Bayesian and adaptive clinical trial designs offer the potential for more efficient processes that result in lower sample sizes and shorter trial durations than traditional designs.

The comparative benefits and harms of transcatheter aortic valve implantation (TAVI) and surgical aortic valve replacement (SAVR) for patients with aortic stenosis are unclear.

Suicide prevention programs have become ubiquitous among military units; identifying temporal trends and nonclinical factors associated with the chosen suicide methods may help improve suicide prevention strategies.

In 2015, a large outbreak of Middle East respiratory syndrome (MERS) occurred in the Republic of Korea. Half of the cases were associated with a tertiary care university hospital.

This issue provides a clinical overview of breast cancer screening and prevention, focusing on risk assessment, screening, prevention, and practice improvement. The content of In the Clinic is drawn from the clinical information and education resources of the American College of Physicians (ACP), including MKSAP (Medical Knowledge and Self-Assessment Program). Annals of Internal Medicine editors develop In the Clinic in collaboration with the ACP's Medical Education and Publishing divisions and with the assistance of additional science writers and physician writers.

In May 2015, the U.S. Preventive Services Task Force issued a guideline on screening for thyroid disease that included a systematic evidence review and an update of its 2004 recommendations. The review assessed the effect of treating screen-detected subclinical thyroid dysfunction on health outcomes. It found adequate evidence that treating subclinical hypothyroidism does not provide clinically meaningful improvements in blood pressure, body mass index, bone mineral density, lipid levels, or quality-of-life measures. The review also concluded that evidence was inadequate to determine whether screening for thyroid dysfunction reduced cardiovascular disease or related morbidity and mortality. In separate guidelines, the American Association of Clinical Endocrinologists and American Thyroid Association advocated aggressive case-finding and recommended screening persons with certain clinical conditions or characteristics rather than the general population. These societies argue that subclinical hypothyroidism adversely affects cardiovascular outcomes and thus merits case-finding. Here, 2 experts discuss their perspectives on whether treating subclinical hypothyroidism reduces morbidity and mortality, whether there are harms of treatment, and how they would balance the benefits and harms of treatment both in general and for a specific patient.

This National Institutes of Health (NIH) Pathways to Prevention workshop was cosponsored by the NIH Office of Disease Prevention; National Heart, Lung, and Blood Institute; and National Institute for Occupational Safety and Health of the Centers for Disease Control and Prevention. A multidisciplinary working group developed the agenda, and an evidence-based practice center prepared an evidence report through a contract with the Agency for Healthcare Research and Quality. During the 1.5-day workshop, experts discussed the body of evidence and participants commented during open discussions. After weighing the data from the evidence report, expert presentations, and public comments, an unbiased, independent panel prepared a draft report that identified research gaps and future research priorities. The report was posted on the NIH Office of Disease Prevention Web site for 5 weeks for public comment. This article highlights 8 recommendations critical for advancing the science of integrated interventions to improve the total health of workers.

The Joint United Nations Programme on HIV/AIDS (UNAIDS) 90-90-90 global treatment target aims to achieve 73% virologic suppression among HIV-infected persons worldwide by 2020.

The Total Worker Health (TWH) program of the National Institute for Occupational Safety and Health aims to advance worker well-being by integrating injury and illness prevention efforts with work-related safety and health hazard efforts.

A weak antibiotic pipeline and the increase in drug-resistant pathogens have led to calls for more new antibiotics. Eight new antibiotics were approved by the U.S. Food and Drug Administration (FDA) between January 2010 and December 2015: ceftaroline, fidaxomicin, bedaquiline, dalbavancin, tedizolid, oritavancin, ceftolozane-tazobactam, and ceftazidime-avibactam. This study evaluates the development course and pivotal trials of these antibiotics for their innovativeness, development process, documented patient outcomes, and cost. Data sources were FDA approval packages and databases (January 2010 to December 2015); the Red Book (Truven Health Analytics); Orange Book: Approved Drug Products with Therapeutic Equivalence Evaluations (FDA); and supplementary information from company filings, press releases, and media reports. Four antibiotics were approved for acute bacterial skin and skin-structure infection. Seven had similar mechanisms of action to those of previously approved drugs. Six were initially developed by small to midsized companies, and 7 are currently marketed by 1 of 3 large companies. The drugs spent a median of 6.2 years in clinical trials (interquartile range [IQR], 5.4 to 8.8 years) and 8 months in FDA review (IQR, 7.5 to 8 months). The median number of patients enrolled in the pivotal trials was 666 (IQR, 553 to 739 patients; full range, 44 to 1005 patients), and median trial duration was 18 months (IQR, 15 to 22 months). Seven drugs were approved on the basis of pivotal trials evaluating noninferiority. One drug demonstrated superiority on an exploratory secondary end point, 2 showed decreased efficacy in patients with renal insufficiency, and 1 showed increased mortality compared with older drugs. Seven of the drugs are substantially more expensive than their trial comparators. Limitations are that future research may show benefit to patients, new drugs from older classes may show superior effectiveness in specific patient populations, and initial U.S. prices for each new antibiotic were obtained from public sources. Recently marketed antibiotics are more expensive but have been approved without evidence of clinical superiority.

Public reporting is seen as a powerful quality improvement tool, but data to support its efficacy are limited. The Centers for Medicare & Medicaid Services' Hospital Compare program initially reported process metrics only but started reporting mortality rates for acute myocardial infarction, heart failure, and pneumonia in 2008.

PROMISE (PROspective Multicenter Imaging Study for Evaluation of Chest Pain) found that initial use of at least 64-slice multidetector computed tomography angiography (CTA) versus functional diagnostic testing strategies did not improve clinical outcomes in stable symptomatic patients with suspected coronary artery disease (CAD) requiring noninvasive testing.

The established molecular heterogeneity of human cancers necessitates the development of new paradigms to serve as a reliable basis for precision medicine. The assumptions underlying some of the conventional approaches to clinical trial design and analysis are no longer appropriate because of the molecular heterogeneity of tumors of a given primary site. This article reviews some clinical trial designs that have been actively applied in the codevelopment of therapeutics and predictive biomarkers to inform their use in oncology. These include the enrichment design, the basket design, and the umbrella design. Oncology leads most other therapeutic areas in development of personalized or precision medicine. Personalized or precision medicine is practiced daily in oncology on the basis of tumor genomics and may evolve in other therapeutic areas as it has in oncology, rather than according to inherited polymorphisms as so often imagined. Consequently, some of the clinical trial designs described here may serve as a possible blueprint for therapeutic development in fields other than oncology.