While clinical care as a research option (CRAACO) is not a new concept, acceptance of the idea is still growing. Jaydev Thakkar, chief operating officer of Biofourmis, discusses how clinical research and care are intertwined, how they traditionally have butted heads, and how bringing them closer together can benefit multiple stakeholders.
OSP: Could you please talk about the relationship between clinical research and patient care—how they complement each other, and ways in which the two fields can sometimes conflict?
JT: Clinical research primarily focuses on developing new treatments or medications to advance the standard of care, whereas clinical (patient) care usually focuses on improving a patient’s health condition with a currently approved standard of care.
They both rely on each other—research needs participants that are “eligible patients” currently undergoing standard clinical care. Clinical care needs innovation and new treatment options that have clear evidence of safety and efficacy; this evidence is gathered from clinical research.
They complement each other in that clinical research provides new care options, particularly for a person with limited access to care. From an affordability perspective, a research sponsor typically will pick up a substantial portion of the cost of care that is not covered under insurance plans, which may make higher quality care and new options available to patients who might otherwise be left out.
Lastly, research often provides much closer monitoring with advanced diagnostics and tests that are essential during research but often not covered by insurance plans as part of the standard of care. This means research can be a nice additive option to the standard of care for even those with some insurance coverage.
An area where clinical research and patient care can conflict is if a research protocol is overly restrictive or too burdensome to patients or the clinical care team. For example, if a patient with a critical illness wants to try a novel therapeutic that is still under clinical trials, one of the inclusion criteria could be not using other supportive therapies.
If there is a safety conflict, it makes sense that someone will need to make a choice, but many research protocols are written to exclude almost everything else, including sleep or pain medications. That could overly restrict patients’ options when participating in research. This restriction could also deter patients with comorbid conditions that require several medications to manage them.
OSP: From your perspective, why might it make sense for researchers and care providers/physicians to work more closely together? What types of benefits come about with CRAACO?
JT: As discussed earlier, clinical research and clinical care are both dependent on each other and can provide benefits for both when they work closely together. Patients and care providers benefit from access to advanced monitoring, diagnostics and technology typically associated with research (e.g. lab tests, imaging tests, wearable sensors, artificial intelligence [AI]/machine-learning tools, etc.).
This closer monitoring can enable physicians to have the opportunity to intervene much sooner. Research sponsors also benefit from working closely with care providers who can identify the eligible patients for the research, expediting time to complete a clinical research project.
OSP: Please tell us about Biofourmis—your history, who your team is, key capabilities, and what sets you apart, as a digital therapeutics specialist.
JT: Biofourmis was founded in 2015 in Singapore by our CEO Kuldeep Singh Rajput, while still a neuroscience PhD candidate; our chief privacy officer Mark Niu, who was a fellow PhD student at that time; and our chief medical officer Maulik Majmudar, who was a practicing cardiologist at the time before becoming a medical officer at Amazon and then joining Biofourmis full-time in 2021.
I met Kuldeep during my 14-year tenure at Amgen. At that time, I was driving Amgen’s digital health strategy and launching several digital health products in partnerships with innovative startups like Biofourmis. Kuldeep’s passion to transform healthcare was contagious, so I joined Biofourmis in January 2020 as the chief operating officer.
Since then, the company has grown over 400% and now employs more than 350 team members across four offices in Boston, Singapore, India, and Zurich. Biofourmis moved its headquarters to Boston in 2019 and has experienced rapid worldwide growth, including forging over 50 partnerships with leading pharmaceutical companies, health systems, and payers; earning more than 80 global patents; completing 15 regulatory authorizations, making three strategic acquisitions, and closing three funding rounds, including a $100m [USD] Series C round led by SoftBank Vision Fund that closed last year.
Biofourmis’ vision is to predict disease before it happens in order to enable timely intervention and improved outcomes. Our singular purpose is to free patients from the exhausting, stressful and costly cycle of clinical exacerbations and hospital readmissions, to help them and their clinical team stay connected, confident, and one step ahead of their disease. We operate at the intersection of care delivery, therapy development, software technology, and artificial intelligence/machine learning.
Our solutions include an end-to-end, robust, technology platform for care-at-home across the continuum of care, including clinical research. This platform is leveraged by the world’s leading pharma and biotech companies, as well as health systems globally, for hospitals at home, remote patient monitoring, and remote disease management throughout the patient journey - acute, post-acute, and complex chronic care.
We have deep expertise in artificial intelligence, machine learning, and data science. Our solutions deliver clinically meaningful and regulatory-cleared clinical deterioration prediction models, smart notifications that reduce clinician burden while improving operational efficiency, and software algorithms that automate medication optimization to improve quality of care and health outcomes while reducing total healthcare costs.
To support pharma partners with virtual/decentralized clinical trials, market access studies, and commercialization of digital therapies, Biofourmis provides a platform for active/passive data capture using digital tools, wearables, and novel patient-centric digital biomarkers that act as surrogates for endpoints.
What sets us apart is that our solutions are not just focused on the patient behavioral- change aspects, but rather leveraging continuous monitoring and continuous data collection and applying AI and machine learning algorithms to crystallize the precise intervention or medicine, personalized to an individual—whether that is a drug, a digital therapeutic, or a combination of digital therapies combined with traditional pharmacotherapy.
Our expertise is in software-as-a-medical-device and integrating our algorithms through clinical evidence pathways. We then make these solutions available as digital therapeutics, as with our BiovitalsHF therapy for heart failure that the FDA recently granted a Breakthrough Device designation. Or we deploy our solutions in research and other collaborations with pharmaceutical companies to develop companion therapies that improve the efficacy and safety profile of traditional drugs.
OSP: How can decentralized trial technology help progress CRAACO?
JT: When a physician is trying to determine if they can recommend a patient for clinical research, part of the decision-making process is patient burden. Often, as much as a patient might benefit from the therapeutic being studied, they might not be able to carry that burden of frequent clinical site visits, for example, due to social determinants of health, disease severity, or comorbidities.
Decentralization of clinical trials offers the opportunity to leverage research more effectively as a care option without necessarily having to take on the burden of visiting sites. This could be through remote video or audio visits, or this could be wearables and sensors that collect the data remotely. By leveraging the technology components that support decentralization, it makes it more feasible to leverage clinical research as a care option (CRAACO) for a wider patient population.
OSP: Could you please talk about some of the tools (wearables, apps, telehealth, and others) that can help clinical care professionals in their DCTs?
JT: The decentralization of clinical trials has two fundamental components that overlap with the innovations on the digital therapeutics side, both of which revolve around being able to collect data and engage patients remotely. The data collection aspect includes wearables and sensors for continuous passive data collection as well as ePROs for active data collection.
The other element is engaging the patient remotely. This can include remote visits (telehealth), reminders, education, and tracking the adherence to the protocol or the therapy. All of this can be done remotely through the mobile apps designed for patients and clinicians with simplicity as the driving design principle.
OSP: Could you talk about some of the advantages such devices could bring about?
JT: Many pharmaceutical companies have started to collect data remotely through wearables and sensors to support clinical research. The next step is to effectively leverage all this data that is coming in near real-time for potential early intervention.
What is needed is a set of AI and machine-learning-based tools that can process multiple parameters coming together and detect the context (e.g. is patient sleeping, running, at rest?) to avoid the false positive notifications that contribute to clinician alert fatigue. For example, Biofourmis’s FDA-cleared algorithm, Biovitals Analytics Engine, can combine activity data with heart rate, respiration rate, and oxygen level to determine if an adverse event is occurring.
Combining this continuous data collection with algorithms that can process the data in near real-time and then integrating the technology into the clinical workflows can notify the care team to engage with the patient by phone or a video telehealth visit if there’s a potential issue. All these pieces coming together is where we see patients’ lives being saved through early interventions on a timely basis and making a huge difference.
For drug research, the way this becomes a very powerful tool is in determining the efficacy and safety profile of a drug. Having this additional mechanism where a patient is monitored continuously can protect their safety and inform investigators early about a drug’s potential side effects before potential harm occurs.
Our Biovitals Analytics Engine, which has received FDA approval as a device for ambulatory monitoring, provides an additional safety net through its AI and machine learning to enable more timely interventions.
OSP: Could you tell us about the evolution of digital therapeutics, and how the field can complement drug therapies for various conditions?
JT: The evolution of digital therapeutics started with mental health and using digital therapies to change behaviors and engage patients in their care. As evidenced by the recent FDA Breakthrough Device designation for our heart failure digital therapy, regulators are very open to these technologies being utilized in a far broader set of disease areas.
A digital therapeutic can be an independent therapy by itself or it can be combined with a traditional pharma or biotech drug to improve its efficacy or safety profile.
Another important therapeutic area is oncology, where it is often critical to carefully manage potential negative side effects of drugs, such as detecting sepsis or cytokine release syndrome associated with CAR-T cell therapy. Another condition, obviously, is COVID-19.
Research involving patients with COVID-19 recently published in Nature has shown that our Biovitals Sentinel solution using our AI and machine learning algorithms and remote monitoring was more accurate at predicting deterioration than traditional, manual methods. Pain has been the other area where digital components can more precisely measure a patient’s condition, objectively translate that into a pain score, and allow the appropriate titration or intervention to pain medications.
OSP: Please share an example of how Biofourmis’s DTx technology is showing promise for various conditions or interesting projects/collaborations you’re working on.
JT: In partnership with Chugai, which is developing a new medication for endometriosis pain, we are developing a digital biomarker for pain. The digital component is derived from wearables data which is then analyzed using AI and machine learning and then correlated with current gold standard tools, such as pain scores, collected through traditional ePROs. Our Biovitals Analytics Engine results have shown that the two are very well correlated and have been quite successfully validated.
Another noteworthy project we are working on in the oncology space, as I mentioned earlier, is detecting cytokine release syndrome (CRS), as well as the early signs of neurotoxicity. Both of these are conditions are frequently a major concern in managing an oncology patient, particularly with classes of therapies called CAR-T and BiTE.
We are working with several leading pharmaceutical and biotech companies on actively monitoring patients undergoing this treatment, enabling the administration of this therapy in an outpatient setting, and early discharge to the patient’s home. This significantly reduces the patient burden as the patient does not have to be kept in the hospital for days and days, but rather can go home and be carefully monitored through our platform. Predicting CRS and neurotoxicity in oncology patients is a rapidly growing area for us and our pharmaceutical partners.
OSP: Do you have any thoughts or information to add not touched upon above?
JT: Patient burden in clinical research could also include the technology selected by the pharmaceutical company or CRO. To improve trial engagement and success, researchers should select technology that minimizes patient burden with low data-entry demands and simple, short forms that can be completed on a mobile device.
For their part, investigators should be focused on data analysis and promoting patient engagement with excellent care, not technology issues. Life science companies and CROs should select a partner that can provide a turn-key solution that includes AI-driven technology platforms and services such as logistics management, tech support with knowledgeable patient-facing representatives to guide patients, and a clinical command center to monitor alerts.
The platform selected should also not limit investigators to what type of device they can use to drive their research. A device-agnostic, fully integrated RPM platform reduces the number of vendors that researchers must manage and makes trial participation more seamless for patients. This flexibility is crucial because few life sciences or CROs study just one therapeutic area.
By choosing a highly modular and scalable digital therapeutic platform to support research, investigators can pursue DCT and hybrid studies across a wider range of conditions and easily expand the number of participants as needed.