PCORI Biweekly COVID-19 Scan: Treating Severe ARDS, COVID Test Initiative (April 29-May 12, 2021)
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.
COVID-19 has had an enormous impact on the US health care system. As we emerge from the acute impacts of the pandemic, some long-established norms of the health care journey are being reconsidered. In particular, the delivery and payment models for nursing and palliative care are being reconsidered in reaction to the harm caused when nursing home residents were separated from their families during the peak of the pandemic and the emerging need for ongoing care for patients with long COVID. Shifts toward in-home care and insurance coverage without a hospice requirement will greatly change the experience of patients and those who care for them.
The current US administration is looking at partnering with dollar stores and fast-food restaurants to reach both the vaccine-hesitant and those who live far from current vaccination sites. A recent study found that more than 90% of the US population would be within 5 miles of a vaccination site if Dollar General stores were added to the network.
As global cases rise, vaccine uptake levels increase to 58.9% of US adults receiving at least 1 dose, and US public health constraints are relaxed, there is still a need for new testing programs and better treatment options for younger patients (see Topics to Watch).
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.
Remestemcel-L (Ryoncil) to Treat Moderate to Severe COVID-19 Acute Respiratory Distress Syndrome
At a Glance
- Remestemcel-L (Ryoncil) is an investigational cell therapy consisting of donor-derived mesenchymal stems cell for treating ventilated patients with moderate to severe COVID-19 acute respiratory distress syndrome (ARDS).
- Remestemcel-L purportedly modulates the body’s immune response to offset the cytokine storm by suppressing pro-inflammatory cytokine production, increasing anti-inflammatory cytokine production, and facilitating the release of naturally occurring anti-inflammatory cells to involved tissues.
- Remestemcel-L was granted Fast Track designation by the US Food and Drug Administration (FDA) and is in phase 3 development in ventilator-dependent COVID-19 patients. In December 2020, a Data Safety Monitoring Board determined that the trial was unlikely to meet its primary end point of reducing mortality and recommended that the trial stop enrollment.
- In April 2021, remestemcel-L’s manufacturer released 60-day results from the 223 patients enrolled before the trial was halted. In a prespecified subgroup of patients younger than 65 years, remestemcel-L reduced the risk of death by 46%, and among patients younger than 65 who were also taking dexamethasone, remestemcel-L reduced the risk of death by 75%. The number of days hospitalized was reduced and the number of days off mechanical ventilation was increased.
- The manufacturer announced plans to discuss next steps with the FDA.
Remestemcel-L (Ryoncil) is an investigational cell therapy consisting of donor-derived (ie, allogeneic) mesenchymal stem cells. It is intended to treat moderate to severe COVID-19 ARDS, a form of severe respiratory failure that is characterized by inflammatory injury and impaired oxygen exchange. Remestemcel-L purportedly modulates the body’s immune response to dampen the ARDS cytokine storm by suppressing pro-inflammatory cytokines, increasing anti-inflammatory cytokines, and facilitating the release of anti-inflammatory cells to involved tissues.
Remestemcel-L is in phase 3 development among ventilator-dependent COVID-19 patients. The treatment was granted Fast Track designation by the FDA. In December 2020, a Data Safety Monitoring Board determined that the phase 3 trial was unlikely to meet its primary end point of reducing mortality and recommended that the trial stop enrollment.
However, in April 2021, remestemcel-L’s manufacturer, Mesoblast (Melbourne, Australia), released 60-day results on the 223 patients who were enrolled before the trial was halted. In a prespecified subgroup of patients younger than 65 years, remestemcel-L reduced the risk of death by 46%. Additionally, among patients younger than 65 years who were also taking dexamethasone, remestemcel-L reduced the risk of death by 75%. The number of days hospitalized was reduced and the number of days off mechanical ventilation was increased. But death risk was not reduced in patients aged 65 years or older. The company announced plans to discuss next steps with the FDA.
Remestemcel-L might improve clinical outcomes by helping the body curb the cytokine storm that often occurs in patients with severe COVID-19 and contributes to poor outcomes.
Early feedback from ECRI internal stakeholders suggested that remestemcel-L might provide a novel treatment for patients with COVID-19–induced ARDS, because of its immunomodulatory and anti-inflammatory actions. Stakeholders expressed concerns about the failure of Remestemcel-L to reach its death-risk end points in the initial cohort of patients. However, the results shown in a prespecified subgroup analysis found remestemcel-L in combination with standard of care (dexamethasone) significantly reduced death rates in patients younger than 65 years.
Stakeholders thought that, because many COVID-19 patients currently hospitalized fall into this age group, the treatment might have a substantial impact on patient health outcomes. The treatment might substantially reduce the burden on hospital resources and costs if the length of hospital stays is reduced and fewer intensive resources are needed. However, stakeholders were also concerned that, if expensive, treatment with remestemcel-L might increase disparities for individuals in need.
- Category: Treatments
- Areas of potential impact: Patient outcomes, health care delivery and process, health care disparities, health care costs
Say Yes! COVID Test Initiative to Reduce the Spread of COVID-19
At a Glance
- The Say Yes! COVID Test Initiative is a cooperative effort among local, state, and federal health authorities to evaluate whether frequent self-administered testing can limit the spread of COVID-19 in communities.
- Federal agencies are providing about 2 million rapid antigen COVID-19 tests to as many as 160 000 residents of Pitt County, North Carolina, and Hamilton County, Tennessee. Up to 2 unvaccinated members of each participating household, those with the most public contact, will give themselves a COVID-19 test 3 times a week for about 1 month.
- A digital assistant will guide the participants through the testing process and give reminders.
- The initiative seeks to determine the effects of frequent self-testing on the knowledge, attitude, and behaviors of people regarding hygiene practices and vaccination, as well as the effects of frequent testing on infection and death rates.
The Say Yes! COVID Test Initiative is a cooperative effort among state and local health departments, the National Institutes of Health (NIH), and the Centers for Disease Control and Prevention (CDC) to evaluate whether frequent self-testing can reduce COVID-19 spread in communities.
For the initiative, NIH and CDC are providing about 2 million rapid antigen COVID-19 tests (the QuickVue At-home test, Quidel Corp, San Diego, California) to as many as 160 000 residents in the communities of Greenville and Pitt County, North Carolina, and Chattanooga and Hamilton County, Tennessee. Up to 2 members (aged 8 years or older) of each participating household will test themselves 3 times a week for about 1 month. Testing should be prioritized to household members with the most contact outside of the home, who are not vaccinated, or have not previously contracted COVID-19. Participants will have access to a digital assistant to guide them through the testing process and to set testing reminders.
The study will monitor COVID-19 infection and death rates in the participating geographic areas and compare them to rates observed in similar, nonparticipating geographic areas. Participants will also have the option to voluntarily enroll in an NIH-sponsored study that will use surveys to assess whether frequent self-testing has led to changes in behavior to prevent COVID-19 spread and has helped participants gain knowledge about preventing viral spread and receiving vaccination shots.
The Say Yes! COVID Test Initiative might reduce community transmission of COVID-19 and improve population and health outcomes. Reducing the time between individuals’ infection with SARS-CoV-2 and their awareness that they are infected would allow quarantine protocols or care to be started sooner. The program might also reduce community transmission of SARS-CoV-2 by increasing awareness and mindfulness of infection risk in unvaccinated people living in multiperson households.
Early feedback from ECRI internal stakeholders suggested that the Say Yes! COVID Test Initiative is a novel and welcome program. It might reduce COVID-19 incidence in targeted communities of unvaccinated people with barriers or reluctance to seek COVID-19 vaccination, as well as in children who are too young to seek COVID-19 vaccination.
Earlier detection of symptomatic and asymptomatic people with high exposure to the public who live with other household members might substantially improve population health outcomes in COVID-19 hotspots. By increasing awareness and education of SARS-CoV-2 infection risk among unvaccinated individuals, the program might also increase vaccine acceptance. However, stakeholders question the financial sustainability of such testing programs if they do not increase vaccine uptake over time.
- Category: Systems and management
- Areas of potential impact: Patient outcomes, population health, clinician and/or caregiver safety, health care delivery and process, health care disparities
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: May 19, 2021
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