January 28

Prashant Yadav

Rx for Global Health: New drug-diagnostic combos are emerging, but are our market structures ready to support them?

We are experiencing rapid advances in the development of new and innovative technologies that address health problems of the poor in developing countries. Scientists and developers are working hard to create new drugs and new diagnostics for disease conditions such as diarrhea, HIV/AIDS, TB, malaria and pneumonia that afflict mostly the poor. We are also seeing technologies across the boundaries of prevention, diagnostics and treatment.

One area where we see immense potential of technologies to interact and combine is diagnostics and treatment.

As we exhaust low-hanging fruits in drug development for infectious diseases, we may find that our new drug candidates can work well only for selected patient segments. Treatment guidelines for infectious diseases of the poor would then gradually transition from a single global treatment regimen to more patient-customized regimens. We would then need to use diagnostics to identify and segment patients into targeted populations for specific drugs. In the developed world we call this personalized medicine. While low and lower middle income countries are still far from benefiting from the potential benefits of personalized medicine, some examples that require special testing before and during treatment make me wonder if this may not be all that far away.

The lines are blurring

Malaria elimination looks more plausible now than ever before. But for its feasibility (especially for P. vivax) we will need to scale up the use of drugs such primaquine that can reduce the transmission of malaria parasites. However, certain people who have a specific enzyme defect known as glucose-6-phosphate dehydrogenase (G6PD) deficiency have the risk of developing severe adverse reactions from primaquine at higher doses. Scaling up the use of primaquine will thus require testing for G6PD deficiency. (According to estimates there are more than 400 million people with G6PD deficiency.) Current methods of G6PD testing require specialized reagents and equipment, and are expensive and time consuming. New rapid diagnostic tests for G6PD deficiency are now in the pipeline. But for these to be used effectively we would need to start thinking about a platform approach for G6PD deficiency testing and primaquine for P. vivax malaria elimination regions.

As malaria burden for plasmodium falciparum (the more dominant strain in Africa) decreases, many patients in sub-Saharan Africa who presumptively treat episodes of fever as malaria end up taking expensive antimalarials (ACTs), when they actually don’t have malaria. Inexpensive rapid diagnostic tests (RDT) for malaria provide an easy way to diagnose malaria. However, the prices of malaria medicines/ACTs and rapid diagnostic tests are such that the incentive structures do not naturally lead to patients choosing adequate diagnosis. Creating ACT/RDT “price bundles” has been challenging because the market structures do not support such pricing or distribution schemes.

Continuous monitoring of individuals receiving antiretroviral therapy (ART) for HIV/AIDS is important to identify adherence problems and determine whether and which ART regimens should be switched in case of treatment failure. In the past, decisions to switch regimens in low income country settings were based on clinical and immunological monitoring. New guidelines from the World Health Organization recommend the use of viral load testing to assess treatment failure. However, most HIV programs in resource-limited settings still do not have access to viral load testing. Viral load testing is currently done on sophisticated instruments by highly-trained technicians.

A number of new point of care viral load monitoring devices are now in advanced stages of development. Viral load monitoring is also critical for treatment initiation for patients infected with hepatitis C. Given that treatments for hepatitis C are still quite expensive and there are side effects, viral load testing can help understand early virological responses and identify nonresponders for whom treatment can be discontinued or switched. As we start thinking about hepatitis C treatment access programs in resource-limited settings this becomes an important issue to consider.

Abacavir is a drug used in conjunction with other antiretroviral agents in the treatment of HIV/AIDS. Abacavir is generally well tolerated but can cause hypersensitivity in 5 percent to 8 percent of patients. Hypersensitivity to abacavir occurs only in individuals with a specific gene, HLA-B*5701 allele. The U.S. Department of Health and Human Services’ Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents recommends screening for HLA-B*5701 before initiating treatment with abacavir. While the HLA-B*5701 allele is less predominant in African populations, HIV treatment programs with abacvair in Eastern Europe require screening patients for the HLA-B*5701 allele.

Dx-Tx combinations

These examples demonstrate that our traditional ways of looking at diagnostics and drugs separately are starting to blur. In the developed world these combined diagnostics and treatment continuums are putting pressure on pharmaceutical and diagnostics companies to create new business models based on new partnership structures. We are seeing the emergence of some new business and partnership models to cope up with these Dx-Tx combos.

However, in most of the developing world, the structures for financing, procurement and delivery for diagnostics and drugs have not imbibed or fully internalized the need for adapting to this drug-diagnostic platform approach. This creates barriers for the effective use of such technologies in the developing world.

We need new business models for getting these boundary-spanning new technologies to the intended populations in low income countries. What new models and ideas have you seen that address this issue?

We also need a new understanding of market dynamics which does not look at each drug and diagnostics category separately but instead analyzes markets with broader definitional boundaries.

Prashant Yadav is a senior research fellow at the William Davidson Institute and director of the Health Care Research Initiative at WDI.

Health Care
healthcare technology, infrastructure