The test evaluation, development and implementation (TEDI) study recruits asymptomatic individuals to provide negative clinical samples with the purpose of developing and validating new point-of-care of diagnostic tests for a range of infectious diseases.

Description of intervention(s) / exposure: This is a prospective study to obtain fresh samples from staff, patients, and visitors at Royal Melbourne Hospital, as well as members of the general public via social media. • Recruitment and sampling: Victorian Infectious Diseases Service (outpatient clinic), Royal Melbourne Hospital, 300 Grattan St, Parkville, VIC. • Research and Development: ZiP Diagnostics Pty Ltd, 24 Cromwell St, Collingwood Victoria, Australia Participant recruitment: A general advertising email will be sent to employees at RMH, as well as posters displayed in common areas around the hospital to invite patients and visitors to participate. For RMH employees, the email will be sent via Heads of Department/Nurse Unit Managers. Members of the general public will be invited to participate through social media advertising. Advertisements include a website address that contains additional information regarding the study, participation involvement and contact details. Potential study participants will be able to make an individual teleconference appointment to discuss the details of the study with the Principal Investigator (PI) or Research Nurse (RN). In addition to recruiting new participants, those who completed the first 12 months of the study will be approached by the RN to ascertain whether they would be interested in reconsenting to the 12-month study extension. Participant consent processes: Individual information sessions will be via teleconference with interested potential participants. The RN will provide potential study participants with a copy of the Patient Informed Consent Form (PICF) and additional verbal information about the study. If a potential participant agrees to participate, they will be asked to sign the PICF which will be posted out to them and returned to the RN by mail in a reply-paid envelope. Once written informed consent is provided the RN will assign the participant a unique Participant Identification (PID) Number. A copy of the PICF will be given to the participants to keep. Sample size and frequency of recruitment: Up to 70 participants will be recruited. This potentially offers a diverse range of specimen types and heterogenous samples that can be collected. The specimen type and sampling frequency will be according to the experimental needs of the projects. The total study duration will be 24, months. As critical experiments are planned, the ZiP Diagnostics contact person will inform the Site Coordinator (SC) about the number and type of samples required. Sample types: Self-collected samples: nasal swabs, throat swabs, nose and throat swabs, skin swabs, saliva, urine, vaginal swabs. These samples are self-collected by participants based on standard operating procedures (SOPs). Nurse-collected samples: blood (venous or fingerprick). Blood samples are collected by trained RN according to the standard operating procedures (SOPs) developed that outlined in study protocol. Sample collection: The study is likely to have variable needs for clinical samples because the test development program is dynamic. To ensure that samples are only collected as required for specific experiments, the R&D team (via the ZiP Diagnostics Study Coordinator) will request the specific specimen types and numbers of samples on a weekly basis. This will allow the SC to email all study participants to request samples, with a minimum of 24 hours’ notice. Participants that are available and willing to donate samples on that occasion will nominate an approximate time for sample self-collection or make an appointment to provide blood samples with the RN. All urine, swab and saliva samples will be self-collected by participants following the sample collection standard operating procedure (SOP) developed as outlined in the study protocol. Due to the current COVID-19 outbreak, participants that are no longer at RMH will be able to take a self-collected sample at home. Participants will be given a self-collection kit by the RN or it may be couriered to them. If a venous or fingerprick blood sample is required, this will be taken by a trained Registered Nurse at the RMH clinic. The RN is trained to collect blood samples according to the sample collection standard operating procedures (SOPs) developed as outlined in the study protocol at the RMH clinic. The RN collects The RN When self-collected samples have been obtained, they will be returned by the participant to the RN, who will contact the courier and inform the ZiP Diagnostics Study Coordinator that a sample will be delivered. Samples collected at home will be couriered directly to the ZiP Diagnostics lab. Each sample is assigned a unique and coded Sample Identification (ID) Number, based on the PID, date the sample was taken and sample type. This will be entered into the laboratory sample log by the Zip Diagnostic Study Coordinator. At no stage will any R&D staff have access to information about the study participants, or access to re-identifiable or decoded data that would disclose the identity of participants. To illustrate how the sample collection process will occur; the Chlamydia trachomatis and Neisseria gonorrhoeae (CT/NG) project may require 3 urine and vaginal samples for a particular experiment, and this experiment might be repeated a second time in the same week. This sample requirement could successfully be met either with 3 people donating twice in that week, or 6 participants donating once. It is likely that over the 12 months of the study, there will be many weeks in which no clinical samples will be required. Study participants may choose to donate one sample type but refuse to provide another sample type. For example, if a request is made for 3 nasal swabs for the SARS-CoV-2 project and 3 urine/ vaginal swab samples for the CT/NG project, then one participant might choose to provide all sample types, but another participant might choose to provide a urine sample but decline to provide a nasal or vaginal swab. This will be at the discretion of the study participant. Participant preferences and the number and frequency of sampling will be managed by the SC. Participants can choose the number and frequency of the sampling. Participants may be asked to provide 2 of the same sample type on the same day for clinical validation testing. On these occasions, one sample will be sent to a NATA-accredited diagnostic laboratory and the other will be used at ZiP Diagnostics. Both test outcomes are expected to be negative. These comparative test results assist in the clinical validation of the test platform demonstrating the new test accurately determines negative test results by comparing them to gold-standard laboratory-based tests. A maximum number of samples is defined to ensure that there is not an excessive burden placed on any of the study participants. Participants can provide samples at each request from the SC or choose to refuse to provide a sample at any time point. The following collection limits will be applied: - Up to but not exceeding 2 nasal swabs per person per day, max limit of three times a week. Mid-turbinate swabs are preferred but anterior nares may also be tested. Deep nasopharyngeal swabs will not be collected. - Up to but not exceeding 2 throat swabs per person per day, max limit of three times a week. - Up to but not exceeding 2 throat and nose swabs per day, max limit of three times a week. - Up to but not exceeding 2 skin swabs per person per day, max limit of three times a week. - Up to but not exceeding 20ml saliva per person per day, max limit of three times a week. - Up to but not exceeding 2 vaginal swabs per person per day, max limit of three times a week. - Up to but not exceeding 200mL of urine per person per day, max limit of three times a week. - Up to but not exceeding 20mL of blood per person per day, max limit of once per week. OUTCOME MEASURES Samples collected in this study will be used to optimise sample processing methods, reagent composition, and result algorithms, and to ascertain early insights into test performance including sensitivity, specificity, and reproducibility for the new point-of-care for a range of infectious diseases. A subset of samples will be used as negative controls for clinical validation purposes (determine sensitivity and specificity.) The point-of-care diagnostic tests are based on DNA/ RNA nucleic acid amplification, as well as lateral flow antigen/ antibody detection methods. These tests are for a range of infectious diseases including respiratory pathogens (SARS-CoV-2, Influenza, RSV,) mosquito-borne diseases (Dengue, Zika, Japanese encephalitis, chikungunya, Ross River virus, Malaria), Blood-borne viruses (e.g., Hepatitis B, Hepatitis C, HIV), Sexually Transmitted Diseases (e.g., gonorrhoea, chlamydia, monkeypox, etc), Vaccine-preventable diseases (measles, tetanus, etc). Current Project: Ethics and governance approval was first obtained for the TEDI study on 14 October 2021. Since that time, negative samples have been collected for the purposes of optimising a new SARS-CoV-2 point-of-care test, called ZiP-CoVx-P2. We recently obtained an ethics amendment to use these samples to validate this SARS-CoV-2 test, comparing it to lab-based RT-PCR. Primary Objective: To optimise novel diagnostic tests for different infectious diseases. This will use a range of negative human specimen types as a clinical matrix with spiked-in microorganisms. Secondary Objective: To undertake analytical test performance testing in early-stage validation studies using mock-infected human samples. Early-stage analytical validation in alpha and beta prototypes will guide design and manufacture revisions to ensure optimal performance. This is to ensure that final analytical testing and clinical trials using final ‘lock-down’ products are likely to meet performance criteria. Sample type: combined oropharyngeal (throat) and bilateral mid-turbinate (nasal) swabs. Comparator: established RT-PCR standard platform. Outcome: 1) Develop an optimised point-of-care test that meets pre-specified test specifications. 2) Determine test sensitivity and specificity (including limit-of-detection and clinical sensitivity/ specificity, compared with lab-based RT-PCR) using 100 positive and 500 negative samples.