Inclusion of Infants and Neonates in Pediatric Orphan Product Approvals.

The Orphan Drug Act (ODA) of 1983 was enacted to provide financial incentives to drug sponsors to develop therapies for rare diseases. Although this act increased the number of orphan products approved, there are still a limited number of products available for the pediatric population because orphan drug products are exempt from the Pediatric Research Equity Act. The objectives of this study were (i) to evaluate the pediatric orphan drug studies submitted to the US Food and Drug Administration (FDA) in the period of 2007-2018 and (ii) to examine whether orphan drug products were fully labeled with a pediatric indication in infants and neonates. Out of the 468 indications evaluated, 171 (37%) were FDA-labeled for use in the pediatric population. Labeling for the 12 to < 18 years age group was most common (98%). Fifty-two percent of FDA-labeled pediatric indications included the newborn to < 2 years of age group. In this newborn to < 2 years age group, the indication was labeled without pivotal clinical trials in 43% of the programs. Of the 60 new indications not labeled down to birth, 50% were found to have an age of onset and diagnosis that occurs earlier than the age approved for use of the product for that indication. In summary, although the ODA has been successful in improving pediatric access to medications for rare diseases, our analysis identified the incomplete labeling for pediatric patients under 2 years of age. Strategies to include the birth to < 2 years old group of pediatric patients in orphan drug development programs should be explored.

Analysis of the Real-Time Oncology Review (RTOR) Pilot Program for Approvals of New Molecular Entities.

The United States Food and Drug Administration (FDA) Oncology Center of Excellence (OCE) established the Real-Time Oncology Review (RTOR) pilot program in 2017 to streamline the review process for oncology drug applications with the applicant and the Agency agreeing upon a piecemeal strategy and timeline for module components. The Prescription Drug User Fee Act (PDUFA) review clock does not officially start until the final component is submitted. Participation requires careful planning of time and resources due to the multiple submissions and interactions with the FDA. Applicants must also meet certain criteria regarding the clinical trial design and development program to be eligible for RTOR. Publicly available databases (Drugs@FDA) and documents were searched for all RTOR applications, which revealed a total of 28 approved applications that participated from February 2018 to August 2020. Initial marketing applications were further reviewed to identify any potential advantages or limitations from participation in the pilot program. These four case studies demonstrated an individualized RTOR process reflecting the program's pilot status. The FDA approved 3 out of the 4 applications approximately three to four months before the PDUFA goal date. The time savings is not guaranteed as other parts of the review may influence the overall timeline. However, the optional biweekly teleconferences increased communication and collaboration between the applicant and the FDA. The full impact of RTOR on applications remains undetermined as the number of approved applications that have participated in the pilot program is still relatively small.

Appropriateness of thrombophilia testing in patients in the acute care setting and an evaluation of the associated costs.

Thrombophilia testing is rarely recommended in acute care settings due to the high likelihood of false-positive and false-negative results. Inappropriately performing these tests in the acute care setting is associated with inaccurate interpretation and an increased economic burden. In this retrospective analysis, the appropriateness of thrombophilia tests ordered for patients in an acute care setting was evaluated in terms of both clinical utility and economic costs. This analysis included adult inpatients discharged from an academic community medical center from November 1, 2016 to November 1, 2017 who received thrombophilia testing. Patients were stratified into two groups: appropriately tested and inappropriately tested based on data abstracted directly from the electronic health record. The primary outcome, the appropriateness of the tests, was based on published criteria for thrombophilia testing and included concurrent anticoagulation use, patient admitting diagnosis, and/or comorbidities associated with thrombosis risk. The secondary endpoint was the financial burden of inappropriate thrombophilia testing based on assay charges. The analytic sample included 200 patients and 1393 thrombophilia tests. In 179 patients (89.5%), 1168 tests (83.8%) were inappropriately conducted. From 179 patients, tests in 85 were inappropriate due to concurrent anticoagulant use and/or provoked venous thromboembolism (VTE), and tests in 94 were inappropriate due to a lack of 2 or more risk factors for thrombophilia. Only 21 patients (10.5%) had appropriate testing with 225 tests (16.2%). The financial impact of inappropriate testing was estimated as excess charges amounting to $148,151.16/year. Restricting testing to avoid unnecessary risks and costs warrants further analysis.