Dataset Information

Extension of Indication for Authorised Oncology Products in the European Union: A Joint Effort of Multiple Stakeholders.

ABSTRACT: After marketing authorisation, the development of a medicinal product often continues with studies investigating new therapeutic indications. Positive results can potentially lead to changes to the terms of the marketing authorisation, such as an extension of therapeutic indication(s). These studies can be initiated and sponsored by the marketing authorisation holder (MAH) or by others. When results from an investigator-initiated trial suggest that an authorised medicinal product is safe and effective for a new therapeutic indication, physicians may want to treat their patients with this medicinal product. In such a situation, it is desirable to extend the therapeutic indication(s) via the regulatory approval process, as this can facilitate patient access within the European Union. There may however be challenges when the MAH did not conduct the study and might not have access to the data. In this perspective, we focus on the possibilities to extend the therapeutic indication(s) of an already authorised medicinal product based on results from investigator-initiated trials. We address: (1) the advantages of an extension of indication; (2) the regulatory requirements for a variation application; (3) investigator-initiated trials as a basis for regulatory approval; (4) the role of the MAH in extending the indication. With this article, we want to emphasize the importance of a collaborative approach and dialogue between stakeholders with the aim to facilitate access to effective medicinal products.

SUBMITTER: Mulder J

PROVIDER: S-EPMC8695872 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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Extension of Indication for Authorised Oncology Products in the European Union: A Joint Effort of Multiple Stakeholders.

Mulder Jorn J Verjans Robin R Verbaanderd Ciska C Pean Elias E Weemers Just J Leufkens Hubert G M HGM Pignatti Francesco F de Boer Anthonius A Voest Emile E EE Stoyanova-Beninska Violeta V VV Pasmooij Anna M G AMG

Frontiers in medicine 20211209

After marketing authorisation, the development of a medicinal product often continues with studies investigating new therapeutic indications. Positive results can potentially lead to changes to the terms of the marketing authorisation, such as an extension of therapeutic indication(s). These studies can be initiated and sponsored by the marketing authorisation holder (MAH) or by others. When results from an investigator-initiated trial suggest that an authorised medicinal product is safe and eff ...[more]

PMID: 34957158

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Project description:IntroductionMedication errors can have serious consequences for patients. To prevent the occurrence of medication errors in clinical practice, safety concerns may be included in the risk management plan and subsequently be addressed with routine and/or additional risk minimisation measures.ObjectiveThis study aims to describe safety concerns around medication errors and the risk minimisation measures for centrally authorised products in the European Union.MethodsAll safety concerns included in the risk management plans of originator centrally authorised products, authorised between 1 January, 2010 and 31 December, 2017, were collected from the European Public Assessment Report registry. Medication error safety concerns were categorised by Anatomical Therapeutic Classification code, year of authorisation, type of medication error and type of risk minimisation measure.ResultsDuring the study period, 311 centrally authorised products were approved, of which 84 had at least one medication error safety concern. The proportion of centrally authorised products with medication error safety concerns showed variation between 2010 and 2017 ranging from 15.2% to 36.4%. In total, 95 medication error safety concerns were identified. The type of medication error was highly variable, drug administration error was listed most frequently (n = 17). For 27 out of 95 medication error safety concerns, corresponding to 23 centrally authorised products, additional risk minimisation measures were required. All additional risk minimisation measures consisted of educational material targeted at healthcare professionals (85.2%) and/or patients (51.9%). For 78.3% of centrally authorised products with additional risk minimisation measures for medication errors, studies to evaluate the effectiveness of the additional risk minimisation measures were agreed upon.ConclusionsMedication error safety concerns were listed for almost a quarter of centrally authorised products approved during the study period. Further research is needed to evaluate the effectiveness and continued need for additional risk minimisation measures for medication errors.

Project description:IntroductionCancer and corresponding available treatments are associated with substantial symptoms and functional limitations. In this context, collection of patient-reported outcomes (PRO) in clinical trials gained special interest and is recommended by regulatory authorities. Within clinical trials framework, PRO may provide evidence to support medicines approval, labeling and marketing claims. This study aims to analyze the existing evidence based on PRO as part of new oncology indications receiving positive opinions issued by the European Medicines Agency (EMA) between 2017 and 2020 and to identify PRO related label claims granted.MethodologyOncology medicinal products and indications approved by the European Commission following a positive opinion from the EMA between 2017 and 2020 were identified. European Public Assessment Report (EPAR) and Summary of Product Characteristics (SmPC) were reviewed for each medicinal product to identify use of PRO and PRO label claims.ResultsA total of 128 oncology indications, corresponding to 76 medicines, were approved; of those, 100 (78.1%) included PRO in the confirmatory clinical trials. Thirty-seven indications were supported by double-blind randomized trials and the remainder 63 by open-label trials. Out of the 104 confirmatory trials analyzed, PRO were defined as a secondary endpoint in 60 studies (57.7%), exploratory in 31 (29.8%) and as both in 13 (12.5%). In total, 54 different PRO measures (PROM) were used, of those 41 (75.9%) were disease-specific measures. Nevertheless, PROM selected relied on the EORTC (41.3%), FACIT (17.1%) and EQ-5D (29.2%) measures. A total of 76 indications (59.4%) had PRO reviewers comments included in the EPAR, however only 22 indications (17.8%) included label claims in the SmPC. The reasons identified in the EMA assessment supporting the exclusion of PRO claims were described for 34 indications (44.7%).ConclusionsDespite growing recognition of the value of PRO data for the development of improved cancer therapies, PRO implementation remains challenging. The main reasons identified in our study are related with study design, missing data, study conduct and PROM selection.

Project description:BackgroundIn situations of unmet medical need or in the interests of public health, expedited approval pathways, including conditional marketing authorisation (CMA) and accelerated assessment (AA), speed up European Medicines Agency (EMA) marketing authorisation recommendations for medicinal products. CMAs are based on incomplete benefit-risk assessment data and authorisation remains conditional until regulator-imposed confirmatory postmarketing measures are fulfilled. For products undergoing AA, complete safety and efficacy data should be available, and postauthorisation measures may include only standard requirements of risk management and pharmacovigilance plans. In the pivotal trials supporting products assessed by expedited pathways, surrogate endpoints reduce drug development time compared with waiting for the intended clinical outcomes. Whether surrogate endpoints supporting products authorised through CMA and AA pathways reliably predict clinical benefits of therapy has not been studied systematically. Our objectives were to determine the extent to which surrogate endpoints are used and to assess whether their validity had been confirmed according to published hierarchies.Methods and findingsWe used European Public Assessment Reports (EPARs) to identify the primary endpoints in the pivotal trials supporting products authorised through CMA or AA pathways during January 1, 2011 to December 31, 2018. We excluded products that were vaccines, topical, reversal, or bleeding prophylactic agents or withdrawn within the study time frame. Where pivotal trials reported surrogate endpoints, we conducted PubMed searches for evidence of validity for predicting clinical outcomes. We used 2 published hierarchies to assess validity level. Surrogates with randomised controlled trials supporting the surrogate-clinical outcome relationship were rated as 'validated'. Fifty-one products met the inclusion criteria; 26 underwent CMAs, and 25 underwent AAs. Overall, 26 products were for oncology indications, 10 for infections, 8 for genetic disorders, and 7 for other systems disorders. Five products (10%), all AAs, were authorised based on pivotal trials reporting clinical outcomes, and 46 (90%) were authorised based on surrogate endpoints. No studies were identified that validated the surrogate endpoints. Among a total of 49 products with surrogate endpoints reported, most were rated according to the published hierarchies as being 'reasonably likely' (n = 30; 61%) or of having 'biological plausibility' (n = 46; 94%) to predict clinical outcomes. EPARs did not consistently explain the nature of the pivotal trial endpoints supporting authorisations, whether surrogate endpoints were validated or not, or describe the endpoints to be reported in the confirmatory postmarketing studies. Our study has limitations: we may have overlooked relevant validation studies; the findings apply to 2 expedited pathways and may not be generalisable to products authorised through the standard assessment pathway.ConclusionsThe pivotal trial evidence supporting marketing authorisations for products granted CMA or AA was based dominantly on nonvalidated surrogate endpoints. EPARs and summary product characteristic documents, including patient information leaflets, need to state consistently the nature and limitations of endpoints in pivotal trials supporting expedited authorisations so that prescribers and patients appreciate shortcomings in the evidence about actual clinical benefit. For products supported by nonvalidated surrogate endpoints, postauthorisation measures to confirm clinical benefit need to be imposed by the regulator on the marketing authorisation holders.

Dataset Information

Extension of Indication for Authorised Oncology Products in the European Union: A Joint Effort of Multiple Stakeholders.

Publications

Extension of Indication for Authorised Oncology Products in the European Union: A Joint Effort of Multiple Stakeholders.

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