Rena M. Conti

Impact of FDA Black Box Advisory on Antipsychotic Medication Use

BACKGROUND In April 2005, the US Food and Drug Administration (FDA) issued an advisory and subsequent black box warning regarding the risks of atypical anti psychotic use among elderly patients with dementia. The impact of these warnings on atypical drug use is unknown. METHODS We used quasi-experimental, interrupted time-series analyses to examine nationally representative data from IMS Healths National Disease and Therapeutic Index from January 2003 through December 2008. The primary measurement from this audit of office-based physicians was the use of an atypical antipsychotic agent. We quantified the impact of the advisory on atypical antipsychotic use among all individuals and those 65 years or older with dementia. RESULTS From January 2003 to March 2005, mentions of total atypical antipsychotic drugs increased at an annual rate of 34%, and among patients with dementia, 16%. In the year prior to the FDA advisory, there were approximately 13.6 million atypical drug mentions, including 0.8 million among those with dementia. In the year following the advisory, atypical drug mentions fell 2% overall and 19% among those with dementia. In 2004, 19% (0.8 of 4.1 million) of drug mentions for dementia were for an atypical agent. By 2008, this proportion decreased to 9% (0.4 of 4.3 million). Atypical drug use slowed for both FDA-approved and off-label indications and declined through 2008 for all populations examined. CONCLUSION The FDA advisory was associated with decreases in the use of atypical antipsychotics, especially among elderly patients with dementia.

Impact of FDA drug risk communications on health care utilization and health behaviors: A systematic review

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.

Personalized Medicine and Genomics: Challenges and Opportunities in Assessing Effectiveness, Cost-Effectiveness, and Future Research Priorities

Personalized medicine is health care that tailors interventions to individual variation in risk and treatment response. Although medicine has long strived to achieve this goal, advances in genomics promise to facilitate this process. Relevant to present-day practice is the use of genomic information to classify individuals according to disease susceptibility or expected responsiveness to a pharmacologic treatment and to provide targeted interventions. A symposium at the annual meeting of the Society for Medical Decision Making on 23 October 2007 highlighted the challenges and opportunities posed in translating advances in molecular medicine into clinical practice. A panel of US experts in medical practice, regulatory policy, technology assessment, and the financing and organization of medical innovation was asked to discuss the current state of practice and research on personalized medicine as it relates to their own field. This article reports on the issues raised, discusses potential approaches to meet these challenges, and proposes directions for future work. The case of genetic testing to inform dosing with warfarin, an anticoagulant, is used to illustrate differing perspectives on evidence and decision making for personalized medicine.

Trends in Attention Deficit Hyperactivity Disorder Ambulatory Diagnosis and Medical Treatment in the United States, 2000-2010

OBJECTIVES Because of several recent clinical and regulatory changes regarding attention deficit-hyperactivity disorder (ADHD) in the United States, we quantified changes in the diagnosis of ADHD and its pharmacologic treatment from 2000 through 2010. METHODS We used the IMS Health National Disease and Therapeutic Index, a nationally representative audit of office-based providers, to examine aggregate trends among children and adolescents younger than 18 years of age. We also quantified how diagnosis and treatment patterns have evolved on the basis of patient and physician characteristics and the therapeutic classes used. RESULTS From 2000 to 2010, the number of physician outpatient visits in which ADHD was diagnosed increased 66% from 6.2 million (95% confidence interval 5.5-6.9M) to 10.4 million visits (95% confidence interval 9.3-11.6 million). Of these visits, psychostimulants have remained the dominant treatment; they were used in 96% of treatment visits in 2000 and 87% of treatment visits in 2010. Atomoxetine use decreased from 15% of treatment visits upon product launch in 2003 to 6% of treatment visits by 2010. The use of potential substitute therapies-clonidine, guanfacine, and bupropion-remained relatively constant (between 5% and 9% of treatment visits) during most of the period examined. During this period, the management of ADHD shifted away from pediatricians and towards psychiatrists (from 24% to 36% of all visits) without large changes in illness severity or the proportion of ADHD treatment visits accounted for by males (73%-77%). CONCLUSIONS In 10 years, the ambulatory diagnosis of ADHD increased by two-thirds and is increasingly managed by psychiatrists. The effects of these changing treatment patterns on childrens health outcomes and their families are unknown.

Racial and ethnic disparities in cardiovascular medication use among older adults in the United States

Despite persistent racial/ethnic disparities in cardiovascular disease (CVD) among older adults, information on whether there are similar disparities in the use of prescription and over‐the‐counter medications to prevent such disease is limited. We examined racial and ethnic disparities in the use of statins and aspirin among older adults at low, moderate, and high risk for CVD.

Overspending driven by oversized single dose vials of cancer drugs.

Peter B Bach and colleagues call for an end to contradictory regulatory standards in the US that allow drug manufacturers to boost profits by producing single dose vials containing quantities that increase leftover drug

Cost-effectiveness of Tyrosine Kinase Inhibitor Treatment Strategies for Chronic Myeloid Leukemia in Chronic Phase After Generic Entry of Imatinib in the United States

Background: We analyzed the cost-effectiveness of treating incident chronic myeloid leukemia in chronic phase (CML-CP) with generic imatinib when it becomes available in United States in 2016. In the year following generic entry, imatinib’s price is expected to drop 70% to 90%. We hypothesized that initiating treatment with generic imatinib in these patients and then switching to the other tyrosine-kinase inhibitors (TKIs), dasatinib or nilotinib, because of intolerance or lack of effectiveness (“imatinib-first”) would be cost-effective compared with the current standard of care: “physicians’ choice” of initiating treatment with any one of the three TKIs. Methods: We constructed Markov models to compare the five-year cost-effectiveness of imatinib-first vs physician’s choice from a US commercial payer perspective, assuming 3% annual discounting (

Trends in Use of Second-Generation Antipsychotics for Treatment of Bipolar Disorder in the United States, 1998–2009

US 2013). The models’ clinical endpoint was five-year overall survival taken from a systematic review of clinical trial results. Per-person spending on incident CML-CP treatment overall care components was estimated using Truven’s MarketScan claims data. The main outcome of the models was cost per quality-adjusted life-year (QALY). We interpreted outcomes based on a willingness-to-pay threshold of

Cost Consequences of the 340B Drug Discount Program

100 000/QALY. A panel of European LeukemiaNet experts oversaw the study’s conduct. Results: Both strategies met the threshold. Imatinib-first (

Changing the cost of care for chronic myeloid leukemia: the availability of generic imatinib in the USA and the EU.

277 401, 3.87 QALYs) offered patients a 0.10 decrement in QALYs at a savings of