US hospital systems validate the safety, clinical utility, and robustness of newly FDA-approved devices, 510(k) cleared, before adopting them into clinical practice. This work occurs alongside evaluating how to integrate the medical device into the hospital system’s diagnostic paradigms, including in relation to quality improvement programs. Companies can have a role but there are 415 US hospital systems (comprising ~5,000 hospitals), and each has a bespoke process and ever-changing set of considerations. Navigating this new reality is challenging for companies and hospital systems. The pandemic only made it more complex and slower. It is important for company executives and hospital system leadership teams to talk about what is working. In that spirit, I am sharing insights from my team at Immunexpress for our lead test, SeptiCyte® RAPID, which is clinically validated and has received FDA 510(k) clearance indicated for the diagnosis of sepsis in adults.
Sepsis accounts for the highest in-patient deaths and costs and is additionally the most under-reimbursed for diagnosis and treatment.
Sepsis diagnosis and management is not standardized across hospital systems. Some have adopted recommendations by Surviving Sepsis Campaign International Guidelines for care management of sepsis and septic shock to have an early warning system. The concept is straightforward, but the implementation is much less so. Acutely ill patients exhibiting signs of a systemic immune response are put through a battery of tests and placed on treatment, termed sepsis bundles, to diagnose sepsis and rule out the infection-negative systemic immune response. There is no consensus on which tests to include in the sepsis bundles, nor how to administer them and interpret the results. The rule-in/rule-out is key to cost-effectively utilizing the space and bandwidth of medical teams in emergency rooms and intensive care units and avoiding the unnecessary prescription of antibiotics which contributes to the global threat of antibiotic resistance. Sepsis, in contrast to infection-negative systemic immune response, is life-threatening, must be treated quickly, and is responsive to an antibiotic, antiviral (most recently as evidenced by the COVID-19 pandemic), or anti-fungal treatments.
What this represents is a sepsis diagnostic and treatment dilemma. There is no gold standard to differentiate systemic immune response with infection (sepsis) versus without infection.
There is an encouraging trend in the US. The majority of hospital systems, especially those comprising larger hospitals, those with more than 200 beds of which there are ~1,300, are examining the performance of their sepsis bundles and exploring how to change them through quality improvement programs. There is a clear incentive: better performance equates to better care and lower costs.
An external motivator is reinforcing the trend. The Centers for Medicare & Medicaid Services (CMS) is evaluating hospitals’ antibiotic stewardship and more recently, in the area of sepsis, hospitals’ compliance with CMS’ 1-h and 3-h sepsis resuscitation guidelines. Every six months, CMS puts out a compliance score for each hospital. There is a lot of room for improvement – the national average is 60% but the range is low 20% to 80%. Hospital systems are dissatisfied with their performance and want both a higher mean and lower variance within their network. They are asking: how do we standardize? The answer is two-part. Conduct quality improvement programs and evaluate new technologies, for potential incorporation, to help from a compliance standpoint.
We understood this context – a drive toward standardization for sepsis diagnosis – and our response was to seek being a partner, not exclusively a seller, to hospital systems. We look for how we can incorporate them without impacting their ongoing clinical care. We meet with sepsis management teams to see how we can improve CMS compliance for the resuscitation guidelines and improve patient outcomes, as well as lower costs and drive higher reimbursement.
Highly worthwhile. But it is no small task. One has to be able to set that up across a broad number of prospective stakeholders focused on improved sepsis patient management, including clinicians and clinical care nurses, laboratorians, and hospital leadership teams.
We recommend listening within the hospital system and being responsive to each having different needs and priorities. I want to give two representative examples but keep in mind there are many more beyond these. The first example is too many false diagnoses of patients having sepsis resulting in attention, already limited in the ER and ICU settings, being diverted to patients that did not need it and patients being accelerated onto treatments that were unnecessary at that time, if not ever. Many hospital systems utilize an electronic warning system that takes in data from the sepsis bundle and applies an algorithm to predict the likelihood of sepsis and puts out a warning if above a decided threshold value. The false positive rate is too high. Our SeptiCyte® RAPID test addresses the issue by improving the sepsis program. One aspect of that is driving higher performance to sepsis bundles, whatever components they might have at a given hospital system which sometimes can be as high as 12 variables. Another aspect is optimizing how the sepsis bundle is implemented within the sepsis diagnosis and care management practices. The second example is too often the discharge of ICU patients is delayed because there is uncertainty about whether the patient has fully recovered from sepsis; our SeptiCyte® RAPID test addresses this need, again by improving the performance of the sepsis program.
What I am getting at is – you need a solution that fulfills essential requirements for the medical community. We highly recommend designing the test for stakeholders from day one and that includes anticipating how to avoid adoption hurdles. We took this approach. That is why our test gives positive and negative predictive values at the early onset of sepsis, the test delivers a result in one hour, the test utilizes a standard blood draw, the test runs not on a novel or dedicated back-end detection system but on a system already proven in medical laboratory settings and used to run multiple tests for clinical care decisions, and the test requires <5min of hands-on time, among other considerations.
One of the hardest transitions is from clinical evaluation of your FDA 510(k) cleared device to being set up for the hospital system adopting and signing long-term contracts for the technology.
From my experience, and I have launched several novel products into the hospital laboratory environment, you have the clinical data that supported your FDA clearances, but it is the user experience that is important. As I mentioned before, there are different reasons why different hospitals might want to utilize the technology. And in different clinical settings – for example, they may have a high issue with post-operative patients acquiring catheter-related infections or oncology patients undergoing chemotherapy that becoming neutropenic. We ask US hospital systems: what are your primary need and the three after that one? If we have a use case that is helpful for that, we ask for permission from the previous customer to bring that out and present it. I have found that customers are often willing to exchange information with others. This exchange can enable broader adoption.
I want to leave you with: A vendor cannot just knock on one door in the hospital and have the expectation of being a seller only. A vendor needs to embrace being a partner. Your FDA 510(k) cleared device must be designed for and evaluated by a number of stakeholders. Find who they are, listen, be a partner first and a seller second.
About Rolland Carlson, PhD | LinkedIn
Rolland Carlson, Ph.D., is CEO of Immunexpress, a molecular test company that focuses on improving outcomes for suspected sepsis patients and more broadly patients with acute host immune response conditions. He has 25+ years of extensive leadership in the molecular diagnostic space across business development, new product R&D and FDA approval, as well as global commercial and general management. Carlson joined Immunexpress in 2018 as CEO. Prior to that, he served as CEO Wafergen Biosystems (NASDAQ: WGBS), CEO at Asuragen for eight years and held several business development roles of increasing responsibility at Abbott Laboratories for over 20 years. He holds a bachelors and a doctoral degree from Southern Illinois University.