UNASSIGNED: Studies show the presence of a mismatch between drug research and disease burden. A study conducted in the European Union found that new drug development was restricted to certain diseases. A study of biosimilar approvals in India found that 87% of drugs were for treating noncommunicable diseases. This study aimed to determine the new drugs approved in India from 2017 to 2021 and the top ten causes of morbidity and mortality and detect the presence of any discordance between these.
UNASSIGNED: A descriptive study was conducted using data on new drug approvals accessed from the Central Drugs Standard Control Organization website. The top ten causes of mortality and morbidity in India from 2015 to 2019 were identified from the Global Burden of Diseases database. Descriptive statistics were used to compare the drug approvals and the leading diseases.
UNASSIGNED: One hundred twenty-six drugs were approved during the study period. Antineoplastic drugs constituted 19.84% of the approvals, antimicrobials 18.25%, and cardiovascular drugs 9.52%. Ischemic heart disease and chronic obstructive pulmonary disease were the two leading causes of morbidity and mortality. Diarrheal diseases, lower respiratory tract infection, and drug-susceptible tuberculosis were among the top ten causes. Ten antibacterials, including four antitubercular drugs, were approved during this period. Two drugs were approved for rare diseases.
UNASSIGNED: Our study showed that the drugs approved were largely in line with the prevalent disease burden, and there was no significant discordance observed. Some diseases, such as ischemic stroke/intracranial hemorrhage, require further efforts in bringing forth newer pharmacotherapy options.

UNASSIGNED: This article presents a strategy that a Drug Delivery Device Developer (DDDD) has adopted to support Abbreviated New Drug Application (ANDA) submissions of drug-device combination products. As per the related FDA guidance, a threshold analysis should be compiled. If \'other differences\' between the Reference Listed Drug (RLD) and the generic drug devices are identified, a Comparative Use Human Factors (CUHF) study may be requested.
UNASSIGNED: The DDDD performed task analysis and physical comparison to assess the pen injector design differences. Then, a formative CUHF study with 25 participants simulating injections using both RLD and the generic pen injectors was conducted.
UNASSIGNED: After each participant completed four simulated injections, similar type and rates of use error between the RLD (0.70) and generic (0.68) pen injectors were observed.
UNASSIGNED: DDDDs can support pharmaceutical companies in the ANDA submission strategy of their drug-device combination product by initiating comparative task analysis and physical comparison of the device as inputs for the threshold analysis. If \'other differences\' are identified, a formative CUHF study can be performed. As shown in our case study, this approach can be leveraged to support the sample size calculation and non-inferiority margin determination for a CUHF study with the final combination product.

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UNASSIGNED: The U.S. antibiotic market failure has threatened future innovation and supply. Understanding when and why clinicians underutilize recently approved gram-negative antibiotics might help prioritize the patient in future antibiotic development and potential market entry rewards.
UNASSIGNED: To determine use patterns of recently U.S. Food and Drug Administration (FDA)-approved gram-negative antibiotics (ceftazidime-avibactam, ceftolozane-tazobactam, meropenem-vaborbactam, plazomicin, eravacycline, imipenem-relebactam-cilastatin, and cefiderocol) and identify factors associated with their preferential use (over traditional generic agents) in patients with gram-negative infections due to pathogens displaying difficult-to-treat resistance (DTR; that is, resistance to all first-line antibiotics).
UNASSIGNED: Retrospective cohort.
UNASSIGNED: 619 U.S. hospitals.
UNASSIGNED: Adult inpatients.
UNASSIGNED: Quarterly percentage change in antibiotic use was calculated using weighted linear regression. Machine learning selected candidate variables, and mixed models identified factors associated with new (vs. traditional) antibiotic use in DTR infections.
UNASSIGNED: Between quarter 1 of 2016 and quarter 2 of 2021, ceftolozane-tazobactam (approved 2014) and ceftazidime-avibactam (2015) predominated new antibiotic usage whereas subsequently approved gram-negative antibiotics saw relatively sluggish uptake. Among gram-negative infection hospitalizations, 0.7% (2551 [2631 episodes] of 362 142) displayed DTR pathogens. Patients were treated exclusively using traditional agents in 1091 of 2631 DTR episodes (41.5%), including \"reserve\" antibiotics such as polymyxins, aminoglycosides, and tigecycline in 865 of 1091 episodes (79.3%). Patients with bacteremia and chronic diseases had greater adjusted probabilities and those with do-not-resuscitate status, acute liver failure, and Acinetobacter baumannii complex and other nonpseudomonal nonfermenter pathogens had lower adjusted probabilities of receiving newer (vs. traditional) antibiotics for DTR infections, respectively. Availability of susceptibility testing for new antibiotics increased probability of usage.
UNASSIGNED: Residual confounding.
UNASSIGNED: Despite FDA approval of 7 next-generation gram-negative antibiotics between 2014 and 2019, clinicians still frequently treat resistant gram-negative infections with older, generic antibiotics with suboptimal safety-efficacy profiles. Future antibiotics with innovative mechanisms targeting untapped pathogen niches, widely available susceptibility testing, and evidence demonstrating improved outcomes in resistant infections might enhance utilization.
UNASSIGNED: U.S. Food and Drug Administration; NIH Intramural Research Program.

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Launched in 1992, the FDA accelerated approval program grants drugs indicated in rare/life threatening diseases the ability to be marketed at a faster pace than through the traditional track. Each manufacturing company presents its drug to the FDA, and within 60 days it will determine if the drug is eligible for this path. Many drugs that were initially approved through this route, subsequently did not demonstrate their clinical benefits. With cancer being a leading cause of death, a vast majority of drugs that have been approved/withdrawn from this pathway are indicated within oncology. There are a wide variety of cancer subtypes and therapeutic target sites that these drugs have been evaluated for. Herein, is an overview of the 17 oncology drugs, spanning 22 cancer-related indications, that had been approved within the accelerated route and subsequently withdrawn.

To evaluate the added benefit and revenues of oncology drugs, explore their association, and investigate potential discrepancies between added benefit and revenues across different approval pathways of the European Medicines Agency (EMA).
Retrospective cohort study.
Oncology drugs and their indications approved by the EMA between 1995 and 2020.
Added benefit was evaluated using ratings published by seven organisations: health technology assessment agencies from the United States, France, Germany, and Italy, two medical oncology societies, and a drug bulletin. All retrieved ratings were recategorised using a four point ranking scale to indicate negative or non-quantifiable, minor, substantial, or major added benefit. Revenue data were extracted from publicly available financial reports and compared with published estimates of research and development (R&D) costs. Finally, the association between added benefit and revenue was evaluated. All analyses were performed within the overall study cohort, and within subgroups based on the EMA approval pathway: standard marketing authorisation, conditional marketing authorisation, and authorisation under exceptional circumstances.
131 oncology drugs with 166 indications were evaluated for their added benefit by at least one organisation within the required timeframe, yielding a total of 458 added benefit ratings; 189 (41%) were negative or non-quantifiable. The median time to offset the median R&D costs ($684m, £535m, €602m, adjusted to 2020 values) was three years; 50 of 55 (91%) drugs recovered these costs within eight years. Drugs with higher added benefit ratings generally had greater revenues. Negative or non-quantifiable added benefit ratings were more frequent for conditional marketing authorisations and authorisations under exceptional circumstances than for standard marketing authorisations (relative risk 1.53, 95% confidence interval 1.23 to 1.89). Conditional marketing authorisations generated lower revenues and took longer to offset R&D costs than standard marketing authorisations (four years compared with three years).
While revenues seem to align with added benefit, most oncology drugs recover R&D costs within a few years despite providing little added benefit. This is particularly true for drugs approved through conditional marketing authorisations, which inherently appear to lack comprehensive evidence. Policy makers should evaluate whether current regulatory and reimbursement incentives effectively promote development of the most effective drugs for patients with the greatest needs.

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OBJECTIVE: Clinical study reports (CSRs) are highly detailed documents that play a pivotal role in medicine approval processes. Though not historically publicly available, in recent years, major entities including the European Medicines Agency (EMA), Health Canada, and the US Food and Drug Administration (FDA) have highlighted the importance of CSR accessibility. The primary objective herein was to determine the proportion of CSRs that support medicine approvals available for public download as well as the proportion eligible for independent researcher request via the study sponsor.
METHODS: This cross-sectional study examined the accessibility of CSRs from industry-sponsored clinical trials whose results were reported in the FDA-authorized drug labels of the top 30 highest-revenue medicines of 2021. We determined (1) whether the CSRs were available for download from a public repository, and (2) whether the CSRs were eligible for request by independent researchers based on trial sponsors\' data sharing policies.
RESULTS: There were 316 industry-sponsored clinical trials with results presented in the FDA-authorized drug labels of the 30 sampled medicines. Of these trials, CSRs were available for public download from 70 (22%), with 37 available at EMA and 40 at Health Canada repositories. While pharmaceutical company platforms offered no direct downloads of CSRs, sponsors confirmed that CSRs from 183 (58%) of the 316 clinical trials were eligible for independent researcher request via the submission of a research proposal. Overall, 218 (69%) of the sampled clinical trials had CSRs available for public download and/or were eligible for request from the trial sponsor.
CONCLUSIONS: CSRs were available from 69% of the clinical trials supporting regulatory approval of the 30 medicines sampled. However, only 22% of the CSRs were directly downloadable from regulatory agencies, the remaining required a formal application process to request access to the CSR from the study sponsor.

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