Day 2 began with Catherina Boehme, CEO of the Foundation for Innovative New Diagnostics (FIND), providing a pipeline overview of new diagnostic technologies emerging from the market. Ms. Boehme believes that at their current stage of development few have reached feasibility, evaluation and demonstration study consideration, though the movement in that direction is eventual. Afterwards she drew on years of experience in technology evaluations to present the FIND approach to developing study protocols and evaluating new diagnostic tests. Following proven templates, and giving consideration to FIND’s recommendations, can ensure a study that produces solid results that can withstand scientific scrutiny. We are certainly well versed in the FIND approach from our participation in the Peru and Vietnam studies.
During the discussion there was continued emphasis on the World Health Organization’s (WHO) Target Product Profiles (as discussed in a previous blog). The highest priority interest is in a screening or triage test, one that rules out the possibility of TB. This would require an affordable diagnostic test that has a high sensitivity and a lower specificity, but can be confirmed by a more specific diagnostic test. Wow! Does this sound like something we have heard before? Connecting the test to a network that can communicate results to physicians quickly is becoming an essential element of the test features.
We adjourned into our smaller group meetings. I participated with representatives from the WHO, NIRT, National TB Institute, and Mahatma Gandhi Institute of Medical Sciences. At different times Catherina and Madhu Pai joined our discussions. The group will focus on technologies associated with smear microscopy. During the discussions it was decided that the group should develop a protocol to evaluate both TBDx™ and ReaMetrix SLR technologies. After much spirited debate it was decided that these technologies should be tested in settings where they are most likely to be first used. So, rather than having one protocol for both technologies, they will be separated. The TBDx™ technology will be evaluated in a reference laboratory[i], and ReaMatrix will be tested in a district microscopy center.
Protocol drafts will be presented to the entire group on Friday. Again, I should stress that these initiatives will require internal funding, however, it was frequently noted that the RNTCP has a keen interest in testing and introducing new TB diagnostic technologies into the country and will give deliberate consideration to the recommendations from the National Institute for Research in Tuberculosis.
At times the discussions outside of the group can be as valuable as the presentations during the meeting. When discussing computer-vision analysis technology, and changes to our algorithms that can improve performance, there was acknowledgement that the improvements could be tested more rapidly leading to faster implementation. Rather than evaluating the improvement in new evaluation studies, it may be possible to test them on the images that were acquired from previous studies. So long as the study sponsors kept the images, it may be acceptable to reuse them to evaluate the performance of new algorithms, thus averting costly new studies.
The discussion then moved to the potential for adding a slide bar as a feature in the TBDx™ application. As more sensitive or more specific algorithms are developed and tested, a slide bar could be used to set the sensitivity or specificity scale to match the intended use of the technology. For example, if the technology was to be used for screening or triage the slide bar could be set to the most sensitive algorithm. If it was to be used for diagnostic purposes, it could be set for the algorithm that is most specific. This is a concept we have discussed at different times in the past, and it was encouraging to hear others explore this concept as well.
In group or individual discussions I have heard an interest in using TBDx™ to assist the Quality Assurance Program, something I also heard quite frequently in discussions at the Union Conference in Barcelona. QA is a vital element of any TB Control Program – checking the accuracy of smeared sputum slides previously read by a local microscopist. Automating that process could not only provide a more consistent review of the slides, but also, TBDx™ could process far more slides. TBDx™ could facilitate an expansion of the QA program allowing for a larger volume of slides to be reviewed, something that would be hard to do if the slides were manually processed.
It has been a terrific workshop. The presentations have been very informative. The group discussions are leading to actionable initiatives. The workshop participants could not have been more professional or more willing to inform you and share ideas.
[i] The Laboratory network for RNTCP in India consists of three designated National Reference Laboratories (NRLs) namely Tuberculosis Research Center, Chennai, National Tuberculosis Institute, Bangalore and LRS Institute of Tuberculosis and Respiratory Diseases, Delhi; about 24 Intermediate Reference Laboratories (IRLs) at state level.