Technologies to Improve Early Cancer Detection in Low Resource Settings: Idea to Field Evaluation
good morning thank you for joining us today I'm Paul Perlman a program director and the lead for Global Health technology at the NCI Center for Global Health in 2021 in commemoration of the CGH 10th anniversary we launched the NCI Global cancer research and control seminar Series in this series we feature Talks by researchers and cancer control experts working in global oncology and provide opportunities for discussion and collaboration around impactful and Innovative work that addresses cancer morbidity and mortality worldwide in today's session I'm very happy to welcome Dr Rebecca Richards Gordon Dr Richard's Cordon is the Rice University Malcolm Gillis University professor of bioengineering the director of rice 360 Institute for Global health and serves as a special advisor to the Provost on health related research and educational initiatives her research has been instrumental in improving early detection of cancers and other diseases especially in low resource settings she's currently working with colleagues and undergraduate students to develop a nursery of the future to provide Technologies necessary to reduce neonatal death in sub-Saharan Africa to rates equivalent to the United States Rebecca's research has led to the development of 40 patents she is the author of The Textbook biomedical engineering for Global Health more than 230 refereed research papers and 11 book chapters her teaching programs research and collab and collaborations have been supported by grants from the National Cancer Institute National Institute Institutes of Health National Science Foundation the U.S Department of Defense the Howard Hughes Medical Institute the bill and mobile Melinda Gates Foundation the Whitaker foundation and the Virginia and Ellie Simmons Family Foundation in addition Dr Richards Gordon is a member of numerous academic associations including the National Academy of Sciences the National Academy of engineering and the American Academy of Arts and Sciences as a member of both the National Academy of Sciences and the National Academy of engineering she has the rarest station of dual membership in the National academies in 2016 the American Institute for medical and biomedical engineering presented its highest on Earth the Peter galletti award to Dr Richard's Gordon in 2008 she was named a Howard Hughes Medical Institute professor and subsequently received a grant for the undergraduate Global health program at Rice this program won the science prize for inquiry-based instruction from Science magazine and the lemelson MIT award for Global innovation I'll add on a personal note that Rebecca was a pi on one of the first Grants awarded by the center for Global Health becoming likewise an active member in the first cohort of the NCI affordable cancer Technologies program investigators as such I've personally benefited immensely from her expertise and contributions to that program before turning things over to Dr Richard's Corden for her presentation today I'll go over a few Logistics please note that today's presentation is being recorded and will be available on our website at cancer.gov Global Health you can find information about future presentations on our site and by by following us on Twitter at NCI Global health questions will be addressed during the designated q a Time immediately following the presentation during that time you may either use the raise hand feature under under found under reactions and wait to be called on or type your question in the chat box if called on please unmute yourself and ask your question we'll now begin our presentation welcome Rebecca um it's really such a pleasure to have the opportunity to join you all today and share the work that our team is doing to develop Technologies to improve early cancer detection in low resource settings and what I wanted to do in my talk today it's really just think about um what are the challenges that our team has encountered as we have worked along the Spectrum from idea all the way to field evaluation and what are the lessons that we have learned and and hopefully are are useful and can be the point of some interesting discussion in the Q a today and so what I wanted to do was actually to start by acknowledging a lot of really important people without whom today's presentation would not be possible first the team at Rice University particularly the work of Dr Chelsea Smith and Jackson cool and David brennas Brady hunt and Sonia para I will feature a lot of work that they did as part of their PHD studies second the really wonderful collaborative team at the MD Anderson Cancer Center led by Kathleen schmaler Ellen Baker and Mila Salcido they are just fantastic collaborators without whom the work that I will share would not have been possible our collaborators at the NCI Dr Bill castle at Baylor College of Medicine Jane montiallegra and Michael schurer at basic health International in El Salvador Mauricio Mazza when he was there and at the barrettos cancer hospital and and berettos Brazil and also in Mozambique at maputo Central Hospital Dr Cecil Tina laurenzoni and then finally I'll share a little bit of work at the end in collaboration with Malawi Polytechnic and the team led by Theresa McConnell I'm going to focus a lot of what I share today on cervical cancer but we're doing similar studies for a lot of different epithelial cancers early detection is really important impactful but not happening in too many low resource setting so the the kinds of things that I'll describe today with cervical cancer we have similar studies underway with oral cancer with bladder cancer with esophageal cancer I think these approaches um can be used for many different types of epithelial cancer and what is unfortunately true for many of these epithelial cancers is that when you look at the global burden of disease as you see in the upper left and this side you see that the global burden of disease is concentrated in low income and underserved regions of the world and within countries if you look at the lower left you can see that within my own state of Texas and the Rio Grande Valley those four counties of the southern tip of the state we have 55 percent higher rates of cervical cancer and that is attributed to a lack of screening in that region fewer than 10 percent of eligible women who are uninsured are actually receiving screening the low resource settings this is a challenge of a lack of Financial Resources a lack of Health Care infrastructure and also a lack of trained Human Resources the map on the right side of the slide shows the number of people per pathologist in different African countries and you can see in the United States or the United Kingdom for reference there's roughly one pathologist for every 15 to 20 000 people and a lot of African countries that ratio is something like one to a million or one to five million and so as technology developers we need to think about this context of lack of Human Resources lack of healthcare infrastructure and lack of Health Care spending when we think about cervical cancer and there we go when we think about cervical cancer progression again the same type of progression from pre-cancer to cancer is a common feature of a lot of types of epithelial cancer the vast majority of cervical cancers are caused by infection with the human papilloma virus and when HPV DNA becomes integrated into the host genome you get the expression of the viral oncoproteins E6 and E7 and these allow for the progression of dysplasia to go through low-grade to high grade dysplasia and in some cases the development of invasive cancer and so in focusing on screening we have this opportunity to identify pre-cancerous lesions and intervene by excising tissue and preventing the development of cancer we also have primary energies with vaccination HPV vaccination but again the challenges associated with scale-up of HPV vaccination are similar to the challenges of scale up of good screening Technologies there's a bit of a lag and advancing my slides sorry so let's think about what works in high resource settings so at a high resource settings what is recommended is screening and okay you can screen with HPV DNA testing for example every five years you can see the sepia Gene expert test is one example of a good HPV DNA test or cytology the pap smear every three years women who screen positive then are followed up for a confirmatory diagnosis and typically that's done with a combination of colposcopy biopsy and histopathology and the women who have biopsy proven high grade disease are typically treated and there are a number of treatments that can be performed in an outpatient setting including cryoablation thermal ablation or The Loop electrode surgical excision procedure these together are very effective and when combined with primary prevention of the HPV vaccine we really have so many tools at our disposal to eliminate cervical cancer require money they require infrastructure and they require trained Personnel that simply are missing in many low resource settings and to give you a sense of that context I have a couple of photos um from some of the places where we and our colleagues have worked and so if you think at the community level the photo on the left was taken at a community health center in the DRC by one of our collaborators from University of North Carolina and you can see in this laboratory setting you've got basically a light microscope and a little hand crank centrifuge and no electricity um and really no effective supply chain for supply and reagents and contrast that to a tertiary Hospital in Ethiopia on the right and this is a laboratory where in particular pep bar put a lot of improvements to bring laboratory uh infrastructure up to a level that can support automated analyzers and things like the the gene expert test so you have sort of a very wide range of types of diagnostic settings when you work in in low resource settings and so in light of that if we look at who recommendations for cervical cancer prevention the recommendations are either HPV dna-based screening and a screen and treat approach so use screen with the HPV DNA test women starting at the age of 30 years and then simply treat all women who test positive we know that this results in some rate of over treatment but it's judged to be an acceptable rate of over treatment given the benefit of cancer prevention and and sufficient resources are available and an alternative strategy to minimize those rates of overtreatment is to implement a screen triage and treat program where you screen women again with HPV DNA testing then Implement a triage test to determine which of those screen positive women do need treatment and then follow up with with treatment and so um and thinking about as Engineers as scientists as clinicians who are collaborating together to think about how we develop approaches that are that will result in Equitable detection of early cervical cancer what I wanted to do today is really focus in on uh four themes so the first is can we provide molecular diagnostics for cancer screening that can be used at any Clinic anywhere the second is can we follow that up with triage tests that allow early cancer detection in Rural and under resource settings and can we better job of sort of pinpointing where diagnostic biopsies should be obtained or where areas of pre-cancerous or neoplastic tissue should be surgically recepted and then finally can we provide the ability to do expert pathology at any Hospital anywhere so I want to share just a little bit on each of these four themes about um the the things that are important as an engineer and and thinking about those four at the about a place on the hospital where technology goes when it doesn't work anymore this is a hospital in blantire Malawi but many many hospitals in low resource settings have a similar room that often is referred to as the equipment graveyard where devices that no longer function are are taken often they can't be repaired because of lack of spare parts and very important to think about this mean for the design strategies that you should use and I personally think we all should think through the lens of devices should come with morning stickers if they're not used they can't be helpful and how how do we think about design so that Technologies can be used consistently over time and so let me Focus first on molecular diagnostics for cancer screening and share a little bit of what we've been doing to develop point of care HPV DNA testing if I think about this available in high resource settings there are tests that are based on hybrid capture the digene hybrid capture test or there are tests and and the care HPV test or there are tests that are based on PCR amplification for detection of HPV DNA that's the gene expert test is a good example of that with requiring infrastructure that is expensive having a per test cost that can be a barrier the most sensitive test is Gene expert but at 15 to 20 dollars a test it's expensive we have been developing point of care tests based on the hybrid capture approach as well as amplification of DNA and I'd like to share just a little bit um both the accomplishments and challenges of those approaches we started looking at hybrid capture which basically is an alasa based approach to detect the presence of high-risk HPV DNA so you take your sample you denature it the HPV DNA is hybridized with complementary RNA of high risk types and then you use an Elisa strategy to detect those RNA antibodies detection antibodies that are functionalized to produce a chemyluminescent signal and in the care HPV test this is done basically um in a 96 well played there's been a lot of advances in two-dimensional paper Diagnostics and our team has developed a two-dimensional paper and plastic device that can implement the hybrid capture reaction and so you cellulose strip running along the right side and then a series of glass fiber pads that contain the lyophilized reagents that are needed to sequentially deliver the reagents to perform the hybrid capture reaction and so how is this test used on the left in this photo you see all of the tools that are needed to implement the test so the sample is collected with a swab placed in a tube of a Tris based buffer then you would take using an exact volume pipette and transfer an amount of the sample to a lysis tube that contains lyophilized ACP key to lice the cells and lyophilized RNA hybrids to capture the high risk DNA of its present it's heated in a heat block at 95 degrees C for five minutes and then placed on the sample collection pad and step four there then you rehydrate all those reagent pads and they contain sequentially the detection antibody and then your your calorimetric reagents and and wash buffer steps you fold it closed so that those pads containing the rehydrated reagents are now in contact with your nitrocellulose strip and you'll get sequential glow of those reagents down the test strip so things will flow past the capture antibody and you'll actually carry it out the reaction and you can read it out visually um there's a brown precipitate that forms at the test line and so we evaluated and optimized this assay sorry just be predictable with the slide advancement here we optimized and tested things using um four targets of increasing biological complexity we started with perfectly complementary short HPV DNA synthetic targets and and RNA probes we then moved to full length HPV DNA using the RNA probes from kyogen we then moved to HPV positive and negative cell lines and then finally to clinical samples great results with the short synthetic Targets on the left you see results with the digene hybrid capture assay using the same targets on the right you see the HPV DNA paper assay the signal to background is plotted on the y-axis we have decreasing concentrations of high risk HP mean DNA on the x-axis and then very importantly a test with low risk HPD DNA at high concentration because we don't want the test to be positive in that case and so you can see we have a little bit better limit of detection with the digene hybrid capture assay but a good limit of detection with the paper assay we then moved to full length DNA again testing decreasing concentrations of high-risk HPV DNA with the paper assay on the left the digene hybrid capture assay on the right and testing the low risk HPV DNA because we don't want false positives there and we have similar limits of detection with the paper assay and the digene hybrid capture assay finally moved to cell lines so we looked at an HPV positive cell line seahaw cells and HPV 18 positive cell line Hela cells and we mixed these together with an HPV negative cell line c33a cells so we kept in all these experiments the total number of cells constant but we decreased the fraction of HPV positive cells and you can see that we get clean negatives with the c33a cells our limit of detection is about 1 times 10 to 5. seahaw cells per ML and 1 times 10 to the four uh or ML and we were able to test this with our lysis procedure using lyopalize reagents and all of the reagents were like authorized on the paper strip and so we were really excited at this point now with all of the control samples that we wanted to test and we moved into looking at clinical samples and so here we tested clinical samples these were provider collected clinical samples that were collected in El Salvador and collaboration with Dr matzah and his team there the gold standard here was the clinical care HPV assay and we selected eight HPV positive samples and eight HPV samples and these samples were tested in a lab in a high resource setting all of the reagents were lyophilized on this strip and it wasn't a field evaluation we didn't try for the strips to a low resource setting and you can see that we were able to get clean negatives on all the negatives and we had one false negative in this evaluation and so next we moved to do a field assessment so again we lyophilized all of the reagents and we took everything to Mozambique now in Mozambique our gold standards a clinical gold standard that's being used is now Gene expert which is a more sensitive both standard and in addition to that these are now self-collected samples collected samples that the concentration of cells is higher and we could see that the samples were significantly more turbid than the samples that we had been testing from El Salvador and you can see again we tested eight HPV negative samples a high-risk HPV positive samples and our results weren't as good and and prior to testing the clinical samples we tested the lines that we transported with us with the fully lyophilized reagents and we got great results everything looked beautiful the HPD positive cell lines were positive the HPV negative cell lines were negative so we were able to successfully transport a sample but all of a sudden you know we weren't getting the same sort of separation between the positives and the negatives and to make a long story short um the the secondary structure associated with cellular RNA is a problem that can drive false positives in a paper-based Elisa it doesn't cause problems when you do this in a 96 well I'll play it but when you do it on a nitrocellulose platform it can lead to false positives and so we took a step back and instead of working with the lyapolis reagents we worked with liquid reagents and we added rnas to our sample preparation strategy and when we did that what we found now what we're looking at on this right graph is the signal to background for our HPV negative and positive samples before and after this rnas treatment and you can see that our false negatives the signal from the negatives goes down the signal for the positives goes down but not to the same degree and we get a little bit better separation and so what this said to us is that it's so important that this process of optimization of the the sample processing happen in field settings with the same kind of samples that you will be testing in those field samples and so I think the um we're working to continue to improve that sample processing procedure to further reduce the amount of secondary structure that gives rise to the the sum of those false positive results and in addition to that we're also working to incorporate a cellular control so that at the concentration of cells is too low that that you are aware of that and your assay and that's something that's missing from the carry HPV assay but included in the gene expert assay for example at the same time we're also exploring assays that are based on the amplification of nucleic acids to get more sensitive results and we've been collaborating with a company called axin to implement an isothermal amplification assay that's based on recombinase RPA amplification um and um in that strategy there is a battery powered device that is used to provide Heat at two steps in the reaction One during the sample processing procedure and one to power the isothermal amplification and so to implement this assay again you would collect the asset the sample using a swap transfer it to the license to incubate that license to burst at room temperature and then at a higher temperature in the heater transfer the lysate to the amplification chamber that contains the lyophilized enzymes for the RPA amplification procedure and heat that amplification chamber for 20 minutes finally take the amplification chamber and twist it on to a lateral flow cartridge that's completely enclosed and then the amplicons run down the lateral flow assay and you can read it out again visually you can see the control line and the two test lines in this case and so we've evaluated this again using clinical samples that were were self-collected in this case and we compared the results to quantitative PCR okay was detecting hpv16 and HPV that are both 16 or 18 positive as well as a number of samples that were negative on the y-axis you see the test line signal from this assay on the x-axis you see the concentration of HPV DNA and you can see above three log copies per reaction we have really excellent results with the assay we also have completely clean negatives and so we need to push the limit of detection down a little bit to be um you to limit a detection that is possible with PCR I'm thinking about what is necessary to move molecular Diagnostics forward we really need to focus on integrated sample to answer testing systems that incorporate sample preparation I think this is an often overlooked component of an assay that often needs significant optimization and I'm thinking about how are tests like this distributed our team and Mozambique still has so many challenges with distribution of Gene expert which is commercially available um and you know the distribution and covering the cost of this test is today still a very significant Challenge and then thinking about how the health system comes together to close the gaps between testing and between treatment so I want to turn now to thinking about once women screen positive and you'd like to do something to confirm that positive test what are the uh what are the opportunities for low-cost Technologies I don't want to share two technologies that I think are really exciting that come from other groups that I think really will change the future of cervical cancer screening and diagnosis and these are digital coposcopes the first is one developed by mobile ODT you can see it's based on a cell phone and it captures a digital image of the cervix and there's been a lot of work to develop AI based interpretation of those digital images for automated diagnosis and then on the right you see the pocket colposcope which was developed by an enemy ramanujam and her team at Duke University also has been commercialized and FDA cleared generates really beautiful digital images of the cervix and we have been collaborating with nimi and her team to think about how to combine those digital images with high resolution images and so I want to share now a little bit of work that we have been doing here you see the mobile ODT coposcope in a clinic at barretto's cancer hospital together with a high resolution fiber optic microscope that can be used with the guidance of a digital coposcope to get the same kind of images of the cervix with cellular resolution that can help whether a region in the cervix is normal as you see on that image in the lower left contains high pre-cancer these little white dots are actually the nuclei of cervical epithelial cells and you can see that increase in nuclear size the nuclear crowding and the nuclear pleomorphism and you can do this in Vivo with that fiber optic probe just in contact with the cervical epithelium and with the develop micro-invasive cancer you can actually see the angiogenesis in the image on the lower middle of the screen you see blood vessels associated with angiogenesis and that micro Invasion and so through the affordable cancer Technologies program we were supported to develop and evaluate this high resolution microscope in Brazil and we demonstrated that you could implement this on a mobile screening van that traveled out to rural areas of Brazil and we were able through a combination of the mobile van and Imaging at a central location at the barrettos Cancer Hospital to evaluate the performance of this compared to colposcopy and biopsy and in a study of 1500 women what we were able to show is that compared to expert clinical impression through the coposcope we had similar sensitivity for the detection of grade 3 cin our sensitivity for both Technologies was 96 percent and similar specificity for cin3 detection our specificity for the high resolution micro endoscope was 59 for colposcopy was 57 and you can see the ROC curve in the um the graph on the upper right we found that if we combined the high resolution micro endoscope image with the results of an HPV test we're able to ship that Roc curve to the left the ROC curve goes up by um about point one um to to 0.9 for the ROC curve and we gain a specificity uh boost of about 10 by having the results of the HPV test available at the time at the Imaging is performed and similarly we've been able to use the same approach in Mobile clinics in Texas here uc1 and the Galveston area and so as we think about the opportunities with imaging as a technology to improve early to cancer detection for women who screen positive we have a lot of opportunities to leverage advances in consumer grade Optical equipment it's really really important to do large-scale field evaluation of this but it's also important to partner with a commercial partner that has an enduring commitment to distribution in low resource settings and here I think on the work that the Duke group has done in particular is really addressing such an important challenge here and I think it's a model that all of us can look to so I wanted to turn um and in the last 10 minutes here to thinking about two important other topics how can we provide better guidance for Diagnostic biopsy and surgical resection and and here we're thinking about the ability to combine other advances in commercial grade technology and so here we're combining the ability to do wide field Imaging um like with the the digital coposcopes high resolution imaging and then Digital Light projection and so in the system that you see here it's being used to image the tongue we're also you'll see in a minute using it to image the cervix but what we're able to do is capture a wide field image process it and then project onto the tissue with a digital light projector an outline of exactly where you want to image with high resolution so in that middle photo on the top you see that blue outline that's to guide the operator of the high resolution imaging system where actually to move that probe and then we can capture images I'll play a video here we can capture those images at a very high frame rate I think the video is going to encounter some struggles with my band but you can capture those images at very high frame rate as you move the probe and you can track where the probe actually was on the tissue and you can build up mosaics of those high resolution images or you can track here now we're doing the same thing in the cervix so you see an image of the cervix it's been stained with blue balls iodine and I'm going to play the video as the probe is moving across first this lesion you can see the images update in real time the graph on the right is scoring those images and things that score above that red line would be high grade pre-cancers and so we'll move across the first lesion you can see the nucleic nuclei get a little bit bigger here now we move into an area of normal tissue and we'll move back into now the second lesion and you'll see the nuclei get a little bit larger here in the second lesion but they're all scored under the threshold and so um we can after the Imaging procedure has been completed we can display for the clinician exactly where the probe tracks they can see that it went through that first lesion which had a clinical impression of low-grade um disease a biopsy was taken in the place where that blue circle is and the biopsy came back with cervicitis and the second we Asian again you can see where the biopsy was and the the clinical impression was a low-grade disease and the biopsy came back just with inflammation and so by combining all of these very affordable Technologies we're able to integrate all of this information and do spatial co-registration and I think the same thing can be done with low-cost confocal Imaging with low-cost vascular and Imaging and we can actually project right onto the tissue to help guide clinical actions like biopsy or like surgical resection and so we need also to do large-scale field evaluations and we have an academic industrial partnership Grant where we are just carrying out a large-scale field evaluation again in collaboration with barreto's cancer hospital in in the case of the cervix so fine briefly some work we're doing to try and make pathology more available at hospitals and so if you think about the resources that are needed to do surgical pathology when a tissue is resected we want to examine that under a microscope and there's a lot of infrastructure that is required to determine whether the margins of that resected tissue are negative or positive when we think about all of the infrastructure that's needed when the resected sample is taken out it's sent down to the Pathology lab and it's red lobed with a scalpel or a razor blade a pathologist would select what slices to examine typically for frozen section those will get processed sectioned into four Micron thick slices stain with an automated slide stainer and then finally they get examined under the microscope and so we've been working with a collaborator here at Rice Ashoka raghavan procedure where you could steam the tissue at the topical die and take the those that have just been dipped into a topical die and place them right on a fluorescence microscope and automatically report the margin status possible with conventional microscopes with conventional microscopes if you want an image with high resolution you have a very narrow depth of field and if you just cut tissue with a scalpel the undulations in the surface profile are much greater than your objective focus and so you end up with blurry images you have to serially refocus across your sample and so that's why we spend all the time and resources to make those very thin Frozen sections what we're doing with Dr Vera ragavin is to introduce a face mask into the brain of the microscope and It Coats the light field to um help make a point spread function less dependent on depth and what that allows us to do is use a neural network to reconstruct the image so that the image is in Focus all across the entire sample and so I'll show you summaries next slide but we're able to extend the depth of focus by about an order of magnitude and so here you see this is a a um a slice of oral tumor that's been resected it's been dipped into a solution of fluorescent vital dyes and then just placed onto a slide on the stage of this fluorescence microscope and you can see in additional images that um are shown on the right side of the slide the conventional images are in focus in some places and out of focus in a lot of places in contrast a deep depth of field microscope or the Deep doff microscope the images are clear and in Focus across the entire specimen and so we're working with Dr Rivera Ben and our colleagues at MD Anderson to implement AI based interpretation algorithms as well and I think by improving our Optics we're able to eliminate a lot of the need for sample processing with better vital dyes and staining protocols potentially this could incorporate molecular Imaging and as I said with deep learning we have the potential to um incorporate real-time analysis and so just coming back to um those those four topics I think we have the opportunity to improve cancer screening to improve cancer detection to improve biopsy and surgical guidance and to improve the ability to do pathology at the same time I think it's really important to how do we approach Equitable technology development how do we democratize the development of these Imaging tools and how do we really demonopolize that process we have been working with a number of African universities to do just that to really work with faculty and resources at these universities to strengthen the ability for Hands-On engineering design and connect that to clinical challenges at the partner medical schools for many of these African universities so the photos that you see here come from the University of Malawi Polytechnic where with support from the Wilson Foundation we were able to really strengthen the rapid prototyping technologies that are available and then put together multi-country multi-disciplinary teams to develop Technologies to improve neonatal care here you see a CPAP device developed by those teams but also to enable the development and the scale up of Technologies for um uh covid and it's a really advancing quite slowly so I'm waiting for the next slide to come up but during the covet pandemic these Design Studios were able to develop base shields for example um that um were provided to health care workers they were able to develop hand washing facilities hand washing systems that were disseminated and they were able to also develop devices for Respiratory Care I just want to with one last technology that relates to early cancer detection that came out of these Design Studios so there was a partnership between Malawi Polytechnic and rice to develop something called Lucia which stands for a low-cost Universal cervical cancer instruction apparatus and this is basically a model of the female reproductive tract that has those that show aceto whitening that demonstrate all of the low-grade and high grade and invasive cancer lesions that are encountered when people perform via when people take uh samples for HPD DNA testing when they do colposcopy it allows them to test thermal ablation it allows them to practice doing leaps you can see here the system being used in Mozambique some of the students who developed it in Malawi were able to participate in that and this device has been used by the the MD Anderson Team all throughout Texas throughout the US and in many different African countries to help provide training for healthcare providers that are learning how to implement cervical cancer prevention and diagnosis and treatment so let me stop there thank you so much I'm happy to take any questions that you might have so uh thank you Rebecca for a great presentation and for covering some of the Magnificent breath of your work um we are going to open for questions if people are able and comfortable we invite you to turn on your cameras so that we can see you for the Q a portion and as a reminder if you have a question or comment you can either use the raise hand feature uh found out our reactions and wait to be called on or type your question to the chat box and uh we'll try to get to as many as we can um I am going to use the chairs prerogative um and ask a question up top I had a somewhat Downstream question for you Rebecca um we all saw throughout the pandemic uh the impact of global life Supply chains on diagnostics manufacturers and really access to Diagnostics in general especially as it related to nitrocellular swabs reagents various resins and vtm and all such challenges are unfamiliar to to many in the U.S this is uh pretty persistent in many lmic's and I was curious curious to
what extent you have strategies that you bring into the earliest sort of design stages of new technologies and interventions to that to sort of think about being resilient issues of scarcity I think it's such an important question and it's it's an everyday problem in low resource settings it's not just a pandemic problem as you noted um and you know I think there's sort of two um there's two competing factors that I think it's really important to think about so one is I think as technology developers I think nobody wants a different set of regulatory standards for high resource settings and low resource settings we don't want poor Technologies for poor people and I think um thinking about what regulatory standards are important and appropriate the decision that our team made for our newborn Care Project was really we're requiring one of the big five regulatory agency approvals and we're required requiring production in an ISO 13 485 environment and I just personally think there is no substitute for that it does require investment it does require infrastructure but I don't think there is a substitute for it that is appropriately safe means if you're going to substitute a reagent you have to really track all of those substitutions and you have to validate all of those reagents I think you can do some of that up front so that you can specify um you know these three types of pad choices are validated and appropriate or you know these three brands are appropriate and I think it's smart to do that all of us learned that in the pandemic um so I think it can be done up front but I think it needs to be done and the right regulatory framework as well thank you um I saw um a Ashish next uh if you'd like to unmute yourself and ask your question thanks Paul uh excellent talk Professor Rebecca loved it um I had a couple of questions one was um uh the the mobile ODP solution that you showed um how cost effective it is I just briefly looked up the website it seems to be a for-profit company so I was just curious uh for the uh deployment that you had did you did they have a like Gratis deployment because it was in a low income country and uh the second question I had was uh have you uh had any deployments in India I'm based in India and I would love to collaborate I was just curious have you had any discussions or deployments in India thank you love the talk so we haven't had any deployments in India for our cervical cancer project we did some work related to oral cancer there um but not with cervical cancer my understanding and I don't want to speak for mobile ODT but my understanding is that the company made a business decision several years ago um to focus more on higher income settings and um there was an original commitment at the company to focus more on on low resource settings and then there was a change and I think you know that is a risk of partnering with any for-profit company is you know at the end of the day it may have business decisions that they have to make I think um I forget about commercializing Technologies from our own side I will say we have partnered with both non-profit and for-profit organizations I think when you think about prioritizing markets and low resource settings it is a huge challenge whether you are a for-profit or a not-for-profit it is a huge challenge just to cover the cost of manufacturing and distribution and break even and so I'll give you an example from our CPAP device that we've developed um you know in that case the cost of goods for the CPAP device it's somewhere around 800 it's sold for 900 so it's sold just to cover the cost of goods distribution in low resource settings you have to plan on adding a back drip to to cover the cost of distribution I wish it wasn't true but it is true and it got even higher in covet because international shipping the price of it skyrocketed and so um they're very real tension and a very real challenge in going to get to scale who is going to write the check pay for the cost of the technology and the cost of the distribution and and um how do organizations that are trying to do that survive and cover their costs it is it is not easy um and I think it it doesn't in my opinion it doesn't get as much attention but it it needs to because um it's a it's a huge problem you can look at you know I think gradient is another example of here's a company they make anesthesia machines for low resource settings and they have a great product in my opinion I have nothing to do with it I just I'm an admirer of it I think it's a great product um and I think you know it's another example of a company that um struggles with this challenge of how do you balance somehow you got to cover your costs but you want to keep the price as low as possible so that people have access to it and a quick quick addendum uh do you feel um training is key because uh you do an initial deployment and then the day-to-day has to be carried out by your partner there so it's very critical to do high quality training and do you like do you visit them often and periodically assess how well they are doing and tell them about new versions and how to improve I think yeah training is absolutely essential and I actually think that's kind of an overlooked area for technology developers thinking about how you how you pay devices that can build Hands-On skills and do um low-dose high frequency training is really critical um we have a collaboration in our neonatal project in Nigeria and one of the big challenges in Nigeria right now is brain drain like you you have so many nurses um who they get trained and then they get a job in another country with a better salary and they leave you're just constantly training and reach training and retraining because there's so much rotation on the clinical team and so thinking about you know affordable tools that can help quickly build and assess competency I think it's a really um uh it's an under explored Niche for technology development great thanks I I see uh ramillas next hello uh uh thank you Rebecca it was a really excellent presentation and a very informative for me and I also I'm ramila from China also focusing on the cervical cancer prevention especially in low resource settings and regarding to your last uh part which is like slide three past five pathology I have a question like in China our practice would be like that if the woman um had biopsy in the preliminary hospitals and diagnosed with high grade Nations and they will be referred to the higher level hospitals for the treatment and if the high uh when they go to the higher level hospitals and if sometimes the doctors from higher level hospitals cannot like confirm their uh like disease status they will ask the woman to take back their Prime free uh preliminary pathology slides to recheck and confirm their disease status to decide the next step of treatment so if we use the slide free biopsies then how can we like track back to their primary biopsy status if we have like a dilemma afterwards thank you yeah I think that's a great question you know I think the digital images would be available um and and could be stored and shared but I think you do lose the ability if you want to recut the sample for example um that's not possible with this approach it's an important issue that you raise um I think that you know that work is at a very early stage um and and sort of thinking about what are all those issues and and um what would you need to be sure that you could enable at the follow-up stage is an important consideration yes thank you thank you uh let's go you're on mute your muted okay can you hear me now yeah okay uh great to see you Rebecca wonderful great great talk and so nice to see how far the project has come and all the new things that has you've added to it um a couple of things just to follow up on the previous question the tissue you said you'd have the digital images but could the tissue be saved could that be frozen so that later on it could be cut or re re-examined yeah for sure you could either preserve it or preset yeah so at least that that would be something that uh if some if somebody wanted to go back and recheck then that would be an option um the issue of uh cost for manufacturing a device you were talking about that we've had those discussions and it's it's a major problem um one of the solutions I think we had or an idea was to have um manifest get get the you know device manufactured in the in the country where it's going to be used if you can find someone there and partner with them then the cost decreases right because you don't have a lot of cost of of uh shipping and uh as is the cost labor costs get get lower um so of course that's always the problem or always a consideration if you can find somebody to to do that to collaborate with um I don't know how one goes about doing that you know that the only thing that can I guess would happen is you have to talk to the collaborators there on the ground and for them to be able to connect to people because sitting here it's very hard to know you know how how to do that has that been uh have you talked I'm sure you've talked about it and you're trying to explore that venue too right yeah no absolutely I think in India and in China both there are many many opportunities for local manufacturing that me all of the appropriate regulatory standards and quality standards that are needed um I think right now outside of South Africa um it's really in my opinion not possible to do it cost effectively in an African country it will cost you significantly more than it would cost to do it in the United States and certainly more than it would cost to do it in India or China and I think there are some good examples of Partnerships with Indian manufacturer so you know one that I'm aware of is there's a non-profit called d-rev in the Bay Area they develop some phototherapy lights they worked with Phoenix medical um in India and you know we're able to scale up quite effectively those lights which were made in India but distributed all over the world including in Africa and so I I think that's probably the most likely route for that is that there's just not yet enough infrastructure um outside of South Africa to do it cost effectively I uh unfortunately have the the sad responsibility to conclude our session um for today and our series for this calendar year I want to thank you again Dr Richard cordum uh for joining us um and I want to remind everyone else on this meeting to join us in the new year for an exciting lineup uh of additional speakers that we'll announce soon on our website at cancer.gov Global Health where you'll also find additional information not only about the upcoming sessions uh but our past recorded sessions funding opportunities events news and more and remember to follow us on Twitter at NCI Global Health uh thanks for joining us U.S Department of Health and Human Services National Institutes of Health National Cancer Institute cancer.gov 1-800 for cancer
2023-02-06 13:02
