Food And Drug Administration Actions Research Articles

Early evaluation of the Food and Drug Administration (FDA) guidance on antimicrobial use in food animals on antimicrobial resistance trends reported by the National Antimicrobial Resistance Monitoring System (2012–2019)

Antimicrobial resistance (AMR) is one of the biggest challenges to global public health. To address this issue in the US, governmental agencies have implemented system-wide guidance frameworks and recommendations aimed at reducing antimicrobial use. In particular, the Food and Drug Administration (FDA) prohibited the extra-label use of cephalosporins in food animals in 2012 and issued the guidance for industry (GFI) #213 about establishing a framework to phase out the use of all medically relevant drugs for growth promotion in 2012. Also in 2015, the FDA implemented veterinary feed directive (VFD) drug regulations (GFI# 120) to control the use of certain antimicrobials. To assess the potential early effects of these FDA actions and other concurrent antimicrobial stewardship actions on AMR in the food chain, we compared the patterns of the phenotypic (minimum inhibitory concentration (MIC) and percentage of resistance) and genotypic resistances for selected antimicrobials before and after 2016 across different enteric pathogen species, as reported by the National Antimicrobial Resistance Monitoring System (NARMS). Most of the antimicrobials analyzed at the phenotypic level followed a downward trend in MIC after implementing the guidance. Although, most of those changes were less than one 1-fold dilution. On the other hand, compared to MIC results, the results based on phenotypic resistance prevalence evidenced higher differences in both directions between the pre- and post-guidance implementation period. Also, we did not find relevant differences in the presence of AMR genes between pre- and post-VFD drug regulations. We concluded that the FDA guidance on antimicrobial use has not led to substantial reductions in antimicrobial drug resistance yet.

Assessment, Complications, and Surveillance of Breast Implants: Making Sense of 2022 FDA Breast Implant Guidance.

As more information about the potential risks and complications related to breast implants has become available, the United States Food and Drug Administration (FDA) has responded by implementing changes to improve patient education, recalling certain devices and updating the recommendations for screening for silicone implant rupture. In addition to staying up-to-date with FDA actions and guidance, radiologists need to maintain awareness about the types of implants they may see, breast reconstruction techniques including the use of acellular dermal matrix, and the multimodality imaging of implants and their complications. Radiologists should also be familiar with some key differences between the updated FDA guidelines for implant screening and the imaging recommendations from the American College of Radiology Appropriateness Criteria. The addition of US as an acceptable screening exam for silicone implant rupture by the FDA is one of the most notable changes that has potentially significant implications.

Med Check: FDA Actions on Xylazine, Austedo XR, and Zuranolone

Back to table of contents Previous article Next article Med CheckFull AccessMed Check: FDA Actions on Xylazine, Austedo XR, and ZuranoloneTerri D’ArrigoTerri D’ArrigoSearch for more papers by this authorPublished Online:23 Mar 2023https://doi.org/10.1176/appi.pn.2023.05.4.1FDA Aims to Curtail Illegal Importation of XylazineThe U.S. Food and Drug Administration (FDA) has taken action to restrict the illegal entry of xylazine ingredients and drug products into the country, according to an announcement released in February. Xylazine is a veterinary medication used to sedate large animals such as horses and deer. However, it has increasingly been found in illicit drugs such as illicitly manufactured fentanyl, and xylazine-related overdose deaths have risen in recent years (Psychiatric News, “Xylazine Increasingly Found in Overdose Deaths”).The FDA’s actions include heightened scrutiny of imports of drugs containing xylazine into the country, and FDA staff may detain shipments if they appear to violate the law. When FDA staff conduct entry reviews of xylazine, they will consider specific evidence offered by importers that the incoming product is properly labeled, not adulterated, and for legitimate veterinary use.According to the announcement, the FDA and its Office of Criminal Investigations are collaborating with federal, state, and local partners to investigate xylazine-related activities that could be subject to criminal prosecution, including online and in-person conduct. The FDA said it is coordinating with stakeholders in animal health to ensure that drugs containing xylazine are available to veterinarians for legitimate use.SAMHSA Publishes Advisory About Cannabidiol ProductsIn February the Substance Abuse and Mental Health Services Administration (SAMHSA) published an advisory about the potential harms, side effects, and unknowns of cannabidiol (CBD).The advisory covers how CBD is derived and how it differs from delta-9-tetrahydrocannabinol (THC). The advisory also explains that CBD products that are not approved do not have to meet any standards for content or potency (Psychiatric News, “Most OTC Cannabinoid Products Mislabeled”). It notes that the FDA has not approved CBD products to be marketed as food additives or dietary supplements and that the FDA has concluded that a new regulatory pathway is needed for CBD products.The advisory provides tips and action steps for health professionals, parents, caregivers, and the general public to take regarding education and awareness of the risk of CBD products.Austedo XR Approved for Treating Tardive Dyskinesia and Huntington’s ChoreaThe FDA has approved Austedo XR (deutetrabenazine extended-release tablets) for the treatment of tardive dyskinesia and chorea associated with Huntington’s disease in adults, Teva Pharmaceuticals announced in February. Austedo XR is taken once per day, compared with Austedo, which is taken twice per day. It will be available in three strengths: 6 mg, 12 mg, and 24 mg, and can be taken with or without food. The same total daily dosage can be used when switching between Austedo tablets and Austedo XR tablets.Austedo XR comes with a boxed warning about depression and suicidality in patients with Huntington’s disease. The warning instructs health professionals who prescribe the medication to monitor patients who take Austedo for the emergence or worsening of depression, suicidality, or changes in behavior. It also instructs health professionals to inform patients, caregivers, and families of the risk of depression and suicidality.FDA Grants Zuranolone Priority Review for Major Depression and Postpartum DepressionThe FDA has granted zuranolone priority review for the treatment of major depressive disorder (MDD) and postpartum depression (PPD), Sage Therapeutics announced in February. Zuranolone is an investigational drug being evaluated as a 14-day, rapid-acting, once-daily, oral treatment in adults with MDD and PPD.In the WATERFALL trial, 543 adults aged 18 to 64 years with MDD received either 50 mg of zuranolone or placebo daily for 14 days. All patients in the study had a Hamilton Rating Scale for Depression (HAMD-17) total score of at least 24 when they enrolled in the study. By day 15 of the trial, patients who took zuranolone had experienced an average drop of 14.1 points on the HAMD-17, compared with an average drop of 12.3 points in those who took placebo.In the SKYLARK trial, 195 women with PPD were randomized to take either 50 mg of zuranolone or placebo once per night for 14 days. On Day 15, scores on the 17-item Hamilton Rating Scale for Depression dropped a mean of 15.6 points among women who took zuranolone compared with a mean decrease in score of 11.6 points among women who took placebo.The FDA’s decision on whether to approve zuranolone for major depressive disorder and postpartum depression is expected by August 5. ■ ISSUES NewArchived

373 Youth Nicotine Addiction: Strategic Defiance of Regulatory Oversight by the Disposable Electronic Nicotine Delivery System Industry

OBJECTIVES/GOALS: To assess the impact of federal regulations and policies relating to disposable Electronic Nicotine Delivery Systems (ENDS) on youth consumption of these products by identifying factors enabling its growing consumption among youth users and its relation to adolescent addiction to nicotine. METHODS/STUDY POPULATION: Disposable ENDS are all-in-one devices with pre-filled nicotine liquid and a built-in battery. Recent data shows increased sales as users, including youth, are switching from pod-based to disposable ENDS. Thus, an understanding of the regulatory landscape for these products will provide insight on how to mitigate youth nicotine addiction. Data from the Centers for Disease Control and Prevention 2021 National Youth Tobacco Survey (NYTS) was analyzed for patterns of adolescent use. FDA statements and actions involving disposable ENDS companies were reviewed to evaluate the current FDA stance. Analyses of both data sets identified factors enabling the growth in sale of disposable ENDS. RESULTS/ANTICIPATED RESULTS: The NYTS reported 53.7% of youth ENDS users report using disposable ENDS and Puff Bar is the leading ENDS device among youth consumers. In March 2021, Puff Bar announced a return to market with “tobacco-free nicotine” after ceasing sales following an FDA warning letter in July 2020. But synthetic nicotine retains the same chemical properties as tobacco-derived nicotine and the same risks for addiction and abuse. The Food and Drug Administration (FDA) maintains synthetic nicotine products will be regulated on a case-to-case basis, suggesting “closed system devices” containing synthetic nicotine may not be regulated as tobacco products. DISCUSSION/SIGNIFICANCE: The growing popularity of disposable ENDS among youth is problematic. Awareness of strategic regulatory defiance (i.e., Puff Bar), will bring light to industry sales tactics. To develop comprehensive data on disposable ENDS use by young adults, an anonymous survey of college students will be conducted.

Assessment of Data Sources That Support US Food and Drug Administration Medical Devices Safety Communications

Medical Device Safety Communications (MDSCs) are used by the US Food and Drug Administration (FDA) to convey important new safety information to patients and health care professionals. The sources of initial safety signals that trigger MDSCs have not been described previously. To assess the sources of initial safety signals that trigger publication of MDSCs and the potential associations among MDSC data source, type of safety issue, and subsequent FDA action. In this cross-sectional study, all MDSCs published on the FDA website between January 1, 2011, and December 31, 2019, were assessed. The MDSC characteristics, sources of initiating safety signals, regulatory approval or clearance pathways of the related medical devices, and subsequent FDA actions were collected from the FDA website. The main outcome was the distribution of sources of initial safety signals that led to publication of MDSCs. Secondary aims included exploration of potential associations among safety signal sources (direct reporting vs other), type of safety issue (death vs other), and FDA action (withdrawal vs other). A total of 93 MDSCs were evaluated. Median time from device approval to MDSC posting was 10 years (interquartile range, 6-16 years). The most common data sources that triggered MDSCs were direct reports to the FDA through the Medical Device Reporting (MDR) program (44 of 93 [47%]) followed by regulator-initiated assessments (32 [34%]). Common safety issues included patient injury (25 [27%]), potential wrong diagnoses (19 [20%]), and death (18 [19%]). Frequent FDA action after MDSC posting included recommendation for increased vigilance and caution (47 [51%]), complete device withdrawal (12 [13%]), and warnings of specific lots or clinics (12 [13%]). There was a statistically significant correlation between direct reports of adverse events to the FDA through the MDR program and risk of death as a safety issue (14 of 44 [32%] for direct reporting vs 4 of 49 [8%] for any other data sources, P = .007). In this cross-sectional study, the most common source of initial safety signals that triggered MDSCs was direct reports of real-world adverse events to the FDA through the MDR program. The delayed detection of postmarketing adverse events highlights the importance of proactive identification of emerging device-related safety issues.

Association Between Food and Drug Administration Advisory Committee Recommendations and Agency Actions, 2008-2015.

The Food and Drug Administration (FDA) convenes advisory committees to provide external scientific counsel on potential agency actions and to inform regulatory decision making. The degree to which advisory committees and their respective agency divisions disagree on recommendations has not been well characterized across product and action types. We examined public documents from FDA advisory committee meetings and medical product databases for all FDA advisory committee meetings from 2008 through 2015. We classified the 376 voting meetings in that period by medical product, regulatory, and advisory committee meeting characteristics. We used multivariable logistic regression to determine the associations between these characteristics and discordance between the advisory committee's recommendations and the FDA's final actions. Twenty-two percent of the FDA's final actions were discordant with the advisory committee's recommendations. Of these, 75% resulted in the FDA making more restrictive decisions after favorable committee recommendations, and 25% resulted in the agency making less restrictive decisions after unfavorable committee recommendations. Discordance was associated with lower degrees of advisory committee consensus and was more likely for agency actions focused on medical product safety than for novel approvals or supplemental indications. Statements by public speakers, advisory committee conflicts of interest, and media coverage were not associated with discordance between the committee and the agency. The FDA disagrees with the recommendation of its advisory committees a minority of the time, and in these cases it tends to be less likely to approve new products or supplemental indications and take safety actions. Deviations from recommendations thus offer an opportunity to understand the factors influencing decisions made by both the agency and its expert advisory groups.

The US Food and Drug Administration and Cardiovascular Medicine: Reflections and Observations.

The US Food and Drug Administration (FDA) is a remarkable hybrid. Part regulatory agency, part public health agency, it sits at the intersection of science, law, and public policy. The FDA’s mission can be considered in the context of 2 broad dimensions: the products it regulates and its core functions. Both fall under the rubric of protecting and promoting the public health. The FDA’s remit is both broad and diverse: altogether, the agency has regulatory responsibility for >20% of the US economy. The products it is charged with overseeing through its various centers1 encompass food and cosmetics (regulated by the Center for Food Safety and Applied Nutrition); food and drugs for animals, including companion animals and animals used for food (regulated by the Center for Veterinary Medicine); and medical devices, drugs, and biologics (regulated by the Centers for Devices and Radiological Health, Drug Evaluation and Research, and Biologics Evaluation and Research, respectively). Tobacco products were added to the FDA’s portfolio by the Tobacco Control Act of 2009, and are overseen by the Center for Tobacco Products. Regardless of the specific product regulated, the FDA’s core mission remains the same: to protect the US population by helping to ensure the fundamental safety of the food Americans consume and the medical products prescribed by their clinicians. At the same time, this primary mission is complemented by a mandate to promote the public health by reviewing research and taking appropriate action on the marketing of regulated products in a timely manner. Not only do people need access to advances in nutrition and medical therapies, but also the American spirit is itself characterized by a strong current of scientific and technological innovation. At first glance, differences in these 2 priorities, protecting the public safety and promoting the public health through encouraging innovation, might …

The FDA's Misplaced Priorities: Premarket Review Under the Family Smoking Prevention and Tobacco Control Act

Among other key objectives, the 2009 Family Smoking Prevention and Tobacco Control Act was designed to end an era of constant product manipulation by the tobacco industry that had led to more addictive and attractive products. The law requires new tobacco products to undergo premarket review by the U.S. Food and Drug Administration (FDA) before they can be sold. To assess the FDA’s implementation of its premarket review authorities, we reviewed FDA actions on new product applications, publicly available data on industry applications to market new products, and related FDA guidance documents and public statements. We conclude that the FDA has not implemented the premarket review process in a manner that prioritizes the protection of public health. In particular, the FDA has: (1) prioritized the review of premarket applications that allow for the introduction of new tobacco products over the review of potentially noncompliant products that are already on the market; (2) misallocated resources by accommodating the industry’s repeated submissions of deficient premarket applications; and (3) weakened the premarket review process by allowing the tobacco industry to market new and modified products that have not completed the required review process.

FDA's misplaced priorities: premarket review under the Family Smoking Prevention and Tobacco Control Act

Among other key objectives, the 2009 Family Smoking Prevention and Tobacco Control Act was designed to end an era of constant product manipulation by the tobacco industry that had led...

FDA Safety Reviews on Drugs, Biologics, and Vaccines: 2007-2013.

In 2002, Congress mandated that the US Food and Drug Administration (FDA) monitor postmarketing pediatric adverse events and present safety reports to the FDA's Pediatric Advisory Committee (PAC). These safety reviews play a critical role in the postmarketing surveillance and identification of pediatric safety issues. This article follows a previous review ending in 2007 and summarizes 6 years of recent pediatric safety reporting, recommendations by the PAC, and actions by the FDA, including labeling changes. An analysis of the FDA's PAC safety reviews performed from November 2007 through September 2013 was conducted. PAC recommendations for subsequent labeling changes, future studies, or other safety issues were reviewed. There were 6930 serious adverse event reports in 181 reviews. These findings resulted in 33 (18%) recommended labeling changes, and 21 (64%) of these changes were adopted. For 10 products, information was added to the Warning and Precautions section of the label. The PAC also discussed or recommended additional studies for certain products. This article highlights the importance of the FDA's ongoing pediatric postmarketing safety reviews of regulated products, advice from the PAC, and FDA actions in the best interest of pediatric patients. This mandated process facilitates detection of safety concerns that may not be identified in prelicensure clinical trials. It continues to identify critical safety concerns, including unlabeled adverse events, frequent off-label use, product misuse, and secondary exposures in children.

The history of efforts to regulate dietary supplements in the USA.

This review examines the emergence of dietary supplements and how the Food and Drug Administration (FDA) attempted to regulate these, beginning with the arrival of vitamins and how these were managed under the 1906 Food and Drugs Act, and ending with the seismic influence of the 1994 Dietary Supplement Health and Education Act (DSHEA). Included are the impact of major laws, key court decisions, and the construction of the FDA's supplement actions and rules from the 1920s to the 1990s for products that were neither drugs nor typical foods. Stiff resistance to the regulations by supplement manufacturers, trade associations, politicians, and especially the public at large is an important part of this story. The paper closes with the passage of DSHEA and how it literally changed the definition and parameters of control of dietary supplements. Copyright © 2015 John Wiley & Sons, Ltd.

Abstract IA13: Connecting science to law: Understanding the policymaking process

Abstract Tobacco use remains the leading cause of preventable death in the U.S., killing 480,000 Americans a year. To address the death and disease caused by tobacco use, Congress enacted the Family Smoking Prevention and Tobacco Control Act (FSPTCA) in 2009, granting the U.S. Food and Drug Administration (FDA) broad authority to regulate the manufacture, marketing, and sale of tobacco products. In order to help build the science base for tobacco regulation, the FDA has invested heavily in “tobacco regulatory science.” In partnership with the National Institutes of Health (NIH), it is investing $273 million over five years in the Tobacco Centers of Regulatory Science (TCORS) initiative. The TCORS program funds 14 centers at academic institutions (including Ohio State) that conduct research relevant to the FDA's regulation of tobacco. This initiative is a unique partnership between a regulatory agency and researchers, developed with the explicit expectation that the research will directly inform the FDA's regulatory actions. To conduct research that will assist the FDA in fulfilling its regulatory mission, researchers must venture outside of their comfort zone and consider the relevant legal and policy environment. More specifically, scientists engaged in tobacco regulatory science must consider at least four different questions: (1) what FDA regulatory action(s) might my research inform?; (2) what types of evidence would the FDA need to consider in order to take such actions?; and (3) if such a regulation were reviewed in court, what questions would the courts ask about the available evidence? Failure to consider these questions may lead to research that, while scientifically valid, does not advance the FDA's ability to fulfill its regulatory mission. Thus, in order for the TCORS program to succeed, there must be a productive and ongoing dialogue between scientists and attorneys familiar with the regulatory landscape. This presentation will discuss the need for better coordination between scientists and attorneys, particularly in the context of tobacco regulatory research. It will also discuss how law acts as a social determinant of health that has a significant impact (both positive and negative) on health disparities. Citation Format: Micah L. Berman. Connecting science to law: Understanding the policymaking process. [abstract]. In: Proceedings of the Seventh AACR Conference on The Science of Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; Nov 9-12, 2014; San Antonio, TX. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2015;24(10 Suppl):Abstract nr IA13.

Association of Attorney Advertising and FDA Action with Prescription Claims: A Time Series Segmented Regression Analysis.

Attorneys sponsor television advertisements that include repeated warnings about adverse drug events to solicit consumers for lawsuits against drug manufacturers. The relationship between such advertising, safety actions by the US Food and Drug Administration (FDA), and healthcare use is unknown. To investigate the relationship between attorney advertising, FDA actions, and prescription drug claims. The study examined total users per month and prescription rates for seven drugs with substantial attorney advertising volume and FDA or other safety interventions during 2009. Segmented regression analysis was used to detect pre-intervention trends, post-intervention level changes, and changes in post-intervention trends relative to the pre-intervention trends in the use of these seven drugs, using advertising volume, media hits, and the number of Medicare enrollees as covariates. Data for these variables were obtained from the Center for Medicare and Medicaid Services, Kantar Media, and LexisNexis. Several types of safety actions were associated with reductions in drug users and/or prescription rates, particularly for fentanyl, varenicline, and paroxetine. In most cases, attorney advertising volume rose in conjunction with major safety actions. Attorney advertising volume was positively correlated with prescription rates in five of seven drugs, likely because advertising volume began rising before safety actions, when prescription rates were still increasing. On the other hand, attorney advertising had mixed associations with the number of users per month. Regulatory and safety actions likely reduced the number of users and/or prescription rates for some drugs. Attorneys may have strategically chosen to begin advertising adverse drug events prior to major safety actions, but we found little evidence that attorney advertising reduced drug use. Further research is needed to better understand how consumers and physicians respond to attorney advertising.

Conservatism, Consumer Choice, and the Food and Drug Administration during the Reagan Era: A Prescription for Scandal, by Lucas Richert

Conservatism, Consumer Choice, and the Food and Drug Administration during the Reagan Era: A Prescription for Scandal, by Lucas Richert. Lanham, Lexington Books, 2014. viii, 221 pp. $90.00 US (cloth). Lucas Richert frames the Food and Drug Administration (FDA) within the rise of conservatism, a force within the Republican Party and one that attracted Ronald Reagan as perhaps its exemplar. In this sense Conservatism, Consumer Choice, and the Food and Drug Administration during the Reagan Era is as much about the FDA as it is about the ideology that has attempted to constrict the agency. In this context the book may be best understood as an example of the triumph of conservatism in modem American life. Scholars have produced many studies of the pharmaceutical industry and the FDA. What Richert delivers is a political narrative of conservatism within the context of capitalism, scientific research, and the rise and fall of ideologies. The author begins his treatment with a brief history of the FDA, tracing its roots to what one might call its proto inception in the US State Department in 1839. Much credit of course is due Upton Sinclair and Harvey Wiley in the first decade of the twentieth century, but the story is too well-known to merit treatment. Within this historical framework it is useful to trace changes in the scope of the FDA's authority. Over the short term Richert focuses sharply on Reagan as the catalyst of modem conservatism. Well-known was the president's penchant for portraying government as antithetical to freedom. Accordingly the discourse shifted toward the prospect of shrinking the size and scope of government. As president, Reagan had the federal government in mind, but plenty of his sycophants applied his principles to state and local governments. Reagan took aim at a number of federal agencies including the FDA. In this context arose questions about the FDA's actions. To what degree did the FDA have the authority to regulate drugs and other substances that Americans ingested? Did this authority conflict with freedom of choice? Did the FDA operate outside the confines of capitalism? Richert explores the tensions within such inquiries, but authoritative judgments are difficult to make. The author stretches his chronology between 1974 and 2008 but spends much of his energy examining the 1970s and 1980s. During this era, pharmaceutical companies were eager that Reagan, certainly by the 1980s, diminish the regulatory powers of the FDA. In this context the innovation argument came to the fore as drug companies argued that federal regulations penalized them for pursuing new lines of research and developing truly novel therapies. …

How Did Multiple FDA Actions Affect the Utilization and Reimbursed Costs of Thiazolidinediones in US Medicaid?

PurposeThe US Food and Drug Administration (FDA) communicated the potential cardiovascular risk of thiazolidinediones (rosiglitazone and pioglitazone) in 2007 and required a Risk Evaluation and Mitigation Strategy (REMS) for rosiglitazone in 2010. It also communicated in 2010 the potential risk of bladder cancer with pioglitazone use. This study examined the effects of these multiple FDA actions on utilization and reimbursed costs of thiazolidinediones in state Medicaid programs. MethodsState Drug Utilization Data from the Centers for Medicare & Medicaid Services were assessed. An interrupted time series design and segmented linear regression models were used to examine changes in market shares according to both prescription volume and reimbursed costs for rosiglitazone and pioglitazone in the Northeast and Midwest regions of the United States after multiple FDA actions. FindingsCompared with expected rates, there were relative reductions of 65.84% (Northeast region) and 55.09% (Midwest region) in the use of rosiglitazone at 1 year after the 2007 FDA actions for thiazolidinediones and cardiac risk. At the same time, relative increases of 7.30% and 9.28% in the use of pioglitazone were observed in the Northeast and Midwest regions, respectively. Changes in both use and costs of rosiglitazone after the 2010 REMS program could not be estimated because of the already low rates (~1%) before REMS was implemented. One year after the 2010 FDA actions for pioglitazone and its possible association with bladder cancer, relative reductions in pioglitazone use of 21.41% (Northeast region) and 18.12% (Midwest region) were detected. ImplicationsThe Northeast and Midwest regions reported similar patterns of changes after the FDA actions. Use and costs of rosiglitazone were substantially reduced after the 2007 FDA actions for cardiovascular risk, and this drug was rarely used after the 2010 REMS program. Conversely, use and costs of pioglitazone were substantially reduced after the 2010 FDA actions regarding the drug’s possible risk of bladder cancer.

Impact of FDA Actions, DTCA, and Public Information on the Market for Pain Medication.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are one of the most important classes of prescription drugs used by primary care physicians to manage pain. The NSAID class of products has a somewhat controversial history, around which a complex regulatory and informational environment has developed. This history includes a boxed warning mandated by the Food and Drug Administration (FDA) for all NSAIDs in 2005. We investigate the impact that various information shocks have had on the use of prescription medications for pain in primary care in the USA. We accomplish this by extracting data on nearly 600,000 patients from a unique nationwide electronic medical record database and estimate the probability of any active prescription for the four types of pain medications as a function of FDA actions, advertising, media coverage, and patient characteristics. We find that even after accounting for multiple sources of information, the FDA label changes and boxed warnings had a significant effect on pain medication prescribing. The boxed warning did not have the same impact on the use of all NSAID inhibitors. We find that the boxed warning reduced the use of NSAID COX-2 inhibitor use, which was the focus of much of the press attention. In contrast, however, the warning actually increased the use of non-COX-2 NSAID inhibitors. Thus, the efficacy of the FDA's black box warning is clearly mixed.

The FDA and 23andMe: violating the First Amendment or protecting the rights of consumers?

One of the largest direct-to-consumer (DTC)2 genetic testing facilities, 23andMe, was ordered by the U.S. Food and Drug Administration (FDA) to cease marketing its Personal Genome Service (PGS) test on Nov. 22, 2013 (1). This occurred after 23andMe failed to respond to questions from the FDA about the analytical and clinical validity of this test (see Table 1 for definitions). In response to the FDA's order, 23andMe no longer provides health-related genetic risk assessments but still provides the genetic data (i.e., genotypes) and ancestry-related genetic reports. Although some support the FDA's actions because of the test's potential for harm to consumers, other personalized medicine advocates are crying foul, saying that the FDA is being overly paternalistic and impeding medical advances. Green and Farahany, in a recent commentary in Nature , argued that the FDA's actions are “unwarranted without evidence of harm” (2). They further stated that these types of FDA regulations are disallowing advertising (“commercial speech”) as well as preventing individuals from their right to receive information, both of which are protected under the First Amendment. The FDA might counter that this medical device is subject to all of the same regulations as all other medical devices. View this table: Table 1. Definitions of terms.a Part of the complaint by some has been that the FDA should not presume that consumers are unable to understand their own genomic information and therefore deny consumers access to these data. However, in its personalized medicine document, the FDA states that its “mission is to protect and promote the health of all Americans through assuring the safety, efficacy, and security of drugs, biologics …, and medical devices. … In the case of medical products, FDA determines that products are safe and effective before marketing through a careful evaluation of benefits and risks that considers the available scientific data in the context …

Impact of FDA Actions, DTCA, and Public Information on the Market for Pain Medication

Non-steroidal anti-inflammatory drugs (NSAIDs) are one of the most important classes of prescription drugs used by primary care physicians to manage pain. The NSAID class of products has a somewhat controversial history, around which a complex regulatory and informational environment has developed. This history includes a boxed warning mandated by the Food and Drug Administration (FDA) for all NSAIDs in 2005. We investigate the impact that various information shocks have had on the use of prescription medications for pain in primary care in the U.S. We accomplish this by extracting data on nearly 600,000 patients from a unique nation-wide electronic medical record database and estimate the probability of any active prescription for the four types of pain medications as a function of FDA actions, advertising, media coverage and patient characteristics. We find that even after accounting for multiple sources of information, the FDA label changes and boxed warnings had a significant effect on pain medication prescribing. The boxed warning did not have the same impact on the use of all NSAID inhibitors. We find that the boxed warning reduced the use of NSAID cox-2 inhibitor use, which was the focus of much of the press attention. In contrast, however, the warning actually increased the use of non-cox-2 NSAID inhibitors. Thus, the efficacy of the FDA’s black box warning is clearly mixed.

Atomoxetine Use During a Period of FDA Actions

The Food and Drug Administration (FDA) issued a Public Health Advisory entitled "Suicidal Thinking in Children and Adolescents Being Treated with Strattera (Atomoxetine)" on September 29, 2005. At FDA's request, the manufacturer subsequently added a boxed warning to the drug's labeling on November 8, 2005. To evaluate whether the boxed warning for suicidal thinking in atomoxetine's labeling was associated with a change in the pattern of attention-deficit/hyperactivity disorder (ADHD) medication use. Patients who had an ADHD diagnosis and were prescribed either atomoxetine or stimulants between January 2004 and December 2007 were selected from IMS LifeLink Health Plan Claims database. In this ecologic analysis, the outcome measure is the incident atomoxetine use rate, defined as the proportion of atomoxetine incident users among all initial ADHD pharmacotherapy users. The impact of the boxed warning was evaluated using interrupted time series analysis. A total of 16,311 patients met the definition of incident ADHD medication users. The incident atomoxetine use rate decreased from January 2004 to September 2005 among all age groups (range, -0.45% to -0.74%); and the rate among adult patients decreased by 11.89% (95% confidence interval, 3.05%-20.74%) from September 2005 to November 2005. No long-term impact was detected. Significant decline of the atomoxetine use rate was observed before the boxed warning in all age groups. No significant change was detected in the atomoxetine use rate among targeted children or adolescents after the FDA's boxed warning concerning suicidal thinking.

A Sisyphean Task: How Electronic Cigarettes are Stymieing Efforts of Both Congress and the FDA to Protect Public Health

The adverse effects of smoking have fostered a natural market for smoking cessation and smoking reduction products. Smokers attempting to quit or reduce consumption have tried everything: "low" or "light" cigarettes; nicotine-infused chewing gum, lozenges, and lollipops; dermal patches; and even hypnosis. The latest craze in the quest to find a safer source of nicotine is the electronic cigarette. Electronic cigarettes (e-cigarettes) have swept the market, reaching a rapidly expanding international consumer base. Boasting nicotine delivery and the tactile feel of a traditional cigarette without the dozens of other chemical constituents that contribute to carcinogenicity, e-cigarettes are often portrayed as less risky, as a smoking reduction or even a complete smoking cessation product, and perhaps most troubling for its appeal to youth, as a flavorful, trendy, and convenient accessory. The sensationalism associated with e-cigarettes has spurred outcry from health and medical professional groups, as well as the Food and Drug Administration (FDA), because of the unknown effects on public health. Inhabiting a realm of products deemed "tobacco products" under recent 2009 legislation, e-cigarettes pose new challenges to FDA regulation because of their novel method of nicotine delivery, various mechanical and electrical parts, and nearly nonexistent safety data. Consumer use, marketing and promotional claims, and technological characteristics of e-cigarettes have also raised decades old questions of when the FDA can assert authority over products as drugs or medical devices. Recent case law restricting FDA enforcement efforts against e-cigarettes further confounds the distinction among drugs and medical devices, emerging e-cigarette products, and traditional tobacco products such as cigarettes, cigars, and smokeless tobacco. This Article investigates the e-cigarette phenomenon in the wake of the recently enacted Family Smoking Prevention and Tobacco Control Act of 2009 (TCA). It examines the tumultuous history of attempts at tobacco regulation by reflecting on the history of Congressional activity to regulate tobacco sales and promotion. Furthermore, this Article suggests a feasible approach to strengthening regulation of e-cigarettes under the existing statutory framework. This approach includes increased scrutiny of manufacturer and distributor claims that trigger drug and medical device provisions, utilization of new tobacco product and modified risk tobacco product provisions, and promulgation of new FDA regulations and guidance specifically directed at e-cigarettes.