Clinical Evaluation of Point of Care Raman Analysis for Diagnosis of Gout

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Gout affects millions of people in the US and the economic burden due to the disease is comparable to other chronic conditions such as Parkinson's disease or migraine. Accurate identification of crystal identity is essential to pursue an appropriate form of treatment. Patients who have gout attacks seek care at hospitals, outpatient centers, urgent care or the ER with hot, swollen and painful joints; therefore, gout symptoms can be confused with other forms of arthritis. Conclusive diagnosis requires observation of synovial aspirates by polarized light microscopy (PLM) to confirm the presence of negatively or positively birefringent crystals. In practice, PLM analysis as a billable service requires a microscope equipped with compensated polarization optics and a Clinical Laboratory Improvement Amendments (CLIA) for the laboratory. Certification by pathologists or rheumatologists is done by professional organizations followed by credentialing and the hospital or lab that performs the analysis and subject to hospital policy about who may report PLM findings. For all intensive purposes, PLM is therefore only feasible in major healthcare centers and central laboratories in selected rheumatology practices. Therefore, clinicians on the front line may be unable to diagnose gout during their clinical encounter or they depend on presumptive diagnosis based on clinical symptoms that lack sensitivity and specificity. The new American College of Rheumatology gout classification criteria are an attempt to address this problem but truly, a facile and automated point of care testing for gout and pseudogout is needed in primary care settings to inform the diagnosis and treatment of these diseases. Point of care Raman device (POCR) is an existing prototype that is developed at Case Western Reserve University (CWRU) with past NIH R21 and R01 to identify MSU and CPPD crystals in synovial fluid. The method involves a simple and facile sample preparation to isolate crystals in a disposable cartridge that is then inserted in a compact, cost-efficient and automated device which identifies the crystal species based on fingerprint molecular spectroscopy. By design, the method should be able to be performed by the non-specialist with minimal training. POCR was evaluated using synovial fluid samples from symptomatic patients (N=174) and there was more than 90% agreement between the diagnoses of POCR and PLM conducted by a certified technician/pathologist. During a prior R01 (Akkus/Singer), clinical synovial sample analyses were performed by researchers. The current version of the device needs a moderate number of modifications and customization to ready it for use by clinicians. This Phase I SBIR will demonstrate that diagnosis of gout/pseudogout by POCR as executed by the non-specialist staff at point of service will agree with the diagnosis by PLM conducted by certified operators. During first aim the prototype developed in CWRU will be transferred to Spectral Energies LLC who will refine it to make a clinically executable prototype. The clinical prototype will be used and evaluated by clinical staff in the second aim. The diagnostic outcome of synovial fluid analysis on freshly collected samples by POCR in the hands of non-expert clinical staff will be compared to PLM analysis performed as standard of care. The Phase I study will provide us with a clinically applicable POCR and pave the way for a multi-site clinical assessment of the device in a follow up Phase II study that aims to demonstrate that POCR enables the diagnosis of gout in settings which are not equipped with PLM and CLIA certified laboratories and accredited operators.