One often-cited study of the cost of the discovery and development of new drugs is that of DiMasi et al. (DiMasi et al. 2003) from the Tufts University Center for the Study of Drug Development (CSDD). Their sound bite number of $800 million per new approved drug (now up to $1.7 billion) is undoubtedly big and has been used by various groups to explain:
- the high cost of drugs (pharma industry);
- the lack of pharma industry interest in low-income markets (global health advocacy groups);
- the reluctance of VCs to invest in biotech (VCs);
- the need for more government and donor money for neglected disease research (global health advocates); and
- why the world needs strong pharma patents (IP lawyers).
While there has been a fair amount of back-and-forth about the study’s methodology (e.g., Rational Argument blog), no one disputes that drug discovery is a challenging scientific process and drug development is a multi-tens-of-millions dollar effort which often fails. A good demonstration of the latter is the list of ten drugs that failed in Phase III trials (supposedly the least, albeit most expensive, phase) in 2010 as compiled by the FierceBiotech newsletter (FB list). Each failure represents years of work and billions in investment. Bernard Munos, a veteran pharma executive, published a recent study of the past 60 years of drug development (costs and output) and made a number of interesting points, including that the DiMasi cost per drug may be an under-estimate but that the many variables make exactness elusive (Munos 2010). Of more interest to me is the author’s summary of the industry’s effort to fix its business model, including investing in product development for the neglected diseases. [I wonder why no one has tried to get a cost estimate by building it from the bottom up, i.e., by finding the costs of each stage for various drugs and adding and averaging; one source of data is the 10-Q filings of the mid-sized public biotech companies who need to report their r and d costs.]
Of course, one of my main interests is how to do drug development faster and cheaper which is needed to get better (or any) drugs for the neglected diseases. In my posting of March 11, I wrote about “accelerated proof of concept” (POC) testing, which uses experiments to make decisions rather than accumulate data (e.g., for registration), and its use in several start-up biotechs whose backers must be POC advocates since it’s their cash that is being burned (that is, if they really want the company to create value as opposed to the appearance of value). Anyhow, in that posting I posited a model for doing neglected disease drug discovery and development “on the cheap”:
- funding by donors and investors with patience and wanting to sleep well;
- licensing of drug prototypes from academia or companies at low/no cost;
- contracting preclinical work globally to get the best price;
- using software platforms to analyze the results and coordinate the work;
- using government resources to conduct clinical trials or contracting with PDPs with experience in conducting trials;
- registering products through a (currently non-existent) expedited process at the USFDA and through (currently non-existent) reciprocity agreements with other countries; and
- manufacturing the product where it is to be used to keep the cost as low as possible.
I was able to add another data point to this model this week when I saw a demonstration of HEOS (“Hit Explorer Operating System”), a “secure web-based drug research information management software platform that supports geographically-distributed scientists and facilitates collaboration,” marketed by Scynexis of North Carolina (Scynexis). The presenters were Terry Marquardt, market development director, and Fred Bost, “the father of HEOS” according to Terry. The system is impressive, primarily, at least to me, a nonscientist, in its ability to allow the combination and analysis of chemical structures and data generated from almost any source. Also to Scynexis’s credit, in addition to their commercial customers, the company is a partner/provider to two prominent neglected disease drug developers, Drugs for Neglected Disease Institute (DNDi) and Medicines for Malaria Venture (MMV), which use HEOS to coordinate their world-wide team of primarily academic scientists but also a smattering of contract and donated company researchers. HEOS is a powerful tool for mining the universe chemical (and biological?) structures for those that may have medicinal effects and for getting to better and cheaper.
However, to me, the amateur drug developer, HEOS could be improved by adding a module for clinical trials management and by improving its project management (decision-making) capabilities, as could a similar platform offered by Collaborative Drug Discovery (CDD) which I mentioned in previous postings. A trials module is not attractive commercially since the clinical (contract) research industry is well-developed and most contractors have their own proprietary systems. However, for the less-endowed not-for-profits, a clinical trials module may be useful since these groups may be using trials sponsored by government or academic teams using non-standardized protocols in remote locations. One solution to this problem would be a HEOS interface to OpenClinica, which is a free data capture and management package developed by Akaza Research (OpenClinica) and is used by some contractors, pharmaceutical, device, and biotech companies, and academic research groups. As for project management, in our discussion Fred Bost mentioned that HEOS was more of a repository than a management tool and noted that its management and decision-making capabilities will be improved. In a recent publication about informatics for neglected disease drug collaborations (Bost et al. 2010), the Scynexis team referenced the development of scientific collaboration software by Acclerys and Microsoft (Sharepoint) and Imaginatik (ChemBioConnect).
So, with some additional tinkering and thanks to companies like Scynexis and CDD, one piece of my “drug development on the cheap” model may soon be available. Now where do I find the others?