Kaaskiri Eesti bioeetika ja inimuuringute nõukogule projekti “Optoakustiliste fenotüübi andmete ja multi-oomika kombineerimine diabeediga seotud tervishoiu edendamiseks (OPTOMICS)” j ätkutaotlus ele nr 5 1. Uurimistöö peamine eesmärk (sama nagu põhitaotlusel): Käesolev uurimistöö viiakse läbi rahvusvahelise Horizon 2020 projekti OPTOMICS raames. See projekt käsitleb diabeeti, mis on kujunenud ülemaailmseks pandeemiaks ning mõjutab kogu maailmas enam kui 420 miljonit inimest. Järgmistel aastakümnetel kasvab haigestunute arv arvatavasti veelgi. Diabeedil on väga heterogeensed väljundid ja patsiendi haigusfaasi täpne tuvastamine või prognoosimine üksikisikute tasandil, kellel võib tõenäoliselt välja areneda haigus ja/või progresseeruda haiguse tüsistusteks, on veel lahendamata kliinilised väljakutsed, mis vajavad kiiret tähelepanu. OPTOMICSi eesmärk on uurida metoodikat, mis võib anda paradigma muutuse teist tüüpi diabeedi käsitluses, integreerides 1) molekulaarse fenotüpiseerimise, 2) uue põlvkonna fenotüübilised mõõtmised inimestel, kellel on diabeet alles kujunemisel või progresseerumisfaasis, mida võimaldab uus portatiivne ja mitteinvasiivne optoakustiline tehnoloogia ja 3) tipptasemel arvutuslikud lähenemisviisid, mis suurendavad tehisintellekti edusamme. 2. Vastutav uurija (sama nagu põhitaotlusel): ees- ja perekonnanimi: Reedik Mägi teaduslik kraad: PhD amet: bioinformaatika professor töökoht: Genoomika instituut, Tartu Ülikool töökoha aadress: Riia 23b/2-517 telefoninumber: 7374045 e-post:
[email protected] 3. Nimetatud uuringule on varem väljastatud järgmised Eesti bioeetika ja inimuuringute nõukogu load: - Põhitaotlusele väljastatud luba 12. oktoobril 2021 (otsus nr 1.1-12/2348) - Jätkutaotlusele nr 1 väljastatud luba 14. detsembril 2021 (otsus nr 1.1-12/2348) - Jätkutaotlusele nr 2 väljastatud luba 1 2 . aprillil 202 2 (otsus nr 1.1-12/1408 ) - Jätkutaotlusele nr 3 väljastatud luba 04 . augustil 2022 (otsus nr 1.1-12/2 619 ) - Jätkutaotlusele nr 4 väljastatud luba 14. aprillil 202 3 (otsus nr 1.1-12/ 1585 ) Taotluse sisu Kokkuvõtvalt: Seoses OPTOMICSi uuringu algusaja edasilükkumisega meist olenemata põhjustel (RSOM instrumendi tarkvara oli vaja täiendada ja testida enne kasutuselevõttu ning seejärel meie meeskonda täiendkoolitada . ) ja selle aja jooksul uuringuprotokollis toimunud muudatuste ja täpsustustega (OPTOMICS partnerid optimeerisid vastuvõtu protokolli, vastavad muudatused on vaja ka meil sisse viia. Selleks toimus täiendkoolitus.) , soovime muuta mõningaid uuringu detaile ja sellest tulenevalt täiendada uuringu avaldust, nõusolekuvormi ja uuringu kutset. Oleme saanud täiendavat tagasisidet uuringu nõusolekuvormile, mistõttu soovime seda muuta lühemaks, selgemaks ja arusaadavamaks. Täiendasime ka kulude hüvitamise taotlust. Uuringu perioodi pikendamine Seoses uuringu algusaja edasilükkumisega meist olenemata põhjustel on taotletud OPTOMICSi projekti koordinaatori poolt Euroopa Liidu Komisjonilt aja pikendust 1 aasta võrra. Palume EBIN-il kooskõlast ada uuringu perioodi pikendami ne . U us lõppkuupäev on 12.2026. (Avaldus lk 5.) Uuringu metoodika muudatused (Avaldus lk 5, 7, 10,11 , 12 ) Kompensatsioon uuringus osalejatele ( Financial compensation ) on suurenenud. Kompenseerime kuni 35 € transpordikulusid (varasema 30 € asemel) ja lisaks pakume kohapeal vett (pudeliga) ja müslibatooni ning kompenseerime täiendavalt 8 € toitlustuskulusid. Kuna Riia 23 majas on kohvik suletud, siis kahjuks kohapealset toitlustust me pakkuda ei saa. Kompensatsiooni saamised peavad uuritavad esitama kuluaruande avalduse koos kuludokumentidega ( Appendix 11). Optoakustilisi mõõtmisi tehakse dominantse käe käsivarrelt ja dominantse jala siseküljelt. Varasemalt oli plaanis teha mõõt misi jala sise - ja väliskül jelt . Optoakustiliste mõõtmiste ajal ei tehta uuritava jäsemetest pilte. Eemaldasime selle osa avaldusest ja nõusolekuvormi l t. Täiendamise sekkumise tüübi peatükki ( type of intervention ) – vastavalt punktis „a“ kirjeldatule ja lisasime, et mansetis hoitakse rõhku sees 3 min (varasemalt oli 1 , 5 min). Kokku tehakse kaks RSOM mõõtmist – staatiline mõõtmine sääre siseküljelt ja dünaamiline mõõtmine mansetiga käsivarrelt. RSOM mõõtmiste tegemisteks võib olla vajalik eemaldada nahapinnalt karvu. Varasemalt oli plaanis kasutada selleks ühekordset raseerijat või depileerimiskreemi . Kuna selgus, et depileerimiskreem võib mõjutada mõõtmistulemusi , eemaldasime selle valikust. Muutsime „Koormus uuritavale“ peatükki ( Burden on the subject ) . Tulenevalt uuringuprotokolli muudatuste st võib vastuvõtu aeg kesta kuni 1 , 5 h (varasema 1 h asemel). Samuti soovime pakkuda uuritavatele võimalust tulla vastuvõtule ka kella 12.00st päeval ning muutsime ära vastuvõttude kirjelduse esimeses ja teises uuringukabinetis. Uuritavaid plaanime kutsuda 45 min vahedega (varasema 30 min asemel), seega saame vastuvõtule kutsuda kuni viis uuritavat päevas. Viisime sisse vastavad muudatused avaldusse ja nõusol e kuvormi. Plaanime edastada uuringu kutseid vaid e- posti teel (2 korda) ja telefonitsi. Tavapostiga me kutseid ei saada (esialgu oli see plaanis). Kustutasime vastava teksti avaldusest. Muudatused nõusolekuvormis M uutsime nõusolekuvormi lühemaks, konkreetsemaks ja selgemaks. Seega on muudatusi tehtud kogu nõusol e kuvormi ulatuses. Olulisemad sisulised muudatused on: Eemaldasime liigsed detailid uuringupartnerite kohta. Uuringu vastuvõtu aeg on varasema 1 h asemel kuni 1 , 5 h. Protseduuride järjekord ja selleks kuluv aeg kahes vastuvõturuumis on muutunud. Kulusid kompenseeritakse suuremas ulatuses (varasema 30 euro asemel kuni 43 eurot transpordi ja toitlustuse kompenseerimiseks) . Täiendamise uuringu kutse id , mi da edastame e- posti teel Olulisemad muudatused esimeses ja teises uuringukutses: Uuendasime kulude kompenseerimise informatsiooni. Kutsele lisatakse lisaks nõusolekuvormile ka uuringu küsimustik, et uuritav saaks sellega soovi korral juba eelnevalt tutvuda ja tal oleks vastuvõtul küsimustele kergem vastata. Lisasime kutsesse info, millistel juhtudel ei sobi kutse saanu uuringusse ja mida ta peab enne uuringu vastuvõtule tulemist silmas pidama. Täiendamise uuringu kulude kompenseerimise avaldust ja selle juhendit. Kompenseerime lisaks sõidukuludele ka toitlustuse kulusid (varasema 30 euro asemel kokku kuni 43 eurot – kuni 35 eurot transpordi ja kuni 8 eurot toitlustuse kompenseerimiseks ) . Kulude kompenseerimiseks peab uuritav meile saatma avalduse ja kuludokumendid vastuvõtult saadud ettemakstud ümbrikuga. Elektroonselt me avaldusi ega kuludokumente ei soovi. 21.08.2023 esitatud t äiendavad küsimused EBINilt ja nende vastused: Nõusolekuvormid on uuendamata (kulude kompenseerimine ja hüved). Vastus: Kogemata on meie viimase taotlusega kaasa pandud vale nõusolekuvormi dokument. Paneme seekord kaasa õige dokumendi, kus on ka kulude kompenseerimise osa korrigeeritud. Uuringu kutses uuritavale peaks olema kirjas, kas uuritav kuulub kontrollgruppi või diabeedigruppi või et kuidas uuritav valimisse sattus? Kui mina peaksin saama sellise uuringukutse, siis see ehmataks mind ära (ma ei ole täna veel diabeedihaige). Vastus: Viisime sisse vastavad muudatused uuringu kutsesse. Tegime eraldi kutsed Eesti g eenivaramu andmetel diabeedi diagnoosiga geenidoonoritele ja ilma diagnoosita geenidoonoritele. Kutse on lisatud eraldi dokumentidena. Isikuandmete töötlemise teema nõusolekus puudu. Vastus: Nõusolekuvormis on eraldi alapeatükk: „ Andmete ja proovide jagamine uuringupartneritega ning nende säilitamine “ , seal on kirjeldatud, millised andmed, millistele partneritele kättesaadavaks tehakse ja kui pikalt neid säilitatakse. Samuti on eraldi välja toodud eritingimused UK partneri puhul. Esitatud dokumentide nimekiri Uuringu muudatustega avaldus Lisa 1. Informeeritud nõusolekuvorm (EST) Lisa 2 . Kutse uuringusse (eraldi juhtudele ja tervetele kontrollidele) Lisa 3. Kaaskiri Lisa 11. Kulude kompenseerimise avaldus ja juhend Vastutav uurija: Reedik Mägi Bioinformaatika professor Genoomika instituut, Tartu Ülikool /allkirjastatud digitaalselt/
APPLICATION TO THE ESTONIAN COMMITTEE ON BIOETHICS AND HUMAN RESEARCH FOR ETHICAL EVALUATION OF THE RESEARCH PROJECT 1. Name of the study (in case of an application in English, the name of the study in Estonian is required in parallel) Combining optoacoustic imaging phenotypes and multi-omics to advance diabetes healthcare (OPTOMICS). Optoakustiliste fenotüübi andmete ja multi-oomika kombineerimine diabeediga seotud tervishoiu edendamiseks (OPTOMICS ). 2. The main purpose of the study (up to 450 characters / 0.25 pages) (in case of an application in English, the main purpose of the study should be provided in Estonian, too) Current research will be carried out within the international Horizon 2020 project OPTOMICS. This project addresses diabetes, which has emerged as a global pandemic affecting more than 420 million people worldwide, a number expected to further rise in the next decades. The disease has very heterogeneous outcomes and accurate patient staging or prediction of subsets of individuals likely to develop disease and/or progress to disease complications are currently unmet clinical challenges in need of urgent attention. OPTOMICS aims to research methodology that can deliver a paradigm shift in type 2 diabetes (T2D) healthcare, by integrating 1) molecular phenotyping, 2) a new generation of phenotypic measurements in humans, representative of diabetes onset and progression, allowed by novel portable and non-invasive optoacoustic technology and 3) cutting-edge computational approaches leveraging progress in Artificial Intelligence. This research will develop and validate a digital twin model that catalyses a step change in shortening the path to translation, enabling applications in the entire spectrum from target identification & prevention/prognosis to patient stratification for T2D and its complications. The Institute of Genomics at the University of Tartu hereby submits an application for the use of gene donor data, depseudonymization of personal data and invitation to the study to fulfil the objectives of the OPTOMICS project. For the preservation and examination of tissue samples outside the territory of the Republic of Estonia, we apply for a corresponding permit from the Senate of the University of Tartu. Käesolev uurimistöö viiakse läbi rahvusvahelise Horizon 2020 projekti OPTOMICS raames. See projekt käsitleb diabeeti, mis on kujunenud ülemaailmseks pandeemiaks ning mõjutab kogu maailmas enam kui 420 miljonit inimest. Järgmistel aastakümnetel kasvab haigestunute arv arvatavasti veelgi. Diabeedil on väga heterogeensed väljundid ja patsiendi haigusfaasi täpne tuvastamine või prognoosimine üksikisikute tasandil, kellel võib tõenäoliselt välja areneda haigus ja/või progresseeruda haiguse tüsistusteks, on veel lahendamata kliinilised väljakutsed, mis vajavad kiiret tähelepanu. OPTOMICSi eesmärk on uurida metoodikat, mis võib anda paradigma muutuse teist tüüpi diabeedi käsitluses, integreerides 1) molekulaarse fenotüpiseerimise, 2) uue põlvkonna fenotüübilised mõõtmised inimestel, kellel on diabeet alles kujunemisel või progresseerumisfaasis, mida võimaldab uus portatiivne ja mitteinvasiivne optoakustiline tehnoloogia ja 3) tipptasemel arvutuslikud lähenemisviisid, mis suurendavad tehisintellekti edusamme. Tartu Ülikooli genoomika instituut esitab käesolevaga taotluse geenidoonorite andmete kasutamiseks, isikuandmete depseudonüümimiseks ja uuringusse kutsumiseks OPTOMICS projekti eesmärkide täitmiseks. Koeproovide säilitamiseks ja uurimiseks väljaspool Eesti Vabariigi territooriumi taotleme v astava loa Tartu Ülikooli s enatilt. 3. Principal investigator(s) and their contact details Given name(s): Reedik Last name: Mägi Position: Professor in Bioinformatics Institution: University of Tartu (UTARTU), Faculty of Science and Technology, Institute of Genomics Phone: 7374045 e-mail:
[email protected] Skype: reedik_m 4. Other researchers involved in the study (add lines as necessary) Researchers from University of Tartu Given name(s): Ene Last name: Reimann Position: Research Fellow of Orthogenomics Institution: University of Tartu, Faculty of Science and Technology, Institute of Genomics Given name(s): Kristi Last name: Läll Position: Research Fellow of Statistical Genetics Institution: University of Tartu, Faculty of Science and Technology, Institute of Genomics Given name(s): Helene Last name: Alavere Position: Head of the Data Collection Office Institution: University of Tartu, Faculty of Science and Technology, Institute of Genomics Given name(s): Karoliina Last name: Kruusmaa Position: Specialist Institution: University of Tartu, Faculty of Science and Technology, Institute of Genomics Given name(s): Tõnu Last name: Esko Position: Professor of Human Genomics, Vice Rector of Estonian Biobank Innovation Centre Institution: University of Tartu, Faculty of Science and Technology, Institute of Genomics Given name(s): Triin Last name: Laisk Position: Associate Professor of Genomics and Reproductive Genetics Institution: University of Tartu, Faculty of Science and Technology, Institute of Genomics Given name(s): Toomas Last name: Haller Position: Associate Professor of Genomics and Metabolomics Institution: University of Tartu, Faculty of Science and Technology, Institute of Genomics Given name(s): Kristjan Last name: Metsalu Position: Head of IT Development Unit Institution: University of Tartu, Faculty of Science and Technology, Institute of Genomics Given name(s): Triinu Last name: Temberg Position: Specialist Institution: University of Tartu, Faculty of Science and Technology, Institute of Genomics Given name(s): Esta Last name: Pintsaar Position: Specialist of Data Collection Institution: University of Tartu, Faculty of Science and Technology, Institute of Genomics Given name(s): Vallo Last name: Volke Position: Professor of Endocrine Physiology, Head of the Department of Pathophysiology Institution: University of Tartu, Faculty of Medicine, Institute of Biomedicine and Translational Medicine, Department of Pathophysiology/Department of Physiology Researchers from the partner institutions: Given name(s): Mikael Last name: Kubista Position: Professor , CEO of TATAA Biocenter Institution: TATAA Biocenter AB (TATAA) Given name(s): Jens Last name: Björkman Position: VP, Director Commissioned Services Institution: TATAA Biocenter AB (TATAA) Given name(s): Gustav Last name: Holmgren Position: NGS Specialist Institution: TATAA Biocenter AB (TATAA) Given name(s): Hanna Last name: Zoric Position: Project Manager Institution: TATAA Biocenter AB (TATAA) Given name(s): Maria Last name: Janeh Position: senior Laboratory Assistant Institution: TATAA Biocenter AB (TATAA) Given name(s): Robert Last name: Sjöback Position: Head of RnD Institution: TATAA Biocenter AB (TATAA) Given name(s): Emmi Last name: Tikkanen Position: Senior data scientist Institution: Nightingale Health OY (NGH) Given name(s): Peter Last name : Wurtz Position: Scientific Director Institution: Nightingale Health OY (NGH) Given name(s): Sini Last name: Aalto Position: Laboratory Specialist Institution: Nightingale Health OY (NGH) Given name(s): Harri Last name: Koskela Position: Laboratory Manager Institution: Nightingale Health OY (NGH) Given name(s): Vasilis Last name: Ntziachristos Position: Professor, Chair Institution: Chair of Biological Imaging, Technical University of Munich (TUM) Given name(s): Ivy Last name: Curren Position: Project Manager Institution: Chair of Biological Imaging, Technical University of Munich (TUM) Given name(s): Angelos Last name: Karlas Position: Group Leader Clinical Bioengineering Institution: Chair of Biological Imaging, Technical University of Munich (TUM) Given name(s): Nikolina-Alexia Last name: Fasoula Position: Doctor, Scientist Institution: Chair of Biological Imaging, Technical University of Munich (TUM) Given name(s): Vassilis Last name: Sarantos Position: CEO and CTO Institution: RAYFOS LTD (RAYFOS) Given name(s): Elin Last name: Lundin Position: Research Engineer Institution: RAYFOS LTD (RAYFOS) Given name(s): Eleftheria Last name: Zeggini Position: Professor, Director of Institute of Translational Genomics Institution: Institute of Translational Genomics (ITG), Helmholtz Zentrum München - German Research Centre for Environmental Health Given name(s): Arthur Last name: Gilly Position: Head of Analytics Institution: Institute of Translational Genomics (ITG), Helmholtz Zentrum München - German Research Centre for Environmental Health Given name(s): William Last name: Rayner Position: Head of Data Informatics Institution: Institute of Translational Genomics (ITG), Helmholtz Zentrum München - German Research Centre for Environmental Health Given Name: Timo Last name: Mägi Institution and position: Tartu Jaan Poska High School, student Given name: Martin Last name: Tootsi Institution: University of Tartu (UTARTU), Faculty of Science and Technology, Institute of Genomics, laboratory assistant Director of the institution or head of the structural unit of the principal investigator(s) and of managers of other institutions or structural units related to the research Given name(s): Mait Last name: Metspalu Position: Director Institution: University of Tartu, Faculty of Science and Technology, Institute of Genomics Given name(s): Eero Last name: Vasar Position: Head of Institute Institution: University of Tartu, Faculty of Medicine, Institute of Biomedicine and Translational Medicine Given name(s): Anu Last name: Tamm Position: Director Institution: Laboratory at the Tartu University Hospital 5. Financing of the study Sources of funding Horizon 2020 Programme, Grant Agreement no 101017802 https://www.etis.ee/Portal/Projects/Display/54ab045d-7522-4a5e-bfa8-1d1324daf248 (01.01.2021-31.12.2025) Total cost of the study (amount) Total cost of the OPTOMICS project is 4,414,126 €, allotment of the University of Tartu is 670,375 € Financial compensation for the study participants (yes, no, explanation and amount) Up to 3 5 € for transport costs related to coming to the appointments (per one visit) will be reimbursed to the biobank participants (BP) on the basis of the submitted documents - public transport tickets or, in the case of using a private car, a fuel check. The calculation of fuel consumption is based on 7 liters per 100 km . BPs are offered a possibility to have a free meal ordered for them to the EstBB building to be served after the appointment. We offer water and muesli bar on site and reinburse up 8 € costs related to catering based on the submitted documents. (please see Appendix 11 Kuluaruande avaldus). Insurance provided for the study participants (yes, no, name of the insurance company and the certificate of insurance (COI)) BP’s will be insured for any unanticipated adverse effects or injuries that are caused by their participation in the study. Quotations for insurance service were taken from 3 companies. One company declined to make an offer. From the two companies that made an offer we chose “AAS "BTA Baltic Insurance Company" Eesti filiaal”, as it was the most suitable. 6. Study period (the beginning and end dates (MM/YYYY)) 10 .2021-12.202 6 7. Information about previous or parallel evaluation of the same study project (incl in other countries) No previous or parallel evaluation. 8. Brief overview of previous studies on the same topic (up to 900 characters / 0.5 pages) With diabetes emerging as a pandemic, OPTOMICS’ ambition is to advance healthcare addressing a global health problem. OPTOMICS will build a unique data set incorporating a novel biosensing concept that uses the skin as a measurement window with deep molecular phenotyping. T2D care already relies on the use of sensors, in particular glucose sensors. Glucose monitoring helps with daily disease management and regulating insulin levels in the blood [1], but it is not appropriate for characterizing the systemic effects of the disease. Conversely, while T2D is generally a disease that continuously progresses, gradually altering tissue pathology if left untreated, the characterization of T2D severity is currently performed based on crude complications that manifest as clinical symptoms [2] and glucose measurements including glycated hemoglobin. This coarse classification of T2D patients has been identified as an impediment to precise care and accurate assessment of intervention effects, prompting recent recommendations for improving T2D measurement approaches for patients [3,4]. The ability to quantify systemic effects of diabetes, not only glucose levels, in a disseminated and portable manner could be critical for health management of such a large patient pool. _____________________________________________________________________________ 1. Pramanik M and Wang LV, Thermoacoustic and photoacoustic sensing of temperature. J Biomed Opt 2009. 14(5):054024. 2. Zimmet P, et al., Global and societal implications of the diabetes epidemic. Nature 2001. 414(6865):782. 3. Yagihashi S, Clinical staging of type 2 diabetes: the time has come. J Diabetes Invest 2012. 3(1):1. 4. Insel RA, et al., Staging presymptomatic type 1 diabetes: a scientific statement of JDRF, the Endocrine Society, and the American Diabetes Association. Diabetes Care 2015. 38(10):1964-1974. 9. Rationale for the planned study and research questions and / or hypotheses (up to 1800 characters, 1 page) T2D has emerged as a global pandemic affecting more than 420 million people worldwide, a number expected to further rise in the next decades [5]. The disease has very heterogeneous outcomes, and accurate patient staging or prediction of subsets of individuals likely to develop disease and/or progress to disease complications are currently unmet clinical challenges in need of urgent attention [6,7]. Even though advances in -omics technologies have led to the discovery of hundreds of genetic risk loci and deep quantitative metabolomic and proteomic characterisation of tissue for the crude clinical diagnosis endpoint of T2D, phenotyping using imaging offers quantitative traits closer to the biological underpinning of T2D that capture the natural history of disease more powerfully. Therefore, imaging phenotypes, combined with –omics information in a digital twin model can improve the precision of target identification and the accuracy of prognostic, diagnostic and stratification strategies, over using –omics information alone. It is therefore critical to couple molecular biomarkers and genomic information to informative sensing and imaging phenotypes that monitor changes in the pathophysiology of disease to build new models for personalized and precision medicine. Nevertheless, phenotypic observations of diabetic pathophysiology today are slow, not readily available to large populations and not always informative. Functional assessment of altered metabolism and other pathophysiological alterations of diabetic patients are rare today due to the need to perform radionuclide imaging, for example using Positron Emission Tomography (PET) that requires ionizing radiation and is thus not widely accessible at a population-scale level. Assessment of metabolic traits with Magnetic Resonance imaging (MRI) circumvents the challenges of ionizing energy but comes at high infrastructure cost and low throughput, similarly, making the technique not readily available to population studies. OPTOMICS develops a twin model that combines molecular biomarkers (metabolites, circulating proteins, genetic variants) with a novel imaging phenotyping concept, which encompasses two key premises: (1) the use of the skin as a window to T2D, since microvascular morphology, endothelial function, oxygen utilization and other parameters accessible in the skin are critically affected by the disease [8-18] and (2) significant recent evidence that inexpensive optoacoustic technology, in particular Raster Scan Optoacoustic Mesoscopy (RSOM) developed by partners the Technical University of Munich (TUM) and Helmholtz Zentrum München - German Research Center for Environmental Health (HMGU), can collect several T2D-related imaging-derived biomarkers from the skin in high detail and precision. Critically, RSOM collects these informative T2D biomarkers in a portable, non-invasive, label-free (no contrast agents), fast and safe way, offering new ability to obtain T2D phenotypes in a highly disseminated use, which can not only facilitate the goals of the study herein but also lead to a long-term comprehensive platform for improving T2D management and healthcare. The whole project’s aims are to: (1) Collect RSOM and –omics measurements from humans (cases and controls) and develop a computational scheme for quality control of the measurements over the course of the study. (2) Glean novel biological insights by enhancing our understanding of aetiopathogenesis and enable therapeutic target discovery through identification of effector genes for T2D risk loci. (3) Develop a digital twin scheme empowered by Artificial Intelligence and statistical methods to model static and dynamic processes in T2D evolution and improve prediction, prognosis and early detection of individuals likely to develop T2D, enabling prevention; and T2D patients at risk of developing disease complications for tailoring early interventions. (4) Fulfil the need to empower precision medicine: extend the abilities of the model to choose the right treatment for the right patient at the right time. (5) Perform exemplary project management, dissemination and communication activities, comply with ethical standards and develop and update an adept exploitation plan for OPTOMICS. University of Tartu, Faculty of Science and Technology, Institute of Genomics, Estonian Biobank (EstBB) will conduct RSOM measurements in humans and combine static and dynamic optoacoustic-based phenotypic measurements, –omics information and systems biology concepts into a common computational scheme, offering unique innovation and impact potential at two time scales. ______________________________________________________________________________ World Health Organization – Diabetes, https://www.who.int/health-topics/diabetes#tab=tab_1 Palmer A, et al., Computer modelling of diabetes and its complications: A report on the fifth Mount Hood Challenge Meeting. Value Health, 2013. 14(4):670-85. Chung WK, et al. Precision medicine in diabetes: a Consensus Report from the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD) . Diabetologia ( 2020). Doi: 10.1007/s00125-020-05181-w Sörensen, B.M., et al., Prediabetes and Type 2 Diabetes Are Associated with Generalized Microvascular Dysfunction. Circulation, 2016. 134(18): p. 1339-1352. Widlansky, M.E., et al., The clinical implications of endothelial dysfunction. J Am Coll Cardiol, 2003. 42(7): p. 1149-1160. McMillan, D.E., Deterioration of the Microcirculation in Diabetes. Diabetes, 1975. 24(10): p. 944-957. Guerci, B., et al., Endothelial dysfunction and type 2 diabetes. Part 2: altered endothelial function and the effects of treatments in type 2 diabetes mellitus. Diabetes Metab, 2001. 27(4 Pt 1): p. 436-447. Khan, F., et al., Relationship between peripheral and coronary function using laser Doppler imaging and transthoracic echocardiography. Clin Sci, 2008. 115(9): p. 295-300. Levy Bernard, I., et al., Impaired Tissue Perfusion. Circulation, 2008. 118(9): p. 968-976. Holowatz, L.A., Human cutaneous microvascular ageing: potential insights into underlying physiological mechanisms of endothelial function and dysfunction. J Physiol, 2008. 586(14): p. 3301-3301. Rizzoni, D., et al., Prognostic Significance of Small-Artery Structure in Hypertension. Circulation, 2003. 108(18): p. 2230- 2235. IJzerman, R.G., et al., Individuals at increased coronary heart disease risk are characterized by an impaired microvascular function in skin. Eur J Clin Invest, 2003. 33 (7): p. 536-542. Serné, E.H., et al., Impaired Skin Capillary Recruitment in Essential Hypertension Is Caused by Both Functional and Structural Capillary Rarefaction. Hypertension, 2001. 38 (2): p. 238-242. Mathiassen, O.N., et al., Small artery structure is an independent predictor of cardiovascular events in essential hypertension. J Hypertens, 2007. 25 (5): p. 1021-1026. 10. Research methodology (up to 1800 characters, 1 page) To address the above challenges in diabetes healthcare, OPTOMICS combines imaging with molecular phenotypes to model disease based on: Sample and data collection at two time points (~2 years apart): Novel static and dynamic T2D biomarkers are read in the skin (on the dominant forearm, and on one side of the dominant lower leg ) using portable, non-invasive and label free RSOM readings. The instrument will be set up at the EstBB and the staff working with it are thoroughly trained to conduct the measurements on EstBB participants (user training confirmations are added in Appendix 9). Additionally, the exact location of RSOM sampling sites are recorded by taking pictures of the limbs (BP faces are not recorded). This is needed to provide a reliable record of the exact location of the sampling site to make sure the measuring is done in the same location at both time points. The pictures are taken with a camera used exclusively for this study and downloaded to a secure server of University of Tartu under a numbered code. Blood samples for metabolomics and proteomics and measuring blood markers required for RSOM measurements calibration and additional diabetes related markers will be collected at two time points, congruently with imaging, to capture time-dependent changes associated with diabetic progression. For these measurements we will collect up to 20 ml of venous blood from each participant at each time point. The collected blood sample is used for the following purposes: (a) Up to 9 ml of blood is collected for plasma extraction. 40 ul of plasma per BP and time point will be sent to the study partner TATAA Biocenter AB (Sweden), where proteomics analyses on Olink Proteomics platform will be conducted (applying Cardiometabolic and CVDIII or more comprehensive proteomics panel, if available at that time) to measure the content and amount of ~200 proteins in the samples (Appendix 7). 350 ul of plasma per BP and time point will be sent to the study partner Nightingale Health OY (Finland), where nuclear magnetic resonance (NMR) technology will be applied to measure ~250 metabolic-disease-relevant metabolites (Appendix 6). (b) Up to 11 ml of blood will be sent to the Laboratory at Tartu University Hospital, where additional markers from blood will be measured (Appendix 5). Additionally, urine samples (up to 10 ml) for the quantification of albumin and creatinine concentration in urine (markers of kidney function) will be collected at two time points during the time of the appointment. Samples will be sent to the Laboratory at Tartu University Hospital for analysis (Appendix 5). Study questionnaire (Appendix 4) will be filled by the EstBB specialist on the basis of the information provided by the participant. The questionnaire is completed electronically during the appointment and it takes about 5 minutes. Questionnaire concerns anthropometric measurements (e.g., BMI, etc.), cardiovascular and metabolic medical history (e.g., duration of T2D, relevant medication/therapy history, etc.), and cardiovascular risk factors (e.g., smoking, hyperlipidemia, hypertension, etc.). With the questionnaire, we specify such facts that may have changed since BP joined the biobank and the EstBB database may not contain accurate and updated data. Data analytics and the digital twin that employ advanced computation: Genome-wide association study (GWAS) between molecular and imaging traits and clinical outcomes using regression-based models. For GWAS genome-wide genetic information is needed to assess the additional value offered by incorporating genomic information in the digital twin for providing comprehensive insights and modelling of T2D longitudinal processes offering precise prediction, prognosis and patient stratification. For that we will apply the genotype data for up to 500 participants who agreed to enter this study (please see point 11 (sample size) for an explanation of the involvement of participants). The genotype data is already existing in EstBB. Characterisation of molecular and imaging Quantitative Loci Traits (QTLs). For that we will perform association testing between genome-wide genotypes and metabolite and protein levels and RSOM imaging data using linear mixed models to construct a map of molecular QTLs. Colocalization analysis will be conducted applying Bayesian colocalization analysis, following a region-based conditional analysis method. This helps to pinpoint whether genetic association signals and molecular or imaging QTLs that reside in the same genomic region both represent the same underlying effect. Establishing RSOM trait differences between the two time-points and between pairs of clinical groups. Testing the performance of Polygenic Risk Scores (PRS) and construction of stratified PRS on TUM dataset and validating on EstBB dataset by applying different computational pipelines. Construction of classifier based on molecular, genetic and imaging data by employing hierarchical clustering analysis followed by testing for correlation of these clusters with clinical parameters. Remarks In case of all analyses TUM biobank participant cohort will be applied by HMGU for initial analysis and EstBB cohort by UTARTU only for replication studies to validate the initial results. Additionally, an inverse variance-based fixed-effects meta-analysis across the two datasets will be conducted in order to maximise power. This means EstBB genotype information will not be shared with study partners and only UTARTU scientists in OPTOMICS team will have access to the pseudonymized genotype data. The sample and data collection for the first time point will start in December 2021 the earliest and will last until we have enough study participants involved. The second time point will be ~2 years apart from the first (start in December 2023). Before that, the par ticipants for the study cohort will be selected and other preparations will be made to start inviting the participants. 11. Study sample and description of recruitment method. Information and consent forms, questionnaires and tests should be submitted as annexes to the application. Sample size, inclusion of control groups We have four study groups: 1) non-diabetic controls (age, sex and BMI matched with T2D groups) 2) T2D without complications 3) T2D with microvascular complications 4) T2D with micro- and macrovascular complications. The sample size requirements of the project are at least 100 BPs to be involved per group at both time points. However, there are several aspects we need to consider: According to EstBB previous experience about 40 % of BPs invited to a study are responding. Thus, the cohort per group receiving the invitation to OPTOMICS study will be 1000 BPs. 200 invitations will be sent out per group at a same time and BPs will be recruited until we have reached the needed number of BPs in our study. We need the same BPs to attend at both timepoints. However, we need to consider that some of the BPs might not be able to attend at the second time point, thus for the first time point we will consider 125 BPs per group (which makes altogether up to 1250 invitations per group). If we are not able to get enough participants into any of the groups (most complicated is to get enough BPs into T2D with micro- and macrovascular complications group), we would increase the number of BPs in other groups accordingly, so we would have altogether 500 BPs recruited at first time point. We will send out invitations until the cohort group is full, thus, altogether up to 5000 BPs would receive the invitation to OPTOMICS study and 500 BPs will be recruited at the first time point. Who recruits and how/where/by whom is informed consent obtained? (if applicable) No new BPs will be recruited for current study; all the study subjects will be chosen from the current EstBB cohort. Prior to participating in the study the BPs must voluntarily sign the OPTOMICS study consent form (Appendix 1), which will be done during the first appointment at EstBB. Introduction of the study and the consent form to the participants will be made by the EstBB employee, who collects samples, takes measurements and fills in the questionnaire (Triinu Temberg , Esta Pintsaar). Participants may ask questions from the same person before signing the consent form. One signed copy of the consent form remains with the researcher, the other with the gene donor. How and from whom are the subjects selected (sampling frame)? What are inclusion or exclusion criteria of subjects? Sampling frame is all BPs (as of the first of January 2021 - 202 282 participants). We will apply the International Statistical Classification of Diseases and Related Health Problems 10 (ICD-10) codes and age, sex and BMI data to decide which BPs are suitable for OPTOMICS study. Please see the Appendix 3 for the detailed inclusion and exclusion criteria applied in the study. Type of interventions (physical, mental or data, including special categories of personal data) At both time points we would collect the following samples and data: Up to 20 ml of venous blood (altogether 40 ml per study) aimed to collect with one needle stick, if possible. Out of 20 ml up to 9 ml is used for plasma extraction and up to 11 ml is used for measuring additional blood markers. Up to 10 ml of urine at both time-points (altogether up to 20 ml per study) collected during the time of the appointment (the test containers are provided by the study specialist). Anthropometric measurements, pulse and blood pressure, as part of the study questionnaire (Appendix 4). Conduct non-invasive RSOM measurements from two different skin locations (on the dominant forearm, and on inner side of the dominant lower leg) . From the forearm dynamic RSOM measurement will be conducted using a flow-mediated dilation test on the dominant forearm that includes a cuff challenge to measure endothelial function. The latter is performed in the inner arm area with measurements taken while a cuff occlusion is applied to the arm and released after 3 min. The response of the vasculature in both the cuff and the release is recorded. In total the one static RSOM measurements (from lower leg) and the one dynamic RSOM examination (from forearm) (including preparation and information) would take approximately 30 minutes. The procedures ar e carried out by trained study specialists. Due to the laser used in the device the method could pose low risks to the subject, such as eye injuries, reddening of the skin or similar symptoms (especially when suffering from hypersensitivity to light). The risk of harmful laser light exposure is mitigated by the requirement that both the participant and the operator wear appropriate laser safety goggles with suitable protection level. The safety goggles will be provided by the specialist. For further safety, a key switch as well as a laser safety foot pedal which needs to be pressed during the whole imaging period are integrated into the RSOM C50 (laser hazard evaluation and declaration of laser safety, as well as instruction manuals are added as Appendix 10). Also, as body hair can produce irregularities in the transmission of incident light and the emitted sound waves, it might be sometimes necessary to shave the BP’s hair in the imaging region using single-use razor . or a depilatory cream . (BP can choose what she or he prefers) Pre-existing genotypes information of up to 500 participants will be used for GWAS analysis. Genotype information will not be shared with study partners and only scientists of the Institute of Genomics (Reedik Mägi, Ene Reimann, Kristi Läll, Triin Laisk, Toomas Haller) will have access to the pseudonymized genotype data. The data will be made available to them via the UT secure server until the end of the study. Burden on the subject (methods of contact, number of visits, type and number of procedures, repetition of invitations, etc.) The BPs will be invited to participate in the study via different channels (Appendix 2: a, b and c ): First we contact the BPs via e-mail. If we receive no answer, we send out another invitation in two weeks. If we receive no answer to two email invitations, we will send the invitation via regular mail once. If we do not receive an answer to our invitation via e-mail in two weeks, we will call the BPs up to three times. We will consider the answer to our invitation as “no”, if we are not able to reach the BP via above-mentioned channels. If the BP is willing to participate in the study the specialist from EstBB (Triinu Temberg, Esta Pintsaar) will call him/her to schedule a 1 , 5 -hour appointment time (at working day, between 8.00-1 2.00 ) for the first time point. For the second time point the specialist from EstBB will call the BP to schedule the second 1 ,5 -hour appointment time (at working day, between 8.00-1 2.00 ). During the call to schedule the appointment, the specialist will ask from the BP the control questions to establish any contraindications that would prevent the subject from participating in the study (defined exclusion criteria listed in Appendix 3), including pregnancy, skin rash, wounds or inflammation at the RSOM measure areas, or previously determined light sensitivity. The appointment is scheduled only if the BP has none of these conditions. Sending out invitations and contacting BP-s by phone is done only by specific persons who have been granted the right by the director of the Institute of Genomics to process personal contact data. The EstBB staff member contacting the BP-s by phone will be granted access to the phone numbers of the gene donors to be invited. The list of phone numbers is kept in a password protected computer. The list with BP´s data will be available for above-mentioned researchers until the end of the project at the latest (Dec 2025) as it contains a schedule of receptions. After that the data will be deleted from the computer. The PBs will be invited twice (first time point will start in December 2021 the earliest and will last until we have enough study participants involved. The second time point will be ~2 years apart from the first (starts in December 2023)) into the EstBB building in Riia Street 23b, Tartu, Estonia. To prepare for the study we will request that BPs abstain from: exercise for at least 48 hours before the measurements, consuming anything except water for at least 9 hours before the planned measurements, consuming any alcohol, coffee and fatty food the day before, smoking on the day of the measurement, taking their regular medication in the morning before the measurements, if possible; the health risk due to not taking medication at home is minimal as the appointments are planned to take place in the morning and BP can take their medication directly after measurements are done. Latter is needed, as these factors affect the blood biomarker pattern and also RSOM results. First appointment contains the following steps: Room 1: ~ 45 min Prior to signing the OPTOMICS study consent form, there is time for questions the BP might have about the study. Also, the workflow and the risks of the study will be explained to the BP. Signing the consent form (if the BP decides not to sign the consent form the following steps will not be conducted). Measuring blood pressure and pulse RSOM measurements Room 2: ~ 45 min Measuring height, weight, hip and waist circumference. Collecting the blood samples Answering the study questionnaire. Collecting urine samples (at a restroom located next to the Room 1 and 2). Second appointment contains the following steps: Room 1: ~ 45 min Reminding the workflow and the risks of the study. Measuring blood pressure and pulse RSOM measurements Room 2: ~ 45 min Measuring height, weight, hip and waist circumference. Collecting the blood samples Answering the study questionnaire. Collecting urine samples (at a restroom located next to the Room 1 and 2). Room 1 and Room 2 will be located in the EstBB building, next to each other. The BPs are invited in 45 min shifts, thus up to five BPs per day can be scheduled. The reception is conducted in two rooms to ensure a smooth flow of visits. The measurements are performed by the following researchers: Triinu Temberg, Esta Pintsaar, Martin Tootsi, Ene Reimann, Helene Alavere , . They all are trained to use RSOM (please see the certificate, Appendix 9). The three first mentioned researchers are the main users of RSOM, the latter two researchers are trained to conduct the measurement when other researchers are busy or on vacation. The greater involvement of researchers in the conduct of admissions is due to the large number of BPs and the limited timeframe. 12. Issuing of tissue samples to third parties (RNA, DNA, plasma etc) The number of gene donors whose tissue samples will be issued and the types of tissue samples to be issued Metabolomics and Proteomics: The plasma samples extracted from the venous blood of the whole study cohort (up to 500 BPs from the first time point and all BPs also participating at the second time point) will be sent to Biocenter AB (Sweden) and Nightingale Health OY (Finland). For sending samples to be preserved and studied outside Estonia, the permission of the S enate of the University of Tartu will be requested. Additional blood markers: The venous blood samples of the whole study cohort (up to 500 BPs from the first time point and all BPs also participating at the second time point) will be sent to the Laboratory at the Tartu University Hospital. Additional markers from urine: urine samples of the whole study cohort (up to 500 BPs from the first time point and all BPs also participating at the second time point) will be collected during the time of the appointment and sent to the Laboratory at the Tartu University Hospital. The amount of tissue sample to be issued per one gene donor Metabolomics and Proteomics: Up to 390 ul of plasma samples per time point per BP will be used (40 ul will be sent to TATAA Biocenter AB (TATAA) and 350 ul to Nightingale Health OY (NGH)), thus altogether during the study period 780 ul of plasma per BP. Additional aliquots might be required, if the proteomics or metabolomics analyses fail in the first attempt. In the latter case, the additional plasma sample will be sent to the partner institute. The additional sample will be aliquoted from the same samples stored at EstBB collected from the first and/or second time point. Thus, the maximum amount of plasma shipped abroad per gene donor throughout the study is 1560 ul. Additional blood markers: Up to 11 ml of blood samples per time point per BP will be used, thus altogether up to 22 ml of venous blood per BP throughout the study. Additional markers from urine: up to 10 ml of urine per time point per BP, altogether up to 20 ml urine per study. The entity to whom tissue samples will be issued (country, institution, address)? TATAA Biocenter AB Odinsgatan 28 Göteborg 411 03 Sweden Contact: Prof. Dr. Mikael Kubista e-mail:
[email protected] Tissue samples: plasma, up to 160 microliters per BP throughout the study 2) Nightingale Health OY Mannerheimintie 164A Helsinki 00300 Finland Contact: Dr. Emmi Tikkanen e-mail:
[email protected] Tissue samples: plasma, up to 1400 microliters per BP throughout the study 3)Laboratory at the Tartu University Hospital L. Puusepa 8 Tartu 50406 Estonia Contact: Dr. Anu Tamm e-mail:
[email protected] Tissue samples: venous blood up to 22 ml per BP throughout the study and urine, up to 20 ml per BP throughout the study Note: The Laboratory at the Tartu University Hospital does not participate in data analysis nor has access to the personal data of BP (all tissue samples are marked with codes). What will be done with the residue samples (will the residue samples be destryed or sent bk to Gene Bank)? Metabolomics and Proteomics: At the partner’s institute (TATAA and NGH) the residue plasma samples will be destroyed after 10 years from the time receiving the samples. This is necessary in case the writing of articles reveals the need for re-analysis. At the EstBB the remaining plasma samples will be stored indefinitely. Long-term plasma preservation is important as it is a valuable biological material that can be used in future research. The relevant information is provided in the consent form. Additional blood markers: At the Laboratory at the Tartu University Hospital the sample residues will be destroyed within 10 days from the analysis. Additional markers from urine: At Laboratory at the Tartu University Hospital the sample residues will be destroyed within 10 days from the analysis. 13. Analysis of the ethical aspects of the study (3600 characters, up to 2 pages). All research involving human subjects must be carried out in compliance with ethical requirements, in particular the principles of respect for autonomy, charity and the prevention of harm, and justice. ( https://www.coe.int/en/web/bioethics/guide-for-research-ethics-committees-members ). The project is carried out on the basis of the Human Genes Research Act (HGRA https://www.riigiteataja.ee/en/eli/ee/Riigikogu/act/508042019001/consolide) and other legislation concerning the work of the EBB. The principles of bioethics have been taken into account when planning activities. 1. The principle of respect for individual autonomy The main features of the first principle are the voluntary nature of participation in the trial, the existence of written consent and the protection of privacy and personal data. This study will include data from volunteer biobank participants (BP) of Estonian Biobank . BP have signed a consent form for joining the Estonian Biobank, allowing to use their data for different research purposes. The consent form to become a gene donor and the following execution and maintenance procedures are set out by the Minister of Health and Labour (https://www.riigiteataja.ee/akt/117042019016). According to HGRA § 12 by signing the consent a gene donor agrees to provide a tissue sample, to have a description of the state of health or the genealogy of the person prepared, to entry of the description of the state of health or the genealogy in the Gene Bank in pseudonymised form and to use thereof for genetic research, assessment of personal health risks and prevention of diseases, public health research and statistical purposes. We ask for permission to depseudonymise the personal data of up to 5000 biobank participants. This is needed for inviting BPs to the study. Scientists analysing data will use only pseudonymised data and no data re-encoding by partners will be permitted. No genomics data of BPs will be sent abroad. Therefore, the threat to the gene donors’ privacy is low. All persons who decide to participate in the study must sign the study consent form. Every subject has the right to leave the study without giving a reason. 2. The principle of not doing harm The present study has a research design developed by competent scientists and has the latest technology for performing analyzes. Implementing high-level technology ensures the accuracy and high quality of the research. The study uses non-invasive techniques that do not alter the examined tissue. A blood sample will be collected from each participant - a standard procedure (usual one peripheral venous puncture) with low risks, carried out only by specialized personnel. The volume of blood collected poses no health risk to the participant. Additionally, each participant will undergo RSOM imaging of their leg and arm. Overall, this imaging technique poses no danger to humans since it uses non-ionizing and safe optical energy. Staff working with the device have already had thorough hands-on training to conduct the measurements on EstBB participants. The room where the RSOM device is placed has been inspected by a specialist from iThera Medical and the necessary adjustments have been made (the window has curtains in front, the mirror has been removed from the room, a warning sign is hung on the door, the door is locked from the inside to prevent people from entering during the ongoing procedure). iThera Medical is a company providing the RSOM apparatus for the study. Safety information and instruction manuals for the device used for the optoacoustic measurements are added as Appendix 10. Threat to the data of individuals is minimized, as it is not used outside the protocol. This study may cause psychological stress to participants as the new technology is used, but researchers can assure that the measurements done using the RSOM technology are safe, painless and non-invasive . All measures and restrictions established by the Government at the time of the appointments for preventing the spread of COVID-19 will be followed. The rooms are ventilated between each appointment and all surfaces that can come in contact with people are cleaned and disinfected. During the appointment, the study specialists are wearing medical face masks. Dispersal between individuals is ensured by pre-registration, the BP-s are advised to arrive at the appointment at the agreed upon time, not significantly earlier or later. Entrance to the EstBB building is equipped with hand sanitizers. 3. The principle of charity EstBB will provide the gene donor with the results of the blood marker analysis and urinalysis performed at the Laboratory of the Tartu University Hospital in case the donor has so requested in the OPTOMICS consent form. The data will be sent to the donor via email, he/she can turn to the general practitioner for interpreting the results. BP will not be informed of the RSOM results, as they are assessed in terms of dynamics, not as an indicator of the current situation. Social charity is manifested through scientific innovation and the improvement of the health system. In the long term, the application of research results will be towards more personalized treatment, prevention and diagnosis. 4. The principle of justice This research creates a prerequisite for more effective, safer and better access to healthcare in society. Estonian Biobank is a population-based biobank, where different social and age groups are represented, the distribution of gender and other demographic features in the Estonian Biobank quite well reflect the composition of the entire Estonian population. Thus, in the long run, all members of society benefit from research. Remarks: According to the Human Gene Research Act (HGRA) EstBB all tissue samples shall be preserved in the territory of the Republic of Estonia. The University of Tartu senate may, if good reasons therefor become evident, grant permission for tissue samples to be preserved and studied outside the territory of the Republic of Estonia if the tissue sample is issued in unpersonalised form and the controller ensures effective control over the tissue samples and that the tissue samples cannot be used in a manner prohibited by legislation. The samples will be issued from the EstBB in accordance with the requirements established in sections of HGRA § 20 (1) and § 22 (4) respectively in pseudonymised form and as a set of data, which means they cannot be used as a basis for characterizing a particular gene donor and that they can only be used for scientific research. An agreement will be concluded with the institution receiving the tissue samples pursuant to §18 (3) of the HGRA. The tissue samples must be issued in accordance with a regulation of the minister responsible for the area “Procedure for Issuing Tissue Samples, DNA Description and Health Description of Gene Donors” (https://www.riigiteataja.ee/akt/86997?leiaKehtiv). 13 a Human subjects Assistance questions No Yes Are people the object of research? If applicable, describe how voluntary participation in the study is ensured and any undue influence on study participants to participate in the study is avoided. Yes, w e will not recruit new participants with this study. The participation in the Estonian Biobank is strictly voluntary and based on signing an informed consent form. The participant rights (incl. obtaining consent and consent withdrawal) are regulated by the Human Genes Research Act. The participants are aware of the use of their data for research purposes based on HGRA §16 and the informed consent. The participants may withdraw their consent of participation and the data of these individuals will not be used in future studies. To participate in the OPTOMICS study, gene donors voluntarily sign a sepa rate consent form. There is no fee offered to participate in the study to avoid bias. Participants have the right to withdraw from the study at any time. Participants will be reimbursed for transport costs and free meals will be offered, if desired. Are the study participants vulnerable individuals or groups? No Indicate to which vulnerable group the study participants belong and what their vulnerability lies in (details of the type of vulnerability). In case the inclusion in the study is based on informed consent, please describe the procedure for obtaining informed consent and include a consent form. These activities must ensure that individuals understand the risks involved in participating in the study. Does the study include persons who cannot themselves give informed consent to participate in the research (incl. persons with limited active legal capacity)? No Describe how the guardian or legal representative is informed and how the consent from them is obtained for participation of the individuals with limited active legal capacity, including children/minors. Are the study participants children/minors? No Please provide an age range. Describe the procedure of obtaining consent from the parents of the child. Describe how the consent of the minor is sought or the opinion of the minor is taken into account in proportion to his or her age and degree of maturity. Describe how the well-being of minors is ensured. Explain the reason for including minors in the study. Are the study participants patients? What disease/condition/disability do they have? The BPs invited to the study have or do not have the T2D diagnosis. Details of the recruitment, inclusion and exclusion criteria and informed consent procedures. During the recruitment into the OPTOMICS study the BPs are not patients; however, it is possible that the EstBB database contains data, which is collected at the time the BPs were patients. The BPs with diabetes diagnosis are patients; however, the data and sample collection does not take place at their doctor’s office but in the office at EstBB specifically set up for the OPTOMICS study. Thus, the doctor’s- patient’s relationship is not inclining the BP to participate in the OPTOMICS study. The BPs are informed that their participating or not participating in OPTOMICS study does not affect the quality of their healthcare services. Detailed informed consent form (included as Appendix 1), notifying the subject about his or her rights, potential risks and benefits of participation is provided together with the invitation to the study. Invitation is sent either via e-mail or regular mail (examples in Appendix 2) or via telephone call, in which case the risks and rights are explained orally. The signed informed consent is obtained from all subjects prior to study inclusion, during their first appointment at EstBB. The inclusion and exclusion criteria of the study participants are listed in Appendix 3. What is your policy on incidental findings? How will the participants be informed about incidental findings? Within this project, no genotyping nor sequencing will be done and therefore there cannot be any incidental findings from genetic data. The BPs participating in OPTOMICS study will have a list of blood and urine markers measured at both timepoints. In case they agree in the OPTOMICS consent form to receive the results of these measurements, we will send them the data via e-mail and they can turn to their general practitioner for interpreting the results. Does the research involve collection of biological samples? Are human biological samples intended for export to a third country ( https://www.aki.ee/et/teenused-poordumisvormid/andmete-edastamine-valisriiki ) ( https://www.aki.ee/en/guidelines/transfer-personal-data-foreign-country-0 ) or import them from another country to Estonia? What type of biological samples will be collected? Venous blood samples and urine samples. What are your procedures for collecting biological samples, including use of previously collected samples? Drawing venous blood samples applying vacuum tubes at EstBB study office by an experienced specialist. The BP will give a urine sample during the time of the appointment, the container will be provided by the study specialist. 3) Explain how the rights of the subjects are ensured. Prior to agreeing to participate in the study and signing the study consent the BP will be informed about the burden and potential risks of the study. The BP has the right to withdraw the consent to participate by sending a simple notification without providing a reason. The procedures for termination of consent are provided in the consent form. 4)Explain what will be done with the biological samples after the end of the study. The remaining plasma samples collected during the study will be stored in EstBB indefinitely. The samples, which are sent to Tartu University Hospital will be destroyed within 10 days from the analysis. The samples, which are sent to study partners abroad will be stored for 10 years after which they are destroyed. Please see further explanation in point 12. 13 b Personal data and datasets No Yes Are personal data collected or analyzed in the study, including special categories of personal data? The full list of variables collected in the study (may be provided as an annex). Please see the Appendix 5 to 7. Confirm that informed consent exists or is obtained before the start of the study if the study is based on consent. Objects of research are participants of EstBB. All participants have signed the consent to become a gene donor before joining the EstBB. All BP-s, who agree to participate in the study will need to voluntarily sign the additional OPTOMICS study consent form. Explain why all data processed are relevant and necessary (based on the principle of data minimization). The OPTOMICS study applies the following data: personal data is needed to contact BPs and invite them to the study; genotype data to evaluate the genetic associations with different phenotypic and clinical traits; blood markers to calibrate the RSOM measurements and find associations with genetic and clinical data; urine markers to find associations with genetic and clinical data; RSOM measurements to find associations with genetics, phenotypic traits and clinical data; study questionnaire to find associations with genetics, other phenotypic traits and clinical data; RSOM measurements, blood and urine marker analyses and filling the study questionnaire is conducted twice as we want to evaluate how these markers change in time and how it correlates with the clinical data. Are the data subjects identifiable? All the data in this study is pseudonymised prior to sending to the EstBB scientists or partners. The tissue samples are marked with codes. The key to the codes are kept in the EstBB coding center 10 years after the end of the study in case the writing of articles reveals the need for re-analysis. Thus, the BPs cannot be identified by scientists. During the course of the study the personalized information can be seen only by the EstBB staff members inviting BPs to the study and collecting the data (specialist of data collection Esta Pintsaar, specialist Triinu Temberg, Research Fellow of Orthogenomics Ene Reimann and Head of the Data Collection Office Helene Alavere). For other study scientists the data will be pseudonymised so that there is no ability to link data to individuals. If yes, please describe how the following conditions are met: after the removal of the personal identifiers, the purposes of data processing are no longer achievable or would be unreasonably difficult to achieve; in the opinion of the persons conducting scientific or official statistics, there is an overriding public interest therein; the scope of obligations of the data subject is not changed based on the processed personal data or the rights of the data subject are not excessively damaged in any other manner. Does the research involve systematic monitoring of an individual, the collection of his or her data profile, or a large-scale processing of data of special categories and /or sensitive data, or the use of (intrusive) data processing techniques in a covert way (eg survival surveys, monitoring, surveillance, audio and video recording, geolocation, etc.) or any data processing that may harm the rights and freedoms of the data subject? Explain which methods are used for surveillance, monitoring and observation of subjects. The BPs will be called twice (~2 years apart) into the EstBB office specifically set up for the study. One visit will last up to 1 hour during which the anthropometric and RSOM measurements will be conducted and up to 20 ml of venous blood plus up to 10 ml of urine will be collected. Additionally, a study questionnaire (questions about lifestyle, recently consumed drugs and general health) will be filled (Annex 5). Explain the methods of creating the profile of the subjects. The BP profile will be put together from the following data sources: genotype data from EstBB phenotype data from EstBB (T2D diagnoses and micro- and macrovascular complications) study questionnaire including anthropometric measurements blood markers (biochemical markers, metabolomics, proteomics) urine markers RSOM markers Explain how subjects are informed about their rights and the potential risks that data processing may entail. The BPs are fully informed of all aspects of the study during invitation (detailed informed consent form notifying the subject about his or her rights, potential risks and benefits of participation is attached to the e-mail or sent via regular mail together with the invitation; via telephone invitation, the risks and rights are explained). If the BPs have additional questions prior to the appointment, they can turn to EstBB via e-mail or telephone. During the appointment the BP can ask additional questions from the EstBB specialists. Explain how data will be collected for the profile of the subjects and how the study participants will be informed about possible consequences and safeguards. genotype data is taken from EstBB, and has been created before the OPTOMICS study; phenotype data from EstBB (T2D diagnoses and micro- and macrovascular complications) has been collected before the OPTOMICS study; study questionnaire including anthropometric measurements, blood pressure and pulse measurements will be filled during both appointments at EstBB; blood markers data (biochemical markers, metabolomics, proteomics) will be measured from the blood samples from both appointments at EstBB; urine markers (albumin and creatinine) will be measured from the samples taken during both appointments at EstBB; RSOM markers will be measured at both appointments at EstBB. The BP will be informed about possible consequences and safeguards during invitation, prior to signing the consent form and also during the second appointment at EstBB. Is there a plan to analyze previously collected personal data? Explain from which database (register) or source the data are obtained. Yes, previously collected data about BP already collected into EstBB servers will be used. The data is obtained from earlier EstBB questionnaires. No data requests from other registers are done. Explain how subjects are informed about their rights and the potential risks that data processing may entail. The BP will be informed about possible consequences and safeguards during the invitation, prior to signing the consent form at the first appointment and also during the second appointment at EstBB. Explain why all data processed are relevant and necessary (based on the principle of data minimization). The OPTOMICS study applies the following data obtained from EstBB: personal data (name, ID number, e-mail address, phone number, home address) is needed to contact BPs and invite them to the study, ID number is necessary to ensure person's identity, which will be checked in the process of signing consent form; genotype data to evaluate the genetic associations with different phenotypic and clinical traits. phenotype data (T2D related diagnoses, age, sex) to evaluate associations with genetic and clinical data. Explain why it is not possible to study the participants in such a way that the data obtained were anonymous or pseudonymous (if applicable). We need to depseudonymize the BP’s as we need to call them back to EstBB to perform additional measurements (blood, urine and RSOM markers) and fill the study questionnaire. Prior to making the data accessible for the study scientists it will be again pseudonymized. Is there a plan to analyze publicly available data? No Explain that the data are publicly available (open data registers and databases) and can be used freely in research. Is there an intention to transfer personal data or provide access to personal data to third countries ( https://www.aki.ee/et/teenused-poordumisvormid/andmete-edastamine-valisriiki )? (https://www.aki.ee/en/guidelines/transfer-personal-data-foreign-country-0) No Explain what personal data are exported or imported. If so, to which and from which countries. Personal data ( name, contacts etc.) will not be transferred or made accessible to third countries. One of the study partners, Rayfos LTD located in UK, will receive the following pseudonymized data, which is needed for them to develop the RSOM algorithms applicable for OTOMICS data analysis tools: study questionnaire data RSOM measurements blood markers needed for RSOM calibrations Genotype data will not be made accessible for partners. It will be made available for EstBB researchers via a server of the University of Tartu. Explain what protection measures are applied, on what grounds (contract, etc.) the data are transferred and how the rights of the subjects are ensured. As Rayfos is located in the United Kingdom, which is located outside the European Economic Area, and therefore in this case additional measures must be used to protect data in accordance with Articles 46 and 49 of the General Regulation on the Protection of Personal Data of the European Union. Everything related to the transmission, storage and destruction of data will be specified in detail in the partnership contracts. The fulfilment of the contract is controlled by the University of Tartu (data controller). Will personal data be destroyed / anonymised at the end of the research? In case the analysis uses data in a form which enables identification the study participants, please 1) describe how personal data will be destroyed / anonymised after the research has been finished and the objectives have been achieved; 2) add an assessment of how the possibility of indirect identification of data subjects is managed after the destruction of data enabling direct identification of a person. The data and biological samples at EstBB will be stored indefinitely. The samples sent to the Laboratory at the Tartu University Hospital will be destroyed within 10 days from the analysis The data and samples sent to OPTOMICS partners abroad will be destroyed 10 years after receival. 13 c Other ethical issues Can conducting research involve ethical risks not described above? No Explain, if necessary, the additional ethical risks that may arise from factors such as artificial intelligence, personal medicine, involvement of military partners, new developments in neurobiology, genetic engineering, nanotechnology, human-machine interaction, android and cyborg creation, etc. 14. Complete in case the research is based on data from a database and/or register Name of database and/or register EstBB Purpose of the processing of personal data Processing of personal data is necessary to conduct a study and administrate the recalling of the EstBB donors. List of variables and period for which data are collected (in annex if necessary) The data is collected between December 2021 and December 2025. The collected data is listed in Appendix 8. 15. Description of personal data protection measures, including data storage, security and erasure, including date of erasure of data and / or code key (up to 1800 characters, 1 page). Describe and justify the storage of data collected for the study and the deadline for storage. For information on biological samples collected please refer to point 12. At the EstBB the remaining biological samples and other collected data such as RSOM measurements and data obtained from the questionnaires will be stored indefinitely (integrated to the gene donor data stored at the EstBB). Researchers of EstBB listed on the application w ill have access to the collected data until the end of the study (31.12.2025) through the secure server of University of Tartu. The residue plasma samples sent to partner institutes (TATAA and HGH) will be preserved for 10 years from the time of receiving. The preservation of plasma samples is needed for future research as well as to provide a possibility for re-analysis for publication purposes. The study participants have been provided with the information in the informed consent to the purposes, uses and retention of the data collected. The consent forms are stored at the EstBB coding center indefinitely, to ensure that in the event of any inquiry from the gene donor, it is possible to establish his/her declaration of intent. Describe the process and means of pseudonymisation of personal data. The data collected on gene donors has been pseudonymized during their accession to the EstBB. For the purpose of the study the subjects are pseudonymized through using a numbered study code, the key of the code is kept at the EstBB coding center for 10 years after the end of the study and is then destroyed. Is there a plan to de-pseudonymise gene donors’ data? Please specify the number of gene donors whose data will be de-pseudonymised. Prerequisite for de-pseudonymisation is to obtain EBIN approval. Contact with a gene donor takes place based on consent to become a gene donor and the Human Gene Research Act. Further activities will take place with the additional consent of the gene donor. Institute of Genomics hereby requests permission from EBIN to de-pseudonymise data of BPs. Up to 5000 BPs will receive the invitation (e-mail, regular post, telephone) to the OPTOMICS study, for that purpose they need to be de-pseudonymized. Please explain the reason for de-pseudonymisation. We need to depseudonymise the BP’s as we need to call them back to EstBB to perform additional measurements (blood, urine and RSOM markers) and fill the study questionnaire. Prior to making the data accessible for the study scientists it will be again pseudonymised. Is there a plan to transport personal data? Please describe how data protection is ensured. The processing of the personal data for inviting is described in p. 11. For transferring the data, the partners will be provided password protected access to the server of the High Performance Computing Center at University of Tartu. From there they can download the data into their secure servers. Prior to the data sharing, contracts between partners and UTARTU will be concluded, where detailed data usage and proceeding conditions will be termed. Describe how the data are protected against unauthorized or unlawful processing. Data on human participants and their biological samples will be collected and processed for purposes relevant to accomplish the OPTOMICS objectives. Only necessary data that are adequate and relevant will be collected and that will not include information that can be regarded as superfluous (‘data minimization principle’). The collection, maintenance and release of the genetic and health data at the Estonian biobank are conducted in accordance with the Human Genes Research Act (HGRA, https://www.riigiteataja. ee/en/eli/508042019001/consolide), which ensures that the identity of participants remains confidential. It also specifies the conditions for sample processing, restrictions on the use of samples and conditions for research activities. All processes have been reviewed and updated in light of the GDPR. All Estonian Biobank participants, aged 18 and up, have signed an informed consent allowing broad genetic research, as well as all activities described in the Estonian Human Genes Research Act (HGRA). Importantly, the act allows re-contacting the participants for specific studies and interventions. For re-contacting biobank participants, additional permission from the Estonian Committee on Bioethics and Human Research will be obtained. For EstBB researchers who perform data analysis data from patients will only be accessible in pseudonymised form. The data are stored securely on a secure server of University of Tartu with a back-up function. OPTOMICS partners will take adequate measures to ensure data protection and confidentiality. The latest local, national and international rules on data protection (in particular, Directive 95/46/EC of the European Parliament and of the Council of 24 October 1995 on the protection of individuals with regard to the processing of personal data and on the free movement of such data) will be followed and no information on the personal details of the study participant will be transferred. I confirm that all researchers are aware of the ethical and personal data protection requirements of the project. Signature of the principal investigator Date of application 27.07.2021 Signed digitally EBIN ID of the application (fills by the assessor) List of additional documents: CV of the principal investigator The CV of the Principal Investigator, Reedik Mägi, can be found on the link below: https://www.etis.ee/CV/Reedik_M%C3%A4gi/est?tabId=CV_ENG Appendix 1. Informed consent form (EST) Appendix 2. Invitation to the study 2a invitation sent by email (1st letter) 2b invitation sent by email (2nd letter) 2c invitation sent by regular mail Appendix 3. Detailed inclusion and exclusion criteria Appendix 4. Study questionnaire Appendix 5. List of additional markers measured from blood and urine Appendix 6. List of metabolites measured from blood Appendix 7. List of proteins measured from blood Appendix 8. List of variables Appendix 9. User Training Confirmations Appendix 10. RSOM C50 Instruction manuals, Laser Hazard Evaluation, Declarations of Absence of Risks, and Laser Safety Appendix 11. Sõidukulude hüvitamise avaldus Remark: All forms sent to participants will be translated also into Russian after getting the approval for the Estonian versions. The approval from Estonian Committee on Bioethics and Human Research will be applied.
Uuritava informeerimise leht ja teadliku nõusoleku vorm Uuringu nimetus: Optoakustiliste fenotüübi andmete ja multi-oomika kombineerimine diabeediga seotud tervishoiu edendamiseks . Uuringu lühike nimetus on OPTOMICS . Hea geenidoonor! Tartu Ülikooli Eesti geenivaramu pöördub Teie poole, kuna olete geenidoonor. Kutsume Teid osalema rahvusvahelises teadusuuringus OPTOMICS , mis käsitleb teist tüüpi diabeeti . Käesolev dokument sisaldab olulist teavet uuringu kohta ja aitab Teil lõplikult otsustada, kas Te soovite uuringus osaleda. Uuritava informeerimise lehe ja nõusoleku vormiga tutvumisel võite esitada küsimusi uurijale, kui soovite midagi täpsustada või midagi on jäänud ebaselgeks. Uuringu eesmärk on leida võimalusi, mis aitaksid parandada teist tüüpi diabeedi käsitlust tervishoius. Selleks analüüsime Teie veres ja uriinis leiduvaid markereid, uurime aparaadiga Teie veresoonte seisundit ja otsime teist tüüpi diabeedi tekkimise ja haiguse kulgemise seoseid pärilike teguritega. Me eeldame, et kõigi nimetatud uurimismeetodite kooskasutamisel saame haigust paremini jälgida ja tüsistuste tekkimist ennetada. Uuringu viivad läbi Tartu Ülikooli Eesti geenivaramu ja Tartu Ülikooli bio - ja siirdemeditsiini instituudi teadlased koostöös teadlastega Saksamaa Liitvabariigi, Rootsi, Soome ja Ühendkuningriikide partnerinstituutidest. Uuringu t on hinnanud Eesti bioeetika ja inimuuringute nõukogu ja andnud loa uuringu läbiviimiseks . Metoodika Uuringu jooksul palume Teil tulla kahel korral vastuvõtule Tartu Ülikooli genoomika instituudi uuringukabinetti desse , mis asu vad Tartus Riia 23b, I korrusel. Visiidid toimuvad umbes kahe-aastase vahega. Kaks erinevat ajapunkti on olulised, et hinnata mõõdetavate markerite võimalikke muutusi aja jooksul. Ühe vastuvõtu pikkuseks on kuni 1 , 5 tundi. Kohaletulek on vajalik, kuna soovime Teid mõõta ja kaaluda, koguda uriini ja veeniverd molekulaarsete markerite määramiseks . Samuti viime läbi mitteinvasiivse ehk naha pinnalt toimuva optoakustilise uuringu veresoonte seisundi hindamiseks. Selleks kasutatav aparaat meenutab ultraheliaparaati, kuid ta kasutab läbi naha mõõtmise tegemiseks kitsast valguskimpu ehk laserit. Esimese ja teise visiidi tegevused on sarnased. Need toimuvad kahes kõrvuti asuvas uuringutoas. Tuba 1: seal viibite kokku kuni 45 minutit Teile selgitatakse veelkord üle teadusuuringu olemus ja eesmärgid ning võimalikud riskid. Kui Teil on uuringu kohta küsimusi, saate need esitada geenivaramu uurijale. Selleks, et uuringus osaleda, on vajalik Teie vabatahtlik nõusolek, mille kinnitamiseks peate esimesel vastuvõtul allkirjastama OPTOMICS uuringu nõusoleku vormi . Teil mõõdetakse vererõhk ja pulss . Teostatakse kaks optoakustili st mõõtmi st juhtiva poole käsivarre ja sääre sisekülje nahal. Käsivarre veresoonte hindamiseks asetatakse õlavarrele mansett, mis on sarnane vererõhu mõõtmise seadmega ja milles hoitakse mõõtmise ajal sees rõhku (3 min) . See on vajalik, et m õõ ta veresoonte seisundit verevarustuse lühiajalisel piiramisel ja selle taastumist pärast vabastamist . Säärepiirkonnas mansetti ei kasutata. Mõõtmine on valutu. Parema mõõtmistulemuse saamiseks võib osutuda vajalikuks mõõtmise piirkondade eelnev raseerimin e ( ühekordse raseerijaga) . Tuba 2: seal viibite kokku samuti kuni 45 minutit Mõõdetakse Teie pikkus, kaal, puusa- ja vööümbermõõt. Teilt kogutakse veenivere proovid (ühe nõelatorkega kogutakse erinevatesse tuubidesse kuni 20 ml verd). Teil palutakse vastata uuringu küsimustikule, kus on küsimused Teie haiguste, tarvitatud ravimite ja elustiili kohta. Samuti mõõdetakse ja märgitakse küsimustikku Teie mõõtmise tulemused. Teil palutakse anda uriiniproov (proovi saate anda uuringutoa vastas asuvas tualettruumis, proovitopsi saate meie käest). Teile kompenseeritakse Tartusse uuringuvisiidile sõiduga seotud transpordikulud kuni 3 5 € ulatus es ja toitlustuse kulud kuni 8 € ulatuses ühe visiidi kohta. Selleks on vajalik meile esitada avaldus koos kuludokumentidega (ühistranspordi piletid või isikliku auto kasutamise korral kütusetšekk, toitlustusasutuse või toidupoe tšekk) . Kulude hüvitamise taotluse koos juhendi ja ettemakstud ümbrikuga saate meie käest vastuvõtu lõpus. Teie õigused uuringus osalemisel Uuringus osalemine on rangelt vabatahtlik. Uuringus osalemine või mitteosalemine ei mõjuta kuidagi Teile osutatavate raviteenuste kvaliteeti. Te võite igal ajal loobuda uuringus osalemisest loobumise põhjust nimetamata. Loobumiseks on vaja teavitada uurijat vabas vormis kirjaliku teatega (paberil avaldus saata postiaadressile: Reedik Mägi, TÜ genoomika instituut, Riia 23b, 51010, Tartu või saata e-kiri aadressile:
[email protected] ). Juba kogutud andmeid ei kustutata ja kasutatakse uuringu kokkuvõtete tegemisel, kuid uusi andmeid enam juurde ei koguta. Uuringust loobumisel ei ole uuringus osaleja jaoks negatiivseid tagajärgi. Uuringu käigus on Teil õigus jätta vastamata küsimustele, mis tunduvad ebamugavad või millele Te ei soovi vastata. Kui Teil on küsimusi seoses enda kui uuritava õigustega, saate pöörduda Eesti bioeetika ja inimuuringute nõukogu poole, e-post
[email protected]. Kui Teil on andmekaitset puudutavaid küsimusi, siis saate pöörduda Andmekaitse Inspektsiooni poole telefon 627 4135, e-post
[email protected] . Võimalikud riskid ja kasu Uuringu käigus kogutakse Teilt veenivereproov kuni 20 ml. Vajaliku väljaõppe saanud ja kogenud personal teeb seda võimalusel ühe torkega, kasutades standardset ühekordset venoosse vere kogumise metoodikat. Veenivere võtmine võib olla valulik ( valu möödub tavaliselt kuni poole tunni jooksul ) ja s üstekohale võib tekkida verevalum ( kaob hiljemalt nädala jooksul ) . Veresoonte seisundi mõõtmise käigus kasutatakse laservalgust , mille silma sattumisel võivad tekkida pöörduvad või pöördumatud silmakahjustused (nt põletused) ning ajutine või püsiv pimedaksjäämine . Selle sattumine silma on vähetõenäoline, kuna aparaadi laserkiirt väljastav otsik on suunatud alla ja mõõtmiste ajal peavad k õik ruumis viibijad kandma kiirguse eest kaitsvaid prille. Kaitseprillid annab geenivaramu uurija ja kontrollib, et need on Teil õigesti ette pandud. Lisaks on oht väiksemateks nahavigastusteks nagu nahaärritus või punetus. Muid riske pole teada ega kirjeldatud. Uuringu käigus kogutud andmeid (uuringuküsimustik, verest ja uriinist mõõdetud markerid, optoakustilised mõõtmised) ja geenivaramus olevaid andmeid (genotüübi ja terviseseisundi kirjelduse andmed) analüüsivad teadlased. Need andmed saavad nad pseudonüümitud ehk kodeeritud kujul, mis tähendab, et nad ei saa infot Teie isiku kohta ja neil pole võimalik Teie isikut tuvastada. Teie andmed kodeerib uuringu käigus TÜ Eesti geenivaramu ja säilitab koodi võtit oma turvalises kodeerimiskeskuses kuni 10 aastat pärast uuringu lõppu . See on vajalik, et oleks võimalik andmeid vaadata, kui selleks tekib vajadus hilisemal andmeanalüüsil ja teadusartiklite kirjutamisel. Uuringuga nõustumisel annate Te nõusoleku oma isikuandmete töötlemiseks. Uurijatele, kes kogutud andmeid analüüsivad väljastatakse ainult isikustamata andmeid. Teadusartiklites avaldatakse andmeid sellisel kujul, mis ei võimalda Teie isiku tuvastamist. Uuringust võite saada Te nii otsest kui kaudset kasu. Kui Te soovite, edastab geenivaramu Teile Tartu Ülikooli Kliinikumi Ühendlaboris mõõdetavate veremarkerite ja/või uriinianalüüsi tulemused. Selleks palume Teil teha valik nõusoleku vormil allpool. Tulemused edastatakse Teile elektrooniliselt Teie poolt nõusoleku vormile märgitud e-posti aadressile. Neid tulemusi aitab Teil tõlgendada Teie perearst, kellega peaksite selleks ise ühendust võtma. Uuringust saadud üldised tulemused Teile otsest kasu ei too , s amas saavad sellest kasu tulevased teist tüüpi diabeedi riskigruppi kuuluvad inimesed või teist tüüpi diabeedi diagnoosi saanud patsiendid . Kõik uuritavad on uuringu jooksul eraldi kindlustuskaitsega kaetud. Andmete ja proovide jagamine uuringupartneritega ning nende säilitamine OPTOMICS uuringuküsimustikust, vere- ja uriiniproovide analüüsimisel ja optoakustiliste mõõtmiste käigus saadud andmeid säilitatakse geenivaramu turvatud ja piiratud juurdepääsuga elektroonilises andmebaasis tähtajatult. Uuringust saadud andmed rikastavad geenivaramu andmekogu. Teadlastele väljastatakse vaid pseudonüümitud ehk kodeeritud andmeid. Ka Teilt võetud proovid märgistatakse koodiga, mitte nime ega isikukoodiga. Uuringu käigus kogutud vere- ja uriiniproove analüüsitakse Tartu Ülikooli Kliinikumi Ühendlaboris. Ühendlaboris hävitatakse analüüsimisest üle jäänud proovid hiljemalt 10 päeva pärast. Verest eraldatud väike kogus vereplasmat saadetakse pärast Eesti bioeetika ja inimuuringute nõukogult ja Tartu Ülikooli senatilt loa saamist Rootsi ja Soome ning neid hoitakse alles maksimaalselt 10 aastat, seejärel need hävitatakse. Osa vereplasmast säilitatakse geenivaramus tähtajatult, et seda kasutada edasistes uuringutes. OPTOMICS uuringu raames jagatakse Teie ja teiste uuringusse kaasatud indiviidide analüüside tulemustest saadud summaarseid andmeid Saksamaa Liitvabariigi partneritega. Summaarsed andmed on üldistatud kujul olevad andmed ja nendest ei saa infot üksikute uuringus osalejate kohta. Vastavad andmed kustutatakse välispartneri juures hiljemalt 10 aastat pärast nende saamist. OPTOMICS uuringu raames jagatakse Teie optoakustiliste mõõtmiste tulemusi, uuringuküsimustiku vastuseid ja veremarkerite mõõtmise tulemusi pseudonüümitult ehk kodeeritult välispartneriga Ühendkuningriikides. Vastavad andmed kustutatakse välispartneri juures hiljemalt 10 aastat pärast nende saamist. Ühendkuni n griigid asu vad väljaspool Euroopa Majanduspiirkonda ning s eetõttu tuleb antud juhul andmete kaitsmiseks kasutada lisameetmeid vastavalt Euroopa Liidu isikuandmete kaitse üldmääruse (IKÜM) artiklite le 46 ja 49. Antud projekti käigus sõlmitakse p artnerlus leping Tartu Ülikooli ja Ühendkuni n griikide partnerite vahel. Lepingutes märgitakse detailselt ära kõik andmete edastamise, säilitamise ning hävitamisega seonduv. Lepingute täitmist kontrollib Tartu Ülikool ( andmete vastutav töötleja). Lisaks on oluline mõista, et andmete edastamiseks Ühendkuni n griikide partnerile peate Te vabatahtlikult sellega nõustuma ja selle kinnitamiseks allkirjastama käesoleva nõusolekuvormi. Nõusoleku vorm Uuringu nimetus: „ Optoakustiliste fenotüübi andmete ja multi-oomika kombineerimine diabeediga seotud tervishoiu edendamiseks “ . Uuringu lühike nimetus on OPTOMICS . Mina, ......................................................................................................................................., ees- ja perekonnanimi / isikukood olen informeeritud ülalmainitud uuringust, olen teadlik läbiviidava uurimistöö eesmärgist, uuringu metoodikast ja uuringuga seotud võimalikest ohtudest ning kinnitan oma nõusolekut selles osalemiseks allkirjaga. Tean, et i sikukood aitab tagada, et minu uuringu küsimustiku vastused seostatakse just minu geeniandmetega . Alljärgnevalt teen valiku, kas soovi n saada oma vere- ja/või uriiniproovide analüüsi tulemusi tehes selleks märke mulle sobiva valikuvariandi ees asuvasse kastikesse. ☐ JAH, SOOVIN SAADA VEREMARKERITE ANALÜÜSI TULEMUSI. Soovin saada uuringu kahel vastuvõtul võetud ja seejärel Tartu Ülikooli Kliinikumi laboris analüüsitud vereanalüüside tulemusi oma e-posti aadressile. Olen teadlik, et saan pöörduda nende tõlgendamiseks oma perearsti poole, kelle juurde pean selleks ise aja broneerima. ☐ EI, MA EI SOOVI SAADA VEREMARKERITE ANALÜÜSI TULEMUSI. Tean, et uuringu käigus analüüsitakse minu vere markereid Tartu Ülikooli Kliinikumi laboris. Nende analüüside tulemusi ma ei soovi. ☐ JAH, SOOVIN SAADA URIINIANALÜÜSI TULEMUSI. Soovin saada uuringu kahel vastuvõtul võetud ja seejärel Tartu Ülikooli Kliinikumi laboris analüüsitud uriinianalüüside tulemusi oma e-posti aadressile. Olen teadlik, et saan pöörduda nende tõlgendamiseks oma perearsti poole, kelle juurde pean selleks ise aja broneerima. ☐ EI, MA EI SOOVI SAADA URIINIANALÜÜSI TULEMUSI. Tean, et uuringu käigus analüüsitakse minu uriini markereid Tartu Ülikooli Kliinikumi laboris. Nende analüüside tulemusi ma ei soovi. Palun saata minu soovitud analüüside tulemused järgmisele e-posti aadressile: ……………………………………………………………………………………………… Uuritava informeerimise leht ja teadliku nõusoleku vorm vormistatakse 2 eksemplaris, millest üks jääb mulle (uuritavale) ja teine uurijale. Minu (uuritava) allkiri: .............................................................................................................. Kuupäev (päev, kuu aasta): ....................................................................................................... Uuritavale informatsiooni andnud isiku nimi: ......................................................................... Uuritavale informatsiooni andnud isiku allkiri: ....................................................................... Kuupäev (päev, kuu aasta): ....................................................................................................... Tean, et uuringu käigus tekkivate küsimuste kohta saan mulle vajalikku täiendavat informatsiooni uuringu juhilt: Reedik Mägi, PhD , Bioinformaatika professor, uuringu vastutav uurija . Tartu Ülikooli g enoomika instituut , Eesti geenivaramu teaduskeskus , Riia 23b, Tartu 51010 , t elefon +372 737 4045 , e -post:
[email protected]
Lisa 2 2a) Kutse uuringusse (esimene e-kiri) Pealkiri: Kutse Eesti geenivaramu diabeedi uuringusse Hea geenidoonor! Pöördume Teie poole, kuna olete liitunud Eesti geenivaramuga ning soovime pakkuda Teile võimalust osaleda teadusuuringus. Teie kontaktandmed oleme saanud geenivaramuga liitumise ajal või andmete täiendamisel rahvastikuregistrist. Tegemist on rahvusvahelise teist tüüpi diabeedi ehk vanema ea suhkruhaiguse uuringuga , mille eesmärk on parandada paljude diabeeti põdevate inimeste heaolu ning elukvaliteeti nii Eestis kui kogu maailmas. Teise tüübi diabeet on kujunenud ülemaailmseks pandeemiaks ning mõjutab kogu maailmas enam kui 420 miljonit inimest. Arvatavasti kasvab see arv järgmistel aastakümnetel veelgi . Uuringusse kaasatakse nii neid geenidoonoreid, kellel on teist tüüpi diabeet kui ka neid, kellel seda haigust pole. Eesti geenivaramu andmetel on Teil diagnoositud teist tüüpi diabeet . Seega oleksite selles uuringus juhtude grupis. Uuringu käigus s oovime leida võimalusi diabeedi kulu paremaks jälgimiseks ja tüsistuste tekkimise prognoosimiseks. Selleks tehakse uuritavatele vere- ja uriinianalüüsid, vaadatakse spetsiaalse aparaadiga nende veresoonte seisundit ja uuritakse, missugune roll on pärilikel teguritel diabeedi kulus. Uuringus osalemiseks palume Teil tulla Tartu Ülikooli Eesti geenivaramusse (Riia 23b, Tartu) kahel korral ligikaudu kaheaastase vahega. Hüvitame Teile sõidukulud Tartusse ja toitlustuse esitatud kuludokumentide alusel kuni 43 euro ulatuses ühe külastuskorra kohta (kuni 3 5 eurot transpordi ja kuni 8 eurot toitlustuse eest) . Et Teil oleks lihtsam otsustada uuringus osalemise üle, võite tutvuda uuringu nõusoleku vormiga , mille leiate järgneva lingi alt : LINK 1 Selle vormi saate allkirjastada esimesel uuringuvisiidil geenivaramus, praegu ei ole seda Teil endal vaja välja printida ega allkirjastada. Samuti saadame Teile eelinfoks uuringu küsimustiku , et saaksite uuringus osalemisel sellega juba enne vastuvõttu tutvuda, et vastuvõtu ajal oleks kergem vastata. Uuringuküsimustiku leiate järgneva lingi alt: LINK 2 Uuringuküsimustikku pole Teil vaja välja printida ega seda ette täita. Seda tehakse vastuvõtu ajal. Oma otsusest osaleda või mitte palume meile teada anda vastates käesolevale meilile . Kui Te pole kahe nädala jooksul meile oma otsusest teada andnud, saadame Teile e-kirjaga veel ühe meeldetuletuse . Kui otsustate uuringus osaleda, võtab Teiega telefoni teel ühendust geenivaramu uurija ja lepib kokku Teile sobiva aja vastuvõtule tulekuks. Selleks palume saata koos vastusega oma telefoninumber, millele uurija saab Teile helistada. VÄGA OLULINE! Uuringust ei saa osa võtta , kui Te olete rase, kui Teil on dominantse käe käsivarrel ja dominantse jala siseküljel nahalööve, haavandid või põletik või Teil on tuvastatud valguse ülitundlikkus. Enne vastuvõtule tulekut palume Teilt järgnevat: 48 tundi enne vastuvõttu hoiduda treeningutest või suurest füüsilisest pingutusest. 9 tundi enne vastuvõttu palume mitte süüa ja joogiks tarvitada vaid puhast vett (ilma maitse- ja muude lisanditeta). Vastuvõtule eelneval päeval palume Teil mitte tarvitada alkohoolseid jooke, kohvi või teisi kofeiini sisaldavaid jooke/toite ja mitte süüa kõrge rasvasisaldusega toitu. Vastuvõtu päeval palume Teil mitte kasutada tubakatooteid. Kui võimalik, siis palume Teil hommikul enne vastuvõttu mitte võtta ravimeid. Ravimid saate sisse võtta kohe pärast vereproovi loovutamist. Treening, toitumine, alkohol, kofeiin, tubakatooted ja ravimid mõjutavad oluliselt Teie veresoonte läbimõõtu, mistõttu on uuringu jaoks väga oluline nendest nõuetest kinni pidada. Kui Teil ei õnnestu esimest nelja tingimust täita, palume Teil kokku leppida uus vastuvõtu aeg . Selleks helistage tööpäevadel kell 10–15 telefonil 520 6959. Palume Teil vastuvõtule kaasa võtta: S öök ja jook ning vajalikud ravimid, mida saaksite kohe pärast vastuvõttu kasutada. Meie pakume Teile vastuvõtu ajal joogiks puhast vett ja pärast vastuvõttu energia batooni. Kohapeal täidetava uurimisküsimustiku jaoks palume Teil kaasa võtta nimekirja ravimitest, mida Te hetkel tar vitate . Vastuvõtule tulles palume Teil kaasa võtta isikut tõendav dokument (pass, ID-kaart või juhiluba). Lisaküsimuste korral saatke e-kiri aadressile
[email protected] või helistage tööpäevadel kell 10 – 15 telefonil 520 6959. Lugupidamisega Reedik Mägi Eesti geenivaramu teaduskeskus bioinformaatika professor uuringu vastutav uurija
[email protected] 2b) Kutse uuringusse (teine e-kiri) Pealkiri: Kutse Eesti geenivaramu diabeedi uuringusse Hea geenidoonor! Pöördume Teie poole, kuna olete liitunud Eesti geenivaramuga ning soovime pakkuda Teile võimalust osaleda teadusuuringus. Teie kontaktandmed oleme saanud geenivaramuga liitumise ajal või andmete täiendamisel rahvastikuregistrist. Tegemist on rahvusvahelise teist tüüpi diabeedi ehk vanema ea suhkruhaiguse uuringuga , mille eesmärk on parandada paljude diabeeti põdevate inimeste heaolu ning elukvaliteeti nii Eestis kui kogu maailmas. Teise tüübi diabeet on kujunenud ülemaailmseks pandeemiaks ning mõjutab kogu maailmas enam kui 420 miljonit inimest. Arvatavasti kasvab see arv järgmistel aastakümnetel veelgi. Uuringusse kaasatakse nii neid geenidoonoreid, kellel on teist tüüpi diabeet kui ka neid, kellel seda haigust pole. Eesti geenivaramu andmetel on Teil diagnoositud teist tüüpi diabeet. Seega oleksite selles uuringus juhtude grupis. Uuringu käigus s oovime leida võimalusi diabeedi kulu paremaks jälgimiseks ja tüsistuste tekkimise prognoosimiseks. Selleks tehakse uuritavatele vere- ja uriinianalüüsid, vaadatakse spetsiaalse aparaadiga nende veresoonte seisundit ja uuritakse, missugune roll on pärilikel teguritel diabeedi kulus. Uuringus osalemiseks palume Teil tulla Tartu Ülikooli Eesti geenivaramusse (Riia 23b, Tartu) kahel korral ligikaudu kaheaastase vahega. Hüvitame Teile sõidukulud Tartusse ja toitlustuse esitatud kuludokumentide alusel kuni 43 euro ulatuses ühe külastuskorra kohta (kuni 3 5 eurot transpordi ja kuni 8 eurot toitlustuse eest) . Et Teil oleks lihtsam otsustada uuringus osalemise üle, võite tutvuda uuringu nõusoleku vormiga , mille leiate järgneva lingi alt : LINK 1 Selle vormi saate allkirjastada esimesel uuringuvisiidil geenivaramus, praegu ei ole seda Teil endal vaja välja printida ega allkirjastada. Samuti saadame Teile eelinfoks uuringu küsimustiku , et saaksite uuringus osalemisel sellega juba enne vastuvõttu tutvuda, et vastuvõtu ajal oleks kergem vastata. Uuringuküsimustiku leiate järgneva lingi alt: LINK 2 Uuringuküsimustikku pole Teil vaja välja printida ega seda ette täita. Seda tehakse vastuvõtu ajal. Oma otsusest osaleda või mitte palume meile teada anda vastates käesolevale meilile. Kui Te pole kahe nädala jooksul meile oma otsusest teada andnud, proovime Teiega ise telefoni teel ühendust saada kuni kolmel korral. Kui otsustate uuringus osaleda, võtab Teiega telefoni teel ühendust geenivaramu uurija ja lepib kokku Teile sobiva aja vastuvõtule tulekuks. Selleks palume saata koos vastusega oma telefoninumber, millele uurija saab Teile helistada. VÄGA OLULINE! Uuringust ei saa osa võtta , kui Te olete rase, kui Teil on dominantse käe käsivarrel ja dominantse jala siseküljel nahalööve, haavandid või põletik või Teil on tuvastatud valguse ülitundlikkus. Enne vastuvõtule tulekut palume Teilt järgnevat: 48 tundi enne vastuvõttu hoiduda treeningutest või suurest füüsilisest pingutusest. 9 tundi enne vastuvõttu palume mitte süüa ja joogiks tarvitada vaid puhast vett (ilma maitse- ja muude lisanditeta). Vastuvõtule eelneval päeval palume Teil mitte tarvitada alkohoolseid jooke, kohvi või teisi kofeiini sisaldavaid jooke/toite ja mitte süüa kõrge rasvasisaldusega toitu. Vastuvõtu päeval palume Teil mitte kasutada tubakatooteid. Kui võimalik, siis palume Teil hommikul enne vastuvõttu mitte võtta ravimeid. Ravimid saate sisse võtta kohe pärast vereproovi loovutamist. Treening, toitumine, alkohol, kofeiin, tubakatooted ja ravimid mõjutavad oluliselt Teie veresoonte läbimõõtu, mistõttu on uuringu jaoks väga oluline nendest nõuetest kinni pidada. Kui Teil ei õnnestu esimest nelja tingimust täita, palume Teil kokku leppida uus vastuvõtu aeg . Selleks helistage tööpäevadel kell 10–15 telefonil 520 6959. Palume Teil vastuvõtule kaasa võtta: S öök ja jook ning vajalikud ravimid, mida saaksite kohe pärast vastuvõttu kasutada. Meie pakume Teile vastuvõtu ajal joogiks puhast vett ja pärast vastuvõttu energia batooni. Kohapeal täidetava uurimisküsimustiku jaoks palume Teil kaasa võtta nimekirja ravimitest, mida Te hetkel tarvitate. Vastuvõtule tulles palume Teil kaasa võtta isikut tõendav dokument (pass, ID-kaart või juhiluba). Lisaküsimuste korral saatke e-kiri aadressile
[email protected] või helistage tööpäevadel kell 10 – 15 telefonil 520 6959. Lugupidamisega Reedik Mägi Eesti geenivaramu teaduskeskus bioinformaatika professor uuringu vastutav uurija
[email protected] 737 4045
Lisa 2 2a) Kutse uuringusse (esimene e-kiri) Pealkiri: Kutse Eesti geenivaramu diabeedi uuringusse Hea geenidoonor! Pöördume Teie poole, kuna olete liitunud Eesti geenivaramuga ning soovime pakkuda Teile võimalust osaleda teadusuuringus. Teie kontaktandmed oleme saanud geenivaramuga liitumise ajal või andmete täiendamisel rahvastikuregistrist. Tegemist on rahvusvahelise teist tüüpi diabeedi ehk vanema ea suhkruhaiguse uuringuga , mille eesmärk on parandada paljude diabeeti põdevate inimeste heaolu ning elukvaliteeti nii Eestis kui kogu maailmas. Teise tüübi diabeet on kujunenud ülemaailmseks pandeemiaks ning mõjutab kogu maailmas enam kui 420 miljonit inimest. Arvatavasti kasvab see arv järgmistel aastakümnetel veelgi . Uuringusse kaasatakse nii neid geenidoonoreid, kellel on teist tüüpi diabeet kui ka neid, kellel seda haigust pole. Eesti geenivaramu andmetel ei ole Teil diagnoositud teist tüüpi diabeet i . Seega oleksite selles uuringus tervete kontrollide grupi s. Kontrollgrupi uuritavate kaasamine on oluline, et saaksime võrrelda haigete ja tervete inimeste andmeid. Uuringu käigus s oovime leida võimalusi diabeedi kulu paremaks jälgimiseks ja tüsi stuste tekkimise prognoosimiseks. Selleks tehakse uuritavatele vere- ja uriinianalüüsid, vaadatakse spetsiaalse aparaadiga nende veresoonte seisundit ja uuritakse, missugune roll on pärilikel teguritel diabeedi kulus. Uuringus osalemiseks palume Teil tulla Tartu Ülikooli Eesti geenivaramusse (Riia 23b, Tartu) kahel korral ligikaudu kaheaastase vahega. Hüvitame Teile sõidukulud Tartusse ja toitlustuse esitatud kuludokumentide alusel kuni 43 euro ulatuses ühe külastuskorra kohta (kuni 3 5 eurot transpordi ja kuni 8 eurot toitlustuse eest) . Et Teil oleks lihtsam otsustada uuringus osalemise üle, võite tutvuda uuringu nõusoleku vormiga , mille leiate järgneva lingi alt : LINK 1 Selle vormi saate allkirjastada esimesel uuringuvisiidil geenivaramus, praegu ei ole seda Teil endal vaja välja printida ega allkirjastada. Samuti saadame Teile eelinfoks uuringu küsimustiku , et saaksite uuringus osalemisel sellega juba enne vastuvõttu tutvuda, et vastuvõtu ajal oleks kergem vastata. Uuringuküsimustiku leiate järgneva lingi alt: LINK 2 Uuringuküsimustikku pole Teil vaja välja printida ega seda ette täita. Seda tehakse vastuvõtu ajal. Oma otsusest osaleda või mitte palume meile teada anda vastates käesolevale meilile . Kui Te pole kahe nädala jooksul meile oma otsusest teada andnud, saadame Teile e-kirjaga veel ühe meeldetuletuse . Kui otsustate uuringus osaleda, võtab Teiega telefoni teel ühendust geenivaramu uurija ja lepib kokku Teile sobiva aja vastuvõtule tulekuks. Selleks palume saata koos vastusega oma telefoninumber, millele uurija saab Teile helistada. VÄGA OLULINE! Uuringust ei saa osa võtta , kui Te olete rase, kui Teil on dominantse käe käsivarrel ja dominantse jala siseküljel nahalööve, haavandid või põletik või Teil on tuvastatud valguse ülitundlikkus. Enne vastuvõtule tulekut palume Teilt järgnevat: 48 tundi enne vastuvõttu hoiduda treeningutest või suurest füüsilisest pingutusest. 9 tundi enne vastuvõttu palume mitte süüa ja joogiks tarvitada vaid puhast vett (ilma maitse- ja muude lisanditeta). Vastuvõtule eelneval päeval palume Teil mitte tarvitada alkohoolseid jooke, kohvi või teisi kofeiini sisaldavaid jooke/toite ja mitte süüa kõrge rasvasisaldusega toitu. Vastuvõtu päeval palume Teil mitte kasutada tubakatooteid. Kui võimalik, siis palume Teil hommikul enne vastuvõttu mitte võtta ravimeid. Ravimid saate sisse võtta kohe pärast vereproovi loovutamist. Treening, toitumine, alkohol, kofeiin, tubakatooted ja ravimid mõjutavad oluliselt Teie veresoonte läbimõõtu, mistõttu on uuringu jaoks väga oluline nendest nõuetest kinni pidada. Kui Teil ei õnnestu esimest nelja tingimust täita, palume Teil kokku leppida uus vastuvõtu aeg . Selleks helistage tööpäevadel kell 10–15 telefonil 520 6959. Palume Teil vastuvõtule kaasa võtta: S öök ja jook ning vajalikud ravimid, mida saaksite kohe pärast vastuvõttu kasutada. Meie pakume Teile vastuvõtu ajal joogiks puhast vett ja pärast vastuvõttu energia batooni. Kohapeal täidetava uurimisküsimustiku jaoks palume Teil kaasa võtta nimekirja ravimitest, mida Te hetkel tar vitate . Vastuvõtule tulles palume Teil kaasa võtta isikut tõendav dokument (pass, ID-kaart või juhiluba). Lisaküsimuste korral saatke e-kiri aadressile
[email protected] või helistage tööpäevadel kell 10 – 15 telefonil 520 6959. Lugupidamisega Reedik Mägi Eesti geenivaramu teaduskeskus bioinformaatika professor uuringu vastutav uurija
[email protected] 2b) Kutse uuringusse (teine e-kiri) Pealkiri: Kutse Eesti geenivaramu diabeedi uuringusse Hea geenidoonor! Pöördume Teie poole, kuna olete liitunud Eesti geenivaramuga ning soovime pakkuda Teile võimalust osaleda teadusuuringus. Teie kontaktandmed oleme saanud geenivaramuga liitumise ajal või andmete täiendamisel rahvastikuregistrist. Tegemist on rahvusvahelise teist tüüpi diabeedi ehk vanema ea suhkruhaiguse uuringuga , mille eesmärk on parandada paljude diabeeti põdevate inimeste heaolu ning elukvaliteeti nii Eestis kui kogu maailmas. Teise tüübi diabeet on kujunenud ülemaailmseks pandeemiaks ning mõjutab kogu maailmas enam kui 420 miljonit inimest. Arvatavasti kasvab see arv järgmistel aastakümnetel veelgi. Uuringusse kaasatakse nii neid geenidoonoreid, kellel on teist tüüpi diabeet kui ka neid, kellel seda haigust pole. Eesti geenivaramu andmetel ei ole Teil diagnoositud teist tüüpi diabeeti. Seega oleksite selles uuringus tervete kontrollide grupis. Uuringu käigus s oovime leida võimalusi diabeedi kulu paremaks jälgimiseks ja tüsistuste tekkimise prognoosimiseks. Selleks tehakse uuritavatele vere- ja uriinianalüüsid, vaadatakse spetsiaalse aparaadiga nende veresoonte seisundit ja uuritakse, missugune roll on pärilikel teguritel diabeedi kulus. Uuringus osalemiseks palume Teil tulla Tartu Ülikooli Eesti geenivaramusse (Riia 23b, Tartu) kahel korral ligikaudu kaheaastase vahega. Hüvitame Teile sõidukulud Tartusse ja toitlustuse esitatud kuludokumentide alusel kuni 43 euro ulatuses ühe külastuskorra kohta (kuni 3 5 eurot transpordi ja kuni 8 eurot toitlustuse eest) . Et Teil oleks lihtsam otsustada uuringus osalemise üle, võite tutvuda uuringu nõusoleku vormiga , mille leiate järgneva lingi alt : LINK 1 Selle vormi saate allkirjastada esimesel uuringuvisiidil geenivaramus, praegu ei ole seda Teil endal vaja välja printida ega allkirjastada. Samuti saadame Teile eelinfoks uuringu küsimustiku , et saaksite uuringus osalemisel sellega juba enne vastuvõttu tutvuda, et vastuvõtu ajal oleks kergem vastata. Uuringuküsimustiku leiate järgneva lingi alt: LINK 2 Uuringuküsimustikku pole Teil vaja välja printida ega seda ette täita. Seda tehakse vastuvõtu ajal. Oma otsusest osaleda või mitte palume meile teada anda vastates käesolevale meilile. Kui Te pole kahe nädala jooksul meile oma otsusest teada andnud, proovime Teiega ise telefoni teel ühendust saada kuni kolmel korral. Kui otsustate uuringus osaleda, võtab Teiega telefoni teel ühendust geenivaramu uurija ja lepib kokku Teile sobiva aja vastuvõtule tulekuks. Selleks palume saata koos vastusega oma telefoninumber, millele uurija saab Teile helistada. VÄGA OLULINE! Uuringust ei saa osa võtta , kui Te olete rase, kui Teil on dominantse käe käsivarrel ja dominantse jala siseküljel nahalööve, haavandid või põletik või Teil on tuvastatud valguse ülitundlikkus. Enne vastuvõtule tulekut palume Teilt järgnevat: 48 tundi enne vastuvõttu hoiduda treeningutest või suurest füüsilisest pingutusest. 9 tundi enne vastuvõttu palume mitte süüa ja joogiks tarvitada vaid puhast vett (ilma maitse- ja muude lisanditeta). Vastuvõtule eelneval päeval palume Teil mitte tarvitada alkohoolseid jooke, kohvi või teisi kofeiini sisaldavaid jooke/toite ja mitte süüa kõrge rasvasisaldusega toitu. Vastuvõtu päeval palume Teil mitte kasutada tubakatooteid. Kui võimalik, siis palume Teil hommikul enne vastuvõttu mitte võtta ravimeid. Ravimid saate sisse võtta kohe pärast vereproovi loovutamist. Treening, toitumine, alkohol, kofeiin, tubakatooted ja ravimid mõjutavad oluliselt Teie veresoonte läbimõõtu, mistõttu on uuringu jaoks väga oluline nendest nõuetest kinni pidada. Kui Teil ei õnnestu esimest nelja tingimust täita, palume Teil kokku leppida uus vastuvõtu aeg . Selleks helistage tööpäevadel kell 10–15 telefonil 520 6959. Palume Teil vastuvõtule kaasa võtta: S öök ja jook ning vajalikud ravimid, mida saaksite kohe pärast vastuvõttu kasutada. Meie pakume Teile vastuvõtu ajal joogiks puhast vett ja pärast vastuvõttu energia batooni. Kohapeal täidetava uurimisküsimustiku jaoks palume Teil kaasa võtta nimekirja ravimitest, mida Te hetkel tarvitate. Vastuvõtule tulles palume Teil kaasa võtta isikut tõendav dokument (pass, ID-kaart või juhiluba). Lisaküsimuste korral saatke e-kiri aadressile
[email protected] või helistage tööpäevadel kell 10 – 15 telefonil 520 6959. Lugupidamisega Reedik Mägi Eesti geenivaramu teaduskeskus bioinformaatika professor uuringu vastutav uurija
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Saatja: Tartu Ülikool <
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Saadetud: 24.08.2023 16:45
Adressaat: <"SM Info">
Teema: Vastused EBINi lisaküsimustele uurimistöö „Optoakustiliste fenotüübi andmete ja
multi-oomika kombineerimine diabeediga seotud tervishoiu edendamiseks (OPTOMICS).“
kohta
Tere!
Esitame vastused EBINi lisaküsimustele uurimistöö „Optoakustiliste fenotüübi andmete ja
multi-oomika kombineerimine diabeediga seotud tervishoiu edendamiseks (OPTOMICS).“
kohta.
Teiega on jagatud Webdesktop-i dokumenti, mis asub järgneval aadressil:
https://dok.ut.ee/sharing/?page=view_shared_item&item_id=2173497883&key=dc437ea4140
dcaf35e0f8368d5754f022a262f0f&lang=et
Lugupidamisega
Ene Mölder
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