H. Lundbeck A/S关于PAES委托法案的立场反思文件 - 公共咨询意见

Aug 29, 2026

H. Lundbeck A/S submits a formal position in response to the European Commission’s public consultation on a delegated act concerning post-authorisation efficacy studies (PAES). The comments emphasize that PAES study methodology—investigational or non-investigational—must be defined by the PAES objectives and the specific efficacy questions raised by competent authorities. The paper argues for case-by-case study designs, considers real-life lifecycle benefit aspects, and calls for appropriate quality, statistical analyses, and external validity beyond RCT limitations. It also highlights the distinction between PAES benefit and PASS risk elements and supports complementary benefit-risk assessment.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages2

Reading Time5 min

AccessFree to download

Subject and Purpose

Study Methodology and Design Fit

Real-life Evidence and External Validity

Legislative Support and Evidence Quality

Benefit-Risk Balance Considerations

9 Ottiliavej DK-2500 Valby [www.lundbeck.com](www.lundbeck.com) Copenhagen Denmark European Commission Health and Consumers Directorate-General Unit SANCO/D/5 BE-1049 Brussels Belgium Att.: sanco-pharmaceuticals-D5@ec.europa.eu Date 2013-02-18 Our ref POUM_ 18022013 Your ref Subject: PCPAES/12/01 – Public Consultation on PAES Position from H. Lundbeck A/S on a delegated act on post-authorisation efficacy studies – Ref. Ares(2012)1405774 – 28/11/2012 Dear Sir/Madam, H. Lundbeck A/S welcomes this reflection paper and appreciates the possibility to provide comments. We support the response submitted by the European Federation of Pharmaceutical Industries and Associations (EFPIA) . We would like to stress that the study methodology (investigational/non-investigational) should be defined according to the purpose of the PAES. As described in the legislation, a PAES aims to respond to specific efficacy question(s) raised by the competent authorities (e.g. CHMP/PRAC) and the design should subsequently be adapted to PAES objectives. Therefore the most suitable PAES design could either be investigational (i.e. RCT) or non-investigational (e.g. observational study) and should be envisaged on a case-by-case basis with the regulators. In addition, benefit aspects of a medicinal product collected during life-cycle management should be considered in real-life settings as well as in classical settings, especially where RCTs would lack appropriate/sensitive efficacy measures to detect the effect in real-life or if the study is not comparative. In this respect it is important to consider the need for external validity where further evaluation in the post-approval setting may be needed to satisfy both regulatory and payer requirements. As stated in the reflection document for a Delegated Act, this external validity will not be achieved with a RCT design per definition, and needs reallife conditions. The current legislation provides support for this interpretation: - Art. 9(4)(cc) of Regulation 726/2004/EC as amended and Art. 21a of Directive 2001/83/EC as amended: PAES may be required after an initial marketing authorisation where ‘concerns relating to some aspects of the efficacy of the medicinal product are identified and can be resolved only after the medicinal product has been marketed’. - Recital 16 of Regulation 1235/2010/EU: ‘such studies (PASS and PAES) may be aimed at collecting data to enable the assessment of safety or efficacy of medicinal products for human use in everyday medical practice’. We acknowledge the Commission’s view that the real-life methodologies ‘have limitations’, including ‘issues concerning data quality and completeness’. However, such concerns should not limit the use of observational studies as they, although yielding a different level of evidence and addressing different populations and designs, can be performed with suitable quality, appropriate design and valid statistical analyses. Finally, while PAES results aim at supplying the benefit aspect of the balance, PASS data, which are mainly collected in real-life conditions, aim at supplying the risk aspect. It would be beneficial that the benefit-risk balance is also assessed (as complementary to potential investigational study) under real-life conditions during life-cycle of the products. This was already highlighted in the EMA reflection paper on benefit-risk assessment methods (EMEA/CHMP/15404/2007, where the EMA recommends expanding the benefit-risk methodology to incorporate post approval safety/effectiveness data into the risk/benefit analysis (lifetime approach) . Yours faithfully, Dr. Iman Barilero, Pharm D, MSc, PhD Vice President Regulatory Development Strategy & Policy H. Lundbeck A/S Ottiliavej 9 DK-2500 Valby, Denmark

FAQs

PAES的研究方法学应如何确定？

应根据PAES的目的来界定研究方法学（研究型/非研究型）。PAES旨在回应主管当局提出的特定疗效问题，研究设计随后应适配PAES目标。

为何强调在真实世界场景中考虑疗效与外部效度？

文件指出，真实世界生命周期管理中收集的获益方面应在真实情境与经典设置中加以考虑，并强调需要外部效度评估。还提到在某些情况下RCT可能缺乏合适或敏感的疗效衡量。

PAES与PASS在目的侧重点上有什么区别？

文中说明，PAES结果主要用于供给“获益”侧面的平衡，而PASS数据主要用于供给“风险”侧面的平衡。建议在产品生命周期的真实情境中对获益-风险平衡进行评估，并作为潜在研究的补充。

Aug 29, 2026

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