EDITORIAL P U B L I C - P R I V AT E P A R T N E R S H I P S
New Frontiers for Collaborative Research
Citation: M. Goldman, New frontiers for collaborative research. Sci. Transl. Med. 5, 216ed22 (2013).
CREDIT: ARNAUD GHYS
10.1126/scitranslmed.3007990
Downloaded from stm.sciencemag.org on December 18, 2013
Michel Goldman is the Executive Director of the Innovative Medicines Initiative, B-1049 Brussels, Belgium. E-mail: michel.goldman@imi. europa.eu
TRANSLATING BIOMEDICAL DISCOVERIES INTO STANDARDS OF CARE IS ESSENTIAL to tackle the numerous unmet public health needs worldwide. In an era of severe fnancial constraints afecting health care systems, as well as academic research and industrial R&D, this endeavor represents a tremendous challenge. It is increasingly apparent that the classical models of drug development are not appropriate to overcome the multiple hurdles that hamper the translation of promising research into therapies for patients. Although all health care stakeholders agree that new approaches centered on patient outcomes are needed, this new vision still seems a distant hope. On the basis of the experience gained at the Innovative Medicines Initiative (IMI), we propose that public-private partnerships, operating under the umbrella of a neutral trusted organization might represent important instruments to ensure sustainable development of the health care sector based on collaborative research. IMI AS A MODEL FOR COLLABORATION IN PHARMACEUTICAL R&D Cofounded by the European Union (EU) and the European Federation of Pharmaceutical Industries and Associations (EFPIA), IMI aims to strengthen the competitiveness of the European pharmaceutical industry, with the ultimate goal of facilitating and accelerating the development of innovative therapies for the beneft of society. Operating since 2009 with a budget of €2 billion ($2.7 billion), IMI has launched 44 public-private consortia that are developing new tools and models to remove bottlenecks in drug development (http:// bit.ly/GT6QSH). Each consortium is initiated by several major pharmaceutical companies agreeing to mutualize resources and share knowledge to address specifc challenges related to discovery, preclinical modeling, clinical validation, or risk-beneft assessment of new treatments. Te research topics are thus noncompetitive by nature, although they might include clinical trials with proprietary compounds in areas of major public health need where pharmaceutical companies lack incentives to invest alone, such as antimicrobial resistance. For each topic, the consortium is complemented by stakeholders eligible for European public funding: academic institutions, small biotech companies, patient organizations, and health policy agencies. Tese publicly funded partners are selected following a competitive call for proposals using independent experts as referees. Importantly, the IMI executive ofce acts as a neutral broker to facilitate consortium agreements, especially on intellectual property matters. As recently assessed by an extensive bibliometric analysis conducted by Tomson Reuters, IMI has fostered a number of collaborative networks across the public and private sectors, as well as across disciplines (http://bit.ly/14Krs9e). Indeed, IMI consortia generated results with a concrete impact on the R&D of new drugs in areas of major importance. In a prototypical IMI project, the EU-AIMS consortium demonstrated the strength of collaborative intelligence to develop innovative approaches for treating autism spectrum disorders (1). In just a few years, this group of academic and industrial scientists demonstrated that brain changes in autism mouse models can be reversed afer completion of brain development, identifed shared pathways between syndromic and non-syndromic forms of autism, and simultaneously launched clinical investigations on more than 1000 children to identify biomarkers for early detection and monitoring of disease activity. Tis unique endeavor prompted the European Medicines Agency to develop new regulatory guidelines to support the development of medicinal products for the treatment of autism (http://bit. ly/1g8MF30). In schizophrenia, through an integrative analysis of data from more than 9171 patients involved in 29 diferent trials conducted by 5 diferent companies, the NEWMEDS consortium provided evidence that the design of trials to assess new drugs for schizophrenia can be streamlined by focusing on recent-onset disease and key symptoms (http://bit. ly/1cAddGm). In fact, public private partnerships like IMI can make a real diference to overcome the most difcult scientifc and regulatory challenges in brain disorders. For example, in Alzheimer’s disease (AD), partners of the EMIF consortium are currently pooling and sharing data on 80,000 subjects with AD, including rare patients with so-called extreme www.ScienceTranslationalMedicine.org 18 December 2013 Vol 5 Issue 216 216ed22
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EDITORIAL
Downloaded from stm.sciencemag.org on December 18, 2013
phenotypes, with the objective to develop new biomarkers that might assist in developing an efcient stratifcation of AD patients for clinical trials and identifying individuals with preclinical disease (2). IMI also has initiated advances in other felds. With the launch of the COMBACTE consortium as part of a large pan-European antimicrobial resistance action plan, IMI has established an unprecedented network of European investigators conducting clinical trials in close partnership with major pharmaceutical companies, according to standards required for regulatory approval of new antibiotics (http://bit.ly/1bhF8so). In the diabetes area, the IMIDIA consortium has developed the frst human pancreatic β cell line that can be used for R&D purposes, such as drug screening (3). Tis cell line generated in an academic laboratory was commercialized by a biotech company and is currently exploited as a screening tool by pharmaceutical companies active in type II diabetes treatment, all members of the same consortium. A major objective of IMI is to support the emergence of a new taxonomy of diseases, an essential step in the development of precision medicine. In this context, the U-BIOPRED consortium has produced an algorithm to stratify asthmatic patients on the basis of clinical parameters, molecular data, and patient-reported outcomes, with the aim of developing tailored therapies for the most severe forms of the disease (http://bit.ly/Irsgam). In the feld of rheumatology, where there is a major need to predict therapeutic responses to biological agents, the BTCure consortium is developing multiplex assays to identify diferent types of rheumatoid arthritis (http://bit.ly/1890ACH), and a new project has just been launched to elaborate a new classifcation of systemic lupus erythematosus. Importantly, these and other achievements made possible through unique collaborative endeavors are valued by patients, as indicated by a recent survey from the London School of Economics (http://bit.ly/IMIpatientsreport) and by the fnancial support provided to IMI projects by patient advocacy groups, such as Juvenile Diabetes Research International and Autism Speaks. ADDRESSING THE NEW CHALLENGES IN DRUG DEVELOPMENT More than ever, it is critical for public and private stakeholders to address and evaluate the impact of innovative therapies on the global economy. Tis has become a core part of IMI’s mission. Tus, IMI’s GETREAL project aims to incorporate real-life clinical data into drug development; meanwhile another project will generate new business models to incentivize research on innovative antibiotics. IMI is also investigating new attractive strategies for shared drug discovery through the European Lead Factory, a public-private platform comprising a compound collection and a screening center for drug candidates from multiple sources (http://bit.ly/1dOb6lj). Te latest IMI call for proposals, launched in December 2013, brings this competitive ambition one step forward by setting up a new framework for the translation of genomic discoveries into the drug development chain. Making clinical trials more efective is another urgent priority that IMI is pursuing for the beneft of both patient communities and the pharmaceutical industry. Special interest is being paid to adaptive design clinical trials that ofer prospectively planned opportunities to streamline the demonstration of drug efcacy by modifying specifed aspects of the study on the basis of interim data analyses (http://1.usa.gov/1c9RXnf). Indeed, IMI will launch in 2014 an unprecedented project for AD in which 12 pharmaceutical companies will collaborate with academic teams to pioneer adaptive trials that will evaluate several potential drugs using a single common placebo arm. Zoonoses represent still another area of interest for IMI through a project that aims to rapidly develop and manufacture vaccines against infectious diseases emerging in animals. Last, but not least, IMI is planning to develop new methodologies to predict the environmental risk of pharmaceutical substances. MOVING THE BOUNDARIES OF TRANSLATIONAL MEDICINE Notwithstanding recent successes, more has to be done to provide unambiguous evidence of the added value of IMI and similar public-private partnership initiatives, in order to overcome so-called consortium fatigue (4). First and foremost, it is essential to ensure that the output of IMI projects is directly useable for decision-making in industry, as well as in regulatory bodies and among health care payers. Te PROTECT consortium coordinated by the European Medicines Agency in which new metrics, algorithms, and visual representation www.ScienceTranslationalMedicine.org 18 December 2013 Vol 5 Issue 216 216ed22
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EDITORIAL methods are developed to assess the risk-beneft of medicines provides striking examples (http://bit.ly/143nF1V). Te transient withdrawal of natalizumab for multiple sclerosis because of rare cases of progressive multifocal leukoencephalopathy, an inappropriate regulatory decision denounced by patient advocacy groups, could have been prevented by the use of such instruments. It is anticipated that IMI will further develop this type of research by exploring new tools to assess drug efectiveness in real-world settings and design new pathways for drug licensing. Now is the time to move the boundaries of translational medicine by integrating economic and societal challenges in order to accelerate the delivery of innovative therapies to patients. – Michel Goldman
Downloaded from stm.sciencemag.org on December 18, 2013
1. W. Spooren, L. Lindemann, A. Ghosh, L. Santarelli, Synapse dysfunction in autism: A molecular medicine approach to drug discovery in neurodevelopmental disorders. Trends Pharmacol. Sci. 33, 669–684 (2012). 2. S. J. B. Vos, C. Xiong, P. J. Visser, M. S. Jasielec, J. Hassenstab, E. A. Grant, N. J. Cairns, J. C. Morris, D. M. Holtzman, A. M. Fagan, Preclinical Alzheimer’s disease and its outcome: a longitudinal cohort study. Lancet Neurol. 12, 957–965 (2013). 3. P. Ravassard, Y. Hazhouz, S. Pechberty, E. Bricout-Neveu, M. Armanet, P. Czernichow, R. Scharfmann, A genetically engineered human pancreatic β cell line exhibiting glucose-inducible insulin secretion. J. Clin. Invest. 121, 3589–3597 (2011). 4. M. Papadaki, G. Hirsch, Curing consortium fatigue. Sci. Transl. Med. 5, 200fs35 (2013). Acknowledgments: The opinions expressed in this article do not necessarily reflect the positions and opinions of the European Commission or the European Federation of Pharmaceutical Industries and Associations.
www.ScienceTranslationalMedicine.org 18 December 2013 Vol 5 Issue 216 216ed22
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New Frontiers for Collaborative Research
Citation: M. Goldman, New frontiers for collaborative research. Sci. Transl. Med. 5, 216ed22 (2013).
CREDIT: ARNAUD GHYS
10.1126/scitranslmed.3007990
Downloaded from stm.sciencemag.org on December 18, 2013
Michel Goldman is the Executive Director of the Innovative Medicines Initiative, B-1049 Brussels, Belgium. E-mail: michel.goldman@imi. europa.eu
TRANSLATING BIOMEDICAL DISCOVERIES INTO STANDARDS OF CARE IS ESSENTIAL to tackle the numerous unmet public health needs worldwide. In an era of severe fnancial constraints afecting health care systems, as well as academic research and industrial R&D, this endeavor represents a tremendous challenge. It is increasingly apparent that the classical models of drug development are not appropriate to overcome the multiple hurdles that hamper the translation of promising research into therapies for patients. Although all health care stakeholders agree that new approaches centered on patient outcomes are needed, this new vision still seems a distant hope. On the basis of the experience gained at the Innovative Medicines Initiative (IMI), we propose that public-private partnerships, operating under the umbrella of a neutral trusted organization might represent important instruments to ensure sustainable development of the health care sector based on collaborative research. IMI AS A MODEL FOR COLLABORATION IN PHARMACEUTICAL R&D Cofounded by the European Union (EU) and the European Federation of Pharmaceutical Industries and Associations (EFPIA), IMI aims to strengthen the competitiveness of the European pharmaceutical industry, with the ultimate goal of facilitating and accelerating the development of innovative therapies for the beneft of society. Operating since 2009 with a budget of €2 billion ($2.7 billion), IMI has launched 44 public-private consortia that are developing new tools and models to remove bottlenecks in drug development (http:// bit.ly/GT6QSH). Each consortium is initiated by several major pharmaceutical companies agreeing to mutualize resources and share knowledge to address specifc challenges related to discovery, preclinical modeling, clinical validation, or risk-beneft assessment of new treatments. Te research topics are thus noncompetitive by nature, although they might include clinical trials with proprietary compounds in areas of major public health need where pharmaceutical companies lack incentives to invest alone, such as antimicrobial resistance. For each topic, the consortium is complemented by stakeholders eligible for European public funding: academic institutions, small biotech companies, patient organizations, and health policy agencies. Tese publicly funded partners are selected following a competitive call for proposals using independent experts as referees. Importantly, the IMI executive ofce acts as a neutral broker to facilitate consortium agreements, especially on intellectual property matters. As recently assessed by an extensive bibliometric analysis conducted by Tomson Reuters, IMI has fostered a number of collaborative networks across the public and private sectors, as well as across disciplines (http://bit.ly/14Krs9e). Indeed, IMI consortia generated results with a concrete impact on the R&D of new drugs in areas of major importance. In a prototypical IMI project, the EU-AIMS consortium demonstrated the strength of collaborative intelligence to develop innovative approaches for treating autism spectrum disorders (1). In just a few years, this group of academic and industrial scientists demonstrated that brain changes in autism mouse models can be reversed afer completion of brain development, identifed shared pathways between syndromic and non-syndromic forms of autism, and simultaneously launched clinical investigations on more than 1000 children to identify biomarkers for early detection and monitoring of disease activity. Tis unique endeavor prompted the European Medicines Agency to develop new regulatory guidelines to support the development of medicinal products for the treatment of autism (http://bit. ly/1g8MF30). In schizophrenia, through an integrative analysis of data from more than 9171 patients involved in 29 diferent trials conducted by 5 diferent companies, the NEWMEDS consortium provided evidence that the design of trials to assess new drugs for schizophrenia can be streamlined by focusing on recent-onset disease and key symptoms (http://bit. ly/1cAddGm). In fact, public private partnerships like IMI can make a real diference to overcome the most difcult scientifc and regulatory challenges in brain disorders. For example, in Alzheimer’s disease (AD), partners of the EMIF consortium are currently pooling and sharing data on 80,000 subjects with AD, including rare patients with so-called extreme www.ScienceTranslationalMedicine.org 18 December 2013 Vol 5 Issue 216 216ed22
1
EDITORIAL
Downloaded from stm.sciencemag.org on December 18, 2013
phenotypes, with the objective to develop new biomarkers that might assist in developing an efcient stratifcation of AD patients for clinical trials and identifying individuals with preclinical disease (2). IMI also has initiated advances in other felds. With the launch of the COMBACTE consortium as part of a large pan-European antimicrobial resistance action plan, IMI has established an unprecedented network of European investigators conducting clinical trials in close partnership with major pharmaceutical companies, according to standards required for regulatory approval of new antibiotics (http://bit.ly/1bhF8so). In the diabetes area, the IMIDIA consortium has developed the frst human pancreatic β cell line that can be used for R&D purposes, such as drug screening (3). Tis cell line generated in an academic laboratory was commercialized by a biotech company and is currently exploited as a screening tool by pharmaceutical companies active in type II diabetes treatment, all members of the same consortium. A major objective of IMI is to support the emergence of a new taxonomy of diseases, an essential step in the development of precision medicine. In this context, the U-BIOPRED consortium has produced an algorithm to stratify asthmatic patients on the basis of clinical parameters, molecular data, and patient-reported outcomes, with the aim of developing tailored therapies for the most severe forms of the disease (http://bit.ly/Irsgam). In the feld of rheumatology, where there is a major need to predict therapeutic responses to biological agents, the BTCure consortium is developing multiplex assays to identify diferent types of rheumatoid arthritis (http://bit.ly/1890ACH), and a new project has just been launched to elaborate a new classifcation of systemic lupus erythematosus. Importantly, these and other achievements made possible through unique collaborative endeavors are valued by patients, as indicated by a recent survey from the London School of Economics (http://bit.ly/IMIpatientsreport) and by the fnancial support provided to IMI projects by patient advocacy groups, such as Juvenile Diabetes Research International and Autism Speaks. ADDRESSING THE NEW CHALLENGES IN DRUG DEVELOPMENT More than ever, it is critical for public and private stakeholders to address and evaluate the impact of innovative therapies on the global economy. Tis has become a core part of IMI’s mission. Tus, IMI’s GETREAL project aims to incorporate real-life clinical data into drug development; meanwhile another project will generate new business models to incentivize research on innovative antibiotics. IMI is also investigating new attractive strategies for shared drug discovery through the European Lead Factory, a public-private platform comprising a compound collection and a screening center for drug candidates from multiple sources (http://bit.ly/1dOb6lj). Te latest IMI call for proposals, launched in December 2013, brings this competitive ambition one step forward by setting up a new framework for the translation of genomic discoveries into the drug development chain. Making clinical trials more efective is another urgent priority that IMI is pursuing for the beneft of both patient communities and the pharmaceutical industry. Special interest is being paid to adaptive design clinical trials that ofer prospectively planned opportunities to streamline the demonstration of drug efcacy by modifying specifed aspects of the study on the basis of interim data analyses (http://1.usa.gov/1c9RXnf). Indeed, IMI will launch in 2014 an unprecedented project for AD in which 12 pharmaceutical companies will collaborate with academic teams to pioneer adaptive trials that will evaluate several potential drugs using a single common placebo arm. Zoonoses represent still another area of interest for IMI through a project that aims to rapidly develop and manufacture vaccines against infectious diseases emerging in animals. Last, but not least, IMI is planning to develop new methodologies to predict the environmental risk of pharmaceutical substances. MOVING THE BOUNDARIES OF TRANSLATIONAL MEDICINE Notwithstanding recent successes, more has to be done to provide unambiguous evidence of the added value of IMI and similar public-private partnership initiatives, in order to overcome so-called consortium fatigue (4). First and foremost, it is essential to ensure that the output of IMI projects is directly useable for decision-making in industry, as well as in regulatory bodies and among health care payers. Te PROTECT consortium coordinated by the European Medicines Agency in which new metrics, algorithms, and visual representation www.ScienceTranslationalMedicine.org 18 December 2013 Vol 5 Issue 216 216ed22
2
EDITORIAL methods are developed to assess the risk-beneft of medicines provides striking examples (http://bit.ly/143nF1V). Te transient withdrawal of natalizumab for multiple sclerosis because of rare cases of progressive multifocal leukoencephalopathy, an inappropriate regulatory decision denounced by patient advocacy groups, could have been prevented by the use of such instruments. It is anticipated that IMI will further develop this type of research by exploring new tools to assess drug efectiveness in real-world settings and design new pathways for drug licensing. Now is the time to move the boundaries of translational medicine by integrating economic and societal challenges in order to accelerate the delivery of innovative therapies to patients. – Michel Goldman
Downloaded from stm.sciencemag.org on December 18, 2013
1. W. Spooren, L. Lindemann, A. Ghosh, L. Santarelli, Synapse dysfunction in autism: A molecular medicine approach to drug discovery in neurodevelopmental disorders. Trends Pharmacol. Sci. 33, 669–684 (2012). 2. S. J. B. Vos, C. Xiong, P. J. Visser, M. S. Jasielec, J. Hassenstab, E. A. Grant, N. J. Cairns, J. C. Morris, D. M. Holtzman, A. M. Fagan, Preclinical Alzheimer’s disease and its outcome: a longitudinal cohort study. Lancet Neurol. 12, 957–965 (2013). 3. P. Ravassard, Y. Hazhouz, S. Pechberty, E. Bricout-Neveu, M. Armanet, P. Czernichow, R. Scharfmann, A genetically engineered human pancreatic β cell line exhibiting glucose-inducible insulin secretion. J. Clin. Invest. 121, 3589–3597 (2011). 4. M. Papadaki, G. Hirsch, Curing consortium fatigue. Sci. Transl. Med. 5, 200fs35 (2013). Acknowledgments: The opinions expressed in this article do not necessarily reflect the positions and opinions of the European Commission or the European Federation of Pharmaceutical Industries and Associations.
www.ScienceTranslationalMedicine.org 18 December 2013 Vol 5 Issue 216 216ed22
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