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R&D dynamics and scientific breakthroughs in HIV/AIDS drugs development: the case of Integrase Inhibitors

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Abstract

Transformations and applications of scientific knowledge into new technologies are usually complex interactive processes. Is it possible to detect, from bibliographic information alone, structural alterations and significant events within these processes that may indicate breakthrough discoveries? In this empirical study we focus on R&D processes leading to HIV/AIDS medicines called Integrase Inhibitors. Where scientific progress and discoveries are reflected in research papers, patents signify inventions and technological achievements. Our temporal analysis of distinctive events in this R&D area, tracing trends within both bibliographic information sources, is driven by three bibliometric indicators: (1) contributions of ‘bridging researchers’ who are also inventors, (2) ‘key papers’ that subject experts in the field considered milestones in the research process, and (3) the multidisciplinary impact of those papers. The main results indicate that a combination of key papers, bridging researchers and multidisciplinary impact might help track potential ‘Charge type’ breakthrough developments.

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Notes

  1. Tracking the citation patterns over a period of 6–24 months after publication, and using this information to predict if a publication exceeds a citation threshold level within 5 years after publication.

  2. Oldest priority data is the date of the earliest filing of a patent application for this invention.

  3. Ciechanover (2009) applies Koshland’s criteria to motivate the classification of the discovery of ‘ubiquitin proteolytic system’ as a ‘Challenge’ rather than a ‘Chance’.

  4. Also known as ‘computer-aided drug design’ or ‘structure-based drug design’.

  5. Lead compounds are, if proven to be an effective drug, the beginning of a group of chemical closely related medicines.

  6. A sixth class is formed by the so called cocktail drugs; combinations of two or more drugs from the other five classes.

  7. Immunology, biochemistry & molecular biology, virology, cell biology, microbiology, infectious diseases, pharmacology and pharmacy, biotechnology and applied microbiology, medicinal chemistry, infectious diseases, and medicine.

  8. The PATSTAT database is the database also known as the EPO Worldwide Patent Statistical Database.

  9. A DOCDB patent family is a collection of closely related equivalent patent publications describing the same invention. 2008 was used as cut-off year because due to procedural regulations more recent patent data were not yet fully available.

  10. This manuscript submission date is however not provided in the databases. For individual publications the submission date of the manuscript can usually be found on the ‘image’ of the publication, but for analysis of larger datasets the use of this date is very laborious and time-consuming, and we therefore had to use the ‘publication date’ provided by the Web of Science. Further research has to be done in this area to estimate the error introduced; Luwel and van Wijk (2012) provides some insights into the nature and extent of this problem.

  11. Although ‘Hazuda 2000’ is seen as an important publication it is just a link in the R&D process that started before this publication, and already produced some patents. The publication of this paper might have been intentionally delayed in order not to infringe with ongoing patent applications. The bibliographic data is insufficient to solve this issue.

  12. Porter and Rafols (2009) and Ponomarev et al. (2012) use the related term ‘interdisciplinarity’ to classify research publications that cover several scientific disciplines.

  13. CWTS uses 250 distinct subject categories based on the ‘standard’ subject categories used by Thomson-Reuters in the Web of Science database; 60 of these CWTS subject categories are related to medical sciences and life sciences; the themes range from fundamental biomedical research to clinical medicine. It is expected that citations start to come from a increasing and more ‘application’ oriented range of subject categories as research progresses.

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Acknowledgments

The authors kindly thank Professor Erik de Clercq for commenting on a concept version of this manuscript, Professor Ton van Raan for comments on an earlier versions of this manuscript, and the anonymous reviewers for their valuable comments during peer-review.

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Authors and Affiliations

  1. Centre for Science and Technology Studies (CWTS), Leiden University, Wassenaarseweg 62A, 2333 AL, Leiden, The Netherlands

    J. J. Winnink & Robert J. W. Tijssen

  2. Leiden University Dual PhD Centre The Hague, P.O. Box 13228, 2501 EE, The Hague, The Netherlands

    J. J. Winnink

  3. Netherlands Patent Office (a Division of Netherlands Enterprise Agency), P.O. Box 10366, 2501 HJ, The Hague, The Netherlands

    J. J. Winnink

  4. DST-NRF Centre of Excellence in Scientometrics and STI Policy, Stellenbosch University, Stellenbosch, South Africa

    Robert J. W. Tijssen

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Winnink, J.J., Tijssen, R.J.W. R&D dynamics and scientific breakthroughs in HIV/AIDS drugs development: the case of Integrase Inhibitors. Scientometrics 101, 1–16 (2014). https://doi.org/10.1007/s11192-014-1330-7

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