TB Diagnostic Development In the Developing World – IP solutions through Public Private Partnerships

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Introduction

Tuberculosis (TB) is a disease of poverty.  TB is a contagious airborne disease that resulted in the deaths of 1.7 million people and 9.4 million new cases in 2009 (WHO 2010).  The vast majority of these victims are in the developing world where most don’t have the financial means or opportunities to receive healthcare.  Since these individuals don’t have the purchasing power or insurance system that the developed world has, treatments for these diseases in the developing world are often neglected by profit driven pharmaceutical companies.  Without a return on investment the major pharmaceutical companies focus their resources on health issues that affect the developed countries. (See figure 1).

FIGURE 1: Banerji, J. P., B. Pragmatic and principled: DNDi’s approach to IP management. In Intellectual property management in health and agricultural innovation: a handbook of best practices, Volumes 1 and 2  2007 pp. 1775-1782

To reach the Millennium Development Goals of halting and reversing TB incidence globally by 2015 (compared to the 1990 rate), a marked increase of public-private partnerships (P3) revolving around intellectual property (IP) incentives will provide a significant pathway to eradicating neglected diseases.  One area in which this partnership would benefit TB prevention and treatment is in diagnostic technology.  In this paper, I will first examine the widely used TB diagnostic technologies and analyze their weaknesses for use in developing countries; and, present some new developments in TB diagnostics that promise efficient and affordable implementation for use in developing countries.  I will then introduce some innovative policies that could help in the development of TB diagnostics and explain, in particular, the function and promise of public-private partnerships in developing TB diagnostic technology specifically, and their role in global health, generally.

Current TB Diagnostic Technologies and their Weaknesses

Continual advancements in TB diagnostics occur, but applicable diagnostics for the developing world are deficient due to the lack of return on investment opportunities for pharmaceutical companies.  TB diagnostics commonly used in the developed world are unrealistic for use in the developing world.  The diagnostics require a clinical infrastructure to house the equipment, technical expertise to perform the diagnostic, and in most cases, multiple tests or an extended turn around time.  These issues are further exacerbated by the geographic isolation of many regions and the inadequacy of financial agency to purchase the diagnostic test.  The combination of these issues has resulted in the common use of a century old diagnostic technique in the developing world.

The core diagnostic technology in current control strategies in the underdeveloped nations is the sputum microscopy.  First developed in the 1880’s, the test requires a sputum sample (spit), a microscope, a trained technician, multiple examinations, and takes days rather than hours to complete. (Perkins, Roscigno et al. 2006).  This diagnostic requires a clinic/laboratory to house the equipment.  Depending on the geography, people may have to travel forty miles on foot to take the test, and since it requires multiple samples, would either have to stay nearby or make the trek several times.  The sputum microscopy is a low sensitive technology, meaning, there must be a high level of TB bacteria to receive a positive result. (Palomino, Leo et al. 2007).  According to World Health Organization (WHO), fewer than 45% of predicted incident smear-positive cases of TB are detected. (Perkins, Roscigno et al. 2006).  Despite developments in automatic microscopes and LED specific lights used with fluorescence microscopy, the test is still inefficient. The inadequacy of the results and the necessity for a clinic, the sputum microscopy test, while being the most used, is certainly not the goal for TB diagnostics in the developing world.

Other methods of TB diagnosis include: clinical signs, x-ray, culture, skin tests, and polymerase chain reaction (PCR) tests.  The clinical signs test utilizes the actual physical symptoms of the patient to diagnose TB.  It provides a rapid diagnosis, but is not specific or conclusive.  The physical symptoms of a patient could be attributed to another disease such as HIV, or with latent TB, a lack of physical symptoms altogether. (Arentz 2009).  X-ray, while readily available in the developed world, is not a sufficient method to diagnosis victims of TB in the developing world.  The test marginalizes those victims who have no access to clinics or can’t afford the procedure.   The use of culture (e.g. blood sample) reading technology had advanced over the years, but is still not an efficient option in heavy-burden TB countries who lack the capabilities of developing an infrastructure to house the equipment; additionally, the turnaround time for results are longer than the sputum test and require more equipment. (Id.).  Tuberculin skin tests require the injection of Tuberculin into the individual’s skin.  A physical reaction possibly indicates TB infection.  Tuberculin skin tests can help in the diagnosis of individuals who are in a low prevalence geographic region.  In developing countries, malnutrition, HIV infection, or BCG immunization, result in decreased test specificity, and, therefore, not an effective means of diagnosis. (Id.).  PCR tests, the most widely used is the nucleic acid amplification test (NAAT), are an excellent tool for developed countries, but once again; developing countries have a difficult time using the process.  It requires a laboratory, extensive experience, and high workloads.  Furthermore, contamination of the culture media is a persistent problem. (Palomino, Leo et al. 2007).

Each of these technologies mentioned above are in continual series of advancements, but as the developing world is in need of point-of-care treatment and rapid response diagnosis, new technologies and further advancement of current technologies must be developed to serve the needs of the heavy burdened regions. (Partnership 2009).  In particular, diagnostic methods for the detection of drug resistant TB, and for individuals with HIV, are essential for interrupting the death rate and transmission of this deadly, but curable disease. (Boehme, Nabeta et al. 2010).  Some fascinating developments include: “simpler, friendly formats (such as MPB-64 Skin patch test), rapid, point-of-care immunodiagnostics (lateral flow formats), innovative use of microscopy (MODS) and rapid simplified cultures (such as TK medium)” will have greater applicability to the developing world. (Chaudhary, Gupta et al. 2010).  Additionally, urine dipstick diagnostics are in the process of development. (Morris 2010).  Despite years of advancement in biotechnology, tuberculosis endemic countries have received little benefit. (Perkins, Roscigno et al. 2006).  The underlying issue still exists – how to incentivize the profit driven corporations to invest in diagnostic tests for use in the developing countries.

Policy Solutions for Effective TB Diagnostic R&D

Incentivization for profit driven companies substantiates policy solutions for increasing R&D in TB diagnostics and other neglected diseases.  Several policies are supranational in nature, requiring a global effort to eradicate diseases.  They either require patent reformation, or provide a large monetary prize for the development of a useful technology.  However, the most efficient and effective way to inspire both innovation while incentivizing for-profit companies, I will argue, is through Public-Private Partnerships (P3) used conjointly with these global policies.  By providing monetary and IP incentives both at the early and later stages of R&D, for-profit companies will show interest in producing technologies that will assist in eradicating the most neglected diseases.

The current fiscal paradigm for TB research falls woefully short of recommendations provided by The Global Plan to Stop TB (a WHO program), which is at least $900 million a year for TB research and development. (Dorman 2010).  In 2007, TB diagnostic research funding from the top 40 institutions was estimated at $41.9 million (drugs at $170 million and vaccines at $71.2 million). (Dorman 2010). Currently, The Global Fund, a P3 committed to fighting neglected diseases, and The Bill & Melinda Gates foundation, are the two biggest donors to TB research. (Ravishankar, Gubbins et al. 2009).  Yet, Over $600 million is still needed to reach The Global Plan to Stop TB goal.  P3 are the solution to the gap in funds, research, and development of TB diagnostics.

P3 are a recent phenomenon in the public health arena.  The innovation occurred in 1980 with the passage of the Bayh-Dole Act, “which allowed universities and public research institutions to patent inventions based on publicly funded research and then license the inventions to the private sector.” (Fraser 2007).  The goal of the Act was the transfer of knowledge from the laboratory to private corporations.  This transfer of knowledge incentivizes the for-profit company to invest in new technology with the ultimate goal of commercializing the product.  Another successful demonstration of P3 is the drug donor programs.  Neglected diseases have benefited the most from these drug donation programs. (Liese, Rosenberg et al. 2010).  Yet, despite the great success of donation programs, they do not inspire innovation in and of themselves.  Particularly with TB diagnostics, we see the current technology is inefficient in heavily burdened regions.  Therefore, P3 that exploit innovative technologies developed in universities and non-profits with the production capacities and know-how of for-profit corporations, will be the pathway in which the most success for neglected diseases, especially TB diagnostics, will occur.

The biggest barrier to the development of TB diagnostics is the lack of a paying customer base.  How can a company receive a profit if its customers are living off a dollar a day?  In our capitalist society, innovation is driven by profit.   Of the 1,556 new drugs that came to the market between 1975-2004, only 21 (1.3%) were for tropical and/or neglected diseases. (Jaya  Banerji 2007).  Further, Jaya and Banerji note that, “[i]nsufficient market incentives are the decisive factor” in pharmaceutical R&D. (Id).  To circumvent this profit barrier in the capitalist system, new technologies developed for neglected diseases require patent licenses to incentivize and attract for-profit corporations.  In other words, patent licenses must benefit the corporation financially.

Public, non-profit institutions, and technology innovators, such as PATH and IDRI, provide a framework through which the R&D process for neglected diseases shifts the market forces to attract private sector involvement.  First, the commercial agency must perceive a reasonable return on the technology and a reasonable level of risk. (Steve Brooke 2007). For this to occur, the public institutions must “co-invest in necessary and suitable technologies, reduce risk, and invigorate private commercial investment through effective PPPs.” (Id).  In relation to TB diagnostic technology, the non-profit or public institution could develop technology with dual uses: one in the resource-poor nation, the other in the developed world.  Through a dual patent licensing structure, the private company would thus act as a bridging agency that would provide funding, manufacturing expertise, production facilities, market channels, and know-how to produce the technology.  In IDRI’s experience, their scientists discovered a TB antigen that reacted with patient sera.  They partnered with ChemBio whom had the technological know-how to put IDRI’s biological component into a platform.  In this situation, IDRI has the patent license for use in developing countries, whereas ChemBio has the license for use in developed countries.  As an example of how this license would look, we will examine PATH’s Preferential Technology Access Program that is written into each agreement with a for-profit or private company.  It generally includes – partner requirements to license their technology on nonexclusive terms to vaccine manufactures in order to maximize the usefulness of the technology, placing a royalty cap on those licensing agreements, and restricting licensing and milestone fees. (Steve Brooke 2007).  Both IDRI and PATH create technology that has a useful basis in treating neglected diseases and offers the for-profit company a return on their investment through a patent license.  This phenomenon is essentially the manifestation of Bill Gate’s “creative capitalism” – the innovative strength of capitalism directed towards improving the lives of the global south.  If this power could be focused on TB diagnostics, then a successful point-of care, rapid response, low cost, solution could materialize.

To supplement P3 and creative capitalism, Global solutions policies can further incentivize for-profit companies.  For example, patent pools, as proposed by WHO and Me´decins Sans Frontie`res (MSF), require universities, private companies, research institutions, and others to pool their patents for use by all in production and further development of useful technologies. (Gold, Kaplan et al. 2010).  The easy access to otherwise complex patent information, patent pools could increase the speed that technologies develop and incentivize for-profit companies by providing advanced technology.  Another solution, the Health Impact Fund is a promising policy whereby developed countries all contribute money to an international fund.  Money is distributed in large or small amounts dependent upon how much health impact the technology has upon the world. (HIF).  However, the money would only be distributed upon the completion of the technology; therefore, requiring companies to fund their own R&D.  Another possible strategy proposed by WHO and MSF is a $100 million prize for TB diagnostic that is affordable and has a licensing structure that benefits the global south. (Morris 2010).  Alone, these programs would not provide enough incentive for profit driven companies to invest in products that the end user can’t afford, but used conjointly with P3, these programs would play a significant factor in eradicating neglected diseases.

Conclusion

The global health paradigm is ready for a transformation.  The capitalist profit model, while advancing health technologies in the developed world, has stagnated the advancement in the developing world.   This is evidenced by the widely used, but century old TB diagnostic test – the sputum microscopy.  Through the assistance of organizations such as The Bill and Melinda Gates foundation and The Global Fund, non-profit organizations can create new technologies to assist in the development of TB diagnostics.  P3 stimulates a relationship with profit driven companies by licensing successful patents for use in the developed world, while at the same time, reserving the license for use in the developing world.  P3 used in conjunction with other global incentive programs can provide the health advancement that developing countries require.  Through this relationship innovations in medicines will occur at a more rapid rate with uses in both developing and the developed countries.