TBDx™ Feasibility Evaluation Launched in Vietnam

Last week Applied Visual Sciences moved one step closer to securing a World Health Organization (WHO) endorsement for TBDx™. Along with our collaboration partner, FIND (Foundation for Innovative New Diagnostics), we installed and trained the management, microbiologists, and laboratory technicians at the Pham Ngoc Thach Tuberculosis and Lung Disease Hospital in Ho Chi Minh City, Vietnam. This particular TB laboratory conducts an extremely high volume, anywhere from 700 to 1,000 slides per day using a staff of eight (8) laboratory technicians.

The primary objectives of this study do not deviate materially from our previous studies in South Africa, Nigeria, and Peru.

  • Determine the sensitivity, specificity, and predictive values of TBDx™ among adult TB suspects, using culture as the gold standard;
  • Compare the performance of TBDx™ to routine laboratory LED fluorescent microscopy (LED/FM); and,
  • Determine the feasibility of using TBDx™ at a high workload reference laboratory.

The secondary objectives of the study are as follows:

  • Determine the minimal training requirements;
  • Determine the time-to-diagnosis compared to routine LED/FM;
  • Assess performance variations between direct and concentrated smears;
  • Determine the performance of TBDx™ as a lead-in triage to Xpert MTB/RIF;
  • Assess the ease-of-use, hands-on time and perceived benefits; and,
  • Identify potential challenges to implementation.

Tosh Sondh, APVS Director of Engineering, conducted the kickoff meeting with the study team officials and installed TBDx™ in the laboratory. Over the succeeding 4-day period he conducted extensive training sessions with the laboratory Director, Dr. Hang, the laboratory Deputy Director, Dr. Ha, and the full laboratory staff.  The training, when combined with the APVS provided Field Manuals, will assist in the successful execution of the study project. The TBDx™ system is connected to the Internet to assist in remote troubleshooting, if necessary.

It is anticipated that the clinical study fieldwork will complete within approximately 30 days. At that time data will be accumulated, analyzed, and reported. That data will form the basis of a publishable article on the performance of TBDx™, as well as add to the mounting data already collected in support of WHO endorsement.

Initial impressions from laboratory personnel were extremely favorable. Dr. Ha, in particular, immediately understood the benefits of automating the diagnostic process thereby reducing human factors limitations, and allowing laboratory staff to be reassigned to other high value assignments.

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BCDx™ Efforts Gaining Momentum

“Cherish your visions and your dreams as they are the children of your soul, the blueprints of your ultimate achievements.”                   Napoleon Hill – American Author

Clinical trials, data collection and analysis, and the completion of scientific validation for TBDx™ remain an intensive effort throughout Applied Visual Sciences and a detailed blog update on those activities will be provided next week.  Current validation of the TBDx™ diagnostic software reduces the demand for new algorithm development and presents an opportunity to redirect our R&D efforts on the completion of the breast cancer detection product, BCDx™, in expectation of filing for FDA approval before year-end.

We routinely receive requests from shareholders, board members, family and friends to apply BCDx™ to suspect breast studies (mammograms, ultrasounds, and/or MRIs).  These studies prove invaluable for our research efforts as they provide suspect cases to test the performance of the technology.  Since BCDx™ does not currently have FDA approval for use, and no one on staff is a licensed medical practitioner, we were unable to provide these interested individuals with a BCDx™ diagnostic outcome.  What we did provide was a report that included BCDx™ processed images of their mammograms along with information on how to interpret the BCDx™ images.  The intent of our report was to provide educational information, in non-medical terms, that the patient could use to better understand their mammogram and to be better educated on the questions they should ask their physician.

Recently we received three cases from women in California, Indiana, and Minnesota.  As we have experienced previously, the cases are from women that are uncomfortable about the diagnostic outcome of their breast studies.  Further, they express a strong desire to contribute their images to assist in benefiting future generations.  Given the developmental stage of BCDx™, we achieve the greatest research benefit from confirmed cases of breast cancer, specifically those cases with multiple years of breast studies. The images received from California provided that level of research value as the woman was diagnosed with breast cancer in July 2014 and had breast studies (mammograms that used the current state-of-art CAD technology and MRIs) dating back to August of 2010.

The moment her 2014 mammogram image appeared on the screen it was immediately visually apparent that she had a significant region of concern that could not be missed by human visual inspection.  BCDx™ identified the lesion’s location and visually presented the various stages of the cancer’s development by characterizing the tissue variations within the cancerous lesion. BCDx™ further indicated that the core of the lesion was distinct and large as represented by the yellow color.  As we have learned through previous pathology reviews, the yellow color response is indicative of necrotic tissue and directly associated with an advanced case of cancer.  The most compelling outcome was that BCDx™ located and identified the cancerous areas in each of the previous breast studies, as far back as August 2010.  BCDx™ diagnosed the cancer development four years before radiologists could identify it.  This is important because earlier detection leads to longer life expectancy.

The radiologist involved in this woman’s case deployed the currently FDA approved computer-aided-detection (CAD) software to assist in diagnosis. The lack of diagnosis in 2010-2013 clearly illustrates that current CAD systems are not a viable solution for assisting radiologists in identifying breast cancer consistently. CAD places marks at areas of concern, but adds no additional knowledge beyond what the human eye can see.  There is no value add to the decision-making process nor is there enhancement in the pathologist’s level of diagnostic confidence.  BCDx™ is a more sophisticated and advanced technology that adds knowledge to the decision-making process through enhanced visualization that represents the cancer tissues response to our algorithms. Further intelligence is extracted from the image and presented to the pathologist in the form of quantitative data about the suspect region.  Increased knowledge increases diagnostic confidence and reduces missed cases of breast cancer.

We all know people or family members who have been diagnosed with cancer.  Some of us have lost family members to complications arising from the disease.  If you or someone you know, have been diagnosed with breast cancer, and you would like to assist us in validating the technology – please speak with your doctor about receiving a copy of your breast studies, for as many years as they are available, on a CD.  Forward the CD to the following address:

Applied Visual Sciences, Inc. • 525K East Market Street, #116 • Leesburg, VA  20176 • Attn:  Tom Ramsay

Please also provide your contact information (preferably an email address) as we may need to contact you for addition information about your case.  WE WILL NEVER DISCLOSE YOUR NAME IN ANY OF OUR MATERIALS – YOUR CONFIDENTIALITY IS GUARANTEED.  We sincerely appreciate your participation in this effort and will return a written report of our findings for your review. You may find it interesting to see the impact BCDx™ may have had on your case.

 

Applied Visual Sciences, Inc. is an image analysis software technology company publicly-traded on the OTC Bulletin Board under the trading symbol, APVS.  The company has developed intelligent, next-generation imaging analytics and informatics technologies for the extraction, analysis, and detection of objects-of-interest within any digital image format (still or video).

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The Kennedy Report – The Sequel

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.

 

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The Kennedy Report from Chennai, India

Sean Kennedy, APVS’s Chief Technology Officer, is representing our interests at The National Institute for Research in Tuberculosis (NIRT) Workshop being held in Chennai, India.

Sean provided the following snapshot of Day 1 ….

The meeting is extremely well attended and the agenda is well organized. There are 7-8 other companies represented at the workshop, including Advenio, Alere, GBD Bio, GeneDrive, ReaMatrix, and TB Biosciences.

The primary objective of the workshop is to introduce NIRT, The All India Institute of Medical Sciences (AIIMS), and other medical and laboratory directors overseeing Indian TB labs to companies possessing TB diagnostic technologies that could potentially be integrated into a laboratory diagnostic algorithm to help in the fight against TB in India. Dr. Madhukar Pai, McGill International TB Centre, and co-chair of the workshop reflected upon the desire of India’s Revised National TB Control Program (RNTCP) to build capacity for enhanced TB diagnostics. That effort requires new diagnostic technologies, which in turn requires scientific evidence to support the diagnostic and operating performance of each currently proposed or future technology. Information generated from these diagnostic test evaluation processes will better educate policy makers on the type of policy changes in diagnostics that could favorably impact the country’s ongoing challenges with TB.

Over the next several days the participants will be educated on the elements associated with well-developed evaluation protocols.  Small groups will meet daily with a goal of crafting evaluation protocols. The intent is to have a specific protocol that could be used to evaluate ALL or some of the diagnostic technologies represented at the workshop.

It is hard to say whether financial support is currently available to fund these evaluations, but the idea is to have a sufficiently well-developed protocol that can be used IF these government agencies choose to move forward.

There are a host of very good technologies represented. Many are molecular-based, though the liquefaction/staining product by ReaMatrix is very interesting. I met one of the principals, and we will be working together in one of the groups.  It could be a nice marriage of technologies. It includes an Auramine-O stain that produces a bit brighter MTB in the image, which was the point of their staining….to help the microscopist “see” the bacilli better.  I don’t know if that would require tweaks to our algorithms or not. But it is definitely worth pursuing.

The TBDx™ presentation went well from my biased impressions. One important fact was made abundantly clear – smear microscopy remains a routine diagnostic approach and is not likely to fade from usage for many more years.  I was asked many very good questions that I took as a sign of high interest in automated smear microscopy. I am confidently hopeful that TBDx™ will be included in the process to develop a protocol to evaluate our technology, and I’ll know more about that as we start the small group meetings starting tomorrow.

Additionally, I will have an opportunity to visit the National and State Laboratories located at NIRT this week, and hope to see a local laboratory later in the week.

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TBDx™ in Nigeria

As mentioned previously, Applied Visual Sciences was invited, as a stakeholder, to the launching of the Nigerian National TB Prevalence Survey Report & National Strategic Plan for TB (2015 – 2020). The event spanned three days from November 18th to the 20th, and was held in the capital of Abuja.

The motto of the event was, “Support TB Elimination in Nigeria. Let’s end TB now!”

Some startling numbers emerged from the Report:

  • In 2013, for every 100,000 persons living in Nigeria – 338 persons developed TB (from the 2014 WHO Global TB Report)
  • In 2013, Nigeria accounted for 15% (about half a million) of the global gap in TB case notification. (from the 2014 WHO Global TB Report)
  • In Nigeria, this gap equates to 83% of estimated total TB positive cases.

Much of the reporting gap can be attributed to the passive nature of TB case detection around the world. Patients must come to the diagnostic health facilities.  In an active diagnostic program the healthcare diagnostic applications would be targeted and delivered proactively to the source of the disease, generally economically distressed areas of big cities or very remote villages.  TBDx™ has been clinically evaluated and proven as a cost-effective screening or triage device that can be easily incorporated into an active case finding initiative. Furthermore, combining TBDx™ with a confirming molecular test can potentially result in cost reductions of up to 75%.  Those cost savings could be used to offset the costs to paradigm shift to active case detection, and to positively impact the transmission rate of TB.

During the opening ceremony, awards were given to those individuals and organizations that have significantly contributed to the fight against TB in Nigeria. We are extremely pleased that our study and research partner, Zankli Medical Center, and in particular Professor Lovett Lawson, were recognized with an award of accomplishment. As evidenced by the award, Professor Lawson and Zankli are at the forefront of TB research in Nigeria.

Representing APVS at the conference was Tosh Sondh, Director of Engineering, who was asked to demonstrate the 200-slide auto-loading, high-volume edition of TBDx™.  Tosh also had the opportunity to conduct one-on-one demonstrations and technology discussions with each of the Nigerian State TB program managers (NTP). Given that these managers rarely leave their states and experience new technologies, it was an opportunity for them to experience TBDx™ in action. Needless to say, interest was very high from those in attendance.

Tosh’s final trip report from Nigeria provided the following summation of the conference, “It was a very intense and emotional event, one that highlighted the need for affordable and accessible TB technologies. Many NTP managers came up to me and expressed interest in installing TBDx™ at their labs”.

Nigeria remains a TB hot bed in many ways. One from a research point of view, thanks to the dedicated efforts of Zankli Medical Centre and Professor Lawson, and from a TB prevalence point of view. TB cases are going unnoticed. Fortunately for all those concerned, TBDx™ is a low-cost, automated, and consistent technological weapon that can be rapidly deployed and utilized in the fight against TB.  Due to the high interest in TBDx™, Nigeria will reside at the top of our sales efforts.  World Health Organization endorsement will open the door to global funding acceptance, which in turn will provide Nigeria with the financial support to acquire TBDx™ in the coming year.

In accordance with the event’s motto, APVS is proud to commit our support to the elimination of TB in Nigeria and elsewhere in the world.

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