PCORI Biweekly COVID-19 Scan: Adoption of Decentralized Clinical Trials, Treatment for Mild to Moderate COVID-19 (March 31-April 13, 2022)
The Briefing provides an at-a-glance view of some important developments in the information universe surrounding COVID-19. The views presented here are solely those of ECRI Horizon Scanning and have not been vetted by other stakeholders.
The COVID-19 pandemic has led to many rapid changes in health care and beyond since it began in 2020. For example, adaptations set in motion by the public health emergency declaration, including emergency authorization for tests and treatments, telehealth access, and expanded Medicaid, have become commonplace. With the emergency declaration due to end on April 16 with a possible extension until mid–July, patients, providers, payers, and regulators are preparing to face continued challenges.
As a driver of change, the overall pandemic experience will itself have longer-lasting impacts. Clinical trials are now likely to be decentralized, thereby making them accessible to patients in broader and more diverse geographic locations (See Topics to watch). Patients themselves, particularly those experiencing post-COVID conditions (or Post-Acute Sequelae of COVID-19 [PASC]), continue what some call a “revolution in medical research” by asking questions that new clinical trials will be designed to answer.
One patient with post-COVID symptoms outlined 4 questions for both research and policy: 1) Why are there no diagnostics for microclots, which seem to be associated with post-COVID conditions, but are not detected in standard lab work? 2) Why is there still no public health warning about the risk of post-COVID conditions? 3) Why haven’t post-COVID treatment trials begun? and 4) What is the plan to support the long-term disability needs of post-COVID patients?
ECRI Horizon Scanning has selected the topics below as those with potential for impact relative to COVID-19 in the United States within the next 12 months. All views presented are preliminary and based on readily available information at the time of writing.
Because these topics are rapidly developing, we cannot guarantee the accuracy of this information after the date listed on this publication. In addition, all views expressed in the commentary section are solely those of ECRI Horizon Scanning and have not been vetted by other stakeholders. Topics are listed in alphabetical order.
Accelerated Adoption of Decentralized Clinical Trials Due to the COVID-19 Pandemic
At a Glance
- Decentralized clinical trials (DCTs) use technology and local health care providers to provide investigative treatments to patients in their home communities. They might help expand patient pools and expedite clinical research.
- DCT adoption began before the COVID-19 pandemic. Travel and operational restrictions due to the COVID-19 pandemic have accelerated a shift toward DCTs.
- Adaptation of DCTs requires robust data acquisition and management platforms, careful consideration of patient privacy protections, and guidance for how this data might be used.
- The FDA has recently released draft guidance for the use of digital health tech (DHT) in clinical trials.
Decentralized clinical trials (DCTs) utilize technology and local health care providers to remotely provide investigative treatments to patients, potentially yielding real-world results faster and getting more patients the medicines they need sooner compared with traditional clinical trial protocols.
A study found that although 87% of patients want to participate in relevant clinical trials, 70% of potential clinical trial patients live more than 2 hours from a study center. Notably, most clinical trials fail to recruit enough patients and experience delays due to recruitment or retention problems. Before the COVID-19 pandemic began, the FDA identified as an agency-wide priority the use of innovative trial designs to modernize clinical trials. Travel and operational restrictions due to the COVID-19 pandemic accelerated this preexisting shift toward DCTs.
Multiple technology platforms have recently been developed to support DCTs. For example, the digital wound care company Swift Medical launched Swift Scientific, which provides a digital imaging platform to support researchers conducting DCTs, and digital health care solutions company Vivalink launched a biometrics data platform that can be used in DCTs.
There are challenges and risks for launching decentralized trials, including the time and resources required to obtain and effectively use new software, ensure data security and patient privacy, and manage the risk of trial protocol deviations. Patients with unreliable internet access or low technology literacy might be excluded from fully remote trials The Cures 2.0 Act called for the FDA to align on regulation of digital health technologies (DHT) in clinical trials. The FDA released draft guidance on the use of DHT for remote data acquisition in clinical trials in December 2021.
The COVID-19 pandemic accelerated a shift towards decentralized approaches to clinical trials and, in many instances, necessitated their adoption.
Early feedback from ECRI internal stakeholders suggested fully or partially virtual trials will continue to rise over time. Stakeholders felt that DCTs improve patient enrollment and management. With appropriate community outreach and technological support, existing disparities in access to clinical trials could be decreased. Reducing or eliminating site visits is not only convenient for patients but might also improve their safety, and that of care providers, by reducing SARS-CoV-2 transmission.
However, trials requiring multiple blood draws or radiological assessments might be difficult to manage in a decentralized format. Data integrity and privacy are also concerns. Effort must be taken to ensure accurate data collection, data management security, and patient privacy maintenance. Wearable devices commonly used in DCTs might improve breadth and frequency of data collection. However, safeguards must be in place to govern what data can be collected and how it can be used.
- Categories: Systems and management
- Areas of potential impact: Patient outcomes, population health, clinical and/or caregiver safety, health care delivery and process, health care disparities, health care costs
Combination Regdanvimab (Regkirona; CT-P59) and CT-P63 to Treat Mild to Moderate COVID-19
At a Glance
- Combination regdanvimab (CT-P59) and CT-P63 is an inhaled monoclonal antibody therapy being investigated to treat adults with mild to moderate COVID-19.
- The treatment is intended to bind to and neutralize SARS-CoV-2, thus preventing the virus from binding to and entering human cells, furthering infection.
- The treatment is inhaled, causing the virus to be neutralized in the mucus of the airways and eliminated as the body clears this mucus, thus preventing local infection.
- Its developer, Celltrion, has submitted an investigational new drug application to the FDA to start a global phase 3 trial investigating the treatment. The anticipated enrollment is 2200 patients with mild to moderate COVID-19.
Combination regdanvimab (Regkirona; CT-P59) and CT-P63 is an inhaled monoclonal antibody therapy being investigated by Celltrion (Incheon, South Korea) to treat adults with mild to moderate COVID-19.
Monoclonal antibodies are laboratory–manufactured proteins designed to mimic the body’s natural immune response, which recognizes and neutralizes foreign pathogens. The SARS-CoV-2 virus is able to enter human host cells through the interaction of viral spike proteins expressed on the surface of the virus, with the broadly expressed angiotensin–converting enzyme 2 (ACE-2) receptors on human cell surfaces. Regdanvimab and CT-P63 are both monoclonal antibodies that target and bind to the spike receptor binding domain of SARS-CoV-2, which purportedly prevents the virus from binding to the ACE-2 receptor and entering host cells. Thus, they are intended to block further viral infection and replication.
Compared with existing monoclonal antibodies for COVID-19 that are administered intravenously, this combination treatment is nebulized and inhaled, purportedly neutralizing the virus locally in the mucus of the airways. The neutralized virus is eliminated from the airways as the body clears the mucus. Preliminary laboratory testing has suggested that the CT-P63 component of the treatment retained neutralization ability against the SARS-CoV-2 Omicron variant (B.1.1.529).
Celltrion announced in February 2022 that the company submitted an investigational new drug application to start a global phase 3 trial enrolling 2200 patients with mild to moderate symptoms of COVID-19.
We were unable to find information regarding the potential cost of a treatment course of regdanvimab and CT-P63.
New and effective treatments for COVID-19 are needed, because emerging SARS-CoV-2 variants are not as susceptible to available therapies. Combination regdanvimab (CT-P59) and CT-P63 might improve patient health outcomes by preventing further SARS-CoV-2 infection in adults with mild to moderate COVID-19.
Early feedback from ECRI internal stakeholders suggested that, if effective, the treatment might reduce hospitalizations, resulting in reductions in costs and workloads of clinical personnel. Since the treatment is inhaled and delivered directly to the lungs, it might have fewer side effects (eg cytokine release syndrome and toxicity) compared with intravenously administered monoclonal antibodies. An inhaled treatment might improve access to care because it might be easier to deliver at home and patients would not need to travel to clinics to receive treatment.
Since phase 3 trials have not yet begun, it might be too early to fully assess potential impacts of the treatment. However, research on this treatment might improve understanding of treating patients infected with SARS-CoV-2 variants.
- Categories: Treatment
- Areas of potential impact: Patient outcomes, population health, health care delivery and process, health disparities, health care costs
Horizon scanning is a systematic process that serves as an early warning system to inform decision makers about possible future opportunities and threats. Health care horizon scanning identifies technologies, innovations, and trends with potential to cause future shifts or disruptions—positive or negative—in areas such as access to care, care delivery processes, care setting, costs of care, current treatment models or paradigms, health disparities, health care infrastructure, public health, and patient health outcomes.
The PCORI Health Care Horizon Scanning System (HCHSS) conducts horizon scanning to better inform its patient-centered outcomes research investments. Initially, PCORI defined the HCHSS project scope to focus on interventions with high potential for disruption in the United States in 5 priority areas: Alzheimer’s disease and other dementias, cancer, cardiovascular diseases, mental and behavioral health conditions, and rare diseases. In addition, the system captures high-level disruptive trends across all clinical areas, which may lead PCORI to expand the project scope to include other priority areas in the future.
In early 2020, the COVID-19 pandemic created a fast-moving, widespread public health crisis. In May 2020, PCORI expanded its HCHSS to elucidate the landscape of potentially impactful applications for COVID-19. The HCHSS COVID-19 supplement scans for, identifies, monitors, and reports on emerging and available COVID-19-related treatments, diagnostics, preventive measures, management strategies, and systems changes with potential for high impact to patient outcomes—for individuals and populations—in the United States in the next 12 months.
The HCHSS COVID-19 supplement produces 3 main outputs:
- Biweekly COVID-19 Scans (eg, this document) provide ECRI Horizon Scanning with a vehicle to inform PCORI and the public in a timely manner of important topics of interest identified during ongoing scanning and topic identification or through the ECRI stakeholder survey process.
- Status Reports (quarterly) briefly list and describe all COVID-19-related topics identified, monitored, and recently archived.
- High Impact Reports (every 4 months) highlight those topics that ECRI internal stakeholders (eg, physicians, nurses, allied health professionals, public health professionals, first responders, health systems experts, clinical engineers, researchers, business and finance professionals, and information technology professionals) have identified as having potential for high impact relative to COVID-19 in the United States.
Commentary in this COVID-19 Scan reflects preliminary views of ECRI Horizon Scanning and internal ECRI stakeholders.
The information contained in this document has not been vetted by other stakeholders.
We welcome your comments on this Scan. Send them by email to [email protected].
Posted: April 25, 2022
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