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The productivity crisis in pharmaceutical R&D

Key Points

  • Pharmaceutical research and development (R&D) has become increasingly challenging for various reasons, including the proliferation of plausible targets to pursue for therapeutic innovation resulting from advances in molecular biology, most of which are yet to be validated.

  • R&D investments tend to focus on new therapeutic targets, which are characterized by high uncertainty and difficulty, but lower expected post-launch competition and higher sales.

  • We find that the reorienting of investments toward high-risk/high-premium targets accounts for most of the recent decline in productivity in pharmaceutical R&D, as measured in terms of attrition rates, development times and the number of NMEs launched.

  • Our analysis also confirms the existence of important differences in the organization of national systems of innovation and regulation in pharmaceuticals. At first glance, the organizations with their headquarters based in European countries are characterized by a higher probability of market launch for compounds entering clinical development.

  • However, when the composition of research portfolios is taken into account, the apparent comparative advantage of European organizations vanishes. By controlling for portfolio composition of research investments, we do not find support to the claim of R&D productivity differences between US and European organizations, as classified according to headquarter location. These findings were confirmed by defining nationality on the basis of the location of patent inventors.

  • When we considered sales of compounds launched in the global marketplace, we found that the average market value of NMEs launched by US companies was higher than European ones.

  • However, the focus on the comparison between Europe and the United States misses an important finding that emerges from our analysis: the most productive organizations in pharmaceutical R&D at present are global companies with innovative activities located on both sides of the Atlantic.

Abstract

Advances in the understanding of the molecular basis of diseases have expanded the number of plausible therapeutic targets for the development of innovative agents in recent decades. However, although investment in pharmaceutical research and development (R&D) has increased substantially in this time, the lack of a corresponding increase in the output in terms of new drugs being approved indicates that therapeutic innovation has become more challenging. Here, using a large database that contains information on R&D projects for more than 28,000 compounds investigated since 1990, we examine the decline of R&D productivity in pharmaceuticals in the past two decades and its determinants. We show that this decline is associated with an increasing concentration of R&D investments in areas in which the risk of failure is high, which correspond to unmet therapeutic needs and unexploited biological mechanisms. We also investigate the potential variations in productivity with regard to the regional location of companies and find that although companies based in the United States and Europe differ in the composition of their R&D portfolios, there is no evidence of any productivity gap.

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Figure 1: Trends in attrition rates of drug development projects.
Figure 2: The distribution of R&D projects by potential sales and probability of success.
Figure 3: Average success rate and distribution of R&D projects according to the characteristics of the disease targeted, size of organization and research methodology.

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References

  1. Griliches, Z. Productivity, R&D, and the data constraint. Amer. Econ. Rev. 84, 1–23 (1994).

    Google Scholar 

  2. Kortum, S. Equilibrium R&D and the patent–R&D ratio: US evidence. Amer. Econ. Rev. 83, 450–457 (1993).

    Google Scholar 

  3. Kortum, S. Research, patenting, and technological change. Econometrica 65, 1389–1419 (1997).

    Article  Google Scholar 

  4. Lanjouw, J. & Schankerman, M. Patent quality and research productivity: measuring innovation with multiple indicators. Econ. J. 114, 441–465 (2004).

    Article  Google Scholar 

  5. Jones, B. The burden of knowledge and the 'death of the reinassance man': is innovation getting harder? Rev. Econ. Stat. 76, 283–317 (2009). A parsimonious explanation for the increase in specialization and teamwork in pharmaceutical R&D.

    Article  Google Scholar 

  6. Everson, R. Patents, R&D and invention potential: international evidence. Amer. Econ. Rev. 83, 463–468 (1993).

    Google Scholar 

  7. Segerstrom, P. Endogenous growth without scale effects. Amer. Econ. Rev. 88, 1290–1310 (1998).

    Google Scholar 

  8. Drews, J. In Quest of Tomorrow's Medicines 1–272 (Springer, Basel, 1998).

    Google Scholar 

  9. Cockburn, I. M. in Innovation Policy and the Economy Vol. 7 Ch. 1 (eds Jaffe, A. B., Lerner, J. & Stern, S.) 1–32 (The MIT Press, 2007). A critical assessment of the productivity crisis in pharmaceutical R&D.

    Google Scholar 

  10. Orsenigo, L., Pammolli, F. & Riccaboni, M. Technological change and network dynamics: lessons from the pharmaceutical industry. Res. Policy 30, 485–508 (2001).

    Article  Google Scholar 

  11. Booth, B. & Zemmel, R. Prospects for productivity. Nature Rev. Drug Discov. 3, 451–456 (2004).

    Article  CAS  Google Scholar 

  12. Paul, S. M. et al. How to improve R&D productivity: the pharmaceutical industry's grand challenge. Nature Rev. Drug Discov. 9, 203–214 (2010).

    Article  CAS  Google Scholar 

  13. DiMasi, J., Hansen, R. & Grabowski, H. The price of innovation: new estimates of drug development costs. J. Health Econ. 22, 151–185 (2003).

    Article  Google Scholar 

  14. Munos, B. Lessons from 60 years of pharmaceutical innovation. Nature Rev. Drug Discov. 8, 959–968 (2009).

    Article  CAS  Google Scholar 

  15. Mervis, J. Productivity counts — but the definition is key. Science 309, 726–726 (2005).

    Article  CAS  Google Scholar 

  16. Pammolli, F. & Riccaboni, M. Innovation and Industrial Leadership: Lessons from Pharmaceuticals (Center for Transatlantic Relations, 2008). This book contains an in-depth analysis of pharmaceutical productivity based on the PhID.

    Google Scholar 

  17. David, E., Tramontin, T. & Zemmel, R. Pharmaceutical R&D: the road to positive returns. Nature Rev. Drug Discov. 8, 609–610 (2009).

    Article  CAS  Google Scholar 

  18. Helpman, E. & Trajtenberg, M. in General Purpose Technologies and Economic Growth (ed. Helpman, E.) 85–119 (The MIT Press, 1998).

    Google Scholar 

  19. Owen-Smith, J., Riccaboni, M., Pammolli, F. & Powell, W. A comparison of U.S. & European university–industry relations in the life sciences. Manage. Sci. 48, 24–43 (2002). An in-depth comparative analysis of the US and European systems of innovation in the life sciences.

    Article  Google Scholar 

  20. Braunwald, E. et al. Harrison's Principle of Internal Medicine 15th edn (McGraw-Hill, 2001).

    Google Scholar 

  21. Abrantes-Metz, R., Adams, C. & Metz, A. Pharmaceutical development phases: a duration analysis. J. Pharma. Fin. Econ. Policy 14, 19–41 (2006).

    Article  Google Scholar 

  22. Adams, C. & Van Brantner, V. Estimating the cost of new drug development: is it really $802 million? Health Affairs 25, 420–428 (2006).

    Article  Google Scholar 

  23. DiMasi, J. & Faden, L. Factors associated with multiple FDA review cycles and approval phase times. Drug Inform. J. 43, 201–225 (2009).

    Article  Google Scholar 

  24. Keyhani, S., Diener-West, M. & Powe, N. Are development times for pharmaceuticals increasing or decreasing? Health Affairs 25, 461–468 (2006).

    Article  Google Scholar 

  25. Ma, P. & Zemmel, R. Value of novelty? Nature Rev. Drug Discov. 1, 571–572 (2002).

    Article  CAS  Google Scholar 

  26. Yin, W. Market incentives and pharmaceutical innovation. J. Health Econ. 27, 1060–1077 (2008).

    Article  Google Scholar 

  27. Coté, T., Kelkar, A., Xu, K., Braun, M. M. & Phillips M. I. Orphan products: an emerging trend in drug approvals. Nature Rev. Drug Discov. 9, 84 (2010).

    Article  Google Scholar 

  28. Trusheim, M. R., Berndt, E. R. & Douglas, F. L. Stratified medicine: strategic and economic implications of combining drugs and clinical biomarkers. Nature Rev. Drug Discov. 6, 287–293 (2007).

    Article  CAS  Google Scholar 

  29. DiMasi, J. & Grabowski, H. G. Economics of new oncology drug development. J. Clin. Oncol. 25, 209–216 (2007).

    Article  Google Scholar 

  30. Acemoglu, D. & Lin, J. Market size in innovation: theory and evidence from the pharmaceutical industry. Q. J. Econ. 119, 1049–1090 (2003).

    Article  Google Scholar 

  31. Kneller, R. The importance of new companies for drug discovery: origins of a decade of new drugs. Nature Rev. Drug Discov. 9, 867–882 (2010).

    Article  CAS  Google Scholar 

  32. Grabowski, H. G. & Wang, Y. R. The quantity and quality of worldwide new drug introductions, 1982–2003. Health Affairs 25, 452–460 (2006).

    Article  Google Scholar 

  33. Friedman, Y. Location of pharmaceutical innovation: 2000–2009. Nature Rev. Drug Discov. 9, 835–836 (2010).

    Article  CAS  Google Scholar 

  34. Light, D. Global drug discovery: Europe is ahead. Health Affairs 28, W969–W977 (2009).

    Article  Google Scholar 

  35. Cohen, W., Nelson, R. & Walsh, J. Protecting their intellectual assets: appropriability conditions and why U.S. manufacturing firms patent (or not). NBER Working Paper No. 7552 (National Bureau of Economic Research, 2000).

  36. Henderson, R. & Cockburn, I. Scale, scope, and spillovers: the determinants of research productivity in drug discovery. Rand. J. Econ. 27, 32–59 (1996).

    Article  CAS  Google Scholar 

  37. Arora, A., Gambardella, A., Pammolli, F. & Riccaboni, M. in Innovation and Competitiveness in the European Chemical Industry (eds Cesaroni, F., Gambardella, A. & Garcia-Fontes, W.) 175–202 (Springer, 2004).

    Book  Google Scholar 

  38. Arora, A., Gambardella, A., Magazzini, L. & Pammolli, F. A breath of fresh air? Firm type, scale, scope and selection effects in drug development. Manage. Science 55, 1638–1653 (2009).

    Article  Google Scholar 

  39. Danzon, P. M. & Chao, L. W. Cross-national price differences for pharmaceuticals: how large, and why? J. Health Econ. 19, 159–196 (2000).

    Article  CAS  Google Scholar 

  40. Drews, J. Drug discovery: a historical perspective. Science 287, 1960–1964 (2000).

    Article  CAS  Google Scholar 

  41. Hopkins, A. L. & Groom, C. R. The druggable genome. Nature Rev. Drug Discov. 1, 727–730 (2002).

    Article  CAS  Google Scholar 

  42. Drews, J. Strategic trends in the drug industry. Drug Discov. Today 8, 411–420 (2003).

    Article  Google Scholar 

  43. Overington, J. P., Al-Lazikani, B. & Hopkins, A. L. How may drug targets are there? Nature Rev. Drug Discov. 5, 993–996 (2006).

    Article  CAS  Google Scholar 

  44. Pammolli, F. & Riccaboni, M. Market structure and drug innovation. Health Affairs 23, 24–43 (2004).

    Article  Google Scholar 

  45. Gambardella, A., Orsenigo, L. & Pammolli, F. Global Competitiveness in Pharmaceuticals: a European Perspective (Directorate General Enterprise of the European Commission, 2001).

    Google Scholar 

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Acknowledgements

This work was supported by a grant from selected members of the Ad Hoc Working Group on the Economics of the Pharmaceutical Industry (AstraZeneca Pharmaceuticals LP, Novartis, Pfizer, and the National Pharmaceutical Council). Discussions with members of funding companies and with B. Munos and W. Looney are gratefully acknowledged. We also benefited from comments and suggestions from anonymous referees.

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Correspondence to Massimo Riccaboni.

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Competing interests

This research was funded, in part, by grants from AstraZeneca Pharmaceuticals, Novartis Pharmaceuticals, Pfizer and the National Pharmaceutical Council. The authors are solely responsible for the design, conduct and analysis of the study, and the conclusions that are drawn.

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Glossary

Knowledge production function

A function that specifies the output of new ideas by an individual, a firm, an industry or the entire economy for all combinations of research and development inputs (labour and the existing stock of knowledge).

New molecular entity

(NME). A medication containing an active ingredient that has not been previously approved for marketing in any form in the United States. NME is conventionally used to refer only to small-molecule drugs, but the term is used here to include biologics as a shorthand for both types of new drug and also to new drugs in all the regions studied, rather than just those approved in the United States.

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Pammolli, F., Magazzini, L. & Riccaboni, M. The productivity crisis in pharmaceutical R&D. Nat Rev Drug Discov 10, 428–438 (2011). https://doi.org/10.1038/nrd3405

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