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Portfolio Decisions in Early Development

Don’t Throw Out the Baby with the Bathwater

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Abstract

Portfolio decisions in early development happen under much uncertainty. Particularly when a novel target or treatment method is being explored, early negative clinical results may lead to the discontinuation of compound development, or even of an entire branch of discovery research. Although we can find examples where ‘failed’ concepts have been picked up later and shown to work, there is no way to estimate how large the percentage of false negative discontinuations may be as this type of information is not routinely added to publicly accessible databases; any analysis therefore is limited to specific articles and personal experience. Factors that favour false negative trials are known, and some of them can be influenced. In many cases, intelligent programme and clinical trial design can prevent false negative results. Well designed dose-finding studies and comparisons against both a placebo and a gold-standard treatment arm play a major role in achieving reliable data. Apart from following a more intelligent way of performing trials, the inherent mechanisms of human decision making need to be understood. Many of those decisions are not purely rational. Therefore, the findings of Kahneman and Tversky are very much applicable to early termination decisions. Thus, there are not only ways to prevent false negative clinical trials, but also clues to the psychology/mental frameworks that lead to erroneous conclusions in development. Awareness of such thinking may reduce the inclination to abandon an entire area of research based on only a few experimental data. The development of diagnostic tests can be used as an analogue to the decisions to be made in early clinical research, as such decisions can be classified according to false positives or false negatives, and so on, depending on the quality of the available information. It is hoped that the analysis of these early portfolio decisions will be based on data from public domain databases such as http://www.clinicaltrials.gov in the future.

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References

  1. Evans R, Hinds S, Hammock D. Portfolio analysis and R&D decision making. Nature Reviews Drug Discovery 2009; 8 (3): 189–90

    Article  PubMed  CAS  Google Scholar 

  2. Paul SM, Mytelka DS, Dunwiddie CT, et al. How to improve R&D productivity: the pharmaceutical industry’s grand challenge. Nature Reviews Drug Discovery 2010; 9 (3): 203–14

    PubMed  CAS  Google Scholar 

  3. Kola I, Landis J. Can the pharmaceutical industry reduce attrition rates? Nat Rev Drug Discov 2004; 3 (8): 711–5

    Article  PubMed  CAS  Google Scholar 

  4. Booth M, Bundy DA. Comparative prevalences of Ascaris lumbricoides, Trichuris trichiura and hookworm infections and the prospects for combined control. Parasitology 1992; 105 (Pt 1): 151–7

    Article  Google Scholar 

  5. Jones D. Potential remains for PPAR-targeted drugs. Nat Rev Drug Discov 2010; 9 (9): 668–9

    Article  PubMed  CAS  Google Scholar 

  6. Arrowsmith J. Trial watch: phase II failures: 2008–2010 [abstract]. Nat Rev Drug Discov 2011; 10 (5): 328–9

    Article  PubMed  CAS  Google Scholar 

  7. Arrowsmith J. Trial watch: phase III and submission failures: 2007–2010. Nat Rev Drug Discov 2011; 10 (2): 87

    Article  PubMed  CAS  Google Scholar 

  8. Leeson PD, Springthorpe B. The influence of drug-like concepts on decision-making in medicinal chemistry. Nat Rev Drug Discov 2007; 6 (11): 881–90

    Article  PubMed  CAS  Google Scholar 

  9. Dickson M, Gagnon JP. Key factors in the rising cost of new drug discovery and development. Nat Rev Drug Discov 2004; 3 (5): 417–29

    Article  PubMed  CAS  Google Scholar 

  10. Dancey JE, Chen HX. Strategies for optimizing combinations of molecularly targeted anticancer agents. Nat Rev Drug Discov 2006; 5 (8): 649–59

    Article  PubMed  CAS  Google Scholar 

  11. Kahneman D, Tversky A. Variants of uncertainty. Cognition 1982; 11 (2): 143–57

    Article  PubMed  CAS  Google Scholar 

  12. Kohlhardt M, Fleckenstein A. Inhibition of the slow inward current by nifedipine in mammalian ventricular myocardium. Br J Clin Pract Suppl. 1980; 8: 3–8

    PubMed  CAS  Google Scholar 

  13. Singhal S, Mehta J, Desikan R, et al. Antitumor activity of thalidomide in refractory multiple myeloma. N Engl J Med 1999; 341 (21): 1565–71

    Article  PubMed  CAS  Google Scholar 

  14. Folkman J. A novel anti-vascular therapy for cancer. Cancer Biol Ther 2004; 3 (3): 338–9

    Article  PubMed  Google Scholar 

  15. A stronger role for science [editorial]. Nat Rev Drug Discov 2011; 10 (3): 159

    Google Scholar 

  16. Arthritis Advisory Committee. Briefing document on belilumab. Rockville (MA): Human Genome Sciences, 2010 Oct 10

    Google Scholar 

  17. Ocana A, Tannock IF. When are “positive” clinical trials in oncology truly positive? J Natl Cancer Inst 2011; 103 (1): 16–20

    Google Scholar 

  18. Hurko O, Jones GK. Valuation of biomarkers. Nat Rev Drug Discov 2011; 10 (4): 253–4

    Article  PubMed  CAS  Google Scholar 

  19. Pritchard JF, Jurima-Romet M, Reimer ML, et al. Making better drugs: decision gates in non-clinical drug development. Nat Rev Drug Discov 2003; 2 (7): 542–53

    Article  PubMed  CAS  Google Scholar 

  20. Munos B. Can open-source R&D reinvigorate drug research? Nat Rev Drug Discov 2006; 5 (9): 723–9

    Article  PubMed  CAS  Google Scholar 

  21. Wehling M. Assessing the translatability of drug projects: what needs to be scored to predict success? Nat Rev Drug Discov 2009; 8 (7): 541–6

    Article  PubMed  CAS  Google Scholar 

  22. Cohen AF. Developing drug prototypes: pharmacology replaces safety and tolerability? Nat Rev Drug Discov 2010; 9 (11): 856–65

    Article  PubMed  CAS  Google Scholar 

  23. Kaitin, KI. Review of new drug development. Presentation at ASENT Meeting, 2010 [online]. Available from URL: http://www.google.com/search?q=jw+van+esser#hl=en&sclient=psy-ab&q=Kaitin%2C+KI.+Review+of+New+Drug+Development.+Presentation+at+ASENT+Meeting%2C+2010+&oq=Kaitin%2C+KI.+Review+of+New+Drug+Development.+Presentation+at+ASENT+Meeting%2C+2010+&aq=f&aqi=&aql=&gs_sm=12&gs_upl=2734∣2734∣1∣7281∣1∣1∣0∣0∣0∣0∣422∣422∣4-1∣1∣0&gs_∣=serp.12…2734∣2734∣1∣7281∣1∣1∣0∣0∣0∣0∣422∣422∣4-1∣1∣0&psj=1&bav=on.2,or.r_gc.r_pw.r_qf.,cf.osb&fp=b9945a0c9d764027&biw=1280&bih=835 [Accessed 2012 Mar 12]

    Google Scholar 

  24. Whitehead J. Stopping clinical trials by design. Nat Rev Drug Discov 2004; 3 (11): 973–7

    Article  PubMed  CAS  Google Scholar 

  25. Jones D. Adaptive trials receive boost. Nat Rev Drug Discov 2010; 9 (5): 345–8

    Article  PubMed  CAS  Google Scholar 

  26. Agid Y, Buzsaki G, Diamond DM, et al. How can drug discovery for psychiatric disorders be improved? Nat Rev Drug Discov 2007; 6 (3): 189–201

    Article  PubMed  CAS  Google Scholar 

  27. van der Greef J, McBurney RN. Innovation: Rescuing drug discovery: in vivo systems pathology and systems pharmacology. Nat Rev Drug Discov 2005; 4 (12): 961–7

    Article  PubMed  Google Scholar 

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Acknowledgements

The author would like to thank Duncan McKay and Peter Walton for comments and additional suggestions for language.

Michael Herschel is an employee of GlaxoSmithKline GmbH&Co. KG, Germany. No sources of funding were used in the preparation of this article.

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  1. Clinical Research, GlaxoSmithKline GmbH & Co. KG, Kellerstrasse 16, D-81667, Munich, Germany

    Michael Herschel

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  1. Michael Herschel
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Correspondence to Michael Herschel.

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Herschel, M. Portfolio Decisions in Early Development. Pharm Med 26, 77–84 (2012). https://doi.org/10.1007/BF03256895

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