Platform trials to overcome major shortcomings of traditional clinical trials in non-alcoholic steatohepatitis? Pros and cons

Pericàs, Juan M.; Anstee, Quentin M.; Mesenbrink, Peter; Prospero, Nicholas A. Di; Ratziu, Vlad; Kjær, Mette Skalshøj; Anstee, Quentin M.; Tacke, Frank; Mesenbrinck, Peter; Rivera‐Esteban, Jesús; König, Franz; Sena, Elena; Manzano, Ramiro; Genescà, Joan; Pais, Raluca; Kara, Leila; Meyer, Elias Laurin; Duca, Anna; Kline, Timothy; Aaes‐Jørgensen, Anders; Balthaus, Tania; Preville, Natalie de; Zhang, Lingjiao; Capuano, George; Morello, Salvatore; Mielke, Tobias; Penna, Sabina Hernandez; Posch, Martin

doi:10.1016/j.jhep.2022.09.021

Cited by 13 publications

(12 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Another aspect involves optimization of the selection of participants, for example enriching studies for patients harbouring known genetic polymorphisms that are associated with an accelerated disease course and adverse outcomes. Adopting new trial designs (for example, platform trials) to efficiently evaluate multiple drugs through adaptive randomization has been proposed in NASH 86 . However, unlike in oncology, platform trials are inherently more challenging to implement in a highly heterogeneous and slowly progressive condition such as NASH, in which molecular subtypes (suitable for specific targeted therapies) have not yet been defined and robust end points (for example, survival) generally do not apply.…”

Section: How Can We Improve Clinical Trials and Enhance Their Outputs?mentioning

confidence: 99%

Antifibrotic therapy in nonalcoholic steatohepatitis: time for a human-centric approach

Brennan

Elsharkawy

Kendall

et al. 2023

Nat Rev Gastroenterol Hepatol

View full text Add to dashboard Cite

Nonalcoholic steatohepatitis (NASH) might soon become the leading cause of end-stage liver disease and indication for liver transplantation worldwide. Fibrosis severity is the only histological predictor of liver-related morbidity and mortality in NASH identified to date. Moreover, fibrosis regression is associated with improved clinical outcomes. However, despite numerous clinical trials of plausible drug candidates, an approved antifibrotic therapy remains elusive. Increased understanding of NASH susceptibility and pathogenesis, emerging human multiomics profiling, integration of electronic health record data and modern pharmacology techniques hold enormous promise in delivering a paradigm shift in antifibrotic drug development in NASH. There is a strong rationale for drug combinations to boost efficacy, and precision medicine strategies targeting key genetic modifiers of NASH are emerging. In this Perspective, we discuss why antifibrotic effects observed in NASH pharmacotherapy trials have been underwhelming and outline potential approaches to improve the likelihood of future clinical success.

show abstract

Section: How Can We Improve Clinical Trials and Enhance Their Outputs?mentioning

confidence: 99%

Antifibrotic therapy in nonalcoholic steatohepatitis: time for a human-centric approach

Brennan

Elsharkawy

Kendall

et al. 2023

Nat Rev Gastroenterol Hepatol

View full text Add to dashboard Cite

show abstract

“…In doing so, we provide a comprehensive view on the design considerations, the developmental phase where PT might find better accommodation, the methodological aspects, as well as the operational and regulatory principles. This review will reflect part of the work conducted within a consortium of 36 private and public partners that have come together in a strategic partnership to deliver on the IMI (Innovative Medicines Initiative) proposal goals to advance the field of PT; the project is called EU Patient‐cEntric clinicAl tRial pLatforms (EU‐PEARL), which includes the preparation of a NASH integrated research platform (IRP) trial 9 …”

Section: Nash: a Burgeoning Yet Elusive Drug Development Fieldmentioning

confidence: 99%

“…This review will reflect part of the work conducted within a consortium of 36 private and public partners that have come together in a strategic partnership to deliver on the IMI (Innovative Medicines Initiative) proposal goals to advance the field of PT; the project is called EU Patient-cEntric clinicAl tRial pLatforms (EU-PEARL), which includes the preparation of a NASH integrated research platform (IRP) trial. 9…”

Section: Na S H: a Burg Eoning Ye T Elus Ive Drug De Velopment Fieldmentioning

confidence: 99%

Review article: The need for more efficient and patient‐oriented drug development pathways in NASH—setting the scene for platform trials

Pericàs

Prospero

Anstee

et al. 2023

Aliment Pharmacol Ther

Self Cite

View full text Add to dashboard Cite

Background and Aims: Non-alcoholic steatohepatitis (NASH) constitutes a significant unmet medical need with a burgeoning field of clinical research and drug development. Platform trials (PT) might help accelerate drug development while lowering overall costs and creating a more patient-centric environment. This review provides a comprehensive and nuanced assessment of the NASH clinical development landscape. Methods: Narrative review and expert opinion with insight gained during the EU Patient-cEntric clinicAl tRial pLatforms (EU-PEARL) project. Results:Although NASH represents an opportunity to use adaptive trial designs, including master protocols for PT, there are barriers that might be encountered owing to distinct and sometimes opposing priorities held by these stakeholders and potential ways to overcome them. The following aspects are critical for the feasibility of a future PT in NASH: readiness of the drug pipeline, mainly from large drug companies, while there is not yet an FDA/EMA-approved treatment; the most suitable design

show abstract

“…Hinsichtlich des letztgenannten Aspekts, den Veränderungen im Zeitverlauf und der Notwendigkeit, den Leberfettgehalt zu quantifizieren, möchten wir daran erinnern, dass bisher nur sehr wenige Medikamente bei NASH einen klinischen Nutzen gezeigt haben – dies hauptsächlich auf histologischer Basis ohne klinische Langzeit-Endpunkte. Die Schwierigkeiten, valide Studien auf diesem Gebiet auszuführen, sind so groß, dass neue Studienformen ins Auge gefasst werden 9 . Für die wenigen wirksamen Medikamente, für welche die nationalen Behörden in Europa keine Kostenerstattung geben, gibt es keine Evidenz, dass eine Abnahme des Leberfettgehalts als Surrogatmarker für dessen Wirksamkeit angesehen werden kann.…”

Section: Leberfett-quantifizierung: Brauchen Wir Das?unclassified

“…In keeping with the latter issue of changes over time and in connection with the need of liver fat quantification we would like to remind that extremely few drugs have provided some evidence of clinical benefit in NASH so far (and mainly on histology, without long term clinical endpoints). The difficulties in achieving positive trials in this field is so big, that new forms of studies are envisioned [9]. For these few effective drugs (and so far none of them widely accepted for reimbursement by National Agencies in Europe) there is no evidence that the decrease in liver fat content can be utilized as a surrogate marker of drug efficacy, limiting the need for liver fat quantification.…”

mentioning

confidence: 99%

Liver Fat Quantification: When do We Need It?

Piscaglia¹,

Stefanini²,

Terzi³

et al. 2023

Ultraschall Med

View full text Add to dashboard Cite

Platform trials to overcome major shortcomings of traditional clinical trials in non-alcoholic steatohepatitis? Pros and cons

Cited by 13 publications

References 31 publications

Antifibrotic therapy in nonalcoholic steatohepatitis: time for a human-centric approach

Antifibrotic therapy in nonalcoholic steatohepatitis: time for a human-centric approach

Review article: The need for more efficient and patient‐oriented drug development pathways in NASH—setting the scene for platform trials

Liver Fat Quantification: When do We Need It?

Contact Info

Product

Resources

About