Thirty Years of Orphan Drug Legislation and the Development of Drugs to Treat Rare Seizure Conditions: A Cross Sectional Analysis

Döring, Jan Henje; Lampert, Anette; Hoffmann, Georg F.; Ries, Markus

doi:10.1371/journal.pone.0161660

Cited by 20 publications

(24 citation statements)

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“…Both the orphan drug regulation and the evolution of the drug development market has led to a rising interest in orphan drug development [6,12]. With more products available, the payers have started pushing back and searching for ways to reduce the costs.…”

Section: Current Orphan Drugs In Rare Epilepsiesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

“…Meanwhile the number of orphan designations has increased over recent years [12]. In 2016, a cross-sectional analysis evaluated the impact of orphan drug designation in the US and in Europe [12]. Although the number of orphan drug designations has dramatically increased over time, the number of approved drugs is four-fold less than the number of orphan drug designations in the same period of time.…”

Section: Introductionmentioning

confidence: 99%

“…Since it is essential for a company to ensure the drug is eligible for commercial incentives, applying for orphan designation may sometimes be a strategy for data protection or to access scientific advice by the regulatory agencies. There have been more orphan designations in the US than in the EU [12], and this is partly because of some differences in drug development and regulatory pathways in both regions as exemplified by the approval of vigabatrin or clobazam [12]. Both drugs have been approved several years ago in EU but went through orphan drug development recently in the US.…”

Section: Introductionmentioning

confidence: 99%

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Drug Development for Rare Paediatric Epilepsies: Current State and Future Directions

Auvin

Avberšek

Bast

et al. 2019

Drugs

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Very few epilepsy syndromes, namely Dravet syndrome, Lennox-Gastaut syndrome and West syndrome, have been subject to orphan drug development.  A large number of compounds are currently under investigation, but mostly in the same rare epilepsy syndromes as in the past  A compound could be relevant for orphan drug development based on its mechanism suggested by the knowledge of the causative gene mutation or by data obtained from animal models  In the absence of pathophysiological hypotheses, exploratory/basket clinical studies could be helpful for identifying a target population

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Section: Current Orphan Drugs In Rare Epilepsiesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Drug Development for Rare Paediatric Epilepsies: Current State and Future Directions

Auvin

Avberšek

Bast

et al. 2019

Drugs

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“…Because of this variation, and variation in seizure types, there is no standard of care for treatment of pediatric drug-resistant epilepsy, with treatment dependent on the nature of a child’s individual disease, which drugs are available in a given jurisdiction, and local practice [8]. Individual antiepileptic drugs may benefit only small groups of patients because of the rare nature of some epilepsy syndromes, and some antiepileptic drugs have designated orphan drug status (e.g., stiripentol for Dravet syndrome [9]). In addition to pharmacologic treatments (i.e., antiepileptic drugs), other treatment options include non-pharmacologic interventions (e.g., surgery to resect the seizure focus, vagus nerve stimulation, deep brain stimulation therapy, ketogenic diet therapy) [3], with increasing interest in the use of alternative therapies, including cannabinoids [10, 11].…”

Section: Introductionmentioning

confidence: 99%

Cost-effectiveness of cannabinoids for pediatric drug-resistant epilepsy: protocol for a systematic review of economic evaluations

et al. 2019

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Background Drug-resistant epilepsy negatively impacts the quality of life and is associated with increased morbidity and mortality and high costs to the healthcare system. Cannabis-based treatments may be effective in reducing seizures in this population, but whether they are cost-effective is unclear. In this systematic review, we will search for cost-effectiveness analyses involving the treatment of pediatric drug-resistant epilepsy with cannabis-based products to inform decision-making by public healthcare payers about reimbursement of such products. We will also search for cost-effectiveness analyses of other pharmacologic treatments for pediatric drug-resistant epilepsy, as well as estimates of healthcare resource use, costs, and utilities, for use in a subsequent cost-utility analysis to address this decision problem. Methods We will search the published and gray literature for economic evaluations of cannabis-based products and other pharmacologic treatments for pediatric drug-resistant epilepsy, as well as resource utilization and utility studies. Two independent reviewers will screen the title and abstract of each identified record and the full-text version of any study deemed potentially relevant. Study and population characteristics, the incremental cost-effectiveness ratio (ICER), as well as total costs and benefits, will be extracted, and quality will be assessed by use of the Drummond and CHEERS checklists; context-specific issues will also be considered. From model-based cost-utility and cost-effectiveness analyses, we will extract and summarize the model structure, including health states, time horizon, and cycle length. From resource utilization studies, we will extract data about the frequency of resource use (e.g., neurology visits, emergency department visits, admissions to hospital). From utility studies, we will extract the utility for each health state, the source of the preferences (e.g., child, parent, patient, general public), and the method of elicitation. Discussion Drug-resistant epilepsy in children is associated with important costs to the healthcare system, and decision-makers require high-quality evidence on which to base reimbursement decisions. The results of this review will be useful to both decision-makers considering the decision problem of whether to reimburse cannabis-based products through public formularies and to analysts conducting studies in this area. Systematic review registration PROSPERO no.: CRD42018099591 . Electronic supplementary material The online version of this article (10.1186/s13643-019-0990-z) contains supplementary material, which is available to authorized users.

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Assessment of Surrogate End Point Trends in Clinical Trials to Approve Oncology Drugs From 2001 to 2020 in Japan

et al. 2023

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ImportanceA surrogate end point (SEP) is an end point used in clinical trials as an alternative for measuring the true clinical benefit. The use of SEPs in trials shortens their duration.ObjectivesTo investigate the use of SEPs in clinical trials to support the approval of anticancer drugs and to determine whether confirmatory studies that use overall survival (OS) as an end point are being conducted in Japan.Design, Setting, and ParticipantsIn this cross-sectional study, drug approvals and background information were obtained from publicly available information, such as the Pharmaceuticals and Medical Devices Agency website, for anticancer drugs approved in Japan from January 2001 to December 2020. Data analysis was performed from September 2021 to March 2022.Main Outcomes and MeasuresCharacteristics of approved oncology drugs in Japan, end points for pivotal clinical trials, and outcomes of confirmatory trials using OS as an end point following drug approval.ResultsThere were 299 anticancer drugs approved in Japan during the study period. Of these, 142 (47.5%) were molecular-targeted drugs, the most common of which targeted non–small cell lung cancer. There were 111 (37.1%) anticancer drugs with orphan designation. From 2001 to 2005, OS was used as an end point in 1 approval (3.6%); however, from 2006 to 2020, OS was used in 86 approvals (31.7%). Of the 212 anticancer drugs approved on the basis of SEPs, confirmatory studies with OS as the end point were conducted for only 37 approvals (17.5%); for the remaining 175 approvals, studies are under way for 35 approvals (16.5%), were waivered for 75 approvals (35.4%), and were not conducted for 65 approvals (30.7%). Furthermore, in 20 drug approvals (9.4%), the conducted confirmatory studies were not effective in determining the OS, but the drugs were approved following re-examination.Conclusions and RelevanceThe findings of this study suggest that starting from 2005, the use of OS as an end point has increased in studies supporting the approval of anticancer drugs in Japan. However, even after 2005, approximately two-thirds of these approvals were SEP based. Postmarketing surveillance studies of the true end points are necessary to validate the use of SEPs.

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Thirty Years of Orphan Drug Legislation and the Development of Drugs to Treat Rare Seizure Conditions: A Cross Sectional Analysis

Cited by 20 publications

References 29 publications

Drug Development for Rare Paediatric Epilepsies: Current State and Future Directions

Drug Development for Rare Paediatric Epilepsies: Current State and Future Directions

Cost-effectiveness of cannabinoids for pediatric drug-resistant epilepsy: protocol for a systematic review of economic evaluations

Assessment of Surrogate End Point Trends in Clinical Trials to Approve Oncology Drugs From 2001 to 2020 in Japan

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