Clinical Trials Due an Overhaul to Conquer the Pharma 'Valley of Death'.
Costs associated with drug development have risen from around $138m in 1975 to over $1 billion in 2005, with clinical trials representing a key factor in this increasing expenditure, according to a new report by healthcare industry experts GBI Research.
The new research* looks at why researchers in the pharma industry now refer to the clinical development process as the 'valley of death', which must be crossed to attain drug approval.
Clinical trials have grown longer and more complex, while volunteer enrolment and retention rates have fallen. More than 30% of experimental drugs that reach Phase III fail at this point. Late stage failures are costly to the industry - Pfizer's torcetrapib, which failed its Phase III trial in 2006, led to the value of Pfizer dropping by $21 billion over night, and 10,000 job losses being announced the following year.
Recent analyses show that this problem has grown in recent years. Overall, clinical approval success rates have fallen to approximately 16%, though this figure varies widely by therapeutic area. Pivotal trial and regulatory failures were recorded for 31 drugs in 2011, with Eli Lilly, Bristol-Myers Squibb, AstraZeneca, Merck, Sanofi, Novartis and GlaxoSmithKline all suffering at least one setback.
The most common reason for drug failure during Phase II development is a lack of efficacy as determined by primary endpoints. Phase III failures tend to be in therapeutic areas that may provide a higher chance of approval and reimbursement, such as cancer or neuroscience. Whilst it is tempting to speculate that drug development is more difficult for drugs with novel mechanisms of action in these areas of unmet need, this data implies that the pressure on companies to keep development pipelines full may also have led to compounds advancing into Phase III on the basis of inadequate or marginal proof-of-concept.
Others have argued that the majority of failures in clinical trials are due to the inadequacy of animal models to predict success in humans, implying a fundamental flaw in drug development processes which use animal testing methods.
It is essential that R&D productivity is improved, and the 'quick win, fast fail' model is being touted as a possible way to achieve this. This model argues that investments made early in the process increase the information available on which to base key decisions, enabling the earlier termination of projects prior to huge investments being made for the Phase III program.
Pathways to Efficient Drug Development - Advances in Modeling and Simulation Outcomes to Fuel Pipeline Productivity
This report examines the reasons why the pharmaceutical industry is looking for improvements in efficiency, whilst acknowledging that pharmaceutical R&D remains a long and risky process. It looks in detail at precompetitive research and evaluates how the industry is pulling together to research solutions to problems that are common to all companies. The report investigates innovation in the clinical drug development arena, documenting modeling and simulation based approaches to improving efficiency, as well as novel clinical trial designs. Lastly, the report examines innovation in business models within the industry that aim to help the industry to achieve its mantra of "doing more with less", which will be critical for its future success.
The report is built using data and information sourced from proprietary databases, primary and secondary research and in-house analysis by GBI Research's team of industry experts.
Abstract
Pathways to Efficient Drug Development - Advances in Modeling and Simulation Outcomes to Fuel Pipeline Productivity
Summary
GBI Research, the leading business intelligence provider, has released its latest research report, "Pathways to Efficient Drug Development - Advances in Modeling and Simulation Outcomes to Fuel Pipeline Productivity". The report examines the reasons why the pharmaceutical industry is looking for improvements in efficiency whilst acknowledging that pharmaceutical R&D remains a long and risky process. It looks in detail at precompetitive research and evaluates how the industry is pulling together to research solutions to problems that are common to all companies. The report investigates innovation in the clinical drug development arena, documenting modeling and simulation based approaches to improving efficiency, as well as novel clinical trial designs. Lastly, the report examines innovation in business models within the industry that aim to help the industry to achieve its mantra of "doing more with less", which will be critical for its future success.
The report is built using information from primary and secondary research including interviews with experts in the field.
GBI Research's analysis shows that collaboration and open innovation will play increasingly important roles in the future by enabling research that would not be possible for companies to undertake individually. Many examples exist, driven in large part by the FDA's Critical Path Initiative and the European Innovative Medicines Initiative, and experiences gained by early consortia will help facilitate the logistical challenges of setting up new collaborations. Within companies, innovations including the increased use of modeling and simulation throughout the drug development process, adaptive clinical trials and exploratory clinical trials have all been studied for some years, suggesting that innovation is hard, but important. Innovation is also occurring in the business models applied within individual companies to enable them to achieve "more with less". Through adoption of new scientific approaches and business models, companies are hoping not only to refuel their pipelines but to regain the confidence of investors and the public in their ability to deliver meaningful treatments for patients at the same time as generating profits in the coming years.
Scope
Detailed analysis of the reasons for the industry to be looking closely at improving efficiency
Definition of precompetitive collaboration, analysis of areas in which precompetitive collaboration is occurring, and discussion of the expansion of this space in the future
Explorations of the key challenges facing consortia and the factors that make them successful
Case studies of key innovations in drug development including model-based drug development, adaptive clinical trials and exploratory clinical trials
Detailed insights into innovation in business models, including virtual networks, open innovation and extensive academic collaborations
Reasons to buy
Identify key projects in the precompetitive space
Learn the most important factors for successful precompetitive collaborations
Develop strategies and priorities for participating in precompetitive collaborations
Understand current thinking on innovative areas of drug development, including model-based drug development, adaptive clinical trials and exploratory clinical trials, from the viewpoints of companies and regulators
Explore the business models and partnerships of the largest pharmaceutical companies to support new drug development strategies
Table of Contents
TOC
1 Table of Contents
1 Table of Contents 5
1.1 List of Tables 7
1.2 List of Figures 8
2 State of the Industry 9
2.1 Introduction 9
2.1.1 The Rising Costs of Drug Development 10
2.1.2 Drug Attrition 12
2.1.3 Patent Expiries 14
2.1.4 Regulatory Hurdles 15
2.1.5 The Fourth Hurdle: Reimbursement 16
2.2 Innovation in the Drug Development Paradigm 16
2.2.1 The Critical Path Initiative 16
2.2.2 The Innovative Medicines Initiative 18
2.3 Improving Drug Development 19
2.4 2012 and Beyond 20
3 Collaboration in the Precompetitive Space 21
3.1 Defining Precompetitive Research 21
3.2 Building Successful Consortia 23
3.2.1 Choosing the Research Topic 23
3.2.2 The Set-Up Phase 23
3.2.3 Project Management 24
3.2.4 Measuring Success 25
3.2.5 Case Study of a Successful Private Public Partnership: The Alzheimer's Disease Neuroimaging Initiative 26
3.3 Qualification of Biomarkers of Efficacy or Safety 26
3.3.1 Case Study: Biomarkers of Kidney Injury 29
3.3.2 Case Study: The Biomarkers Consortium 31
3.4 Open Innovation Platforms 32
3.4.1 Case Study: OpenPHACTS 33
3.4.2 Case Study: Sage Bionetworks 34
3.5 Data Standards 35
3.5.1 BioSharing: Standard Cooperating Procedures 35
3.5.2 Clinical Data Standards 36
3.5.3 Data Standards and the FDA 36
3.6 Conclusions 37
4 Improving Drug Development Efficiency 38
4.1 Modeling and Simulation 38
4.1.1 Modeling and Simulation: A View from the Regulators 39
4.1.2 Model Qualification 40
4.1.3 Modeling and Simulation Expertise and Consultancy 40
4.2 Innovative Approaches to Clinical Trials 41
4.2.1 Adaptive Clinical Trials 42
4.2.2 Case Study: The I-SPY 2 Trial 44
4.2.3 Exploratory Clinical Trials 45
4.3 Engaging Stakeholders 46
4.3.1 Patients 46
4.3.2 Regulators 47
4.3.3 Payers 47
4.4 Conclusions 47
5 Business Models 48
5.1 Introduction 48
5.2 R&D Reorganization 48
5.2.1 Mimicking the Biotech Environment 48
5.2.2 The Fully Integrated Pharmaceutical Network Model 49
5.3 Open Innovation 50
5.3.1 Case Study: An Open Innovation Incubator 51
5.3.2 Case Study: Open Innovation Drug Discovery at Eli Lilly 52
5.4 Funding for External Innovation 53
5.4.1 Collaborative Commercialization 54
5.5 Academic Partnerships and Translational Medicine 55
5.5.1 Translational Science in the US 57
5.5.2 Case study: Medical Research Council/AstraZeneca 58
5.6 Conclusions 59
6 Appendix 60
6.1 Abbreviations 60
6.2 Methodology 61
6.2.1 Primary Research 61
6.2.2 Secondary Research 62
6.3 References 62
6.4 Contact Us 66
6.5 Disclaimer 66
List of Tables
1.1 List of Tables
Table 1: Pathways to Efficient Drug Development, Clinical and FDA Approval Times across Therapeutic Classes (2005-2009) 11
Table 2: Pathways to Efficient Drug Development, Transition Probability at Each Stage of Clinical Drug Development 12
Table 3: Pathways to Efficient Drug Development, Overall FDA Approval Success Rate for New Chemical Entities by Therapeutic Area 12
Table 4: Pathways to Efficient Drug Development, Loss of US Sales Revenues Due to Patent Expiries ($m; 2010-2013) 14
Table 5: Pathways to Efficient Drug Development, Drugs Withdrawn from the Market in the US (1992-2010) 15
Table 6: Pathways to Efficient Drug Development, Ongoing Projects of the Critical Path Institute 17
Table 7: Pathways to Efficient Drug Development, Proposed Network for Evaluating PPPs in the Pharmaceutical Sciences 25
Table 8: Pathways to Efficient Drug Development, Biomarkers qualified by the FDA for use in drug development 27
Table 9: Pathways to Efficient Drug Development, Biomarkers qualified by the EMA for use in drug development 27
Table 10: Pathways to Efficient Drug Development, Ongoing Public-Private Partnerships for Biomarker Identification and Qualification 28
Table 11: Pathways to Efficient Drug Development, Pharmaceutical Companies Involved in the Predictive Safety Testing Consortium, IMI SAFE-T Project and the Biomarkers Consortium Kidney Project 30
Table 12: Pathways to Efficient Drug Development, Ongoing and Completed Projects being Undertaken by The Biomarkers Consortium 31
Table 13: Pathways to Efficient Drug Development, Open Innovation Platforms to Enhance Drug Discovery 33
Table 14: Pathways to Efficient Drug Development, Disease Specific Models Developed by the FDA 39
Table 15: Pathways to Efficient Drug Development, Pharmacometric Consultancies 41
Table 16: Pathways to Efficient Drug Development, Examples of Companies Offering Accelerator Mass Spectrometry Services 45
Table 17: Pathways to Efficient Drug Development, Eli Lilly's Long-Term Service Providers 49
Table 18: Pathways to Efficient Drug Development, Open Innovation Business Models that Place Research Results in the Public Domain 51
Table 19: Pathways to Efficient Drug Development, Examples of Pharmaceutical Corporate Venture Capital Funds 53
Table 20: Pathways to Efficient Drug Development, New Companies Launched by Enlight Bioscience 54
Table 21: Pathways to Efficient Drug Development, Projects Funded by Pfizer's Centers for Therapeutic Innovation 55
Table 22: Pathways to Efficient Drug Development, Examples of Recent Collaborations Between Academia and the Pharmaceutical Industry 56
Table 23: Pathways to Efficient Drug Development, AstraZeneca Compounds Made Available for Research (December 2011) 58
List of Figures
1.2 List of Figures
Figure 1: Pathways to Efficient Drug Development, Number of New Drug and Biologic FDA Approvals and Global R&D Expenditure by the Pharmaceutical Industry (2004-2011) 9
Figure 2: Pathways to Efficient Drug Development, Drivers for Innovation in the Pharmaceutical Industry 10
Figure 3: Pathways to Efficient Drug Development, The Rising Cost of Drug Development 1975-2005 10
Figure 4: Pathways to Efficient Drug Development, Changes in Clinical Trial Parameters between 2000-2003 and 2004-2007 11
Figure 5: Pathways to Efficient Drug Development, Failure Rates According to Therapeutic Area in Phase II and Phase III/Submission 13
Figure 6: Pathways to Efficient Drug Development, History of the European Innovative Medicines Initiative and its Strategic Research Agenda 18
Figure 7: Pathways to Efficient Drug Development, European Innovative Medicines Initiative: Strategic Research Agenda (updated 2012) 19
Figure 8: Pathways to Efficient Drug Development, New Drug Applications Filed with the FDA Centre for Drug Evaluation and Research (1996-2011) 20
Figure 9: Pathways to Efficient Drug Development, Key Areas of Precompetitive Research 21
Figure 10: Pathways to Efficient Drug Development, Disease, Drug and Trial Models: Pharmacometrics in Drug Development 39
Figure 11: Pathways to Efficient Drug Development, The I-SPY2 Adaptive Clinical Trial 44
Pathways to Efficient Drug Development - Advances in Modeling and Simulation Outcomes to Fuel Pipeline Productivity published by GBI Research in September 30, 2012. This report consists of Pages: 66 and the price starts from US $ 3500.
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Press Release
Pathways to Efficient Drug Development - Advances in Modeling and Simulation Outcomes to Fuel Pipeline Productivity
October 10th, 2012
Global Information Inc. would like to present a new market research report, "Pathways to Efficient Drug Development - Advances in Modeling and Simulation Outcomes to Fuel Pipeline Productivity" by GBI Research.
Over the past 15 years the number of applications for new drugs and biologic licenses that have been approved by the US Food and Drug Administration (FDA) has fallen steadily, despite rising R&D expenditure. The industry has been forced to consider its business strategies in the light of this changing environment. Companies are concerned by the fact that they rely ever more on revenue from a few products, many of which are now losing patent protection, and by investors lack of confidence in future product pipelines, which is adversely affecting their market capitalization. These facts, in combination with other industry statistics including rising drug development costs, increasing attrition rates and higher perceived regulatory hurdles, have caused the industry and regulators to work together in recent years to explore improved pathways for drug discovery and development. This report provides an overview of the current state of the industry, key initiatives in this area, and their progress towards improving the efficiency of drug development.
Collaborations Aim to Tackle Major Scientific Challenges
Collaboration and open innovation through public-private partnerships enable research that would not be possible for companies to undertake individually. Many examples of collaborative projects exist and these are funded in large part by the FDAs Critical Path Initiative and the European Innovative Medicines Initiative. The areas of research tackled by these consortia are those viewed as critical to more efficient drug development and are generally termed precompetitive. In other words, they are fields of activity in which large companies agree to collaborate and invest jointly (despite the fact that they compete in the drug market) because the activities do not provide an immediate commercial advantage to any particular participant. Key areas of research include qualification of biomarkers of efficacy or safety, knowledge management strategies to exploit large datasets, data standards and models of disease processes.
Experiences gained by early consortia have helped facilitate the logistical challenges of setting up new collaborations. The viable collaborative models that have emerged over the past few years still represent different and experimental approaches to public-private partnerships. Over the next few years those in the field will continue to learn from these early experiences and build on those projects found to be most successful. The field will not stand still as newer models, such as the Arch2POCM project which does not involve intellectual property sharing or generation, push the boundaries of precompetitive research and open innovation. Whether or not they succeed, these partnerships could represent a major change to the way in which pharmaceuticals are researched and value created, setting the stage for future collaborations.
Scientific and Business Innovations Collide to Change Drug Development
Industry has a challenging goal in bringing safer and more efficacious drugs to the market more efficiently. Innovations including adaptive clinical trials, exploratory clinical trials and the increased use of modeling and simulation throughout the drug development process have all been studied for some years, suggesting that innovation is hard, but important. These methods are now permeating drug development at different speeds in different companies and as experience with each grows their real value will become more apparent. Ongoing efforts to validate and qualify the different approaches will be important for building regulators confidence in their use in decision making processes. Key groups of stakeholders will play pivotal roles in driving the future of the industry to achieve more efficient drug development.
Innovation is also occurring in the business models applied within individual companies to enable them to achieve "more with less". The efforts of the largest pharmaceutical companies to redesign their drug development process and spend more time looking externally for new products should provide more opportunities for entrepreneurial scientists - either those in start-up companies or academia - to pursue new molecules or targets. To a large extent, these efforts reflect the same trend towards greater openness and collaboration that is seen in the precompetitive space. One significant feature of many of the collaborations is the extent to which companies are making internally developed and proprietary compounds available to academic groups for screening against new drug targets. Companies are developing networks of providers for new products and services, but it remains to be seen to what extent these will really contribute to improved efficiency in the drug development process.
Through adoption of these new scientific approaches and business models, companies are hoping not only to refuel their pipelines but to regain the confidence of both investors and the public in their ability to deliver meaningful treatments for patients while at the same time generating profits.
