Claire Packer,  Sue Simpson and  Rosimary Terezinha de Almeida

Iñaki Gutierrez-Ibarluzea,  Sue Simpson,  Gaizka Benguria-Arrate;  Members of EuroScan International Network

Sue Simpson,  Claire Packer,  Per Carlsson,  Jill M Sanders,  Iñaki Gutiérrez Ibarluzea,  Anne-Florence Fay,  Inger Norderhaug

Orsolina I Martino   ¹ ,  Derek J Ward,  Claire Packer,  Sue Simpson,  Andrew Stevens

Nora Ibargoyen-Roteta,  Iñaki Gutierrez-Ibarluzea,  Gaizka Benguria-Arrate,  Lorea Galnares-Cordero,  José Asua

Claudia Wild,  Thomas Langer

Nguyen QL, Hees K, Hernandez Penna S, König F, Posch M, Bofill Roig M, Meyer EL, Freitag MM, Parke T, Otte M, Dauben HP, Mielke T, Spiertz C, Mesenbrink P, Gidh-Jain M, Pierre S, Morello S, Hofner B.

Although platform trials have many benefits, the complexity of these designs may result not only in increased methodological but also regulatory and ethical challenges. These aspects were addressed as part of the IMI project EU Patient-Centric Clinical Trial Platforms (EU-PEARL). We reviewed the available guidelines on platform trials in the European Union and the United States. This is supported and complemented by feedback received from regulatory interactions with the European Medicines Agency and the US Food and Drug Administration. Throughout the project we collected the needs of all relevant stakeholders including ethics committees, regulators, and health technology assessment bodies through active dialog and dedicated stakeholder workshops. Furthermore, we focused on methodological aspects and where applicable identified the corresponding guidance. Learnings from the guideline review, regulatory interactions, and workshops are provided. Based on these, a master protocol template was developed. Issues that still need harmonization or clarification in guidelines or where further methodological research is needed are also presented. These include questions around clinical trial submissions in Europe, the need for multiplicity control across the whole master protocol, the use of non-concurrent controls, and the impact of different randomization schemes. Master protocols are an efficient and patient-centered clinical trial design that can expedite drug development. However, they can also introduce additional operational and regulatory complexities. It is important to understand the different requirements of stakeholders upfront and address them in the trial. While relevant guidance is increasing, early dialog with relevant stakeholders can help to further support such designs.

Pollyanna Teresa Cirilo Gomes   ^{1   2} ,  Verónica Elizabeth Mata   ¹ ,  Thais Conceição Borges   ¹ ,  Dayani Galato   ²

Irene Eriksson   ^{1   2} ,  Björn Wettermark   ^{1   2} ,  Marie Persson   ³ ,  Morgan Edström   ⁴ ,  Brian Godman   ^{5   6   7} ,  Anna Lindhé   ⁸ ,  Rickard E Malmström   ^{2   6} ,  Helena Ramström   ¹ ,  Mia von Euler   ^{2   6   9} ,  Anna Bergkvist Christensen   ¹⁰

Nora Ibargoyen-Roteta   ¹ ,  Iñaki Gutierrez-Ibarluzea,  José Asua,  Gaizka Benguria-Arrate,  Lorea Galnares-Cordero

Antonio Migliore   ¹ ,  Maria Rosaria Perrini,  Tom Jefferson,  Marina Cerbo

Kieran Murphy   ¹ ,  Claire Packer,  Andrew Stevens,  Sue Simpson

Claudia Wild   ¹ ,  Sue Simpson,  Karla Douw,  Sabine Geiger-Gritsch,  Stefan Mathis,  Thomas Langer

Wan Qing Wong   ¹ ,  Liang Lin   ¹ ,  Hong Ju   ¹ ,  Kwong Ng   ¹

Abinaya Rajan,  Iñaki Gutierrez-Ibarluzea and  Montse Moharra

Karla Douw   ¹ ,  Hindrik Vondeling