Making genomic medicine evidence-based and patient-centered: a structured review and landscape analysis of comparative effectiveness research.

Comparative effectiveness research (CER) in genomic medicine (GM) measures the clinical utility of using genomic information to guide clinical care in comparison to appropriate alternatives. We summarized findings of high-quality systematic reviews that compared the analytic and clinical validity and clinical utility of GM tests. We focused on clinical utility findings to summarize CER-derived evidence about GM and identify evidence gaps and future research needs. We abstracted key elements of study design, GM interventions, results, and study quality ratings from 21 systematic reviews published in 2010 through 2015. More than half (N = 13) of the reviews were of cancer-related tests. All reviews identified potentially important clinical applications of the GM interventions, but most had significant methodological weaknesses that largely precluded any conclusions about clinical utility. Twelve reviews discussed the importance of patient-centered outcomes, although few described evidence about the impact of genomic medicine on these outcomes. In summary, we found a very limited body of evidence about the effect of using genomic tests on health outcomes and many evidence gaps for CER to address.Genet Med advance online publication 13 April 2017.

SPIRIT 2013 Statement: defining standard protocol items for clinical trials.

The protocol of a clinical trial serves as the foundation for study planning, conduct, reporting, and appraisal. However, trial protocols and existing protocol guidelines vary greatly in content and quality. This article describes the systematic development and scope of SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) 2013, a guideline for the minimum content of a clinical trial protocol. The 33-item SPIRIT checklist applies to protocols for all clinical trials and focuses on content rather than format. The checklist recommends a full description of what is planned; it does not prescribe how to design or conduct a trial. By providing guidance for key content, the SPIRIT recommendations aim to facilitate the drafting of high-quality protocols. Adherence to SPIRIT would also enhance the transparency and completeness of trial protocols for the benefit of investigators, trial participants, patients, sponsors, funders, research ethics committees or institutional review boards, peer reviewers, journals, trial registries, policymakers, regulators, and other key stakeholders.

SPIRIT 2013 statement: defining standard protocol items for clinical trials.

The protocol of a clinical trial serves as the foundation for study planning, conduct, reporting, and appraisal. However, trial protocols and existing protocol guidelines vary greatly in content and quality. This article describes the systematic development and scope of SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) 2013, a guideline for the minimum content of a clinical trial protocol.The 33-item SPIRIT checklist applies to protocols for all clinical trials and focuses on content rather than format. The checklist recommends a full description of what is planned; it does not prescribe how to design or conduct a trial. By providing guidance for key content, the SPIRIT recommendations aim to facilitate the drafting of high-quality protocols. Adherence to SPIRIT would also enhance the transparency and completeness of trial protocols for the benefit of investigators, trial participants, patients, sponsors, funders, research ethics committees or institutional review boards, peer reviewers, journals, trial registries, policymakers, regulators, and other key stakeholders.

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.

Reconciling primary care and specialist perspectives on prostate cancer screening.

When specialists propose screening guidelines for primary care clinicians to implement, differences in perspectives between the 2 groups can create conflicts. Two recent specialty organization guidelines illustrate this issue. The American Urological Association guideline panel and National Comprehensive Cancer Network recommend that average-risk men first be counseled about the risks and benefits of prostate-specific antigen screening for prostate cancer at age 40 rather than at the previously recommended age of 50 years. There is no direct evidence, however, that this recommendation has any impact on prostate cancer-specific mortality. To avoid distracting primary care clinicians from providing services with proven benefit and value for patients, professional organizations should follow appropriate standards for developing guidelines. Primary care societies and health care systems should also be encouraged to evaluate the evidence and decide whether implementing the recommendations are feasible and appropriate.

Building a strategic framework for comparative effectiveness research in complementary and integrative medicine.

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.

Comparative effectiveness research: a progress report.

Sixteen months ago, comparative effectiveness research (CER) began its rapid rise, when the American Recovery and Reinvestment Act of 2009 allocated $1.1 billion for CER. This progress report summarizes how the recipients of the funds-the National Institutes of Health, Agency for Healthcare Research and Quality, and Office of the Secretary of the U.S. Department of Health and Human Services-are spending the $1.1 billion, how the Institute of Medicine priority topics have fared in the agencies' funding programs, and the developing plans for a national CER program. As the United States works to absorb 32 million currently uninsured people into the health care system while simultaneously improving the quality of care and slowing cost increases, CER will increasingly be a necessary component of this change.

Defining comparative effectiveness research: the importance of getting it right.

Defining comparative effectiveness research (CER) was the first order of business for the Institute of Medicine Committee on Initial Priorities for CER. The Institute of Medicine committee approached the task of defining CER by identifying the common theme in the 6 extant definitions. The definition follows: "Comparative effectiveness research 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. The purpose of CER is to assist consumers, clinicians, purchasers, and policy makers to make informed decisions that will improve health care at both the individual and population levels." The key words in this definition are "generation and synthesis of evidence" (which implies both original research and systematic reviews), "alternative methods" (which implies making head to head comparisons in study populations typical of daily practice), and "to make informed decisions" (which implies a focus on data that helps to decide between alternatives). Defining CER requires us to decide what we want from decisions about health care. Definitions also serve a bureaucratic function: they can set boundaries that delineate which research is eligible for CER program funding. Definitions--and the funding that advances their goals--can reshape the research environment.