­­Evaluating blood sampling strategies within the SIREN study: the experience from a large cohort of healthcare workers in the UK

­­Evaluating blood sampling strategies within the SIREN study: the experience from a large cohort of healthcare workers in the UK | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article ­­Evaluating blood sampling strategies within the SIREN study: the experience from a large cohort of healthcare workers in the UK Nipunadi Hettiarachchi, Debbie Blick, Tom Coleman, Ashley Otter, and 10 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5804123/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 01 Jul, 2025 Read the published version in BMC Medical Research Methodology → Version 1 posted 10 You are reading this latest preprint version Abstract Background Delivering research studies that require a large number of samples to monitor specific populations is complex, often resulting in high costs and intricate logistics. We aim to describe the processes for blood sample collection and management and evaluate alternative sampling methods within a large cohort of healthcare workers in the UK (the SIREN study). Methods We conducted a process evaluation. First, we described blood sample collection and management across different study periods from June 2020 to March 2024 and how these evolved over time. Secondly, we compared alternative methods of blood sampling: venous phlebotomy (hospital-based) vs. capillary sampling (at-home). Results The main challenges with blood sampling within SIREN stemmed from the scale and use of decentralised phlebotomy across 135 hospital sites during the COVID-19 pandemic. We adapted our sampling processes as the study progressed, overcoming most of these challenges. When comparing hospital-based and at-home sampling, overall, return rates of samples taken at home were higher than site- based samples (80% vs 71%, respectively). At-home samples took less time to be returned to UKHSA Laboratory for testing compared to hospital-based samples (median 2 days; interquartile (IQ) 2-3) vs 6 days; IQ 3-8). However, at-home samples were more likely to be considered void (4%) when tested compared to hospital-based samples (0%). Cost for hospital-based sampling was almost 3-times higher than at-home sampling (£34.05 vs £11.50, respectively), however larger sample volumes were obtained via hospital-based sampling when compared to at-home sampling (8 ml vs 600 µl of whole blood). Conclusions Sample collection and management in large scale research studies are complex. Our results support at-home blood sampling as an effective and cheaper strategy when compared to hospital-based phlebotomy and therefore should be considered as alternative sampling method for future research. Trial registration number: ISRCTN11041050 - registration date 12/01/2021. Evaluation Blood Specimen Collection Phlebotomy Cohort Studies Figures Figure 1 BACKGROUND Sample collection is a key element for clinical health research, involving several types of biological specimens depending on the study objectives. Blood samples are among the most common specimens required for surveillance studies, as they are relatively easy to obtain and can provide several insights into diagnosis of diseases, participants’ immune response and medical conditions. ( 1 ) The global COVID-19 pandemic required investigating multiple features of an emerging pathogen, including assessing population immunity. To address this, several studies were established and required large numbers of blood samples for immunological testing. However, implementing efficient processes for blood collection at scale during an ongoing pandemic has been challenging. The ideal blood sampling method depends on several aspects, including factors related to the study design, the infrastructure available and participant acceptability. ( 2 , 3 ) Recently, at-home self-sampling has become more popular and has been applied by clinical studies in a variety of settings, including research on human immunodeficiency virus (HIV), other sexually transmitted infections (STI) and rheumatoid arthritis (RA). ( 4 , 5 ) A community-based study in the United Kingdom (UK) was one of the first to use capillary blood samples to evaluate the antibody responses following SARS-CoV-2 vaccination and successfully provided insights into SARS-CoV-2 immune response early in the pandemic. ( 6 ) The SARS-CoV-2 Immunity and Reinfection Evaluation (SIREN) study is a large cohort of healthcare workers in the UK set up in June 2020. The study originally aimed to evaluate whether the presence of antibodies against SARS-CoV-2 would reduce the risk of SARS-CoV-2 reinfection, requiring large scale blood sampling for serological testing. ( 7 ) Venous phlebotomy at hospital sites was carried out by trained personnel from the beginning of the study. However, in 2024, at-home capillary sampling was implemented for participants from sites that no longer offered phlebotomy, as an alternative method for sample collection. In this analysis, we aimed to describe the evolving methods for blood sample collection across the course of the SIREN study (2020–2024) and evaluate processes and outcomes for venous phlebotomy (hospital-based) and capillary sampling (at-home). METHODS Study design We conducted a process evaluation of blood sampling within in the SIREN study. The SIREN study protocol is described elsewhere (Wallace et al., 2021). Description and review of blood sample collection and management processes over the study period For the purpose of this analysis, SIREN 1.0 corresponds to the period between June 2020 and March 2023 and SIREN 2.0 corresponds to the period between May 2023 and March 2024. We described and compared the two different study periods in terms of bleeding schedule, sampling methods, sample flows, sample labelling and sample testing. We then reviewed challenges across the periods for the same aspects mentioned above, based on internal reviews and feedback from hospital sites collected in real-time over the duration of the study. Evaluation of processes and outcomes for hospital-based and at-home blood sampling (dup: abstract ?) We compared metrics on logistics, sample recovery and costs to evaluate whether there was a superior method for blood sample collection. Data collection For serum samples collected at hospital sites within SIREN 1.0, study participant IDs, study sample IDs and collection dates were obtained from the electronic manifest shared by the site with the UKHSA Sero-epidemiology Unit team. These data were checked against the samples received at the UKHSA laboratories, errors investigated and corrected, and the data uploaded to a custom database built for the SIREN study. For blood samples collected at hospital sites within SIREN 2.0, study sample IDs and collection dates were obtained from the electronic manifest shared with the UKHSA SIREN team, which was uploaded into the UKHSA Laboratory Information Management System (LIMS) and checked against the samples received at the UKHSA laboratories. For at-home blood sampling, participants were asked to complete a referral form including their study sample ID and collection dates. These were entered manually into LIMS by the laboratory team upon receipt of samples. The UKHSA LIMS also captured information on sample receipt date and antibody testing results, which were linked to participants via study sample IDs. Data analysis Sample return rates were calculated by using the number of returned samples divided by the number of expected samples for a specific study period. The number of returned samples was retrieved from LIMS, based on their arrival and logging of associated data in LIMS. The expected number of samples was calculated for each hospital site based on the number of participants recruited who had not withdrawn at time of the scheduled bleeds. The timeliness of sample return was determined by calculating the median days between sample collection and laboratory receipt dates. We described the rates of void samples for each sampling method by using the number of void samples divided by the total number of samples returned. Samples could be considered void due to insufficient volume for processing, clotted, or if they fail the assay’s quality control criteria. The cost per sample for phlebotomy was calculated based on information from the financial reports provided by hospital sites. For at-home sampling, we used costs associated with procuring and assembling sample kits and inbound shipment. Outbound shipments, either from hospital sites to UKHSA or from participants to UKHSA, were calculated for both methods. Sample volumes were provided based on the requirements described at the study protocol for hospital-based sampling. For at-home sampling, maximum volumes were obtained from the manufacture of capillary blood kits utilised in this study. RESULTS Description and review of blood sample collection and management processes over the study period Over 44,000 participants joined the SIREN study between June 2020 and March 2021 from 135 hospital sites across the UK, who underwent frequent PCR and serological testing locally. They were initially followed-up for 12-months and offered two subsequent opportunities to extend their participation in the study until March 2023 (SIREN 1.0). From May 2023, a subset of 6,047 participants from the original cohort joined another phase of the study, named as SIREN 2.0, and resumed PCR sampling at home (May 2023-March 2024) with phlebotomy and subsequent serological testing at hospital sites (September 2023-March 2024). At-home blood sampling was established between January and March 2024 for a subset of SIREN 2.0 participants whose hospital sites were not offering serological testing (Fig. 1 ). During SIREN 1.0, hospital sites carried out monthly or quarterly venous phlebotomy depending on site capacity. Blood samples were transferred to local laboratories, where they were tested for SARS-CoV-2 antibodies utilising locally validated assays. A serum aliquot from each sample was obtained, labelled, and shipped to UKHSA laboratories for biobanking and further testing (if required). In SIREN 2.0, all participants linked to hospital sites were bled at four defined timepoints (September 2023, November 2023, January 2024, and March 2024). Full blood samples were labelled and sent to a UKHSA laboratory for SARS-CoV-2 antibody testing and biobanking. Participants not linked to hospital sites were offered at-home sampling and provided with capillary blood kits (finger prick devices) at two time points: January 2024 (Postal bleed 1) and March 2024 (Postal bleed 2). Sample tubes were pre-identified with correspondent study sample IDs and returned to UKHSA Porton Down by participants using the pre-paid postal service for testing. A comparison of the main processes related to blood sample collection and management for each study period is captured in Table 1 . Multiple issues were identified in SIREN 1.0 across all aspects analysed (Table 2 ). Managing different bleeding schedules for each site and participants required considerable staff capacity, both from research and phlebotomy teams. Given the large number of participants per site and frequency of bleeds, several samples were incorrectly labelled or did not match electronic records, which delayed sample shipment and generated a large volume of sample discrepancies. Having antibody testing performed at different laboratories utilising different assays was also problematic and often required confirmatory testing at a UKHSA laboratory for subsequent specific analyses. Fewer challenges were encountered in SIREN 2.0, demonstrating quality improvement over time. SIREN 2.0 hospital-based sampling had a lower number of sample discrepancies or mislabelling than SIREN 1.0. However, some sites in SIREN 2.0 had issues with setting up couriers for sample shipment, which was more time-sensitive than in SIREN 1.0 due to the shipment of whole blood rather than serum. The use of centralised antibody testing at UKHSA laboratories reduced costs and sample logistics at hospital sites. For SIREN 2.0 at-home sampling, most of the remaining issues related to hospital-based sampling were overcome; for example, samples being directly sent to the UKHSA laboratory by participants optimised sample return and pre-labelling minimised any sample discrepancies. Nonetheless, some participants reported challenges with the capillary sampling method and some samples had insufficient volumes for testing (Table 2 ). Table 1 Comparing different processes related to sample collection and management by study period. SIREN 1.0 SIREN 2.0 Hospital-based sampling At-home sampling Bleeding schedule Monthly bleeds from June 2020 to March 2021 for all hospital sites. From March 2021 onwards, hospital sites could choose to perform quarterly bleeds instead of monthly. Different bleeding schedules for each site and, within a site, different bleeding schedule for each participant. All hospital sites and participants followed the same schedule for bleeds, every two months (September 2023, November 2023, January 2024, and March 2024). Two pre-defined time points for sample collection (January and March 2024). Blood sampling and sample flows Blood samples were collected by phlebotomy/research teams at the hospital sites. Local laboratories would extract sera from whole blood samples and send an aliquot to UKHSA laboratory. Blood samples were collected by phlebotomy/research teams at hospital sites. Whole blood samples were centrifuged and shipped to UKHSA Porton Down. Participants were provided with a capillary sampling blood kits via post. Sample labelling Sample labels for all participants and bleeds provided at the beginning of the study period. Sample labels provided at 4 time-points for the immediately upcoming bleed. Capillary sampling kit included a pre-labelled blood tube. Sample shipping Electronic manifests should capture all samples included in the physical shipment and be sent to UKHSA team at least 2 days prior to shipment. Monthly shipments to UKHSA laboratory. Electronic manifests should capture all samples included in the physical shipment and be sent to UKHSA team at least 2 days prior to shipment. Samples should be shipped to UKHSA laboratory within ~ 7 days after collection. Whole blood sampled were sent directly to UKHSA laboratory by participants using a pre-paid postal service, as soon as the sample was taken. Sample processing and testing Samples tested for SARS-CoV-2 serology at hospital sites, utilising locally validated assays. If further testing was required, serum samples were shipped from SEU to UKHSA Porton Down. All testing was carried out at UKHSA Porton Down. All testing was carried out at UKHSA Porton Down. Table 2 Challenges related to blood sample collection and management throughout the SIREN study. SIREN 1.0 SIREN 2.0 Hospital-based sampling At-home sampling Bleeding schedule Each site and participant had their own bleeding schedules to manage, creating considerable staffing demands for phlebotomy clinics and research teams. No issues reported. No issues reported. Blood sampling and sample flows Phlebotomy clinics required skilled staff and considerable resources, which were costly to the study. Samples required aliquoting and processing at local laboratories, which was time and resource consuming. Hospital sites were not shipping samples frequently enough, delaying analyses using antibody data. Phlebotomy clinics required skilled staff and considerable resources, which were costly to the study. Few participants reported issues with capillary blood collection, mainly related to not being familiar with finger prick testing. Sample labelling At the beginning of the study, pre-defined sample ID labels were provided to sites based on an estimated number of participants and bleeds. There were delays in sending out the first batches of labels to certain hospital sites due to logistical issues, which led to some sites having to manually write sample IDs to identify samples. If participants missed visits, this would create leftover labels that could mistakenly be used for future bleeds. Initially, extra labels could be ordered via email, which may have increased errors in label printing and shipment. A label request form for ad hoc label requests was further implemented. Delays on delivering additional sample ID labels in time for bleeds during the first study extension resulted in some hospital sites printing their own labels or handwriting labels, leading to transcription errors. Minimal issues with sample mislabeling. No issues reported. Sample shipping Several shipments received did not match the electronic manifest, requiring in-depth investigation to be resolved and delaying samples getting recorded into the LIMS. The electronic manifest was not always sent prior to the physical shipment, which impacted on the ability of managing large shipments in a timely manner. Electronic manifests were not completed utilising a barcode reader, which lead to transcription errors. A small number of shipments received where samples did not match the electronic manifest, requiring in-depth investigation to be resolved and delaying samples getting recorded into the LIMS. The electronic manifest was not always sent prior to sending the physical shipment, which impacted on the ability managing large shipments in a timely manner. Challenges in setting up couriers for sample collection at some hospital sites. Minimal delays on returning samples to the laboratory, only delays associated to postage strikes. Sample processing and testing Hospital sites conducted different SARS-CoV-2 serological assays. This meant the specificity and sensitivity of these results were not uniform and consistent throughout the study. If additional testing was required at UKHSA, samples would have to be transported to a different laboratory, impacting on delays in testing. No reported issues. A few samples were classified as void. Due to insufficient volume or due to the blood sample being clotted, samples can fail the assay’s quality control criteria. Evaluation of processes and outcomes for hospital-based and at-home blood sampling In total, 6,047 SIREN participants consented to join SIREN 2.0. Of those, 3,624 participants underwent hospital-based sampling, whereas 1,423 participants joined at-home sampling. For hospital-based sampling, sample return rates varied by bleed timepoint from 61–77% based on expected numbers of samples. For at-home sampling, the average return rate was higher (80%) (Table 3 ). When comparing the time between sample collection and return to the UKHSA laboratory, samples taken at hospitals took a median of 6 days (IQR 3–8) to be returned whereas samples taken at-home were returned within a median of 2 days (IQR 2–3) (Table 4 ). Overall, hospital-based samples were less likely to be considered void (0%) compared to at-home sampling (4%) (Table 5 ). Most frequent reason for void samples from at-home sampling was due to insufficient volume. Regarding costs, hospital-based sampling was approximately 3-times more expensive compared to at-home sampling (Table 6 ), excluding consumable costs for hospital-based sampling. When considering sample volumes, hospital-based sampling offered larger volumes of blood via phlebotomy. As per protocol, during SIREN 1.0, at least 2 mL of sera should be obtained from participants from each bleed. For SIREN 2.0, 8 mL of whole blood samples were expected to be shipped to UKHSA Porton Down for testing for each bleed (ensuring a minimum of 2 mL of sera per bleed). In contrast, capillary blood sampling yields very small volumes; in our study, the maximum volume of blood obtained via at-home finger-prick sampling was 600 µL. SIREN 2.0 Hospital-based sampling At-home sampling Bleed 1 Bleed 2 Bleed 3 Bleed 4 Postal bleed 1 Postal bleed 2 Table 3 Return rates from SIREN 2.0 hospital-based and at-home sampling. Numbers of expected samples excludes anyone who had withdrew from the study at time of bleeds. Expected samples (n) 3,624 3,557 3,488 3,459 1,423 1,411 Returned samples (n) 2,735 2,564 2,424 2,081 1,180 1,090 Return rates (%) 75% 73% 70% 61% 83% 77% Average return rate per pathway (mean %) 70% 80% Table 4 Timeliness of serology samples received at UKHSA Laboratory from SIREN 2.0 hospital-based and at-home sampling. SIREN 2.0 Hospital-based sampling At-home sampling Bleed 1 (n = 2,735) Bleed 2 (n = 2,564) Bleed 3 (n = 2,424) Bleed 4 (n = 2,081) Postal bleed 1 (n = 1,180) Postal bleed 2 (n = 1,090) Number of days for sample return per bleed (median (p50); IQR) 7 ( 5 – 8 ) 6 ( 3 – 8 ) 5 ( 3 – 7 ) 6 ( 3 – 7 ) 2 ( 2 – 3 ) 2 ( 2 – 3 ) Overall number of days for sample return per pathway (median; IQR) 6 (IQR 3–8) 2 (IQR 2–3) Table 5 Proportion of void samples from SIREN 2.0 hospital based and at-home sampling. SIREN 2.0 Hospital-based sampling At-home sampling Bleed 1 (n = 2,735) Bleed 2 (n = 2,564) Bleed 3 (n = 2,424) Bleed 4 (n = 2,081) Postal bleed 1 (n = 1,180) Postal bleed 2 (n = 1,090) Void samples (n; %) 1 (0%) 0 (0%) 0 (0%) 0 (0%) 66 (6%) 19 (2%) Overall number of void samples per pathway (mean %) 0% 4% Table 6 Estimation of overall cost per sample from SIREN 2.0 hospital-based and at-home sampling. *Shipping charges include both outbound and return mailing costs for at-home sampling.**Phlebotomy charge excludes consumables, given those were covered by the hospital sites. Study stage SIREN 2.0 Hospital-based sampling At-home sampling Shipping charges £1.11 £6.00* Serology/ Phlebotomy charge** £16.49 N/A Participant admin per month per participant £7.65 N/A Nurse time per month per participant £8.80 N/A Capillary sampling kit charges N/A £5.50 Total £34.05 £11.50 DISCUSSION In this study, we described the different processes for blood collection within the SIREN study and how those evolved as the study progressed. Continuous improvement cycles are key to deliver large scale responsive research, as we have demonstrated. Our option to utilise a decentralised approach for sample collection and testing in SIREN 1.0 has proved to be complex, requiring extensive logistical arrangements and research site’s local capability. Troubleshooting by UKHSA and the study sites to resolve sample discrepancies was a resource heavy activity. However, by collecting feedback and consistently reviewing processes for sample collection and management, we were able to overcome these challenges in SIREN 2.0, e.g. by standardising bleeding schedules and having centralised testing at UKHSA Laboratories, as opposed to local testing on a range of assays. Some studies have explored the concept of home visits by phlebotomists; however, this is impractical for large scale studies. ( 8 ) These processes were further improved by implementing at-home sampling. When comparing hospital-based and at-home sampling, we have demonstrated that self-blood collection was superior in terms of logistics, sample return and costs. Our findings are supported by previous studies, that have found that capillary blood sampling was an accurate and advantageous method for blood sample collection for assessing SARS-CoV-2 antibodies and other serological markers. ( 9 – 11 ) Furthermore, in the context of an outbreak of a new or emerging pathogen, at-home sampling minimises the risk of disease transmission between individuals. (12) Despite low numbers, at-home sampling provided a higher rate of voided samples upon testing when compared to phlebotomy, generally due to insufficient volumes of samples, which could have implications for specific analyses. It should be recognised that at-home sampling can only extract low sample volumes, that could become insufficient for testing if the correct instructions for blood collection are not followed and limiting the options of running additional testing or biobanking samples. (13) In addition, at-home sampling would not be suitable for specific analysis that require rapid sample processing. Therefore, these are key limitations of self-sampling methods and should be considered when designing new research studies, to ensure the study requirements are fulfilled. Another important aspect when considering different methods for blood sampling is participant experience. Previous studies have demonstrated self-collection methods to be highly accepted by participants, ( 3 , 4 , 10 ) although some reported it to be uncomfortable or painful. (14) We collected SIREN participant’s feedback on hospital-based and at-home sampling and preliminary analysis found that although both methods were acceptable, at-home sampling was preferable compared to hospital-based (55% vs 23%, respectively). This will be described in more details in a separate analysis. Our evaluation comparing hospital-based and at-home sampling did not include post-analytical metrics related to the performance of the assay, as quality indicators were not available at the time of this analysis. We acknowledge this as a limitation. However, previous studies have shown high rates of concordant SARS-CoV-2 antibody results between the two different methods. ( 3 , 5 , 11 ) Overall, we have demonstrated capillary blood collection is advantageous compared to venous phlebotomy, mindful of limited sample volumes, with additional benefits in terms of logistical arrangements and convenience for sampling. CONCLUSIONS Large scale research studies that require the collection of blood samples can face challenges related to sample collection and management. Overall, at-home blood sampling is a valuable tool for research testing, providing cost-effectiveness and convenience for participants. Declarations Ethics approval and consent to participate The study protocol was approved by the Berkshire Research Ethics Committee on May 22, 2020. Informed consent was obtained from all participants included in the study. Consent for publication Not applicable. Competing interests All authors declare that they have no competing interest. Author Contribution AA, NH, AO, SF, VH, JI and SH conceptualised this analysis and contributed to the study design. NH, DB, JK and SF were responsible for curation of sample data. NH, JK and SF verified the data and performed the data analysis for this study. NH and AA did the literature search and drafted the manuscript. DB, TC, AD, EL, MJC, MC and AO contributed to sample management and testing. All authors read and approved the final manuscript, had full access to all the data in the study, and had final responsibility for the decision to submit for publication. SH is the chief investigator for SIREN. Acknowledgement We would like to thank all participants who have contributed to the SIREN study. We would also like to thank the research teams and staff at hospital sites throughout the years for their hard work and commitment to the SIREN study. We thank all colleagues from UKHSA Porton Down, UKHSA Seroepidemiology Unit and UKHSA Colindale laboratories for their great efforts to support the sera biobank and serological testing for SIREN over the years. Data Availability Anonymised datasets used and/or analysed during the current study are available from the corresponding author on reasonable request. References Lima-Oliveira G, Lippi G, Salvagno GL, Picheth G, Guidi GC. Laboratory Diagnostics and Quality of Blood Collection. J Med Biochem. 2015;34(3):288-94. Wong MP, Meas MA, Adams C, Hernandez S, Green V, Montoya M, et al. Development and Implementation of Dried Blood Spot-Based COVID-19 Serological Assays for Epidemiologic Studies. Microbiol Spectr. 2022;10(3):e0247121. Wixted D, Neighbors CE, Pieper CF, Wu A, Kingsbury C, Register H, et al. Comparison of a Blood Self-Collection System with Routine Phlebotomy for SARS-CoV-2 Antibody Testing. Diagnostics (Basel). 2022;12(8). Knitza J, Tascilar K, Vuillerme N, Eimer E, Matusewicz P, Corte G, et al. Accuracy and tolerability of self-sampling of capillary blood for analysis of inflammation and autoantibodies in rheumatoid arthritis patients-results from a randomized controlled trial. 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Evaluation of independent self-collected blood specimens for COVID-19 antibody detection among the US veteran population. Diagn Microbiol Infect Dis. 2022;104(2):115770. Hendelman T, Chaudhary A, LeClair AC, van Leuven K, Chee J, Fink SL, et al. Self-collection of capillary blood using Tasso-SST devices for Anti-SARS-CoV-2 IgG antibody testing. PLoS One. 2021;16(9):e0255841. Wickremsinhe E, Fantana A, Berthier E, Quist BA, Lopez de Castilla D, Fix C, et al. Standard Venipuncture vs a Capillary Blood Collection Device for the Prospective Determination of Abnormal Liver Chemistry. J Appl Lab Med. 2023;8(3):535-50. King ER, Garrett HE, Abernathy H, Cassidy CA, Cabell CR, Shook-Sa BE, et al. Comparison of capillary blood self-collection using the Tasso-SST device with venous phlebotomy for anti-SARS-CoV-2 antibody measurement. J Immunol Methods. 2023;520:113523. Conserve DF, Mathews A, Choko AT, Nelson LE. Preparing for severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) self-testing implementation: Lessons learned from HIV self-testing. Front Med (Lausanne) [Internet]. 2020;7:599521. Available from: http://dx.doi.org/10.3389/fmed.2020.599521. Zoratto N, Klein-Cerrejon D, Gao D, Inchiparambil T, Sachs D, Luo Z, et al. A Bioinspired and Cost-Effective Device for Minimally Invasive Blood Sampling. Adv Sci (Weinh). 2024;11(18):e2308809. Liu Y, Rafkin LE, Matheson D, Henderson C, Boulware D, Besser REJ, et al. Use of self‐collected capillary blood samples for islet autoantibody screening in relatives: a feasibility and acceptability study. Diabet Med [Internet]. 2017;34(7):934–7. Available from: http://dx.doi.org/10.1111/dme.13338 Additional Declarations No competing interests reported. Supplementary Files SupplementaryMaterialSIRENStudyGroupv1.docx Cite Share Download PDF Status: Published Journal Publication published 01 Jul, 2025 Read the published version in BMC Medical Research Methodology → Version 1 posted Editorial decision: Revision requested 29 Apr, 2025 Reviews received at journal 29 Apr, 2025 Reviewers agreed at journal 29 Apr, 2025 Reviews received at journal 25 Apr, 2025 Reviewers agreed at journal 16 Apr, 2025 Reviewers invited by journal 22 Jan, 2025 Editor invited by journal 20 Jan, 2025 Editor assigned by journal 19 Jan, 2025 Submission checks completed at journal 19 Jan, 2025 First submitted to journal 10 Jan, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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Agency","correspondingAuthor":false,"prefix":"","firstName":"Michelle","middleName":"","lastName":"Cole","suffix":""},{"id":417031116,"identity":"d21ff01c-7ae9-4597-b2e0-177047431ebb","order_by":8,"name":"Michelle Cairns","email":"","orcid":"","institution":"UK Health Security Agency","correspondingAuthor":false,"prefix":"","firstName":"Michelle","middleName":"","lastName":"Cairns","suffix":""},{"id":417031117,"identity":"17353ed1-8bc5-4116-8818-905c4d294059","order_by":9,"name":"Jasmin Islam","email":"","orcid":"","institution":"UK Health Security Agency","correspondingAuthor":false,"prefix":"","firstName":"Jasmin","middleName":"","lastName":"Islam","suffix":""},{"id":417031118,"identity":"b0f47d66-6985-4fab-a98a-e086589b27fa","order_by":10,"name":"Sarah Foulkes","email":"","orcid":"","institution":"UK Health Security Agency","correspondingAuthor":false,"prefix":"","firstName":"Sarah","middleName":"","lastName":"Foulkes","suffix":""},{"id":417031119,"identity":"eed53c1b-5ded-404b-86ef-55932e7f9601","order_by":11,"name":"Susan Hopkins","email":"","orcid":"","institution":"UK Health Security Agency","correspondingAuthor":false,"prefix":"","firstName":"Susan","middleName":"","lastName":"Hopkins","suffix":""},{"id":417031120,"identity":"980ffd54-ef8d-48ce-9949-576670b44859","order_by":12,"name":"Victoria Hall","email":"","orcid":"","institution":"UK Health Security Agency","correspondingAuthor":false,"prefix":"","firstName":"Victoria","middleName":"","lastName":"Hall","suffix":""},{"id":417031121,"identity":"d5650be4-eae7-43af-994d-1b6286adc8e8","order_by":13,"name":"Ana Atti","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA6ElEQVRIiWNgGAWjYBADHn4GNjY4j7GBoIYEAx7JBlK1MBgcIFYL/+zmBww/f/yRMb6RlvbwRw2DXb9EApvkDDxaJO4cM2DsATrM7EbacWOeYwzJM2cAtWzA56YbQEfxgLWkt0kzsDEkG5w5wCb5AI8O+RvpHxj/ALUYz0hvk/zxjwgtBjdyDJhBthhIpB2T4G1jsDM43oDfYYY3cgoOy6QZ80iceZYmzdsnkSDZ3thsic/7cjfSNz58YyNnz9+eZib545uNPT8z88GbPfi8DwQHkNgSiQ3ERCQKsCdN+SgYBaNgFIwEAAAookfs2Auv/QAAAABJRU5ErkJggg==","orcid":"","institution":"UK Health Security Agency","correspondingAuthor":true,"prefix":"","firstName":"Ana","middleName":"","lastName":"Atti","suffix":""}],"badges":[],"createdAt":"2025-01-10 13:38:18","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-5804123/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-5804123/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s12874-025-02599-x","type":"published","date":"2025-07-01T15:58:01+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":76684281,"identity":"2a651a7f-677d-4783-a525-68f04d9aad1b","added_by":"auto","created_at":"2025-02-19 15:47:15","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":17097,"visible":true,"origin":"","legend":"\u003cp\u003eDescription of study periods and blood sample collection throughout the SIREN study.\u003c/p\u003e","description":"","filename":"floatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-5804123/v1/de8292061600d7a8efbef355.png"},{"id":86179099,"identity":"e1192258-3ff6-4955-8da8-dd6710371a4e","added_by":"auto","created_at":"2025-07-07 16:15:42","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1184982,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5804123/v1/4ab4b636-d10b-4b21-99c3-40c031c1d378.pdf"},{"id":76684282,"identity":"7f35d007-fa9e-4759-adfd-bba39bc25cf3","added_by":"auto","created_at":"2025-02-19 15:47:15","extension":"docx","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":41690,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementaryMaterialSIRENStudyGroupv1.docx","url":"https://assets-eu.researchsquare.com/files/rs-5804123/v1/b0014d970963758012b95bde.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"­­Evaluating blood sampling strategies within the SIREN study: the experience from a large cohort of healthcare workers in the UK","fulltext":[{"header":"BACKGROUND","content":"\u003cp\u003eSample collection is a key element for clinical health research, involving several types of biological specimens depending on the study objectives. Blood samples are among the most common specimens required for surveillance studies, as they are relatively easy to obtain and can provide several insights into diagnosis of diseases, participants\u0026rsquo; immune response and medical conditions. (\u003cspan class=\"CitationRef\"\u003e1\u003c/span\u003e)\u003c/p\u003e\n\u003cp\u003eThe global COVID-19 pandemic required investigating multiple features of an emerging pathogen, including assessing population immunity. To address this, several studies were established and required large numbers of blood samples for immunological testing. However, implementing efficient processes for blood collection at scale during an ongoing pandemic has been challenging.\u003c/p\u003e\n\u003cp\u003eThe ideal blood sampling method depends on several aspects, including factors related to the study design, the infrastructure available and participant acceptability. (\u003cspan class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e3\u003c/span\u003e) Recently, at-home self-sampling has become more popular and has been applied by clinical studies in a variety of settings, including research on human immunodeficiency virus (HIV), other sexually transmitted infections (STI) and rheumatoid arthritis (RA). (\u003cspan class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e5\u003c/span\u003e) A community-based study in the United Kingdom (UK) was one of the first to use capillary blood samples to evaluate the antibody responses following SARS-CoV-2 vaccination and successfully provided insights into SARS-CoV-2 immune response early in the pandemic. (\u003cspan class=\"CitationRef\"\u003e6\u003c/span\u003e)\u003c/p\u003e\n\u003cp\u003eThe SARS-CoV-2 Immunity and Reinfection Evaluation (SIREN) study is a large cohort of healthcare workers in the UK set up in June 2020. The study originally aimed to evaluate whether the presence of antibodies against SARS-CoV-2 would reduce the risk of SARS-CoV-2 reinfection, requiring large scale blood sampling for serological testing. (\u003cspan class=\"CitationRef\"\u003e7\u003c/span\u003e) Venous phlebotomy at hospital sites was carried out by trained personnel from the beginning of the study. However, in 2024, at-home capillary sampling was implemented for participants from sites that no longer offered phlebotomy, as an alternative method for sample collection.\u003c/p\u003e\n\u003cp\u003eIn this analysis, we aimed to describe the evolving methods for blood sample collection across the course of the SIREN study (2020\u0026ndash;2024) and evaluate processes and outcomes for venous phlebotomy (hospital-based) and capillary sampling (at-home).\u003c/p\u003e"},{"header":"METHODS","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\n \u003ch2\u003eStudy design\u003c/h2\u003e\n \u003cp\u003eWe conducted a process evaluation of blood sampling within in the SIREN study. The SIREN study protocol is described elsewhere (Wallace et al., 2021).\u003c/p\u003e\n\u003c/div\u003e\n\u003ch3\u003eDescription and review of blood sample collection and management processes over the study period\u003c/h3\u003e\n\u003cp\u003eFor the purpose of this analysis, SIREN 1.0 corresponds to the period between June 2020 and March 2023 and SIREN 2.0 corresponds to the period between May 2023 and March 2024. We described and compared the two different study periods in terms of bleeding schedule, sampling methods, sample flows, sample labelling and sample testing. We then reviewed challenges across the periods for the same aspects mentioned above, based on internal reviews and feedback from hospital sites collected in real-time over the duration of the study.\u003c/p\u003e\n\u003ch3\u003eEvaluation of processes and outcomes for hospital-based and at-home blood sampling (dup: abstract ?)\u003c/h3\u003e\n\u003cp\u003eWe compared metrics on logistics, sample recovery and costs to evaluate whether there was a superior method for blood sample collection.\u003c/p\u003e\n\u003ch3\u003eData collection\u003c/h3\u003e\n\u003cp\u003eFor serum samples collected at hospital sites within SIREN 1.0, study participant IDs, study sample IDs and collection dates were obtained from the electronic manifest shared by the site with the UKHSA Sero-epidemiology Unit team. These data were checked against the samples received at the UKHSA laboratories, errors investigated and corrected, and the data uploaded to a custom database built for the SIREN study.\u003c/p\u003e\n\u003cp\u003eFor blood samples collected at hospital sites within SIREN 2.0, study sample IDs and collection dates were obtained from the electronic manifest shared with the UKHSA SIREN team, which was uploaded into the UKHSA Laboratory Information Management System (LIMS) and checked against the samples received at the UKHSA laboratories.\u003c/p\u003e\n\u003cp\u003eFor at-home blood sampling, participants were asked to complete a referral form including their study sample ID and collection dates. These were entered manually into LIMS by the laboratory team upon receipt of samples.\u003c/p\u003e\n\u003cp\u003eThe UKHSA LIMS also captured information on sample receipt date and antibody testing results, which were linked to participants via study sample IDs.\u003c/p\u003e\n\u003cdiv id=\"Sec7\" class=\"Section2\"\u003e\n \u003ch2\u003eData analysis\u003c/h2\u003e\n \u003cp\u003eSample return rates were calculated by using the number of returned samples divided by the number of expected samples for a specific study period. The number of returned samples was retrieved from LIMS, based on their arrival and logging of associated data in LIMS.\u003c/p\u003e\n \u003cp\u003eThe expected number of samples was calculated for each hospital site based on the number of participants recruited who had not withdrawn at time of the scheduled bleeds. The timeliness of sample return was determined by calculating the median days between sample collection and laboratory receipt dates.\u003c/p\u003e\n \u003cp\u003eWe described the rates of void samples for each sampling method by using the number of void samples divided by the total number of samples returned. Samples could be considered void due to insufficient volume for processing, clotted, or if they fail the assay\u0026rsquo;s quality control criteria.\u003c/p\u003e\n \u003cp\u003eThe cost per sample for phlebotomy was calculated based on information from the financial reports provided by hospital sites. For at-home sampling, we used costs associated with procuring and assembling sample kits and inbound shipment. Outbound shipments, either from hospital sites to UKHSA or from participants to UKHSA, were calculated for both methods.\u003c/p\u003e\n \u003cp\u003eSample volumes were provided based on the requirements described at the study protocol for hospital-based sampling. For at-home sampling, maximum volumes were obtained from the manufacture of capillary blood kits utilised in this study.\u003c/p\u003e\n \u003cp\u003e\u003c/p\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n\u003c/div\u003e"},{"header":"RESULTS","content":"\u003cdiv id=\"Sec9\" class=\"Section2\"\u003e\n \u003ch2\u003eDescription and review of blood sample collection and management processes over the study period\u003c/h2\u003e\n \u003cp\u003eOver 44,000 participants joined the SIREN study between June 2020 and March 2021 from 135 hospital sites across the UK, who underwent frequent PCR and serological testing locally. They were initially followed-up for 12-months and offered two subsequent opportunities to extend their participation in the study until March 2023 (SIREN 1.0). From May 2023, a subset of 6,047 participants from the original cohort joined another phase of the study, named as SIREN 2.0, and resumed PCR sampling at home (May 2023-March 2024) with phlebotomy and subsequent serological testing at hospital sites (September 2023-March 2024). At-home blood sampling was established between January and March 2024 for a subset of SIREN 2.0 participants whose hospital sites were not offering serological testing (Fig. \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e\n \u003cp\u003eDuring SIREN 1.0, hospital sites carried out monthly or quarterly venous phlebotomy depending on site capacity. Blood samples were transferred to local laboratories, where they were tested for SARS-CoV-2 antibodies utilising locally validated assays. A serum aliquot from each sample was obtained, labelled, and shipped to UKHSA laboratories for biobanking and further testing (if required).\u003c/p\u003e\n \u003cp\u003eIn SIREN 2.0, all participants linked to hospital sites were bled at four defined timepoints (September 2023, November 2023, January 2024, and March 2024). Full blood samples were labelled and sent to a UKHSA laboratory for SARS-CoV-2 antibody testing and biobanking. Participants not linked to hospital sites were offered at-home sampling and provided with capillary blood kits (finger prick devices) at two time points: January 2024 (Postal bleed 1) and March 2024 (Postal bleed 2). Sample tubes were pre-identified with correspondent study sample IDs and returned to UKHSA Porton Down by participants using the pre-paid postal service for testing. A comparison of the main processes related to blood sample collection and management for each study period is captured in Table \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e\n \u003cp\u003eMultiple issues were identified in SIREN 1.0 across all aspects analysed (Table \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e). Managing different bleeding schedules for each site and participants required considerable staff capacity, both from research and phlebotomy teams. Given the large number of participants per site and frequency of bleeds, several samples were incorrectly labelled or did not match electronic records, which delayed sample shipment and generated a large volume of sample discrepancies. Having antibody testing performed at different laboratories utilising different assays was also problematic and often required confirmatory testing at a UKHSA laboratory for subsequent specific analyses.\u003c/p\u003e\n \u003cp\u003eFewer challenges were encountered in SIREN 2.0, demonstrating quality improvement over time. SIREN 2.0 hospital-based sampling had a lower number of sample discrepancies or mislabelling than SIREN 1.0. However, some sites in SIREN 2.0 had issues with setting up couriers for sample shipment, which was more time-sensitive than in SIREN 1.0 due to the shipment of whole blood rather than serum. The use of centralised antibody testing at UKHSA laboratories reduced costs and sample logistics at hospital sites. For SIREN 2.0 at-home sampling, most of the remaining issues related to hospital-based sampling were overcome; for example, samples being directly sent to the UKHSA laboratory by participants optimised sample return and pre-labelling minimised any sample discrepancies. Nonetheless, some participants reported challenges with the capillary sampling method and some samples had insufficient volumes for testing (Table \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e\n \u003cdiv class=\"gridtable\"\u003e\u0026nbsp;\u003cbr\u003e\n \u003ctable id=\"Tab1\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eComparing different processes related to sample collection and management by study period.\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\" rowspan=\"2\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003eSIREN 1.0\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003eSIREN 2.0\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eHospital-based sampling\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eAt-home sampling\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBleeding schedule\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMonthly bleeds from June 2020 to March 2021 for all hospital sites. From March 2021 onwards, hospital sites could choose to perform quarterly bleeds instead of monthly.\u003c/p\u003e\n \u003cp\u003eDifferent bleeding schedules for each site and, within a site, different bleeding schedule for each participant.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAll hospital sites and participants followed the same schedule for bleeds, every two months (September 2023, November 2023, January 2024, and March 2024).\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTwo pre-defined time points for sample collection (January and March 2024).\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBlood sampling and sample flows\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBlood samples were collected by phlebotomy/research teams at the hospital sites.\u003c/p\u003e\n \u003cp\u003eLocal laboratories would extract sera from whole blood samples and send an aliquot to UKHSA laboratory.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBlood samples were collected by phlebotomy/research teams at hospital sites.\u003c/p\u003e\n \u003cp\u003eWhole blood samples were centrifuged and shipped to UKHSA Porton Down.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eParticipants were provided with a capillary sampling blood kits via post.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSample labelling\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSample labels for all participants and bleeds provided at the beginning of the study period.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSample labels provided at 4 time-points for the immediately upcoming bleed.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCapillary sampling kit included a pre-labelled blood tube.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSample shipping\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eElectronic manifests should capture all samples included in the physical shipment and be sent to UKHSA team at least 2 days prior to shipment.\u003c/p\u003e\n \u003cp\u003eMonthly shipments to UKHSA laboratory.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eElectronic manifests should capture all samples included in the physical shipment and be sent to UKHSA team at least 2 days prior to shipment.\u003c/p\u003e\n \u003cp\u003eSamples should be shipped to UKHSA laboratory within ~\u0026thinsp;7 days after collection.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eWhole blood sampled were sent directly to UKHSA laboratory by participants using a pre-paid postal service, as soon as the sample was taken.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSample processing and testing\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSamples tested for SARS-CoV-2 serology at hospital sites, utilising locally validated assays.\u003c/p\u003e\n \u003cp\u003eIf further testing was required, serum samples were shipped from SEU to UKHSA Porton Down.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAll testing was carried out at UKHSA Porton Down.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAll testing was carried out at UKHSA Porton Down.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003c/div\u003e\n \u003cdiv class=\"gridtable\"\u003e\u0026nbsp;\u003ctable id=\"Tab2\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eChallenges related to blood sample collection and management throughout the SIREN study.\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\" rowspan=\"2\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003eSIREN 1.0\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003eSIREN 2.0\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eHospital-based sampling\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eAt-home sampling\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBleeding schedule\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eEach site and participant had their own bleeding schedules to manage, creating considerable staffing demands for phlebotomy clinics and research teams.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNo issues reported.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNo issues reported.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBlood sampling and sample flows\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePhlebotomy clinics required skilled staff and considerable resources, which were costly to the study.\u003c/p\u003e\n \u003cp\u003eSamples required aliquoting and processing at local laboratories, which was time and resource consuming.\u003c/p\u003e\n \u003cp\u003eHospital sites were not shipping samples frequently enough, delaying analyses using antibody data.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePhlebotomy clinics required skilled staff and considerable resources, which were costly to the study.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eFew participants reported issues with capillary blood collection, mainly related to not being familiar with finger prick testing.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSample labelling\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAt the beginning of the study, pre-defined sample ID labels were provided to sites based on an estimated number of participants and bleeds.\u003c/p\u003e\n \u003cp\u003eThere were delays in sending out the first batches of labels to certain hospital sites due to logistical issues, which led to some sites having to manually write sample IDs to identify samples.\u003c/p\u003e\n \u003cp\u003eIf participants missed visits, this would create leftover labels that could mistakenly be used for future bleeds.\u003c/p\u003e\n \u003cp\u003eInitially, extra labels could be ordered via email, which may have increased errors in label printing and shipment. A label request form for ad hoc label requests was further implemented.\u003c/p\u003e\n \u003cp\u003eDelays on delivering additional sample ID labels in time for bleeds during the first study extension resulted in some hospital sites printing their own labels or handwriting labels, leading to transcription errors.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMinimal issues with sample mislabeling.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNo issues reported.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSample shipping\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSeveral shipments received did not match the electronic manifest, requiring in-depth investigation to be resolved and delaying samples getting recorded into the LIMS.\u003c/p\u003e\n \u003cp\u003eThe electronic manifest was not always sent prior to the physical shipment, which impacted on the ability of managing large shipments in a timely manner.\u003c/p\u003e\n \u003cp\u003eElectronic manifests were not completed utilising a barcode reader, which lead to transcription errors.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eA small number of shipments received where samples did not match the electronic manifest, requiring in-depth investigation to be resolved and delaying samples getting recorded into the LIMS.\u003c/p\u003e\n \u003cp\u003eThe electronic manifest was not always sent prior to sending the physical shipment, which impacted on the ability managing large shipments in a timely manner.\u003c/p\u003e\n \u003cp\u003eChallenges in setting up couriers for sample collection at some hospital sites.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMinimal delays on returning samples to the laboratory, only delays associated to postage strikes.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSample processing and testing\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHospital sites conducted different SARS-CoV-2 serological assays. This meant the specificity and sensitivity of these results were not uniform and consistent throughout the study.\u003c/p\u003e\n \u003cp\u003eIf additional testing was required at UKHSA, samples would have to be transported to a different laboratory, impacting on delays in testing.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNo reported issues.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eA few samples were classified as void.\u003c/p\u003e\n \u003cp\u003eDue to insufficient volume or due to the blood sample being clotted, samples can fail the assay\u0026rsquo;s quality control criteria.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003c/div\u003e\n\u003c/div\u003e\n\u003ch3\u003eEvaluation of processes and outcomes for hospital-based and at-home blood sampling\u003c/h3\u003e\n\u003cp\u003eIn total, 6,047 SIREN participants consented to join SIREN 2.0. Of those, 3,624 participants underwent hospital-based sampling, whereas 1,423 participants joined at-home sampling.\u003c/p\u003e\n\u003cp\u003eFor hospital-based sampling, sample return rates varied by bleed timepoint from 61\u0026ndash;77% based on expected numbers of samples. For at-home sampling, the average return rate was higher (80%) (Table \u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e\n\u003cp\u003eWhen comparing the time between sample collection and return to the UKHSA laboratory, samples taken at hospitals took a median of 6 days (IQR 3\u0026ndash;8) to be returned whereas samples taken at-home were returned within a median of 2 days (IQR 2\u0026ndash;3) (Table \u003cspan class=\"InternalRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e\n\u003cp\u003eOverall, hospital-based samples were less likely to be considered void (0%) compared to at-home sampling (4%) (Table \u003cspan class=\"InternalRef\"\u003e5\u003c/span\u003e). Most frequent reason for void samples from at-home sampling was due to insufficient volume.\u003c/p\u003e\n\u003cp\u003eRegarding costs, hospital-based sampling was approximately 3-times more expensive compared to at-home sampling (Table \u003cspan class=\"InternalRef\"\u003e6\u003c/span\u003e), excluding consumable costs for hospital-based sampling.\u003c/p\u003e\n\u003cp\u003eWhen considering sample volumes, hospital-based sampling offered larger volumes of blood via phlebotomy. As per protocol, during SIREN 1.0, at least 2 mL of sera should be obtained from participants from each bleed. For SIREN 2.0, 8 mL of whole blood samples were expected to be shipped to UKHSA Porton Down for testing for each bleed (ensuring a minimum of 2 mL of sera per bleed). In contrast, capillary blood sampling yields very small volumes; in our study, the maximum volume of blood obtained via at-home finger-prick sampling was 600 \u0026micro;L.\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\u0026nbsp;\u0026nbsp;\u003cbr\u003e\n \u003ctable id=\"Tab3\" border=\"1\"\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\" rowspan=\"3\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\" colspan=\"6\"\u003e\n \u003cp\u003eSIREN 2.0\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003cth align=\"left\" colspan=\"4\"\u003e\n \u003cp\u003eHospital-based sampling\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003eAt-home sampling\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eBleed 1\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eBleed 2\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eBleed 3\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eBleed 4\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003ePostal bleed 1\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003ePostal bleed 2\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eReturn rates from SIREN 2.0 hospital-based and at-home sampling. Numbers of expected samples excludes anyone who had withdrew from the study at time of bleeds.\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003ctbody\u003e\u003c/tbody\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eExpected samples (n)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3,624\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3,557\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3,488\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3,459\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1,423\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1,411\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eReturned samples (n)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2,735\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2,564\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2,424\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2,081\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1,180\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1,090\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eReturn rates (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e75%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e73%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e70%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e61%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e83%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e77%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eAverage return rate per pathway (mean %)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"4\"\u003e\n \u003cp\u003e70%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e80%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cdiv class=\"gridtable\"\u003e\n \u003cdiv align=\"left\" class=\"colspec\"\u003e\u003cbr\u003e\u003c/div\u003e\u0026nbsp;\u003ctable id=\"Tab4\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eTimeliness of serology samples received at UKHSA Laboratory from SIREN 2.0 hospital-based and at-home sampling.\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\" rowspan=\"3\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\" colspan=\"6\"\u003e\n \u003cp\u003eSIREN 2.0\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003cth align=\"left\" colspan=\"4\"\u003e\n \u003cp\u003eHospital-based sampling\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003eAt-home sampling\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eBleed 1 (n\u0026thinsp;=\u0026thinsp;2,735)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eBleed 2 (n\u0026thinsp;=\u0026thinsp;2,564)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eBleed 3 (n\u0026thinsp;=\u0026thinsp;2,424)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eBleed 4 (n\u0026thinsp;=\u0026thinsp;2,081)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003ePostal bleed 1 (n\u0026thinsp;=\u0026thinsp;1,180)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003ePostal bleed 2 (n\u0026thinsp;=\u0026thinsp;1,090)\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eNumber of days for sample return per bleed (median (p50); IQR)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e7 (\u003cspan class=\"CitationRef\"\u003e5\u003c/span\u003e\u0026ndash;\u003cspan class=\"CitationRef\"\u003e8\u003c/span\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6 (\u003cspan class=\"CitationRef\"\u003e3\u003c/span\u003e\u0026ndash;\u003cspan class=\"CitationRef\"\u003e8\u003c/span\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5 (\u003cspan class=\"CitationRef\"\u003e3\u003c/span\u003e\u0026ndash;\u003cspan class=\"CitationRef\"\u003e7\u003c/span\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6 (\u003cspan class=\"CitationRef\"\u003e3\u003c/span\u003e\u0026ndash;\u003cspan class=\"CitationRef\"\u003e7\u003c/span\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2 (\u003cspan class=\"CitationRef\"\u003e2\u003c/span\u003e\u0026ndash;\u003cspan class=\"CitationRef\"\u003e3\u003c/span\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2 (\u003cspan class=\"CitationRef\"\u003e2\u003c/span\u003e\u0026ndash;\u003cspan class=\"CitationRef\"\u003e3\u003c/span\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eOverall number of days for sample return per pathway (median; IQR)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"4\"\u003e\n \u003cp\u003e6 (IQR 3\u0026ndash;8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e2 (IQR 2\u0026ndash;3)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cdiv class=\"gridtable\"\u003e\n \u003ctable id=\"Tab5\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 5\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eProportion of void samples from SIREN 2.0 hospital based and at-home sampling.\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\" rowspan=\"3\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\" colspan=\"6\"\u003e\n \u003cp\u003eSIREN 2.0\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003cth align=\"left\" colspan=\"4\"\u003e\n \u003cp\u003eHospital-based sampling\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003eAt-home sampling\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eBleed 1 (n\u0026thinsp;=\u0026thinsp;2,735)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eBleed 2 (n\u0026thinsp;=\u0026thinsp;2,564)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eBleed 3 (n\u0026thinsp;=\u0026thinsp;2,424)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eBleed 4 (n\u0026thinsp;=\u0026thinsp;2,081)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003ePostal bleed 1 (n\u0026thinsp;=\u0026thinsp;1,180)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003ePostal bleed 2 (n\u0026thinsp;=\u0026thinsp;1,090)\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eVoid samples\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(n; %)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1 (0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0 (0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0 (0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0 (0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e66 (6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e19 (2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eOverall number of void samples per pathway (mean %)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"4\"\u003e\n \u003cp\u003e0%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e4%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cdiv class=\"gridtable\"\u003e\n \u003cdiv align=\"left\" class=\"colspec\"\u003e\u003cbr\u003e\u003c/div\u003e\u0026nbsp;\u003ctable id=\"Tab6\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 6\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eEstimation of overall cost per sample from SIREN 2.0 hospital-based and at-home sampling. *Shipping charges include both outbound and return mailing costs for at-home sampling.**Phlebotomy charge excludes consumables, given those were covered by the hospital sites.\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003eStudy stage\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003eSIREN 2.0\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eHospital-based sampling\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eAt-home sampling\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eShipping charges\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026pound;1.11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026pound;6.00*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSerology/ Phlebotomy charge**\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026pound;16.49\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eN/A\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eParticipant admin per month per participant\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026pound;7.65\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eN/A\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNurse time per month per participant\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026pound;8.80\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eN/A\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCapillary sampling kit charges\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eN/A\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026pound;5.50\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eTotal\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026pound;34.05\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026pound;11.50\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e"},{"header":"DISCUSSION","content":"\u003cp\u003eIn this study, we described the different processes for blood collection within the SIREN study and how those evolved as the study progressed.\u003c/p\u003e \u003cp\u003eContinuous improvement cycles are key to deliver large scale responsive research, as we have demonstrated. Our option to utilise a decentralised approach for sample collection and testing in SIREN 1.0 has proved to be complex, requiring extensive logistical arrangements and research site\u0026rsquo;s local capability. Troubleshooting by UKHSA and the study sites to resolve sample discrepancies was a resource heavy activity. However, by collecting feedback and consistently reviewing processes for sample collection and management, we were able to overcome these challenges in SIREN 2.0, e.g. by standardising bleeding schedules and having centralised testing at UKHSA Laboratories, as opposed to local testing on a range of assays. Some studies have explored the concept of home visits by phlebotomists; however, this is impractical for large scale studies. (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e)\u003c/p\u003e \u003cp\u003eThese processes were further improved by implementing at-home sampling. When comparing hospital-based and at-home sampling, we have demonstrated that self-blood collection was superior in terms of logistics, sample return and costs. Our findings are supported by previous studies, that have found that capillary blood sampling was an accurate and advantageous method for blood sample collection for assessing SARS-CoV-2 antibodies and other serological markers. (\u003cspan additionalcitationids=\"CR10\" citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e) Furthermore, in the context of an outbreak of a new or emerging pathogen, at-home sampling minimises the risk of disease transmission between individuals. (12)\u003c/p\u003e \u003cp\u003eDespite low numbers, at-home sampling provided a higher rate of voided samples upon testing when compared to phlebotomy, generally due to insufficient volumes of samples, which could have implications for specific analyses. It should be recognised that at-home sampling can only extract low sample volumes, that could become insufficient for testing if the correct instructions for blood collection are not followed and limiting the options of running additional testing or biobanking samples. (13) In addition, at-home sampling would not be suitable for specific analysis that require rapid sample processing. Therefore, these are key limitations of self-sampling methods and should be considered when designing new research studies, to ensure the study requirements are fulfilled.\u003c/p\u003e \u003cp\u003eAnother important aspect when considering different methods for blood sampling is participant experience. Previous studies have demonstrated self-collection methods to be highly accepted by participants, (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e) although some reported it to be uncomfortable or painful. (14) We collected SIREN participant\u0026rsquo;s feedback on hospital-based and at-home sampling and preliminary analysis found that although both methods were acceptable, at-home sampling was preferable compared to hospital-based (55% vs 23%, respectively). This will be described in more details in a separate analysis.\u003c/p\u003e \u003cp\u003eOur evaluation comparing hospital-based and at-home sampling did not include post-analytical metrics related to the performance of the assay, as quality indicators were not available at the time of this analysis. We acknowledge this as a limitation. However, previous studies have shown high rates of concordant SARS-CoV-2 antibody results between the two different methods. (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e) Overall, we have demonstrated capillary blood collection is advantageous compared to venous phlebotomy, mindful of limited sample volumes, with additional benefits in terms of logistical arrangements and convenience for sampling.\u003c/p\u003e"},{"header":"CONCLUSIONS","content":"\u003cp\u003eLarge scale research studies that require the collection of blood samples can face challenges related to sample collection and management. Overall, at-home blood sampling is a valuable tool for research testing, providing cost-effectiveness and convenience for participants.\u003c/p\u003e"},{"header":"Declarations","content":" \u003cp\u003e \u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e \u003cp\u003eThe study protocol was approved by the Berkshire Research Ethics Committee on May 22, 2020. Informed consent was obtained from all participants included in the study.\u003c/p\u003e \u003c/p\u003e \u003cp\u003e \u003cstrong\u003eConsent for publication\u003c/strong\u003e \u003cp\u003eNot applicable.\u003c/p\u003e \u003c/p\u003e\u003cp\u003e \u003ch2\u003eCompeting interests\u003c/h2\u003e \u003cp\u003eAll authors declare that they have no competing interest.\u003c/p\u003e \u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eAA, NH, AO, SF, VH, JI and SH conceptualised this analysis and contributed to the study design. NH, DB, JK and SF were responsible for curation of sample data. NH, JK and SF verified the data and performed the data analysis for this study. NH and AA did the literature search and drafted the manuscript. DB, TC, AD, EL, MJC, MC and AO contributed to sample management and testing. All authors read and approved the final manuscript, had full access to all the data in the study, and had final responsibility for the decision to submit for publication. SH is the chief investigator for SIREN.\u003c/p\u003e\u003ch2\u003eAcknowledgement\u003c/h2\u003e\u003cp\u003eWe would like to thank all participants who have contributed to the SIREN study. We would also like to thank the research teams and staff at hospital sites throughout the years for their hard work and commitment to the SIREN study. We thank all colleagues from UKHSA Porton Down, UKHSA Seroepidemiology Unit and UKHSA Colindale laboratories for their great efforts to support the sera biobank and serological testing for SIREN over the years.\u003c/p\u003e\u003ch2\u003eData Availability\u003c/h2\u003e\u003cp\u003eAnonymised datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eLima-Oliveira G, Lippi G, Salvagno GL, Picheth G, Guidi GC. Laboratory Diagnostics and Quality of Blood Collection. J Med Biochem. 2015;34(3):288-94.\u003c/li\u003e\n\u003cli\u003eWong MP, Meas MA, Adams C, Hernandez S, Green V, Montoya M, et al. Development and Implementation of Dried Blood Spot-Based COVID-19 Serological Assays for Epidemiologic Studies. Microbiol Spectr. 2022;10(3):e0247121.\u003c/li\u003e\n\u003cli\u003eWixted D, Neighbors CE, Pieper CF, Wu A, Kingsbury C, Register H, et al. Comparison of a Blood Self-Collection System with Routine Phlebotomy for SARS-CoV-2 Antibody Testing. Diagnostics (Basel). 2022;12(8).\u003c/li\u003e\n\u003cli\u003eKnitza J, Tascilar K, Vuillerme N, Eimer E, Matusewicz P, Corte G, et al. Accuracy and tolerability of self-sampling of capillary blood for analysis of inflammation and autoantibodies in rheumatoid arthritis patients-results from a randomized controlled trial. Arthritis Res Ther. 2022;24(1).\u003c/li\u003e\n\u003cli\u003eNorelli J, Zlotorzynska M, Sanchez T, Sullivan PS. Scaling Up CareKit: Lessons Learned from Expansion of a Centralized Home HIV and Sexually Transmitted Infection Testing Program. Sex Transm Dis. 2021;48(8S):S66-S70.\u003c/li\u003e\n\u003cli\u003eShrotri M, Fragaszy E, Nguyen V, Navaratnam AMD, Geismar C, Beale S, et al. Spike-antibody responses to COVID-19 vaccination by demographic and clinical factors in a prospective community cohort study. Nat Commun. 2022;13(1):5780.\u003c/li\u003e\n\u003cli\u003eWallace S, Hall V, Charlett A, Kirwan PD, Cole M, Gillson N, et al. Impact of prior SARS-CoV-2 infection and COVID-19 vaccination on the subsequent incidence of COVID-19: a multicentre prospective cohort study among UK healthcare workers - the SIREN (Sarscov2 Immunity \u0026amp; REinfection EvaluatioN) study protocol. BMJ Open. 2022;12(6):e054336.\u003c/li\u003e\n\u003cli\u003eMohammed T, Brewer JVV, Pyatt M, Whitbourne SB, Gaziano JM, Edson C, et al. Evaluation of independent self-collected blood specimens for COVID-19 antibody detection among the US veteran population. Diagn Microbiol Infect Dis. 2022;104(2):115770.\u003c/li\u003e\n\u003cli\u003eHendelman T, Chaudhary A, LeClair AC, van Leuven K, Chee J, Fink SL, et al. Self-collection of capillary blood using Tasso-SST devices for Anti-SARS-CoV-2 IgG antibody testing. PLoS One. 2021;16(9):e0255841.\u003c/li\u003e\n\u003cli\u003eWickremsinhe E, Fantana A, Berthier E, Quist BA, Lopez de Castilla D, Fix C, et al. Standard Venipuncture vs a Capillary Blood Collection Device for the Prospective Determination of Abnormal Liver Chemistry. J Appl Lab Med. 2023;8(3):535-50.\u003c/li\u003e\n\u003cli\u003eKing ER, Garrett HE, Abernathy H, Cassidy CA, Cabell CR, Shook-Sa BE, et al. Comparison of capillary blood self-collection using the Tasso-SST device with venous phlebotomy for anti-SARS-CoV-2 antibody measurement. J Immunol Methods. 2023;520:113523.\u003c/li\u003e\n\u003cli\u003eConserve DF, Mathews A, Choko AT, Nelson LE. Preparing for severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) self-testing implementation: Lessons learned from HIV self-testing. Front Med (Lausanne) [Internet]. 2020;7:599521. Available from: http://dx.doi.org/10.3389/fmed.2020.599521.\u003c/li\u003e\n\u003cli\u003eZoratto N, Klein-Cerrejon D, Gao D, Inchiparambil T, Sachs D, Luo Z, et al. A Bioinspired and Cost-Effective Device for Minimally Invasive Blood Sampling. Adv Sci (Weinh). 2024;11(18):e2308809.\u003c/li\u003e\n\u003cli\u003eLiu Y, Rafkin LE, Matheson D, Henderson C, Boulware D, Besser REJ, et al. Use of self‐collected capillary blood samples for islet autoantibody screening in relatives: a feasibility and acceptability study. Diabet Med [Internet]. 2017;34(7):934\u0026ndash;7. Available from: http://dx.doi.org/10.1111/dme.13338\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-medical-research-methodology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bmrm","sideBox":"Learn more about [BMC Medical Research Methodology](http://bmcmedresmethodol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bmrm/default.aspx","title":"BMC Medical Research Methodology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Evaluation, Blood Specimen Collection, Phlebotomy, Cohort Studies","lastPublishedDoi":"10.21203/rs.3.rs-5804123/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5804123/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eDelivering research studies that require a large number of samples to monitor specific populations is complex, often resulting in high costs and intricate logistics. We aim to describe the processes for blood sample collection and management and evaluate alternative sampling methods within a large cohort of healthcare workers in the UK (the SIREN study).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe conducted a process evaluation. First, we described blood sample collection and management across different study periods from June 2020 to March 2024 and how these evolved over time. Secondly, we compared alternative methods of blood sampling: venous phlebotomy (hospital-based) vs. capillary sampling (at-home).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults \u003c/strong\u003e\u003cbr\u003e\n The main challenges with blood sampling within SIREN stemmed from the scale and use of decentralised phlebotomy across 135 hospital sites during the COVID-19 pandemic. We adapted our sampling processes as the study progressed, overcoming most of these challenges. When comparing hospital-based and at-home sampling, overall, return rates of samples taken at home were higher than site- based samples (80% vs 71%, respectively). At-home samples took less time to be returned to UKHSA Laboratory for testing compared to hospital-based samples (median 2 days; interquartile (IQ) 2-3) vs 6 days; IQ 3-8). However, at-home samples were more likely to be considered void (4%) when tested compared to hospital-based samples (0%). Cost for hospital-based sampling was almost 3-times higher than at-home sampling (£34.05 vs £11.50, respectively), however larger sample volumes were obtained via hospital-based sampling when compared to at-home sampling (8 ml vs 600 µl of whole blood).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eSample collection and management in large scale research studies are complex. Our results support at-home blood sampling as an effective and cheaper strategy when compared to hospital-based phlebotomy and therefore should be considered as alternative sampling method for future research.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTrial registration number:\u003c/strong\u003e ISRCTN11041050 - registration date 12/01/2021.\u003c/p\u003e","manuscriptTitle":"­­Evaluating blood sampling strategies within the SIREN study: the experience from a large cohort of healthcare workers in the UK","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-02-19 15:47:10","doi":"10.21203/rs.3.rs-5804123/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-04-29T14:37:42+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-04-29T10:40:48+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"293004503108626997518400256270975791496","date":"2025-04-29T10:18:21+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-04-25T16:20:36+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"71100773898513585074902326988525454252","date":"2025-04-16T15:32:26+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-01-22T09:27:44+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2025-01-20T18:08:58+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-01-20T03:22:06+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-01-20T03:21:58+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Medical Research Methodology","date":"2025-01-10T13:31:37+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-medical-research-methodology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bmrm","sideBox":"Learn more about [BMC Medical Research Methodology](http://bmcmedresmethodol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bmrm/default.aspx","title":"BMC Medical Research Methodology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"6fff4920-bbf0-4e62-8559-2a97e34525b1","owner":[],"postedDate":"February 19th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-07-07T16:05:01+00:00","versionOfRecord":{"articleIdentity":"rs-5804123","link":"https://doi.org/10.1186/s12874-025-02599-x","journal":{"identity":"bmc-medical-research-methodology","isVorOnly":false,"title":"BMC Medical Research Methodology"},"publishedOn":"2025-07-01 15:58:01","publishedOnDateReadable":"July 1st, 2025"},"versionCreatedAt":"2025-02-19 15:47:10","video":"","vorDoi":"10.1186/s12874-025-02599-x","vorDoiUrl":"https://doi.org/10.1186/s12874-025-02599-x","workflowStages":[]},"version":"v1","identity":"rs-5804123","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5804123","identity":"rs-5804123","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}