STUDY OBJECTIVE: To develop a prioritized list of individual drugs for which future research regarding off-label uses is warranted.

DESIGN: Retrospective, cross-sectional study.

DATA SOURCES: Commercial database that provides ongoing estimates of drug prescribing practices of office-based physicians in the United States and an Internet database of comprehensive evidence-based drug information.

MEASUREMENTS AND MAIN RESULTS: The base analyses incorporated three key factors based on the theory of value of information: volume of off-label use with inadequate evidence, drug safety, and cost and market considerations. Nationally representative prescribing data were used to estimate the number of off-label drug uses by indication from January 1, 2005-June 30, 2007, in the United States, and these indications were then categorized according to the adequacy of scientific support. Black-box warnings and safety alerts, drug cost, date of market entry, and marketing expenditures were also incorporated into the final model to produce a priority score. Sensitivity analyses were conducted by varying key model parameters. Our findings identified a high volume of off-label prescribing in the absence of good evidence for a substantial number of drugs, particularly antidepressants, antipsychotics, and anxiolytic-sedatives. Drugs that consistently ranked high in both our base model and sensitivity analyses were quetiapine, warfarin, escitalopram, risperidone, montelukast, bupropion, sertraline, venlafaxine, celecoxib, lisinopril, duloxetine, trazodone, olanzapine, and epoetin alfa.

CONCLUSION: Future research into off-label drug use should focus on drugs used frequently with inadequate supporting evidence, particularly if further concerns are raised by known safety issues, high drug cost, recent market entry, and extensive marketing. Our quantitative analysis identified particular concerns with the off-label use of antipsychotic and antidepressant drugs. Targeted research and policy activities on our list of prioritized drugs have high potential value.

Our study assesses how work-related monetary and nonmonetary factors affect physicians' job satisfaction at three academic medical centers in Germany and the United States, two countries whose differing health care systems experience similar problems in maintaining their physician workforce. We used descriptive statistics and factor and correlation analyses to evaluate physicians' responses to a self-administered questionnaire. Our study revealed that German physician respondents were less satisfied overall than their U.S. counterparts. In both countries, participation in decision making that may affect physicians' work was an important correlate of satisfaction. In Germany other important factors were opportunities for continuing education, job security, extent of administrative work, collegial relationships, and access to specialized technology. In the U.S. sample, job security, financial incentives, interaction with colleagues, and cooperative working relationships with colleagues and management were important predictors of overall job satisfaction. The implications of these findings for the development of policies and management tactics to increase physician job satisfaction in German and U.S. academic medical centers are discussed.

The American College of Physicians developed this guideline to present the available evidence on the pharmacologic management of the acute, continuation, and maintenance phases of major depressive disorder; dysthymia; subsyndromal depression; and accompanying symptoms, such as anxiety, insomnia, or neurovegetative symptoms, by using second-generation antidepressants.

METHODS: Published literature on this topic was identified by using MEDLINE, EMBASE, PsychLit, the Cochrane Central Register of Controlled Trials, and International Pharmaceutical Abstracts from 1980 to April 2007. Searches were limited to English-language studies in adults older than 19 years of age. Keywords for search included terms for depressive disorders and 12 specific second-generation antidepressants-bupropion, citalopram, duloxetine, escitalopram, fluoxetine, fluvoxamine, mirtazapine, nefazodone, paroxetine, sertraline, trazodone, and venlafaxine-and their specific trade names. This guideline grades the evidence and recommendations by using the American College of Physicians clinical practice guidelines grading system.

RECOMMENDATIONS

1. The American College of Physicians recommends that when clinicians choose pharmacologic therapy to treat patients with acute major depression, they select second-generation antidepressants on the basis of adverse effect profiles, cost, and patient preferences (Grade: strong recommendation; moderate-quality evidence).
2. The American College of Physicians recommends that clinicians assess patient status, therapeutic response, and adverse effects of antidepressant therapy on a regular basis beginning within 1 to 2 weeks of initiation of therapy (Grade: strong recommendation; moderate-quality evidence).
3. The American College of Physicians recommends that clinicians modify treatment if the patient does not have an adequate response to pharmacotherapy within 6 to 8 weeks of the initiation of therapy for major depressive disorder (Grade: strong recommendation; moderate-quality evidence).
4. The American College of Physicians recommends that clinicians continue treatment for 4 to 9 months after a satisfactory response in patients with a first episode of major depressive disorder. For patients who have had 2 or more episodes of depression, an even longer duration of therapy may be beneficial (Grade: strong recommendation; moderate-quality evidence).

BACKGROUND: Small asymptomatic lung nodules are found frequently in the course of cardiac computed tomography (CT) scanning. However, the utility of assessing and reporting incidental findings in healthy, asymptomatic subjects is unknown.

METHODS: The sample comprised 1023 60- to 69-year-old subjects free of clinical cardiovascular disease and cancer who participated in the Atherosclerotic Disease, VAscular functioN and genetiC Epidemiology Study. All subjects underwent cardiac CT for determination of coronary calcium between 2001 and 2004, and the first 459 subjects were assessed for incidental pulmonary findings. We used health plan clinical databases to ascertain 24-month health care use and clinical outcomes.

RESULTS: Noncalcified pulmonary nodules were reported in 81 of 459 subjects (18%). Chest CT was performed on 78% of participants in the 24 months after notification, compared with 2.5% in the previous 24 months. Chest x-ray use increased from 28% to 49%. The mean number of chest CT scans per subject was 1.3 (range, 0-5). Although no malignant lesions were diagnosed in the group who had pulmonary findings read, 1 lung cancer case was diagnosed in the group who did not have lung findings read. Among the 63 participants followed up by CT, the original lesion was not identified in 22 participants (35%), the lesion had decreased or remained stable in 39 participants (62%), and there was interval growth in 2 participants (3%).

CONCLUSION: Reporting noncalcified pulmonary nodules resulted in substantial rescanning that overwhelmingly revealed resolution or stability of pulmonary nodules, arguing for benign processes.

The U.S. health system has been described as the most competitive, heterogeneous, inefficient, fragmented, and advanced system of care in the world. In this paper, we consider two questions: First, is the U.S. healthcare system productively efficient relative to other wealthy countries, in the sense of producing better health for a given bundle of hospital beds, physicians, nurses, and other factor inputs? Second, is the United States allocatively efficient relative to other countries, in the sense of providing highly valued care to consumers? For both questions, the answer is most likely no. Although no country can claim to have eliminated inefficiency, the United States has high administrative costs, fragmented care, and stands out with regard to heterogeneity in treatment because of race, income, and geography. The U.S. healthcare system is also more likely to pay for diagnostic tests, treatments, and other forms of care before effectiveness is established and with little consideration of the value they provide. A number of proposed reforms that are designed to ameliorate shortcomings of the U.S. healthcare system, such as quality improvement initiatives and coverage expansions, are unlikely by themselves to reduce expenditures. Addressing allocative inefficiency is a far more difficult task but central to controlling costs.