 So today, we are very pleased to welcome our first keynote speaker, Dr. Victoria Nembaware, who is joining us all the way from South Africa. Vicky is the project manager for the Sickle Cell Africa Data Coordinating Centre, where she directs research capacity development and training. Vicky is particularly involved in study design, data management planning, and big data analytics, and as well as ontology development, all applied to the research of Sickle Cell disease. So Vicky carried her doctoral studies in bioinformatics at the University of Cape Town in South Africa and was also a visiting postdoc at Stanford University. She had different positions in the public health sector, including information and communication technology, monitoring and evaluation, as well as teaching. For example, one of the things she did was developing a mobile phone app to engage and educate the public on her identity and health in Africa. So today, Vicky will share with us her experiences in designing and implementing life-scale policy-driven efforts to combat sickle cell disease in the sub-Saharan region. And she will tell us about the focus and strategy of her Institute, which was founded in 2017, so rather recently. Yeah, we are really looking forward to her talk, where we'll listen about delivering results when you are in a resource-constrained healthcare facilities and how the African genetic diversity impacts disease outcomes. Thank you very much for having me. It's a great privilege to present this seminar on behalf of the Sickle Africa Data Coordinating Centre, or SADAC. We are based at the University of Cape Town in South Africa. It's actually winter, so the weather is similar to what's on the photograph. We are supported by the University of Cape Town Clinical Research Centre and by ASHRAE BINET. Our centre, which I'll call SADAC going forward, is led by Professor Ambrose Wonkham, who's a medical geneticist with a background in managing sickle cell patients for many years. He's supported in this leadership role by Professor Nicola Mouda. Our team is multidisciplinary, with lots of people coming from a diverse range of backgrounds, including bioinformatics, LC, lab and biorepository management, mathematical modelling, epidemiology, and so on. A very quick overview of my talk, I'll give a little bit of background on sickle cell disease. Most of you might be familiar with this disease, as it's a classical example, which is included in most high school textbooks, and I hope to highlight with this talk the reality on the ground, far from the textbook experiences you might have had. I will discuss a little bit about the SADAC mission and vision and how we build partnerships and also about the work we do in building a registry or LC work, training and research. Sickle cell disease is actually a group of blood disorders, with the most common one being sickle cell anemia, which is caused by a single nucleotide polymorphism, which causes no more blood red cells to become sickle celled in shape, which then distorts the ability to transport oxygen around the body, and it also results in clogging, or these sickle cell shaped cells clogging the blood vessels, which can lead to a range of symptoms and complications. These symptoms and complications, we don't still understand them because they can range from mild to severe and chronic. Unfortunately, our own African beliefs and cultures can distort our understanding of the disease. In addition, most of our healthcare workers are ill-equipped or ill-educated to actually care for the complications that people have. When my oldest daughter was three years old, friends introduced us to another professional young couple with another three-year-old daughter, but unfortunately this daughter was very, this little girl was very lonely because no one in their circles wanted to play with her. She had a tendency of screaming uncontrollably, you know, uncontrollable for hours on end. Her eyes would turn yellowish, her hands would swell every now and again, and her feet, she got infections very easily, she got tired very easily, she couldn't play that well. So this young couple had really basically given up time to socialize, so we got in touch with them and our kids started to play. We learned later on that this young couple had given up taking the child to the emergency centers here in Cape Town, South Africa, because the healthcare workers could never seem to make a really meaningful diagnosis of the child. The neighbors had first suspected child abuse, and then eventually they concluded that this child was bewitched or possessed by some spirit, and unfortunately this young couple was actually beginning to believe this, believe from the neighbors. And this is kind of the scenario which is in Africa, and these are young professionals, not more of people who have lower education and lower literacy levels. The prevalence of sickle cell disease is very frequent in Africa. Africa contributes more than 75% of the life births of sickle cell, and it is estimated that over 300 babies are born with sickle cell globally every year. And basically the reason why there is such high prevalence in Africa is because of malaria, people who inherit the mutation or are carriers of the mutation are more resistant to malaria. And for a long time sickle cell was a neglected disease globally. No one cared about it, but unfortunately a group of advocates from Africa made of politicians of clinicians and healthcare workers all got together and lobbied the United Nations and in 2008 they were successful in that sickle cell disease became recognized as a public health problem. And as you can see on this red map, although sickle cell disease was discovered in 1910, it was only more than 80 years later that the first drug was FDA approved to be used for sickle cell disease. And this drug was even a repurposed drug, it hadn't been developed specifically for sickle cell disease. SADEC was actually initiated in 2017, and we're hoping that with this coordinated effort we'll be able to contribute or facilitate the contribution of new drug therapies that can improve the quality of life of sickle cell patients and even increase their lifespan. We've been very well accepted resource for increasing research and understanding diseases as registries. And unfortunately there isn't a registry in most of the hard heat regions of sickle cell disease. On this map in 2017 we did a very informal quick scan of what are the registries out there on sickle cell disease. We realized that if you see on the map the red parts mark the really hard heat sickle cell regions, and the blue dots are the registries, and as you can see there is a disconnect of registries and the hardest heat regions. So there is an urgent need to really develop sickle cell registries and develop long chewed nose studies. So SADEC as mentioned previously is really hoping and working towards building research capacity in sickle cell disease so that we can understand this disease better and address it better and also increasing healthcare capacity through coordination of sickle cell stakeholders across the globe and especially in sub-Saharan Africa. We also are strengthening research training, LC, ethical, legal, social implications, and healthcare. And for coordination we are specifically funded by the National Institute of Health, USA, to support SPARCO, which is the Sickle Pan-African Research Consortium. This consortium is headed by Professor Julie McCunney who is based in Tanzania. And the SPARCO sites are linked to hospitals or healthcare facilities where they specialize mainly in sickle cell disease. And these sites are based in Ghana, Nigeria, and Tanzania, some of the hardest heat countries by sickle cell disease. Together SADEC and SPARCO we form what we call the Sickle in Africa Consortium. In addition to supporting SPARCO we also build networks and partnerships with others amongst other sickle cell disease stakeholders, clinicians and researchers spread across 21 countries in Africa and also we've got researchers from our network who are based in Brazil, Jamaica, the U.S. and U.K. and we're hoping that Asia will join this network soon. And this loose connection of researchers in sickle cell disease is called the Sickle Cell Pan-African Network and we created a sickle cell disease ontology working group out of the Sickle in Africa Consortium and SPARCO. And based on this network we managed to create a community supported sickle cell disease ontology and this ontology is based around the roots of hemoglobinopathies and this disease ontology actually addresses different sections of the different issues and areas of the disease itself from quality of life and care to research to diagnostics to therapeutics. We have translated this ontology into French and we're currently translating, finalized translating into Portuguese and also we have developed a layman's version of the ontology for patients to empower patients about their own health. As most of you might have noticed, the title is Sickle Cell Disease of this talk also known as a banana cell and one of the key deliverable of our ontology which we're very proud of is that this ontology has got terms and descriptions that do not exist in other ontologies and I just highlighted there with one example, sickle cell disease was coined in 1910 out of an African context. Most people don't even know what a sickle is so most of the clinicians especially Ambrose advocated that we create another synonym for sickle cell which is banana cell disease. It makes it easier for researchers, for healthcare workers to explain what sickle cell disease is to other African patients or stakeholders. For the registry itself we have over 10,000 patients who have been recruited into our registry because of the high mortality rate and the reduced lifespan of sickle cell disease most of our registry participants are children. We're working hard towards making this registry fair starting internally while we address data sharing and governance issues and also for us to mine the data efficiently before we make it available to the general research community. So we've got a dashboard and a curable database in house and on this graph you can actually see that Nigeria is contributing the largest number of sickle cell disease because it actually has a higher prevalence or the highest, one of the highest on the continent. Because our team is made up of data analysts and people who've got lots of experience analyzing data this was a really exciting opportunity for the data analyst in our team to be involved in addressing data quality issues which take up a lot of our time when we use publicly available data sets. So for this aspect we did a lot of work together with the consortium of developing data standards and data elements which are harmonized across the sites and we agreed on a core data set of 66 elements which each site collects and they're free to collect anything else but these core data elements which are key to understanding sickle cell are being collected the same across the sites that we're working with. Again to emphasize data quality assurance we also have data quality certificates when the sites send data to our data coordinating center we check it thoroughly for quality and we send it back again to the sites to correct whenever we've got any issues and this is something that we do on a regular basis whenever data is shared is copied across as we are custodians of the data and also are responsible for the data quality. In terms of data collection most of the sites we work with or some of them were using paper based data collection and paper based has got many problems if a fire comes you know your data will all be gone so we moved and are promoting a tablet based data collection where most of our sites do not have stable internet connectivity so they collect their data using tablets offline and whenever they've got connectivity it's uploaded onto servers and we're using the red cap system for this data collection and we also do site visits to actually make sure that data is being collected in an ethical way and in a standardized manner and in the ethos of building capacity we also pressure servers for each site to make sure that this data is being backed up and we don't have any data losses and also to make data transferable easier to transfer to the SADAC center. For the ethical, legal and social implications we've had a lot of heated debates about these issues and we cannot say we've addressed all the issues around data sharing and data governance but we did try to implement and address a lot of these ethical issues right at the beginning so before the data collection started we brought all the stakeholders together and we tried to look at each and every aspect that we could think of and to address it as much as possible. For instance we actually assessed ethical, legal, any restrictions that could hinder data sharing in the future at an institutional level and at a national level for each country. We assessed consent forms that were being used by each site which ended up making us actually develop templates together with the sites which would promote data sharing later on. We're still grappling with other issues and are now designing research studies around this ascent. Most of our participants are children so they really understand the consent. Can we develop graphics or cartoons for them to understand better? Benefit sharing. How are we going to share any new discoveries that come out of this data with the participants, with the rest of the stakeholders, data access committees who's going to govern this data efficiently. Right now SADAC is trying as best as we can but do we need an external board, data security issues. There are so many issues that we're still trying to address and we are doing this with patients as partners which is really one of the ethos of the work that we do. We work collaboratively with partners. We've got patient representatives from each of the four countries that we work in. From South Africa we've got Paul, Arafa from Tanzania and Adebole who's 61 years old and a sickle cell disease patient which is fantastic and she's from Nigeria and we also have Emmanuel from Ghana. We also support their advocacy work. I've just highlighted there one of the president for the sickle South Africa support group, Gravages, who was featured in a nature paper recently due to some links we made for him. We also create public engagement material and we're continually trying to improve this material. We've got effect sheets explaining what sickle cell disease is, hoping that that will reach far. We celebrate World Sickle Cell Day which is coming up very soon on the 19th of June. This year we've developed a video explaining our work and also we plan on sharing aggregated data as a way of feeding back our progress to the patients because I'm sure they would like to know what we've been doing with the data we've been collecting. In terms of training, we also really focus on competency or skills-based training approach. The one training we've implemented and has been incrementally going more intensive, getting more intensive and more complex, more advanced is data capturing and data management because our training for the registry is really centered around the data management cycle. We have now reached out to other people developing data stewardship training so that we can finalize the training we've got. We've got a standard operating procedure platform because you can create standard operating procedures to facilitate standardization of processes and of data across the size but how can you assess that people are actually reading and taking note of these soaps and following them. We've developed a platform which then assesses comprehension of all our site members and we are now ready to pilot and assess how effective that will be. We also have training that we have developed. Most of this training and system administration and also manuscript development so that we can promote first and last author publications from our consortia. Most of the training material that I've described here is currently being finalized and will be implemented towards the end of this year but the data management and capturing is something that we do continuously during site visits and in workshop and its sites and one of our flagship training we are really proud of is the big data analytics. This is really aimed at equipping the sites to analyze their own data both epidemiological data and also genomic data that they are starting to produce from their patients and one other thing is we strategically recruited data managers into the big data analytics course and this was to actually promote the data managers to appreciate the importance of data quality and what better way it is to actually promote data quality by making them carry their own water then they will learn that the value of each of the drop the value of each data element and the quality is really important for data quality and we're hoping to also assess the impact of this pilot based on real data from the data quality and we're hoping that the data quality will improve substantially now that the data managers have got some data analysis skills. In terms of healthcare our team contributes heavily to the African Genomic Medicine Training Initiative which is really geared at upskilling nurses in understanding genomics and and and just how to address that in the healthcare and during this training as well as our personal experiences we have observed that sickle cell is really important for us to develop a separate module which specializes mainly on sickle we've got a clinician who's now focusing on on just creating that module and we hope to to actually implement that this year as well. In addition we look backwards how can we promote uptake of careers how can you promote interest in understanding in genomics and in life sciences in general and we do this through the MGen Africa platform where we provide high school learners from disadvantaged areas with role models from our team and our networks and collaborators and we also have online quizzes which then happen physically once a year here in a very huge quiz competition where there are big prices we we've been doing this with the Department of Education in Cape Town for this for for a few districts and we're hoping that this will be scaled up to other countries there are already two countries that are very interested in taking this model to inspire the young upcoming and future researchers. In terms of healthcare Sparkle our sister consortia has developed standards of care guidelines which most of our training for healthcare workers will be based on and what's fantastic about these healthcare guidelines they've just not been adopted from elsewhere they've been adapted for the resource limited setting for example for instances where exchange transfusion would be ideal they recommend top-up transfusion because that's what's available and for new born screening there are some places where there isn't a new born screening or you've run out of tests to test whether a baby is has got sickle cell they recommend that you actually treat the little baby with folic acid and penicillin prophylaxis until you can perform a screening test in the near future or when the resources become available we're also using the sickle cell disease ontology as a framework to design applications which can help healthcare workers with better diagnosis and better care for the patients and also some of these applications are mobile phone based one is almost complete for active surveillance of pain so that we understand pain better if we've got live data coming from from from the patients because sometimes a patient goes into a crisis because the temperature has changed are the other things that trigger pain crisis these are the things we would like to collect and it will also enhance the data in our registry the potential of impact of this research is what's exciting the team most a lot amongst other things for example one of the most cited paper which I've already cited which estimated over 300 live birds of sickle cell disease in globally is based on mathematical modeling we're hoping with data from this consortium we'll be able to provide concrete data and even better estimates of the prevalence of sickle cell disease we'll be better able to understand why there is so much variability in in in the manifestation of these diseases different people and different haplotypes and different sickle cell diseases we're also hoping to contribute make our small contribution to increasing the african genomic data that's available um in public databases and to promote retrospective data analysis um because there's a lot of data that exists in individual sites using the ontology we are now we've already piloted harmonizing existing data can the sickle cell disease ontology be used as a framework for for developing other genetic disease ontologies we've already done so or proved um that is possible by developing the hearing impairment ontology based on this framework in addition um a question that we're grappling with and trying to address could sickle cell be disease be could it facilitate um precision medicine uh through multi-omics data harmonization and integration for the machine learning algorithms based on um how this data can be brought together and be harmonized using the sickle cell disease um ontology i'd like to thank the SADEC team and the entire SPACO team and our initially BI and funders um that's our website and our our um Twitter handle uh thank you so much for this opportunity thank you once again and welcome questions great thank you very much Vicki for that great talk um it looks like you were exactly on time in fact we have time for one question and I want to remind all the participants that after this um there's the meet Vicki session so uh further follow-up questions can be asked but um the top question that we have right now is coming from Anika Gabel and she's asking the question how much are the current drugs improving quality of life and are they affordable for patients unfortunately right now most of the patients are treated using folic acid and um antibiotics to try and limit infections um there's also hydroxyl but it's not accessible to everyone uh most countries patients have to purchase um in Ghana um uh the site in Ghana has managed to partner with Novartis and the government to try and improve access to hydroxyl for for their patients and this is a model that we're hoping can be implemented throughout Africa and we're hoping it will increase the quality of life and uh probably also um reduce the mortality rates uh but yes um we're hoping maybe this work would lead to better in the long run more affordable drugs um yeah great question all right well thank you for that answer I think now we'll um end this session and go to the meet the speaker session and there's a number of other questions that I've been collecting so we can continue there so we'd like to thank you again for the great talk and starting off sub days 2020 thank you so much