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Background: Pragmatic trials comparing "standard of care" treatments provide comparative effectiveness data to make practice of medicine more evidence-based. With electronic health records, recruiting and conducting such trials can be relatively inexpensive. But some worry that the traditional research ethics framework poses unnecessary obstacles and is not appropriate for evaluating such clinical trials. This concern is based on the view (which we call the "Standard of Care Principle") that such research is similar to usual clinical practice and therefore does not raise significant ethical issues since everyone in the research study will receive an accepted standard of care treatment., Methods: A case study of a pragmatic randomized clinical trial (Blood Pressure Medication Timing study) comparing morning versus nighttime dosing of antihypertensive medications. The Blood Pressure Medication Timing study has been proposed as a paradigm example of why the Standard of Care Principle obviates the need for traditional levels of ethical scrutiny and how the current regulatory framework poses unnecessary obstacles to research. We provide an ethical analysis of the Blood Pressure Medication Timing study, drawing on the empirical literature as well as on normative analysis., Results: The Standard of Care Principle is the main ethical rationale given by commentators for asserting that the Blood Pressure Medication Timing study does not require "significant ethical debate" and by investigators for the assertion that the Blood Pressure Medication Timing study is minimal risk and thus eligible for lessened regulatory requirements. However, the Blood Pressure Medication Timing study raises important ethical issues, including whether it is even necessary, given the considerable randomized clinical trial evidence in support of nighttime dosing, a much larger (N≈17,000) confirmatory randomized clinical trial already in progress, evidence for safety of nighttime dosing, and the cost-free availability of the intervention. Furthermore, the Standard of Care Principle provides a misleading basis for analyzing the informed consent requirements, especially regarding the requirement to disclose alternative courses of treatment that "might be advantageous to the subject.", Conclusion: The Standard of Care Principle is ethically inadequate and misleading even when it is applied to the pragmatic randomized clinical trial proposed as a paradigm case for its application., (© The Author(s) 2015.)

One of the provisions of the health care reform legislation in 2010 was for funding pragmatic clinical trials or large observational studies for comparing the effectiveness of different approved medical treatments, involving broadly representative patient populations. After reviewing pragmatic clinical trials and the issues and challenges that have made them just a small fraction of comparative effectiveness research (CER), we focus on a recent development that uses point-of-care (POC) clinical trials to address the issue of "knowledge-action gap" in pragmatic CER trials. We give illustrative examples of POC-CER trials and describe a trial that we are currently planning to compare the effectiveness of newly approved oral anticoagulants. We also develop novel stage-wise designs of information-rich POC-CER trials under competitive budget constraints, by using recent advances in adaptive designs and other statistical methodologies., (Published by Elsevier Inc.)

Dissemination and implementation science addresses the application of research findings in varied health care settings. Despite the potential benefit of dissemination and implementation work to primary care, ideal laboratories for this science have been elusive. Practice-based research networks (PBRNs) have a long history of conducting research in community clinical settings, demonstrating an approach that could be used to execute multiple research projects over time in broad and varied settings. PBRNs also are uniquely structured and increasingly involved in pragmatic trials, a research design central to dissemination and implementation science. We argue that PBRNs and dissemination and implementation scientists are ideally suited to work together and that the collaboration of these 2 groups will yield great value for the future of primary care and the delivery of evidence-based health care., (© Copyright 2014 by the American Board of Family Medicine.)

Limited health research capacity in one of the factors that prevents developing countries from attaining optimal health outcomes and achieving the Millennium Development Goals. We report here, the details of a workshop on pragmatic knowledge translation trials for Cameroonian researchers, the material covered and additional resources to support capacity development. At the end of this workshop, knowledge gains were noted and participants were able to initiate proposals for funding. These proposals were aimed at improving the clinical management of diabetes, hypertension and malaria.

Objectives: The way clinical research and care are currently separated encourages the practice of unverifiable medicine. Some pragmatic trials can be designed (1) to guide proper medical conduct in the presence of uncertainty and (2) to govern the distinction between unvalidated and validated care., Methods: Care trials are simple randomized trials integrated into a practice they regulate in the interest of present patients. The fundamental principle guiding the design of a care trial is the protection of the patient being offered medical care that has not yet been validated. Selection criteria are inclusive, to assist most current patients confronted with the problem. The trial entails no extra tests or risks beyond what is proven beneficial. Endpoints are pre-defined, simple, valuable and resistant to bias. Follow-up visits and tests are routine. Data is collected in simple case-report forms., Results: Care trials protect present patients from both unverifiable medicine and research performed for extraneous interests. They provide prudent care when evidence is lacking. They should not be obstructed by the need for separate funding, or by bureaucracy., Conclusion: Care trials can identify which medical alternative should be standard therapy. In the meantime, they provide optimal care in the presence of uncertainty., (Copyright © 2014 Elsevier Inc. All rights reserved.)

The creation of the Patient-Centered Outcomes Research Trust Fund and the Patient-Centered Outcomes Research Institute (PCORI) through the Patient Protection and Affordable Care Act of 2010 presents new opportunities for funding patient-centered comparative effectiveness research (CER) in radiology. We provide an overview of the evolution of federal funding and priorities for CER with a focus on radiology-related priority topics over the last two decades, and discuss the funding processes and methodological standards outlined by PCORI. We introduce key paradigm shifts in research methodology that will be required on the part of radiology health services researchers to obtain competitive federal grant funding in patient-centered outcomes research. These paradigm shifts include direct engagement of patients and other stakeholders at every stage of the research process, from initial conception to dissemination of results. We will also discuss the increasing use of mixed methods and novel trial designs. One of these trial designs, the pragmatic trial, has the potential to be readily applied to evaluating the effectiveness of diagnostic imaging procedures and imaging-based interventions among diverse patient populations in real-world settings., (Copyright © 2014 AUR. Published by Elsevier Inc. All rights reserved.)

Background: Reviews of maternity services highlight the need for a reduction of medical interventions for women with low risk pregnancies and births to prevent the potential cascade of interventions and their associated risks. Complementary medicines (CM) such as acupuncture and acupressure have claimed to be effective in reducing interventions in labour; however, systematic reviews of evidence to date are conflicting., Aims: To examine current evidence from systematic reviews on the topic of acupuncture and acupressure for pain management in labour and birth, and to evaluate the methodological and treatment frameworks applied to this evidence., Methods: A search limited to systematic reviews of the MEDLINE, CINAHL, PUBMED, EMBASE and Cochrane databases was performed in December 2013 using the keywords 'CAM', 'alternative medicine', 'complementary medicine', 'complementary therapies', 'traditional medicine', 'Chinese Medicine', 'Traditional Chinese Medicine', 'acupuncture', 'acupressure', cross-referenced with 'childbirth', 'birth', labo*r', and 'delivery'. The quality of the evidence is also evaluated in the context of study design., Results: The RCTs included in these systematic reviews differed in terms of study designs, research questions, treatment protocols and outcome measures, and yielded some conflicting results. It may be inappropriate to include these together in a systematic review, or pooled analysis, of acupuncture for labour with an expectation of an overall conclusion for efficacy. Trials of acupuncture and acupressure in labour show promise, but further studies are required., Conclusion: The use of current systematic reviews of the evidence for acupuncture and acupressure for labour and birth may be misleading. Appropriate methods and outcome measures for investigation of acupuncture and acupressure treatment should more carefully reflect the research question being asked. The use of pragmatic trials designs with woman-centred outcomes may be appropriate for evaluating the effectiveness of these therapies., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

There has been a recent surge of eHealth programs in cancer and other content areas, but few reviews have focused on the methodologies and designs employed in these studies. We conducted a systematic review of studies on eHealth interventions on cancer prevention and control published between 2001 and 2010 applying the Pragmatic Explanatory Continuum Indicator Summary (PRECIS) criteria and external validity components from the Reach Effectiveness Adoption Implementation Maintenance (RE-AIM) framework. We identified 113 studies that focused on cancer prevention and control of eHealth interventions. Most studies fell midway along the explanatory/pragmatic trial continuum, but few reported on various practical feasibility criteria for translation. Despite vast interest in cancer eHealth and the applied nature of this field, few studies considered key external validity issues. There is a need for use of alternative pragmatic study designs and transparent reporting of external validity components to produce more rapid and generalizable results.

Background: Pharmaceutical pragmatic clinical trials (PCTs) are designed to provide the type of evidence that is desired by patients, clinicians and payers but too often missing from traditional regulatory trials., Purpose: This paper presents framework for designing pragmatic trials incorporating evidence desired by post-regulatory decision makers while remaining within acceptable standards for regulatory approval., Methods: Following a stakeholder meeting convened in May of 2009 to identify gaps in information collected in Phase 3 trials, CMTP staff and the authors drafted recommendations for Pragmatic Phase 3 Pharmaceutical Trials. This draft was circulated first to technical working group members for their comments. After revising the document based on these comments, it was distributed electronically to other select experts and then made available for public comment. The final version of the EGD appears on the CMTP website., Results: The process resulted in a set of 10 recommendations for conducting Phase 3 trials that met regulatory needs while addressing information important to physicians, patients, payers, and policy-makers. These recommendations encompassed three primary areas: generalizability from the trial participants to the clinical population of interest; effectiveness relative to active comparators; and consistently measured relevant outcomes for coverage and treatment decisions., Limitations: While stakeholders were involved throughout the process, not all recommendations will meet the needs of all stakeholders., Conclusions: Pragmatic trial design need not be deferred until a product is in widespread use. Incremental movement toward the more pragmatic design of Phase 3 trials is desirable., (© 2013.)

We describe a conceptual analytic framework for aligning observational and randomized controlled trial (RCT) data. The framework allows one to 1) use observational data to estimate treatment effects comparable to their RCT counterparts, 2) properly include early events that occur soon after treatment initiation in the analysis of observational data, 3) estimate various treatment effects that are of clinical and scientific relevance while appropriately adjusting for time-varying confounders in both the RCT and observational analyses, 4) assess the generalizability of RCT findings in the more diverse populations generally found in the observational data, and 5) combine both types of data to study associations that cannot be addressed by one study or a single dataset. We describe the theoretical application of this framework to the Women's Health Initiative data to examine the relation between postmenopausal hormone therapy and coronary heart disease. The analytic framework can be tailored to specific exposure-outcome associations and data sources, and may be refined as more is learned about its strengths and limitations.

With increased attention to the importance of translating research to clinical practice and policy, recent years have seen a proliferation of particular types of research, including pragmatic trials and dissemination and implementation research. Such research seeks to understand how and why interventions function in real-world settings, as opposed to highly controlled settings involving conditions not likely to be repeated outside the research study. Because understanding the context in which interventions are implemented is imperative for effective pragmatic trials and dissemination and implementation research, the use of mixed methods is critical to understanding trial results and the success or failure of implementation efforts. This article discusses a number of dimensions of mixed methods research, utilizing at least one qualitative method and at least one quantitative method, that may be helpful when designing projects or preparing grant proposals. Although the strengths and emphases of qualitative and quantitative approaches differ substantially, methods may be combined in a variety of ways to achieve a deeper level of understanding than can be achieved by one method alone. However, researchers must understand when and how to integrate the data as well as the appropriate order, priority, and purpose of each method. The ability to demonstrate an understanding of the rationale for and benefits of mixed methods research is increasingly important in today's competitive funding environment, and many funding agencies now expect applicants to include mixed methods in proposals. The increasing demand for mixed methods research necessitates broader methodological training and deepened collaboration between medical, clinical, and social scientists. Although a number of challenges to conducting and disseminating mixed methods research remain, the potential for insight generated by such work is substantial., (Copyright © 2013 Academic Pediatric Association. Published by Elsevier Inc. All rights reserved.)

There is at present some confusion about the relative value of clinical trials performed to investigate efficacy vs. those designed to investigate effectiveness. This is particularly challenging when studies performed as experiments for regulators by companies are used to shape and inform clinical practice, especially if studies conducted under more real life conditions fail to support predicted benefits. We review the field in relation to the new antipsychotics, in particular. Other indications, including mood disorders, which are also briefly touched upon, have so far received less definitive attention, but are likely to encounter the same difficulties. We conclude that, where the results of efficacy trials are positive and an effectiveness trial is negative, one should not necessarily prefer the effectiveness trial - it may simply have failed. Where efficacy trials and effectiveness trials point to similar conclusions, then the findings are mutually supportive.