R&D crisis in drug discovery for neglected diseases: scope for an open source approach to pharmaceutical research
article by Narendan Thiruthy
Thiruthy’s article analyses open source initiatives for drug discovery. In order to do so, the author covers the bases of the IP-centred research and development (r&d) model. Specifically, the introductory parts tackle issues of lack of innovation by pharmaceutical companies and lack of access to medicines due to high prices.
The innovation crisis is described in terms of two “eras”, one of “abundance” (from 1996 to 2004), the other of “scarcity” (from 2005-2010) in drug r&d. In the latter, r&d productivity has fallen, with 85-90% of all new drugs providing “few or no clinical advantages for patients and even result[ing] in considerable harm” (p. 600).
This crisis refers to internal innovation, conducted in-house. The author evidences that, due to this lack of productivity, Morgan Stanley has recommended pharmaceutical companies to abandon internal r&d and investing in licensing instead, while Deloitte has presented open innovation models as a means to increase productivity in r&d.
All this comes to show that external innovation may be a better option for r&d productivity in pharmaceutical companies. Open innovation models incorporate this idea, with the added principles of openness and accessibility. The author, then, proposes an analysis of the feasibility of these open innovation models based on drug discovery for neglected diseases.
Neglected diseases aren’t the main focus of the article, them being used solely as analytical supports for the open innovation models. The author highlights that these diseases affect over 1 billion people living in poverty and result in around 10 million deaths each year and that they are neglected by drug companies due to their incidence mainly in poor populations.
In terms of r&d investment and results, only 1% of overall investments in 2010 were dedicated to neglected diseases and, out of the 850 new therapeutic products registered between 2000-2011, only 37 (4%) were indicated for neglected diseases. The author further points that companies invest only 1.3% of their revenues in the discovery of new molecules, as opposed to 25% on promotion and market and that “more than four-fifths of all funds for basic research to discover new drugs and vaccines come from public sources” (p. 604).
Aiming to place open innovation between current proposed and implemented models for alternative r&d, the author then analyses a few of these models. Orphan drug schemes are rejected, as they link research incentives to market monopoly and drug pricing, effectively continuing the issue. Transferable IP rights show similar limitations in the author’s view.
Prizes are presented as an alternative that actually de-links r&d costs from drug prices, with the drawback of depending on governmental and non-governmental resources. Green Intellectual property is a scheme that draws funding from the monetary flow related to patents, but it does not resolve the issue of de-linkage. Patent pools are presented as a framework under which open source drug discovery may be applied. Finally, the idea of an international binding r&d agreement under the WHO is analysed, to which the author gives credit for its potential to overcome “the problem of under-funding and the lack of global coordination of pharmaceutical research” (p. 607).
Following on to the analysis of open source models for pharmaceutical r&d, the author states that open source “implies a set of cultural practices, collaborative production methodology with continuous peer review and a licensing model that relies on a distinctive use of property to facilitate access rather than to prevent it” (p. 607).
Open source for drug discovery would be possible due to the phase-by-phase manner in which r&d is conducted, allowing for collaboration. However, a few challenges would have to be overcome. The issue of incentives to collaborate is a first: while in open source software factors like ideology, personal satisfaction, the chance to learn new skills, peer- and professional recognition are in play, what would incentivize researchers to collaborate over drug discovery?
Another limitation in comparison with the open source example is peer-review. While in open source the users become testers and even developers, in drug discovery there are rigid rules for trials that cannot be overcome due to safety concerns.
One additional issue is cost. The drug discovery pathway contains many cost barriers, such as registration fees for the drugs and their patents, laboratory infrastructure and expensive clinical trials. Finally, there is the issue that, while open source is based on the wide availability of data for collaboration, patenting requires secrecy preceding the patent request.
The author responds to these issues by demonstrating that there are open source drug discovery projects already in place – Open Source Malaria (OSM) and Open Source Drug Discovery (OSDD). They overcome the cost barriers by obtaining previous funding and utilizing public domain material. Research is crowdsourced via the internet and results are freely available for commercial or non-commercial use, under the condition that further research be equally available.
The author’s conclusion is that open source may be a path to overcome the pharmaceutical industry’s innovation crisis, while at the same time resolving the issue of pricing by de-linking the cost of research from the price and the issue of neglect for poor populations’ health needs.
References deserving further study:
- Shaeffer, J. M. and MacDonald, S. (2014) Innovation: Open Source and Nonprofit Models in Drug Discovery, in Collaborative Innovation in Drug Discovery (ed R. Chaguturu), John Wiley & Sons, Inc., Hoboken, NJ, USA. doi: 10.1002/9781118778166.ch3
- Marcia Angell, MD, The truth about the Drug Companies – How they deceive us and what to do about it. New York: Random House, 2004.
- D. W. Light, Basic research funds to discover important new drugs: Who contributes how much?, in: M. A. Burke (ed.), Monitoring the financial flows for health research 2005: Behind the global numbers. Global Forum for Health Research, 2006, Geneva, Switzerland.
- Gagnon MA, Lexchin J (2008) The Cost of Pushing Pills: A New Estimate of Pharmaceutical Promotion Expenditures in the United States. PLoS Med 5(1): e1. doi: 10.1371/journal.pmed.0050001.
- Henry Grabowski. Patents, Innovation and Access to New Pharmaceuticals.
J Int Economic Law (2002) 5 (4): 849-860 doi:10.1093/jiel/5.4.849
- Røttingen, John-Arne et al. Mapping of available health research and development data: what’s there, what’s missing, and what role is there for a global observatory? The Lancet , Volume 382 , Issue 9900 , 1286 – 1307
- Deloitte Center for Health Solutions, Executing an open innovation model: Cooperation is key for biopharmaceutical companies. Deloitte, 2015.
- CMR International pharmaceutical R&D factbook 2015.
- Light Donald W, Lexchin Joel R. Pharmaceutical research and development: what do we get for all that money? BMJ 2012; 345 :e4348.
- PAMMOLLI, F.; MAGAZZINI, L.; RICCABONI, M. The productivity crisis in pharmaceutical R&D. Nat Rev Drug Discov, v. 10, n. 6, p. 428–438, jun. 2011.
- Jeff Hewitt, J. David Campbell and Jerry Cacciotti, Beyond the shadow of a drought – The need for a new mindset in pharma R&D. Oliver Wayman, 2011.