BackgroundAvailable evidence for many prescription drugs comes from clinical trials that often exclude older patients. Real-world evidence (RWE) generated post-approval can provide new evidence on effectiveness and safety for these populations. We sought to understand physicians' perceptions of clinical trial and RWE for prescribing decisions. To frame the study, we used examples of drugs for heart failure and anticoagulation, which are more like to be prescribed to older adults.MethodsWe conducted an interview study of 15 US physicians specializing in geriatrics, cardiology, or primary care and affiliated with academic medical centers. Interviews were coded using a qualitative thematic analysis approach to construct themes and identify patterns in responses.ResultsAll participants described limitations in current believed real-world evidence could help inform patient care and their practice. However, they had concerns about the data. If clinical trial and RWE findings diverged, all would need more information to determine which findings to follow.ConclusionsPhysicians who routinely prescribe to older patients are optimistically cautious about RWE for drugs but would rely on trusted sources, like professional society guidelines, for incorporating it into practice. Therefore, RWE researchers should identify opportunities to work alongside guideline developers and database editors on the practice-relevant interpretation and dissemination of the evidence.

Objectives To assess the additional therapeutic value of Food and Drug Administration (FDA) breakthrough-designated drugs using ratings from four international organizations and to address the implications of these evaluations for the program’s limitations and effectiveness. Methods We compiled a list of all breakthrough-designated new drugs from FDA reports from the start of the program in 2012 to the end of 2022. Therapeutic value was assessed using ratings from agencies in Canada, France, and Germany, as well as a nonprofit French drug bulletin. If a drug was rated by more than one organization, then the highest rating was used. Key findings The FDA approved 121 breakthrough therapies. Therapeutic evaluations were available for 96 drugs. Twenty-two (22.9%) offered major additional therapeutic benefits, 32 (33.3%) offered moderate benefits, and 42 (43.8%) minor benefits. Our findings align with prior studies suggesting a misalignment between FDA designations and actual therapeutic value. Conclusions Less than one in four drugs with a breakthrough designation that were evaluated by external organizations offered a major therapeutic advance. Given that the FDA has approved new molecular entities with limited therapeutic gain, these findings suggest a need for greater scrutiny of breakthrough designations. The FDA should periodically reevaluate approved breakthrough drugs based on new evidence that has emerged since their initial approval and withdraw the designation when drugs are shown to fall short of the early expectations on which initial breakthrough status was based.

To combat the growing threat of antimicrobial resistance, Congress has considered legislation such as the PASTEUR Act that would provide "market entry rewards" of up to $3 billion for each new FDA-approved drug. As policymakers consider such rewards, they should appreciate valuation challenges long known to the intellectual property community but under-acknowledged in health policy circles. For new drugs, these challenges include hidden government costs already expended, foregone opportunities to pursue alternate means of reducing patient morbidity and mortality, and the risk posed by creeping political influence to future value assessments. It will also be important for legislators to consider the disappointing outcomes of similar past laws, such as the GAIN Act.

Over the past three decades, the U.S. health care system has experienced numerous shortages of commonly-used older medicines that are both off-patent and inexpensive. Commentators seeking to explain shortages have often pointed to manufacturing quality and low profit margins as principal causes. These proximate causes, however, do not explain why there was a sudden and dramatic increase in shortages between 2007 and 2012, when shortages almost tripled from 154 to 456, or why they have persisted at similar levels into the 2020s despite repeated efforts to address them. This Article posits that low prices and quality problems derive from underlying shifts in the market environment, and that these shifts in turn are largely the result of Congressional legislation. The role of such well-intentioned legislation over the past fifty years is evaluated, including the 1984 Hatch-Waxman Act, the 2003 Medicare Modernization Act, the 2012 Generic Drug User Fee Act, and the 2015 Bipartisan Budget Act. The analysis reveals these laws have inadvertently squeezed profitability out of the generic drug market and thereby served as a true root cause of many drug shortages. Also considered are the potential effects on drug shortages of more recent legislation, including the 2021 American Rescue Act Plan and the 2022 Inflation Reduction Act.

We report on an experience with impostor research participants, people who misrepresent themselves, and identify characteristics that can be used by investigators to screen out such participants. We compare the responses of impostor and valid participants, showing that impostors meaningfully change qualitative study findings with implications for policy interventions or follow-on research informed by the study. It is important for investigators to be alert to the potential for impostor participants and plan their research accordingly.

The authors respond to a letter by Mitchell Berger in the March-April 2024 issue of the Hastings Center Report concerning their essay "Securing the Trustworthiness of the FDA to Build Public Trust in Vaccines."

BACKGROUND:After a new drug or medical device is approved by the US Food and Drug Administration (FDA), physician-patient communication about benefits and risks is critical, including whether the product was approved through an expedited pathway based on limited evidence. In addition, physician reporting of drug- and device-related adverse events in real-world use is necessary to have a complete safety profile. We studied physician-reported communication and safety-reporting practices related to drugs and devices. METHODS:We surveyed a random national sample of American Board of Internal Medicine-certified internists, cardiologists, and oncologists between October 2021 and September 2022 about the sources of information used to prescribe a drug or medical device, details of communication with patients, and reporting of adverse events. RESULTS:Among 509 respondents (39% response rate), 387 (76%) reported that FDA approval influenced their decision "a lot" to prescribe a new drug or recommend use of a medical device. Half (122; 50%) of the 244 physicians randomized to receive a question about their own communication of trial endpoints reported "usually" telling patients when products were approved based on surrogate measures and 126 (52%) "usually" reported telling patients if a postapproval trial was required to evaluate safety and effectiveness. Two-thirds (165) said they were likely to report drug- or device-related adverse events to FDA. CONCLUSIONS:Physician self-reporting of communication with patients about drugs and devices suggests that half include characteristics of the pivotal trials such as use of clinically meaningful endpoints or continued requirement for evidence generation. IMPLICATIONS:More consistent discussions with patients about the quality of evidence supporting new drugs and devices and increased reporting of adverse events could ensure optimal use of these products in clinical practice. HIGHLIGHTS:Among 509 board-certified internists, cardiologists, and oncologists, half reported telling patients when drugs or medical devices were approved based on surrogate measures and when there was an FDA-mandated postapproval trial to further evaluate safety and effectiveness.As drugs and medical devices are increasingly approved by the FDA through expedited pathways based on data with lingering uncertainties, discussion with patients about issues such as the nature of the endpoints assessed and existence of postapproval testing requirements can help inform patient decision making.

Physicians' knowledge of Food and Drug Administration (FDA) approval processes is important in informing clinical decisions and patient discussions. Among a randomly selected national sample of 509 internists, cardiologists, and oncologists, 41 percent reported moderate or better understanding of the FDA's drug approval process, and 17 percent reported moderate or better understanding of the FDA's medical device approval process. Nearly all physicians thought that randomized, blinded trials that met primary endpoints should be very important factors required to secure regulatory approval. Also, nearly all physicians thought that the FDA should revoke approval for acceleratedapproval drugs or breakthrough devices that did not show benefit in postapproval studies. Our findings suggest that physicians commonly lack familiarity with drug and medical device regulatory practices and are under the impression that the data supporting FDA drug and high -risk device approvals are more rigorous than they often are. Physicians would value more rigorous premarket evidence, as well as regulatory action for drugs and devices that do not demonstrate safety and effectiveness in the postmarket setting.

Building trust in public health agencies like the US Food and Drug Administration (FDA) has become a key government priority. Understanding the roots of FDA mistrust is important if the agency is to develop targeted messaging and reforms aimed at building confidence in the agency. We conducted a survey of 2,021 respondents in the US probing attitudes toward the FDA. The primary outcome was FDA trust, defined as the mean score that each respondent assigned to the FDA across four prespecified axes: (1) competence and effectiveness; (2) commitment to acting in the best interests of the American public; (3) abiding by the rules and regulations set forth by policy or law; and (4) expertise in health, science, and medicine. On multivariable ordinal logistic regression, FDA mistrust was associated with female gender (odds ratio [OR] = 0.74, 95% confidence interval [CI] 0.62–0.88), rural community (OR 0.85, 95% CI 0.75–0.96), conservative political views (OR 0.77, 95% CI 0.74–0.81), worse self‐reported health (OR 0.89, 95% CI 0.80–0.98), lower satisfaction with health care received (OR 0.63, 95% CI 0.56–0.71), less attention to health and science news (OR 0.72, 95% CI 0.64–0.80), and not having children under the age of 18 (OR 0.72, 95% CI 0.60–0.86). These findings underscore the challenges faced by US political leaders in convincing a heterogeneous American public to trust the FDA. The FDA should develop and deploy targeted outreach strategies to populations with lower levels of trust and strengthen internal processes that minimize biases and ensure sound decision‐making.

Patent applications filed after a New Drug Application (NDA) is approved are uncommon and do not appear to substantially delay approval of generic drugs in most cases.

The authors have no conflicts of interest. Supplementary Methods S1. Focus group recruitment, methods, and additional themes on perceptions of evidence. Table S1. Participant characteristics (self-reported). Table S2. Additional themes identified and illustrative quotes. Table S3. COREQ checklist. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

This cohort study assesses the frequency of approval and marketing of skinny-label biosimilars and their savings to Medicare.

To treat diabetes, one of the most prevalent diseases globally and in the USA,1 the US Food and Drug Administration (FDA) has approved a wide range of synthetic insulin products since the early 1980s. Despite this range of products, access to insulin remains challenging in part due to product prices. Drastically increased per-person expenditures on insulin products have been accompanied by a shift from animal and human insulins to high-cost analogue versions with modified new chemical structures, delivery devices, or other changes.

Background and Objective To assess the characteristics and extent of variation of the endpoints used in trials supporting the US Food and Drug Administration (FDA) approval of medications treating migraine. Methods Using the Drugs@FDA online database, we identified novel prescription medications approved by the FDA between January 2001 and September 2022, for migraine with or without aura, for both acute and preventive treatment, and for episodic and chronic presentations. For each medication, we used the most recent FDA-approved labeling to identify indication, mechanism of action, mode of administration, manufacturer, approval year, number of pivotal trials, trial design, and primary endpoints. Results Sixteen FDA-approved medications for the acute or preventive treatment of migraine were supported by 45 pivotal trials. There were 5 primary endpoint types: (1) change in mean monthly migraine days from baseline; (2) change in mean monthly migraine attacks from baseline; (3) change in mean monthly headache days from baseline; (4) mild to no pain After 2 hours; (5) pain free at 2 hours. There were 3 combinations of coprimary endpoints: (1) Headache Pain Free at 2 Hours and Most Bothersome Symptom Free at 2 Hours; (2) Pain Free at 2 Hours and Sustained Pain Free from 2-24 Hours Postdose; (3) Pain Free at 2 Hours and 2–24 Hours Sustained Pain Free and 2-Hour Pain Relief. Of the 8 preventive migraine medications, the timing of endpoint measurement included the full double-blind period, segments of the double-blind period, and the final month of the double-blind period. Discussion Migraine medication trial endpoints were inconsistent within the same indication (episodic or chronic), mechanistic class, and route of administration, frustrating direct comparison among these medications. Furthermore, inconsistent definitions for the indications “episodic” and “chronic” migraine were also observed. Consistent endpoint selection for medications approved for preventive and acute migraine treatment would enhance the ability of patients, physicians, and payers to make informed choices among these medications.

The Covid-19 pandemic highlighted the need to examine public trust in the U.S. Food and Drug Administration (FDA) vaccine approval process and the role of political influence in the FDA's decisions. Ensuring that the FDA is itself trustworthy is important for justifying public trust in its actions, like vaccine approvals, thereby promoting public health. We propose five conditions of trustworthiness that the FDA should meet when it reviews vaccines, even during emergencies: consistency with rules, proper expert or political decision-makers, proper decision-making and noninterference, connection to public preference, and transparency of both reasons and procedures. The five conditions provide a road map of procedural and substantive requirements, which the FDA has variably implemented, focused on ensuring appropriate influence of political interests. While being a trustworthy agency cannot guarantee the public's trust, implementing these conditions builds a groundwork for public trust.

Despite advertising imagery portraying cancer medicines as offering substantial improvement or cure, most patients can expect modest or no incremental benefit from most new treatments, according to pre-specified criteria. When improvements in overall survival are demonstrated, they average just 2.1 months. Despite limited benefits, drug prices have risen while median household incomes have remained largely unchanged, and these higher prices are poorly correlated with improved outcomes. Better alignment of perception with demonstrated drug benefit could be achieved by limitations on advertising and improved labeling or other disclosures. Reforms are also needed to remove financial incentives to prescribe costlier drugs.

In June 2021, the US Food and Drug Administration (FDA) granted accelerated approval to aducanumab, a monoclonal antibody indicated for the treatment of Alzheimer's disease. The accelerated approval decision was controversial due to concerns about the use of an unvalidated surrogate measure, beta-amyloid, as the basis for approval and a lack of clinical outcome benefit. Between October 2021 and September 2022, we conducted a survey of a nationally representative group of internists, medical oncologists, and cardiologists to understand perspectives around aducanumab's approval and how this FDA decision may influence trust in other drugs approved through the accelerated approval program. Among 214 physician respondents familiar with the accelerated approval of aducanumab, 184 (86%) would not prescribe or recommend aducanumab. Further, 143 (67%) physicians reported losing trust in other drugs approved through the accelerated approval program due to the FDA's decision with aducanumab. As a growing number of similar novel Alzheimer's disease treatments are on the horizon, the first of which, lecanemab, already has received accelerated approval in January 2023, our survey findings provide insight into the impact of the FDA's regulatory decisions on the perspectives and prescribing behavior of physicians concerning these novel drug treatments.