G. Caleb Alexander

Objective: To review literature on the impact of The Food and Drug Administration (FDA) drug risk communications on medication utilization, health care services use, and health outcomes. Data Sources: The authors searched MEDLINE and the Web of Science for manuscripts published between January 1990 and November 2010 that included terms related to drug utilization, the FDA, and advisories or warnings. We manually searched bibliographies and works citing selected articles and consulted with experts to guide study selection. Study Selection: Studies were included if they involved an empirical analysis evaluating the impact of an FDA risk communication. Data Extraction: We extracted the drug(s) analyzed, relevant FDA communication(s), data source, analytical method, and main outcome(s) assessed. Results: Of the 1432 records screened, 49 studies were included. These studies covered 16 medicines or therapeutic classes; one third examined communications regarding antidepressants. Most used medical or pharmacy claims and a few rigorously examined patient-provider communication, decision making, or risk perceptions. Advisories recommending increased clinical or laboratory monitoring generally led to decreased drug use, but only modest, short-term increases in monitoring. Communications targeting specific subpopulations often spilled over to other groups. Repeated or sequential advisories tended to have larger but delayed effects and decreased incident more than prevalent use. Drug-specific warnings were associated with particularly large decreases in utilization, although the magnitude of substitution within therapeutic classes varied across clinical contexts. Conclusions: Although some FDA drug risk communications had immediate and strong impacts, many had either delayed or had no impact on health care utilization or health behaviors. These data demonstrate the complexity of using risk communication to improve the quality and safety of prescription drug use, and suggest the importance of continued assessments of the effect of future advisories and label changes. Identifying factors that are associated with rapid and sustained responses to risk communications will be important for informing future risk communication efforts.

Objective: To describe how critical care physicians manage conflicts with surrogates about withdrawing or withholding patients’ life support. Design: Qualitative analysis of key informant interviews with critical care physicians during 2010. We transcribed interviews verbatim and used grounded theory to code and revise a taxonomy of themes and to identify illustrative quotes. Setting: Three academic medical centers, one academic-affiliated medical center, and four private practice groups or private hospitals in a large Midwestern city Subjects: Fourteen critical care physicians. Interventions: None. Measurements and Main Results: Physicians reported tailoring their approach to address specific reasons for disagreement with surrogates. Five common approaches were identified: 1) building trust; 2) educating and informing; 3) providing surrogates more time; 4) adjusting surrogate and physician roles; and 5) highlighting specific values. When mistrust was an issue, physicians endeavored to build a more trusting relationship with the surrogate before readdressing decision making. Physicians also reported correcting misunderstandings by providing targeted education, and some reported highlighting specific patient, surrogate, or physician values that they hoped would guide surrogates to agree with them. When surrogates struggled with decisionmaking roles, physicians attempted to reinforce the concept of substituted judgment. Physicians noted that some surrogates needed time to “come to terms” with the patent’s illness before agreeing with physicians. Many physicians had witnessed colleagues negotiate in ways they found objectionable such as providing misleading information, injecting their own values into the negotiation or behaving unprofessionally toward surrogates. Although some physicians viewed their efforts to encourage surrogates’ agreement as persuasive, others strongly denied persuading surrogates and described their actions as “guiding” or “negotiating.” Conclusions: Physicians reported using a tailored approach to resolve decisional conflicts about life support and attempted to change surrogates’ decisions in accordance with what the physician thought was in the patients’ best interests. Although physicians acknowledged their efforts to change surrogates’ decisions, many physicians did not perceive these efforts as persuasive. (Crit Care Med 2012; 40:–1087)

Objective:The authors examined trends in the use of second-generation antipsychotics for treatment of bipolar disorder before and after the U.S. Food and Drug Administration's approval in 2000 of olanzapine for use in treating acute manic episodes of bipolar disorder. Methods:The IMS Health National Disease and Therapeutic Index was used to derive monthly patient treatment visits between January 1998 and December 2009 by individuals 18 and older with a diagnosis of bipolar disorder who were treated with one or more pharmacotherapies. Results:The percentage of treatment visits in which a second-generation antipsychotic was prescribed increased from 18% in 1998 to 49% in 2009. Use of mood stabilizers and first-generation antipsychotics declined substantially. In the 12 months after approval of olanzapine for bipolar disorder, its use increased by 92%, and use of other second-generation antipsychotics increased by 42%. Conclusions:Second-generation antipsychotics are increasingly used for bipolar disorder, a...

BACKGROUND Despite reductions in morbidity and mortality and changes in guidelines, little is known regarding changes in asthma treatment patterns. OBJECTIVE To examine national trends in the office-based treatment of asthma between 1997 and 2009. PARTICIPANTS AND DESIGN We used the National Ambulatory Care Survey (NAMCS) and the National Disease and Therapeutic Index™ (NDTI), nationally representative audits of office-based physicians, to examine patients diagnosed with asthma less than 50 years of age. MEASUREMENTS Visits where asthma was diagnosed and use of six therapeutic classes (short-acting β₂ agonists [SABA], long-acting β₂ -agonists [LABA], inhaled steroids, antileukotrienes, anticholinergics, and xanthines). RESULTS Estimates from NAMCS indicated modest increases in the number of annual asthma visits from 9.9 million [M] in 1997 to 10.3M during 2008; estimates from the NDTI suggested more gradual continuous increases from 8.7M in 1997 to 12.6M during 2009. NAMCS estimates indicated declines in use of SABAs (from 80% of treatment visits in 1997 to 71% in 2008), increased inhaled steroid use (24% in 1997 to 33% in 2008), increased use of fixed dose LABA/steroid combinations (0% in 1997 to 19% in 2008), and increased leukotriene use (9% in 1997 to 24% in 2008). The ratio of controller to total asthma medication use increased from 0.5 (1997) to a peak of 0.7 (2004). In 2008, anticholinergics, xanthines, and LABA use without concomitant steroids accounted for fewer than 4% of all treatment visits. Estimates from NDTI corroborated these trends. CONCLUSIONS Changes in office-based treatment, including increased inhaled steroid use and increased combined steroid/long-acting β₂-agonist use coincide with reductions in asthma morbidity and mortality that have been demonstrated over the same period. Xanthines, anticholinergics, and increasingly, LABA without concomitant steroid use, account for a very small fraction of all asthma treatments.

The adoption and use of a new drug would ideally be guided by its innovation and cost-effectiveness. However, information about the relative efficacy and safety of a drug is typically incomplete even well after market entry, and various other forces create a marketplace in which most new drugs are little better than their older counterparts. Five proposed mechanisms are considered for promoting innovation and reducing the use of therapies ultimately found to offer poor value or have unacceptable risks. These changes range from increasing the evidence required for U.S. Food and Drug Administration approval to modifying the structure of drug reimbursement. Despite the challenges of policy implementation, the United States has a long history of successfully improving the societal value and safe use of prescription medicines.

Opinion from JAMA Internal Medicine — Seeding Trials and the Subordination of Science — Comment on “Study of Neurontin — Titrate to Effect, Profile of Safety (STEPS) Trial”

Objective: To evaluate patterns of antipsychotic use.Design, setting, and measurements: We used nationally representative data from the IMS Health National Disease and Therapeutic Index to describe outpatient antipsychotic use. The primary outcome was the volume of visits where antipsychotics were used for specific indications (treatment visits). We also quantified use without U.S. Food and Drug Administration approval (off‐label use) and off‐label use with compendium data suggesting an uncertain evidence base.Results: Antipsychotic use increased from 6.2 million (M) treatment visits (95% CI, 5.4–7.0) in 1995 to 16.7 M visits (15.5–18.2) in 2006, then declined to 14.3 M visits (13.0–15.6) by 2008. A shift occurred from typical agents in 1995 (84% of all antipsychotic visits) to atypical agents by 2008 (93%). As they declined, typical medications shifted toward use in schizophrenia (30% in 1995 to 48% 2008). In contrast, use of atypical agents expanded for bipolar affective disorder (10 to 34%), remained stable for depression (12 to 14%), and declined for schizophrenia (56 to 23%). Overall, antipsychotic use for indications without FDA approval increased from 4.4 M visits in 1995 to 9.0 M in 2008. The estimated cost associated with off‐label use in 2008 was US$6.0 billion.Conclusions: Atypical use has grown far beyond substitution for the now infrequently used typical agents. Antipsychotics are increasingly used for conditions where FDA approval and associated clinical evidence is less certain. Despite the value of innovation, the benefits of widening atypical antipsychotic use should be weighed against their cost, regulatory status, and incomplete nature of available evidence. Copyright © 2011 John Wiley & Sons, Ltd.

Although adequate self‐esteem is essential for psychological health, people with high but fragile self‐esteem have been shown to exhibit defensive, often aggressive behavior when their self‐esteem is threatened. We measured physician narcissism (as a proxy for high but fragile self‐esteem) and used a subtle manipulation to examine how physicians who varied in levels of narcissism responded to an ego threat. We found that physicians high in narcissism, as compared with those lower in narcissism, were more likely to respond to ego threat by attempting to bolster their self‐image. Concerned about self‐image, physicians in this situation may be insufficiently receptive to new information and instead attempt to justify initial opinions.

OBJECTIVES: To explore the degree to which physicians report reliance on patient preferences when making medical decisions for hospitalized patients lacking decisional capacity. DESIGN: Cross‐sectional survey. SETTING: One academic and two community hospitals in a single metropolitan area. PARTICIPANTS: Two hundred eighty‐one physicians who recently cared for hospitalized adults. MEASUREMENTS: A self‐administered survey addressing physicians' beliefs about ethical principles guiding surrogate decision‐making and physicians' recent decision‐making experiences. RESULTS: Overall, 72.6% of physicians identified a standard related to patient preferences as the most important ethical standard for surrogate decision‐making (61.2% identified advanced directives and 11.4% substituted judgment). Of the 73.3% of physicians who reported recently making a surrogate decision, 81.8% reported that patient preferences were highly important in decision‐making, although only 29.4% reported that patient preference was the most important factor in the decision. Physicians were significantly more likely to base decisions on patient preferences when the patient was in the intensive care unit (odds ratio (OR)=2.92, 95% confidence interval (CI)=1.15–7.45) and less likely when the patient was older (OR=0.76 for each decade of age, 95% CI=0.58–0.99). The presence of a living will, prior discussions with the patient, and the physicians' beliefs about ethical guidelines did not significantly predict the physicians' reliance on patient preferences. CONCLUSION: Although a majority of physicians identified patient preferences as the most important general ethical guideline for surrogate decision‐making, they relied on a variety of factors when making treatment decisions for a patient lacking decisional capacity.