Title: ChromaDose: In-vitro diagnostic device development and validation, enabling point-of-care therapeutic drug monitoring for dose optimisation of anthracycline chemotherapy in paediatric cancer settings.
Funder: Department of Health and Social Care

Abstract: Determining anthracycline dosage in childhood cancer is a clinical dilemma due to significant drug exposure variability between children. Despite their propensity to inflict dose-related cardiotoxicity, anthracyclines are prescribed in over half of childhood cancer cases. Current dosing regimens are suboptimal, with dose adjustments not following clear pharmacological rationale. Standardised dosing models would reduce variable therapy intensity and subsequent side-effects, however, implementation is hampered by scarce pharmacokinetic data to validate drug exposure-response relationships. Therapeutic drug monitoring (TDM) provides data on how individuals process drugs, guiding personalised methods of dosing based on patient pharmacokinetic characteristics. However, current TDM involves centralised analysis, inducing pre-analytical errors via sample degradation and handling inconsistencies. Such methodology incurs decision delays, has poor scope for scalability and distance stakeholders from care pathways. We aim to deliver ChromaDose: a point-of-care companion monitoring device; generating drug exposure data to support pharmacokinetic-led dose optimisation in paediatric oncology. Across 30-months, a lab-proven technology will be developed into a clinic and CE-ready, anthracycline monitoring tool for second-generation TDM, offering automated quantification from blood samples, faster, cheaper and with equivalent accuracy to national laboratory benchmarks. UCL and Vesynta Ltd shall lead device development, with Newcastle University providing reference measurement and clinical pharmacology input. ChromaDose is supported by pan-UK Young Persons Advisory Groups, NIHR London in-vitro-diagnostic cooperative, regulatory experts, research nurses, paediatric oncologists and parents. Iterative technology development shall capture the needs of stakeholders and build a CE-ready technical file. The final in-vitro diagnostic shall undergo validation via independent quality assessments (using spiked and banked blood samples). Output dissemination will occur via a white-paper publication, conferences and patient-developed information media, aimed at patients, public and healthcare professionals. ChromaDose lays the foundation for bedside pharmacokinetic-led dose personalisation, improving anthracycline safety in children, with potential to scale to multiple drug classes and patient populations in the future.

Lay abstract: ChromaDose: A blood-testing tool helping to personalise the amount of medicine for children with cancer. How does a doctor choose the right amount of medicine for you? Until now, the best way has been to use each patient s height and weight as a guide. The problem with this method is that medicines can move around the bodies of two people (with the same height and weight) very differently. What is the problem? Anthracyclines are anti-cancer medicines given to more than 10,000 children with cancer in the UK (adults too). Unfortunately, these medicines can cause heart problems for 65% of children; these side effects are linked to unnecessarily high medicine &ldquo;exposure&rdquo;. Medicine &ldquo;exposure&rdquo;... ...is the concentration of medicine in our blood and the length of time it stays there. It is different for each patient because everyone processes medicine differently: even if we are all given the same amount of medicine, our &ldquo;exposures&rdquo; will be different. This impacts how effective medicines are for different people and the unwanted side effects they may experience. What is the project aim? It is impossible to accurately predict what someone s medicine &ldquo;exposure&rdquo; will be without doing a blood test. During this project, we will develop a new tool called ChromaDose that will help nurses do these tests at each patient s bedside. ChromaDose will be easy to use, quick and give a reliable result. How would ChromaDose work? A nurse will take a few drops of blood at different times and put these samples into the ChromaDose bedside machine (about the size of an old printer). The machine will automatically measure the amount of medicine within each blood drop by placing the blood samples on a metal plate and then taking a fluorescent photo (higher amounts of medicine will produce a brighter image). With this information, ChromaDose can calculate the patient s medicine &ldquo;exposure&rdquo;. How would treatment change? Medicine &ldquo;exposure&rdquo; information from ChromaDose would help a doctor decide whether to increase or decrease the amount of medicine they give to each patient. This personalisation could improve the chance of the medicine working and reduce unwanted side effects. Automated testing (whilst the patient is in the room) is the quickest way to select the right amount of medicine. Why can t we post these tests to a laboratory? Time delays sending blood samples make the medicine &ldquo;exposure&rdquo; measurement inaccurate because anthracyclines degrade quickly. What happens next? Three things need to happen for ChromaDose to become widely used in hospitals: Refine the blood testing method and create patient information resources (through discussions with patients and parents). Ensure ChromaDose is easy to use (in partnership with nurses and doctors). Improve and document ChromaDose s performance to gain official approval as being &ldquo;safe-to-use&rdquo;.

Research activity codes: 4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES
Health categories: CANCER AND NEOPLASMS