Diagnostics
Evidence-based disease control strategies are now in place for most of the major infectious diseases affecting developing countries. Implementing these strategies depends on accurate diagnostic methods. Progress has been made in securing adequate drug supplies to treat or prevent diseases such as tuberculosis (TB), and in many instances, the most pressing need is for improved diagnostics to ensure wider and wiser use of effective therapies. Thus, an urgent need exists to develop diagnostic tests that are simple, cost-effective, and robust enough to be used in resource-constrained settings with endemic diseases.
Diagnostics Development Priorities for Developing Countries
The top priorities for developing new diagnostic methods pertain to HIV, TB, and malaria. In the field of HIV/AIDS, where the goal is to simplify the diagnosis of HIV, the need is for a noninvasive, inexpensive, and simple but highly sensitive and specific HIV test for saliva, sputum, urine, or other body secretions, as well as tests for monitoring highly active antiretroviral therapy.
In diagnosis of mycobacterium TB, the limited sensitivity of microscopy and the diagnostic challenges posed by smear-negative, extra pulmonary, and pediatric TB emphasize the need to find an alternative approach. In this context, the Gen-Probe Amplified Mycobacterium Tuberculosis Direct Test (Coll and others 2003; O'Sullivan and others 2002) and nucleic acid amplifications assays, as well as serological tests (Perkins 2000), have great potential. Diagnosing latent mycobacterium TB infection using tuberculin skin testing has major limitations, including the inability to differentiate latent TB from active TB. The QuantiFERON-TB test (Mazurek and Villarino 2003), which was approved by the FDA for detecting latent mycobacterium TB infection, and the MPB64 patch test (Perkins 2000), a mycobacterial antigen test (Nakamura and others 1998) specific to the mycobacterium TB complex, are promising and should undergo further evaluation.
For specific diagnosis of malaria, the most useful approach would be a rapid test to determine whether patients who present with fever have malaria. If this rapid test has the capability of estimating parasite density, it may help predict those at higher risk of progression to severe disease or treatment failure.
For the major noncommunicable diseases—for instance, cardiovascular diseases—portable imaging devices, such as radiographic or ultrasound machines, are becoming the new standard for diagnosis. Adaptation of these technologies to settings in developing countries is urgently needed.
Economics of Diagnostics R&D
R&D for new drugs and vaccines poses major challenges in developing countries because of financial constraints and lack of infrastructure. By contrast, both the timelines and the costs of developing diagnostics are significantly lower even though the process of developing diagnostics is in many respects similar to the development of drugs or vaccines. Whereas the costs related to clinical trials and the opportunity cost of funds are lower, the process does have additional engineering requirements. For diseases with relatively large at-risk populations, large and small biotechnology companies have been sufficiently attracted to invest in diagnostic R&D and stand to generate adequate commercial returns even for inexpensive products. For less common diseases or diagnostic indications, industry investment has been minimal, and direct R&D investment by the Special Programme for Research and Training in Tropical Diseases (TDR) (http://www.who.int/tdr) and other public sector agencies or PPPs will be needed if products are to be developed.
Diagnostics activity in the TDR's Product Research and Development Unit currently focuses on two disease areas through work carried out by the TB Diagnostics Initiative (http://www.who.int/tdr/diseases/tb/tbdi.htm) and the Sexually Transmitted Diseases Diagnostic Initiative. This work is done in partnership with academic researchers, disease control experts, public health officials from disease-endemic countries, and industry. The TDR has recently invested substantially in its capacity to support the clinical development and registration of new diagnostics and will work closely with industry, regulatory agencies, and ministries of health in industrial countries and disease-endemic countries to improve the quality and standardization of diagnostic trials and to facilitate the implementation and appropriate use of proven technologies. As an example, the mission of the TB Diagnostics Initiative is to work closely with interested parties to stimulate interest; identify obstacles; and facilitate the development, evaluation, approval, and appropriate use of new diagnostics for TB in LICs (http://www.who.int./tdr/about/resources/contributions.htm). Current activities include research on new diagnostic targets and methodologies, product development programs to facilitate commercial and noncommercial R&D, and formal laboratory and field product evaluation trials. The Sexually Transmitted Diseases Diagnostic Initiative is a 10-year-old collaborative project established in recognition of the critical need for improved diagnostic tools for common sexually transmitted diseases. Its mission is to promote the development, evaluation, and application of diagnostic tests appropriate for use in primary health care settings in developing countries, with a focus on syphilis, chlamydia, and gonorrhea.
Cost Estimates of Diagnostics R&D
No systematic estimates of the costs of developing diagnostics are available that are comparable to the studies for pharmaceuticals. The costs of developing new diagnostics depend on the type of tool; the duration from discovery to approval; and the technicalities involved in technology acquisition, patent fees, market research, laboratory and field trials, marketing and product launch, and support costs. Table 6.1 summarizes costs related to the development of selected diagnostics for TB. Note that these are out-of-pocket costs and do not include the opportunity cost of capital (http://www.who.int./tdr/about/resources/contributions.htm).
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