ReDuX

Last week I wrote about why vaccine development and new vaccines may be important in global health in the coming year, one of which is their cost-effectiveness (they prevent rather than treat).  What I did not note is that, as something that is put into people, assuring their safety and effectiveness is time- and labor-intensive and therefore costly.  The generic cost cited by pharma is $600 million to $1 billion and even the laudable sum of $50 million for getting the new PATH/Gates/WHO meningitis vaccine to market is daunting (my post of 12/16/10).  Another technology lever for global health which has lower development costs, and one that I have posted on previously (c.f., 5/13/10, 7/1/10, 7/15/10), is diagnostics, which are methods to determine who, when, and what to treat and how effective and safe is the treatment.

The list of diagnostics needed for the developing world is long and their specifications are demanding given the under-resourced environments in which they are needed (e.g., Nature:  Diagnostics for the Developing World).  One of the primary PDP (product development partnership) organizations for developing the these diagnostics is the Foundation for Innovative New Diagnostics (FIND) which has an annual budget of about $30 million funded by grants from the Gates Foundation, Google, European Union, Netherlands, Irish Aid, and UNITAD (2008 Annual Report).  FIND is focused on three diseases (tuberculosis [TB], malaria, and human African trypanosomiasis [HAT]) and aims to develop and field test, but not necessarily commercialize, new diagnostics (FIND About), apparently using a build-it-[the test]-and-they-[the diagnostic test companies]-will-come strategy.  However, to their credit, FIND also has undertaken programs in India, Uganda, and Ethiopia to build the human and physical infrastructure needed to utilize diagnostics effectively and hence is working create a market (Community Level Dx).

FIND has been successful in getting two tests to the point of use.  The first is an improved kit for detecting trypanosomic parasite that causes HAT in blood which is now manufactured and sold by the Institut National de Recherche Biomédicale (INRB) in Kinshasa, Democratic Republic of Congo (FIND HAT Program).  The second is a new TB diagnostic and a bit of a head-scratcher to me.  Clearly, better TB diagnostics are needed since TB is widespread (one-third of all humans are infected), highly contagious, deadly (1.7 million deaths per year) especially in HIV patients, and the current primary diagnostic method, looking for the TB-causing mycobacteria in sputum by microscopy, finds only half of the cases, is slow, and doesn’t work well in HIV patients.  And some strains are resistant to a second-line antibiotic, rifampicin and finding them requires a weeks-long test (FIND TB Program).  In December 2010, FIND announced that WHO had endorsed the use of the Xpert®MTB/RIF test, a rapid test for tuberculosis and rifampicin-resistant TB (FIND Press Release).  The test was a result of a collaboration between FIND and Cepheid, Inc., a publicly-held, almost-profitable (annual revenues about $200 million) company in Sunnyvale, CA (Cepheid), that began in 2006 (Another FIND PR) and was funded mostly by the Gates Foundation (amount?) and partly by the NIH/NIAID ($3.3 million, Bizjournal Article).  The assay uses the automated nucleic acid amplification of Cepheid’s GeneXpert platform, basically a very sophisticated table-top machine and cartridges containing all the required reagents to which the sample is added (FIND TB Project).

My head-scratching is because the test doesn’t address the primary need, rapid identification of cases where they occur (local clinics).  According to the WHO “Roadmap for rolling out Xpert MTB/RIF” (WHO Roadmap), because the system requires maintenance, a reliable electricity source, and training and is too costly at about $18 per test, the WHO recommends it be used for individuals suspected of having drug-resistant TB and/or HIV in laboratories at a district and sub-district level (next level above the clinics).   But it seems in making this recommendation, the WHO did not consider the capital costs of the apparatus (its price plus delivery and set up) and its relatively low throughput, which, according to the FIND FAQ (FIND FAQ), is 20 tests in 8 hours (a more expensive version of the reader can do 1000 test/day).  So I’m not sure if these data were used in a cost/benefit analysis which, I would think, would be helpful in making the recommendation.  In the section “About Cost-Effectiveness and Affordability,” the Roadmap states that use of the test will not cost more than 2% of amount budgeted for TB control in the Stop TB Partnership/WHO Global Plan 2011-2015 which seems to me to be a statement about budgeting and not about saving lives and reducing overall costs.

As for price paid by users, FIND apparently thought about it from the start and negotiated a cost-plus price with Cepheid in the collaboration agreement.  Hence the price to health care providing organizations in a designated set of countries is based on Cepheid’s manufacturing cost (using Cepheid’s data) plus royalties (if any) plus a “small margin” (WHO Roadmap), a great approach for both parties.  FIND gives the prices as $17,000 for the box and about $17 for the cartridge (with decreases on volume) and says they are 75% lower than what Cepheid claims to charge buyers in high-income countries (FIND Price List).  Also FIND did a great job in field testing, running both controlled clinical validation studies (1,730 individuals) and demonstration studies (6,673 individuals in six settings) (WHO Roadmap p. 2).  FIND also did a good job in “pre-selling” to potential customers.  The Roadmap states that PEPFAR, USAID, the Stop TB Partnership, the World Bank, UNITAID, South Africa, and India are committed to using or expressed interest in using the system (WHO Roadmap p. 9).  It’s not stated how many units will be purchased or if FIND gets a commission (which they should).

The bottom line for me is that the Xpert®MTB/RIF system will be an improvement by identifying rifampicin-resistant TB and HIV TB cases days sooner, and treatment can start and hence lives and costs will be saved, but it seems like a huge effort to address an (unquantified) part of the problem.  Of course, my hindsight is perfect and, while FIND’s efforts in developing and deploying the system are laudable and are a good model for other global health diagnostics, I recommend that, before committing to a similar effort, FIND do better cost/benefit studies and a better review of competing technologies and approaches.

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