the National Heart, Lung and Blood Institute (NHLBI) recently held a workshop to identify gaps in our understanding and treatment of childhood lung diseases and to define strategies to enhance translational research in this field. Leading experts with diverse experience in both laboratory and patient-oriented research reviewed selected areas of pediatric lung diseases, including perinatal programming and epigenetic influences;mechanisms of lung injury, repair, and regeneration; pulmonary vascular disease (PVD); sleep and control of breathing; and the application of novel translational methods to enhance personalized medicine. This report summarizes the proceedings of this workshop and provides recommendations for emphasis on targeted areas for future investigation. The priority areas identified for research in pediatric pulmonary diseases included: (1) epigenetic and environmental influences on lung development that program pediatric lung diseases, (2) injury, regeneration, and repair in the developing lung, (3) PVD in children, (4) development and adaptation of ventilatory responses to postnatal life, (5) nonatopic wheezing: aberrant large airway development or injury? (6) strategies to improve assessment, diagnosis, and treatment of pediatric respiratory diseases, and (7) predictive and personalizedmedicine for children.
epigenetics; pediatric; respiratory; lung disease
Comparative effectiveness research (CER) has received considerable research attention in recent months, and efforts to promote CER are part of the newly enacted Patient Protection and Affordable Care Act. In this paper, we define CER, how it complements traditional efficacy research in asthma, and discuss how CER can help provide the basis for rational decision-making about the care of individual patients with asthma and how best to deliver this care in real-world settings. We present information about the challenges and opportunities to conduct CER, including enhanced patient registries for observational CER and effectiveness trials (also called pragmatic trials). We discuss the urgent need to define the appropriate methodologies for CER and to develop and prioritize a research agenda for CER studies in asthma with the help of a diverse group of stakeholders.
Comparative effectiveness research; comparative clinical effectiveness research; observational studies; effectiveness trials; efficacy trials; pragmatic trials; explanatory trials; asthma
With the ongoing debate over health care reform in the United States, public health and policy makers have paid growing attention to the need for comparative effectiveness research (CER). Recent allocation of federal funds for CER represents a significant move toward increased evidence-based practice and better informed allocation of constrained health care resources; however, there is also heated debate on how, or whether, CER may contribute to controlling national health care expenditures. Economic evaluation, in the form of cost-effectiveness or cost-benefit analysis, is often an aspect of CER studies, yet there are no recommendations or guidelines for providing clinical investigators with the necessary skills to collect, analyze, and interpret economic data from clinical trials or observational studies. With an emphasis on multidisciplinary research, the Clinical and Translational Science Award (CTSA) consortium and institutional CTSA sites serve as an important resource for training researchers to engage in CER. In this article, the authors discuss the potential role of CTSA sites in integrating economic evaluation methods into their comparative effectiveness education goals, using the Columbia University Medical Center CTSA as an example. By allowing current and future generations of clinical investigators to become fully engaged not only in CER, but in the economic evaluations that result from such analyses, CTSA sites can help develop the necessary foundation for advancing research to guide clinical decision making and efficient use of limited resources.
The upper airway serves three important functions: respiration, swallowing, and speech. During development it undergoes significant structural and functional changes that affect its size, shape, and mechanical properties. Abnormalities of the upper airway require prompt attention, because these often alter ventilatory patterns and gas exchange, particularly during sleep when upper airway motor tone and ventilatory drive are diminished. Recognizing the relationship of early life events to lung health and disease, the National Heart, Lung, and Blood Institute (NHLBI), with cofunding from the Office of Rare Diseases (ORD), convened a workshop of extramural experts, from many disciplines. The objective of the workshop was: (1) to review the state of science in pediatric upper airway disorders; (2) to make recommendations to the Institute to fill knowledge gaps; (3) to prioritize new research directions; and (4) to capitalize on scientific opportunities. This report provides recommendations that could facilitate translation of basic research findings into practice to better diagnose, treat, and prevent airway compromise in children.
To improve formulary design processes and support payers in providing more effective health care, policy makers should consider involving commercial payers in the development of comparative effectiveness research and creation of research and treatment guidelines.
The perspective of commercial payers on comparative effectiveness research (CER) has not been well researched. This study aims to describe how US commercial payers use and value CER for formulary decision making in different disease states.
We recruited 20 medical and pharmaceutical directors from national and regional plans who are involved in pharmaceutical and therapeutics committees to participate in the study. We conducted in-depth qualitative interviews with the payers and asked them to rate the usefulness of CER study types across various disease states and market conditions. The results were analyzed for thematic content.
Our findings indicate that payers are interested in a broad range of CER study types, are unsatisfied with the current state of CER, and would like to partner with research groups to develop research and treatment guidelines to better leverage CER. Payers value CER less so in oncology than in other disease states because of limitations in their ability to manage oncology therapies.
To improve formulary design processes and support payers in providing more effective health care, policy makers should consider involving commercial payers in the development of CER as well as in the creation of research and treatment guidelines.
Comparative effectiveness research and pragmatic clinical trials are valued methods to address the limitations of traditional randomized trials, answer questions of cost-effectiveness or noninferiority, and inform data-driven dialogue and decision making by stakeholders.
Although much effort has focused on identifying national comparative effectiveness research (CER) priorities, little is known about the CER priorities of community-based practitioners treating patients with advanced cancer. CER priorities of managed-care–based clinicians may be valuable as reflections of both payer and provider research interests.
We conducted mixed methods interviews with 10 clinicians (five oncologists and five pharmacists) at five health plans within the Health Maintenance Organization Cancer Research Network. We asked, “What evidence do you most wish you had when treating patients with advanced cancer?” and questioned participants on their impressions and knowledge of CER and pragmatic clinical trials (PCTs). We conducted qualitative analyses to identify themes across interviews.
Ninety percent of participants had heard of CER, 20% had heard of PCTs, and all rated CER/PCTs as highly relevant to patient and health plan decision making. Each participant offered between three and 10 research priorities. Half (49%) involved head-to-head treatment comparisons; another 20% involved comparing different schedules or dosing regimens of the same treatment. The majority included alternative outcomes to survival (eg, toxicity, quality of life, noninferiority). Participants cited several limitations to existing evidence including lack of generalizability, funding biases, and rapid development of new treatments.
Head-to-head treatment comparisons remain a major evidence need among community-based oncology clinicians, and CER/PCTs are highly valued methods to address the limitations of traditional randomized trials, answer questions of cost-effectiveness or noninferiority, and inform data-driven dialogue and decision making by all stakeholders.
The Clinical and Translational Science Awards (CTSAs) were initiated to improve the conduct and impact of NIH's research portfolio, transforming training programs and research infrastructure at academic institutions and creating a nationwide consortium. They provide a model for translating research across disciplines and offer an efficient and powerful platform for comparative effectiveness research (CER), an effort that has long struggled but enjoys renewed hope under health care reform. CTSAs include study design and methods expertise, informatics, and regulatory support; programs in education, training, and career development in domains central to CER; and robust programs in community engagement, both of the general public and of clinical practice communities.
Albert Einstein College of Medicine of Yeshiva University and Montefiore Medical Center have entered a formal partnership that places their CTSA at a critical intersection for clinical and translational research. Their CTSA leaders were asked to develop a strategy for enhancing CER activities, and in 2010 they developed a model that encompasses four broadly defined “compartments” of research strength that must be coordinated for this enterprise to succeed: evaluation and health services research, biobehavioral research and prevention, efficacy studies and clinical trials, and social science and implementation research.
This article provides historical context for CER, elucidates Einstein-Montefiore’s CER model and strategic planning efforts, and illustrates how a CTSA can provide a vision, leadership, coordination, and services to support an academic health center’s collaborative efforts to develop a robust CER portfolio and thus contribute to the national effort to improve health and health care.
Increasing numbers of Americans are living with multiple chronic conditions (MCCs) and disabilities. Addressing health care needs of persons with MCCs or disabilities presents challenges on many levels. For health services researchers, priorities include (1) considering MCCs and disabilities in comparative effectiveness research (CER) and assessing quality of care; and (2) identifying and evaluating the data needed to conduct CER, performance measure development, and other research to inform health policy and public health decisions concerning persons with MCCs or disabilities. Little information is available to guide CER or treatment choices for persons with MCCs or disabilities, however, because they are typically excluded from clinical trials that produce the scientific evidence base. Furthermore, most research funding flows through public and private agencies oriented around single organ systems or diseases. Likely changes in the data landscape—notably wider dissemination of electronic health records (EHRs) and moving toward updated coding nomenclatures—may increase the information available to monitor health care service delivery and quality for persons with MCCs and disabilities. Generating this information will require new methods to extract and code information about MCCs and functional status from EHRs, especially narrative texts, and incorporating coding nomenclatures that capture critical dimensions of functional status and disability.
Chronic conditions; disability; functional status; comparative effectiveness research; quality measurement; health information technology; coding nomenclatures
The Division of Lung Diseases of the National Heart, Lung, and Blood Institute, with the Office of Rare Diseases Research, held a workshop to identify priority areas and strategic goals to enhance and accelerate research that will result in improved understanding of the lung vasculature, translational research needs, and ultimately the care of patients with pulmonary vascular diseases. Multidisciplinary experts with diverse experience in laboratory, translational, and clinical studies identified seven priority areas and discussed limitations in our current knowledge, technologies, and approaches. The focus for future research efforts include the following: (1) better characterizing vascular genotype–phenotype relationships and incorporating systems biology approaches when appropriate; (2) advancing our understanding of pulmonary vascular metabolic regulatory signaling in health and disease; (3) expanding our knowledge of the biologic relationships between the lung circulation and circulating elements, systemic vascular function, and right heart function and disease; (4) improving translational research for identifying disease-modifying therapies for the pulmonary hypertensive diseases; (5) establishing an appropriate and effective platform for advancing translational findings into clinical studies testing; and (6) developing the specific technologies and tools that will be enabling for these goals, such as question-guided imaging techniques and lung vascular investigator training programs. Recommendations from this workshop will be used within the Lung Vascular Biology and Disease Extramural Research Program for planning and strategic implementation purposes.
right ventricle; pulmonary hypertension; metabolism; genomics; phenotyping
Genome-wide association studies (GWAS) have revealed novel genes and pathways involved in lung disease, many of which are potential targets for therapy. However, despite numerous successes, a large proportion of the genetic variance in disease risk remains unexplained, and the function of the associated genetic variations identified by GWAS and the mechanisms by which they alter individual risk for disease or pathogenesis are still largely unknown. The National Heart, Lung, and Blood Institute (NHLBI) convened a 2-day workshop to address these shortcomings and to make recommendations for future research areas that will move the scientific community beyond gene discovery. Topics of individual sessions ranged from data integration and systems genetics to functional validation of genetic variations in humans and model systems. There was broad consensus among the participants for five high-priority areas for future research, including the following: (1) integrated approaches to characterize the function of genetic variations, (2) studies on the role of environment and mechanisms of transcriptional and post-transcriptional regulation, (3) development of model systems to study gene function in complex biological systems, (4) comparative phenomic studies across lung diseases, and (5) training in and applications of bioinformatic approaches for comprehensive mining of existing data sets. Last, it was agreed that future research on lung diseases should integrate approaches across “-omic” technologies and to include ethnically/racially diverse populations in human studies of lung disease whenever possible.
genetics; epigenetics; genomics; bioinformatics; lung disease
Comparative effectiveness research (CER) using observational data requires informatics methods for the extraction, standardization, sharing, and integration of data derived from a variety of electronic sources. In the Oncoshare project, we have developed such methods as part of a collaborative multi-institutional CER study of patterns, predictors, and outcome of breast cancer care. In this paper, we present an evaluation of the approaches we undertook and the lessons we learned in building and validating the Oncoshare data resource. Specifically, we determined that 1) the state or regional cancer registry makes the most efficient starting point for determining inclusion of subjects; 2) the data dictionary should be based on existing registry standards, such as Surveillance, Epidemiology and End Results (SEER), when applicable; 3) the Social Security Administration Death Master File (SSA DMF), rather than clinical resources, provides standardized ascertainment of mortality outcomes; and 4) CER database development efforts, despite the immediate availability of electronic data, may take as long as two years to produce validated, reliable data for research. Through our efforts using these methods, Oncoshare integrates complex, longitudinal data from multiple electronic medical records and registries and provides a rich, validated resource for research on oncology care.
Background Clinical trials are widely considered
the gold standard in comparative effectiveness research (CER) but the high cost
and complexity of traditional trials and concerns about generalizability to
broad patient populations and general clinical practice limit their appeal.
Unsuccessful implementation of CER results limits the value of even the highest
quality trials. Planning for a trial comparing two standard strategies of
insulin administration for hospitalized patients led us to develop a new method
for a clinical trial designed to be embedded directly into the clinical care
setting thereby lowering the cost, increasing the pragmatic nature of the
overall trial, strengthening implementation, and creating an integrated
environment of research-based care.
Purpose We describe a novel randomized clinical
trial that uses the informatics and statistics infrastructure of the Veterans
Affairs Healthcare System (VA) to illustrate one key component (called the
point-of-care clinical trial – POC-CT) of a ‘learning healthcare
system,’ and settles a clinical question of interest to the VA.
Methods This study is an open-label, randomized
trial comparing sliding scale regular insulin to a weight-based regimen for
control of hyperglycemia, using the primary outcome length of stay, in non-ICU
inpatients within the northeast region of the VA. All non-ICU patients who
require in-hospital insulin therapy are eligible for the trial, and the
VA’s automated systems will be used to assess eligibility and present
the possibility of randomization to the clinician at the point of care.
Clinicians will indicate their approval for informed consent to be obtained by
study staff. Adaptive randomization will assign up to 3000 patients,
preferentially to the currently ‘winning’ strategy, and all care
will proceed according to usual practices. Based on a Bayesian stopping rule,
the study has acceptable frequentist operating characteristics (Type I error
6%, power 86%) against a 12% reduction of median length
of stay from 5 to 4.4 days. The adaptive stopping rule promotes implementation
of a successful treatment strategy.
Limitations Despite clinical equipoise, individual
healthcare providers may have strong treatment preferences that jeopardize the
success and implementation of the trial design, leading to low rates of
randomization. Unblinded treatment assignment may bias results. In addition,
generalization of clinical results to other healthcare systems may be limited by
differences in patient population. Generalizability of the POC-CT method depends
on the level of informatics and statistics infrastructure available to a
Conclusions The methods proposed will demonstrate
outcome-based evaluation of control of hyperglycemia in hospitalized veterans.
By institutionalizing a process of statistically sound and efficient learning,
and by integrating that learning with automatic implementation of best practice,
the participating VA Healthcare Systems will accelerate improvements in the
effectiveness of care.
Ceramides (Cer) in the stratum corneum are essential for epidermal permeability barrier function. Thus, topical Cer replacement therapy has been employed to improve barrier function in clinical situations associated with Cer deficiency, e.g., atopic dermatitis. Because of the disadvantages of both natural- and skin identical-Cer (CNS origins and cost, respectively), synthetic chemical mimics, or pseudoceramides (pseudo-Cer), have been utilized as Cer substitutes. Whereas increased levels of intracellular Cer trigger cell growth inhibition and apoptosis, Cer levels are maintained by metabolic/catabolic pathways protecting cells from Cer-induced apoptosis. However, since the metabolic fates of each pseudo-Cer remain unknown, their wide-spread deployment in topical agents has raised concern about potential toxicities.
We compared the effects of two chemically-unrelated commercially-available pseudo-Cer to exogenous cell-permeant (C2)- or natural (C18)-Cer on cell growth and apoptosis thresholds in cultured human keratinocytes (CHK).
Cell growth and cell toxicity of CHK exposed to either C2-Cer or pseudo-Cer were assessed by MTT and lactate dehydrogenase release assays. Mitochondrial membrane potential, an indicator of apoptosis, was measured using membrane permeabilized semi-intact keratinocytes exposed C2-Cer, natural-Cer or pseudo-Cer.
While the cell-permeant-Cer inhibits keratinocyte growth and increases cell toxicity, neither of the pseudo-Cer showed these effects. Decreased mitochondrial membrane potential occurred in CHK incubated with cell-permeant- and natural-Cer, but not pseudo-Cer.
Taken together with preclinical safety studies of these pseudo-Cer and their wide-spread use over the counter without evidence of toxicity, these studies provide further assurance about the safety of these pseudo-Cer for topical use.
apoptosis; atopic dermatitis; ceramide; permeability barrier; pseudoceramide
The National Heart, Lung, and Blood Institute (NHLBI) convened a conference call working group, consisting of experts in stroke and cerebrovascular biology on January 28, 2005. The purpose of this working group was to develop a prioritized set of recommendations for NHLBI to establish a focused and comprehensive set of research activities in cerebrovascular biology and disease. Three thematic areas of research emerged: (1) molecular and cellular neurobiology of cerebral blood vessels, focusing on genomics and proteomics, neurovascular signaling and cerebrovascular embryogenesis, development and plasticity; (2) resource development, involving the development of new methodological approaches for normal and altered function of the neurovascular unit, collaborative research, and training in cerebrovascular pathobiology; and (3) cerebrovascular diseases and translational approaches, addressing vascular mechanisms of disease, the role of risk factors, importance of biomarkers with the ultimate goal of developing new treatments.
cerebrovascular disease; microcirculation
The first work reporting synthesis of glucosylceramide (cerebrin, GlcCer) by yeasts was published in 1930. During approximately 70 years members of this class of glycosphingolipids (GSL) were considered merely structural components of plasma membrane in fungi. However, in the last decade GlcCer was reported to be involved with fungal growth, differentiation, virulence, immunogenicity, and lipid raft architecture in at least two human pathogens. Fungal GlcCer are structurally distinct from their mammalian counterparts and enriched at the cell wall, which makes this molecule an effective target for antifungal activity of specific ligands (peptides and antibodies to GlcCer). Therefore, GSL are promising targets for new drugs to combat fungal diseases. This review discusses the most recent information on biosynthesis and role of GlcCer in fungal pathogens.
glucosylceramide; fungal pathogens; antifungal targets
In the last year increased attention has been focused on translating federally sponsored health research into improved health for Americans. Since the passage of the American Recovery and Reinvestment Act (ARRA) on February 17, 2009, this focus has been accelerated by ARRA funds to support Comparative Effectiveness Research (CER). A high proportion of topical areas of interest in CER affect the older segment of the population. The Department of Veterans Affairs (VA), the National Institute on Aging (NIA), and the Agency for Healthcare Research and Quality (AHRQ) have supported robust research portfolios focused on aging populations that meet the varying definitions of CER. In this short paper we briefly describe the research missions of the AHRQ, NIA, and VA. We then review the various definitions of CER as put forward by the Congressional Budget Office, the Institute of Medicine, and the ARRA established Federal Coordinating Council; as well as important topics for which CER is particularly needed. Finally, we set forth approaches in which the three agencies support CER involving the aging population and outline opportunities for future CER research.
patient outcomes; comparative effectiveness; research
During the National Neurotrauma Symposium 2010, the DG Research of the European Commission and the National Institutes of Health/National Institute of Neurological Disorders and Stroke (NIH/NINDS) organized a workshop on comparative effectiveness research (CER) in traumatic brain injury (TBI). This workshop reviewed existing approaches to improve outcomes of TBI patients. It had two main outcomes: First, it initiated a process of re-orientation of clinical research in TBI. Second, it provided ideas for a potential collaboration between the European Commission and the NIH/NINDS to stimulate research in TBI. Advances in provision of care for TBI patients have resulted from observational studies, guideline development, and meta-analyses of individual patient data. In contrast, randomized controlled trials have not led to any identifiable major advances. Rigorous protocols and tightly selected populations constrain generalizability. The workshop addressed additional research approaches, summarized the greatest unmet needs, and highlighted priorities for future research. The collection of high-quality clinical databases, associated with systems biology and CER, offers substantial opportunities. Systems biology aims to identify multiple factors contributing to a disease and addresses complex interactions. Effectiveness research aims to measure benefits and risks of systems of care and interventions in ordinary settings and broader populations. These approaches have great potential for TBI research. Although not new, they still need to be introduced to and accepted by TBI researchers as instruments for clinical research. As with therapeutic targets in individual patient management, so it is with research tools: one size does not fit all.
comparative effectiveness research; clinical research; clinical trials; methodology; systems biology; traumatic brain injury
The United States aspires to use information from comparative effectiveness research (CER) to reduce waste and contain costs without instituting a formal rationing mechanism or compromising patient or physician autonomy with regard to treatment choices. With such ambitious goals, traditional combinations of research designs and analytical methods used in CER may lead to disappointing results. In this paper, I study how alternate regimes of comparative effectiveness information help shape the marginal benefits (demand) curve in the population and how such perceived demand curves impact decision-making at the individual patient level and welfare at the societal level. I highlight the need to individualize comparative effectiveness research in order to generate the true (normative) demand curve for treatments. I discuss methodological principles that guide research designs for such studies. Using an example of the comparative effect of substance abuse treatments on crime, I use novel econometric methods to salvage individualized information from an existing dataset.
individualization; comparative effectiveness research; potential outcomes; latent factor models
The National Heart, Lung, and Blood Institute (NHLBI) convened a workshop of cardiologists, cardiac electrophysiologists, cell biophysicists, and computational modelers on August 20 and 21, 2007, in Washington, DC, to advise the NHLBI on new research directions needed to develop integrative approaches to elucidate human cardiac function. The workshop strove to identify limitations in the use of data from nonhuman animal species for elucidation of human electromechanical function/activity and to identify what specific information on ion channel kinetics, calcium handling, and dynamic changes in the intracellular/extracellular milieu is needed from human cardiac tissues to develop more robust computational models of human cardiac electromechanical activity. This article summarizes the workshop discussions and recommendations on the following topics: (1) limitations of animal models and differences from human electrophysiology, (2) modeling ion channel structure/function in the context of whole-cell electrophysiology, (3) excitation–contraction coupling and regulatory pathways, (4) whole-heart simulations of human electromechanical activity, and (5) what human data are currently needed and how to obtain them. The recommendations can be found on the NHLBI Web site at http://www.nhlbi.nih.gov/meetings/workshops/electro.htm.
arrhythmia; cardiovascular diseases; contractility; electrophysiology; mechanics
Recent advances in genomic research have demonstrated a substantial role for genomic factors in predicting response to cancer therapies. Researchers in the fields of cancer pharmacogenomics and pharmacoepidemiology seek to understand why individuals respond differently to drug therapy, in terms of both adverse effects and treatment efficacy. To identify research priorities as well as the resources and infrastructure needed to advance these fields, the National Cancer Institute (NCI) sponsored a workshop titled “Cancer Pharmacogenomics: Setting a Research Agenda to Accelerate Translation” on July 21, 2009, in Bethesda, MD. In this commentary, we summarize and discuss five science-based recommendations and four infrastructure-based recommendations that were identified as a result of discussions held during this workshop. Key recommendations include 1) supporting the routine collection of germline and tumor biospecimens in NCI-sponsored clinical trials and in some observational and population-based studies; 2) incorporating pharmacogenomic markers into clinical trials; 3) addressing the ethical, legal, social, and biospecimen- and data-sharing implications of pharmacogenomic and pharmacoepidemiologic research; and 4) establishing partnerships across NCI, with other federal agencies, and with industry. Together, these recommendations will facilitate the discovery and validation of clinical, sociodemographic, lifestyle, and genomic markers related to cancer treatment response and adverse events, and they will improve both the speed and efficiency by which new pharmacogenomic and pharmacoepidemiologic information is translated into clinical practice.
For Comparative Effectiveness Research (CER) there is a need to develop scales for appraisal of available clinical research. Aims were to 1) test the feasibility of applying the pragmatic-explanatory continuum indicator summary tool and the six CER defining characteristics of the Institute of Medicine to RCTs of acupuncture for treatment of low back pain, and 2) evaluate the extent to which the evidence from these RCTs is relevant to clinical and health policy decision making.
We searched Medline, the AcuTrials™ Database to February 2011 and reference lists and included full-report randomized trials in English that compared needle acupuncture with a conventional treatment in adults with non-specific acute and/or chronic low back pain and restricted to those with ≥30 patients in the acupuncture group. Papers were evaluated by 5 raters.
From 119 abstracts, 44 full-text publications were screened and 10 trials (4,901 patients) were evaluated. Due to missing information and initial difficulties in operationalizing the scoring items, the first scoring revealed inter-rater and inter-item variance (intraclass correlations 0.02–0.60), which improved after consensus discussions to 0.20–1.00. The 10 trials were found to cover the efficacy-effectiveness continuum; those with more flexible acupuncture and no placebo control scored closer to effectiveness.
Both instruments proved useful, but need further development. In addition, CONSORT guidelines for reporting pragmatic trials should be expanded. Most studies in this review already reflect the movement towards CER and similar approaches can be taken to evaluate comparative effectiveness relevance of RCTs for other treatments.