Technologies to Improve Early Cancer Detection in Low Resource Settings: Idea to Field Evaluation

Technologies to Improve Early Cancer Detection in Low Resource Settings:  Idea to Field Evaluation

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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 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 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 1-800 for cancer

2023-02-06 13:02

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