Is poor research the cause of the declining productivity of the pharmaceutical industry? An industry in need of a paradigm shift.

For the past 20 years target-based drug discovery has been the main research paradigm used by the pharmaceutical industry and billions of dollars have been invested into this approach. However, recent industry data strongly indicate that the target-based approach is not an effective drug discovery paradigm and is likely to be the cause of the productivity crisis the industry is experiencing. However, from a theoretical and scientific perspective the target-based approach appears sound, so why is it not more successful? The purpose of this paper is first to analyse the real-life implementation of the target-based approach to identify possible reasons for the high failure rate and second to suggest changes to the drug discovery approach, which can improve productivity.

[1]  D. Fabbro,et al.  Targeting cancer with small-molecular-weight kinase inhibitors. , 2012, Methods in molecular biology.

[2]  T. Merigan.  Treatment of AIDS with combinations of antiretroviral agents. , 1991, The American journal of medicine.

[3]  D. Corbett,et al.  Overexpression of APP provides neuroprotection in the absence of functional benefit following middle cerebral artery occlusion in rats , 2007, The European journal of neuroscience.

[4]  I. Kola,et al.  Can the pharmaceutical industry reduce attrition rates? , 2004, Nature Reviews Drug Discovery.

[5]  F. Sams-Dodd.  A Test of the Predictive Validity of Animal Models of Schizophrenia Based on Phencyclidine and D-Amphetamine , 1998, Neuropsychopharmacology.

[6]  R. Silverman,et al.  From basic science to blockbuster drug: the discovery of Lyrica. , 2008, Angewandte Chemie.

[7]  Stroke Therapy Academic Industry Roundtable.  Recommendations for standards regarding preclinical neuroprotective and restorative drug development. , 1999, Stroke.

[8]  G. Birk,et al.  The Selective mGlu5 Receptor Antagonist MTEP, Similar to NMDA Receptor Antagonists, Induces Social Isolation in Rats , 2007, Neuropsychopharmacology.

[9]  F. Pammolli,et al.  The productivity crisis in pharmaceutical R&D , 2011, Nature Reviews Drug Discovery.

[10]  J. Arrowsmith.  Trial watch: Phase II failures: 2008–2010 , 2011, Nature Reviews Drug Discovery.

[11]  J. Joyce,et al.  D2 but not D3 receptors are elevated after 9 or 11 months chronic haloperidol treatment: Influence of withdrawal period , 2001, Synapse.

[12]  F. Sams-Dodd.  Phencyclidine‐induced stereotyped behaviour and social isolation in rats: a possible animal model of schizophrenia , 1996, Behavioural pharmacology.

[13]  F. Barone,et al.  Pharmacological interventions for stroke: failures and future , 2002, Expert opinion on investigational drugs.

[14]  D. Stephenson,et al.  Amyloid precursor protein accumulates in regions of neurodegeneration following focal cerebral ischemia in the rat , 1992, Brain Research.

[15]  D. Swinney,et al.  How were new medicines discovered? , 2011, Nature Reviews Drug Discovery.

[16]  C. Ayata,et al.  Cerebrovascular lesions induce transient β-amyloid deposition. , 2011, Brain : a journal of neurology.

[17]  I. Cree,et al.  Efficacy of anti-cancer agents in cell lines versus human primary tumour tissue. , 2010, Current opinion in pharmacology.

[18]  H. Silver,et al.  Dopamine and serotonin metabolism in response to chronic administration of fluvoxamine and haloperidol combined treatment , 2007, Journal of Neural Transmission.

[19]  F. Sams-Dodd.  Target-based drug discovery: is something wrong? , 2005, Drug discovery today.

[20]  K. W. Jung,et al.  A series of case studies: practical methodology for identifying antinociceptive multi-target drugs. , 2012, Drug discovery today.

[21]  F. Sams-Dodd,et al.  Research & market strategy: how choice of drug discovery approach can affect market position. , 2007, Drug discovery today.