• Comment |

    Cloud-based systems for data submitted by sponsors to drug regulatory agencies have the potential to accelerate drug development, streamline regulatory review and enhance regulatory decision-making. Here, we provide a vision for integrating cloud-enabled practices in drug regulation globally.

    • Andrew S. Robertson
    • , Hilary Malone
    • , Fabio Bisordi
    • , Helen Fitton
    • , Carlos Garner
    • , Stacy Holdsworth
    • , Peter Honig
    • , Mathias Hukkelhoven
    • , Robert Kowalski
    • , Sandra Milligan
    • , Liza O’Dowd
    • , Khyati Roberts
    • , Michelle Rohrer
    • , Jerry Stewart
    • , Mark Taisey
    • , Roopal Thakkar
    • , Karin Van Baelen
    •  & Max Wegner
  • Comment |

    A lack of robust knowledge of the number of rare diseases and the number of people affected by them limits the development of approaches to ameliorate the substantial cumulative burden of rare diseases. Here, we call for coordinated efforts to more precisely define rare diseases.

    • Melissa Haendel
    • , Nicole Vasilevsky
    • , Deepak Unni
    • , Cristian Bologa
    • , Nomi Harris
    • , Heidi Rehm
    • , Ada Hamosh
    • , Gareth Baynam
    • , Tudor Groza
    • , Julie McMurry
    • , Hugh Dawkins
    • , Ana Rath
    • , Courtney Thaxon
    • , Giovanni Bocci
    • , Marcin P. Joachimiak
    • , Sebastian Köhler
    • , Peter N. Robinson
    • , Chris Mungall
    •  & Tudor I. Oprea
  • Comment |

    The European Medicines Agency and the US Food and Drug Administration have committed to engaging patients in their regulatory processes to promote patient-focused medicinal product development, as well as improve transparency and trust in the regulatory system. Here, we highlight exchanges of experience between the agencies and some impacts on patient engagement.

    • Maria Mavris
    • , Andrea Furia Helms
    •  & Nathalie Bere
  • Comment |

    Real-world evidence is increasingly valued by regulators and payers. Central to this evidence base is patient-reported outcome data describing the impact of drugs on quality of life, daily activities and symptoms. Here, we highlight key challenges with current real-world, patient-reported outcome data and describe collaborative next steps for international stakeholders to overcome these issues.

    • Melanie J. Calvert
    • , Daniel J. O’Connor
    •  & Ethan M. Basch
  • Comment |

    It is increasingly important that regulatory agencies catalyse the translation of scientific and technological innovation into improved patient-centred health care. Here, we highlight the strategic goals of the European Medicines Agency to advance regulatory science and optimize the opportunities arising in areas such as cell and gene therapies, big data and artificial intelligence.

    • Philip A. Hines
    • , Richard H. Guy
    • , Anthony J. Humphreys
    •  & Marisa Papaluca-Amati
  • Comment |

    One aspect of the ongoing debate about drug pricing is the added therapeutic benefit of new drugs compared with existing — and potentially cheaper — therapies. Here, we discuss the merits and pitfalls of proposals that are being discussed with regard to the role of regulatory agencies in establishing added therapeutic benefit.

    • Hans-Georg Eichler
    • , Harald Enzmann
    •  & Guido Rasi
  • Comment |

    The Biomarkers Consortium aims to facilitate drug development with biomarkers across a range of diseases. Here, we briefly highlight its accomplishments so far and its recent expansion in scope to include related tools along the lines of the Biomarkers, EndpointS and other Tools (BEST) resource, such as patient-reported outcomes and clinical outcome assessments.

    • Joseph P. Menetski
    • , Christopher P. Austin
    • , Linda S. Brady
    • , Guy Eakin
    • , Chris Leptak
    • , Abbey Meltzer
    •  & John A. Wagner
  • Comment |

    Investment in drug development for neurodevelopmental disorders has suffered from recent failures in clinical trials that were based on promising preclinical findings. Here, we discuss development and validation of translational biomarkers of neurodevelopmental disorders that can enable more informative clinical experiments and translational success in these diseases.

    • Mustafa Sahin
    • , Stephanie R. Jones
    • , John A. Sweeney
    • , Elizabeth Berry-Kravis
    • , Barry W. Connors
    • , Joshua B. Ewen
    • , Adam L. Hartman
    • , April R. Levin
    • , William Z. Potter
    •  & Laura A. Mamounas
  • Comment |

    The development of oncology drugs traditionally begins by studying them in heavily pretreated patients, and then working ‘upstream’ to populations with earlier-stage disease. The recent FDA approval of an androgen receptor antagonist first in prostate cancer patients without demonstrable metastatic disease but at high-risk for metastasis, based on a novel metastasis-free survival end point developed by the FDA, could provide a template for a paradigm shift.

    • William N. Hait
    •  & Peter F. Lebowitz
  • Comment |

    A specialized platform for innovative research exploration — ASPIRE — in preclinical drug discovery could help study unexplored biologically active chemical space through integrating automated synthetic chemistry, high-throughput biology and artificial intelligence technologies.

    • G. Sitta Sittampalam
    • , Dobrila D. Rudnicki
    • , Danilo A. Tagle
    • , Anton Simeonov
    •  & Christopher P. Austin
  • Comment |

    The definition and acceptability of an orphan condition is pivotal for the assessment of European orphan medicinal product designation applications, and consequently the eligibility for incentives. Here, based on the experiences of the Committee for Orphan Medicinal Products, we discuss how to define orphan conditions in the context of the European regulatory framework.

    • Daniel J. O’Connor
    • , Maria E. Sheean
    • , Matthias P. Hofer
    • , Stelios Tsigkos
    • , Segundo Mariz
    • , Laura Fregonese
    • , Kristina Larsson
    • , Virginie Hivert
    • , Kerstin Westermark
    • , Frauke Naumann-Winter
    • , Violeta Stoyanova-Beninska
    • , Ingeborg Barišić
    • , Giuseppe Capovilla
    • , Armando Magrelli
    •  & Bruno Sepodes
  • Comment |

    Clinical trials for Alzheimer disease drugs have an exceptionally high failure rate, discouraging investment in the field despite the unmet medical need. Drug developers need to more effectively harness existing and emerging data and digital technologies to improve the likelihood of success.

    • Eric Perakslis
    • , Henry Riordan
    • , Lawrence Friedhoff
    • , Azmi Nabulsi
    •  & Emilio Merlo Pich
  • Comment |

    'Adaptive' approaches to bringing drugs to market have been widely discussed in recent years. Here, we describe the evolution of the adaptive approach and of concepts developed by ADAPT SMART, a multi-stakeholder consortium funded by the European Innovative Medicines Initiative.

    • Hans-Georg Eichler
    • , Richard Barker
    • , Nicola Bedlington
    • , Jacoline C. Bouvy
    • , André W. Broekmans
    • , Anna Bucsics
    • , Francesca Cerreta
    • , Solange Corriol-Rohou
    • , Alicia Granados
    • , Yann Le Cam
    •  & Ad Schuurman
  • Comment |

    The NIH has launched the Somatic Cell Genome Editing (SCGE) programme to accelerate the development of safer and more effective genome-editing therapeutics.

    • Mary Ellen Perry
    • , Kayla M. Valdes
    • , Elizabeth Wilder
    • , Christopher P. Austin
    •  & Philip J. Brooks
  • Comment |

    Drug repurposing has been proposed as a strategy to develop new therapies that has fewer risks, lower costs and shorter timelines than developing completely new drugs. However, the potential of this strategy has not been as widely realized as hoped, in part owing to legal and regulatory barriers. Here, we highlight these barriers and consider how they could be overcome.

    • Alasdair Breckenridge
    •  & Robin Jacob
  • Comment |

    Since its launch a decade ago, the European Innovative Medicines Initiative (IMI), a leading public–private partnership in life sciences, has catalysed scientific breakthroughs and the development of strategies to address complex challenges in various biomedical fields. Here, we discuss the progress of IMI projects related to vaccine research and development.

    • Philippe Denoel
    • , Patricia Londoño-Hayes
    • , Magda Chlebus
    •  & Magdalena Rodriguez de Azero
  • Comment |

    The term 'translation' has emerged as a dominant concept in biomedical science over the last decade, but confusion around what the term means, and how it differs from translational research and translational science, is common. This article aims to help address this issue by clarifying the distinctions.

    • Christopher P. Austin
  • Comment |

    Recent progress in the discovery, development and evaluation of new drugs and combination regimens for drug-resistant tuberculosis through greater collaboration between industry, donors and academia provides renewed hope for overcoming the challenges in tuberculosis treatment.

    • Michael J. Vjecha
    • , Simon Tiberi
    •  & Alimuddin Zumla
  • Comment |

    Much biomedical research continues to focus on a small proportion of the human genome that has already been studied intensively. The Illuminating the Druggable Genome programme, initiated as a pilot project by the US National Institutes of Health Common Fund in 2014, is now being implemented to accelerate the investigation of subsets of understudied proteins that have potential therapeutic relevance.

    • Griffin Rodgers
    • , Christopher Austin
    • , James Anderson
    • , Aaron Pawlyk
    • , Christine Colvis
    • , Ronald Margolis
    •  & Jenna Baker
  • Comment |

    The uptake of a new medicine represents a balance between benefit–risk assessment and value considerations. In the case of products approved via accelerated pathways, the increased uncertainty adds to the challenge. Here, we suggest solutions so that regulators, companies, payers and patients can align around management of the uncertainties and expectations.

    • Alasdair Breckenridge
    •  & Lawrence Liberti
  • Comment |

    The development of anticancer therapies is evolving with the advent of novel targeted drugs. In this Comment, I summarize some of the key changes and discuss the various choices for the optimal development of a new generation of cancer therapeutics.

    • Shivaani Kummar
  • Comment |

    The past 5 years have seen an unprecedented rate of discovery of genes that cause rare diseases and with it a commensurate increase in the number of diagnosable but nevertheless untreatable disorders. Here, we discuss the increasing opportunity for diagnosis and therapy of rare diseases and how to tackle the associated challenges.

    • Kym M. Boycott
    •  & Diego Ardigó
  • Comment |

    The availability of targeted anticancer drugs and the relative affordability of genomic analyses has led to a growing expectation among patients with cancer that they can receive personalized treatment based on the genomic signature of their tumour. Here, we discuss some of the challenges and steps needed to bring such approaches into routine practice.

    • Roberto Salgado
    • , Helen Moore
    • , John W. M. Martens
    • , Tracy Lively
    • , Shakun Malik
    • , Ultan McDermott
    • , Stefan Michiels
    • , Jeffrey A. Moscow
    • , Sabine Tejpar
    • , Tawnya McKee
    •  & Denis Lacombe
  • Comment |

    The sharing of legacy preclinical safety data among pharmaceutical companies and its integration with other information sources offers unprecedented opportunities to improve the early assessment of drug safety. Here, we discuss the experience of the eTOX project, which was established through the Innovative Medicines Initiative to explore this possibility.

    • Ferran Sanz
    • , François Pognan
    • , Thomas Steger-Hartmann
    • , Carlos Díaz
    • , Montserrat Cases
    • , Manuel Pastor
    • , Philippe Marc
    • , Joerg Wichard
    • , Katharine Briggs
    • , David K. Watson
    • , Thomas Kleinöder
    • , Chihae Yang
    • , Alexander Amberg
    • , Maria Beaumont
    • , Anthony J. Brookes
    • , Søren Brunak
    • , Mark T. D. Cronin
    • , Gerhard F. Ecker
    • , Sylvia Escher
    • , Nigel Greene
    • , Antonio Guzmán
    • , Anne Hersey
    • , Pascale Jacques
    • , Lieve Lammens
    • , Jordi Mestres
    • , Wolfgang Muster
    • , Helle Northeved
    • , Marc Pinches
    • , Javier Saiz
    • , Nicolas Sajot
    • , Alfonso Valencia
    • , Johan van der Lei
    • , Nico P. E. Vermeulen
    • , Esther Vock
    • , Gerhard Wolber
    •  & Ismael Zamora
  • Comment |

    Scientific advances, in combination with government incentives and commercial opportunity, have fuelled strong investment in orphan drugs, resulting in many innovative therapies. Here, we discuss the approach of the FDA to a range of issues that remain crucial to maintaining this momentum, such as the use of the totality of evidence in evaluating orphan drugs.

    • Nina L. Hunter
    • , Gayatri R. Rao
    •  & Rachel E. Sherman
  • Comment |

    Commercializing innovations in academic environments is notoriously challenging. Here, we describe the progress of the NIH Centers for Accelerated Innovations program — initiated in 2013 to address these challenges — which we believe could help set a new standard for the early-stage commercialization of biomedical innovations in academic environments.

    • Elliott M. Antman
    • , Paul E. Di Corleto
    • , Mason W. Freeman
    • , Tomas Ganz
    • , David E. Golan
    • , Roger Kitterman
    • , Joseph Loscalzo
    • , Mark Low
    • , Erin McKenna
    • , Alan C. O'Connor
    • , Michael Palazzolo
    • , John Parrish
    • , Ofer Reizes
    • , Robert S. Ross
    • , Cheryl Vaughan
    • , D. Geoffrey Vince
    •  & Lesley Watts
  • Comment |

    New opportunities to develop innovative — and often complex — products that combine drugs, devices and/or biological components are rapidly emerging, raising questions about how such products should be regulated. Here, we discuss the ongoing efforts of the FDA to develop a modern, transparent, flexible and consistent science-based regulatory approach for combination products.

    • Nina L. Hunter
    •  & Rachel E. Sherman
  • Comment |

    Tumour evolution, which results in the existence of multiple distinct populations of cancer cells within the same tumour and the same patient, is increasingly appreciated to have a key role in drug resistance. In this article, we discuss the implications for drug development, including approaches to reduce the likelihood of the emergence of drug resistance.

    • Samra Turajlic
    •  & Charles Swanton
  • Comment |

    Few biomarkers progress from discovery to become validated tools or diagnostics. To bridge this gap, three European biomedical research infrastructures — EATRIS-ERIC (focused on translational medicine), BBMRI-ERIC (focused on biobanking) and ELIXIR (focused on data sharing) — are paving the way to developing and sharing best practices for biomarker validation.

    • Alain J. van Gool
    • , Florence Bietrix
    • , Eric Caldenhoven
    • , Kurt Zatloukal
    • , Andreas Scherer
    • , Jan-Eric Litton
    • , Gerrit Meijer
    • , Niklas Blomberg
    • , Andy Smith
    • , Barend Mons
    • , Jaap Heringa
    • , Wim-Jan Koot
    • , Martin J. Smit
    • , Marian Hajduch
    • , Ton Rijnders
    •  & Anton Ussi
  • Comment |

    Despite a decade of intensive preclinical research, the translation of cancer nanomedicine to the clinic has been slow. Here, we discuss how recent lessons learned from the successes with immuno-oncology therapies could be applied to cancer nanomedicine and how this may help to overcome some of the key technical challenges in this field.

    • Wen Jiang
    • , Hengfeng Yuan
    • , Charles K. Chan
    • , Christina A. von Roemeling
    • , Zuoqin Yan
    • , Irving L. Weissman
    •  & Betty Y. S. Kim
  • Comment |

    It has been argued that patents impede the development and access of medicines for tropical diseases such as malaria. However, we believe that intellectual property can be a key tool to enable timely progression of drug development projects involving multiple partners and to ensure equitable access to successful products.

    • Sylvie Fonteilles-Drabek
    • , David Reddy
    •  & Timothy N. C. Wells
  • Comment |

    Growing access to diverse 'real-world' data sources is enabling new approaches to close persistent evidence gaps about the optimal use of medical products in real-world practice. Here, we argue that contrary to widespread impressions, existing FDA regulations embody sufficient flexibility to accommodate the emerging tools and methods needed to achieve this goal.

    • Rachel E. Sherman
    • , Kathleen M. Davies
    • , Melissa A. Robb
    • , Nina L. Hunter
    •  & Robert M. Califf
  • Comment |

    Poor adherence to medicines in clinical trials can undermine the value of the trials; for example, by compromising estimates of the benefits and risks of a medicine. In this article, we highlight such consequences and also discuss approaches to tackle this problem.

    • Alasdair Breckenridge
    • , Jeffrey K. Aronson
    • , Terrence F. Blaschke
    • , Dan Hartman
    • , Carl C. Peck
    •  & Bernard Vrijens
  • Comment |

    Many organizations are attempting to harness emerging digital technologies and the surge in the amount of health-related data to drive advances in the development and use of medicines. Focusing on just a few well-proven and readily available strategies could enable such organizations to quickly realize greater value from data and digital technologies.

    • Eric D. Perakslis
  • Comment |

    Despite the vast amount of research on schizophrenia and depression in the past two decades, there have been few innovative drugs to treat these disorders. Precompetitive research collaborations between companies and academic groups can help tackle this innovation deficit, as illustrated by the achievements of the IMI-NEWMEDS consortium.

    • Francesc Artigas
    • , Esther Schenker
    • , Pau Celada
    • , Michael Spedding
    • , Laia Lladó-Pelfort
    • , Noemi Jurado
    • , Mercedes Núñez
    • , Noemi Santana
    • , Eva Troyano-Rodriguez
    • , Maurizio S. Riga
    • , Hanna van den Munkhof
    • , Anna Castañé
    • , Hamdy Shaban
    • , Thérèse M. Jay
    • , Anushree Tripathi
    • , Bill P. Godsil
    • , Claude Sebban
    • , Jean Mariani
    • , Philippe Faure
    • , Samir Takkilah
    • , Zoe A. Hughes
    • , Chester J. Siok
    • , Mihaily Hajos
    • , Karsten Wicke
    • , Natalia Gass
    • , Wolfgang Weber-Fahr
    • , Alexander Sartorius
    • , Robert Becker
    • , Michael Didriksen
    • , Jesper F. Bastlund
    • , Mark Tricklebank
    • , Céline Risterucci
    • , Andreas Meyer-Lindenberg
    •  & Adam J. Schwarz
  • Comment |

    The growth of precision medicine presents challenges for the regulators of medicines, related to aspects that include the basis of evidence generation, patient involvement in the regulatory process, cost of new medicines and the need for new regulatory models. It also raises questions about the tolerance of risk, especially with early interventions for life-threatening diseases.

    • Alasdair Breckenridge
    • , Hans-Georg Eichler
    •  & Jonathan P. Jarow
  • Comment |

    There is a growing consensus that drug discovery thrives in an open environment. Here, we describe how the malaria community has embraced four levels of open data — open science, open innovation, open access and open source — to catalyse the development of new medicines, and consider principles that could enable open data approaches to be applied to other disease areas.

    • Timothy N. C. Wells
    • , Paul Willis
    • , Jeremy N. Burrows
    •  & Rob Hooft van Huijsduijnen
  • Comment |

    A global response to the chronic shortfall in antibiotic innovation is urgently needed to combat antimicrobial resistance. Here, we introduce CARB-X, a new global public–private partnership that will invest more than US$350 million in the next 5 years to accelerate the progression of a diverse portfolio of innovative antibacterial products into clinical trials.

    • Kevin Outterson
    • , John H. Rex
    • , Tim Jinks
    • , Peter Jackson
    • , John Hallinan
    • , Steve Karp
    • , Deborah T. Hung
    • , Francois Franceschi
    • , Tyler Merkeley
    • , Christopher Houchens
    • , Dennis M. Dixon
    • , Michael G. Kurilla
    • , Rosemarie Aurigemma
    •  & Joseph Larsen
  • Comment |

    Rare disease drug development could benefit substantially from increased patient engagement and input to enhance understanding of the key aspects of disease impact, ways to measure these impacts and patients' perspectives on the benefit–risk profile of potential therapies.

    • Max G. Bronstein
    •  & Emil D. Kakkis
  • Comment |

    Drug candidates may fail in clinical trials for many reasons. Biomarker-guided clinical trial design can mitigate the risk of failure and enable more informative clinical experiments regardless of outcomes.

    • Michael J. Townsend
    •  & Joseph R. Arron
  • Comment |

    While the pharmaceutical industry overall has faced huge challenges in drug R&D in recent years, some major companies have consistently been much more productive than average. Here, we highlight 'organizational effectiveness' as a key factor underlying this superior performance and explain how it can be enhanced.

    • Peter Tollman
    • , Valery Panier
    • , Diana Dosik
    • , Paul Biondi
    •  & Francis Cuss
  • Comment |

    Integrating a wide range of biomedical data such as that rapidly emerging from the use of next-generation sequencing is expected to have a key role in identifying and qualifying new biomarkers to support precision medicine. Here, we highlight some of the challenges for biomedical data integration and approaches to address them.

    • Antigoni Elefsinioti
    • , Tanja Bellaire
    • , Albert Wang
    • , Karsten Quast
    • , Henrik Seidel
    • , Michael Braxenthaler
    • , Gernot Goeller
    • , Anastasia Christianson
    • , David Henderson
    •  & Joachim Reischl
  • Comment |

    Japanese clinical research and regulatory frameworks have evolved considerably in the past two decades to reduce the delay in the introduction of new drugs in Japan compared with other major markets. However, recently introduced changes related to access to unapproved drugs might have the opposite effect and might not benefit all patients.

    • Yasuhiro Fujiwara
  • Comment |

    Global collaboration in translational science promises to accelerate the discovery, development and dissemination of new medical interventions. Here, we introduce a new international collaboration of translational science organizations and highlight our initial strategy to reduce or remove bottlenecks in translation.

    • C. Taylor Gilliland
    • , Dorit Zuk
    • , Petr Kocis
    • , Mike Johnson
    • , Stewart Hay
    • , Marian Hajduch
    • , Florence Bietrix
    • , Gregorio Aversa
    • , Christopher P. Austin
    •  & Anton E. Ussi
  • Comment |

    Technological advances coupled with novel collaborative strategies for compound sourcing and management are poised to transform the utility of high-throughput screening.

    • Steve Rees
    • , Philip Gribbon
    • , Karen Birmingham
    • , William P. Janzen
    •  & Garry Pairaudeau